Dilemmas in Diagnosis and Management of Gastroenteropancreatic Mixed Neuroendocrine Non-neuroendocrine Neoplasms: First Single-Centre Report from India.

PURPOSE: Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is a rare neoplasm comprising of exocrine and neuroendocrine elements, each representing ≥ 30% lesion. It is commonly misdiagnosed as adenocarcinoma or grade-3 neuroendocrine neoplasm (NEN). Management is not well-defined. METHODS: Retrospective analysis of prospectively entered data at our centre from January 2011 to January 2018 revealed 16 MiNENs off 130 neuroendocrine neoplasms (NENs). These were analysed for demographics, clinicopathological characteristics, management strategies and prognosis. RESULTS: Four out of 16 patients, metastatic at presentation, were started on chemotherapy. Eleven of remaining 12 patients had pre-operative biopsy. Only two were diagnosed MiNEN. Four patients (33.34%) received 5-fluorouracil (5-FU)-based neoadjuvant chemotherapy and underwent curative surgery with adjuvant cisplatin+etoposide (Cis-Eto). Out of these, two patients (16.6%) developed metastasis and were shifted to capecitabine+temozolomide (Cap-Tem). Six patients (50%) with neuroendocrine-dominant MiNEN received adjuvant Cis-Eto after surgery. Two (16.6%) developed metastases for which Cap-Tem was started. One of them developed locoregional and liver metastasis. Three patients (25%) have succumbed to progressive disease, three (25%) are on treatment, and six (50%) are disease-free at 4-30 months. CONCLUSION: Preoperative diagnosis of MiNEN is challenging, and it needs quality histopathological examination and immunohistochemistry. The 30% criteria is therapeutically insignificant, and treatment based on most aggressive component is prognostically more relevant. Neoadjuvant 5-FU-based regimens may downstage adenocarcinoma-dominant tumours. There are no guidelines on adjuvant Cis-Eto. Cap-Tem can be considered second-line chemotherapy. Poor survival is reported irrespective of site of origin and adjuvant therapy.

Multimodality management, recurrence patterns, and long-term outcome of gastroenteropancreatic neuroendocrine neoplasms: Progress over 17 years.

BACKGROUND: Many advances in the management of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) happened in the last two decades. This study highlights the progress in its management over 17 years, outcomes, recurrence patterns, and follow up protocols. METHODS: This retrospective analysis of prospectively maintained database at a single tertiary center included GEP-NEN patients from January 2001 to August 2017. Management protocols were based on European Neuroendocrine Tumor Society guidelines. Recurrences were categorized as follows: localized nodal, regional, distant hepatic, or combined. Patients were divided into cohorts: cohort 1 (2001-2006), cohort 2 (2007-2011), and cohort 3 (2012-2017). Survival patterns were analyzed. RESULTS: One hundred and ninety-two patients were included with 98 (51.04%) grade (G) 1, 64 (33.34%) G2, and 30 (15.63%) G3. One hundred and four (54.16%) underwent curative surgery (58 G1, 27 G2, and 19 G3). Overall follow up ranged from 3 to 276 months; 39 were lost to follow up. Ninety-six patients had recurrences: 44 regional + distant and 40 liver-limited recurrences. One-, 3-, and 5-year survivals show significant differences among different treatment groups (p < 0.05). Significant increase in curative resections, chemotherapy utilization, and reduced recurrences were noted in cohort 3. Curative (R0) resection offered 1- and 3-year overall survival of 93.3% and 66.7% in cohort 1; 95.8% and 83.1% in cohort 2; and 100% and 92.9% in cohort 3. CONCLUSION: Curative resection is the most significant factor for improved survival. Debulking surgerical procedure have a role whereas upfront peptide receptor radionuclide therapy is questionable. Chemotherapy improves overall survival in inoperable/metastatic setting. Recurrence patterns indicate that a long-term follow up greater than 10 years is necessary.

Transduodenal ampullectomy for ampullary tumors.

Transduodenal ampullectomy (TDA) is indicated for large ampullary tumors, for presence of dysplasia on endoscopic biopsy, for poor surgical candidates for pancreaticoduodenectomy, and in cases not indicated for endoscopic ampullectomy. Retrospective review of data from 2009 to 2015 revealed 11 patients who underwent TDA. Magnetic resonance imaging cholangiopancreatography (MRI-MRCP), contrast-enhanced computed tomography (CECT) scan, side-viewing endoscopy, and endoscopic ultrasound (EUS) were used for investigating the patients as required. Preoperative biopsy was done in all. Out of the 11 patients, only one had recurrence. Two patients had adenocarcinoma and were treated with pancreaticoduodenectomy. TDA is a safe surgical procedure for treatment of well-selected benign ampullary pathologies. It is also a treatment option for the cases of ampullary adenomas not amenable to endoscopic resection.

