Isolated familial pheochromocytoma as a variant of von Hippel-Lindau disease.

Inherited pheochromocytomas are often part of familial syndromes, especially multiple endocrine neoplasia type 2 (MEN 2), retinal cerebellar hemangioblastomatosis [von Hippel-Lindau (vHL) disease] or neurofibromatosis type 1. It is not clear whether isolated familial pheochromocytoma exists as a separate clinical entity. In a family with pheochromocytomas in three generations and with at least seven affected members, we investigated by clinical and genetic analyses the presence or absence of associated conditions. The clinical investigations included ophthalmological and radiological studies for von Hippel-Lindau disease (magnetic resonance imaging of the brain, computed tomography of the abdomen, and direct ophthalmoscopy after mydriasis) and annual calcitonin stimulation tests for C cell disease in five members who agreed to regular follow-up. Besides the pheochromocytomas (so far, these have been multiple in five of seven individuals) no definite second associated condition was found. Genetic analysis did not identify any MEN 2-specific RET protooncogene point mutations (which are present in 97% of MEN 2a families). However, despite the complete absence of other clinical manifestations of the vHL disease (besides pheochromocytomas), a previously undescribed germline missense mutation in the vHL tumor suppressor gene was found (C775G transversion with a predicted substitution of a leucine by a valine at codon 259 in the putative vHL protein). We conclude that in this family the sole occurrence of pheochromocytoma is a variant of vHL disease

The Importance of Screening for Medullary Thyroid Carcinoma in Families of Patients with MEN 2

Family .screening for medullary thyroid cancer (MTC) is important for detecting members of multiple endocrine neoplasia type 2 (MEN 2) families who may be gene carriers but show no clinical evidence of the disease. Most members of our MEN 2 families are screened yearly by measuring basal and pentagastrin-stimulated calcitonin (CT) levels. A 15-year-old first-degree relative of an affected member of the D-kindred showed a normal basal and an elevated stimulated CT level. Clinical examination, ultrasonography, and scintigraphy were normal. Thyroidectomy and bilateral neck dissection revealed a multicentric MTC with no lymph node involvement. In the O-kindred we detected elevated basal and/or stimulated CT levels in three asymptomatic first-degree relatives. At surgery we found a small multicentric MTC in one family member, C-cell hyperplasia in another member, and bilateral lymph node metastases in one member who had been previously thyroidectomized. Basal and stimulated CT estimations in MEN 2 family members provide an effective method for detecting MTC in early, treatable stages

Comparison of the collagen haemostat Sangustop(R) versus a carrier-bound fibrin sealant during liver resection; ESSCALIVER-study

Background: Haemostasis in liver surgery remains a challenge despite improved resection techniques. Oozing from blood vessels too small to be ligated necessitate a treatment with haemostats in order to prevent complications attributed to bleeding. There is good evidence from randomised trials for the efficacy of fibrin sealants, on their own or in combination with a carrier material. A new haemostatic device is Sangustop(R). It is a collagen based material without any coagulation factors. Pre-clinical data for Sangustop(R) showed superior haemostatic effect. This present study aims to show that in the clinical situation Sangustop(R) is not inferior to a carrier-bound fibrin sealant (Tachosil(R)) as a haemostatic treatment in hepatic resection. Methods: This is a multi-centre, patient-blinded, intra-operatively randomised controlled trial. A total of 126 patients planned for an elective liver resection will be enrolled in eight surgical centres. The primary objective of this study is to show the non-inferiority of Sangustop(R) versus a carrier-bound fibrin sealant (Tachosil(R)) in achieving haemostasis after hepatic resection. The surgical intervention is standardised with regard to devices and techniques used for resection and primary haemostasis. Patients will be followed-up for three months for complications and adverse events. Discussion: This randomised controlled trial (ESSCALIVER) aims to compare the new collagen haemostat Sangustop(R) with a carrier-bound fibrin sealant which can be seen as a "gold standard" in hepatic and other visceral organ surgery. If non-inferiority is shown other criteria than the haemostatic efficacy (e.g. costs, adverse events rate) may be considered for the choice of the most appropriate treatment. Trial Registration: NCT0091861

Transplantation for metastatic liver disease

The liver is a common site of metastases from many cancers, particularly those originating in the gastrointestinal tract. Liver transplantation is an uncommonly used but promising and at times controversial treatment option for neuroendocrine and colorectal liver metastases. Transplantation with meticulous patient selection has been associated with excellent long-term outcomes in individuals with neuroendocrine liver metastases, but questions remain regarding the role of transplantation in those who could also be eligible for hepatectomy, the role of neoadjuvant/adjuvant treatments in minimising recurrence, and the optimal timing of the procedure. A prospective pilot study of liver transplantation for unresectable colorectal liver metastases that reported a 5-year overall survival rate of 60% reinvigorated interest in this area following initially dismal outcomes. This has been followed by larger studies, and prospective trials are ongoing to quantify the potential benefits of liver transplantation over palliative chemotherapy. This review provides a critical summary of currently available knowledge on liver transplantation for neuroendocrine and colorectal liver metastases, and highlights avenues for further study to address gaps in the evidence base

Timing of Disease Occurrence and Hepatic Resection on Long-Term Outcome of Patients with Neuroendocrine Liver Metastasis

Background and objectives: The objective of the study was to evaluate the impact of timing of disease occurrence and hepatic resection on long-term outcome of neuroendocrine liver metastasis (NELM). Methods: A total of 420 patients undergoing curative-intent resection for NELM were identified from a multi-institutional database. Date of primary resection, NELM detection and resection, intraoperative details, disease-specific (DSS), and recurrence-free survival (RFS) were obtained. Results: A total of 243 (57.9%) patients had synchronous NELM, while 177 (42.1%) developed metachronous NELM. On propensity score matching (PSM), patients with synchronous versus metachronous NELM had comparable DSS (10-year DSS, 76.2% vs 85.9%, P = 0.105), yet a worse RFS (10-year RFS, 34.1% vs 59.8%, P = 0.008). DSS and RFS were comparable regardless of operative approach (simultaneous vs staged, both P > 0.1). Among patients who developed metachronous NELM, no difference in long-term outcomes were identified between early (≤2 years, n = 102, 57.6%) and late (>2 years, n = 68, 42.4%) disease on PSM (both P > 0.1). Conclusions: Patients with synchronous NELM had a higher risk of tumor recurrence after hepatic resection versus patients with metachronous disease. The time to development of metachronous NELM did not affect long-term outcome. Curative-intent hepatic resection should be considered for patients who develop NELM regardless of the timing of disease presentation.info:eu-repo/semantics/publishedVersio

Unusual presentation of metastatic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>The most common tumours of the adrenal gland are adenoma, pheochromocytoma, adrenocortical carcinoma, and metastases. Although the imaging features of these tumours are established, the imaging characteristics of uncommon adrenal masses are less well known. In patients with extradrenal tumour, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy.</p> <p>Case presentation</p> <p>A 52 year-old female was diagnosed with oesophageal adenocarcinoma and treated with oesophagectomy and adjuvant chemotherapy. Sixteen months later on staging CT scan a 2 × 2 cm adrenal mass was detected, which increased in size over a period of time to 3 × 3 cm in size. Adrenalectomy was performed and histological examination revealed metastatic adenocarcinoma within an adrenal adenoma.</p> <p>Conclusion</p> <p>The present case highlights the unusual behaviour of an oesophageal adenocarcinoma causing metastasis to an adrenocortical adenoma.</p

Correction: Assessing tumor molecular profiling to guide treatments for patients with advanced female genital tract malignancy

Correction to article DOI: https://dx.doi.org/10.18632/oncotarget.2367

Clinical translation of a click-labeled 18F-octreotate radioligand for imaging neuroendocrine tumors

© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. We conducted the first-in-human study of 18F-fluoroethyl triazole [Tyr3] octreotate (18F-FET-βAG-TOCA) in patients with neuroendocrine tumors (NETs) to evaluate biodistribution, dosimetry, and safety. Despite advances in clinical imaging, detection and quantification of NET activity remains a challenge, with no universally accepted imaging standard. Methods: Nine patients were enrolled. Eight patients had sporadic NETs, and 1 had multiple endocrine neoplasia type 1 syndrome. Patients received 137-163 MBq (mean ± SD, 155.7 ± 8 MBq) of 18F-FET-βAG-TOCA. Safety data were obtained during and 24 h after radioligand administration. Patients underwent detailed wholebody PET/CT multibed scanning over 4 h with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated with OLINDA 1.1. Results: All patients tolerated 18F-FET-βAG-TOCA with no adverse events. Over 60% parent radioligand was present in plasma at 60 min. High tumor (primary and metastases)-to-background contrast images were observed. Physiologic distribution was seen in the pituitary, salivary glands, thyroid, and spleen, with low background distribution in the liver, an organ in which metastases commonly occur. The organs receiving highest absorbed dose were the gallbladder, spleen, stomach, liver, kidneys, and bladder. The calculated effective dose over all subjects (mean ± SD) was 0.029 ± 0.004 mSv/MBq. Conclusion: The favorable safety, imaging, and dosimetric profile makes 18F-FET-βAGTOCA a promising candidate radioligand for staging and management of NETs. Clinical studies in an expanded cohort are ongoing to clinically qualify this agent

Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3:a multicenter cohort study

Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.acceptedVersio