Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-67<55% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

SummaryIncidence and mortality for sex-unspecific cancers is higher among men and is largely unexplained1,2. Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal haematopoietic cells3,4, but the phenotypic consequences of LOY have been elusive5–10. From analysis of 1153 elderly men, we report that LOY was associated with risks of all-cause mortality (HR=1.91, 95% CI=1.17-3.13, events=637) and non-haematological cancer mortality (HR=3.62, CI=1.56-8.41, events=132). LOY affected at least 8.2% of subjects in this cohort and median survival among men with LOY was 5.5 years shorter. Risk of all-cause mortality and LOY was validated in an independent cohort (HR=3.66), in which 20.5% of subjects displayed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.

Poor prognostic factors for midgut carcinoid patients were multiple liver metastases, presence of carcinoid syndrome and high levels of the tumor markers studied. In this study the only independent predictors of bad prognosis in midgut, carcinoid patients were advanced age, which however is inherently related to overall survival, and plasma chromogranin A > 5000 micrograms/l. Thus, chromogranin A may prove to be an important prognostic marker for patients with carcinoid tumors.

Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m 2

For the first time, m.lgllm and da.lgllm, LTL, PC, and EAM are demonstrated to be independent prognostic factors by multivariate analysis. Locoregional removal of the PT/m.lgllm. was a positive prognostic factor by crude and adjusted analysis and may influence survival.

The purpose of these guidelines is to assist physicians caring for patients with neuroendocrine neoplasia in considering eligibility criteria for peptide receptor radionuclide therapy (PRRT) and in defining the minimum requirements for PRRT. It is not these guidelines' aim to give recommendations on the use of specific radiolabelled somatostatin analogues for PRRT as different analogues are being used, and their availability is governed by varying international regulations. However, a recent randomized controlled trial, NETTER-1, has provided evidence that may establish ¹⁷⁷Lu-DOTA-octreotate (LutaThera®) as the first widely approved agent. It also makes recommendations on what minimal patient, tumour, and treatment outcome characteristics should be reported for PRRT to facilitate robust comparisons between studies.

Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females. This observation, together with the fact that males have a higher incidence of, and mortality from, most non-sex-specific cancers, remain unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of non-hematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts (TwinGene: odds ratio [OR]=4.3, 95% CI =2.8-6.7; ULSAM: OR=2.4, 95% CI=1.6-3.6; and PIVUS: OR=3.5, 95% CI=1.4-8.4) encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY-status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.

We have evaluated survival and tumor-related symptoms in the presence of mesenteric lymph node and liver metastases in relation to surgical procedures in 314 patients (148 women, mean age at diagnosis 61 years; 249 with liver metastases) treated for midgut carcinoid tumors. Of the operated patients, 46% presented with severe abdominal pain and intestinal obstruction and were operated on before the diagnosis. Medical treatment (somatostatin analogs, interferon-a) was initiated in 67% and 86%, respectively. Surgical attempts included small intestine or ileocecal/right-sided colon resection with excision of mesenteric lymph node metastases. Most of the patients (n = 286) had mesenteric lymph node metastases; 33% of them had unresectable mesenteric lymph node metastases and underwent surgery without mesenteric dissection. Patients who underwent resection for the primary tumor had a longer survival than those with no resection (median survival 7.4 vs. 4.0 years; p <0.01). Patients who underwent successful excision of mesenteric metastases had a significantly longer survival than those with remaining lymph node metastases. Patients operated on for a primary tumor but with remaining lymph nodes but no liver metastases and who subsequently received interferon and somatostatin analog treatment had a median survival of 7.4 years. Resection of the primary tumor and the mesenteric lymph node metastases led to a significant reduction in tumor-related symptoms. Surgery to remove the primary intestinal tumor including mesenteric lymph node metastases is supported by the present results, even in the presence of liver metastases. Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival.