Treatment options for PNET liver metastases. a systematic review

Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms. About 40-80% of patients with PNET are metastatic at presentation, usually involving the liver (40-93%). Liver metastasis represents the most significant prognostic factor. The aim of this study is to present an up-to-date review of treatment options for patients with liver metastases from PNETs

The staging of gastritis with the olga system in the italian setting. histological features and gastric cancer risk

BACKGROUND: Recently OLGA (Operative Link on Gastritis Assessment) classification has been proposed to identify high-risk forms of gastritis that can evolve in gastric cancer (stages III and IV). Helicobacter pylori infection and age older than 40 have been considered as independent risk factor for high-risk OLGA stages

SMO Inhibition Modulates Cellular Plasticity and Invasiveness in Colorectal Cancer

Colon Cancer (CC) is the fourth most frequently diagnosed tumor and the second leading cause of death in the USA. Abnormalities of Hedgehog pathway have been demonstrated in several types of human cancers, however the role of Hedgehog (Hh) in CC remain controversial. In this study, we analyzed the association between increased mRNA expression of GLI1 and GLI2, two Hh target genes, and CC survival and recurrence by gene expression microarray from a cohort of 382 CC patients. We found that patients with increased expression of GLI1 showed a statistically significant reduction in survival. In order to demonstrate a causal role of Hh pathway activation in the pathogenesis of CC, we treated HCT 116, SW480 and SW620 CC cells lines with GDC-0449, a pharmacological inhibitor of Smoothened (SMO). Treatment with GDC-0449 markedly reduced expression of Hh target genes GLI1, PTCH1, HIP1, MUC5AC, thus indicating that this pathway is constitutively active in CC cell lines. Moreover, GDC-0449 partially reduced cell proliferation, which was associated with upregulation of p21 and downregulation of CycD1. Finally, treatment with the same drug reduced migration and three-dimensional invasion, which were associated with downregulation of Snail1, the EMT master gene, and with induction of the epithelial markers Cytokeratin-18 and E-cadherin. These results were confirmed by SMO genetic silencing. Notably, treatment with 5E1, a Sonic Hedgehog-specific mAb, markedly reduced the expression of Hedgehog target genes, as well as inhibited cell proliferation and mediated reversion toward an epithelial phenotype. This suggests the existence of a Hedgehog autocrine signaling loop affecting cell plasticity and fostering cell proliferation andmigration/invasion in CC cell lines. These discoveries encourage future investigations to better characterize the role of Hedgehog in cellular plasticity and invasion during the different steps of CC pathogenesis.Peer reviewe

A longitudinal study of C1q and anti-C1q autoantibodies in homologous and heterologous pregnancies for predicting pre-eclampsia

C1q, the recognition molecule of the classical pathway of the complement system, plays a central role in pregnancy. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure. C1q can be the target of an antibody response: anti-C1q autoantibodies (anti-C1q) are present in several infectious and autoimmune diseases. The presence of these autoantibodies has been detected also in 2-8% of the general population. Recent evidence indicates that women who undergo assisted reproductive technology (ART) have an increased risk of developing pre-eclampsia (PE), particularly oocyte donation (OD) pregnancies. The aim of this study was to characterize the levels of C1q and anti-C1q in PE gestations, in healthy spontaneous, homologous and heterologous ART pregnancies. Serum of the following four groups of women, who were followed throughout two or three trimesters, were collected: PE, patients diagnosed with PE; OD, oocyte donation recipients; HOM, homologous ART women; Sp, spontaneous physiological pregnancy. Our results indicate that PE patients have lower levels of anti-C1q. In ART pregnant women, the trend of C1q and anti-C1q levels were similar to PE patients, even though these women did not develop PE-like symptoms during pregnancy. This finding suggests an immunological dysfunction at the foetal-maternal interface in ART pregnancies, a hypothesis confirmed by the observation of C1q deposition in placentae derived from OD, comparable to PE. Since significantly lower levels of anti-C1q were detected in PE compared to healthy control sera, we hypothesize the possible binding on placental syncytiotrophoblast microvesicles (STBM), which are increased in the circulation of PE mothers. Furthermore, the characterization of the binding-epitope of anti-C1q revealed that "physiological" autoantibodies were mainly directed against C1q globular domain. We concluded that anti-C1q could have a physiological role in pregnancy: during the healthy spontaneous pregnancy the raised levels of these autoantibodies can be important for the clearance of STBM. In PE and in pathological pregnancies (but also in OD pregnancies), the increase in syncytiotrophoblast apoptosis and consequent increase of the circulating STMB levels lead to a consumption of C1q and anti-C1q

