ΜΕΤΑΠΤΥΧΙΑΚΟ ΠΡΟΓΡΑΜΜΑ ΣΠΟΥΔΩΝ: ‘‘ΕΛΑΧΙΣΤΑ ΕΠΕΜΒΑΤΙΚΗ ΧΕΙΡΟΥΡΓΙΚΗ, ΡΟΜΠΟΤΙΚΗ ΧΕΙΡΟΥΡΓΙΚΗ ΚΑΙ ΤΗΛΕΧΕΙΡΟΥΡΓΙΚΗ’’
ΕΘΝΙΚΟ ΚΑΙ ΚΑΠΟΔΙΣΤΡΙΑΚΟ ΠΑΝΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ ΙΑΤΡΙΚΗ ΣΧΟΛΗ
ΔΙΠΛΩΜΑΤΙΚΗ ΕΡΓΑΣΙΑ
ΘΕΜΑ:
MINIMALLY-INVASIVE LYMPHADENECTOMY IN OVARIAN CANCER
ΜΕΤΑΠΤΥΧΙΑΚΗ ΦΟΙΤΗΤΡΙΑ :
ΚΑΡΑΧΑΛΙΟΥ ΧΡΙΣΤΙΝΑ
ΑΜ : 20130758
ΑΘΗΝΑ, ΔΕΚΕΜΒΡΙΟΣ 2016 ΠΡΑΚΤΙΚΟ ΚΡΙΣΕΩΣ ΤΗΣ ΣΥΝΕΔΡΙΑΣΗΣ ΤΗΣ ΤΡΙΜΕΛΟΥΣ ΕΠΙΤΡΟΠΗΣ ΓΙΑ ΤΗΝ ΑΞΙΟΛΟΓΗΣΗ ΤΗΣ ΔΙΠΛΩΜΑΤΙΚΗΣ ΕΡΓΑΣΙΑΣ Της Μεταπτυχιακής Φοιτήτριας Καραχάλιου Χριστίνας
Εξεταστική Επιτροπή
• Αλέξανδρος Παπαλάμπρος, Λέκτορας Χειρουργικής ( Επιβλέπων ) • Χρήστος Π. Τσιγκρής, Ομότιμος Καθηγητής Χειρουργικής & Επιστημονικός Υπεύθυνος του Π.Μ.Σ. • Θεόδωρος Διαμαντής, Καθηγητής Χειρουργικής
Η Τριμελής Εξεταστική Επιτροπή η οποία ορίσθηκε από την ΓΣΕΣ της Ιατρικής Σχολής του Παν, Αθηνών Συνεδρίαση της ....ης ...... 20..... για την αξιολόγηση και εξέταση της υποψηφίου κας Καραχάλιου Χριστίνας, συνεδρίασε σήμερα .../.../.....
Η Επιτροπή διαπίστωσε ότι η Διπλωματική Εργασία της Κας Καραχάλιου Χριστίνας με τίτλο : «MINIMALLY-INVASIVE LYMPHADENECTOMY IN OVARIAN CANCER» είναι πρωτότυπη, επιστημονικά και τεχνικά άρτια και η βιβλιογραφική πληροφορία ολοκληρωμένη και εμπεριστατωμένη.
Η εξεταστική επιτροπή αφού έλαβε υπ' όψιν το περιεχόμενο της εργασίας και τη συμβολή της στην επιστήμη, με ψήφους ...... προτείνει την απονομή του Μεταπτυχιακού Διπλώματος Ειδίκευσης ( Master's Degree ), στον παραπάνω Μεταπτυχιακό Φοιτητή.
Στην ψηφοφορία για την βαθμολογία ο υποψήφιος έλαβε για τον βαθμό ‹‹ ΑΡΙΣΤΑ ›› ψήφους ...... , για τον βαθμό ‹‹ ΛΙΑΝ ΚΑΛΩΣ ›› ψήφους ...... , και για τον βαθμό ‹‹ ΚΑΛΩΣ ›› ψήφους ...... Κατά συνέπεια, απονέμεται ο βαθμός ‹‹ ...... ››.
Τα μέλη της Εξεταστικής Επιτροπής
• Αλέξανδρος Παπαλάμπρος ( Επιβλέπων ) ( Υπογραφή )
• Χρήστος Π. Τσιγκρής ( Υπογραφή )
• Θεόδωρος Διαμαντής ( Υπογραφή )
2
The procedure of developing a study is always creative and educational. Nevertheless, it requires a lot of time and patience both of the writer and the people around him. In my case I owe gratitude to those who stood by me during this effort. I would like to thank my family, my teachers, my colleagues and above all Ilias Gkizis who gave me precious advice to accomplish and complete this task.
3 TABLE OF CONTENTS
INTRODUCTION...... 6
PART I
1. OVARIAN CANCER...... 7
2. INCIDENCE AND EPIDEMIOLOGY...... 8
3. OVARIAN TUMORS...... 9 3.1 EPITHELIAL OVARIAN TUMORS...... 9 3.2 FALLOPIAN TUBE CANCER...... 10 3.3 OVARIAN GERM CELL TUMORS...... 10 3.4 OVARIAN STROMAL TUMORS...... 11
4. DIAGNOSIS...... 12
5. STAGING OF OVARIAN CANCER...... 13
6. MANAGEMENT...... 16
7. LYMPHATIC SYSTEM...... 18
8. OVARIAN CANCER AND LYMPHADENECTOMY...... 21 8.1 LYMPHADENECTOMY FOR EARLY OVARIAN CANCER...... 22 8.2 LYMPHADENECTOMY FOR ADVANCED OVARIAN CANCER...... 24
PART II
MINIMALLY-INVASIVE LYMPHADENECTOMY IN OVARIAN CANCER
9. MINIMALLY-INVASIVE SURGERY...... 28 9.1 INTRODUCTION...... 28 9.2 BENEFITS OF MINIMALLY-INVASIVE PROCEDURES...... 29
10. LAPAROSCOPIC LYMPHADENECTOMY...... 30 10.1 LAPAROSCOPIC PROCEDURE...... 32 10.2 LAPAROSCOPIC PELVIC LYMPHADENECTOMY...... 36
4 10.3 LAPAROSCOPIC PARA-AORTIC LYMPHADENECTOMY...... 43 10.3.1 ANATOMY AND SURGICAL PROCEDURES FOR PARA-AORTIC LYMPHADENECTOMY...... 43 10.3.2 APPROACHES...... 43 A) TRANSPERITONEAL...... 44 B) EXTRAPERITONEAL...... 55
11. SINGLE-PORT LAPAROENDOSCOPY SURGERY...... 63
12. ROBOTIC-ASSISTED LYMPHADENECTOMY...... 71 12.1 ROBOTIC PELVIC LYMPHADENECTOMY...... 71 12.2 ROBOTIC TRANSPERITONEAL INFRARENAL AORTIC LYMPHADENECTOMY...... 76 12.3 ROBOTIC EXTRAPERITONEAL AORTIC LYMPHADENECTOMY.....84 12.4 ROBOTIC SINGLE-PORT LYMPHADENECTOMY...... 92
DISCUSSION...... 97
CONCLUSION...... 105
ABSTRACT...... 106
ΠΕΡΙΛΗΨΗ...... 107
REFERENCES...... 108
5
INTRODUCTION
Ovarian cancer metastases disseminate via lymphatic system. The metastases occur in the pelvic nodes and also in the aortic nodes.The upper aortic infra-renal lymph nodes are of special concern because of the direct drainage from the left ovarian vein to the left renal vein and the right ovarian vein to infra-renal vena cava. Because of the high incidence of lymphatic metastasis, bilateral pelvic and aortic lymphadenectomy is indicated in all ovarian cancers.
In early stage ovarian cancer, systematic lymph node dissection is required in order to perform accurate clinical staging and to select an adequate adjuvant chemotherapy. For advanced cancer with minimal tumour residuals of up to 10mm, systematic lymphadenectomy will produce a significant benefit in progression- free survival, and may improve the 5- year overall survival.
Laparotomy remained for years the prevailing method for the management of ovarian cancer, including pelvic and para-aortic lymphadenectomy. Although, minimally-invasive surgery has been dramatically increased in the recent years and has been widely adopted in gynecological procedures, providing a few of benefits.
The aim of this study is to present and understand all the available minimally-invasive techiques that have been reported for pelvic and para-aortic lymphadenectomy in ovarian cancer and successfully end up to the most feasible, minimal invasive, efficient and most economic. The parameters which will be analyzed is the operative time, the estimated intraoperative blood loss, the postoperative pain, the length of hospital stay, the number of lymph nodes yielded and the complication rates.
6 PART I
1. OVARIAN CANCER
Ovarian cancer begins in the ovaries. Ovaries are reproductive glands found only in females. The ovaries produce eggs (ova) for reproduction. The eggs travel through the fallopian tubes into the uterus where the fertilized egg implants and develops into a fetus. The ovaries are also the main source of the female hormones estrogen and progesterone. One ovary is on each side of the uterus in the pelvis.
Picture 1. (http://www.medicinenet.com/ovarian_cancer/article.htm) The ovaries are made up of 3 main kinds of cells. Each type of cell can develop into a different type of tumor: Epithelial tumors start from the cells that cover the outer surface of the ovary. Most ovarian tumors are epithelial cell tumors. Germ cell tumors start from the cells that produce the eggs (ova). Stromal tumors start from structural tissue cells that hold the ovary together and produce the female hormones estrogen and progesterone. Most of these tumors are benign (non-cancerous) and never spread beyond the ovary. Benign tumors can be treated by removing either the ovary or the part of the ovary that contains the tumor. Malignant (cancerous) or low malignant potential ovarian tumors can spread (metastasize) to other parts of the body and can be fatal.
7 2. INCIDENCE AND EPIDEMIOLOGY
The estimated number of new ovarian cancer cases in Europe in 2012 was 65 538 with 42 704 deaths [1]. There is variation in the incidence rate across the continent with a higher incidence in northern European countries. In the USA, there were 20 400 newly diagnosed cases and 14 400 deaths in 2009 [2]. Ovarian cancer is the fifth most common type of cancer in women and the fourth most common cause of cancer death in women. The estimated lifetime risk for a woman developing ovarian cancer is about 1 in 54. Ovarian cancer is predominantly a disease of older, postmenopausal women with the majority (>80%) of cases being diagnosed in women over 50 years. The exact cause of ovarian cancer remains unknown but many associated risk factors have been identified. A woman’s reproductive history appears to contribute significantly to her lifetime risk of ovarian cancer. Those women who have had multiple pregnancies have a lower risk than those with fewer pregnancies, who in turn have a lower risk than nulliparous women. Early menarche and late menopause also seem to contribute to a greater risk of ovarian cancer, while use of the oral contraceptive pill, tubal ligation, breastfeeding and suppression of ovulation offer protection against ovarian cancer. All of these risk factors point to ovulation being correlated with the development of ovarian cancer. Further risk factors are obesity and possibly the use of talcum powder. Family history plays a very important role in the development of ovarian cancer, although in a recent study 44% patients with high-grade serous ovarian cancer and a germline BRCA mutation did not report a family history of cancer [3].Women with a first-degree relative have more than a twofold increase in risk of ovarian cancer compared with women with no family history. However, only 10% of ovarian cancer cases have an identifiable genetic mutation, e.g. the known susceptibility genes BRCA 1 and BRCA 2. An inherited BRCA 1 mutation confers a 15%–45% lifetime risk of developing ovarian cancer and ≤85% risk of developing breast cancer. A BRCA 2 mutation increases the lifetime risk of ovarian cancer to 10%–20% and breast cancer risk of ≤85%.Women with hereditary ovarian cancer tend to develop the disease 10 years earlier than women with non hereditary ovarian cancer. There are no clear guidelines for referral of ovarian cancer patients for testing. Referral is made on the basis of a family history and ethnic background. The importance of identifying BRCA mutations has increased as, in addition to risk-reducing surgery and surveillance for breast cancer in the patient and in family members, there are new treatments emerging specifically for BRCA-related cancers.
8 3. OVARIAN TUMOURS
3.1. Epithelial ovarian tumors
Benign epithelial ovarian tumors Most epithelial ovarian tumors are benign, don’t spread, and usually don’t lead to serious illness. There are several types of benign epithelial tumors including serous cystadenomas, mucinous cystadenomas, and Brenner tumors.
Tumors of low malignant potential When looked at under the microscope, some ovarian epithelial tumors don’t clearly appear to be cancerous. These are called tumors of low malignant potential (LMP tumors). They are also known as borderline epithelial ovarian cancer. These are different from typical ovarian cancers because they don’t grow into the supporting tissue of the ovary (called the ovarian stroma). Likewise, if they spread outside the ovary, for example, into the abdominal cavity (belly), they might grow on the lining of the abdomen but often don’t grow into it. LMP tumors tend to affect younger women than the typical ovarian cancers. These tumors grow slowly and are less life-threatening than most ovarian cancers. LMP tumors can be fatal, but this isn’t common.
Malignant epithelial ovarian tumors Cancerous epithelial tumors are called carcinomas. About 85% to 90% of ovarian cancers are epithelial ovarian carcinomas. When someone says that they had ovarian cancer, they usually mean that they had this type of cancer. These tumor cells have several features (when viewed under a microscope) that can be used to classify epithelial ovarian carcinomas into different types. The serous type is by far the most common, but there are other types like mucinous, endometrioid, and clear cell. If the cells don't look like any of these 4 subtypes, the tumor is called undifferentiated. Undifferentiated epithelial ovarian carcinomas tend to grow and spread more quickly than the other types. Epithelial ovarian carcinomas are classified by these subtypes, but they are also given a grade and a stage. The grade classifies the tumor based on how much it looks like normal tissue on a scale of 1, 2, or 3. Grade 1 epithelial ovarian carcinomas look more like normal tissue and tend to have a better prognosis (outlook). Grade 3 epithelial ovarian carcinomas look less like normal tissue and usually have a worse outlook. Grade 2 tumors look and act in between grades 1 and 3. The tumor stage describes how far the tumor has spread from where it started in the ovary. Epithelial ovarian cancers tend to spread to the lining and organs of the pelvis and abdomen (belly) first. This may lead to the build-up of fluid in the abdominal cavity (called ascites). As it becomes more advanced, it may spread to the lung and liver, or, rarely, to the brain, bones, or skin.
Other cancers that are similar to epithelial ovarian cancer Primary peritoneal carcinoma Primary peritoneal carcinoma (PPC) is a rare cancer closely related to epithelial ovarian cancer. At surgery, it looks the same as an epithelial ovarian cancer that has spread through the abdomen.
9 Under a microscope, PPC also looks just like epithelial ovarian cancer. Other names for this cancer include extra-ovarian (meaning outside the ovary) primary peritoneal carcinoma (EOPPC) and serous surface papillary carcinoma. PPC seems to develop from cells in the lining of the pelvis and abdomen. This lining is called the peritoneum. These cells are very similar to the cells on the surface of the ovaries. Some experts believe that PPC may start in the cells lining the fallopian tubes. Like ovarian cancer, PPC tends to spread along the surfaces of the pelvis and abdomen, so it is often difficult to tell exactly where the cancer first started. This type of cancer can occur in women who still have their ovaries, but it is of more concern for women who have had their ovaries removed to prevent ovarian cancer. This cancer does rarely occur in men. Symptoms of PPC are similar to those of ovarian cancer, including abdominal pain or bloating, nausea, vomiting, indigestion, and a change in bowel habits. Also, like ovarian cancer, PPC may elevate the blood level of a tumor marker called CA-125. Women with PPC usually get the same treatment as those with widespread ovarian cancer. This could include surgery to remove as much of the cancer as possible , followed by chemotherapy like that given for ovarian cancer. Its outlook is likely to be similar to widespread ovarian cancer.
3.2. Fallopian tube cancer This is another rare cancer that is similar to epithelial ovarian cancer. It begins in the tube that carries an egg from the ovary to the uterus (the fallopian tube). Like PPC, fallopian tube cancer and ovarian cancer have similar symptoms. The treatment for fallopian tube cancer is much like that for ovarian cancer, but the outlook (prognosis) is slightly better.
3.3. Ovarian germ cell tumors Germ cells usually form the ova or eggs in females and the sperm in males. Most ovarian germ cell tumors are benign, but some are cancerous and may be life threatening. Less than 2% of ovarian cancers are germ cell tumors. Overall, they have a good outlook, with more than 9 out of 10 patients surviving at least 5 years after diagnosis. There are several subtypes of germ cell tumors. The most common germ cell tumors are teratomas, dysgerminomas, endodermal sinus tumors, and choriocarcinomas. Germ cell tumors can also be a mix of more than a single subtype.
Teratoma Teratomas are germ cell tumors with areas that, when seen under the microscope, look like each of the 3 layers of a developing embryo: the endoderm (innermost layer), mesoderm (middle layer), and ectoderm (outer layer). This germ cell tumor has a benign form called mature teratoma and a cancerous form called immature teratoma. The mature teratoma is by far the most common ovarian germ cell tumor. It is a benign tumor that usually affects women of reproductive age (teens through forties). It is often called a dermoid cyst because its lining is made up of tissue similar to skin (dermis). These tumors or cysts can contain different kinds of benign tissues including, bone, hair, and teeth. The patient is cured by surgical removal of the cyst, but sometimes a new cyst develops later in the other ovary. Immature teratomas are a type of cancer. They occur in girls and young women, usually younger
10 than 18. These are rare cancers that contain cells that look like those from embryonic or fetal tissues such as connective tissue, respiratory passages, and brain. Tumors that are relatively more mature (called grade 1 immature teratoma) and haven’t spread beyond the ovary are treated by surgical removal of the ovary. When they have spread beyond the ovary and/or much of the tumor has a very immature appearance (grade 2 or 3 immature teratomas), chemotherapy is recommended in addition to surgery.
Dysgerminoma This type of cancer is rare, but it is the most common ovarian germ cell cancer. It usually affects women in their teens and twenties. Dysgerminomas are considered malignant (cancerous), but most don’t grow or spread very rapidly. When they are limited to the ovary, more than 75% of patients are cured by surgically removing the ovary, without any further treatment. Even when the tumor has spread further (or if it comes back later), surgery, radiation therapy, and/or chemotherapy are effective in controlling or curing the disease in about 90% of patients.
Endodermal sinus tumor (yolk sac tumor) and choriocarcinoma These very rare tumors typically affect girls and young women. They tend to grow and spread rapidly but are usually very sensitive to chemotherapy. Choriocarcinoma that starts in the placenta (during pregnancy) is more common than the kind that starts in the ovary. Placental choriocarcinomas usually respond better to chemotherapy than ovarian choriocarcinomas do.
3.4. Ovarian stromal tumors About 1% of ovarian cancers are ovarian stromal cell tumors. More than half of stromal tumors are found in women older than 50, but about 5% of stromal tumors occur in young girls. The most common symptom of these tumors is abnormal vaginal bleeding. This happens because many of these tumors produce female hormones (estrogen). These hormones can cause vaginal bleeding (like a period) to start again after menopause. In young girls, these tumors can also cause menstrual periods and breast development to occur before puberty. Less often, stromal tumors make male hormones (like testosterone). If male hormones are produced, the tumors can cause normal menstrual periods to stop. They can also make facial and body hair grow. If the stromal tumor starts to bleed, it can cause sudden, severe abdominal pain. Types of malignant (cancerous) stromal tumors include granulosa cell tumors (the most common type), granulosa-theca tumors, and Sertoli-Leydig cell tumors, which are usually considered low- grade cancers. Thecomas and fibromas are benign stromal tumors. Cancerous stromal tumors are often found at an early stage and have a good outlook, with more than 75% of patients surviving long-term.
11 4. DIAGNOSIS
Patients with ovarian cancer confined to the ovary may have few or no symptoms, making clinical diagnosis of early ovarian cancer more difficult. Symptoms are most commonly seen with advanced disease. Recognised symptoms of all stages include abdominal or pelvic pain, constipation, diarrhoea, urinary frequency, vaginal bleeding, abdominal distension and fatigue. In advanced ovarian cancer, ascites and abdominal masses lead to increased abdominal girth, bloating, nausea, anorexia, dyspepsia and early satiety. Extension of disease across the diaphragm to the pleural cavities can produce pleural effusions and the development of respiratory symptoms. Patients may become aware of an abdominal or nodal mass either in the inguinal region, axillae or the supraclavicular fossa. Following a full clinical assessment, measurement of serum CA 125 is routinely used to aid diagnosis. However, its utility to detect early disease is questionable as it is elevated only in about 50% of patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I disease. In advanced disease, CA 125 is elevated in about 85% of patients. It is not specific for ovarian cancer and raised CA 125 levels may be found in nongynaecological malignancies (e.g. breast, lung, colon and pancreatic cancer) and benign disease (e.g. endometriosis, pelvic inflammatory disease and ovarian cysts). Serum carcinoembryonic antigen (CEA) and CA 19–9 levels are sometimes measured in situations where it is unclear whether an ovarian mass is of gastrointestinal origin, or a primary mucinous ovarian tumour. Similarly, in these situations, colonoscopy and/or gastroscopy are sometimes considered, particularly when CA 125/CEA ratio is ≤25. Ultrasonography of the abdomen and pelvis is usually the first imaging investigation recommended for women in whom ovarian cancer is suspected. Transvaginal ultrasonography has improved the visualisation of ovarian structures, thus improving the differentiation of malignant versus benign conditions [4]. A number of morphological variables have been identified as being strongly associated with ovarian cancer. The presence of a large lesion, multi-locular cysts, solid papillary projections, irregular internal septations and ascites are highly suggestive of ovarian cancer. A ‘risk of malignancy’ index can be calculated from clinical factors, ultrasound and CA 125 and can be used to refer patients to a specialist gynaecological oncology team. Computed tomography (CT) scans are routinely used to determine the extent of disease and to aid in surgical planning. Imaging of the chest with CT or chest X-ray should be done to look for pleural effusions and disease above the diaphragm. A pleural effusion cannot be regarded as malignant and indicative of FIGO stage IV disease without confirmation of positive cytology. Magnetic resonance imaging (MRI) scans do not form part of routine investigations.
Picture 2. Ultrasound images. ( http://www.meddean.luc.edu/lumen/meded/radio/curriculum/obgyn/ovarian_tumor1.htm, http://emedicine.medscape.com/article/404450-overview )
12 5. STAGING OF OVARIAN CANCER
TNM and FIGO Classifications for Ovarian Cancer The tumor-node-metastasis (TNM) and International Federation of Gynecology and Obstetrics (FIGO) classifications for staging ovarian cancer are provided below [5,6,7].
Table 1. TNM and FIGO Classifications for Ovarian Cancer Primary tumor (T) TNM FIGO TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 I Tumor limited to the ovaries (one or both) Tumor limited to one ovary; capsule intact, no tumor on ovarian surface; no T1a IA malignant cells in ascites or peritoneal washings Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface; no T1b IB malignant cells in ascites or peritoneal washings Tumor limited to one or both ovaries with any of the following: capsule ruptured, T1c IC* tumor on ovarian surface, malignant cells in ascites or peritoneal washings T2 II Tumor involves one or both ovaries with pelvic extension Extension and/or implants on the uterus and/or tube(s); no malignant cells in ascites T2a IIA or peritoneal washings Extension to and/or implants in other pelvic tissues; no malignant cells in ascites or T2b IIB peritoneal washings Pelvic extension and/or implants (T2a or T2b) with malignant cells in ascites or T2c IIC* peritoneal washings Tumor involves one or both ovaries with microscopically confirmed peritoneal T3 III* metastasis outside the pelvis T3a IIIA* Microscopic peritoneal metastasis beyond the pelvis (no macroscopic tumor) Macroscopic peritoneal metastasis beyond the pelvis 2 cm or less in greatest T3b IIIB* dimension Macroscopic peritoneal metastasis beyond the pelvis >2 cm in greatest dimension T3c IIIC* and/or regional lymph node metastasis Regional lymph nodes (N) TNM FIGO NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 IIIC Regional lymph node metastasis Distant metastasis (M) TNM FIGO M0 No distant metastasis M1 IV* Distant metastasis (excludes peritoneal metastasis) *Changes have been made to FIGO Staging Criteria that have not yet been resolved with the TNM system. FIGO Stage IIC has been eliminated.
