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The possibility of surgical resection strongly overrules medical oncologic treatment and is the only modality, causa sine qua non, long-term survival can be achieved in patients with pancreatic cancer. For this reason, the clinical classification of local resectability, subdividing tumors into resectable, borderline resectable, and locally advanced cancer, that is very technical in nature, is the one most widely used and accepted. As multimodality treatment with potent agents, particularly in the neoadjuvant setting, seems to be stepping forward as the new standard of treatment of pancreatic cancer, the established technical surgical landmarks tend to get challenged. This review aims to highlight the grey zones in the current classifications for local tumor involvement with respect to the observed patient outcome in the current multimodality treatment era. It summarizes the latest reported series on the outcome of resected primary resectable, borderline and locally advanced pancreatic cancer, and particularly vascular resections during pancreatectomy, in the background of different types of neoadjuvant therapy. It also hints what the new horizons of cancer biology tend to reveal whenever the technical hinders start being pushed aside. The current calls for the necessity of re-classification of the clinical categories of pancreatic cancer, from technically oriented to biology-focused individualized approach, are being elucidated., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-2020-slapc-04). The series “Surgery for Locally Advanced Pancreatic Cancer” was commissioned by the editorial office without any funding or sponsorship. ER served as the unpaid Guest Editor of the series. The authors have no other conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: A patient with unresectable periampullary malignancy found at laparotomy has traditionally received a prophylactic double bypass (biliary and duodenal), associated with considerable morbidity. With modern endoscopic treatments, surgical bypass has become questionable. This study aims to compare the two strategies. Sahlgrenska University Hospital (SU) performs a double bypass (DoB) routinely, and Skåne University Hospital Lund (SUL) secures biliary drainage endoscopically and treats only symptomatic duodenal obstruction (Wait and See, WaS)., Method: Between 2004 and 2013, 73 patients from SU and 70 from SUL were retrospectively identified. Demographics, tumour-related factors and postoperative outcomes during the remaining lifetime were noted., Results: The DoB group had significantly more complications (67% vs. 31%, p = 0.00002) and longer hospital stay (14 vs. 8 days, p = 0.001) than the WaS-group. The two groups had similar proportion of patients in need of readmission. The DoB patients and the WaS patients with metallic biliary stents were comparable regarding their need of re-interventions and hospitalisation due to biliary obstruction. Surgical duodenal bypass did not prevent future duodenal obstructions., Conclusion: Patients with unresectable periampullary malignancies can safely be managed with endoscopic drainage on demand and with lower morbidity and shorter hospital stay than with surgical prophylactic bypass., (Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: A patient with unresectable periampullary malignancy found at laparotomy has traditionally received a prophylactic double bypass (biliary and duodenal), associated with considerable morbidity. With modern endoscopic treatments, a surgical bypass has become questionable. This study aims to compare the two strategies. Sahlgrenska University Hospital (SU) performs a double bypass (DoB) routinely, and Skåne University Hospital Lund (SUL) secures biliary drainage endoscopically and treats only symptomatic duodenal obstruction (Wait and See, WaS)., Method: Between 2004 and 2013, 73 patients from SU and 70 from SUL were retrospectively identified. Demographics, tumour-related factors and post-operative outcomes during the remaining lifetime of the patients were noted., Results: The DoB group had significantly more complications (67% versus 31%, P = 0.00002) and a longer hospital stay (14 versus 8 days, P = 0.001) than the WaS group. The two groups had a similar proportion of patients in need of readmission. The DoB patients and the WaS patients with metallic biliary stents were comparable regarding their need of re-interventions and hospitalization as a result of biliary obstruction. A surgical duodenal bypass did not prevent future duodenal obstructions., Conclusion: Patients with unresectable periampullary malignancies can safely be managed with endoscopic drainage on demand and with a lower morbidity and a shorter hospital stay than with a surgical prophylactic bypass., (© 2015 International Hepato-Pancreato-Biliary Association.)

Background & Aims: Angiotensin II is a potent activator of smooth muscles but has not been much investigated with regard to gastrointestinal motor activity. This study explores expression of the renin-angiotensin system (RAS) in human esophageal musculature and actions by Angiotensin II both in vitro and in vivo., Methods: Muscular specimens of esophageal body and lower esophageal sphincter were obtained from patients undergoing resection as a result of mucosal neoplasm. Healthy volunteers participated in functional examinations of esophageal motility assessed by high-resolution manometry and multiple transmucosal potential-difference measurements., Results: Gene transcripts of key components of RAS were found in the esophageal musculature. Immunohistochemistry revealed a distinct staining for Angiotensin II type 1 (AT(1)) receptors in the muscular bundles and blood-vessel walls, whereas Angiotensin II type 2 receptors were confined to blood vessels only. Angiotensin II caused concentration-dependent contractions in vitro, which were inhibited by the AT(1) receptor antagonist losartan but not by the Angiotensin II type 2 receptor antagonist PD123319. Administration of the AT(1) receptor antagonist candesartan reduced the amplitude of swallow-induced peristaltic contractions and both the length and pressure amplitude of baseline high-pressure zone at the esophagogastric junction. Neither swallow-induced axial movements, nor the contraction after transient lower esophageal sphincter relaxations, were influenced by candesartan pretreatment., Conclusions: The study demonstrates a local RAS in the musculature of the distal esophagus and that Angiotensin II is a potent stimulator of esophageal contractions via the AT(1) receptor. The results suggest that Angiotensin II participates in the physiological control of the human esophageal motor activity.