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Background: Despite exocrine pancreatic insufficiency (EPI) being a significant consequence of pancreatic surgery, there is still no consensus on its perioperative management. This study aimed to evaluate unselective pancreatic enzyme replacement therapy (PERT)., Methods: A prospective, observational study of patients undergoing partial pancreatectomy was conducted. EPI status was assessed pre- and postoperatively, based on three fecal-elastase measurements each. Characteristic symptoms were evaluated by questionnaire. In 85 post-surgical patients, the subjective burden of PERT was measured., Results: 101 patients were followed prospectively. Preoperative EPI screening was available for 83 patients, of which 48% were diagnosed with preexisting EPI. Of those patients with regular exocrine function, 54% developed EPI de novo; this rate being higher following pancreatic head resections (72%) compared to left-sided pancreatectomies (LP) (20%) (p = 0.016). Overall postoperative EPI prevalence was significantly greater following pancreatic head resections (86%) than LP (33%) (p < 0.001). Only young and female patients described a significant burden related to PERT., Conclusion: For all patients undergoing pancreatic head resection PERT should be considered beginning prior to surgery, due to the subgroup's high EPI rate and the comparatively low burden of PERT. Patients with LP are at lower risk and should be pre- and postoperatively screened and supplemented accordingly., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The immune system plays a pivotal role in cancer progression. Interleukin 22 binding protein (IL-22BP), a natural antagonist of the cytokine interleukin 22 (IL-22) has been shown to control the progression of colorectal cancer (CRC). However, the role of IL-22BP in the process of metastasis formation remains unknown., Methods: We used two different murine in vivo metastasis models using the MC38 and LLC cancer cell lines and studied lung and liver metastasis formation after intracaecal or intrasplenic injection of cancer cells. Furthermore, IL22BP expression was measured in a clinical cohort of CRC patients and correlated with metastatic tumor stages., Results: Our data indicate that low levels of IL-22BP are associated with advanced (metastatic) tumor stages in colorectal cancer. Using two different murine in vivo models we show that IL-22BP indeed controls the progression of liver but not lung metastasis in mice., Conclusions: We here demonstrate a crucial role of IL-22BP in controlling metastasis progression. Thus, IL-22 might represent a future therapeutic target against the progression of metastatic CRC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Giannou, Kempski, Zhang, Lücke, Shiri, Zazara, Belios, Machicote, Seeger, Agalioti, Tintelnot, Sagebiel, Tomczak, Bauditz, Bedke, Kocheise, Mercanoglu, Fard-Aghaie, Giorgakis, Lykoudis, Pikouli, Grass, Wahib, Bardenhagen, Brunswig, Heumann, Ghadban, Duprée, Tachezy, Melling, Arck, Stringa, Gentilini, Gondolesi, Nakano, Thomson, Perez, Li, Mann, Izbicki, Gagliani, Maroulis and Huber.)

Background: KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations., Methods: 221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis., Results: Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008)., Conclusions: KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients-at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients-guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility., (©American Association for Clinical Chemistry 2023.)

Pancreatic cancer remains one of the biggest challenges in oncology, as most patients are diagnosed in a stage of regional lymphatic or systemic spread of the disease. 10% of the patients present with peritoneal carcinomatosis upon diagnosis. In the past decades, cytoreductive surgery (CRS) combined with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) has been developed and presents a new, individualized treatment option for patients with peritoneal disseminated cancer. This case report presents the case of a 39-year-old male with the initial diagnosis of a carcinoma of the pancreatic tail with localized peritoneal carcinomatosis. As an individualized approach, neoadjuvant chemotherapy was recommended with an option for a second exploration. Re-Staging revealed a reduction in tumor size. Cytoreductive surgery (CRS) including a distal splenopancreatectomy was performed and followed by HIPEC. Postoperatively, the patient developed a clinically relevant pancreatic fistula, however recovered and was able to receive adjuvant chemotherapy. Taken together, in pancreatic cancer with localized peritoneal carcinomatosis CRS and HIPEC are a valid option in highly selective cases with potential extended overall survival and an acceptable quality of life., (Celsius.)

Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to an incomplete understanding of tumor contexts in which OXPHOS is essential. Here, we report the discovery of IACS-010759, a clinical-grade small-molecule inhibitor of complex I of the mitochondrial electron transport chain. Treatment with IACS-010759 robustly inhibited proliferation and induced apoptosis in models of brain cancer and acute myeloid leukemia (AML) reliant on OXPHOS, likely owing to a combination of energy depletion and reduced aspartate production that leads to impaired nucleotide biosynthesis. In models of brain cancer and AML, tumor growth was potently inhibited in vivo following IACS-010759 treatment at well-tolerated doses. IACS-010759 is currently being evaluated in phase 1 clinical trials in relapsed/refractory AML and solid tumors.

Background: Since its introduction, endovascular aortic aneurysm repair (EVAR) has proved as a favourable alternative to open surgery (OR) in the treatment of abdominal aortic aneurysms (AAA). Long-term outcomes of EVAR and OR are similar while complications are more likely to develop after EVAR. Risk factors for mortality and complications after AAA surgery have been identified, however, a general overview is lacking., Methods: In a systematic literature search via PubMed, we identified publications on the topic of factors influencing the postoperative outcome of AAA surgery., Results: Patient age > 80 years was found to be a significant predictor of increased mortality, whereas the influence of aneurysm diameter on OR remains moderate, the outcome of EVAR performed in AAA > 6.5 cm is associated with higher mortality and increased complication rates. In patients with ruptured AAA the postoperative mortality is higher than in those with intact aneurysms. Preoperative haemodynamic instability has a crucial influence on patient outcome and is strongly associated with intra- and postoperative death. The prevalence of cardiovascular co-morbidity leads to increased long-term mortality. Preoperative statin medication was found to reduce short- and long-term mortality by the factor of 0.5. Patients suffering from chronic lung disease such as COPD and patients with a deficiency in renal function are more likely to experience adverse events including death. While the prevalence of cerebrovascular disease is associated with an increase in mortality by the factor of 1.5 or higher, findings on patients with diabetes mellitus are conflicting with no definite point to be made., Conclusion: Several factors influencing the outcome of surgery for AAA present a condition developed from factors involved in the pathogenesis of AAA. The impact of non-disease factors like patient age and aneurysm diameter can be reduced by the means of population-wide screening for AAA, and optimised treatment of disease-related risk factors can reduce mortality. Studies comparing the outcome of EVAR and OR in patients with risk factors should be performed to support decision-making about the ideal individual treatment., (Georg Thieme Verlag KG Stuttgart · New York.)

The prevalence of diabetes throughout the world continues to increase and has become a major health issue. Recently there have been several reports of inhibitors directed toward the sodium-dependent glucose cotransporter 2 (SGLT2) as a method of maintaining glucose homeostasis in diabetic patients. Herein we report the discovery of the novel O-xyloside 7c that inhibits SGLT2 in vitro and urinary glucose reabsorption in vivo.