13
Notes:The presence of nonmalignant ascites is not classified; the presence of ascites does not affect staging unless malignant cells are present.
Liver capsule metastasis is T3/stage III; liver parenchymal metastasis, M1/stage IV. Pleural effusion must have positive cytology for MI/stage IV.
FIGO staging criteria for cancer of the ovary, fallopian tube, and peritoneum FIGO updated its staging criteria in 2014. The equivalent proposed TNM staging is included for each FIGO stage, although this TNM staging has not yet been formally published. Stage I Stage I (T1-N0-M0) consists of tumor limited to the ovaries or fallopian tubes. Stage IA (T1a-N0-M0) includes the following: Tumor limited to one ovary (capsule intact) or fallopian tube No tumor on the external surface of the ovary or fallopian tube No malignant cells in ascites or peritoneal washings Stage IB (T1b-N0-M0) includes the following: Tumor limited to both ovaries (capsules intact) or fallopian tubes No tumor on the external surface of the ovaries or fallopian tubes No malignant cells in ascites or peritoneal washings Stage IC includes tumor limited to one or both ovaries or fallopian tubes, with any of the following: Stage IC1: (T1C1-N0-M0) Surgical spill Stage IC2: (T1C2-N0-M0) Capsule ruptured before surgery, or tumor on ovarian or fallopian tube surface Stage IC3: (T1C3-N0-M0) Malignant cells in the ascites or peritoneal washings Stage II In stage II (T2-N0-M0) tumor involves one or both ovaries or fallopian tubes, with pelvic extension (below pelvic brim) or primary peritoneal cancer . Stage IIA: (T2a-N0-M0) Extension and/or implants on the uterus and/or ovaries and/or fallopian tubes Stage IIB: (T2b-N0-M0) Extension to other pelvic intraperitoneal tissues Stage III In stage III, tumor involves one or both ovaries or fallopian tubes, or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes (T1/T2-N1-M0). Stage IIIA includes the following: Stage IIIA1: (T1/2-N1-M0) Positive (cytologically or histologically proven) retroperitoneal lymph nodes only Stage IIIA1(i) Metastasis up to 10 mm in greatest dimension
14 Stage IIIA1(ii) Metastasis more than 10 mm in greatest dimension Stage IIIA2: (T3a2-N0/N1-M0) Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes Stage IIIB (T3b-N0/N1-M0) involves macroscopic peritoneal metastasis beyond the pelvis up to 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes. Stage IIIC (T3c-N0/N1-M0) involves macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes. Stage IIIC includes extension of tumor to the capsule of liver and spleen without parenchymal involvement of either organ. Stage IV Stage IV (any T–any N–M1) consists of distant metastasis, excluding peritoneal metastases, and includes the following: Stage IVA: Pleural effusion with positive cytology Stage IVB: Parenchymal metastases and metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity)
15 6. MANAGEMENT Standard treatment for women with ovarian cancer involves aggressive debulking surgery followed by chemotherapy. The aim of cytoreductive surgery is to confirm the diagnosis, define the extent of disease, and resect all visible tumor. Surgery The type of procedure depends on whether or not disease is visible outside the ovaries. No disease should be visible outside the ovaries, and patients must be adequately surgically staged (including peritoneal cytology, multiple peritoneal biopsies, omentectomy, and pelvic and para-aortic lymph node sampling). Individualize surgery for patients with stage IV disease. The following are surgeries that may be performed in women with ovarian cancer: Surgical staging : the staging procedure should include the following:peritoneal cytology, multiple peritoneal biopsies, omentectomy, pelvic and para-aortic lymph node sampling. Cytoreductive surgery. According to the 2015 National Comprehensive Cancer Network (NCCN) [8] ovarian cancer guidelines, in newly diagnosed invasive epithelial ovarian cancer that involves the pelvis and upper abdomen, residual disease of less than 1 cm is evidence of optimal cytoreduction, although the greatest possible effort should be made to remove all obvious disease. The NCCN notes that one or more of the following procedures may be considered for optimal surgical cytoreduction : bowel resection and/or appendectomy, stripping of the diaphragm or other peritoneal surfaces, splenectomy, partial cystectomy and/or ureteroneocystotomy, partial hepatectomy, partial gastrectomy, cholecystectomy,distal pancreatectomy. Patients with advanced ovarian cancer are classified in three groups as follows, based on the postoperative residual tumor: - Good risk :Microscopic disease outside the pelvis (stage IIIa) or macroscopic disease less than 2 cm outside the pelvis (stage IIIb) - Intermediate risk : Macroscopic disease less than 2 cm outside the pelvis only after surgery - Poor risk : Macroscopic disease more than 2 cm after surgery or disease outside the peritoneal cavity Interval debulking. Interval debulking can be performed in patients whose cancer was not adequately debulked at the time of initial surgery. It should also be considered in those patients in whom an initial debulking surgery was not attempted. Patients receive three cycles of postoperative chemotherapy. Approximately 60% of patients are then able to undergo optimal resection. Surgical treatment is followed by three more cycles of chemotherapy. A prospective, randomized, clinical trial conducted in Europe demonstrated that this approach improves the outcome of patients with advanced ovarian cancer [9]. However, this was not confirmed in a study conducted in the United States [10].A major difference between both studies was the extent of the initial debulking procedure. In the US study, initial optimal debulking was attempted in all patients. A meta-analysis found no conclusive evidence regarding the possible survival benefit of interval debulking but noted apparent benefit only in patients whose primary surgery was not performed by gynecologic oncologists or was less extensive [11]. Laparoscopic surgery. According to guidelines developed by the American College of Obstetricians and Gynecologists, laparoscopy may be used for diagnostic purposes in a patient at low risk for ovarian cancer and to remove cystic masses. The mass must be 10 cm or smaller as viewed by a sonogram, must have a distinct border and no solid parts, and must
16 not be associated with ascites. The serum CA125 level must be normal (< 35 U/mL), and the patient must have no family history of ovarian cancer. If a chance exists that ovarian cancer may be present, surgery is best arranged in conjunction with a specialist in gynecologic cancer surgery. The patient can then undergo all necessary surgery for her cancer during a single anesthetic session, without delay. As part of initial treatment of epithelial ovarian cancer, laparoscopic surgery may be performed for early-stage disease when no disease is visible outside of the ovaries. Its use in more advanced disease, when spread is visible outside the ovaries, is more limited due to the scope of cytoreductive surgery necessary and the risk of port-site recurrence. Laparoscopy also has a role in second-look inspection and in the staging of apparently early-stage disease found by chance during another surgery. The 2015 NCCN ovarian cancer guidelines state that minimally invasive surgery may be used by an experienced surgeon in selected patients to achieve surgical staging and debulking. In addition, the NCCN considers that minimally invasive surgery may be useful when evaluating whether maximum cytoreduction can be achieved in patients with newly diagnosed or recurrent ovarian cancer [8]. Secondary surgery. An assessment by Park et al found that secondary cytoreductive surgery is safe and effective in patients with platinum-sensitive recurrent ovarian cancer. The surgery was most beneficial in patients who had remained disease free for more than 24 months after primary treatment and in those who achieved optimal cytoreduction [12]. Chemotherapy For primary chemotherapy, the National Comprehensive Cancer Network (NCCN) recommends three to six cycles of intravenous taxane/carboplatin adjuvant chemotherapy for high-risk stage IA, IB, or IC epithelial ovarian cancer. In stage II-IV disease, the recommended options include intraperitoneal chemotherapy, in patients with <1 cm optimally debulked stage II and III disease; or intravenous taxane/carboplatin for six to eight cycles. NCCN guidelines recommend that patients wishing to preserve fertility be referred to a fertility specialist prior to initiation of therapy [8]. For patients with stage II-IV disease who achieve complete remission with primary treatment, the NCCN recommends observation alone, participation in a clinical trial, or postremission paclitaxel (category 3) or pazopanib (category 2B). For a first recurrence, the NCCN prefers combination platinum-based chemotherapy. Agents for platinum-resistant disease include the following: Docetaxel Etoposide Gemcitabine Liposomal doxorubicin +/- bevacizumab Paclitaxel +/- bevacizumab Topotecan +/- bevacizuab Agents for targeted therapy include bevacizumab and olaparib. Hormonal therapy agents may include aromatase inhibitors, leuprolide, megestrol, or tamoxifen. Radiation therapy Radiation has not been widely accepted as a routine treatment modality in the initial treatment of patients with epithelial ovarian cancer, despite reports of efficacy for higher-risk stage I and II disease and in stage III disease where small-volume residual disease is present after surgery. In selected cases, pelvic diseases may respond to palliative dosing regimens with minimal toxicity.
17 7. LYMPHATIC SYSTEM The lymphatic system is a system of thin tubes and lymph nodes that run throughout the body. These tubes are called lymph vessels or lymphatic vessels. The lymph system is an important part of our immune system. It plays a role in fighting bacteria and other infections and destroying old or abnormal cells, such as cancer cells. The lymphatic system is similar to the blood circulation. The lymph vessels branch through all parts of the body like the arteries and veins that carry blood. But the lymphatic system tubes are much finer and carry a liquid called lymph. Lymph contains a high number of a type of white blood cells called lymphocytes that fight infection and destroy damaged or abnormal cells. As the blood circulates around the body, fluid leaks out from the blood vessels into the body tissues. This fluid carries food to the cells and bathes the body tissues to form tissue fluid. The fluid then collects waste products, bacteria, and damaged cells. It also collects any cancer cells if these are present. This fluid then drains into the lymph vessels. The lymph then flows through the lymph vessels into the lymph glands, which filter out any bacteria and damaged cells. From the lymph glands, the lymph moves into larger lymphatic vessels that join up. These eventually reach a very large lymph vessel at the base of the neck called the thoracic duct. The thoracic duct then empties the lymph back into the blood circulation.
Lymph nodes (lymph glands) The lymph glands are small bean shaped structures, also called lymph nodes.
Picture 3. Lymph node. ( https://en.wikipedia.org/wiki/Lymph_node )
There are lymph nodes in many parts of the body, including :
PELVIC LYMPH NODES Pelvic lymph nodes are two major groups: parietal, or parietal, sites, and splanchnic or visceral sites.Parietal nodes collect lymph from the walls of the pelvis and include external, internal iliac
18 and common nodes.
Lymphatic vessels and nodes of pelvis 1 -lumbar lymph nodes; 2 - external iliac lymph nodes; 3 - internal iliac lymph nodes; 4 - superficial inguinal lymph nodes; 5 - deep inguinal lymph nodes
Picture 4. Lymph nodes of pelvis.
Splanchnic sites serve internal organs, and are divided into okolopryamokishechnye, okolomochepuzyrnye, okolovlagalischnye and parauterine. Lymphatic vessels bound from the bladder to carry lymph external and internal iliac, lumbar and sacral lymph nodes. Lymph from the vagina and uterus is going to the lumbar nodes, superficial inguinal nodes, external and internal iliac and sacral lymph nodes. Of testicular and prostate cancer lymph node enters the lumbar, external and internal iliac lymph nodes. Superficial inguinal lymph nodes taken from the lymph vulva. Efferent vessels of the external and internal iliac nodes are sent to the common iliac lymph nodes from which the lymph enters the lumbar nodes.
AORTIC LYMPH NODES The paraaortic lymph nodes (also known as para-aortic, periaortic, peri-aortic, and lumbar) are a group of lymph nodes that lie in front of the lumbar vertebral bodies near the aorta. These lymph nodes receive drainage from the gastrointestinal tract and the abdominal organs. The paraaortic lymph node group is divided into three subgroups: preaortic, retroaortic, and right and left lateral aortic. The preaortic group drains the abdominal part of the gastrointestinal tract above the mid- rectum. The retroaortic group drains from the lateral and preaortic glands. The lateral group drains the iliac lymph nodes, the ovaries, and other pelvic organs. The lateral group nodes are located adjacent to the aorta, anterior to the spine, extending laterally to the edge of the psoas major muscles, and superiorly to the crura of the diaphragm. When dissected, the dissection usually includes the region from the bifurcation of the aorta to the superior mesenteric artery or the renal veins.
19
Picture 5. Aortic lymph nodes. (http://intranet.tdmu.edu.ua/data/kafedra/internal/anatomy/classes_stud/en/med/lik/ptn/2/31 LYMPHATIC VESSELS AND NODES OF ABDOMEN AND PELVIS..htm)
20
8. OVARIAN CANCER AND LYMPHADENECTOMY Epithelial ovarian cancers are the most lymphophilic tumors among the genital cancers. Ovarian cancer spreads via the retroperitoneal lymphatic channels, and these lymph nodes frequently contain metastasis. Lymphatic dissemination to the pelvic and para- aortic lymph nodes is common, particularly in an advanced stage disease [ 14-16 ]. Spread through the lymphatic channels of the diaphragm and through the retroperitoneal lymph nodes can lead to dissemination above the diaphragm, especially to the supraclavicular lymph nodes. Burghardt et al [16], perfomed systematic pelvic and para- aortic lymphadenectomy on 123 patients and reported that 78% of patients with stage III disease have metastases to the pelvic lymph nodes. In another series, the rates of positive para- aortic lymph nodes were 18% in stage I, 20% in stage II, 42% in stage III and 67% in stage IV [17]. The frequency of lymph node metastasis is real high, even in early stages. [18- 25,26,27]. In 1988, the International Federation of Gynecology and Obstretics (FIGO) published a surgical staging scheme for ovarian cancer that included pelvic and para- aortic lymph node sampling or lymphadenectomy. In general, sampling means the resection of single lymph nodes, mostly of bulky nodes, whereas systematic lymph node dissection is defined by the resection of enlarged and non- enlarged lymph nodes by the preparation of all pelvic and para- aortic lymph node regions. Systematic pelvic and paraaortal lymphadenectomy includes the removal of lymph nodes in specific areas such as : the upper para-aortic region above the inferior mesenterial artery (IMA), the lower para-aortic region between the IMA and the birfucation aortae, the inter-aorto-caval region, the right paracaval region, the ilica communis region, the iliaca externa region, the fossa obturatoria region and the iliaca interna region.
Picture 6. Para-aortic region with landmarks exposed. ( [55] )
21 8.1 LYMPHADENECTOMY FOR EARLY OVARIAN CANCER Few studies have shown any benefit of lymphadenectomy in patients with early stage disease. Tumor involvement of pelvis lymph nodes has been reported to occur in 5% - 14% of patients with pT1 disease and the para-aortic nodes are involved in 4%- 12%.
Table 2 . The frequency of lymph node metastasis in pT1 disease according to the stage and site. Stage (%) Stage (%) Stage (%) Positive Positive rate (%) rate (%) Aythor No. of Positive Ia Ib Ic PLN PAN patients rate (%) Sakuragi et 78 5.1 3.2 NA 6.4 0 5.1 al (2000) [26] Suzuki et 47 10.6 5.6 NA 13.8 8.5 4.3 al (2000) [28] Cass et al 96 14.5 - NA NA 9.4 7.3 (2001) [25] Takeshima 156 12.8 9.3 33.3 15.4 7.1 9.6 et al (2005) [27] Harter et al 48 6.2 0 25.0 8.0 NA NA (2007) [29] Fournier et 54 9.3 3.8 0 17.4 NA NA al (2009)[30] Nomura et 60 13.3 28.0 0 9.1 8.3 11.7 al (2010) [31] Mikami et 89 12.3 4 50 17.6 10.1 6.7 al (2014) [32] PAN, para- aortic lymph node, PLN, pelvic lymph node
Lymphatic spread of early stage ovarian cancer upstages the patient to FIGO stage III, making them appropriate canditates for adjuvant chemotherapy after surgery. The accurate assessment of lymph node metastasis and therefore, accurate staging of the tumor may be the main value of systematic lymphadenectomy. Also, when the initial surgical staging is correct, patients with low – risk disease may be spared from undergoing cytotoxic chemotherapy. In 2006, Maggioni and co-workers [33] published the first randomized study on the value of
22 systematic aortic and pelvic lymphadenectomy (SL) in comparison with lymph node sampling in ovarian cancer macroscopically confined to the pelvis. Overall, 268 out of 310 patients were randomized: 138 to systematic lymphadenectomy and 130 to lymph node sampling (control group). After a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95% CI=0.46-1.21, p=0.16) and death (HR=0.85, 95% CI=0.49-1.47, p=0.56) were lower, but in the SL group, were no more statistically significant than the control arm. Five-year progression-free survival for the control group and the SL group was 71.3 and 78.3% respectively, and 5-year overall survival was 81.3 and 84.2% , thus slightly favouring the SL group. These differences were, however, not significant.
Chan et al [34] ,conducted a large – scale retrospective study to assess the impact of lymphadenectomy on survival in patients with clinical stage I ovarian cancer. In 2007, Chan and co- workers reported a significant association of lymphadenectomy and overall survival in stage I ovarian cancer patients.Overall, 6,686 patients with stage I ovarian cancer were included in this analysis. The 5 year survival was significantly better in the group of patients with lymphadenectomy (92.6% compared to 87% , p<0.001). In 2008, Chan and co-workers [35], evaluated the progress and trends in the treatment and survival of women with early stage (I–II) epithelial ovarian cancer, again in relation to the SEER database. Of the 8,372 patients, a total of 6,152 patients (73.4% ) presented with stage I and 2,220 (26.5% ) with stage II disease. Over the periods 1988-1992, 1993- 1997, and 1998-2001, 3-year disease- specific survivals increased from 86.1 to 87.2 to 88.8% (p=0.076) (6). At the same time, the number of patients who underwent a lymphadenectomy also increased significantly from 26.2 to 38.7 to 54.2% over the study period (p<0.001). In conclusion, in early stage ovarian cancer, systematic lymph node dissection is required in order to perform accurate clinical staging and to select an adequate adjuvant chemotherapy. Nevertheless, the effect of lymph node dissection on progression-free survival and on overall survival is still unclear. There is no randomized controlled trial that shows any therapeutic efficacy of lympadenectomy.
23 8.2 LYMPHADENECTOMY FOR ADVANCED OVARIAN CANCER The first study documenting the incidence of lymph node involvement in patients with advanced ovarian cancer was published in 1966, by Bergman et al [36]. Chen et Lee reported on selective lymph node biopsies in 1983 [37]. In 1986, Burghardt and his group [38] in Graz reported on 82 patients with stage III ovarian cancer who had systematic pelvic lymphadenectomy and para-aortic lymph nodes sampling. The incidence of positive pelvic nodes was 78%. Para-aortic nodes were positive in 41.4% of cases, but only when pelvic nodes were also positive. Patients with negative nodes had a survival of 74.7%, compared to 45.9% for patients with positive nodes. The 5-year actuarial survival rate for patients with stage III disease was 53% after pelvic lymphadenectomy compared to 13% in those having no lymph node dissection. In 1991, Burghardt [39] published a second series based on systematic resection of both pelvic and para-aortic lymph nodes. Among 67 patients with stage III disease, 51% (34 of 67) had positive pelvic and paraaortic nodes, 13% (nine of 67) had positive pelvic but negative para-aortic nodes, and 13% (nine of 67) had positive para-aortic but negative pelvic nodes. Actuarial 5-year survival rates were 69% for patients with negative nodes, 58% for patients with one positive node, and 28% for patients with more than one positive node. Based on his own observations and that of others (Table 3), Burghardt concluded that ‘‘the rate of pelvic and para-aortic lymph node involvement in this disease is high and chemotherapy seems ineffective in eradicating tumor deposits in the nodes.’’ The data suggested that lymph nodes may act as a pharmacological sanctuary, and the issue at stake was whether or not there was any role for systematic pelvic and para-aortic lymphadenectomy in patients with advanced ovarian cancer, as opposed to just resecting bulky lymph nodes in order to reduce the extent of residual disease.
Table 3. Lymph node involvement in stage III epithelial ovarian cancer at primary or second-look surgery Primary operation Second- look
Author number positive % number positive % nodes nodes Burghardt et 70 55 79 12 9 75 al. [39] Di Re et al. 82 46 56 60 24 40 [40] Wu et al. 59 38 64 15 14 93 [41] Tulusan et 59 41 69 22 17 77 al. [42] Total 270 180 66 109 64 59
To evaluate the importance of lymphadenectomy in patients with advanced epithelial ovarian cancer, Kigawa et al. [43], in 1994, retrospectively assessed the outcome of 53 patients with stage III disease. The patients were divided into two groups, which were matched for age and postoperative chemotherapy, but differed in that one group received a retroperitoneal lymphadenectomy, including resection of para-aortic nodes, in addition to the standard primary
24 cytoreductive surgery. The 2-year survival rate for the group having the lymphadenectomy was significantly better than that for the other group, but the 5-year survival for both groups was the same. The 2-year survival rate for patients with positive nodes who underwent lymphadenectomy was similar to that of patients with negative nodes. Spirtos et al., in 1995 [44], reported a single arm, prospective study of planned pelvic and paraaortic lymphadenectomy in all patients with stages IIIa–IVa epithelial ovarian cancer in whom the largest residual intraperitoneal disease after primary cytoreduction was 1 cm. Fifty-six patients were entered onto the study with a median follow-up of 30 months; there was no significant difference in survival between patients with negative nodes (ten of 20, 50%), microscopically positive nodes (six of 13, 46%), or macroscopically positive but surgically resected nodes (ten of 23, 43%). The authors concluded that removal of grossly positive nodes was important, but that removal of macroscopically negative lymph nodes offered little benefit to the patients.The numbers are too small to draw any real conclusions, but the findings are basically consistent with those of Kigawa et al., the short-term survival of patients with positive nodes who underwent lymphadenectomy was similar to that of patients with negative nodes. Also in 1995, Scarabelli et al. [45], reported a case–control study of systematic pelvic and para- aortic lymphadenectomy for patients with stages IIIC–IV epithelial ovarian cancer who had ,2 cm residual diseasen on peritoneal surfaces following their cytoreductive surgery. There were 105 patients in the study, and they were subdivided into two groups depending on whether or not they had been pretreatedb with chemotherapy at another institution. Each group was statistically equivalent with respect to stage, histology, grade, age, performance status, largest diameter metastasis (.10 cm), type of surgery, and varietynof cytoreductive operations performed. Systematic lymphadenectomy significantly improved the survival of previously untreated patients (59% vs 16% at 2 years; P , 0.001), but not of pretreated patients. The following year, a retrospective study was reported by di Re et al. [46] of 488 patients with advanced ovarian cancer, of whom 248 patients (50.8%) had systematic lymphadenectomy as part of their primary cytoreduction, 80 (16.4%) had lymph node sampling, and 160 (32.8%) had no lymphadenectomy. For patients having both optimal and suboptimal cytoreduction in the peritoneal cavity, there was a significant benefit in terms of median 5-year survival for patients having lymphadenectomy. These studies were certainly provocative and did support the hypothesis that the retroperitoneal lymph nodes may act as a pharmacological sanctuary. However, the studies were not randomized.In addition, Onda et al. [47] reported that patients who had stage III disease only on the basis of positive retroperitoneal lymph nodes had an 84% 5-year survival, which was significantly better than the survival for patients with stage III disease on the basis of intraperitoneal spread. This was not consistent with the poor survival for patients with positive nodes reported by Burghardt.
