Original Article

Laparoscopic adrenalectomy: A single center experience

Suresh Kumar, Moley K Bera, Mukesh K Vijay, Arindam Dutt, Punit Tiwari, Anup K Kundu Department of , Institute of Post-Graduate Medical Education and Research (IPGMER) and Seth Sukhlal Karnani Memorial Hospital (SSKM), - 700 020,

Address for correspondence: Dr. Suresh Kumar, 601 Doctors PG Hostel, 242 AJC Bose Road, IPGMER and SSKM Hospital, Kolkata - 700 020, , India. E-mail: [email protected]

Abstract performed via the transperitoneal or retroperitoneal route- the former via the lateral or anterior approach and the latter AIMS: To evaluate the efficacy and safety of laparoscopic via the posterior approach. Robot-assisted laparoscopic adrenalectomy in benign adrenal disorders. METHODS adrenalectomy may also be performed if facilities are AND MATERIAL: Since July 2007, twenty patients available. Each technique has its own advantages and have undergone laparoscopic adrenalectomy for various benign adrenal disorders at our institution. Every patient disadvantages. It is now an established fact that different underwent contrast enhanced CT-abdomen. Serum advantages of the laparoscopic approach include less corticosteroid levels were conducted in all, and urinary morbidity, better cosmesis, reduction in wound infection, metanephrines, normetanephrines and VMA levels minimal need for analgesia, decreased hospital stay and early were performed in suspected pheochromocytoma. All return to work.[2-4] We report our experience of laparoscopic the patients underwent laparoscopic adrenalectomy via adrenalectomy using the transperitoneal approach in 20 the transperitoneal approach. : The patients RESULTS patients with different adrenal . This prospective were in the age range of 18-57 years, eleven males study was conducted in our Urology Department to evaluate and nine females, seven right, eleven left, two bilateral. The mean operative time was 150 minutes (120-180), the efficacy and safety of laparoscopic adrenalectomy in mean hospital stay four days (3-5), mean intraoperative benign adrenal disorders blood loss 150 ml and mean post-operative analgesic need was for 36 (24-72) hours. One out of twenty-two MATERIALS AND METHODS laparoscopic operations had to be converted into open adrenalectomy due to intra-operative complications. Between July 2007 and September 2009, a total of 20 patients CONCLUSIONS: Laparoscopic adrenalectomy is a safe, effective and useful procedure without any major post- underwent laparoscopic adrenalectomy at our institution. operative complication and is the gold standard for all Exclusion criteria were tumour size > 7 cm and / or suspicion benign adrenal disorders. of malignancy on contrast-enhanced CT scan. Peri-operative data were collected and analysed. The total number of Key words: Laparoscopic adrenalectomy, benign adrenal patients was 20, Male-eleven, female-nine. Patients were disorders, lesser morbidity in age ranging from 18-57 years (mean age-38.55 years). Twenty-two laparoscopic adrenalectomies were performed DOI: 10.4103/0972-9941.72595 in20 patients (bilateral adrenalectomy in two cases)

In our study, indications for laparoscopic adrenalectomy INTRODUCTION were pheochromocytoma (n = 8), Conn’s syndrome (n = 1), cortisol secreting adenoma (n = 4), myelolipoma (n = Traditionally, adrenalectomy is done by an open 3) and Ectopic ACTH-dependent adrenal hyperplasia (n = procedure since 1914, when Sargent performed 2). Two cases were incidenteloma (n = 2) detected during first planned adrenalectomy.[1] In the modern era of investigation for nonspecific backache. minimally invasive (MIS), laparoscopy is being increasingly used. Laparoscopic adrenalectomy can be All patients were assessed by history and physical

