Piero F. Alesina

Laparoscopic and retroperitoneoscopic treatment of pheochromocytomas and retroperitoneal paragangliomas : Results of 161 tumors in 126 patients

BackgroundLaparoscopic and retroperitoneoscopic excisions of pheochromocytomas and retroperitoneal paragangliomas are challenging surgical procedures because of extensive intraoperative catecholamine release, extreme vascularization, and demanding localization.MaterialsIn a prospective clinical study 161 chromaffine neoplasias (134 pheochromocytomas, 27 paragangliomas) were removed endoscopically in 126 patients (67 males, 59 females, age 41.7 ± 16.4 years; 130 operations). Six patients showed multiple (2–5) tumors. Tumor size ranged from 0.5 to 12 cm (mean 3.5 ± 1.9 cm). Forty-two patients suffered from hereditary diseases. Twenty-four patients had bilateral adrenal diseases; in 14 patients pheochromocytomas were removed on both sides synchroneously. Ten neoplasias were local or loco-regional recurrences (7 pheochromocytomas, 3 paragangliomas). The laparoscopic route was chosen in 16 operations; the retroperitoneoscopic technique was performed in 128 others. Partial adrenalectomies were performed in 57 operations (in all but one of the patients with bilateral disease). High-dosage α-blockade with phenoxybenzamine was routinely used.Results and DiscussionConversion to open surgery occurred once. Perioperative complications were minor (17%); mortality was zero. Operating time for unilateral retroperitoneoscopically removed primary pheochromocytomas (n = 113) was 82 ± 49 minutes (range: 20–300 minutes) and depended on tumor size (< 3 cm vs. ≥ 3 cm; P < 0.05) and gender (P < 0.001), but not on extent of resection (partial vs. total, P = 0.266). Operating time for paragangliomas ranged from 55 to 600 minutes. Median blood loss was 20 ml. Median duration of postoperative hospitalization was 4 days. In 22 of 24 patients with bilateral disease, complete preservation of cortical function was achieved. Locoregional and/or distant metastatic recurrence were found in 5 patients.ConclusionsEndoscopic removal of solitary, bilateral, multiple, and recurrent pheochromocytomas and retroperitoneal paragangliomas is feasible and safe, but surgeons need extensive experience in minimally invasive techniques, as well as in endocrine surgery.

Complementary somatic mutations of KCNJ5, ATP1A1, and ATP2B3 in sporadic aldosterone producing adrenal adenomas

Primary aldosteronism (PA) is the most common form of secondary hypertension, accounting for 8–13% among hypertension patients (Mulatero et al. 2013). It is characterized by constitutive production of aldosterone by the adrenal cortex. Among the subtypes of PA, aldosteroneproducing adenomas (APAs), also known as Conn tumors, are characterized by tumors in the adrenal cortex and account for 30–40% of the cases. The two most important physiological stimuli of aldosterone secretion are angiotensin II and serum potassium. Decrease in blood volume activates the renin–angiotensin system, in which angiotensin II signals via the angiotensin receptor. The K concentration across the membrane sets the resting membrane potential. Hyperkalemia causes depolarization of the membrane and generates an action potential to open a voltage-gated Ca channel. In both cases, enhanced intracellular Ca provides the normal signal for aldosterone production. In APAs, autonomous production of aldosterone is found independently of angiotensin II. Recently, next generation sequencing has revealed novel genes frequently mutated in APAs: KCNJ5, ATP1A1, and ATP2B3 (Choi et al. 2011, Taguchi et al. 2012, Beuschlein et al. 2013, Mulatero et al. 2013). In these pivotal studies, mutations in KCNJ5, encoding an inwardly rectifying K channel, were identified in about 30–45% of patients. The K channel encoded by KCNJ5 exists both as homo-tetramer and as a hetero-tetramer with another potassium channel encoded by KCNJ3. The latter has been found more active than homo-tetramers (Choi et al. 2011). More recently, mutations in ATP1A1 (encode a Na/K pump ATPase a subunit) and ATP2B3 (plasma membrane Ca ATPase) have been reported, each of which appears in about 6 and 2% of the tumors respectively (Beuschlein et al. 2013). In this study, we investigated KCNJ5, KCNJ3, ATP1A1, and ATP2B3 for mutations in a series of 35 consecutive patients with

Pattern of and reason for postoperative residual disease in patients with advanced ovarian cancer following upfront radical debulking surgery

OBJECTIVE Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy. METHODS All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis. RESULTS 739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival. CONCLUSIONS Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

Minimally invasive video-assisted parathyroidectomy (MIVAP) for secondary hyperparathyroidism: report of initial experience

BACKGROUND Minimally invasive video-assisted parathyroidectomy (MIVAP) has become a well-accepted procedure for patients with primary hyperparathyroidism. Because it allows bilateral neck exploration, the authors began using this technique for patients with secondary hyperparathyroidism. In this preliminary study, the authors report their initial experience. METHODS From July 2006 to November 2008, 12 patients (6 women, 6 men; mean age, 45.5 +/- 16.9 years (range, 23-71 years) underwent MIVAP with bilateral exploration for secondary hyperparathyroidism. The operation was performed through a central 2-cm to 3-cm skin incision; a 30 degrees 5-mm endoscope was used for magnification. RESULTS MIVAP was successfully completed in 11 patients (92%). The mean operative time was 81 +/- 37 minutes (range, 35-130 minutes). No major complications were registered. After a mean follow-up period of 11.4 months (range, 3-30 months), 1 patient showed recurrence. CONCLUSIONS MIVAP appears to be a safe and feasible procedure in patients with secondary hyperparathyroidism.