The first prospective randomized study looking at the role of systematic retroperitoneal lymphadenectomy in patients with advanced ovarian cancer was published in 2005, by Maggioni et al [48]. It was an international study which was restricted to patients with stages IIIb/c and Iva epithelial ovarian cancer, and residual intraperitoneal nodules 1 cm in diameter after primary cytoreductive surgery. These patients were randomized to systematic pelvic and para-aortic lymphadenectomy, or resection of bulky nodes only. Nodes were considered bulky if they were 1 cm in diameter. In the lymphadenectomy arm, patients had to have resection of 25 pelvic nodes and 15 para-aortic nodes. There were 452 patients recruited to the study from 13 centers in five countries, of whom 427 were eligible for intention-to-treat analysis—211 in the control arm and 216 in the lymphadenectomy arm. The two arms were well matched with respect to age, stage, residual disease, tumor grade, and cell type. A median of four nodes were removed in the control arm and 51.5 in the lymphadenectomy arm. Median operating time was 90 min longer in the lymphadenectomy arm and
25 blood loss 350 mL greater, but postoperative hospital stay was the same in both arms (9 days). Intraoperative morbidity was also the same in both arms, but postoperative morbidity was higher in the lymphadenectomy arm because of the increased frequency of lymphocytes and lymphedema. After a median follow-up of 68.4 months, there was a 7-month benefit in progression-free survival for patients in the lymphadenectomy arm (29.4 vs 22.4 months) but no benefit in terms of overall survival.
At the International Gynaecological Cancer Society meeting in Santa Monica in late 2006, Du Bois et al. [49] reported on a retrospective analysis of three chemotherapy trials (OVAR 3, OVAR 5, and OVAR 7). A total of 3,336 patients were entered into these three trials, of whom 1059 (32%) had no residual disease following primary cytoreductive surgery. Of these patients, 757 (72%) had some extent of lymphadenectomy. The 5-year survival for patients having a lymphadenectomy was 66%, compared to 55% for patients having no lymphadenectomy (P = 0.003). Interestingly, there was no significant survival advantage for patients having a lymphadenectomy if there was any residual disease at all in the peritoneal cavity, which is consistent with the large prospective study(Maggioni et al).
In addition, in 2006, Aletti and co- workers [50], reported on a series og 219 patients with advanced ovarian cancer. A surgical lymph node assessment was perfomed on 93 ( 41% ) of the patients : in 61 cases as systematic lymphadenectomy (LND) and in 32 as sampling (LNS). Overall 5- year survival was 26 %. In patients with optimal cytoreduction with more systematic lymphadenectomy , the 5- year overall survival was 50 %, in contrast to 33% in the sampling collective, and only 29% in patients without any lymphadenectomy. In the poatient cohort with residual disease, no association between the type of lymph node dissection and the clinical outcome was observed. Chan and co-workers [51] have explored the SEER database concerning the impact of lymph node dissection on the clinical outcome (2007). Of 13,918 women with stage III–IV epithelial ovarian cancer, a total of 4,260 (30.6% ) underwent lymph node dissections with a median number of six resected nodes. For all patients, a more extensive lymph node dissection (0, 1, 2-5, 6-10, 11-20, and >20 nodes) was associated with an improved 5-year disease-specific survival of 26.1, 35.2, 42.6, 48.4, 47.5, and 47.8% , respectively (p<0.001). Of the stage IIIC patients with nodal metastasis, the extent of nodal resection (1, 2-5, 6-10, 11-20, and >20 nodes) was associated with improved survival of 36.9, 45.0, 47.8, 48.7, and 51.1% , respectively (p=0.023). On multivariate analysis, the extent of lymph node dissection and number of positive nodes were significant independent prognostic factors adjusting for age, year at diagnosis, stage, and grade of disease. Since then, several studies have been conducted, but the efficacy of systematic lymphadenectomy remains highly controversial [52-55]. Japan Society of Gynecologic Oncology recently revised its Ovarian Cancer Treatment Guidelines ( Mikiami, 2014) [32]. This Guidelines state that lymphadenectomy, in patients with advanced stage tumors, should be concidered if optimal debuliking has been performed. In their series, patients with small residual tumor (<1 cm) who underwent complete pelvic and para- aortic node dissection showed better overall survival than those who underwent only pelvic node dissection or those who did not undergo lymph node resection (p<0.001).
26
Diagram 1. Overall survival of patients with FIGO III- IV with residual tumor < 1 cm according to the performance of lymphadenectomy.
The same year, Yang et al [56], reported a meta- analysis of multiple epidemiology studies. The wanted to evaluate the role of systematic lymphadenectomy in epithelial ovarian cancer by comparing 5- year overall survival rates between systematic and unsystematic lymphadenectomies. Fourteen relevant studies including 3488 subjects were included in the analysis. The value of pooled relative ratios of all qualified studies revealed tha the 5- year overall survival rate in the lymphadenectomy group was higher than that in the unsystematic lymphadenectomy group ( relative ratio= 1.08, P= 0.001), which was duplicated in the subgroup analysis of observational studies ( relative ratio=1.07, P=0.002) and advanced stage ( relative ratio= 1.21.P= 0.012) epithelial ovarian cancer. No sugnificant differencies were observed in randomised controlled trials ( relative ratio=1.01,P=0.0858), early stage epithelial ovarian cancer( relative ratio= 1.06, P=0.064) or patients with residual tumor < 2 cm ( relative ratio=1.05, P=0.125).
In conclusion, systematic pelvic and para-aortic lymphadenectomy should be performed in all patients who are likely to achieve optimal cytoreduction. For advanced cancer with minimal tumour residuals of up to 10mm, systematic lymphadenectomy will produce a significant benefit in progression- free survival, and may can improve the 5- year overall survival. However, the German AGO study group has initiated a large international trial (LION) [57] in an attempt to answer the clinically relevant question of whether systematic lymph node dissection does indeed influence the overall survival in advanced ovarian cancer. In this trial, patients with advanced ovarian cancer aged 18-75 are randomly allocated to one of two groups.One group,with no gross residual disease and no bulky nodes, undergoes standard surgery for advanced ovarian cancer without lymphadenectomy, while the other group undergoes standard surgery and lymphadenectomy. Patient survival, quality of life and complications are assessed in the two groups. Until, results become unavailable, patients with advanced ovarian cancer shoud be informed in detail about the pros and cons of lymph node dissection.
27 PART II MINIMALLY INVASINE LYMPHADENECTOMY IN OVARIAN CANCER
9.MINIMALLY-INVASIVE SURGERY 9.1 Introduction Minimally-invasive procedures (also known as minimally-invasive surgeries - MIS) have been enabled by the advance of various medical technologies. Surgery by definition is invasive and many operations requiring incisions of some size, are referred to as open surgery. Incisions made can sometimes leave large wounds that are painful and take a long time to heal. Minimally-invasive surgery refers to surgical techniques that limit the size of incisions needed and so lessens wound healing time, associated pain and risk of infection. Typically, MIS involves small incisions, usually 0.1 – 1.5 cm, and includes laparoscopic, laparoscopically assisted, robotic, thoracoscopic, and endoscopic surgical procedures. Special medical equipment may be used, such as fiber optic cables, miniature video cameras and special surgical instruments handled via tubes inserted into the body through small openings in its surface. The images of the interior of the body are transmitted to an external video monitor and the surgeon has the possibility of making a diagnosis, visually identifying internal features and acting surgically on them. Minimally invasive surgery is the most important revolution in surgical technique since the early 1900s. Until 1950, gynecologists were considered the first movers. Since 1985, laparoscopic cholocystectomy was widely accepted, and several others procedures are now well established. In 2001[59], a complete tele-surgical operation was performed successfully by Professor Jacques Marescaux and his team in Strasbourg, which is called the Lindbergh operation. The procedure consisted of a cholecystectomy on a 68-year-old female patient in surgical ward A in Strasbourg Civil Hospital, in Eastern France. From New York, the surgeon controlled the arms of the ZEUS Robotic Surgical System, designed by Computer Motion, to operate on the patient. The link between the robotic system and the surgeon was provided by a high-speed fiberoptic service deployed thanks to the combined efforts of several France Telecom group entities.
Picture7. Transatlantic robot-assisted telesurgery. (https://rctom.hbs.org/submission/the-doctor-is-in-remote-surgery-in-the-digital-age/)
28 9.2 Benefits of minimally-invasive procedures
A completely non-invasive local therapy would require less anaesthesia, would reduce recovery time, could avoid infections and scar formation, and possibly also reduce cost [60]. Using minimally invasive surgery (MIS) techniques, offers patients many benefits over traditional surgeries. They include:
Less Pain MIS procedures cause less post-operative pain and discomfort. Studies have shown that patients undergoing MIS procedures report less pain and require smaller doses of pain relievers than patients undergoing traditional surgeries.
Shorter Hospital Stay Shorter hospital stay and quicker return to normal activities. Patients who undergo MIS procedures are usually able to go home sooner. And, in many cases, the patient is able to return to normal activities and work more quickly.
Less Scarring MIS procedures require a smaller incision -which means smaller, less noticeable scars. The scars that do form as a result of MIS typically have a less jagged edge - giving them a more appealing look.
Less Injury to Tissue Most traditional surgeries require a long incision. This incision usually has to be made through muscle. Muscle needs a significant time to heal after surgery. Because there are no long incisions in MIS, surgeons often do not have to cut through muscles to complete the procedure - leading to less tissue damage and quicker recovery.
Higher Accuracy Rate A higher accuracy rate for most procedures. Because MIS procedures use video-assisted equipment, the surgeon has better visualization and magnification of internal organs and structure. For patients, this translates into a more accurate and definitive procedure.
29 10. LAPAROSCOPIC LYMPHADENECTOMY
Laparoscopic pelvic lymphadenectomy was first described in 1989 by Querleu et al [61]. In 1991, in France, Querleu et al [62], reported an initial experience for laparoscopic surgical staging with pelvic and/or aortic node dissection for gynecologic cancers. In 1990, there was a relative case report by Reich et al [63]. A woman with stage I ovarian cancer refused traditional treatment and was managed laparoscopically. Both ovaries were removed intact via a culdotomy incision. Vaginal hysterectomy, omentectomy and laparoscopic lymphadenectomy followed. In 1993, Querleu et al [64], reported a preliminary experience for laparoscopic para-aortic node sampling. Selective sampling of the lower para-aortic nodes in two cases of cervical carcinoma and of the infrarenal para-aortic nodes in two cases of early ovarian carcinoma were successfully completed by laparoscopy . Next year, [65] he tried to investigate the feasibility of laparoscopic para-aortic lymphadenectomy in the restaging of ovarian carcinomas. Nine patients with ovarian carcinoma ( eight patients) and tubal (one patient) carcinoma who had experienced substandard staging during a previous laparotomy or laparoscopy, underwent laparoscopis paraaortic lymphadenectomy as part of a surgical staging procedure that includes peritoneal fluid sampling and other biopsies. Omentectomy, appendectomy, pelvic lymphadenectomy, salpingo- oophorectomy, salpinge ctomy or laparoscopically vaginal hysterectomy was perfomed during the same session when necessary. All nine lymphadenectomies up to the level of the renal veins were successfully completed. So, laparoscopic procedure seemed to be an acceptable surgical approach for para-aortic lymph node sampling. Since then, many investigators have adopted the laparoscopic surgical approach for many gynecologic malignancies and tried to demonstrate the feasibility of this technique [66-83]. In the table bellow we can see a summary of laparoscopic pelvic and aortic dissections in the management of gynecologic malignancies and the mean number of the nodes yielded.
Table 4. Laparoscopic pelvic and aortic dissections - PLN: pelvic lymphadenectomy – PAN : para- aortic lymphadenectomy.
Author Number of patients PLN PAN Reich (1990) [63] 1 with ovarian cancer 11 (only left) Not done Querleu et al (1991) 39 8.7 - [62] Querleu et al (1993) 2 with ovarian cancer 12 9 [64] Querleu et al (1994) 8 with ovarian cancer Not indicated 8.6 (5-17) [65] Pomel et al (1995) [66] 10 with ovarian cancer 6 (4-13), homolateral 8 (7-9), homolateral Spirtos et al (1995) [67] Su et al (1995) [68] 38 15 - Chu et al (1997) [69] 67 26.7 8 Possover et al (1998) 150 26.8 7.3 [70] Vidaurreta et al (1999) 84 18.5 -
30 [71] Dottino et al (1999) 94 11.9 3.7 [72] Altgassen et al (2000) 108 21-24.3 5.1-10.6 [73] Scribner et al (2001) 103 23.2 6.8 [74] Schlaerth et al (2002) 67 32.1 12.1 [75] Vergote et al (2002) 42 - 6 [76] Spirtos et al (2002) 84 23.8 10.3 [77] Chi D et al (2003) [78] 114 10.3 5.3
In 2004, Κοhler et al [83], reported an anlysis of 650 laparoscopic pelvic and/or para-aortic transperitoneal lymphadenectomies, between August 1994 and September 2003, and they concluded that with this technique an adequate number of lymph nodes can be removed in an adequate time and indepent from body mass index. The complication rate was low and could be minimized by standarization of the procedure. The techniques of laparoscopic lymphadenectomy and their developments during the years, are described at the follwing topics.
31 10.1 LAPAROSCOPIC PROCEDURE
Picture 8. Abdominal entry. ( [84] ) The laparoscopic procedure [84] begins with the introduction of the laparoscope. Techniques for placement of the initial trocar ( open versus direct insertion versus pneumoperitoneum ) vary depending on surgeon preference but, in general, the laparoscope is placed through an umbilical port. Some practitioners believe that the open laparoscopic technique can minimize the risk of injury to underlying tissues, particularly in the patient who has undergone prior abdominal or pelvic surgery.
Picture 9. Inferior epigastric vessels. ( [84] ) After the introduction of the laparoscope, accessory trocars must be placed. The placement of the
32 lateral accessory trocars is crucial, since improper placement can make the procedure difficult. Given that the procedure requires access to both the abdomen and the pelvis , accessory trocars are usually placed in a position lateral to the inferior epigastric vessels and rectus muscles. These vessels should be visualized before introduction of the lateral trocars. Indentification of the inferior epigastric vessels can be aided by simple external pressure applied in the inguinal region, which distends the vessels.
Picture 10. Placement of accessory trocars. ( [84] ) The size of the accessory trocars depends on the diameter of the instruments tha the surgeon prefers to use. Several fundamental principles should be adhered to when placing any sized trocar : the insertion should be under direct visualization and the direction of insertion shoud be perpendicular to the abdominal wall to avoid “tunneling”.
Picture 11. Trocars in situ. ( [84] )
33 One of several final trocar configurations is shown here. The procedure can be conducted through reusable or disposable trocars. The reusable trocars certainly provide cost savings over time time. However, lymph node removal is often more efficient with disposable trocars that have superior vents and caps. Five millimeter lateral trocars, which can accommodate many instruments, are shown in this figure. Whwn larger devices such as argon- beam coagulator or the endoscopic stapler are used, these lateral trocars are replaced with larger diameter trocars.
Picture12. Laparoscopic inspection of the pelvis. ( [84] )
The procedure begins with a thorough exploration of the pelvic structures. The pelvic organs and peritoneal surfaces should be carefully examined. Laparoscopy is helpful in examinig these surfaces since the surgeon's view is magnified.
Picture 13. Survey of the abdomen. ( [84] ) Picture 14. View of the left lobe of the liver and left diaphragm. ( [84] )
34 Once the pelvic inspection is completed, the upper adbomen should be inspected for metastatic disease. This should be done systematically, usually starting from the cecum in the right lower quadrant and working up the paracolic gutter toward the hepatic flexure where the gallblader can be inspected. Next, the transverse colon and omentum should be examined, foollowed by the descending colon, left paracolic gutter, and the sigmoid colon. The small bowel should also be inspected in its entirety. The intestinal surfaces are examined closely. Both the right and left diaphragms and the liver surface should be scrutinized for evidence of disease. The laparoscopic view facilitates this portion of the exploration of the upper abdomen.
Picture 15. Peritoneal washings. ( [84] )
Prior to commencing any portion of the dissection, peritoneal cytology should be obtained. If peritoneal fluid is present, this can be aspirated. If there is no obvious peritoneal fluid, washings should be obtained by irrigating the abdomen and the pelvis and then, aspirating the fluid. The fluid is aspirated from the most dependent portion of the pelvis in order to remove the irrigation completely and obtain a representative sample.
35 10.2 LAPAROSCOPIC PELVIC LYMPHADENECTOMY Procedure
Picture 16. Begining the pelvic lymph node dissection. ( [84] ) In this procedure, the dissection is performed with the argonbeam coagulator [84,85]. However, other forms of energy ( bipolar, monopolar, ultrasound ) can be used. The pelvic lymph node dissection begins by identifying the round ligament. This is grasped with a forceps to tent the posterior leaf of the broad ligament. Alternatively, a uterine manipulator is used to create tension on the broad ligament.
Picture 17. Opening the posterior leaf of the broad ligament. ( [84] )
36 Making an incision parallel to the round ligament opens the posterior leaf of the broad ligament. This incision is started laterally and continued medially towards the uterus. A second incision is made parallel to the infundibulopelvic ligament. This two- incision technique provides ample access to the retroperitoneum. When complete, all intervening peritoneum has been dissected away from the round ligament and the infundibulopelvic ligament.
Picture 18. Identifying the external iliac artery. ( [84] )
Prior to removing the lymphatic tissue, the external iliac artery should be clearly identified. This can be done with gentle blunt dissection using atraumatic forceps or the tip of the argon- beam coagulator. Identifying normal anatomic structures is an important way of minimizing vascular complications during pelvic or paraaortic lymph node dissections.
Picture 19. Dissecting the external iliac lymph nodes. ( [84] )
The lymphatic tissue can be dissected off the underlying vessels by grasping the tissue and placing it under tension. The argon- beam coagulator is used to bluntly free the lymphatic tissue and apply coagulation when hemostasis is required. The lymphatic tissue may be retracted laterally or medially to provide the best orientation for lymph node removal. This will be dependent upon the
37 location of the lymphatic tissue , as well as the orientation of the instruments.
Picture20. Distal limit of the external iliac dissection. ( [84] )
The distant extent of the external iliac dissection is the deep circumflex iliac vein. Normally, the circumflex iliac vein passes over the external iliac artery, but in certain cases the vein may oass beneath the artery. Removal of the nodal tissue surrounding the external iliac vessels should procced with caution in this region, as injury to these vessels may be difficult to control.
Picture 21. Identifying the external iliac vein. ( [84] )
After the nodal tissue from the external iliac artery has been removed, the external iliac vein should be identified. Once again, this can be done with careful dissection, using atraumatic forcps or the tip of the argon- beam coagulator. The picture above, illustrates the identification of the left external iliac vein , just below the artery.
38
Picture 22. Removing nodal tissue from the external iliac vein. ( [84] )
The surrounding nodal tissue can be grasped and dissected free using the argon- beam coagulator. Since the wall of the vein is pliable, it can easily be damaged if one is not careful during the dissection. Additionally, carbon dioxide gas that has been used to insufflate the peritoneum often compresses the vein. Since the argon- beam coagulator will deliver a short stream of electrical current, care should also be taken to ensure that the energy is not misdirected into one of the vascular structures.
Picture23. Exposing the obturator space. ( [84] )
After the external iliac vessels have been cleaned of the surrounding lymphatic tissue, they can retracted medially to expose the obturator space. This must be done carefully, so as not to disrupt the networks of veins that inhabit the obturator space. If the external vessels have been thoroughly cleaned from the bifyrcation of the common iliac vessels down to the deep circuflex iliac vein, they
39 will have sufficient mobility to permit adequate access to the obturator space.
Picture 24. Identifying the obturator nerve. ( [84] ) After exposing the obturator space, the obturator nerve must be identifying before attempting to remove any lymphatic tissue. The nerve can be identified with gentle blunt dissection of the lymphatic tissue in the obturator space. Once, the nerve has been identified, the lymphatic tissue can be grasped and elevated away from it. The argon- beam coagulator can now be used safely to free the nodal package from its attachments.
Picture25. Final dissection of the obturator space. ( [84] )
40 The last remaining nodal tissue can be easily removed from the obturator space once the nerve and the obturator muscle are visualized. The artery and vein lie below the obturator nerve, so caution must be used when dissecting in this region.
Picture 26. Medial approach to the obturator nodes. ( [84] )
An alternative approach to removing the obturator nodes is to expose the space from the medial aspect. This is done by retracting the iliac vessels laterally and gently dissecting through the fatty lymphatic tissue to identify the obturator nerve. If the nerve is difficult to identify by one approach ( medial or lateral ) then alternative approach may prove more fruitful.
Picture 27. Removing the obturator nodes by a medial approach. ( [84] )
The lymph nodes above the obturator nerve and below the external iliac vein can be grasped and dissected using a combination of blunt dissection and coagulation.
41
Picture 28. Completed pelvic lymphadenectomy. ( [84] )
Once the pelvic lymphadenectomy is complete, no further lymph node tissue is visible. The medial view of the obturator space dissection shows that all the nodal tissue has been removed and that the normal anatomic structures remain. From the lateral approach, many of the same structures are visible. However, the most lateral aspect of the deep pelvic sidewall is not seen. The external iliac artery and vein are completely seperated from one another.
42 10.3 LAPAROSCOPIC PARA- AORTIC LYMPHADENECTOMY
10.3.1 Anatomy and surgical procedures for para-aortic lymphadenectomy Para-aortic lymph nodes in the gynecologic oncologic field are subgrouped into b1 and b2 lymph nodes; b1 lymph nodes are the located between the lower margin of the left renal vein and the upper margin of the inferior mesenteric artery (IMA), whereas b2 lymph nodes are located between the upper margin of the IMA and the bifurcation of the abdominal aorta. The procedure of para-aortic lymphadenectomy is divided into two types: right-sided and left-sided para-aortic lymphadenectomy with respect to the center of the aorta. Right-sided para-aortic lymphadenectomy is performed by dissecting the lymph nodes of the precaval and paracaval area up to the level of the origin of the right ovarian vein in the inferior vena cava (IVC) or the right renal vein. Conversely, left-sided para-aortic lymphadenectomy is performed by dissecting the lymph nodes on the aorta from the level of bifurcation to the left renal vein. The abdominal aorta has important branch vessels, such as the renal artery, ovarian artery, IMA, lumbar artery, and median sacral artery, and has variations as well. The IVC also has variations. Possover et al, in 1998 [86], evaluated the anatomy of the infrarenal portion of the IVC by dividing it into three portions: Level 1 is the area of the bifurcation of the vena cava, Level 2 is the area between the bifurcation and the IMA, and Level 3 is the area between the IMA and the right ovarian vein. The mean numbers of tributaries were 3 in Level 1, 1.7 in Level 2, and 1 in Level 3. The most important and basic requirements of lymphadenectomy are the maintenance of a clear surgical field and precise anatomy of vessels in case of an accidental injury. In case of a vessel injury, compression by a gauze to decrease the bleeding is necessary. Then skeletonization of the vessel following the detection of the bleeding point has to be performed. If the procedures prove difficult, the use of a hemostatic agent can be considered. An injury of a larger vessel may require suture repair with monofilament and nonabsorbable sutures. Removal of positive lymph nodes has to be performed taking care not to cause any injury to the main vessels, especially the IVC, due to affluent artery and vein to lymph nodes.