Journal of Minimal Access Surgery | October-December 2010 | Volume 6 | Issue 4 100 Kumar, et al.: Laparoscopic adrenalectomy examinations. Contrast-enhanced computed tomogram measured. After measuring the plasma rennin-aldosterone (CECT)-abdomen was performed in each case. Serum ratio, the patient underwent a sodium loading test with 2 l cortisol 8.0 am, 11.0 pm, and 1 mg post-dexamethasone intravenous normal saline, after which CECT-abdomen was serum cortisol levels were conducted in all patients. Twenty- performed. four hour urinary metanephrines, nor-metanephrines and Vanillylmandelic acid (VMA) levels were performed In case of adrenal hyperplasia with ectopic adrenocorticotropic in suspected pheochromocytoma. Complete hemogram, hormone (ACTH) secretion, one patient underwent pituitary coagulation profile, and biochemical parameters, including magnetic resonance imaging (MRI), Chest computed serum electrolytes were completed in all patients. Pre- tomography (CT) scan and a high-dose dexamethaone operative patients profile including various indications of suppression test (2 mg every 6 hours for 2 days). The laparoscopic adrenalectomy is summarized in Table 1. pituitary MRI and Chest CT scan were normal and there was no suppression in serum cortisol. The other patient was a Patients with pheochromocytoma were treated pre- known case of non-small-cell bronchogenic carcinoma with operatively with prazosin and other antihypertensive and ectopic ACTH secretion. Prior to induction, intravenous third all patients received propranolol one week prior to surgery. generation cephalosporin was given to all patients. After general anaesthesia, a nasogastric tube and Foley catheter Patients with cortisol secreting adenoma were treated with were introduced. Outcome measures included were-operative intravenous hydrocortisone during the day of the operation time, intraoperative open conversion rate, estimated blood and on the first post-operative day and further substitution loss, post-operative complications, duration and dose of was performed orally, with hydrocortisone tablets. analgesic need and post-operative hospital stay. Patients were placed in the lateral decubitus position with side of The Conn’s syndrome patient underwent plasma renin the lesion being elevated to 45 degrees. activity and plasma aldosterone level, after correction of hypokalemia. Plasma aldosterone renin ratio was then Right adrenalectomy was usually performed with four ports.

Table 1: Pre-operative patients profile Age and Side Functional status Tumour size Indication Sex RT / LT (cm) on CECT-scan 22 F RT Cortisol (11 pm): raised and post-dexamethasone cortisol raised 3.4 Cortisol secreting adenoma 28 M BL Serum Cortisol and ACTH raised, pituitary MRI-normal, Chest CT-normal, 3.2, Cushing’s syndrome high-dose dexamethasone suppression test showed no suppression. 3.0 18 M RT 24-hour urinary metanephrines and normetanephrines raised 6.5 pheochromocytoma 55 M LT Non-functional 6.0 myelolipoma 52 F LT Non-functional 7.0 myelolipoma 36 F LT Non-functional 4.2 backache (incidentaloma) 35 F RT 24-hour urinary metanephrine and normetanephrine raised 5.5 cm pheochromocytoma 57 M BL Ectopic ACTH secretion, secondary to cancer of lung 3.0, Cushing’s syndrome 2.8 22 M RT Cortisol (11 pm): raised and post-dexamethasone cortisol raised 3.8 Cortisol secreting adenoma 35 M RT 24-hour urinary metanephrines and normetanephrines raised 5.8 pheochromocytoma 32 F LT 24-hour urinary metanephrines and normetanephrines raised 6.1 Pheochromocytoma 25 M LT Cortisol (11 pm): raised and post-dexamethasone cortisol raised 3.3 cortisol secreting adenoma 57 F LT Non-functional 6.9 myelolipoma 42 F LT 24-hour urinary VMA raised 7.0 Pheochromocytoma with neurofibromatosis 33 M RT Cortisol (11 pm): raised and post-dexamethasone cortisol raised 3.2 cortisol secreting adenoma 36 F LT 24-hour urinary VMA, metanephrines and normetanephrines raised 6.5 Pheochromocytoma 43 F LT Non-functional 3.0 Backache (incidenteloma) 47 F RT 24-hour urinary metanephrines and normetanephrines raised 6.8 Pheochromocytoma 40 M LT Persistent hypokalemia with aldosterone / rennin ratio-44 2.4 Conn’s adenoma 56 M LT 24-hour urinary metanephrines and normetanephrines raised 5.6 Pheochromocytoma RT: right, LT: left, BL: bilateral, M: male, F: female

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After making a skin incision, a primary Camera port 10 mm was mobilised and the phrenic vessels supplying the gland was placed about 3 cm lateral and cephalad to the umbilicus, were divided. The medial aspect of the adrenal gland was using the close method. Two working ports, 5 mm and 10 mm mobilised from the aorta and the vessels supplying the gland were placed in the midclavicular position, the upper one (5 were divided using LigaSure. Finally, the lateral attachments mm) below the costal margin, and the lower one (10 mm), 10- of the gland were divided, to free the gland fully from the 12 cm below the upper one. Another 5 mm port was placed surrounding tissue. in the sub-xiphisternal position for liver retraction. A fifth 5 mm port, if required, was placed in the right anterior line, to An abdominal tube drain was inserted in all patients and it facilitate retraction. The right colon was mobilised along the was usually removed after 48 hours. For specimen extraction, line of Toldt. Via sub-xiphisternal port, the liver was retracted we either used gloves or an indigenous plastic envelope. The using a fan retractor and the triangular ligament was specimen was extracted via a 10 mm port, either by enlarging transected. The posterior peritoneum was incised along the the incision or via ovum forceps, in pieces. The port sites surface of the liver, extending from the line of Toldt laterally, were closed using the standard technique. up to the inferior vena cava (IVC) medially. Subsequently, the duodenum was mobilised medially, to expose the renal RESULTS hilum. Hepatodiaphragmatic attachments were identified and dissected. The right adrenal vein entering into the IVC A total of 22 laparoscopic adrenalectomies were performed, was identified and isolated, and a hem-o-lok clip [Figure but one required conversion to open, due to uncontrolled 1a] or Ligaclip (depending upon the need) was applied and intra-operative bleeding from the right adrenal vein (patient transected. Subsequently, small superior and inferior adrenal 7 in the list). Post-operative complications occurred in vessels were coagulated and cut with LigaSure, completing three patients: one patient developed port site infection, the dissection of adrena gland tumour [Figure 1b] one patient had atelactasis and one patient post-operative hypotension. All were managed conservatively. Twenty-two Usually three ports were used in case of left adrenalectomy. laparoscopic adrenalectomies were performed, seven on the A fourth 5 mm port, if required, was placed in the left right side, eleven on the left side and bilateral in two patients. mid-axillary line to facilitate the retraction. The colon was Mean intra-operative and post-operative blood loss was 150 mobilised along the line of Toldt, with a release of the ml (120-180 ml). Mean operative time was 150 minutes (120- splenocolic and phrenocolic ligaments. Subsequently, the 180 minutes). Mean post-operative analgesic need was for 36 lienorenal ligament was incised. After incising the gerota hours (24-72 hours), with 50 mg tramadol twice a day. Oral fascia, the upper pole of the kidney was visualised. Dissection nutrition was resumed after an average of two (1-3) days. along the medial aspect of the kidney was continued till Mean hospital stay was four days (3-5), excluding the patient the left renal vein was identified. Next, dissection along the who needed conversion to open adrenalectomy. superior aspect of the renal vein identified the left adrenal vein, which was clipped and divided. Sometimes, the gonadal Final diagnosis ( after histopathology), number of patients in vein helped in identifying the adrenal vein. After controlling each group and mean tumour size in each group is illustrated the adrenal vein, the superior aspect of the adrenal gland in Table 2.

Figure 1a: Ligation of right adrenal vein. Figure 1b: Dissecting adrenal gland tumour.

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Table 2: Adrenal tumour characteristics Final diagnosis No. of Mean tumour patients size (cm) Cortisol secreting adenoma 4 3.4 Aldosterone secreting adenoma 1 2.4 Adrenocortical hyperplasia 2 3.0 pheochromocytoma 8 6.2 Myelolipoma 3 6.6 Non functional cortical adenoma 2 3.6 (Incidentaloma)

DISCUSSION

Gagner performed the first laparoscopic adrenalectomy in 1991.[5] Pre-operatively, the surgeon was primarily interested in Figure 2: CECT-Right adrenal cortical adenoma. the size of the gland, its vascularity, proximity or involvement of the surrounding structures and functional status. Adenomyelolipoma are usually well-circumscribed with (-100 to -200 HFU) soft tissue density lesion and may show Contraindications for laparoscopic adrenalectomy, reported calcification, which may be diffuse or spotty. In our study, in recent literature, are invasive adrenocortical carcinoma, only one patient showed calcification [Figure 3]. large tumour > 10-12 cm in diameter and malignant ACTH secreting pheochromocytoma with lymphadenopathy and Conn’s syndrome can be due to adenomas, adrenal hyperplasia adrenocortical carcinoma with caval thrombus.[6] On account of or very rarely due to carcinoma. Adenoma in Conn’s syndrome the aggressive nature of the adrenocortical carcinoma, an open is typically small, mean diameter 1.5 cm, ranging from 0.5- approach allows en block resection and potential removal of 3.5 cm. Hence, a thin CT scan section (3-5 mm) is mandatory the surrounding organs.[7,8] Other absolute contraindications for the reliable detection of adenoma. Accuracy of the CT include uncorrectable coagulopathy, severe cardiopulmonary scan in detecting the aldosteronoma depends upon its size, disease and uncontrolled pheochromocytoma. A previous although with newer scanning techniques (breath-hold thin abdominal scar is no longer a contraindication to laparoscopic sections), the overall detection rate is in the range of 80%.[12] adrenalectomy. In our study, the adenoma was 2.4 cm in size, on a CECT scan.

A relative contraindication to laparoscopic surgery is the Adrenal hyperplasia on a CT scan usually shows diffuse tumour size. By initial experience, many laparoscopists used thickening and elongation of the adrenal rami or may rarely cut off of 5 or 6 cm. Mac Gilliv Ray and Henry recommended show prominent glands bilaterally, within normal range.[13] an upper size limit of 12 cm for laparoscopic adrenalectomy. In our study, both patients of ectopic ACTH secretion have Although adrenal masses of up to 10-15 cm are resectable shown thickening and elongation of the adrenal rami. laparoscopically, dissection may be difficult, time consuming and the exposure may not be optimal due to the limited working space. Furthermore, a tumour with a diameter > 6-8 cm carries a risk of malignancy.[9] Hence, we carried out laparoscopic adrenalectomy in tumours measuring up to 7 cm.

Radiological imaging contrast-enhanced CT scan or MRI localizes the adrenal mass. On CECT, cortisol secreting adenomas are usually well-defined and small in size, 2-5 cm, homogenous, and show low enhancement with contrast (0-30 HU).[10] Calcification, haemorrhage and necrosis is uncommon in them [Figure 2]. In our study, the mean size was 3.4 cm. Patients demonstrating an excess of cortisol have an increased amount of adipose tissue and some have argued that laparoscopic approach in these patients is most Figure 3: CECT-Right adrenal mass with negative soft tissue density with [11] appropriate. calcification (myelolipoma).

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Pheochromocytoma are the tumours derived from chromaffin had a left adrenal mass of 4.2 cm and another one had a left cells that produce and often secrete catecholamines.Highest adrenal mass of 3.0 cm. The final histopathology revealed incidence occurs during the fourth and fifth decade of life and cortical adenoma in both. is nearly identical in both the sexes.[14] Pheochromocytoma are usually large and have areas of haemorrhage and necrosis Malignant masses on CT scan are usually large, with irregular [Figure 4] and may even have fluid-filled levels within margins, inhomogenous density and thick irregular enhancing them.[13] In multiple endocrine neoplasia (MEN) syndrome rims. Central necrosis, calcification and invasion of adjacent patients, tumours are bilateral and tend to be smaller.[15] structures may be present in them. Patients with any of these Generally, intravenous contrast material is not essential for features were excluded from the study. detection of adrenal pheochromocytoma, but good oral contrast for the opacification of the gastrointestinal tract is Different laparoscopic techniques have been described for essential for detecting the retroperitoneal tumour, because adrenal masses. Each laparoscopic approach has its own unopacified bowel can simulate a para-aortic mass. advantages and disadvantages. The main difference between individual techniques is between the transperitoneal and In our study, the mean diameter of the tumour, in the retroperitoneal approaches. The choice of the approach case of the pheochromocytoma, was 6.2 cm. Previously depends upon the experience of the surgeon. Several studies pheochromocytoma was considered to be a relative have shown no advantage of one approach over the other.[20] contraindication to laparoscopic surgery, but now The lateral transperitoneal approach allows a wide surgical laparoscopic adrenalectomy for pheochromocytoma has exposure and inspection of other intra-abdominal organs. been performed successfully and reported in several In all our patients, we have used this approach because [16,17] series. Regarding pheochromocytoma surgery, it is it provides familiar anatomical landmarks, a relatively important to have early stage control of the main adrenal large working space and allows the viscera to gravitate vein, with the intention of reducing blood pressure away from the area of dissection.[21] The retroperitoneal [18] decompensation, yet it is questionable these days. approach carries an elevated risk of hypercapnia and Approximately 10-15% of the pheochromocytoma are subcutaneous emphysema.[22] However, in case of extensive malignant. In order to diagnose malignant behaviour, one intra-abdominal adhesions, the retroperitoneal approach must document invasion of the adjacent organs or metastatic may be beneficial. disease. The most frequent sites of metastases are the liver, lung, bone, particularly the spine, skull and ribs. There are no Robot-assisted adrenalectomy has recently been proposed absolute, clinical, imaging or laboratory criteria to predict the using the Da Vinci system. Morino et al. published a malignancy. However, patients with malignant disease tend prospective randomised trial with 20 patients, comparing the to have a larger tumour and higher urinary metanephrines.[19] outcome of Robot-assisted (RA) versus lateral transperitoneal laparoscopic adrenalectomy. This study showed that In our series, we came across two patients of incidentaloma RA is associated with longer operative time, increased during the work-up, for nonspecific backache. One patient cost and higher morbidity when compared to the lateral transperitoneal approach. However, further studies are needed to define the role of the RA approach.[23]

Mean operating time (150 minutes) is significantly longer for laparoscopic adrenalectomy, but obvious advantages are less morbidity, better cosmesis, reduction in wound infection, minimal need for analgesia, decreased hospital stay and early return to work. In published literature, operating times ranging between 100 and 202 minutes have been reported.[24,25]

The mean hospital stay was four days in our study. Several authors have reported a mean hospital stay of less than three days.[26] The hospital stay could be shortened by admitting the patient on the day of operation and not the day before. We Figure 4: CECT-Left adrenal mass with areas of haemorrhage and necrosis (pheochromocytoma). admit all our patients one day before the operation.

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Patient no.7 in our series needed conversion to open 10. Dunnick NR, Doppman JL, Gill JR Jr, Strott CA, Keiser HR, Brennan MF. adrenalectomy because of intra-operative bleeding from Localization of functional adrenal tumours by computed tomography and venous sampling. Radiology 1982;142:429-33. the right adrenal vein. Reasons for conversion to open 11. Gotoh M, Ono Y, Hattori R, Kinukawa T, Ohshima S. Laparoscopic adrenalectomy are usually uncontrollable bleeding, adrenalectomy for pheochromocytoma: Morbidity compared with malignancies or widespread adhesions. In other studies, adrenalectomy for tumours of other pathology. J Endourol 2002;16:245-9. 12. Dunnick NR, Leight GS Jr, Roubidoux MA, Leder RA, Paulson E, Kurylo L. CT [22,25] conversion to open surgery has been reported in 3-6%. in the diagnosis of primary aldosteronism: Sensitivity in 29 patients. AJR Am J Roentgenol 1993;160:321-4. 13. Smith CD, Weber CJ, Amerson JR. Laparoscopic adrenalectomy: New gold Intra-operative haemorrhage is the most common complication standard. World J Surg 1999;23:389-96. reported in open and laparoscopic adrenalectomy, accounting 14. Karagiannis A, Mikhailidis DP, Athyros VG, Harsoulis F. Pheochromocytoma: for 40% of the overall complications. Other complications An update on genetics and management. Endocr Relat Cancer 2007;14:935-56. include injury to bowel, spleen, pancreas, liver, kidney and 15. Dunnick NR. Adrenal imaging: Current status. AJR Am J Roentgenol diaphragm.[27] The overall complication rate in various reports 1982;154:927-36. of laparoscopic adrenalectomy is 9.5%.[28] In our study, none 16. Ku JH, Yeo WG, Kwon TG, Kim HH. Laparoscopic adrenalectomy for functioning and non-functioning adrenal tumours: Analysis of surgical of the patients developed any major complication, except aspects based on histological types. Int J Urol 2005;12:1015-21. bleeding in one of them, who needed conversion to open. 17. Edwin B, Kazaryan AM, Mala T, Pfeffer PF, Tønnessen TI, Fosse E. Three patients (13.63%) developed minor complications-port Laparoscopic and open surgery for pheochromocytoma. BMC Surg 2001;1:2. 18. Lang B, Fu B, Ou Yang JZ, Wang BJ, Zhang GX, Xu K, et al. Retrospective site infection (Patient No.12), chest infection (Patient No.2) comparison of retroperitoneoscopic versus open adrenalectomy for and post-operative hypotension (Patient No.14); all were pheochromocytoma. J Urol 2008;179:57-60. managed conservatively. 19. Mittendorf EA, Evans DB, Lee JE, Perrier ND. Pheochromocytoma: Advances in genetics, diagnosis, localization and treatment. Hematol Oncol Clin North Am 2007;21:509-25. In conclusion, laparoscopic adrenalectomy is a safe, effective 20. Rubinstein M, Gill IS, Aron M, Kilciler M, Meraney AM, Finelli A, et and useful procedure, without any major post-operative al. Prospective randomized comparison of transperitoneal versus retroperitoneal laparoscopic adrenalectomy. J Urol 2005;174:442-5. complications and is the current standard of care for all 21. Brunt LM, Doherty GM, Norton JA, Soper NJ, Quashbarth MA, Moley JF. benign adrenal disorders. Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Coll Surg 1996;183:1-10. 22. Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A. Laparoscopic REFERENCES adrenalectomy: Lessons learned from 100 consecutive procedures. Ann Surgery 1997;226:238-47. 1. Chow GK, Blute ML. Surgery of the adrenal glands. In: Wein AJ, Kavoussi 23. Brunaud L, Bresler L, Ajay A, Zarnegar R, Raphoz AL, Levan T, et al. LR, Novick AC, Partin AW, Peters CA editors. Campbell-Walsh Urology. 9th Robotic assisted adrenalectomy: What advantages compared to lateral ed. Philadelphia: WB Saunder; 2007. p. 1868-88. transperitoneal laparoscopic adrenalectomy? Am J Surg 2008;195:433-8. 2. Schell SR, Talamimi MA, Udelsman R. Laparoscopic adrenalectomy for 24. 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Results of 108 operations in unselected cases. Surg Endos 2000;14:920-5. 5. Gagner M, Lacroix A, Bolte E. Laparoscopic adrenalectomy in Cushing’s 27. Goitein D, Mintz Y, Gross D, Reissman P. Laparoscopic adrenalectomy: syndrome and pheochromocytoma. N Engl J Med 1992;327:1033. Ascending the learning curve. Surg Endosc 2004;18:771-3. 6. Young WF Jr, Thompson GB. Laparoscopic adrenalectomy for patients who 28. Assalia A, Gagner M. Laparoscopic adrenalectomy. Br J Surg 2004;91: have Cushing’s syndrome. Endocrinol Metab Clin North Am 2005;34:489-99. 1259-74. 7. Schulick RD, Brenna MF. Adrenocortical carcinoma. World J Urol 1999;17: 26-34. Cite this article as: Kumar S, Bera MK, Vijay MK, Dutt A, Tiwari P, Kundu 8. Schulick RD, Brenna MF. Long term survival after complete resection and AK. Laparoscopic adrenalectomy: A single center experience. J Min Access repeat resection in patients with adrenocortical carcinoma. Ann Surg Oncol Surg 2010;6:100-5. 1999;6:719-26. 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