Multi-organ resection for locally advanced adrenocortical cancer: surgical strategy and literature review
F. GUIDA, M. CLEMENTE, L. VALVANO, C. NAPOLITANO
SUMMARY: Multi-organ resection for locally advanced adreno- cortical cancer: surgical strategy and literature review.
F. GUIDA, M. CLEMENTE, L. VALVANO, C. NAPOLITANO
Adrenocortical carcinoma (ACC) is a rare and aggressive endo- crine malignancy with an estimated worldwide incidence of 0.5-2 per million/year.
Complete surgical removal of ACC represents the current treat- ment of choice for this tumor.
A disease-free resection margin (R0) is an important predictor of long-term survival: surgery is demanding and must be performed by a highly experienced surgical team.
We report the surgical strategy adopted in a patient with locally advanced ACC and virilization to obtain a R0 resection.
KEY WORDS: Adrenal cancer - Endocrine - Laparotomy - Virilization.
Introduction
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an estimated worldwide incidence of 0.5-2 per million/year (1, 2).
We report the surgical strategy adopted in a patient with locally advanced ACC and virilization to obtain a R0 resection.
Case report
AM, a 66-year-old female patient referred to our ho- spital for 2-month onset of hypertension and hirsuti- sm. Hormonal examinations revealed the presence of high levels of testosterone (252 ng/dl).
Abdominal CT revealed the presence of a large neoformation of 96x65 mm localized in the left adre- nal space with regular borders and colliquation inside. This mass also compressed the left kidney with urostasis
and the tail of pancreas and spleen. Medially the tu- mor was near the superior mesenteric artery, and po- steriorly it was very close to the aorta and the diaph- ragm (Figure 1).
To obtain a complete resection of the tumor she un- derwent a laparotomic multi-organ resection. By a me- dian laparotomy, we mobilized the right colon and we did a Kocher maneuver. Then we isolated from the ri- ght side the left renal vein (Figure 2). Then we proceed with the dissection of the splenic artery on the celiac trunk and its section (Figure 3). Dissection of the pan- creatic isthmus from the portal vein and section with Harmonic Ace® (Figure 4). Section of the splenic vein (Figure 5) and of the inferior mesenteric vein with Endo - GIA. Splenic flexure mobilization and disinsertion of transverse mesocolon from the inferior border of the pancreas. Section of left gonadal vessels and of ureter (Figure 6). Full mobilization of the kidney and of the spleen and pancreas from the diaphragm. Separation of the mass from the superior mesenteric artery, the left border of aorta and the lumbar vertebral column. Af- ter complete control of the renal hilum (Figure 7), it was sectioned with mechanic suture (Echelon®): left nephroadrenalectomy en bloc with caudal splenopan- creasectomy (Figure 8).
A suction drain was positioned in the subphrenic space and haemostasis was carefully controlled.
Postoperative course was uneventful and the drai-
nage was removed in 8th. Oral intake was started from 2nd p.o. day with initial parenteral integration.
Histolgical examination revealed the presence of an aggressive ACC with microvascular invasion, numerous atypical mithosis and anaplasia. Immunoistochemical analysis showed: CK8-18+/-, vimentyn +, synaptofy- sin -, chromogranin -, S-100 -, alpha inhibin +, CD10 -, Cd56 -, CKpan -, calretinin -. Resection mar- gins were not infiltrated (RO resection).
Discussion
Adrenocortical carcinoma (ACC) is a rare and ag- gressive endocrine malignancy.
The age distribution is reported as bimodal with a
first peak in childhood and a second higher peak in the fourth and fifth decade (3, 4). Moreover there is a sli- ghtly female predominance (4).
This neoplasm is characterized by a high risk of re- currence and a dismal prognosis owing to unsatisfac-
Ethicon
tory overall 5-year survival that ranges between 23% and 60% (5).
Approximately 60% of patients present with symp- toms of excess hormone secretion, most commonly in the form of cortisol hyperincretion (most commonly,
Vasi gonadici
Uretere
hypercortisolism: Cushing’s syndrome), with or without virilization. Hormonal secretion patterns can vary ac- cording to size, differentiation, and stage of the tumor: androgen secreting ACCs in women induce hirsutism and virilization. On the contrary, estrogen-secreting adrenal tumors in males lead to gynecomastia and te- sticular atrophy (6). High level of DHEA-S is another marker suggesting ACC, whereas decreased serum DHEA-S concentrations are suggestive of a benign ade- noma (6). ACC producing aldosterone is very rare and present with hypertension and pronounced hypokale- mia (7).