10.3.2 APPROACHES
There are two approaches to para-aortic lymphadenectomy: transperitoneal and extraperitoneal. The transperitoneal approach offers a greater working space and familiar landmarks, but sometimes requires bowel mobilization. The advantages of the extraperitoneal approach include operative feasibility in spite of previous abdominal surgery, decreased risk of direct bowel injury, and bowel adhesion formation. The disadvantages are a small working space, limited landmarks, and the risk of becoming disoriented [87].
43 A) TRANSPERITONEAL Childers et al [88], introduced transperitoneal para-aortic lymphadenectomy using four trocars. One large 10-mm trocar was placed in the umbilicus and one in the midline near the symphysis pubis. Two 5-mm trocars were placed laterally midway between the umbilicus and the anterior superior iliac crest. Since the evolution of this approach, many authors have used five trocars: one at the umbilicus, one at the suprapubic area, two at the lower quadrants, and a 10-mm trocar at the left upper quadrant, which is used as a retractor or for removal of lymph nodes [89,90]. In another report, Lee et al [91,92], reported the efficiency with five trocars (two 10-mm and three 5-mm). The 10-mm laparoscope was introduced at the midpoint between the umbilicus and the xiphoid process (Lee–Huang point), and all other ancillary ports were inserted laterally. They reported the safety and feasibility in the field of gynecologic malignancies [92,93].
Picture 29. Trocar placements for transperitoneal paraaortic lymphadenectomy. ( [199] )
Procedure
Picture30. Preparation for the paraaortic lymph node dissection. ( [84] )
Following the pelvic lymph node [84], attention is turned to the paraaortic region. In preparation for
44 the paraaortic lymph node dissection, the small bowel should be backed into the left upper quadrant to expose the aortic bifurcation. Meticulous packing of the bowel will facilitate the dissection.
Picture 31. Opening the peritoneum. ( [84] )
The transperitoneal paraaortic lymph node dissection is begun by identifying the right common iliac artery. The peritoneum over the artery is tented up with a grasper and is incised with thw argon- beam coagulator or similar istrument. Once the peritoneum has been incised, the incision is extended cephalad from the right common iliac artery to the bifurcation of the aorta. The pneumoperitoneum may help with the dissection – when gas enters the retroperitoneal space it helps elevate the posterior peritoneum off the underlying vessels.
Picture 32. Identification of the right ureter. ( [84] )
Prior to beginning the right paraaortic dissection, the right ureter must be identified and retracted laterally. This entails elavating the posterior peritoneum while exploring, with blunt dissection, the retroperitoneal space lateral to the right common iliac artery. Once ureter is identified, it can be moved out of the operative field.
Picture33. Beginning the right paraaortic dissection. ( [84] )
The nodal tissue overlying the vena cava is grasped and elevated. Using gentle blunt dissection this tissue is seperated from the underlying vessel. The vena cava should be clearly identified before any
45 attempt is made to remove the lymphatic tissue.
Picture 34. Removing the right paraaortic lymph nodes. ( [84] )
Once the vena cava has been identified, the process of removing the overlying lymphatic tissue can begin. This region has many perforating vessels from the vena cava to the lymphatic tissue. These small vessels should be coagulated prior to removing the nodal package. The lymphatic tissue is elevated with a laparoscopic grasper ; pedicles are created with the argon- beam coagulator or another blunt- tipped instrument. The base of these nodal packets is then transected with cautery.
Picture 35. Identifying the “ fellow' s vein ” . ( [84] ) The precaval lymphatic package contains the fellow' s vein. Avulsing this vessel can lead to profuse bleeding, that may be difficult to control laparoscopically. As the nodal package is dissected from the vena cava, the surgeon must note the presence of this vessel. Once the vessel is identified, it should be clipped or coagulated and cut.
Picture 36. Removing the lateral caval nodes. ( [84] )
Lymph nodes lateral to the vena cava are removed in similar fashion. They are grasped and dissected off the vena cava using blunt dissection and coagulation with the argon- beam coagulator.
46 Careful attention should be given to the location of the ureter and the underlying lumbar veins.
Picture 37. Identification of the right ovarian vein. ( [84] )
The precaval and lateral caval lymph nodes are removed to the level of the right ovarian vein. This is important given the drainage pattern of the right ovary. The lymphatic tissue typically runs in the same direction as venous drainage. The insertion of the ovarian veins is the prime landing zone for nodal metastases. If the dissection is not carried up to this level, important sites of metastatic disease may be overlooked.
Picture 38. Removing interaortocaval lymph nodes. ( [84] )
The interaortocaval lymph nodes are removed in similar fashion. They are grasped and elevated off the aorta. The aorta is visualized, and the nodes are removed using a combination of blunt dissection and coagulation.
47
Picture 39. Begging the left paraaortic dissection. ( [84] ) The left-sided dissection can be more challenging. This is in part due to the presence of the inferior mesenteric artery. Prior to beginning, the left ureter should be identified and pushed laterally.
Picture 40. Removing the left paraaortic lymph nodes. ( [84] ) After retracting the left ureter laterally, dissection can be undertaken. The nodal packages are elevated with laparoscopic grasping forceps as described previously. The coagulator can be used to create pedicles that can then be detached from the aorta.
Picture 41. Superior aspect of the dissection. ( [84] ) The inferior mesenteric artery is usually surrounded by lymphatic tissue and should be cleared to
48 identify it unmistakably to avoid injuring this vessel, and to ensure that the dissection is carried out high enough. In ovarian cancer the upper limit of the dissection is the left renal vein.
Picture 42. Removing the subaortic lymph nodes. ( [84] ) The subaortic lymph nodes can be removed using a similar technique to that described previously. This nodal package overlies the left common iliac vein. There may be some vascular connections to the nodal package and thus this area must be approached with caution. The lymph nodes should be fully freed from the vein to prevent tearing during nodal removal. The dissection should be perfomed carefully, so that the underlying vascular structure is not punctured or lacerated. Not being aware of this anatomic relationship can lead to serious injury to the left common iliac vein, resulting in a potential life – threatening hemorrhage.
Picture 43. Removing the specimens. ( [84] ) The harvested lymph nodes may be removed directly throygh the trocar using a strong reliable grasper. Larger lymph node packets, or those suspicious for metastatic disease, may be removed in an andoscopic bag. The bag can be removed through a large diameter trocar ( 10 or 12 mm) or if a hysterectomy is to be perfomed as part of the procedure, placed into the pouch of Douglas and removed at the time of vaginal colpotomy.
49
Picture 44. Completed dissection. ( [84] ) This figure illustrates the completed paraaortic dissection to the level of the inferior mesenteric artery (IMA). The left paraaortic lymph nodes will be found between the IMA and the aorta, as well as lateral to the IMA.
Infrarenal left- sided lymphadenectomy For patients with ovarian cancer para-aortic lymphadenectomy up to the level of the renal vessels is standard of care. In 2003, Kohler et al [89], tried to evaluate whether left-sided para-aortic inframesenteric lymphadenectomy can be extended up to the left renal vein by laparoscopy. In this study, 46 consecutive patients with cervical (n = 26), or endometrial (n =16), or early ovarian cancer (n = 4) underwent right-sided paraaortic lymphadenectomy up to the level of the right ovarian vein and left-sided inframesenteric paraaortic lymphadenectomy. Lymphadenectomy was extended up to the level of the left renal vein in 20 patients with high risk for lymph node metastasis. Patients were seperated into two groups : patients with infrarenal lymphadenectomy ( group 1 ) akd patients without infrarenal lymphadenectomy ( group 2 ). Duration of lymphadenectomy was 31.3 min longer in group 1. Number of para-aortic lymph nodes was on average 19.6 in group 1, compared to a mean of 9 nodes in group 2.
Description of the technique Infrarenal left-sided lymphadenectomy is started by mobilizing and elevating duodenum and pancreas. The surgeon holds an atraumatic grasping forceps in the right hand (left 5 mm trocar) and a 1.5-mm bipolar coagulation forceps in the left hand (middle 5 mm trocar). The first assistant holds an atraumatic grasping forceps in the left hand (right 5 mm trocar) and the optic (10 mm trocar— umbilicus) with mounted camera in the right hand. The second assistant uses an atraumatic 10-mm grasping forceps (10 mm trocar—left upper abdomen). Both assistants form a “tent” by elevating the peritoneum, the ascending and descending mesocolon, and the duodenum.
50
Picture 45. Peritoneum, ascending and descending mesocolon, duodenum, and pancreas are elevated and a “tent” is formed. The argin of the tent is marked as a green line. ( [89] )
By form such a tent all small bowel can be retained in the upper abdomen. Lymph nodes along the vena cava are mobilized in cranial direction starting at the level of the right ovarian vein. Preventively small blood and lymph vessels are coagulated to ensure a dry operating field. The confluence of the left renal vein and the vena cava is identified and the upper border of the renal vein is the cranial limit of lymphadenectomy. Dissection is now carried out laterally following the left renal vein. While doing so the preaortic lymph node and fat tissue are not dissected at this point in order to ensure en bloc resection of lymph nodes.
51 Picture 46. The confluence of the left renal vein and the vena cava is shown. The arrows show the direction of the dissection following first the vena cava and then the left renal vein. ( [89] )
The left ovarian vein is identified underneath the mesocolon descendence and the confluence of left ovarian and renal vein is freed of surrounding tissue. The left ureter is identified and pushed laterally. If this procedure proves difficult the inframesenteric part of the ureter where it crosses the common iliac vessels is identified and the ureter can be easily followed cranially. The ureter and left ovarian vein form the lateral border of lymph node dissection. The lymph node tissue is dissected away from the inferior mesenteric artery. Thus, the inferior mesenteric artery is isolated over a distance of 2 cm and can be preserved.
The lymph node and fat tissue are dissected away from the anterior and lateral aspect of the aorta up to the level of the left renal vein. The lymph nodes en bloc removed and the at tissue are placed in an endobag which is retrieved through the upper 10-mm trocar. The upper limit of infrarenal lymphadenectomy is marked with clips for planning radiation. Lymphadenectomy in the area of the renal vessels has to be done carefully due to possible vessel abnormities.
52
Picture 47. Dissection is done following the left ovarian vein toward the renal vein (superior arrow) and toward the origin of the inferior mesenteric artery (inferior arrow). ( [89] )
Picture 48. Final situs following infrarenal paraaortic lymphadenectomy. For better demonstration only the origins of the ovarian arteries are shown. ( [89] )
53
Picture 49.Final situs following laparoscopic transperitoneal infrarenal paraaortic lymphadenectomy. Vena cava (1) and aorta (2) have been completely isolated from the lymphatic tissue. Confluence of right ovarian vein (3) and vena cava and of left ovarian vein (4) and left renal vein (5) are visible. The inferior mesenteric artery (6) has been isolated and preserved. ( [89] )
Picture 50. Anatomic variation of the left renal vein (1) which lies dorsally to the aorta (2). The left ovarian vein (3), the right (4) and the left (5) renal artery, and the inferior mesenteric artery (6) can easily be seen. ( [89] )
Kohler et al, demonstrated that left-sided para-aortic lymphadenectomy could be performed safely in adequate duration transperitoneally by laparoscopy. Compared to inframesenteric lymphadenectomy the number of lymph nodes could be doubled.
54 B) EXTRAPERITONEAL Laparoscopic extraperitoneal paraaortic lymphadenectomy was first described by Vasilev and McGonigle, in 1996 [94]. They developed an entirely extraperitoneal laparoscopic technique for para-aortic lymph node dissection in a pig model, followed by human subject application. Using latex balloon dissection technology, the technique is as follows. After inductions of anesthesia, a 15-mm incision was performed just below the mid left costal margin. Sharp and blunt dissection with electro-cautery was used to dissect down to the peritoneal envelope. Using gentle blunt dissection, a 10-cm-long extraperitoneal pocket was created to accommodate a latex balloon dissector.
Picture 51. The latex balloon dissector is shown bluntly separating the peritoneal envelope form the abdominal wall, in an area overlying the aortocaval retroperitoneal region. ( [94] )
A clamp was used to occlude the skin opening to the diameter of the dissector shaft. The balloon device was then inflated with 500–1000 cc of air under direct visualization via a laparoscope which was placed through the dissector shaft . Once an adequate extraperitoneal space was developed within the loose areolar tissue, hemostasis of small vascular perforators was ascertained by keeping the balloon inflated for 5 min. The balloon was deflated and the trocar was replaced with a 10-mm Hason-type Origin Blunt Tip trocar. A pneumoretroperitoneum was established with CO gas at a flow rate of 5 liters/min. A preset pressure of 10–15 mm Hg was adequate retract the peritoneal sac and its intestinal contents. Additional 5- and 10-mm trocars were placed into the extraperitoneal space.
Picture 52. The left flank cut-away demonstrates placement of operating instruments and extraperitoneal para-aortic lymph node dissection. ( [94])
55 Using U.S. Surgical Endoshears and Endodissect instruments and minimal use of a suction irrigation device, electrocautery-assisted sharp dissection was carried out to free the remaining fibrous bands between the peritoneal sac, Gerota’s fascia, and the psoas muscle. An Endoclip applicator was used to secure the ovarian vessels and other vascular structures during dissection. After ipsilateral ureteral identification, the attachment between the peritoneal sac and Gerota’s fascia was incised, reflecting the kidney away from the peritoneal envelope, exposing the aorta and vena cava from the renal vessels down to the common iliac vessels. The inferior mesenteric artery (IMA) was identified and preserved. With upward or ventral retraction of the peritoneal envelope via a fourth 5-mm port, the retroperitoneum was completely exposed, allowing visualization of the contralateral ureter. The ipsilateral ureter was dissected free of the peritoneal envelope in order to keep it out of the lymph node dissection field. This technique application was then approved as an investigational approach in human subjects by the City of Hope Institutional Review Board. Four subjects had this procedure performed. In the human model, this technique provided rapid, good visualization of the ipsilateral aorta inferior to the IMA with minimal dissection . With additional dissection and retraction, adequate visualization of the precaval area below the IMA allowed contralateral sampling. A mean of five lymph nodes (range 1–9, median 5) were recovered without the use of defatting techniques. The estimated blood loss was 50 cc in each case and the operative times was 120–140 min. There were no intra- or postoperative complications. This initial experience demonstrated that laparoscopic extraperitoneal para-aortic access and node sampling was feasible.
Following, these there have been reports describing the technique and its feasibility. Dargent et al and Querleu et al, reported that extraperitoneal lymphadenectomy is preferred as it is more effective in decreasing the formation of adhesions with fewer resultant bowel complications than the transperitoneal approach. • Querleu et al [95], in 2000, described the classic technique, as follow : The patient lays flat on the operating table. The senior surgeon stands on the left side of the patient, the assistant standing on his left side. Both watch the monitor screen placed on the right side of the patient. The operation starts as a standard laparoscopy. After the pneumoperitoneum has been created, a 10-mm endoscope is placed at the inferior margin of the umbilicus. An additional 5-mm trocar can be placed in the right lower quadrant to accommodate a palpator or a needle for sampling of the peritoneal fluid or a biopsy forceps in case of suspected peritoneal involvement. Additional information concerning the adnexa is obtained.
Picture 53. Trocar placement for extraperitoneal paraaortic lymphadenectomy. ( [199] )
56 A 15-mm incision is made 3–4 cm medial to the left iliac spine. The skin, fascia, transverse muscles, and deep fascia are incised, taking care not to open the peritoneum, which can be avoided if the laparoscopic view is used to check the undersurface of the abdominal wall of the left lower quadrant. The surgeon’s left forefinger is introduced in the incision and frees the peritoneal sac from the deep surface of the muscles of the abdominal wall under laparoscopic monitoring. The dissection is easy in the iliac fossa, and the finger soon reaches the psoas muscle, then, more medially, the left common iliac artery. Both landmarks are easily identified with the fingertip as a result of shape (psoas muscle) or beating (common iliac artery). Both landmarks can be safely freed from the peritoneal sac as much as possible: the wider the finger preparation is, the shorter the endoscopic dissection will be. The separation of the peritoneum is more difficult in the cephalic direction, with a thinner and more attached peritoneal sac. It is, however, possible to separate a surface of the abdominal wall large enough to allow the introduction of two trocars, gengenerally a 10-mm trocar higher and posterior to the first incision (on the middle axillary line), then a 5-mm trocar on the anterior axillary line approximately 5 cm below the ribs. Finally, the 15-mm incision is used to place a balloon trocar designed for open laparoscopy. The balloon is placed in the extraperitoneal space under laparoscopic guidance, inflated with saline and secured to the abdominal wall to ensure pneumostasis. The corresponding trocar is used to accommodate the endoscope. The peritoneal cavity is deflated while the extraperitoneal space is inflated with CO2 up to a maximum pressure of 10 mm of mercury.
The endoscopic view of the part of the extraperitoneal space prepared with the finger is clear from the very beginning of the introduction of the endoscope. The left psoas muscle, the left ureter, and the left common iliac artery are identified before any endoscopic dissection. The instrumental trocars accommodate grasping forceps, monopolar scissors, and, when required, bipolar cautery. Endoscopic clips must be available to control bleeding from large vessels or to radiologically localize fixed lymph nodes.
Picture 54. Extraperitoneal endoscopic view of the left psoas muscle (1), the common iliac artery (2), the ureter (3), and the ovarian vein (4) after finger preparation of the extraperitoneal space is shown. ( [95] )
The endoscopic blunt dissection is guided by three major landmarks: the psoas muscle, the ureter, and the common iliac artery. The psoas muscle is freed up to the fascia of the kidney, which can be entered using scissors if the space is too narrow. The ureter is separated from the common iliac
57 artery and lifted along with the peritoneal sac. Actually, only the lumbar and iliac segments of the ureter can be elevated, as the pelvic ureter and the upper lumbar ureter stay at the bottom of the dissection. As a result, the ureter forms a bow above the operative field throughout the dissection. The lateral aspect of the common iliac artery is used as a guide to dissect caudally down to the level of its bifurcation and up to the aortic bifurcation, then to the renal vessels. The surgeon then frees the anterior aspect of the common iliac artery vessels, knowing that the peritoneal sac and the ureter are attached to the iliac artery by small vessels that must be controlled before section. The surgeon frees the anterior aspect of the inframesenteric aorta, taking care not to injure the inferior mesenteric artery. After these steps are achieved, the lateroaortic nodes and the lateral common iliac nodes can be easily detached from the large vessels, the lumbar vessels, the prevertebral fascia, and the sympathic nerves.
Picture 55. Final view of the dissection in the aortic area is shown. The aorta (1), the common iliac arteries (2 and 3), and the inferior mesenteric artery (4) are dissected. A left lumbar artery (5) also can be seen. ( [95] )
The next step consists in reaching the right common iliac area. The peritoneal sac is elevated from the left common iliac vein, then from the sacral promontory. The bifurcation of the inferior vena cava is identified. Care must be taken not to injure the middle sacral vessels. The right common iliac vein then the right common iliac artery are freed by using blunt dissection. Further enlargement of the surgical space in this area requires pushing caudally, i.e., to the left side of the screen, the sigmoid colon, which is attached to the inferior mesenteric artery. Once identified, the right common iliac artery is followed in a caudal direction down to the level of its bifurcation. The crossing of the right ureter with the iliac vessels is reached. The right ureter then is elevated and separated from the iliac vessels and from the psoas muscle. The right ovarian vein is identified at the undersurface of the mesocolon. The presacral nodes and the right lateral common iliac nodes are ready for removal.
58
Picture 56. Final view of the dissection in the common iliac area is shown. In addition to the two common iliac arteries (1 and 2), the left common iliac vein (3), the promontory (4), and the right ureter (5) are visible. A left lumbar vein (6) and the left sacrolumbar vein (7) also can be seen. ( [95] )
The precaval lymph nodes then are identifed and detached from the inferior vena cava. They usually stay attached to the vena cava by small vessels. They must be gently grasped and slightly elevated to identify, to control, then to cut these small vessels generally by using monopolar cautery. The inframesenteric preaortic lymph nodes are generally attached to the peritoneal sac and are easy to dissect. The laterocaval nodes can be dissected using the same dissection plane or alternately may be reached after division of two or three sets of lumbar vessels and elevation of the aorta and vena cava from the prevertebral fascia. The standard common iliac and inframesenteric dissection is completed. The infrarenal dissection requires great care and knowledge of the normal anatomy and of anatomic variants. It starts at the lateral aspect of the aorta. The ateroaortic lymph nodes located below the left renal vessels are dissected first. The lateroaortic part of the left renal vein is reached using blunt dissection. The venous network, including the lomboazygos vein and the end of the left ovarian vein, is carefully dissected. Generally, the dissection ends with the removal of the high preaortic and left lateroaortic lymph nodes. The dissection of the anterior aspect of the aorta and of the preaortic segment of the left renal vein requires the division of the left ovarian artery. In the same way, the separation of the aorta from the prevertebral fascia and the removal of the retrovascular (retrocaval and retroaortic) lymph nodes is feasible.
59
Picture 57. Final view of the dissection in the infrarenal area is shown. The aorta (1) and inferior mesenteric artery (2), two lumbar arteries (3 and 4), the left renal vein (5), the lombo azygos vein (6), a left polar artery (7), and corresponding vein (8) have been dissected. The sympathic nerve chain (9) is also an important landmark. ( [95] )
The procedure ends after a careful check of the hemostasis and cleaning of the operative field by using irrigation and suction. The extraperitoneal space is deflated. The 15-mm fascial incision is closed. Since the occurrence of a bowel obstruction due to an incisional hernia through the umbilicus, routinely the 10-mm umbilical fascial incision is closed. The other incisions are superficially closed using skin sutures or staples. In the same way as in case of transperitoneal para-aortic lymphadenectomy, dissection of right-sided para-aortic lymph nodes is performed cranially up to the level of the right renal vein with attention to the affluent vessels at the IVC and lumbar veins.
• Dargent et al, in 2000 [96], described the left extraperitoneal route as follow : Τhe patient is in the dorsal decubitus position, the surgeon stands to the left of the patient and the assistant to the left of the surgeon. The surgeon and the assistant watch the monitor placed to the right of the patient. A 15-mm incision is performed at the left MacBurney point, 3 cm medial to the left anterior superior iliac spine ( mark 1 ).
Picture 58. Trocar placament. ( [96] )
60 Skin, subcutaneous fat, and fascia are opened sharply along the same oblique axis. Large muscles are opened bluntly while separating their horizontally oriented bundles lateral to their fascial insertion. The fascia parietalis must be opened, but the fascia peritonealis is preserved as far as possible to protect the peritoneum. The surgeon introduces his right forefinger into the incision to develop the extraperitoneal space under the control of transperitoneal laparoscopy. Digital dissection is performed caudally until the anterior surface of the psoas muscle is identified. Dissection is then continued cranially along the psoas muscle to the level of the iliac crest and then laterally. Once the preperitoneal space has been prepared, a 10-mm BluntTip trocar is introduced and the laparoscope is transferred to this point. The preperitoneal space is insufflated through the trocar sheath and the peritoneal cavity is simultaneously exsufflated. The extraperitoneal insufflation pressure is identical to that used for transperitoneal laparoscopy (12 mm Hg). Two additional trocars are then introduced in the midaxillary line in the preperitoneal space under laparoscopic guidance. A 5-mm trocar is placed immediately above the iliac crest for introduction of a cannula, to which the insufflation tube is connected ( mark 2). This cannula is used to extend the preperitoneal cavity cranially and a 10-mm trocar is then introduced just below the ribs ( mark 3).
