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Background 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. Methods A systematic literature search was performed using the PubMed database to identify all pertinent studies published up to May 2018. Results The literature search evaluated all the therapeutic options for patients with liver metastases of PNETs, including surgical treatment, loco-regional therapies, and pharmacological treatment. All the different treatment options showed particular indications in different presentations of liver metastases of PNET. Surgery remains the only potentially curative therapeutic option in patients with PNETs and resectable liver metastases, even if relapse rates are high. Efficacy of medical treatment has increased with advances in targeted therapies, such as everolimus and sunitinib, and the introduction of radiolabeled somatostatin analogs. Several techniques for loco-regional control of metastases are available, including chemo- or radioembolization. Conclusions Treatment of patients with PNET metastases should be multidisciplinary and must be personalized according to the features of individual patients and tumors.

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. 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. 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. 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.

HIGHLIGHTS Preliminary results of this work were presented at the 2016 Academic Surgical Congress, Jacksonville (FL), February 2-4 2016 (Original title: Selective Smo-Inhibition Interferes With Cellular Energetic Metabolism In Colorectal Cancer)This study was funded by "Sapienza-University of Rome" (Funds for young researchers) and "AIRC" (Italian Association for Cancer Research)Hedgehog inhibitor was kindly provided by Genentech, Inc.®. 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 and migration/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.

Aim 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.