In cases without clinical hormone overactivity, the most common presentation is related to tumor growth and encroachment on the surrounding viscera, with symptoms such as abdominal discomfort, back pain, and nausea or vomiting (8, 9).
The diagnosis of malignancy of adrenocortical tu- mors relies not only on careful clinical and biological investigations, but above all on radiological imaging such as computerized tomography (CT) or magnetic reso- nance imaging (MRI) and more recently the use of 18F- FDG PET to distinguish between benign and malignant lesions (10, 11).
Survival for patients with ACC is poor and related to stage at time of diagnosis: up to 70% of patients pre- sent with extra-adrenal disease (12).
Five-year survival for patients with disease confined to the adrenal gland is size-dependent and varies from 61 to 82%. Those with distant metastases at dia- gnosis have a five-year survival of only 18% (13).
The classification of ACC by the International Union against Cancer (UICC) and the World Health Organi- zation (WHO) in 2004 is based on the tumor, lymph node and metastasis (TNM) criteria; in 2008, the Eu- ropean Network for the Study of Adrenal Tumors (EN- SAT) proposed a revision of this staging, in which sta- ge III is defined by tumour infiltration in surrounding tissue or tumour thrombus in vena cava/renal vein or positive lymph nodes, and stage IV is defined only by the presence of distant metastases (14).
Unfortunately, ACC prognosis is very poor. It de- pends largely on the stage of tumor: the rate of survi- val at 5 years is estimated at 60% for patients with sta- ge I cancer, 58% for stage II tumors, 24% for stage III tumors, and 0% for disease stage IV (15).
Patients with stage I and II of disease are amenable to potentially curative surgery. They have a prolonged survival compared to patients with stage III and IV (15).
Complete surgical removal of ACC represents the current treatment of choice for this tumor. The like- lihood of achieving a healing is by radical surgery, espe- cially in the lower stages of cancer (I and II). A disea- se-free resection margin (RO) is also an important pre- dictor of long-term survival. However, locoregional re- currence or the appearance of distant metastases during the subsequent follow up is common (85%) even af- ter complete resection of the tumor (16-18).
The probability of failure increases in advanced sta- ge of disease. This happens when the lesion is greater than 12 centimeters in maximum diameter, with a high mitotic rate and intralesional hemorrhage (19).
Therefore surgery is demanding and must be perfor- med by a highly experienced surgical team using a lapa- rotomic approach.
Intraoperatively, maintaining tumor capsule inte- grity and preventing tumor spillage are key conside- rations (20). Notably, presence of tumor thrombi and vascular invasion are not contraindications to resection. In cases with extensive vascular involvement, usage of cardiopulmonary bypass can facilitate successful re- section (21). A transabdominal, open surgical approach allows maximal exposure. This facilitates en bloc ex- cision of tumor and other involved organs (usually kid- ney, spleen, pancreas or liver), maintenance of the tu- mor capsule, and effective vascular control when ne- cessary.
Metastatic disease debulking surgery, which removes as much of the tumor as possible, helps to reduce the
Multi-organ resection for locally advanced adrenocortical cancer: surgical strategy and literature review
blockage caused by a mass, usually large as well as the hormonal excess produced by the tumor. However, the- re is no significant effect of this therapy, since the me- dian survival of patients with incomplete resection of the primary tumor or inoperable metastatic disease not removable by surgery appears to be less than 12 months. Surgical resection of recurrent disease is ac- cepted as a treatment option of choice, as it is associated in a different series with an increase in median overall survival (21, 22).
Radiotherapy treatment is indicated in patients with R1-R2 resections, stage III disease and metastatic di- sease (bones) (23, 24).
Medical therapy includes regimens with cytotoxic agents such as mitotane alone or in combinations with streptozocin, etoposide/doxorubicin/cisplatin (25-28).
Conclusion
Adrenocortical carcinoma (ACC) is a rare and ag- gressive tumor with poor survival.
Complete surgical removal of ACC represents the current treatment of choice for this tumor, and a di- sease-free resection margin (RO) is an important pre- dictor of long-term survival.
Therefore surgery for ACC removal is demanding and must be performed by a highly experienced surgical team using a laparotomic approach.
Conflict of interests
The authors declare they have no conflict of interests.
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