The left psoas muscle is released from the peritoneum by using these two ancillary trocars and by extending the peritoneum medially. The left ureter identified on the anterior surface of the psoas muscle is retracted with the peritoneum. Extending more medially, the left common iliac artery and aorta are identified and dissection is continued cranially as far as the inferior mesenteric artery and left renal vein. Lymph node dissection is commenced below the left renal vein. All nodes between the aorta and psoas muscle are removed. The left and ventral surfaces of the aorta and left common iliac artery are then dissected, while preserving collateral vessels (ovarian, inferior mesenteric, and lumbar arteries). The next step of dissection involves the dorsal aspect of the aorta. The fourth and/or fifth lumbar arteries are clipped and cut to open the retrovascular space. As soon as the lumbar vessels are divided, the space between the aorta and the common vertebral ligament opens, and it is often possible to go on and join the interaorticocaval space and, further, the dorsal and ventral aspect of the vena cava. If not, a third ancillary port must be opened as medial as possible in order to introduce a third instrument in order to elevate the aorta (mark 4).
Dargent et al, evaluated the accuracy of the left extraperitoneal route in 21 cases, by comparing the transperitoneal route in nine cases with the bilateral extraperitoneal route in 14 cases. There was no statistically significant difference in the total number of aortic nodes removed; however, the operating time was significantly shortened using the left extraperitoneal route. They concluded that infrarenal para-aortic lymphadenectomy by the left extraperitoneal route was feasible.
After Dargent and Querleu, several reports have been done to describe the technique and its feasibility. Surgical approaches have been improved, with a mean operating time of 105.4 min. In the table bellow there are summarized findings of extraperitoneal para-aortic lymphadenectomy.
61 Table 5. Summarized findings of extraperitoneal paraaortic lymphadenectomy, NA = not available. No. No. Affected Operative Vascular Lymphoce Conversion of patients of nodes lymph time (min) complications le (%) to nodes (%) laparotomy Source, (%) year Dargent et 18 15 13.3 119 NA NA 14 al, 2000 [96] Querleu et 53 20.7 32 126 NA NA NA al, 2000 [95] Vergote et 21 6 18 64 4.7 NA NA al, 2002 [98] Sonoda et 111 18 27 158 0 9.9 NA al, 2003 [99] Mehra et al, 32 12 25 80 0 3.1 NA 2004 [100] Lowe et al, 32 14 25 163 NA 3.1 NA 2006 [101] Tillmanns 18 10 NA 108 0 5.5 NA and Lowe, 2007 [102] Gil-Moreno 69 02/15/16 NA 140 0 2.8 0 et al, 2008 [103] Franco- 15 7.7 60 157 0 6.6 6.6 Camps et al, 2010 [104] Morales et 28 15 42.8 147 7.1 3.5 3.5 al, 2013 [105]
Extraperitoneal paraaortic lymph node dissection is a minimally invasive procedure that is an excellent and safe approach to the paraaortic area, for the diagnosis of paraaortic lymph node recurrences of gynecologic cancers,with a low complication rate, low morbitity, sufficient number of lymph nodes, and short hospital stay. It seems to be a good alternative to the classic transperitoneal approach [105]. It can be effectively applied in staging early ovarian cancers to determine the need for adjuvant chemotherapy [100]. Radio-chemotherapy treatment began immediately after laparoscopy because of its minimal aggression [103]. Special laparoscopic material is not required and if it is performed by a team trained in technical endoscopics it is not difficult.
62 11. SINGLE- PORT LAPAROENDOSCOPY SURGERY Minimal invasive surgeries have spread to the field of gynecologic oncology and the number of gynecologic oncologists who use laparoscopic surgery to treat gynecologic cancer is increasing. As the instruments and surgical techniques of surgeons improved , surgeries with a smaller incision have emerged. These novel approaches include single - port laparoscopy or laparoendoscopic single-site (LESS) surgery . Laparoendoscopic single-site surgery entails performing laparoscopic surgery using a multichannel port system, typically placed through a single umbilical skin incision. Preliminary advances in LESS as applied to urologic and gastrointestinal surgeries demonstrate that the techniques are feasible provided that both laparoscopic surgical expertise and optimal instrumentation are available [109,110]. • Escobar et al [111] in 2010, reported pelvic and para-aortic staging surgery using the single- port laparoscopic approach for early- stage gynecologic cancers tranperitoneally for the first time in 2010. They introduced the procedures performed through a single 2-3 cm umbilical incision using a single- port device, a deflecting- tip laparoscope, and multifunctional instrumentation. The median pelvic and para-aortic node counts were 14 ( range, 7-19 ) and 6 ( range, 2-14 ), respectively, and in two of 21 cases conversion to a conventional multiport laparoscopy was carried out.
Description of LESS Pelvic and Para-Aortic Lymph Node Dissection Technique Once the patient is anesthetized, she is placed in the low lithotomy position and her arms are tucked appropriately and padded at her sides. After prepping and draping the patient, a Foley catheter is inserted into the bladder, and a high-definition monitor is positioned between the patient's legs at the eye-level of the operating surgeons. A single 2.0- to 3.0-cm vertical incision is made at the base of the umbilicus via an open Hasson approach. A multichannel, single-port device (that allows up to 3 laparoscopic instruments to be used simultaneously through separate channels) is positioned through the incision. Three 5-mm trocars are positioned in a triangulated fashion through the device. The abdomen is insufflated to 15 to 20 mm Hg of carbon dioxide gas through a separate cannula on the single-port device, and a 5-mm 30-degree rotatable deflecting-tip laparoscope is inserted through the most cephalad port.
Picture 59. Patient position for single- port pelvic lymphadenectomy. ( [111] )
63 The patient is then placed in the steep Trendelenberg position, and pelvic exposure is optimized by folding the small bowel and rectosigmoid colon gently out of the pelvis with atraumatic graspers. The lymphadenectomy is started on the right side of the pelvis by the surgeon on the contralateral side of the operating table. The surgical assistant controls the laparoscope, whereas the primary surgeon controls both operating instruments. The position of the laparoscope is this so that the external iliac vessels are viewed horizontally, similar to the view seen during open pelvic lymphadenectomy by the contralateral surgeon. The bifurcation of the common iliac and the right external iliac, hypogastric arteries, veins, and the right ureter are identified. Using a roticulating soft tissue grasper and a multifunctional 5-mm laparoscopic instrument (which allow tissue fusion/vessel sealing, spot coagulation, and in some cases, endoscissor functions in 1 instrument), the dissection is initiated lateral to the external iliac artery. The peritoneum between the external iliac artery and the psoas muscle is elevated and incised parallel to the artery. The external iliac vessels are then skeletonized anteriormedially and laterally, away from the psoas muscle, taking care to avoid injury to the genitofemoral nerve, which runs anteriorly along the muscle. The pararectal and paravesical spaces are created by gentle blunt dissection using the grasper. All nodal tissue are then removed from the midportion of the common iliac artery superiorly to the circumflex iliac vein inferiorly and from the midportion of the psoas muscles laterally to the ureters and the hypogastric artery and vein medially. Furthermore, the nodal tissue within the obturator fossa is also carefully dissected and excised, anterior to the obturator nerve and vessels. The dissection is performed with a combination of gentle blunt dissection with either the roticulating soft tissue grasper or the tip of a suction aspirator. The excised nodal tissue is placed in a sterile endoscopic bag, and the bag is left in the pelvis or the right paracolic gutter until the end of the case.
Picture 60. Single-port pelvic lymphadenectomy. ( [111] ) Dissection of the left pelvic lymph nodes is performed in a similar fashion and within the same anatomic boundaries as the right pelvic lymph nodes. Notably, on the left side, it is often necessary to first divide physiologic adhesions from the sigmoid to the left pelvic sidewall (with endoscissors
64 or the tip of the multifunctional instrument) to optimize exposure of the left pelvic vasculature and nodal-bearing tissues. Once the left pelvic lymphadenectomy is performed, the nodes are placed in a separate endoscopic bag, and both the right- and left-sided bags are removed through the umbilicus after removal of the single-port device. The device is then reinserted into the umbilical incision, the abdomen is reinsufflated with carbon dioxide gas, and the dissection beds irrigated with sterile water and inspected to ensure hemostasis. In a similar fashion, a para-aortic dissection is carried out to the level of the inferior mesenteric artery. The peritoneum on top of the lower aorta is elevated and incised parallel to the artery; of note, this is started cephalad to the bifurcation of the common iliacs. Gently, the ureter is dissected laterally using the roticulator graspers; the nodal tissue is then gently removed. The dissection is then carried out distally, exposing the bifurcation of the common iliacs and left common iliac vein. Of note, on the left side, the sigmoid has to be mobilized depending on the approach for the dissection of left common iliac artery lymph nodes. At the end of the procedure, the multichannel single port is again removed from the umbilicus; the fascial incision is closed and the skin also.
Description of High-Para-Aortic Dissection Technique Single-port laparoscopic transperitoneal aortic lymphadenectomy to the level of the renal veins is performed in the following fashion. The abdomen is insufflated to 15 to 20 mm Hg of carbon dioxide gas through a separate cannula on the single-port device, and a 5-mm 30-degree rotatable deflecting-tip laparoscope is inserted through the most inferior port on the single-port device. The patient is then placed in the steep Trendelenberg and semiflank position (tilt to patient's right); exposure of aorta is optimized by folding the small bowel to the patient's right flank. The descending colon is either dissected and mobilized medially through the white line of Toldt or left in situ for a transmesenteric approach to the aorta, depending on patient characteristics (obesity, short intestinal mesentery, intestinal adhesions, and/or distended bowel). The peritoneum and nodal tissue are grasped and dissected away from the aorta and vena cava from the aortic bifurcation to the left renal vein in a caudal to cranial direction. The inferior mesenteric artery is preserved in all cases.
Picture 61. Patient position in a single- port para-aortic lymphadenectomy. ( [111] )
65
Since Escobar et al introduced tranperitoneal para-aortic lymphadenectomy, most surgeons reported the efficacy and feasibility of the extraperitoneal approach. The procedure of single- port extraperitoneal lymphadenectomy starts with the standard transumbilical diagnostic laparoscopy with a single- port inserted via a 2-3 cm incision to assess the peritoneal cavity and obtain a peritoneal fluid sample. • Gouy et al performed extraperitoneal lymphadenectomy with an incision at a point situated one- third of the way along the line from the anterior superior iliac spine toward to the umbilicus [112]. Description of the thechnique For this single-port extraperitoneal para-aortic lymphadenectomy procedure, a single 2- to 3-cm left iliac incision is made. This incision is made perpendicular to a point situated two-thirds of the way along a line drawn from the umbilicus to the anterior superior iliac spine or a point situated one-third of the way along the line from the anterior superior iliac spine toward the umbilicus.
Picture 62. A 2- to 3-cm incision was made perpendicular to a point situated two-thirds of the way along a line drawn from the umbilicus to the anterior superior iliac spine or a point situated one-third of the way along the line from the anterior superior iliac spine toward the umbilicus. ( [112] )
First, the fascia is incised in front of the left rectus abdominis muscle and divided them in the direction of their fibers, plane by plane, up to the peritoneum, which is opened to introduce the single device used to perform the transperitoneal step.
Picture 63. The fascia is incised in front of the (A) left rectus abdominis muscle and divided them in the direction of their fibers, plane by plane, up to the (B) peritoneum, which was (C) opened. ( [112] )
66 Carbon dioxide is insufflated at a pressure of 10 mmHg to 12 mmHg through a separate cannula on the single-port device. The laparoscope (10-mm, 0-degree angle) and 2 conventional, rigid, straight, dissection forceps are introduced into the 3 channels. In the absence of peritoneal or ovarian spread, peritoneal cytology is performed, the single-port device is removed, and a PA lymphadenectomy is performed through the same incision via a left-sided extraperitoneal approach. For this second step, through the same incision, the fascia is incised in front of the anterior-lateral abdominal muscles, they are splited in the direction of their fibers, plane by plane, after a large finger dissection to introduce the single-port into the extraperitoneal space.
Picture 64. Through the same incision, the (A) fascia is incised in front of the (B) anterior-lateral abdominal muscles, they are splited in the direction of their fibers, plane by plane, after a (C) large finger dissection of the extraperitoneal space. ( [112] )
Carbon dioxide is insufflated at a pressure of 10 mmHg to 12mmHg through a separate cannula on the single-port device. Because the transperitoneal incision of the peritoneum is performed at the level of the left rectus abdominis, the gas is not transfered from the extraperitoneal to the intraperitoneal cavity because the peritoneal incision and the skin scar are not at the same level. Indeed, the peritoneum is opened near the area where the peritoneum is opened by the transperitoneal approach (which is used in the conventional multiport laparoscopy). So, the peritoneum is opened in the same area by the new single- port procedure and by the conventional laparoscopy procedure, and there isn't any difference between the 2 procedures in term of gas transfer. The surgeon is positioned to the left of the patient during the procedure. The assistant stands on the left of the patient and left of the surgeon. For ergonomic reasons, the assistant can be placed between the legs of the patient, especially during the dissection of the left renal vein. For dissection of the aortic bifurcation, which is easy as conventional multiport laparoscopy, the assistant stands on the left of the surgeon.
67
Picture 65. The position of the surgeon. ( [112] )
The nodal tissues are grasped and dissected away from the aortic bifurcation to the left renal vein. The inferior mesenteric artery is preserved in all cases. Lymph nodes are extracted through the single-port device.
Picture 66. Appearance at the end of para-aortic lymphadenectomy. ( [112] )
After completing the procedures, the single-port device is removed, the peritoneum is closed, the fascial incisions, and the skin too.
Picture 67. Appearance of the skin at the end of the procedure. ( [112] )
68 • Lambaudie et al and Hurdy et al introduced the incision at the patient's left side between the iliac crest and the last ribs [113,114]. Lambaudie et al demonstrated the feasibility of single-port-access laparoscopy for extraperitoneal aortic lymphadenectomy. The lymph node count was similar to that described in the published experience of conventional laparoscopic extraperitoneal dissection. This preliminary report showed that Single- Port Surgery is usable for extraperitoneal aortic dissection and that it is possible to perform this procedure using only one skin incision compared with the three or four incisions required for conventional laparoscopy. Description of the technique The patient is placed in dorsal decubitus position, the same position used for conventional extra peritoneal dissection, as described by Querleu et al [117]. The procedure starts with a standard transperitoneal laparoscopy. A systematic exploration is performed to eliminate intra-abdominal carcinomatosis and to realize a peritoneal fluid sampling. For the extraperitoneal approach, only one 3–4 cm incision is necessary on the patient’s left side between the iliac crest and the lasts ribs.
Picture 68. Skin incision. ( [113] )
The skin, fascia, transverse muscles, and deep fascia are incised, with care taken not to open the peritoneum. The landmarks for finger dissection are well known and include the iliac fossa, the psoas muscle and, more medially, the left common iliac artery. When the dissection is complete, the single-port dispositive is introduced into the extraperitoneal space.
Picture 69. The position of the surgeon during gthe dissection. ( [113] )
69 The skin, fascia, transverse muscles, and deep fascia are incised, with care taken not to open the peritoneum. The landmarks for finger dissection are well known and include the iliac fossa, the psoas muscle and, more medially, the left common iliac artery. When the dissection is complete, the single-port dispositive is introduced into the extraperitoneal space. The peritoneal cavity is deflated, whereas the extraperitoneal space is inflated with carbon dioxide up to a maximum pressure of 10 mmHg. A 10 mm 0°laparoscope and 5 mm standard instruments including fenestrated forceps, bipolar forceps, and monopolar scissors are used. The procedure is conducted as described for conventional laparoscopy using the same landmarks: from the common iliac bifurcation caudally up to the left renal vein cranially and between both ureters and the gonadal vessels laterally [117]. At the end of the procedure, after a check of the hemostasis, the extraperitoneal space is deflated. A marsupialization of the peritoneum under transperitoneal laparoscopic control is performed to reduce the risk of symptomatic lymphocele. The facial incision is closed. The remaining incisions are superficially closed using skin sutures and glue to limit postoperative care.
Many authors reported the feasibility of para-aortic lymphadenectomy via the extraperitoneal approach. They also, reported that this procedure can be radical, and the median number of lymph nodes removed is similar to that of conventional multiport laparoscopic para-aortic lymphadenectomy [113,115,116]. However, the technical constraints required a longer operative time. Moreover, the learning curve to perform all the procedures by a single incision may be slower compared with conventional laparoscopy. On the other hand, Hudry et al [114] reported that the mean operative time was shorter than that of the conventional multiport laparoscopic lymphadenectomy, and this surgical technique was feasible for surgeons familiar with extraperitoneal laparoscopy.
70 12. ROBOTIC-ASSISTED LYMPHADENECTOMY 12.1 ROBOTIC PELVIC LYMPHADENECTOMY Since 2000, the Da Vinci surgical system has allowed the development of new minimal invasive surgical techniques in cardiac, urological, general and gynaecological surgery. In 2005, the Food and Drug Administration of the USA approved the da Vinci Surgical system for gynecological surgery. The da Vinci Surgical system has some advantages, such as three dimensional vision, better ergonomics, a higher degree of freedom of the robotic instruments, and reduction of tremor interference, when compared to conventional laparoscopic surgery [118]. The development of robotic technology has facilitated the application of minimally invasive techniques for complex operations in gynecologic oncology, and the data of gynecologic cancer show comparable results for robotic surgery when compared with laparoscopy or laparotomy in terms of blood loss, length of hospital stay, and complications [119].
• In 2008, Lambaudie et al [120], tried to evaluate the feasibility and the outcome of gynaecological cancer surgery with the Da Vinci Surgical system. From February 2007 to September 2007, 28 patients underwent 32 gynecologic surgeries for various indications with the Da Vinci surgical system (four-arm model). Surgical procedures consisted of total hysterectomy, bilateral oophorectomy, and pelvic and/or lombo-aortic lymphadenectomy. All patients were placed in low lithotomy position with arms padded and tucked to the side. The position of the Da Vinci surgical system was modified according to the surgical procedure. The Da Vinci patient unit was positioned between the legs for all pelvic procedure with or without lombo- aortic exploration. Five ports were placed: four for the Da Vinci surgical system’s arms (one camera port, three instrument ports) and the fifth as a classical laparoscopic port for the assistant. The first port was placed after opening the abdominal cavity with a small abdominal incision to introduce the camera; its position depended on the anatomical site of the intended procedure. For pelvic surgery, the camera port was placed 1–2 cm above the umbilicus and the four additional ports were placed in a curved line, keeping a 7- or 8-cm distance between the ports. A similar position was chosen when a concomitant lombo-aortic lymph node dissection was indicated, but ports were placed more cranially in the abdomen. After routine exploration of the peritoneal cavity the Da Vinci patient unit was docked.
Picture 70. Port placement. O: the 12-mm camera port was placed 1 or 2 cm above the umbilicus or very high on the abdomen as shown, depending on the necessity or not to realize lombo-aortic lymph node staging. 1, 2 and 3: 8-mm ports for robotic instruments. A: 10-mm port for the assistant (suction, clips, endobag). Green: pelvic, lombo-aortic procedure. Red: pelvic procedure. Blue: isolated lombo-aortic procedure. ( [120] )
71
Picture 71. Definitive position after docking time. ( [120] )
• The set-up and technique of robotic surgery have been well introduced by Madhuri et al [121], in 2012. They described the initial docking between the patient's legs ( tail docking). This was followed by docking on the patient' s left lateral side at a angle of 30º (side docking). Left side docking is preferable for a left-handed surgeon. Also, this technique improves vaginal access for tissue removal or if vaginal repair of a prolapse is required. Subsequently, the surgeons moved to right side docking, which enables two different intruments to be switched between arms 1 and 3 on the right side of the patient.
• In 2014, Escobar et al [125], described the technique as follow : Equipment and robotic column Two monitors are located at each side of the operative table at the level of the patient's knees. The robotic tower and the tower containing electrosurgical generators and active smoke evacuators are positioned to the right or left of the patient's feet, depending on the operating room organization.
Trocar placement and docking As it has been described, an open Hasson transumbilical entry technique with a 12mm trocar is prefered. A CO2 pneumoperitoneum is created once intraperitoneal entrance is confirmed. The robotics laparoscope is used to perform a survey of the upper abdomen and the pelvis. Two 8mm robotic trocars are placed bilaterally, 10cm distal to and at the level of the umbilicus. An accessory 10mm trocar is placed 3 cm cranial and equidistant between the umbilical and the left lateral ports. An additional 8mm robotic trocar is placed in the right lower quadrant at the level of the cecum.The patient is placed in Trendelemburg position to shift the small bowel and sigmoid of the pelvis.
72
Picture 72. Trocar placement. ( [125] )
The robotic column is side-docked to the patient's right. A EndoWrist monopolar spatula or scissors,depending on the surgeon's preference, is inserted through the right lateral trocar and a EndoWrist bipolar grasper is inserted through the left lateral trocar. EndoWrist ProGrasp forceps is inserted through the right lower quadrant trocar, as the fourth arm and is used for retraction. A Thermoflator and a high-flow insufflator at 30 L/min are used. Reusable insufflation tubes are attached to the trocar valves for passive smoke evacuation and dropped by gravity into a bottle containing saline solution.
Pelvic Lymphadenectomy Technique A pelvic lymphadenectomy is performed by dissecting the paravesical space and occasionally the pararectal space.
Picture 73. (a,b) Pelvic lymphadenectomy is perfomed by dissecting the paravesical space. ( [125] )
73 Picture 74. Pelvic lymphadenectomy occasionally involves the pararectal space. ( [125] ) The anatomic borders of the paravesical space are medially, the superior vesical artery; laterally, the external iliac artery; anteriorly, the pubic ramus; posteriorly, the parametrium. The dissection is carried down to the levator ani, being careful to identify the obturator nerve. The margins of the pararectal space are medially, the ureter; laterally, the inernal iliac artery; anteriorly, the parametrium; inferiorly, the levator muscle. The superior margin of the pelvic lymphadenectomy is the bifurcation of the common iliac arteries and the distal margin is the inguinal ligament.
Picture 75. Lateral common iliac arteries. The bifurcation of the arteries is the superior margin of the lymphadenectomy. ( [125] ) The external iliac nodes overlying and lateral to the external iliac vessels are removed, followed by the superficial lateral common iliacs and the internal iliac and obturator nodes.
Picture 76. The external iliac nodes overlying and lateral to the external iliac vessels are removed. ( [125] )
74 The common iliac artery and vein, the external iliac and the internal iliac arteries, the anterior bifurcation vessels of the internal iliac artery and the obturator nerve, should be clearly visible at the completion of pelvic lymphadenectomy.
Picture 77. At the completion of the pelvic lymphadenectomy, the common iliac artery and vein, the external and the internal iliac arteries, the anterior bifurcation vessels of the internal iliac artery and the obturator nerve are clearly visible. ( [125] )
75 12.2 ROBOTIC TRANSPERITONEAL INFRARENAL AORTIC LYMPHADENECTOMY The Da Vinci and da Vinci S robotic systems do not provide access tο the entire abdomen without relocating the robotic column. This relocation is a major limitation for full staging or excision, or both, of early or disseminated gynaecologic malignancies, including removal of the infrarenal aortic nodes. Relocation of the robotic column is not recommended because of the column's large size and weight and the lengthy time required [132]. • Magrina et al [133], in 2009, designed a study to develop a technique for robotic infrarenal aortic lymphadenectomy in cavaders and to evaluate the results in patients with gynecologic malignancies. Two unembalmed female cadavers were used to evaluate the feasibility of performing an infrarenal aortic lymphadenectomy with the da Vinci and da Vinci S robotic systems with the robotic column positioned between the patient's lower extremities or at the patient's head. An operating table rotation system was developed to accommodate abdominal operations and infrarenal aortic lymphadenectomy after robotic pelvic surgery. The newly developed technique of robotic transperitoneal infrarenal aortic lymphadenectomy was performed in 33 patients undergoing surgical treatment between July 2005 and June 2008 for ovarian (n = 20), endometrial (n = 6), cervical (n = 4), vaginal (n = 1), and peritoneal (n = 2) malignancies. The technique is as follow : The trocar placement for the pelvic portion of the robotic operation has been previously described. A new set of trocars was placed in the lower pelvis for the infrarenal aortic lymphadenectomy after pelvic surgery. An optical 12-mm trocar was inserted 2 or 3 fingerbreadths suprapubically and 1 or 2 fingerbreadths to the left of the midline. Two robotic trocars were inserted 10 to 12 cm to the right and the left of the optical trocar. Either a monopolar spatula or a monopolar scissors, but not both, was used on the right robotic arm, and a plasma kinetic grasper was used on the left robotic arm. Two accessory trocars were placed 2 cm caudally and equidistant to the right and left of the optical trocar.
Picture 78. Trocar placement for robotic pelvic surgery, abdominal procedures and infrarenal aortic lymphadenectomy. The robotic column is located at the patient's head for abdominal and aortic operations. ( [133] ) The patient was placed in Trendelenburg position, and the robotic column was positioned at the patient's head. The assistant stood between the patient's legs and used the left hand to retract the
76 duodenum and pancreas ventrally with a 10-mm fan bowel retractor introduced through the left assistant trocar and the right hand for lateral retraction of the sigmoid mesentery, insertion of a vessel-sealing-cutting device, and suction and irrigation using the right assistant trocar.
Picture 79. Assistant's position for abdominal and aortic operations. ( [133] )
A small (3-4 cm) incision was made on the peritoneum overlying the midportion of the right common iliac artery and extended to the aortic bifurcation. The subperitoneal loose areolar tissue was dissected over the main vessels until the left renal vein was identified. A small tent was then created by gently elevating the peritoneum ventrally with the fan bowel retractor, preventing the small bowel from sliding into the aortic field. The right aortic nodes over the vena cava and aorta were excised first, as well as the interaortic nodes if a separating space existed between these 2 vessels. The dissection was extended cranially until no nodal tissue was present, usually at or above the level of the insertion of the right ovarian vein to the vena cava. To access the inframesenteric left aortic nodes, the surgeon extended the peritoneal incision from the aortic bifurcation caudally and over the left common iliac artery for approximately 4 to 5 cm. The sigmoid mesentery was retracted laterally by the assistant surgeon, exposing the psoas muscle and the left ureter. The right aortic nodes were removed first, followed by removal of the left inframesenteric nodes. The inferior mesenteric artery was transected with the EnSeal tissue-sealing device or the LigaSure V vessel-sealing instrument to increase exposure by allowing additional lateral mobilization of the left colon mesentery and to facilitate removal of the left infrarenal nodes. Temporary clamping of the inferior mesenteric artery before its division was performed when needed to check for sigmoid viability. The left ovarian vein and the cranial border of the left renal vein were the lateral and upper limits of left aortic dissection, respectively. Lumbar veins or arteries, or both, were transected by the assistant when needed. The mean console time was 42 minutes (range, 19-64 minutes). The mean number of nodes was 12.9 (range, 2-27); the mean number of positive nodes was 2.6 (range, 0-8). There was 1 conversion to laparotomy. Magrina et al, concluded that the robotic transperitoneal infrarenal lymphadenectomy is feasible,
77 adequate and safe when performed with the robotic column at the patient's head. Operating table rotation (180°) and additional trocar sites are needed when used in conjunction with robotic pelvic surgery. • Jacob et al [135], in 2011, described a left lateral approach for robotic transperitoneal infrarenal aortic lymphadenectomy using a right lateral decubitis position. Minimal patient repositioning (60°) provides access for pelvic surgery using the same abdominal trocar placement. The technique is as follow : Patients were positioned on the operating table as described by Martin et al. [136] with a slight modification. The patient rested supine atop an underlying antiskid material withn a 10-pound sandn bag bump placed under the left flank. Then left arm was supported, padded, and tucked to the left side. The right arm was secured and extended outward on an arm board. The legs were slightly flexed at the knees with pillow support and a pillow between the knees. The torso, hips, and knees were secured with padding and tape, allowing for extreme rotation of the table to the right exposing the patient’s left flank. Allen stirrups were secured and rotated beneath the table so that they could be rotated outward for placement of the patient’s legs when the pelvic portion of the procedure ensued. The security of the patient was verified by carefully rotating the patient into extreme right tilt before surgical preparation and draping.
Picture 80. Patient positioning: View from the patient’s right side (left); view from head of right lateral table tilt (right). ( [135] )
A 12-mm trocar was inserted at the umbilicus. Assessment of the entire abdomino-pelvic cavity was performed assessing for any evidence of gross metastatic disease. Ancillary trocars were placed with the patient in the supine position as follows : (1) A 12-mm trocar at the left mid-clavicular line
78 3–4 cephalad to the umbilicus. This port housed the 0 robotic camera. (2) An 8-mm robotic trocar placed 2 cm left of midline just below the costal margin. (3) A 8-mm robotic trocar 4 cm above the pubic symphysis and 2 cm left of midline. (4)A5-mm bladeless trocar placed 10 cm left lateral of the umbilicus for the assistant. The patient was then placed in extreme right lateral decubitus and the da Vinci S robotic system docked over the patients left hip at a 60 angle to the legs. Robotic EndoWrist (Intuitive Surgical) instrumentation included a fenestrated bipolar grasper on the left and monopolar scissors on the right. The assistant sat on the right side of the patient and provided tissue retraction, clip application, vessel-sealing, and suction/irrigation via the umbilical and the left lateral trocar.
Picture 81. Trocar placement for aortic dissection while in right lateral decubitus position: (A) Umbilical assistant port; (B) Left midclavicular, robotic camera; (C) Subcostal robotic left arm; (D) Suprapubic robotic right arm; (X) Left lateral assistant port, later used as robotic left arm for pelvic dissection. ( [135] )
Picture 82. Aortic and pelvic access: Trocar, patient, and robotic column positioning. ( [135] )
The infrarenal aortic lymphadenectomy was performed first due to complications or technical difficulties of this portion of the procedure being the most likely to require conversion to
79 laparotomy. The white line of Toldt was incised from the pelvic brim to the splenic flexure to mobilize the descending colon medially exposing the aortic nodes. Gravity directed the colon out of the operative field. Peritoneum overlying the psoas muscle was elevated and the left ureter isolated and mobilized laterally. The left gonadal vein was transected distally and dissected cephalad to its insertion into the renal vein. Endoscopic clips were applied at the insertion into the left renal vein that delineated the most cephalad border of the aortic lymphadenectomy. The nodal dissection was started at the mid left common iliac artery and continued cephalad removing all nodal tissue anterior and lateral to the aorta up to the left renal vein. The right aortic nodes were removed from the mid-right common iliac artery to the insertion of the right gonadal vein at the inferior vena cava, the cephalad border of the right lymphadenectomy. Division of the IMA was occasionally necessary to obtain adequate exposure and accessibility to underlying lymphatics.
Once the aortic lymphadenectomy was completed, the robotic system was undocked. The patient was positioned supine, sand bag removed, Allen stirrups rotated outward, and nthe legs positioned in the standard low dorsal lithotomy position. The operating table was rotated 45 and the patient placed in steep Trendelenburg. This was accomplished without removing the sterile drapes. One additional 8-mm trocar was inserted 10 cm to the right of the umbilical port for the right robotic arm. The left 5-mm trocar was converted to an 8-mm trocar for the left robotic arm and the robotic system docked caudally between the legs. The camera was advanced transumbilically and the left mid-clavicular port was used for the assistant. A hysterectomy, salpingo-oophorectomy, with pelvic lymphadenectomy was performed as customary. A total of six trocars were used for both the dissection of the aortic lymphadenectomy as well as the pelvic dissections.
· Vizza et al [137], in 2012, described a new developing strategy for robotic transperitoneal aortic lymphadenectomy without relocating the robotic column or the patient. Patients with histologically confirmed cervical cancer, early ovarian cancer, or endometrial carcinoma with suspected risk factors indicating aortic lymphadenectomy were eligible for the robotic transperitoneal aortic lymphadenectomy using the Da Vinci robotic system as part of the surgical treatment of gynecologic malignancies. The technoque was as follow : Patients were placed in the lithotomy position with their arms tucked at each side. After creation of a pneumoperitoneum to 12 mmHg with a transumbilical Veress needle, a 12-mm trocar was placed at 5–7 cm cranial to the umbilical. Three 8-mm trocars, specific for the Da Vinci robotic systems (Intuitive Surgical) were placed: one (arm 1) on the right side of the abdominal wall, medial and cranial to the right anterior upper iliac spine, and two on the left side of the abdominal wall, the first (arm 2) on the left lowest rib and the second (arm 3) medial and cranial to the left anterior upper iliac spine on the same line of the right trocar, and fastened to the robotic arms. An assistant 10-mm trocar was placed on the right side of the abdominal wall, 7–10 cm laterally, from the supraumbilical trocar. After they obtained the Trendelenburg position, the Da Vinci robotic column was positioned near the operating table between the patient’s feet and docked.
80 Picture 83. Port site placement. ( [137] )
The instruments were introduced: a bipolar grasper and a PK grasper on the left robotic trocars (arms 2 and 3), and a monopolar scissor on the right robotic trocar (arm 1). A 30 Surgical Intuitive endoscope was used during all operations. They divided their technique for robotic aortic lymphadenectomy into four steps. In the first step, the assistant, using a laparoscopic endotract, packed the small bowel into the upper abdomen to improve the exposure of the common iliac artery. The peritoneum over the right common iliac artery was grasped and incised with monopolar scissors, following the right side of the aorta until the ligament of Treitz was reached, thus mobilizing the duodenum. The dissection of he retroperitoneal areolar tissue was performed in the direction of the right psoas muscle, which represented the lateral limit of their dissection. The genitofemoral nerve, ovarian vessels, and ureter are visualized. The lateral peritoneum was grasped with the ProGrasp device, and the ureter was reflected laterally.
Picture 84. Peritoneum incision. RCIA right common iliac artery, A aorta, SMS submesenteric space, IMA inferior mesenteric artery. ( [137] )
In the second step, node dissection was performed from the bifurcation of the common iliac vessels just below the left renal vein (LRV). The dissection proceeded from the medial to the lateral side,
81 creating small pedicles of lymphatic and venous vessels that were safety coagulated. During this time, they visualized the inferior mesenteric artery (IMA) and LRV successively. To gain exposure to the surgical field, robotic arm 3 grasped the peritoneum reflection over the aorta and gently placed it laterally, carrying the ureter and the left ovarian vessels, which are coated to the lateral peritoneum (white line of Toldt). Once en-bloc dissection was completed, the nodes were placed into an endobag and removed through the assistant trocar.
Picture 85. Identification of the IMA and LRV. A aorta. ( [137] )
In the third step, the dissection plane was created by opening the retroperitoneal tissue under the IMA until they reached the left common iliac artery, in the direction of the left psoas muscle, which marked the lateral limit of their dissection. Then dissection was performed below the IMA to the left common vessels, and the nodes, which they placed into an endobag, were removed trough the assistant trocar. At this time, a wide field of dissection was essential for an optimal exposure, so they preferred a 30 endoscope camera. An assistant created a backstop for the small bowel.
Picture 86. SMS development. SMS submesenteric space, RCIA right common iliac artery, A aorta, IMA inferior mesenteric artery. ( [137] )
In the fourth step, the dissection of the left paraaortic region above the IMA insertion into the aorta until the LRV started with a change in position of the 30 camera. The camera was positioned into the assistant trocar and docked to the robotic arm while the assistant moved the instruments through
82 the central trocar. The change of the camera’s position improved the exposure of the left surgical aortic space up to the LRV (the upper limit of their dissection) without our having to relocate the robotic column. The retroperitoneal space was opened from IMA to the LRV in the direction of the left ovarian vessels, the lateral limit of the dissection. The lymph nodes were dissected en-bloc from IMA to the LRV, placed into an endobag, and removed via the central trocar. The lumbar vessels were not ligated, and the retrocaval and retroaortic nodes were not removed. Retroperitoneal drainage was inserted via the 8-mm right port cranial upper iliac spine.
Picture 87. IRAS development. LRV left renal vein, IRAS infrarenal aortic space, SMS submesenteric space, IMA inferior mesenteric artery, A aorta. ( [137] )
The mean operating time was 224 min (range 160–300 min), and the mean console time for aortic lymphadenectomy was 43 min (range 30–75). The median hemoglobin fall was 1.3 g/dL range (0.8–2 g/dL), the median number of removed aortic lymph nodes was 12.5 (range 7–17), and the median length of the hospital stay was 2 days (range 1–4 days).
With this initial experience Vizza et al, demonstrated tha robotic aortic lymphadenectomy to the LRV after pelvis dissection ( including lymphadenectomy) is feasible and safe, and it can also be carried out without relocating the robotic column or the patient.
83 12.3 ROBOTIC EXTRAPERITONEAL AORTIC LYMPHADENECTOMY To overcome some of the limitations of the transperitoneal route and in an attempt to reduce the formation of postoperative intestinal adhesions, an extraperitoneal approach to aortic lymphadenectomy was developed and has been reported by numerous authors.
· Vergote et al, [138] in 2008, published a series og 5 lympadentenectomies extending to the inferior mesenteric artery, using the robotic Da Vinci system. The technique was as follow : From the second patient they realized that it was better to tilt the patient slightly on the left side and to install the left arm parallel to the patient in order to avoid collision between the robotic arms and the left arm of the patient. The operation was started with a transperitoneal laparoscopy through an umbilical 10 mm Hassan trocar. A transperitoneal port is needed in order to evacuate leaking of CO 2 from the retroperitoneal to the intraperitoneal cavity. The peritoneal cavity was inspected.
Picture 88. Placement of the patient with lifting of the left flank of the patient and positioning of the left arm parallel to the patient. ( [138] )
At this point the robotic retroperitoneal paraaortic lymphadenectomy was started. The port placement was performed with the surgeon on the left side of the patient at the height of the left hip and the assistant on the left side at the height of the upper leg. The video screen was placed on the right side at the level of the patient’s head. In the first patient the extraperitoneal access was made at the level of the left Mc Burney point and the 2 robotic ports were placed cranially of this endoscope port as reported earlier with the laparoscopic technique. However, this resulted in some collision of the 2 robotic arms and therefore from the second patient onward the endoscope was placed in the middle port. In the last 4 patients a 12 mm incision was performed just cranial of the left anterior supper iliac spine. Skin, subcutaneous fat and fascia were opened sharply along the same access. The large muscles were opened bluntly with opening of the parietal fascia but not of the peritoneal fascia. The surgeon introduced the right finger into the incision and developed the extraperitoneal space. Digital dissection was performed until the anterior surface of the left psoas muscle and the common iliac artery on the right side were identified. Next a 12 mm blunt-tip balloon trocar was introduced and the zero angle Da Vinci laparoscope and camera were introduced through this port. The extraperitoneal insufflation pressure was 15 mmHg. Two additional robotic trocars were introduced, one 8-10 cm distal and medial to the scope trocar and one under the left lowest rib on the same line as the laparoscopic trocar at a distance of 8-10 cm of the endoscopic port. A fourth
84 port of 10 mm trocar was inserted at about 1 cm above the right corner of the pubic hair for the assistant in order to lift the peritoneum with the ureters and ovarian vessels, and to remove the lymph nodes.
Picture 89. Positioning of the ports. ( [138] )
The Da Vinci S robotic system was docked from the patients right side with the robotic arms reaching over the patient. The third robotic surgical arm was not used in this procedure due to the limited space to place the ports. In the first 2 patients an ultrasonic harmonic scalpel was introduced in the left robotic port (left-handed surgeon) and a bipolar forceps in the right robotic port. In the last 3 patients a Gyrus bipolar forceps was used through the right port and a monopolar scissor through the left port. This had clearly advantages as the Gyrus bipolar instrument has articulating tips (as the monopolar scissors) while the Ultracision has currently not. In addition, the Gyrus bipolar coagulator has a higher energy than the traditional bipolar coagulation forcepses. The zero degree Surgical Intuitive endoscope was used for the dissection of the para-aortic and preaortic region. However, for the dissection of the lateral part of the caval vein we changed to the 30◦ scope, which gave a better view on the paracaval area. The bifurcation of the aorta and the vena cava, the left and the right ureter were identified and the lymph nodes were removed from the bifurcation of the aorta to the level of the inferior mesenteric artery. It was the first report on robotic retroperitoneal para-aortic lymphadenectomy in patients with gynecologic cancer.
· Because robotic technology provides advantages over conventional laparoscopic instrumentation, in particular when working on a limited surgical field, Magrina et al [139] in 2009, also developed an extraperitoneal approach for the performance of aortic lymphadenectomy to renal vessels using the da Vinci S robotic system. Two fresh frozen female torso cadavers were used to develop correct placement of the robotic column and trocars to allow a safe and adequate performance of aortic lymphadenectomy. The
85 resulting technique was applied to a patient with cervical cancer Stage IB2 presenting with enlarged aortic nodes. On the first torso, a small incisionwas made 3 cm medial to the anterosuperior iliac spine. The extraperitoneal space was developed by finger dissection of the peritoneum over the psoas muscle and left flank. CO2was insufflated and the space widened. The laparoscope was introduced through the left flank, equidistant between the iliac crest and left costal margin, and 10 cm distant from the first trocar. Under visual laparoscopic control, different robotic trocar positions were selected and tried. Peritoneal perforations occurred when the left costal margin trocars were placed too medial, requiring suturing. An optimal trocar position which would avoid arm collision and would allow adequate instrument movement was finally identified. The assistant’s trocar was inserted between the laparoscope and the caudal robotic trocar to provide ventral retraction of the peritoneum, suction and irrigation and removal of specimens without interference with the robotic arms. An additional assistant's trocar site was identified equidistant to the laparoscope and the cranial robotic trocar. The aortic nodes were removed from the aortic bifurcation to the renal vessels. The left external and common iliac nodes were also removed. Zero and 30 degree scopes were tried. Measurements, video and photographs were obtained. The robotic column, situated to the patient's right, was initially perpendicular to the torso but restriction on the arm movements required an adjustment to about 15° of angulation to the torso in a caudal direction. This resulted in expansion of the field of movement of the robotic instruments and avoided arm collisions.
Picture 90. The robotic column was located on the right side of the torso and at a 15 degree angle to the operating table. ( [139] ) On a subsequent date, an optimal trocar placement, as discovered with the first torso, was applied to the second torso and subsequently used in a patient. A 10–12 mm Spacemaker Plus Dissector System was inserted 3 cm medial to the anterosuperior iliac spine. The correct extraperitoneal space was identified with the index finder. The obturator with a balloon was inserted in a cranio-lateral direction through the trocar and the balloon inflated to its maximum. The obturator was removed and an 8 mm robotic trocar was inserted through the 10–12 mm Spacemaker Plus Dissector System which was left in place. The 12 mm optical trocar was introduced through the patient's left flank along the posterior axillary line, 10 cm cranial, and lateral, from the caudal robotic trocar. A second 8 mm robotic trocar was placed 10 cm cranial, and medial, to the laparoscope, immediately below the left costal margin and in line with the caudal robotic trocar. The assistant trocar was inserted immediately adjacent to them anterosuperior iliac spine, equidistant between the laparoscope and
86 the caudal robotic trocar. A 30 degree laparoscope was used. A retroperitoneal lymphadenectomy was performed including the left external iliac, presacral, and bilateral common iliac pelvic nodes, the aortic nodes from the aortic bifurcation to the renal vessels, including the retroaortic and retrocaval nodal groups, and the suprarenal nodes up to the superior mesenteric artery. The inferior mesenteric artery was transected to evaluate the effect of additionalm exposure. There were no limiting robotic arm collisions. For the removal of the presacral and common iliac nodes the laparoscope was rotated 45° counterclockwise which provided additional instrument reach by avoiding collision of the robotic arms with the scope.
In the case of the patient Prior to the patient entering the operating room, the robotic column was parked in the usual location for robotic pelvic surgery and the operating table swiveled counterclockwise about 90° in such away that the robotic column was on the right side of the operating table and would be facing the right side of the patient's abdomen.
Picture 91. Robotic column location. ( [139] )
The trocar sites were marked as in the second torso, the trocars were introduced orderly as described above.
Picture 92. Trocar sites placement. ( [139] )
87 The extraperitoneal space was developed with a 10–12 mm Spacemaker Plus Dissector System. No transumbilical trocar was inserted initially. A 30 degree laparoscope was inserted through the left flank 12 mm trocar. A PK grasper and a monopolar spatula were used through the caudal and cranial robotic trocars, respectively. The caudal robotic trocar was inserted through the balloon trocar, which was kept in place. The assistant's trocar was placed cranial and equidistant between the laparoscope and the cranial robotic trocar (this site was more favorable than the caudal position used on the second torso). The robotic column was advanced at a 15 degree angle to the patient's right abdomen and the arms docked to the robotic trocars. The peritoneum was reflected from the psoas muscle to the right margin of the vena cava and from below the aortic bifurcation to the left renal vein in a caudal to cranial direction. The left ovarian vessels and left ureter were mobilized ventrally and followed cranially until the left renal vein was identified. The inferior mesenteric and both ovarian arteries were preserved. Enlarged left aortic nodes were identified at and above the aortic bifurcation and below the left renal vein. They were selectively removed without difficulty. A single enlarged right aortic node was identified above the aortic bifurcation and removed. No additional enlarged nodes were seen. The robotic arms were undocked and the robotic column separated from the operating table. The trocar sites were closed and the operating table swiveled clockwise such that the robotic column became situated between the patient lower extremities. The operating, docking, and console times for the aortic lymphadenectomy were 103, 3.5, and 49 min, respectively. The blood loss was 30 ml. Magrina et al, reported dissection of two caveders and selective lymph node dissection in one patient up to the left renal vein. · In the same year, Narducci et al [140], described their early experience with robotic- assisted laparoscopy for extraperitoneal para-aortic lymphadenectomy up to the left renal vein, including Da Vinci robot positioning. Six patients underwent robotic-assisted laparoscopy using the Da Vinci apparatus. The patients included a man with a pT2 non-seminomatous germ cell tumour of the left testicle treated by chemotherapy with an incomplete response (mature teratoma), four women with locally advanced cervical cancer, and one case of bulky cancer of the vaginal cuff. The procedure was carried out using four port sites: one for the camera, one each for the no. 1 and no. 3 arms of the Da Vinci robot system, and one for the assistant.
Picture 93. Positioning of the Da Vinci surgical system at the right shoulder of the patient. ( [140] )
88 The Da Vinci Surgical system was positioned at the right shoulder of the patient . A 20 mm incision was made 2 cm cephalic to the left iliac spine. The skin, fascia, transverse muscles and deep fascia were incised, with special care in order not to open the peritoneum. The surgeon's left fore finger was introduced to check the landmarks in the extraperitoneal space, left psoas muscle and left common iliac artery. A 12 mm laparoscopic port was introduced under finger control into the left flank. The camera was then introduced into the port side of the left flank and a 5 mm laparoscopic port was placed on the anterior axillary line about 5 cm below the ribs. A fourth 12 mm laparoscopic port was placed above the left iliac crest. Finally, the 2 cm incision was used to place a 12 mm balloon port. Care was taken to maintain a 7–8 cm distance between the ports. The 12mmleft iliac crest port and 12 mm left flank port were used to introduce an 8 mm port dedicated to the robot (telescoping) for the robot's arms 1 and 3 (arm no. 3 was placed on the same side as arm no. 1. Arm no. 2 was not used for the extraperitoneal procedure). The robotic camera was introduced into the 12 mm left iliac spine port. The assistant used the 5 mm port below the ribs.
