Angiogenesis index CD105 (Endoglin)-CD31 (PECAM-1) as a predictive factor for invasion and proliferation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas

Background: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is an increasingly diagnosed entity since its definition by the World Health Organization in 1996. It has a broad clinical spectrum ranging from benign to malignant tumors. Optimum treatment is controversial and a better understanding of the development of IPMN of the pancreas and identification of potential prognostic factors will help to address this. Angiogenesis plays an elementary role in the development of malignant tumors and may well also be important in the development of IPMN of the pancreas. Therefore we investigated endothelial cell marker CD31 (PECAM-1) and angiogenesis associated marker CD105 (Endoglin) by immunohistochemistry. Methods: Thirty-two cases of surgically resected IPMN were chosen retrospectively and clinical data were obtained. Specimens were stained for proliferation marker (Ki-67), CD31 and CD105 by immunohistochemistry. A CD105/CD31 Angiogenesis ratio (AR) was established to determine the proliferating fraction of endothelial cells. Results: The AR is significantly elevated in invasive IPMN of the pancreas (Mann-Whitney-U Test, p<0.05) and is associated with the Ki-67-labelling-index, demonstrating synergy between tumor-growth and neovascularisation. Invasive IPMN of the pancreas is associated with significantly lower recurrence-free and overall survival. Conclusions: Neovascularisation plays an important role in the tumorigenesis of invasive IPMN of the pancreas, and therefore angiogenesis-associated molecules like CD105 and CD31 might be useful tools as prognostic markers. Furthermore, the results indicate a potential role for adjuvant anti-angiogenic therapies in selected patients with recurring and/or invasive IPMN of the pancreas

Screening for frailty with the frail scale: a comparison with the phenotype criteria

sem informaçãoReliable and valid frailty screening instruments are lacking. The aim of the present studywas to compare the diagnostic properties of the FRAIL-BR with Fried’s frailty phenotype (CHS), which hasnot been done.Cross-sectional observational study of 124 olde187592596sem informaçãosem informaçãosem informaçã

Protocol for generating lung and liver metastasis in mice using models that bypass intravasation

Summary: Forced metastasis models, those in which the step of intravasation is bypassed, can be used to investigate the mechanisms underlying metastasis and evaluate potential therapeutic targets. Here, we present a protocol for using three forced models of lung and liver metastasis to generate metastasis within 3–4 weeks in approximately 99% of injected mice. We describe steps for cancer cell preparation, mouse analgesia and anesthesia; injecting through intrasplenic, intraportal, and intravenous techniques; and daily evaluation of metastasis.For complete details on the use and execution of this protocol, please refer to Giannou et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

The role of vascular adhesion molecules PECAM-1 (CD 31), VCAM-1 (CD 106), E-Selectin (CD62E) and P-Selectin (CD62P) in severe porcine pancreatitis

Inflammatory cytokines have been shown to mediate organ damage by their action on vascular endothelia and leukocytes, in part by upregulating the expression of adhesion molecules, which in turn convey transmigration of leukocytes into tissue. The upregulation and activation of vascular cell adhesion molecules on the endothelial cells avail firm leukocyte adhesion to the vascular endothelium and enhance their transmigration and consecutive tissue injury. The aim of this study was to evaluate the expresion of vascular adhesion molecules CD 31 (PECAM-1), CD 106 (VCAM-1), CD 62E (E-Selectin) and CD 62P (P-Selectin) in the pancreas and distant organs of pigs suffering from acute necrotizing pancreatitis (AP). AP was induced in 13 pigs by a combination of intravenous cerulein and intraductal glycodeoxycholic acid. For immunostaining of vascular adhesion molecules slides of porcine pancreas, lung, kidney and liver tissue were stained with monoclonal antibodies (Ab) against PECAM-1-1, VCAM-1 E- and PSELECTIN. The endothelial cell expression of CD 31 (PECAM- 1), CD 106 (VCAM), CD 62E (E-Selectin) and CD 62P (P-SELECTIN) in severe porcine pancreatitis is detectable and upregulation is partly significantly

Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients

Abstract Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki‐67 labeling index, and associated with earlier PSA recurrence (P < .0001). Survivin loss was significantly more common in cancers carrying TMPRSS2:ERG fusions (61% survivin negative) than in ERG wild‐type cancers (32% survivin negative; P < .0001). Multivariate analysis revealed that reduced cytoplasmic survivin expression predicted poor prognosis independent from Gleason score, pT, pN, and serum PSA level. This was valid for ERG‐positive and ERG‐negative cancers. Survivin expression loss even retained its prognostic impact in 1020 PTEN deleted cancers, a group that is already characterized by dismal patient prognosis. In conclusion, reduced survivin expression is associated with more aggressive tumors and inferior prognosis in prostate cancer

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms

Purpose!#!Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8!##!Methods!#!The density of CD8!##!Results!#!We found that the median CD8!##!Conclusion!#!These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors

Defining Major Surgery: A Delphi Consensus Among European Surgical Association (ESA) Members

Background: Major surgery is a term frequently used but poorly defined. The aim of the present study was to reach a consensus in the definition of major surgery within a panel of expert surgeons from the European Surgical Association (ESA). Methods: A 3-round Delphi process was performed. All ESA members were invited to participate in the expert panel. In round 1, experts were inquired by open- and closed-ended questions on potential criteria to define major surgery. Results were analyzed and presented back anonymously to the panel within next rounds. Closed-ended questions in round 2 and 3 were either binary or statements to be rated on a Likert scale ranging from 1 (strong disagreement) to 5 (strong agreement). Participants were sent 3 reminders at 2-week intervals for each round. 70% of agreement was considered to indicate consensus. Results: Out of 305 ESA members, 67 (22%) answered all the 3 rounds. Significant comorbidities were the only preoperative factor retained to define major surgery (78%). Vascular clampage or organ ischemia (92%), high intraoperative blood loss (90%), high noradrenalin requirements (77%), long operative time (73%) and perioperative blood transfusion (70%) were procedure-related factors that reached consensus. Regarding postoperative factors, systemic inflammatory response (76%) and the need for intensive or intermediate care (88%) reached consensus. Consequences of major surgery were high morbidity (>30% overall) and mortality (>2%). Conclusion: ESA experts defined major surgery according to extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes