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T cell exclusion causes resistance to cancer immunotherapies via immune checkpoint blockade (ICB). Myeloid cells contribute to resistance by expressing signal regulatory protein-α (SIRPα), an inhibitory membrane receptor that interacts with ubiquitous receptor CD47 to control macrophage phagocytosis in the tumor microenvironment. Although CD47/SIRPα-targeting drugs have been assessed in preclinical models, the therapeutic benefit of selectively blocking SIRPα, and not SIRPγ/CD47, in humans remains unknown. We report a potent synergy between selective SIRPα blockade and ICB in increasing memory T cell responses and reverting exclusion in syngeneic and orthotopic tumor models. Selective SIRPα blockade stimulated tumor nest T cell recruitment by restoring murine and human macrophage chemokine secretion and increased anti-tumor T cell responses by promoting tumor-antigen crosspresentation by dendritic cells. However, nonselective SIRPα/SIRPγ blockade targeting CD47 impaired human T cell activation, proliferation, and endothelial transmigration. Selective SIRPα inhibition opens an attractive avenue to overcoming ICB resistance in patients with elevated myeloid cell infiltration in solid tumors.

The technique of hepatic arterial infusion (HAI) for the treatment of liver metastases from colorectal cancer has been developed over more than 30 years. Although the indications and protocols for this technique have evolved with time, HAI is not routinely performed in clinical practice. Studies have been heterogeneous, with different regimens of intra-arterial drugs, associated or not with systemic chemotherapy, and with unconvincing outcomes. Technical difficulties for catheter placement have limited the implementation of this method in routine practice. The aim of this review is to present recent studies, highlighting technical improvements and promising combinations of oxaliplatin-based HAI with systemic treatments. HAI is being investigated in both the metastatic setting - in the first line and beyond - and in the adjuvant setting, and we will discuss its potential place in current and future patient management., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The prognosis of gallbladder cancer is basically dependent on the histological stage at diagnosis. In practice, the discovery of a small cancer of the bladder, generally during cholecystectomy give the patient a better care for curative treatment. The advent of laparoscopy has increased the number of cholecstectomies and could increase the frequency of this situation but also raises the difficult problem of metastatic dissemination. In the literature the figures on parietal metastasis after laparoscopy have ranged from 125% to 19%. The median delay to diagnosis of recurrence is 6 months. The cause of this phenomenon (role of the pneumoperitoneum) remains poorly elucidated. Risk factors for the development of a metastasis on the trocar orifice are: rupture of the gallbladder perioperatively and extraction of the gallbladder without protection. It is important to keep in mind this exceptional but serious risk and apply rigorous operative technique. In case of suspected gallbladder we do not advocate laparoscopy. Surgery (hepatectomy, lymphodenectomy, possibly resection of the biliary tract) would be indicted for all stages except pTis and T1a, taking into consideration the localization of the tumor and the patient's general status. It is also classical to recommend resection of the trocar orifices after laparoscopic cholecystectomy. There is a dual challenge today for small-sized gallbladder cancer: improving treatment and avoiding poorer prognosis due to the specific problems raised by laparoscopy.

Hypothesis: Resection of intraductal papillary mucinous tumors of the pancreas (IPMTP) should be tailored to longitudinal spreading into the pancreatic ductal system and the presence of malignant transformation., Objective: To review a single institutional experience with IPMTP, focusing on the operative strategy of tailoring resection to the extent of disease., Design: Retrospective study., Setting: Academic tertiary referral center., Patients: Thirteen patients with IPMTP were referred for resection during the past 10 years. Malignant growth was present in 7 patients (54%). According to the determination of tumor extent, distal pancreatic resection was performed in 3 patients, pancreatoduodenectomy was done in 9 patients, and total pancreatectomy was performed in 1 patient. The median follow-up time in this series was 46 months (range, 3-104 months)., Main Outcome Measures: Preoperative and perioperative diagnosis, final pathologic results, and long-term outcome., Results: A correct preoperative or perioperative diagnosis of IPMTP was achieved in 9 patients (69%). Routine frozen section of the surgical margin was used in all patients, changing the operative strategy in 3 (23%) of 13 patients by extending resection or leading to total pancreatectomy in 2 patients and 1 patient, respectively. A perioperative endoscopic examination of the Wirsung duct was performed in 3 patients with a correct preoperative or perioperative diagnosis of IPMTP and a dilated pancreatic duct. This allowed the examination of the entire pancreatic ductal system and staged intraductal biopsies, changing the operative strategy in 1 of these patients. Finally, after pancreatoduodenectomy, pancreaticogastric anastomosis was constructed in 5 patients, allowing endoscopic assessment of the pancreatic stump during long-term follow-up. The 5-year actuarial survival rate was 56.8% in the whole series. All patients with benign or microinvasive malignant disease remained disease-free, whereas all patients with invasive malignant disease died of tumor recurrence., Conclusions: Accurate determination of the extent of ductal disease and residual malignant growth, when present, is critical during surgical exploration to achieve radical resection and cure. Operative strategy should be based on routine frozen section of the surgical margin and perioperative endoscopic examination of the Wirsung duct with staged intraductal biopsies when technically feasible. The routine use of pancreaticogastric anastomosis after pancreatoduodenectomy allows easy, safe, and efficient long-term endoscopic assessment of the pancreatic stump.