Impact of sarcopenia on outcomes after pancreatectomy for malignancy. Preliminary results

INTRODUCTION: Sarcopenia, a subclinical loss of skeletal muscle mass, is commonly observed in patients with malignancy. Few studies have examined the association between sarcopenia and out- comes after pancreatic surgery. The aim of this study was to deter- mine the prevalence of sarcopenia among patients who underwent pancreatectomy for cancer and its correlation with morbidity and mortality. METHODS: Skeletal muscle index (SMI) was measured on preop- erative CT imaging in 75 patients undergoing pancreatectomy for cancer between 2010 and 2014. Sarcopenia was defined using pre- viously published sex-adjusted SMI cut-offs. The impact of sarco- penia on morbidity and mortality was assessed relative to other clinico-pathologic factors. RESULTS: Mean age was 66.35 years and 56% were female. Pancreatic adenocarcinoma represented 68% of all cases. Pancrea- ticoduodenectomy was performed in 77.3%. Fifty patients (66.7%) were sarcopenic, 37 (49.4%) were overweight/obese, and 21 (42%) were both (p1⁄4 0.044). Mean SMI among men (46.47 cm2/m2) was greater than among women (36.63 cm2/m2, p1⁄40.001). Univariate analysis found BMI (p1⁄40.001), female sex (p<0.001), and preoperative serum albumin (p1⁄40.004) as predic- tors of sarcopenia. On multivariate analysis, preoperative serum al- bumin was confirmed to be an independent predictor of sarcopenia (p1⁄40.0268). Sarcopenia was associated with a difference, although not significant, in terms of overall morbidity and 90-day mortality (p1⁄40.131 and p1⁄40.735, respectively). CONCLUSIONS: Sarcopenia was present in two-thirds of patients who underwent pancreatectomy for cancer. It is an occult condi- tion in overweight/obese patients, easily identified using CT scans. Preoperative serum albumin is a predictor of sarcopenia. This con- dition is not associated with increased risk of complications or 90- day death

Esophagectomy with esophagocoloplasty for malignancies. indications, technique (with Video), and results. systematic review of the literature

Introduction: Esophagocoloplasty represents a useful technique to restore the intestinal continuity after esophagogastrectomy. This technique has been used mainly after esophagogastric caustic injuries. The aim of this review is to assess the role of esophagogastrectomy with esophagocoloplasty for esophageal or gastric neoplasms. Methods: A systematic literature search was performed using Embase, Medline, Cochrane, and PubMed databases to identify all studies published in the previous 25 years (1991–2016) reporting cases of esophagocoloplasty after esophagogastrectomy for malignancies. The systematic review was conducted according to the PRISMA guidelines. Results: The systematic review of the literature shows a morbidity rate of 57% and a mortality rate of 15% in the 93 reported cases of esophagocoloplasty performed for malignant diseases. However, R0 rate ranged from 76.1 to 85%, and 5-year survival was obtained in 11.9–32.8% of patients in the different series. Conclusions: In highly selected cases of primary or relapsing gastric or esophageal neoplasms, esophagogastrectomy with esophagocoloplasty is a viable and useful option, which may guarantee complete tumor resection and long-term survival

Routine extra-hepatic bile duct resection in gallbladder cancer patients without bile duct infiltration. A systematic review

The optimal treatment for advanced gallbladder cancer, in particular T2 stage cancer, is unclear. The use of "radical cholecystectomy" or more extended procedures with extra-hepatic bile duct resection are matter of debate. Due to the lack of consensus regarding the oncological significance of routine extra-hepatic bile duct (EBD) resection for gallbladder carcinoma, we decided to perform a systematic review investigating the real benefit of this procedure focusing on the primary outcomes of overall survival and disease-free survival. METHODS: A systematic literature search was performed using PubMed, EMBASE, Scopus and the Cochrane Library Central according to the PRISMA statement guidelines for conducting and reporting systematic reviews. Multiple primary and secondary outcomes were analyzed. RESULTS: The selected articles included 424 patients who underwent routine EBD resection without bile duct infiltration. Only two papers discussed the number of dissected lymph nodes during EBD resection for gallbladder carcinoma. Four of the seven included papers reported on tumor involvement in lymph nodes at rates ranging between 39% and 83%. All of the studies included in this systematic review reported on results of overall survival. In general, 5-years OS rate of the EBD-resected patients was not significantly different than that of the EBD-preservation group, while the mobility was significantly higher in the EBD resection group. CONCLUSIONS: Routine EBD resection in gallbladder cancer patients without bile duct infiltration is not associated with improved overall survival, improved lymph-node harvesting or with minor recurrence rate, but it is associated with higher morbidity rates. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved