ANTICANCER RESEARCH 34: 5087-5090 (2014)

Surgical Considerations for Removal of Giant Tumor of the Right Adrenal

GIUSEPPE PEDULLÀ, PAOLO SAPIENZA, ANNALISA PALIOTTA, ALESSIO GIORDANO, DANIELE CROCETTI and GIORGIO DE TOMA

Pietro Valdoni Department of , Sapienza University of Rome, Rome, Italy

Abstract. Background/Aim: Complete surgical removal is In the era of minimally-invasive techniques, a matter of the only potentially curative approach for adrenal tumors. debate is the use of laparoscopic adrenalectomy for adrenal Our series of patients affected with giant right adrenal tumor resection. Minimally-invasive adrenalectomy has tumors, as well as the open surgical modalities used to become the treatment of choice for benign adrenal lesions obtain a complete tumor resection with safe vascular control with a diameter of less than 6 cm (4). However, at present, were analyzed. Materials and Methods: Nine patients (mean there is a consensus that open adrenalectomy remains the age=57 years) affected with a giant right adrenal tumor who operation of choice for adrenal tumors with invasion of underwent open surgical removal of the mass form the basis adjacent organs, enlarged regional lymph nodes, or that are of the present analysis. A midline incision was performed. larger than 10-12 cm in size (3). Furthermore, retrohepatic Large mobilization of the was performed to obtain good adrenal tumors can be challenging to resect because of their and safe exposure of the vascular pedicles. Results: An en proximity or adhesion to the infrahepatic portion of the bloc R0 tumor resection was accomplished in all cases. inferior vena cava, which puts any attempt at operative Histology revealed an adrenal cortical carcinoma in all removal at high risk for uncontrollable bleeding (3). patients. No local recurrence was noted at a mean follow-up Various open operative techniques have been described for of 14 months. Conclusion: Radical surgery is the only achieving removal of a right adrenal tumor. Herein we report curative approach and is recommended for all patients, our series of patients affected with giant right adrenal tumors whenever technically feasible, through open access in cases and the open surgical modalities used to obtain a complete of giant right adrenal carcinoma. tumor resection with safe vascular control.

An adrenal is a devastating tumor because of the Patients and Methods short life expectancy and severe impact on quality of life. The reported annual incidence of this neoplasm is 0.5-2 cases per Between January 2009 and April 2014, 201 patients affected with million of the population and progress in the development of an adrenal tumor were referred to our Institution. The tumor affected the right in 86 cases and the left in 115. Nine out of treatment options beyond surgery has been limited (1). 86 patients presented a right adrenal tumor greater than 10 cm in Complete surgical removal is the only potentially curative diameter and form the basis of our study. Preoperative and approach for adrenal tumor and has the most significant impact postoperative clinical and laboratory details were retrieved from on a patient’s prognosis. In particular, an R0 resection is hospital charts. associated with a superior prognosis. Surgery often needs to be extensive, with en bloc resection of invaded organs, and Diagnostic techniques. The preoperative workup consisted of regularly includes lymphadenectomy. It is of greatest ultrasonography, computed tomography and magnetic resonance imaging. The presence of eventual metastatic disease was always importance to leave the tumor capsule intact, thereby avoiding evaluated with a bone scan and thoracic computed tomography. tumor spillage and reducing risk for local recurrence (2, 3). Surgical technique. A midline abdominal approach was used to reach the peritoneal cavity. The mobilization of the liver started with the section of the round ligament up to the individuation of the right Correspondence to: Giuseppe Pedullà, MD, Pietro Valdoni Department hepatic vein. This was followed by dissection of the triangle of Surgery , Sapienza University of Rome, Policlinico Umberto I°, ligament with a gentle mobilization upward of the right lobe of liver Viale del Policlinico 151, 00161 Rome, Italy. Tel: +39 0649972197, to dissect the right coronal ligament, thus obtaining a complete Fax: +39 0649972197, e-mail: [email protected] visualization of the inferior vena cava. The aberrant hepatic veins draining the first or fourth hepatic segment were ligated and Key Words: Giant adrenal tumor, adrenalectomy, radical surgery. sectioned when indicated.

0250-7005/2014 $2.00+.40 5087 ANTICANCER RESEARCH 34: 5087-5090 (2014)

Figure 1. Axial magnetic resonance image showing a large, solid, irregularly-shaped mass of the right adrenal.

Pathology. Histological examination confirmed the diagnosis of Ultrasonography confirmed by computed tomography adrenal tumor in all cases. was diagnosed permitted diagnosis of the adrenal mass in all cases. Magnetic using established criteria (2). These included areas of confluent resonance imaging was used in seven cases to better- necrosis; mitoses, including atypical mitoses; vascular and capsular characterize the infiltration of the surrounding tissues, which invasion; and nuclear atypia (2). was clearly evident in four cases. One (11%) patient had Follow-up. Follow-up information (mean=14 months; range=6-48 metastatic disease. months) were retrieved from outpatient charts and patients were The mean tumor size was 13 cm (range =10-20 cm). There evaluated every six months for clinically relevant data. Abdominal were no intra- or postoperative deaths. The mean operative computed tomographic scan was repeated during follow-up every time was 162 minutes (range=108-207 minutes). An en bloc six months. Follow-up was complete in all patients until death or R0 tumor resection was accomplished in all cases. An completion of the study. ultrasound device and hemostatic materials were used in all patients to obtain optimal hemostasis. Vena cava dissection Results was always performed. No right nephrectomy was necessary to remove the entire tumor mass. There was a distinct diners Our study included four men and five women; mean age at delineation between the adrenal tumor and hepatic capsule presentation was 57 years (range=24-72, median=60 in all cases. Use of an ultrasound device and biological glue years). enabled precise and efficient bleeding control. Five patients presented symptoms of abnormal All patients recovered well from surgery. No early secretion. One patient had increased serum corticosteroid complications occurred. levels, one high serum concentration, one had a Histology revealed nine (100%) adrenal cortical carcinomas. phechromocytoma and two had more than one abnormal No positive surgical margin was detected. hormone secretion. The remaining four had a normal The mean follow-up period was 14 (range=6-48) months. hormonal profile. No patient had tumor local recurrence. No postoperative Clinical manifestations consisted of (55%) based on mitotane was needed. Eight (90%) and Cushing’s syndrome (11%), and a palpable abdominal patients are disease-free and or (10%) had pulmonary mass was present in all cases. at three months.

5088 Pedulla et al: Giant Right Adrenal Tumors

Figure 2. A: Large adrenal mass in the right suprarenal region. IVC: Inferior vena cava. B: Cut section of the mass showing areas of hemorrhage and necrosis.

Discussion Mitotane, an inhibitor of steroid synthesis, is still the most used chemotherapeutic agent and is shown to increase survival (7). Adrenocortical carcinoma is a rare malignancy, frequently In the past decades, the laparoscopic approach has shown presenting at an advanced stage, and with a higher prevalence consistent benefits, such as a shorter hospital stay, reduced in the female population (5). Because of the rarity of the morbidity, decreased analgesic requirement, smaller wound, disease, it was only in 2004 that the International Union reduced intraoperative loss, and rapid patient recovery, Against defined the TNM criteria and published the and it is widely accepted as the approach of choice for first staging classification for adrenocortical carcinoma (6). adrenal tumor. Furthermore, the magnification of the This classification had several limitations and therefore it was laparoscope provides excellent visualization of the anatomic modified in 2009 (5). At present, in stages I-III, complete region. Laparoscopic adrenalectomy permits access to an tumor removal by a specialized surgeon offers by far the best anatomic region which otherwise requires an extensive chance for cure. The 5-year survival rate after R0 surgery is transperitoneal exposure. Small benign functioning tumors 50-60%. However, even after complete resection, recurrent and or , incidentalomas or metastases and metastatic disease is very common (7). Palliation by malignant tumors for which a radical resection can easily be radiotherapy and radiofrequency ablation may be offered to performed, can be safely treated with a laparoscopic those who are not surgical candidates. Radiotherapy is the approach (9, 10). treatment of choice for most metastases; metastases at selected However, we should keep in mind that an incomplete sites and local recurrences can sometimes be palliated resection of a malignant adrenal tumor is associated with a surgically (8). A combination chemotherapy regimen consisting particularly poor prognosis. In most studies, the median survival of cisplatin, doxorubicin and etoposide along with mitotane is is less than 12 months (11). The involvement of the surrounding widely used to eliminate microscopic residual disease after tissue or adrenal and caval veins by a malignant lesion is an surgery or to make an unresectable tumor amenable to surgery. absolute contraindication to laparoscopy. In these cases, in our

5089 ANTICANCER RESEARCH 34: 5087-5090 (2014) opinion, open laparotomy is still the treatment-of- choice, as well good results obtained with this approach were due to our strict as in all cases where the preoperative diagnosis is not certain. selection of patients. In our series, we described the results of complete resection of giant right adrenal tumor that was always accomplished References through a midline incision with a wide mobilization of the 1 Choyke PL: ACR Appropriateness Criteria® on Incidentally liver. The major technical difficulty is in fact the dissection discovered adrenal mass. J Am Coll Radiol 3: 498-504, 2006. between the tumor and the liver to provide a complete en bloc 2 Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, resection. We believe that the surgical approach to a Fassnacht M and Pentheroudakis G: Adrenal cancer: ESMO retrohepatic tumor should be avoided if the vascular control of clinical practice guidelines for diagnosis, treatment and follow-up. inferior vena cava is not achievable. Complete mobilization of Ann Oncol 23: 131-138, 2012. 3 Fassnacht M, Kroiss M and Allolio B: Update in adrenocortical the right liver with the individuation of right hepatic vein carcinoma. J Clin Endocrinol Metab 98: 4551-4564, 2013. controlled outside the liver whenever a suspicion of liver 4 Schteingart DE: Management of patients with adrenal cancer: infiltration is present should be a standard approach during recommendations of an international consensus conference. Endocr removal of giant malignant adrenal tumor. This approach is Relat Cancer 12: 667-680, 2005. considered essential in reducing blood loss. Injudicious 5 Fassnacht M, Johanssen S, Quinkler M, Bucsky P, Willenberg HS, mobilization of the right liver may lead to excessive bleeding Beuschlein F, Terzolo M, Mueller HH, Hahner S and Allolio B: caused by tearing of the liver capsule and parenchyma from Limited prognostic value of the 2004 International Union Against Cancer staging classification for adrenocortical carcinoma: proposal neoplastic tissue invasion or avulsion of the hepatic veins, or for a Revised TNM Classification. Cancer 115: 243-250, 2009. prolonged ischemia of the liver remnant from rotation of the 6 Weiss LM, Bertagna X, Chrousos GP, Kawashima A, Kleihues P, hepatoduodenal ligament. In our opinion, these features are the Koch CA, Giordano TJ, Medeiros LJ, Merino MJ, Ordonez NG major limitations to a laparoscopic approach to resection of and Sasano H: Adrenal cortical carcinoma. In: Pathology & giant right adrenal tumors. genetics. Tumours of endocrine organs (DeLellis RA, Lloyd RV, The nature of an adrenal tumor may be difficult to Heitz PU and Eng C (eds.). Lyon, IARC Press, pp. 139-142, 2004. 7 Allolio B and Fassnacht M: Adrenocortical carcinoma: clinical demonstrate preoperatively but the risk of treating a malignant update. J Clin Endocrin Metab 91: 2027-37, 2006. lesion increases with the size of the lesion (the median size of 8 Schulick RD and Brennan MF: Adrenocortical carcinoma. World J adrenal carcinoma is more than 11 cm) (14). High-resolution Urol 17: 26-34, 1999. imaging technology can help; however, at present, the accepted 9 Javadpour N, Woltering EA and Brennan MF: Adrenal . criteria for malignancy are distant metastases or local invasion. Curr Prob Surg 17: 1-52, 1980. An adrenal mass is difficult to characterize as carcinoma with 10 Elfenbein DM, Scarborough JE, Speicher PJ and Scheri RP: certainty using current imaging methods. We know that Comparison of laparoscopic versus open adrenalectomy: results from American College of Surgeons National Surgery Quality diagnosis of a benign adrenal lesion by unenhanced computed Improvement Project. J Surg Res 184: 216-220, 2013. tomographic scan is associated with a threshold of ≤10 11 Bittner JG, Gershuni VM, Matthews BD, Moley JF and Brunt LM: Hounsfield units (HU). Computed tomographic scan with Riskfactors affecting operative approach, conversion, and morbidity delayed contrast media washout using a cut-off of 50% for adrenalectomy: a single institution series of 402 patients. Surg washout and an absolute value of >35 HU after 10-15 min has Endosc 27: 2342-2350, 2013. a good diagnostic accuracy in tumor identification. Magnetic 12 Icard P, Goudet P, Charpenay C, Andreassian B, Carnaille B, Chapuis Y, Cougard P, Henry JF and Proye C: Adrenocortical resonance imaging including chemical shift and washout carcinomas: surgical trends and results of a 253-patient series from analysis is probably equally accurate (12). Furthermore, all the French Association of Endocrine Surgeons study group. World patients with suspected adrenal carcinoma require a chest J Surg 25: 891-897, 2001. computed tomographic scan for pulmonary metastases before 13 Sangwaiya MJ, Boland GWL, Cronin CG, Blake MA, Halpern EF surgery (13-15). and Hahn PF: Incidental adrenal lesions: accuracy of In our series, all patients were treated for a suspected characterization with contrast-enhanced washout multidetector malignant adrenal tumor because preoperative diagnostic tools CT–10-minute delayed imaging protocol revisited in a large patient cohort. Radiology 256: 504-510, 2010. demonstrated local tumor invasion. 14 Guerrisi A, Marin D, Baski M, Guerrisi P, Capozza F and Catalano We suggest operating on all patients affected with a giant C: Adrenal lesions: spectrum of imaging findings with emphasis right adrenal tumor through an open laparotomy; our policy is on multi-detector computed tomography and magnetic resonance different for giant masses of the left adrenal. In these cases, a imaging. J Clin Imaging Sci 3: 61, 2013. laparoscopic approach is also feasible in the presence of local 15 Elsayes KM, Mukundan G, Narra VR, Lewis JS, Shirkhoda A, invasion if the surgeon is confident at achieving complete Farooki A and Brown JJ: Adrenal masses: MR imaging features with pathologic correlation. Radiographics 24: S73-86, 2004. tumor removal. In conclusion, our findings demonstrate that open Received May 23, 2014 adrenalectomy is the procedure of choice for patients with Revised June 30, 2014 known or suspected malignant giant adrenal tumors and that Accepted July 1, 2014

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