Trends in diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in India: A report of multicenter data from a web-based registry.

INTRODUCTION: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors. We report data of 407 GEP-NET cases from a neuroendocrine tumor (NET) registry in India. METHODS: The AP-NET registry is an open-label, multicenter, longitudinal observational registry of patients with GEP-NETs in which six tertiary care oncology centers contributed data. Data was prospectively entered in a dedicated computerized database and was reviewed retrospectively. The patients were divided into three cohorts-those diagnosed from 2001 to 2005, from 2006 to 2010, and from 2011 to 2016. RESULTS: Of the 407 cases registered, 37 were in Cohort I, 136 in Cohort II, and 234 in Cohort III. Majority were symptomatic with only 98 patients (24.0%) asymptomatic. The most common presentation of non-functional tumors was abdominal pain (42.4%), while functional tumors presented most commonly with carcinoid syndrome. Use of DOTA-PET, introduced in 2011, has increased evaluation in 33.3% patients in Cohort III. The most common primary site was pancreas in all three cohorts. Male preponderance (58.3%) was seen. Histopathological grading was obtained in 230 (56.5%) patients-118 (29%) Grade I, 74 (18.2%) Grade II, and 36 (8.8%) Grade III NET. CONCLUSION: This report highlights changing trends in the diagnosis and reporting of NETs over the last 15 years.

Radiofrequency ablation of liver tumors: experience with open and percutaneous approach.

BACKGROUND: Radiofrequency ablation (RFA), a thermal coagulation technique, has been used for ablation of primary and secondary liver tumors. METHODS: Over a 24-month period, 41 patients, including 20 with hepatocellular cancer (HCC), 14 with liver metastases from colorectal tumors and 7 with metastases from other tumors, underwent RFA in our institution. Ablation was done using intra-operative (n=27) or percutaneous ultrasonographic (n=14) guidance. A zone of ablation larger than the size of the lesion on CT scan indicated successful RFA. RESULTS: The mean size of lesions was 4.9 cm for HCC and 3.1 cm for metastases. Among 20 patients with HCC, 16 had complete tumor ablation and one had failure of localization. All patients with liver metastases had successful tumor ablation. There was no procedure-related death. Two patients had hemoperitoneum and one experienced skin burn. During a median follow up of 16 months, five patients with HCC and two with colorectal metastases died. One patient had tumor recurrence at the ablation site and two developed fresh solitary metastatic lesions; all three are disease-free after repeat ablation treatment. CONCLUSIONS: RFA is a safe and promising technique for the treatment of non-resectable HCC and liver metastases, in the short term.

Neuroendocrine tumor of common hepatic duct.

Extrahepatic bile ducts (EHBD) remain one of the rarest primary sites for neuroendocrine tumors (NETs) accounting for 0.1 % to 0.2 % of all NETs of the gastrointestinal tract. We present one such case, a 28-year-old female with vague abdominal symptoms and periportal lymph node enlargement on radiological examination. Endoscopic retrograde cholangiopancreaticography revealed 1.5 cms long common hepatic duct stricture and brush cytology showed no malignant cells. Endoscopic ultrasound guided fine needle aspiration cytology from the lymph nodes reported malignant cells. Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy was done. The diagnosis of well-differentiated neuroendocrine carcinoma was confirmed on histological and immunohistochemical studies. NETs of biliary tract are difficult to diagnose preoperatively. The aggressive use of curative and cytoreductive surgery is the frontline of treatment. But the rare alternative diagnosis of NETs should be kept in mind by the surgeon for proper timely management.

Calcitonin-secreting tumor of the pancreas.

Pancreatic endocrine tumors (PETs) are unusual tumors arising from cells belonging generically to the amine precursor uptake and decarboxylation systems. We present a case of a calcitonin-secreting PET in a 56-year-old female who presented with watery diarrhea, dehydration and hypokalemia. Investigation revealed hypercalcemia, hyperphosphatemia, hypercalcitonemia and a well-defined mass in the head of the pancreas on CT scan. Following a pancreaticoduodenectomy her serum calcitonin levels returned to normal and diarrhea disappeared. The identification of this particularly rare presentation of a calcitonin-secreting PET provides the opportunity to examine this pathological entity within the context of the very few previously reported instances of this disease.