Picture94. Position of the surgical ports. ( [140] ) Narducci et al, described robotic-assisted lymphadenectomy can be carried out using the Da Vinci system safely and effectively with a short learning period for an experienced oncological team.
• Gorostidi et al [141], in 2014, performed nfra- and supramesenteric dissection up to the renal vein following their hospital protocol, as follow : The procedure begins with a transperitoneal inspection of the abdominal cabity through a 10 mm umbiligal trocar to rule out peritoneal dissemination. The trocars are placed in a manner similar to that described by Dargent et al.
Picture 95. Robotic trocars disposition. Blue: 12 mms trocar por transperitoneal and retroperitoneal optics. Red: 8 mmss trocar for robotic arms. Green: 10 mms trocar for assistant. ( [141] )
89 All procedures are performed using bipolar forceps and monopolar scissors. A 0 camera is used for the aortic and left aortic nodes. In the event of difficulties, a 30 camera can be used for interaortocaval and precaval dissection. In all cases, a retroperitoneal infrarenal para-aortic lymphadenectomy was performed, conserving the inferior mesenteric artery. If transperitoneal access to the pelvis was required after complete para-aortic lymphadenectomy for more pelvic surgical procedures (hysterectomy, pelvic lymphadenectomy, and so on), we repositioned the da Vinci system for classic pelvic docking. They added a single 8-mm procedures were required: lateral for the retroperitoneum, cephalic for the transperitoneal para-aortic lymphadenectomy because of peritoneal perforation, and between the legs for the pelvic procedure.
Picture 96. Robotic trocars disposition used for transperitoneal approach after retroperitoneal lymphadenectomy. ( [141] )
In the picture bellow we can see different trocars dispositions explored in the development of the technique.
Picture 97. Different trocars dispositions. ( [141] )
A few authors have described their technique for the execution of extraperitoneal robotic-assisted PAL, reporting encouraging results, as we can see in the table bellow.
90 Table 6. Extraperitoneal robot-assisted PAL.
Author Institut Year Study Study Surgic Roboti Roboti Extend Numb Patient Operat Intraop Conve ion of period design al c cases c arms of er of s ive erative rsion public indicat lymph aortic underg time compli rate ation ion adenec nodes oing (min) cations (%) tomy yielde conco d mitant proced ure Gorost Donostia 2013 2011- PS 2 13 N/R Ifrarenal 12 12 323 1 (7,7%) 3 (23%) idi M Universi 2013 Cervical PAL (92,3%) ty cancer [141] Hospital 9 , Endomet Sebastia rial n, cancer Spain 2 Ovarian cancer Fastrez Leuven 2013 2007- PS 7 7 4 Inframes 9,5 0 (0%) 100 1 0 (0%) M Cancer 2011 Cervical enteric (7-12) (60-140) (14,2%) Institute, cancer PAL [142] KU/Uni versity Hospital Leuven, Leuven, Belgium Bats Europea 2014 2010- RS 15 24 3 Infraren 18 12 240 2 (8,3%) 6 (25%) AS n 2013 Cervical al PAL (14-25) (50%) (180- Georges cancer 12 300) [143] - 8 isolated Pompido Endomet PAL u rial 12 non Hospital cancer* isolated , 2 PAL Paris, Ovarian France cancer Dıaz- Hospital 2014 2009- PS 17 17 N/R Infraren 17 0 (0%) 150 0 (0%) 0 (0%) Feijoo Vall 2013 Cervical al PAL (10-31) (85-270) d’Herbo cancer B[144] n, Bacelon a, Spain Nardu Oscar 2015 2008- RS 30 37 4 Infraren 18,7 0 (0%) 220,9 2 (5,4%) 1 (2,7%) cci F Lambert 2014 Cervical al PAL Center, cancer [145] Lille 6 cedex, Endomet France rial Paoli cancer Calmette 1 s Fallopia Insitute, n tube Marsille, cancer France
All these studies [141-147], demonstated that the robotic extraperitoneal para-aortic lymphadenectomy is feasible and offers the advantages of retroperitoneal access. Intra-operative and postoperative morbidity were low. There was a high rate of symptomatic lymphocyst. More lymph nodes were removed during an isolated transperitoneal PAL dissection compared with a combined procedure with hysterectomy. Extraperitoneal approach seems attractive, relative to transperitoneal dissection, but the superiority of one or the other way is not demonstrated yet.
91 12.4 ROBOTIC SINGLE- PORT LYMPHADENECTOMY Recent technologic advances in endoscopic instrumentation and optics have allowed the development of single-port laparoscopy (SPL), also known as laparoendoscopic single-site surgery (LESS). Preliminary advances in LESS, as applied to gynecologic surgery, demonstrate that the techniques are feasible provided that both laparoscopic surgical expertise and optimal instrumentation are available [148,149]. Unique aspects of LESS such as instrument crowding, loss of depth of perception, and need for significant laparoscopic skills challenges the reproducibility and diffusion of LESS. Robotic surgery has greatly improved surgeon dexterity, surgical precision, visualization, ergonomics and allowed procedures that were performed by laparotomy to be performed by laparoscopy. However, robotic surgery has substantially increased the number and size of ports required compared with conventional laparoscopy. Escobar et al, reported promising results on the feasibility of a dedicated single-port robotic platform, for the da Vinci system for gynecologic and urologic surgery in the porcine model [150,151]. • Escobar et al [152], in 2011, demonstrated that the performance of various oncology procedures using the new da Vinci single-site robotic platform is feasible. Three fresh frozen female human cadavers were used to develop the correct placement of the robotic column, docking sequence, optimal position and ergonomics, and reproducibility of procedures (performed on the animal model) to allow for a safe and adequate performance of hysterectomy, pelvic and aortic lymphadenectomy using the da Vinci Si-single-site platform. Procedures performed in this training protocol included : hysterectomy, bilateral salpingo-oophorectomy, modified radical hysterectomy, six pelvic lymph node dissections and one para-aortic node dissection. To enable single incision surgery, the curved cannulae are placed in the patient's umbilicus (or other suitable location), with the curves of the cannulae crossing over each other. This allows alignment of the remote center and effectively re-creates triangulation of the Instruments. When the single- port instruments are docked into the da Vinci Si System, they are automatically reassigned so the right hand of the Surgeon's Control will control the left instrument and vice versa. From the Surgeon's Console, the surgeon controls the movement and position of each individual instrument's arm as necessary to perform the surgical procedure just as with the existing EndoWrist instruments.
Picture 98. Robotic single-site platform, and port system. ( [152] )
92 All the procedures were technically successful with no need of additional ports or conversions to a standard laparoscopy. The median time of port insertion and BMI was 6 min range (4–10) and 33 min range (25–56) respectively. The median time for a left and right pelvic lymph node dissection was 22 min range (22–23) and 28 min range (26–38) respectively. There was significant difference in operating times for symmetrical procedures (pelvic lymphadenectomy).
• The robotic sinlgle site approach has analytically been described, in 2013, by Vizza et al [153]. The exact thechnique is as follow :
The first step starts with an initial access, with an 2 cm long incision that is made over the lower rim of the umbilicus down to the level of the fascia, which is opened along the longitudinal axis of the body. Lubrication of the single-site port by dipping it in a sterile solution (e.g., saline or water) is performed before insertion. Using an atraumatic clamp, the single-site port is grasped just above the lower rim. The leading edge of the folded port is inserted into the incision with a downward motion while countertraction is provided by retractors within the incision. Pneumoperitoneum is established after insufflation of the abdomen up to a pressure of 12 mm Hg. The proper positioning of the port is achieved when the top port flange lies flat against the abdominal wall and the port is not bulging or deformed.
Picture 99. a) Single-site port (Intuitive Surgical). b) Handle of the port. c) Positioning the port in the umbilical incision. ( [153] )
In the second step, the table is placed in the Trendelenburg position (30). Before docking, the da Vinci robotic column is positioned between the patient’s feet, and the robotic arms are opened in the appropriate positions: the setup joints are extended in a straight line, and the camera arm is fixed in the ‘‘sweet spot’’ of the blue stripe on the arm. Then the system is further advanced in a straight line until the camera arm is situated above the port site. A 8.5 mm endoscope cannula is inserted vertically. A careful inspection of the entire abdominal cavity is performed in order to identify any suspicious peritoneal lesion that would exclude the patient from having the procedure completed by
93 robotic single site. A 5 * 250 mm curved cannula (arm 2) is then lubricated and inserted through the designated lumen while the external rim of the port is held by the assistant to avoid displacement. The tip of the cannula is constantly visualized with the endoscope by rotating the tab on the cannula bowl slightly toward the patient’s feet. The cannula is guided near the uterus and then held still to allow docking. This is done by holding the cannula still in one hand while the other hand brings and mounts the arm to the second 5 * 250 mm curved cannula (arm 1). Finally, the instruments are introduced: a monopolar cautery on arm 2 and a curved scissor on arm 1. The assistant’s 5 mm accessory cannula, which the assistant uses to hold and move either a suction/irrigator or a multifunctional versatile laparoscopic device that grasps, coagulates, and transects simultaneously or a suction/irrigator, is inserted last, and a da Vinci Si 8.5 mm 30 endoscope is used during the operation.
A) B)
C) D) Picture 100. The da Vinci Si Surgical system. (A) Before docking. (B) After docking. (C) Platform. (D) Abdominal wall after platform removed. ( [153] )
• Tateo et al [154], in 2014, pointed out that robotic single-site pelvic lymphadenectomy using bipolar forceps and monopolar hook is feasible. Since then, papers have described the feasibility of robotic-single site hysterectomy [153,155,156] for benign and malign pathologies but only with the development of new single site 5 mm instruments as the bipolar forceps, robotic single site
94 platform could be safely utilized also for lymphadenectomy. A 65 year-old, multiparous patient with a body mass index of 22.5 and diagnosed with well differentiated adenocarcinoma of the endometrium underwent a robotic single-site peritoneal washing, total hysterectomy, bilateral adnexectomy and pelvic lymphadenectomy. The procedure was performed using the da Vinci Si Surgical System through a single 2,5 cm umbilical incision, with a multi-channel system and two single site robotic 5 mm instruments. A 3-dimensional, HD 8.5 mm endoscope and a 5 mm accessory instrument were also utilized. Type I lymphonodes dissection for external iliac and obturator regions was performed [157]. Total operative time was 210 min; incision, trocar placement and docking time occurring in 12 min. Total console time was 183 min, estimated blood losswas 50ml, no intra-operative or post-operative complications occurred. Hospital discharge occurred on post operative day 2 and total number of lymphnodes removed was 33.
• In 2014, Ha-Na Yoo et al [158], in Korea, reported a pilot study to discuss the feasibility of single- site robotic surgery for benign gynecologic tumors and early stage gynecologic cancers, in 6 patients. In their study, the surgeon successfully dissected the pelvic lymph nodes in four cases. While assisted by a roticulator grasper, dragging the obliterated hypogastric artery to the medial side simplified the procedure. This required collaboration with an assistant surgeon. When dissecting pelvic lymph nodes, the surgeon switched the position of the instruments between hands. This was to avoid collision between the instruments inside the abdomen. For example, when dissecting the right lymph node, the surgeon would hold the monopolar hook in his right hand while pulling the lymph node to the left with a Maryland dissector held in his left hand. When dissecting the left lymph node, the operator dragged the lymph node to the right with a Maryland dissector in his right hand and so on. To remove the dissected lymph nodes, a 5-mm cannula was changed to a 10-mm cannula at the end of the surgery. Then, dissected lymph nodes were removed from the pelvic cavity with an endobag.
Picture 101. Lymph node dissection with the assistant's grasper. ( [158] )
A lot of studies have been done to evaluate the feasibility of robotic single-port surgery for gynecologic malignancies, that included especialy pelvic lymph node dissection or lymphadenectomy. In the table bellow we can see the median number of pelvic lymph nodes yielded in some of these surgeries.
95 Table 7. Studies for robotic single- port surgery. CR: Case report; R: Retrospective; P: Prospective;NR: Not reported; *:Sentinel node biopsy. Author Type of study No. of patients Median No. of Convertions (%) pelvic lymph nodes Mereu L (2012) R 4 NR 0 [155] Vizza E (2013) P 17 NR 0 [153] Tateo S (2014) CR 1 33 0 [154] Bogliolo S (2015) CR 1 27 0 [159] Bogliolo S(2015) P 17 NR 0 [160] Sinno AK (2015) CR 1 2* 0 [161] Yoon A (2015) CR 1 11 0 [162] Corado G (2016) R 125 13(3-32) 1 (0,8%) [163]
• A new article has been accepted recently, by the Journal of MinimallyInvasive Gynecology. In this study, Murkazel et al [164], tried to assess the feasibility of incorporating robotic laparoendoscopic single-site (R-LESS) surgery into gynecologic oncology care. Patients undergoing R-LESS hysterectomy for gynecologic malignancies, preinvasive disease, or risk reduction performed by a single gynecologic oncologist between 2014 and 2016. They identified 30 patients undergoing R-LESS hysterectomy meeting study criteria over a two- year period. Indications for surgery included uterine cancer (n=13), preinvasive cervical or uterine disease (n=9), cervical cancer (n=3), and hereditary gynecologic cancer risk (n=5). The median age was 52 years (range, 35 – 77), and body mass index was 26 kg/m2 (range, 19 – 34). Median uterine size was 8 cm (range, 5.5 – 11). Eighteen patients had prior abdominal surgery (60%). Twenty- seven patients underwent R-LESS extra-fascial hysterectomy, 11 of whom underwent only RA- TLH +/- BSO with a median operative time of 140 minutes (range,115–179). Procedures performed concurrently for the remainder included pelvic sentinel lymph node mapping (n=14) and pelvic lymphadenectomy (n=2), with respective median operative times of 175 (range, 150–230) and 233 minutes. One patient with endometrial cancer was converted to multiport robotic surgery to complete a pelvic and para-aortic lymphadenectomy due to high-risk disease on frozen section. Three patients underwent R-LESS radical hysterectomy, BSO, SLN mapping and pelvic lymphadenectomy with a median operative time of 412 minutes (range, 336–451). No perioperative complications were encountered and all patients were discharged within 24 hours of surgery. Murkazel et al, concluded that in highly selected patients, R-LESS extra-fascial and radical hysterectomy is associated with acceptable operative times and perioperative outcomes. With additional experience, surgeons may offer this approach to patients undergoing increasingly complex procedures, even in the gynecologic oncology setting.
96 DISCUSSION Ovarian cancer metastases disseminate via the lymphatic system. The metastases priliminary occur in the para-aortic nodes although they are also periodically identified in the pelvic nodes [53,165]. Reported studies have doccumented a 22% incidence of this condition in ovarian cancer patients after a systematic lymphadenectomy [33]. It has been observed a higher rate of positive aortic nodes (84%) than pelvic node metastases (78%) especially in early ovarian cancer.The incidence of positive nodes bilaterally and positive aortic nodes indicates the need for bilateral pelvic and aortic lymphadenectomy, extending above the inferior mesenteric artery, in all patients regardless of laterality of primary tumor [166]. Lymphadenectomy has initially been performed via open surgery, using large incisions during the laparotomy [167]. Minimally-invasive approaches are currently applied to complicated surgeries in the field of gynecologic cancer providing a few benefits. However, in ovarian cancer, the resection area is broader than in other gynecologic cancers, so dissemination occuring from exfoliation of tumor cells and a larger risk of intraoperative tumor rupture remain limitations of laparoscopic staging surgery.Although, due to recent advances in laparoscopic techniques and instruments, it is possible to perform the procedure laparoscopically. Since the initial report by Dargent et al in the late 1980s, laparoscopic lymphadenectomy has been utilized in the management of gynecologic malignancies. After Dargent's description of the first pelvic lymhadenectomy performed laparoscopically, Nezhat et al described the first para-aortic lymphadenectomy performed laparoscopically for cancer of the uterine cervix. Many reports since, have described the safety and effectiveness of laparoscopic lymphadenectomy for gynecologic malignancies. Over recent years, there has been an expanding literature available regarding outcomes and complicatios of the minimally-invasive techniques ( laparoscopic and robotic). Laparoscopy offers multiple advantages in the management of malignancy, including smaller incisions, shorter hospital stay, quicker recovery, improved visualization, less need for postoperative analgesics and a lower risk of complications, such as blood loss, wound infection, herniation and ileus. These characteristics may prove particularly important in the setting of oncology where a shorter recovery period may facilitate a shorter interval to postoperative treatments sush as chemotherapy or radiation. Disadvantages include a long lurning curve, counterintuitive motions and limited-depth perception as imaging is limited to 2- dimensional views. In an effort to overcome these limitations, multiple innovations have evolved over the last years. Laparoscopic instrumentation has expanded to include several different vessel sealing devices with integrated cutting capabilities, endoscopic staplers, articulating instrument tips, 3- dimensional capabilities and computer-enhanced technology in the form of robotics [168]. Complications of laparoscopic lymphadenectomy can be divided into two general groups. The first group includes those that are inherent to laparoscopy itself and the second group includes those that are inherent to the procedure of lymphadenectomy, regardless of the method by which it is performed. The major complications are : • Vascular injuries. Vascular injuries related to lymphadenectomy are potentially life- threatening complications. The most common injury is that of the inferior epigastric and other superficial anterior abdominal wall vessels. Kavoussi et al [169] in a series of laparoscopic lymphadenectomies reported that 7 out of 9 vascular complications occurred as a result of trocar injury to the anterior abdominal wall vasculature. Vascular injuries can also occur as a result of Veress needle insertion. A systematic review of 696,502 cases from 55 articles by Azevedo et al. [170] showed a total of 1,575 injuries caused by insertion of Veress needle. Of these, 98 were vascular injuries, 42 of which were major vascular injuries including the aorta and the common iliac arteries. Potential vascular compromise
97 specific to pelvic lymphadenectomy include injury to the obturator, internal ilia, external iliac or the common iliac vessels. Vessels at risk during a para- aortic lymphadenectomy include the aorta and vena cava, the common iliac, inferior mesenteric, lumbar, gonadal and renal vessels. Querleu and Leblanc [171] in their series of 1000 gynecologic patients who underwent laparoscopic pelvis and/ or para-aortic lymphadenectomy reported a significant vascular injury rate of 1.1%. current reports confirm the low incidence of vascular injury during laparoscopic lymphadenectomy. • Gastrointestinal injuries Bowel injury is a potential complication of any laparoscopic procedure. Bowel can be easily damaged at trocar or Veress insertion, adhesiolysis or thermal injury during dissection. Querleu and Leblanc reported a bowel injury rate of 0.4% [171]. Also, bowel herniation can result as a consequence of absent or inadequate fascial closure of the trocar defects [172]. • Genitourinary injury Cystotomy during trocar insertion, adhesiolysis or dissection has been delineated as a complication of laparoscopic lymphadenectomy. This can occur during the insertion of the suprapubic trocar or when opening the paravesical or pararectal spaces. Specific to lymphadenectomy is a possible uretal injury. Pelvic lymphadenectomy places the ureter at risk for sharp, crush or thermal injury [169,173]. The lumbar portion of the ureter is at risk during para-aortic lymphadenectomy, especially on the left side. This can be take place if the lateral dissection overlying the psoas muscle is carried out above the ureter instead of in the correst surgical plane. • Neurologic injury Genitofemoral nerve injury is the most likely to occur during removal of the lateral pelvic lymph nodes. Obturator nerve is a more worrisome complication of laparoscopic lymph node dissection.This complication only occurs if the nerve is not reliably identified prior to resecting the obturator lymph node package. The femoral nerve, which lies within the body of the psoas muscle in the pelvis, is also at risk during pelvic lymphadenectomy. It can occur if the nerve is superficial in the belly of the muscle and is exposed to extensive electrocautery during the dissection. The ulnar nerve can also be traumatized if not properly padded in the course of tucking the arms for the operative procedure. Other peripheral neuropathies can also occur secondary to poor patient positioning. • Abdominal wall metastases and peritoneal tumor dissemination Abdominal wall metastaseshave been reported after both laparoscopy and laparotomy. The incidence of these complications is 1% after laparotomy and 1% to 3% after laparoscopy. The most likely mechanism for port- site metastase seems to be by direct contamination during the procedure. Port sites can be contaminated during tumor extraction or during the removal of contaminated ports. Several studies lave reported the recurrence at port sites [174-180]. Although, no prospective evidence exists indicating that port-site metastases worsen prognosis [174,177]. A Few clinical reports, have also raised concerns regarding possible intraperitoneal tumor dissemination during laparoscopy. Canis et al. Reported a case of pelvic dissemination found at a restaging procedure 3 weeks after initial adenectomy foe well- differentiated serous adenocarcinoma of the ovary [181]. Althoygh, removal of all specimens using an endobag and removal of all ports once the pneumoperitoneum is reduced is recommended to prevent possoble contamination. • Other complications Lymhoceles and lymphedema have been reported to occur following laparoscopic lymphadenectomies. Infectious complications have also been reported and include infected pelvic hematoma, clostridium difficile infection and wound complications. Thromboembolic events can complicate any operative procedure in the pelvis, especially in cancer patient, such as venous
98 thrombosis or pulmonary emboli, at the postoperative period. Gas embolism is another complication concernig the laparoscopic procedure. Most of these complications can be reduced with a thorough preoparative bowel preparation, a steep Trendelenburg patient positioning, an adequate pneumoperitoneum,a bladder decompression with a Foley catheter and a good experience of the surgeon. On the other hand, robotic-assisted procedures have several advantages. Binocular vision and 3- dimensional views permit improved depth perception, which may facilitate advanced laparoscopic procedures. The console is located away from the patient and permits the surgeon to operate in a comfortable, suited position, thus making operator positioning more ergonimoc. Tremor filtration is another benefit of robotic-assisted surgery, as the video laparoscope is no longer in a human hand, which may tire or move, but rather is fixed in posotion by the robotic arm. This feature permits finer surgical movements with more precise dissections. The articulating instrument tips that are utilized in traditional laparoscopy are taken to a new level with not only rotational capabilities but an independent 90- degree articulation of the tip. These features make robotic surgery more intuitive, with a shorter learning curve. Additional robotic arms have been introduced to further minimize the need for surgical assistants in instituitions that may have limited staff. Robotic-assisted procedures are not, however, without their limitations. The equipment is still very large, bulky and expensive. The stuff must be trained specifically on draping and docking the apparatus to maintain efficient operative times. Functional limitations include luck of haptic feedback, limited vaginal access, limited instrumentation and larger port incisions requiring fascial closure. In terms of haptic feedback, visual cues become imperative to ensure that tissue manipulation is not performed with yndye force. Intracorporeal knots must be tried carefully such that the suture is not avulsed by the strength improsed by the robotic arm. Limited vaginal access can be problematic in gynecologic surgery as frequent uterine or vaginal manipulation is necessary, particularly in extirpative procedures. Once the robot has ascended into place, access to the vagina becomes limited. Robotic trocars are 8mm in size with a 12mm laparoscope. These incision sizes are larger than 5mm accessories that are frequently used in traditional laparoscopy and also require fascial closure, with higher risk of herniation. The robot is also limited in its intrumentation. Exchanging instruments become more cumbersome and require a surgical assistant to change them. As expertise with minimally- invasive surgery has improved, this approach has been favorably utilizised for comprehensive staging of ovarian cancer. Pioneering work comparing the peri- operative and survival outcomes of minimally-invasive surgical staging of ovarian cancer has been reported by Magrina et al [124], in 2011. The author compared 25 robotic, 27 laparoscopic and 119 laparotomy ovarian cancer debulking procedures. The surgical procedures were categorized as Type I debulking (hysterectomy with adnexectomy, omentectomy, pelvic and infra-rebal aortic lymphadenectomy, appendectomy and excision of metastatic peritoneal disease), Type II (Type I debulking plus one aditional major procedure) and Type III (Type I debulking plus two or more major procedures). Complete debulking was achieved in 84% of patients in robotic group, 93% in the laparoscopy group and 56% in the laparotomy group. Both robotic and laparoscopic approaches for Type I and Type II had favorable blood loss, length of hospital stay, intra-operative and post- operative complications except for longer operative times in the robotic group as compared to laparoscopy and laparotomy. There was no overall improvent in morbidity or hospitalization in Type III debulkings using the robot and because of excessive operative time requirements the author advised laparotomy foe these cases. He emphasized that optimal debulking is more important than the type of the surgical method, as there was no difference in the overall and progression-free survival fro robotic and laparotomy patients. However, one of the most important factors to consider is the challenge associated with the need to explore all four quadrants of the abdomen in cases of advanced ovarian cancer with carcinomatosis. For this reason, Magrina et al suggested the rotation of operative table and redocking the robot at the patient's head. This way, it was easier to
99 excise para-aortic lymph nodes to higher levels and other upper abdominal metastases. Numerous studies have evaluated the utility of laparoscopic staging of early ovarian cancer, although there are scan data documenting the use of this procedure via robotic-assisted surgery. In the table bellow there are studies that evaluated the laparoscopic and robotic-assisted staging outcomes in the management of early- stage ovarian cancer.
Table 8. Laparoscopic and robotic-assisted surgery lymph node staging outcomes in the management of early-stage ovarian cancer. Author Year Size,n Surg Operative EBL, ml PLN, n PAL, n Complic Hospital type time,min ations, stay, d n(%) Ghezzi 2007 26 LS 348 250 24.5 9.8 0 4 et al [182] Colome 2008 20 LS 223 NA 18 11.3 1 (5) 3 r et al [183] Park et 2008 19 LS 220 240 27.2 6.6 1 (5.3) 8.9 al [184] Liu et al 2013 35 LS 210 197 18.23 * 4 (11.4) 16.3 [185] Feuer et 2013 63 RS 139 95 NA NA 10 2.3 al [186] (15.9) Gorosti 2013 13 RS 323 NA 12.8 12 4 (30.7) 3.4 di et al [187] Brown 2014 26 RS 174 63 14.6 5.8 0 0.77 et al [188]
Ghezzi et al [182], compared the results of laparoscopic staging of apparent early ovarian cancer with those obtained with comprehensive surgical staging laparotomy. They found that there were no significant differences between the two groups with regard to median number of lymph nodes and likelihood of identifying metastatic disease. No conversion to laparotomy and no intraoperative complication occurred in the laparoscopy group. Operative time was significantly longer in the laparoscopy group when compared with the laparotomy group (377±47 vs. 272±81 min, P=0.002). One patient in the LPS group had a retroperitoneal haematoma recognized in the postoperative period, and this required laparotomy and ligature of the hypogastric arteries to achieve haemostasis. Minor postoperative complications occurred in 1 (6.7%) patient in the laparoscopy group and in 8 (42.1%) patients in the laparotomy group. Hospital stay was significantly shorter in the LPS group. Median (range) follow-up time was 16 (4–33) and 60 (32–108) months in the laparoscopy and laparotomy group, respectively. There were no recurrences in the laparoscopy group whereas 4 (7.1%) recurrences occurred in the laparotomy group. Overall survival was 100% in both groups. They concluded that laparoscopic method is safe but with a longer operative time. Liu et al [185], compared the results of staging of early-stage ovarian cancer between 35 patients who went laparoscopically and 40 patients who were treated via open surgery. They found that there
100 was no significant differences in operative time, intraoperative blood loss, number of dissected lymph nodes, tumor rupture rate, complication rate, upstaging rate and rate of postoperative chemotherapy. They also mentioned that the laparoscopy group had significantly shorter hospital stay and time of first postoperative flatus and had significantly lower rate of poor wound healing than the laparotomy group. Liu et al, demonstrated that laparoscopic way is a safe technique and has many advantages. Park et al [189], in 2013, tried to perform a quantitative analysis on operative outcomes of laparoscopic staging surgery in patients with presumed early-stage ovarian cancer using a metaanalysis. They identified 11 observational studies. The combined results showed that the estimated blood loss in laparoscopy was significantly lower than for laparotomy. The overall upstaging rate after laparoscopy was 22.6%, without significant heterogeneity among all studies. The overall incidence of convertion from laparoscopy to laparotomy was 3.7%. Only 1 case with port-site metastases in 11 studies in this article was reported [190]. Through their quantative analysis, Park et al concluded that the operative outcomes of a laparoscopic approach in patients with early-stage ovarian cancer could be compatible with those of laparotomy. In 2014, Brown et al [188], as we can at the table above, reported their own experience with the use of robotic-assisted surgical staging in the management of early-stage ovarian cancer. They identified a total of 26 early-stage ovarian cancer patients. They reported a very short operative time ( 174 min ) and a very low intraoperative blood loss (63 ml). In their series, there were no intra-operative complications, the mean number of pelvic and para-aortic lymph nodes removed was14.6 and 5.8, respectively. The patient's mean duration of hospital stay was only 18.4 hours. With these results, the robot-assisted procedure seemed to be safe with a minimal patient complication rate. Minimally invasive surgery to treat localized ovarian cancer results in equivalent oncological outcomes and decreased morbidity, pain and recovery time when compared to laparotomy [191].A few studies have reported on the feasibility of robotic-assisted surgery for the management of ovarian cancer [124,127,192-193] . However, the recommendation was to constrain minimally invasive surgery to localized cases due to the limited data available for advanced disease. Neoadjuvant cytoreductive chemotherapy followed by interval surgery has been presented as an alternative approach to major upfront debulking surgery in cases of advanced ovarian cancer [194]. It has been suggested that the selective use of neoadjuvant chemotherapy may broaden the patient population eligible for a minimally invasive approach [192]. Therefore, Feuer et al [186], tried to evaluate the feasibility and efficacy of robotic-assisted management of epithelial ovarian cancer, including patients with neoadjuvant chemotherapy. There were 63 robotic and 26 abdominal cases. Patient characteristics were similar for age, uterine weight, and BMI, with prior abdominal surgery more common in the abdominal group. Robotic operative time was longer, while blood loss and hospital stay were reduced. Major complication rates (16% vs. 23%, p = 0.4209) and lymphadenectomy yields (13 vs. 11 nodes, p = 0.2310) were similar. Neoadjuvant chemotherapy was more common in the robotic group (52% vs. 15%). Residual disease rates for all cases and for Stage II–IV cases were equivalent. Follow-up was longer for the abdominal group; however, an equivalent percentage of patients had at least 1 year of follow-up. At 1 year, survival and no evidence of disease rates were equivalent for all cases (survival: 97% vs. 90%, p = 0.2501) and for Stage II–IV cases (survival: 96% vs. 88%, p = 0.3080). In 2015, Chen et al [196], reported that robotic surgery, with a careful patient selection, could be a feasible and potentially optimal approach for managing epithelial ovarian cancer, and that robotic and laparoscopic approach had similar results. In their study, they retrospectively analysed 138 women with stage IA-IIIC epithelial ovarian cancer and borderline tumors and compared the surgical performance of robotic, laparoscopic and laparotomy surgery.All enrolled cases were reviwed for patient demographics, perioperative parameters, complications and survival.
101 The operation time and blood loss was significantly reduced in the robotic and laparoscopic groups. Moreover, robotic surgery was associated with decreased postoperative pain score. The length of hospital stay and time to full diet resumption were also shortened for those who underwent robotic and laparoscopic procedures. Survival analysis and complication rates were similar between the two groups. The results are shown in the table bellow.
Table 9. The results of the comparison between robotic, laparoscopic and laparomy approach in treating epithelial ovarian cancer, in 138 patients. Parameters Robotic approach Laparoscopic Laparotomy Significance (n=44) approach (n=21) approach (n=73) Operation time 176.8 (54.3) 232.3 (85.4) 287.2 (144.0) 0.001 (min) Estimated blood 96.9 (83.2) 326.2 (368.7) 848.6 (666.9) <0.001 loss (ml) Tranfusion rate, % 0 14.3 46.6 <0.001 Conversion to 0 9.5 - - laparomy, % Lymph node yield 24.2 21.4 25.9 0.37 Postoperative pain 2.7 4.6 5.2 <0.001 score Time to full diet 1.9 (1.3) 2.1 (1.4) 3.7 (2.2) 0.001 resumption (days) Length of hospital 3.5 (1.9) 5.5 (3.0) 9.7 (6.4) <0.001 stay (days) Total 2.3 4.8 12.3 0.13 complications, % Intraoperative 2.3 4.8 9.6 0.28 complications, % Postoperative 0 0 2.7 0.41 complications, % Follow-up time 13.1 (5.3) 29.6 (19.0) 26.7 (17.7) (months) Overall survival, 100% 100% 95.8% 0.35 analysis at 13.1 months
Recents years, there is an ongoing debate on which approach, transperitoneal or extraperitoneal, is superior for the performance of laparoscopic para-aortic lymphadenectomy for the surgical staging of gynecologic cancer. The reported studies observed no significant differences between both surgical approaches for perioperative outcomes and number of aortic nodes. In last years, the extraperitoneal approach seems to be associated with shorter surgical duration, whereas the transperitoneal, due to better ergonomy, enables laparoscopic management of operative complications. In the table below, we can see different studies comparing the extraperitoneal and transperitoneal para-aortic lymphadenectomy.
102
Table 10. Overview of different studies comparing the extraperitoneal and transperitoneal laparoscopic para-aortic lymphadenectomy. Study Study no. Sample size Aortic Operative Conv Conv Intrao Postop type, of nodes time ersio ersio perati erative cancer patie n to n to ve compli type nts lapar trans compl cations otom perito ication y neal s Parkish Retrosp 194 34 extraperitoneal 10 339.5 0 0.088 0.059 0 et all ective, [197] EC 160 tranperitoneal 4.5-5 286-297.5 0.118 - 0.044 0.038 Morales Retrosp 47 28 extraperitoneal 15 ± 5.9 173 ± 51 0.035 NS 0.071 0.036 et al ective, [198] EC, OC 19 transperitoneal 17.4 ± 8.6 211 ± 18 0.021 - 0 0.053 Akladio Retrosp 72 21 extraperitoneal 13 125.6 0 0.142 0.143 0.238 s et al ective, [199] EC, OC 51 transperitoneal 16 200 0.013 - 0.098 0.313 EC endometrial cancer, OC ovarian cancer, NS not significant
In 2016, a prospective randomized trial comparing transperitoneal versus extraperitoneal laparoscopic aortic lymphadenectomy for staging of endometrial and ovarian cancer, the STELLA trial [200], was published. Patients with endometrial or ovarian carcinoma requiring aortic lymphadenectomy for surgical staging were randomized to an extraperitoneal or transperitoneal approach by laparoscopy or robot-assisted laparoscopy.A total of 60 patients were entered into the study, 48 with endometrial cancer (80 %) and 12 with ovarian cancer (20 %). Thirty-one patients (51.6 %) were randomly assigned to the extraperitoneal group and 29 to the transperitoneal group (48.3 %). The means operating time was 90 min in both group (p = 0.343). The mean (range) blood loss was 105 (10–400) mL for extraperitoneal versus 100 (5–1000) mL for transperitoneal group (p = 0.541). There were no differences in the number of collected lymph nodes between the two groups [median (range) for extraperitoneal 12 (4–41) vs. 13 (4–29) for transperitoneal (p = 0.719)]. The extraperitoneal and transperitoneal approaches are two different techniques for laparoscopic or robotic-assisted para-aortic lymphadenectomy with advantages and drawbacks, and therefore patient selection for each approach is preferable. Factors to account for the choice of approach are primarily patient habitus, location of nodal disease, and, importantly, the type of other procedures required for the completion of cancer surgery. Lymph node staging seems to be better if the procedure is isolated. In case of combined procedures, the surgical approach should be modified regarding patient BMI and the associated procedure, to increase lymph node count ( Lambaudie et al,2012 [201]). Therefore, gynecologic oncologists with advanced laparoscopic and/ or robotic skills should be versed in both techniques to accommodate the optimal approach for each patient.
Regarding the comparison of robotic-assisted versus conventional laparoscopy for extraperitoneal laparoscopy, the perioperative outcomes seems to be similar. A lower blood loss and a little higher number of aortic nodes can be removed in the robotic approach, but both of which are not clinically significant [202].
103 The use of minimally invasive surgery has increased dramatically in gynecologic oncology. During the last years, interest in laparoendoscopic single-site surgery (LESS), also increased. Several studies have shown that LESS is a feasible and safe technique that minimize the parietal trauma and improve cosmesis for benign gynecologic conditions [203-205]. Other studies have shown improved postoperative pain scores in the immediate postoperative setting in patients undergoing LESS versus standard multiport laparoscopy [206-208]. Although there are potential benefits of LESS, they are accompanied by select ostacles, especially when this surgical approach is considered for more complex procedures. Technical issues with LESS include instrument crowiding and clashing, ergonomic difficulties image instability, loss of instrument triangulation, loss of robust traction and limited range of motion [209-210]. The robotic single-site platform offers one approach to overcome the limitations of LESS. Robotic- assisted laparoendoscopic single-site surgery (R-LESS) is feasible and safe and has been shown to possibly reduce morbidity versus multiport syrgery in a number of small case series of patients udergoing benign gynecologic procedures[211-212]. However, this has not been widely evaluated in more complex oncologic procedures. In 2016, Murkazel et al [164], suggested some criteria for a safe successful R-LESS program. The criteria are th following : 1. The surgeon must have a commitment to learning the R-LESS technique. This should include performing a large number of R-LESS in the learning curve period. 2. Patient selection is critical. The best candidates are patients with a BMI under 30. 3. A history of prior abdominal or pelvic surgery requires individualized consideration 4. The indication for surgery should influence the decision of selecting an R-LESS approach. 5. The surgeons consider R-LESS only if they are comfortable with multiport robotic surgery as this is the most relevant platform from which the transition to R-LESS can be made. Large prospective studies comparing R-LESS to standard multiport procedures do not exist, so there is the need of further exploring the use of this innovative surgical platform in gynecologic oncology and ascertaining the benefits of R-LESS approach compared with multiport procedures.
104 CONCLUSION Lymphadenectomy is indicated in all ovarian cancers because of the high incidence of lymphatic metastasis. The upper aortic infra-renal lymph nodes are of special concern because of the direct drainage from the left ovarian vein to the left renal vein and the right ovarian vein to infra-renal vena cava. Recent stages in FIGO staging reflect the relative prognostic influence of lymph node staging, stratified by the size of the lymph node metastasis. Complete surgical debulking of advanced ovarian carcinoma including pelvic and aortic lymphadenectomy has been associated with improved survival. For years, laparotomy remained the prevailing method for the management of ovarian cancer, and especially of advanced stage cancer. Since 2000, the use of minimally-invasive surgery has dramatically increased in gynecologic oncology, providing a few benefits. In this study, all the minimally-invasive techniques for pelvic and para-aortic lymphadenectomy were analytically presented : laparoscopic and robotic procedures, transperitoneal and extraperitoneal approaches for paraaortic lymphadenectomy and single- port surgery strategies. Each one, has advantages and disadvantages. All techiques seem to be safe and feasible. Robotic and laparoscopic approaches seem to have similar results : a shorter operative time, a lower estimated blood loss, a decreased postoperative pain score, a shorter length of hospital stay and a shorter time to full diet resumption. Survival analysis, number of lymph nodes yielded and complication rates seem also to be similar between the two groups. Robotic lymphadenectomy seem to be a feasible alternative approach in managing ovarian cancer, with a careful patient selection. However, large case-control studies to evaluate the efficacy of using robotic surgery in treatment of ovarian cancer are still lacking. Furthermore, the equipement is still very large, bulky and expensive, and the stuff must be trained specifically on draping and docking the apparatus to maintain efficient operative times. Regarding to the single-port surgery approaches, large prospective studies also are needed, in order to evaluate the use of this innovative surgical technique in lymphadenectomy for ovarian cancer. All the presented minimally-invasive techniques have been utilized safely. The most feasible, efficient and economic seem to be the laparoscopic approach. Although, patient selection can be preferable. Careful consideration should be given to the patient habitus, the location of nodal disease and especially the type of other procedures required for the completion of cancer surgery. As a result of the improvement of technology, gynecologic oncologists have to get advanced laparoscopic and robotic skills, in order to be able to accommodate the optimal technique for each patient.
105 ABSTRACT Backround The purpose of this study was to present all the available minimally-invasive techniques for pelvic and para-aortic lymphadenectomy in ovarian cancer and to compare the surgical outcomes of these approaches. Methods A review study of the literature, since 1989 up to date, regarding to the role of lymphadenectomy in ovarian cancer, the development of minimally-invasive surgery for this procedure and the outcomes of these surgical approaches. Pubmed (MEDLINE), Web of Science, ClinicalTrials.gov and various Scientific Texts were searched for original studies. Parameters such as operative time, estimated intraoperative blood loss, postoperative pain, length of hospital stay, number of lymph nodes yielded and complication rates were evaluated in this study. Results In early ovarian cancer systematic lymph node dissection is required in order to perform accurate clinical staging and to select an adequate adjuvant chemotherapy. Recent changes in FIGO staging reflect the relative prognostic influenceof lymph node staging, stratified by the size of lymph node metastasis. Complete surgical debulking of advanced ovarian carcinoma including pelvic and paraaortic lymphadenectomy has been associated with improved survival. A systematic lymphadenectomy in advanced cancer will produce a significant benefit in progression-free survival and may improve the 5-year overall survival. The results of a large international trial (LION) will show whether systematic lymph node dissection does indeed influence the overall survival in advanced ovarian cancer. Minimally-invasive procedures (MIS-minimal invasive surgery) for lymphadenectomy in ovarian cancer include : laparoscopic pelvic lymphadenectomy, laparoscopic para-aortic lymphadenectomy, tranperitoneal or extraperitoneal, single-port laparoscopic lymphadenectomy (LESS), transperitoneal or extraperitoneal, robotic pelvic lymphadenectomy, robotic para-aortic lymphadenectomy, transperitoneal or extraperitoneal, and robotic single-port lymphadenectomy (R- LESS). The operation time and blood loss was significantly reduced in the robotic and laparoscopic groups. Moreover, robotic surgery was associated with decreased postoperative pain score. The length of hospital stay and time to full diet resumption were also shortened for those who underwent robotic and laparoscopic procedures. Survival analysis and complication rates were similar between the two groups. The robotic equipment stil remains large and expensive and the stuff has to be well-trained. The reported studies regarding to the comparison between the transperitoneal and extraperitoneal approach observed no significant differences between both surgical approaches for perioperative outcomes and number of aortic nodes. In last years, the extraperitoneal approach seems to be associated with shorter surgical duration. A lower blood loss and a little higher number of aortic nodes can be removed during robotic extraperitoneal lymphadenectomy (not clinically significant). LESS and R-LESS improve cosmesis and have been associated with a lower postoperative pain and a lower morbidity versus multiport laparoscopic surgery. Large prospective studies are needed, in order to evaluate the use of these techniques in lymphadenectomy for ovarian cancer. Conclusion Laparoscopic pelvic and para-aortic lymphadenectomy is a safe, feasible and economic alternative approach to laparotomy in the management of ovarian cancer. Robotic lymphadenectomy seem to be a feasible alternative approach in managing ovarian cancer, with a careful patient selection. However, large case-control studies to evaluate the efficacy of using robotic surgery in treatment of ovarian cancer are still lacking.
106 ΠΕΡΙΛΗΨΗ
Ιστορικά οι χειρουργικές επεμβάσεις έχουν συνδεθεί με τον πόνο, τις μεγάλες και εμφανείς τομές στο σώμα, τον κίνδυνο για σοβαρές επιπλοκές, τη μακρά νοσηλεία και φυσικά τη δύσκολη ανάρρωση. Η σύγχρονη χειρουργική με την αλματώδη εξέλιξη της τεχνολογίας και τη συστηματική κλινική έρευνα έρχεται να αλλάξει εντελώς τα δεδομένα. Η χειρουργική του σήμερα είναι Ελάχιστα Επεμβατική (Minimally Invasive Surgery), δηλαδή με τη λιγότερη δυνατή παρέμβαση στον ασθενή. Αυτό επιτυγχάνεται με τις σύγχρονες τεχνικές της Λαπαροσκόπησης, της Ρομποτικής και της Ενδοσκόπησης. Η Ελάχιστα Επεμβατική Χειρουργική προσφέρει πληθώρα πλεονεκτημάτων, όπως η οπτική μεγέθυνση του χειρουργικού πεδίου και η καλύτερη ακρίβεια της επέμβασης, η μειωμένη απώλεια αίματος, η ελάττωση του πόνου μετά το χειρουργείο, ο συντομότερος χρόνος για την επάνοδο της εντερικής λειτουργίας και τη λήψη τροφής, η ταχεία ανάρρωση, η μικρότερη διάρκεια νοσηλείας, η ελαχιστοποίηση της πιθανότητας μετεγχειρητικών επιπλοκών σχετικές με τις τομές, η σχεδόν εξάλειψη των μετεγχειρητικών συμφύσεων που μπορούν να προκαλέσουν ειλεό, το άριστο αισθητικό αποτέλεσμα και η ταχεία επάνοδος στην εργασία.
Οι τεχνικές της Ελάχιστα Επεμβατικής Χειρουργικής έχουν άψογα εφαρμοστεί και στην γυναικολογική ογκολογία. Στον καρκίνο ωοθηκών η αμφοτερόπλευρη πυελική και παρααορτική λεμφαδενεκτομή θεωρείται απαραίτητη, τόσο για την ακριβή σταδιοποίηση της νόσου όσο και γιατί έχει συσχετισθεί με βελτιωμένο ποσοστό επιβίωσης. Οι ελάχιστα επεμβατικές τεχνικές που έχουν αναπτυχθεί για την λεμφαδενεκτομή αφορούν τη λαπαροσκόπηση και τη ρομποτική χειρουργική. Ο πλήρης λεμφαδενικός καθαρισμός μπορεί να πραγματοποιηθεί είτε ενδοπεριτοναικά είτε εξωπεριτοναικά. Η “λαπαροσκόπηση μονής οπής” είναι μία μέθοδος που έχει αναπτυχθεί τα τελευταία χρόνια. Οι αρχές αυτής της τεχνικής έχουν χρησιμοποιηθεί και στη ρομποτική χειρουργική.
Κάθε μία από αυτές τις τεχνικές έχει πλεονεκτήματα, όπως και μειονεκτήματα. Μέσα από ένα σύνολο μελετών που έχουν γίνει μέχρι σήμερα, φαίνεται ότι η λαπαροσκοπική πυελική και παρααορτική λεμφαδενεκτομή αποτελεί μία ασφαλή, επαρκή και οικονομική εναλλακτική τεχνική για την αντιμετώπιση του καρκίνου των ωοθηκών, παρέχοντας αρκετά πλεονεκτήματα συγκριτικά με την καθιερωμένη λαπαροτομία. Η καθιέρωση αυτών των τεχνικών, ωστόσο, στην καθημερινή ιατρική πράξη, απαιτεί ακόμα μεγαλύτερες και τυχαιοποιημένες μελέτες. Μέλημα των γυναικολόγων ογκολόγων αποτελεί η απόκτηση εξειδικευμένων δεξιοτήτων, ώστε να μπορούν να ανταποκριθούν επαρκώς στις σύγχρονες απαιτήσεις της Ελάχιστα Επεμβατικής Χειρουργικής.
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