Exploring definitions of graft pancreatitis following pancreas transplantation: A scoping review.

Despite the clinical relevance of graft pancreatitis (GP) after pancreas transplantation (PT), a universally accepted definition is lacking. Aim of this scoping review was to provide a systematic overview of GP definitions reported in the literature. MEDLINE, Web of Science and Embase were searched for relevant articles. Prospective/retrospective studies reporting a GP definition were included. The included series (n = 20) used four main criteria (clinical, biochemical, radiological and pathological) to define GP. Overall, 9 studies defined GP using a single criterion (n = 8 biochemical, n = 1 pathological), 7 series using two criteria (n = 3 clinical + biochemical, n = 3 biochemical + radiological, n = 1 clinical + radiological), 3 series using three criteria (n = 3 clinical + biochemical + radiological), and 1 series using four criteria. Overall, 20 definitions of GP were found. GP rate was reported by 19 series and ranged between 0% and 87%. This scoping review confirms that a universally accepted definition of GP is absent, and there is no consensus on the criteria on which it should be grounded. Future research should focus on developing a validated definition of GP.

Fat-to-blood recirculation of partially dysfunctional PD-1+CD4 Tconv cells is associated with dysglycemia in human obesity.

Obesity is characterized by the accumulation of T cells in insulin-sensitive tissues, including the visceral adipose tissue (VAT), that can interfere with the insulin signaling pathway eventually leading to insulin resistance (IR) and type 2 diabetes. Here, we found that PD-1+CD4 conventional T (Tconv) cells, endowed with a transcriptomic and functional profile of partially dysfunctional cells, are diminished in VAT of obese patients with dysglycemia (OB-Dys), without a concomitant increase in apoptosis. These cells showed enhanced capacity to recirculate into the bloodstream and had a non-restricted TCRß repertoire divergent from that of normoglycemic obese and lean individuals. PD-1+CD4 Tconv were reduced in the circulation of OB-Dys, exhibited an altered migration potential, and were detected in the liver of patients with non-alcoholic steatohepatitis. The findings suggest a potential role for partially dysfunctional PD-1+CD4 Tconv cells as inter-organ mediators of IR in obese patients with dysglycemic.

Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge.

Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.

Laparoscopic wedge resection for gastrointestinal stromal tumour of the duodenum.

We report the case of a 40-year-old male patient who presented with melaena and acute anaemia. Endoscopic ultrasound examination revealed a lesion with a central depression measuring 2.5 cm, arising from the lateral wall of the second portion of the duodenum. Because of this rare location, a very invasive procedure (duodenopancreatectomy) might have been required for tumour resection. We avoided this operation and implemented an alternative solution. A laparoscopic wedge resection of the duodenal tumour was successfully completed. Operating time was 200 min and blood loss 50 ml. The patient was discharged on postoperative day 3, after an uneventful postoperative recovery. Histopathologically, the tumour was diagnosed as a low-risk gastrointestinal stromal tumour. Despite the fact that laparoscopic surgery requires more complex technique than open surgery and the acquisition of advanced laparoscopic skills depending on prior laparoscopic experience, laparoscopic wedge resection should be considered as a valid treatment for duodenal stromal tumour.

Apoptosis-dependent subversion of the T-lymphocyte epitope hierarchy in lymphoma cells.

Tumor cells undergoing programmed death are an attractive source of tumor-associated antigens, and evidences are available for their therapeutic efficacy in vivo when used either alone or in association with dendritic cells. However, little is known about the specificity of the immune response induced by such antigen formulation. Indeed, activation of specific proteases during apoptosis may influence the cytoplasmic degradation of proteins and the generation of CTL epitopes. We show here that on injection of C57BL/6 mice either with RMA lymphoma cells induced to apoptosis or bone marrow-derived dendritic cells pulsed with apoptotic RMA cells, a specific and protective CTL response is induced, which, however, is not directed against the immunodominant CTL epitope gag(85-93). Lack of in vivo expansion of gag(85-93)-specific CTL in vaccinated mice is attributable to the apoptosis-dependent loss of gag(85-93) in dying tumor cells. Indeed, we found loss of gag(85-93) in RMA, MBL-2, and EL-4G+ lymphoma cells, which share gag(85-93) as an immunodominant CTL epitope, induced to apoptosis by UV irradiation, mitomycin C, doxorubicin, or daunorubicin. This phenomenon appears to be caspase-dependent, because caspase inhibition by N-benzyloxycarbonyl-Val-Ala-asp-fluoromethylketone prevents apoptosis of lymphoma cells and loss of gag(85-93). Therefore, subversion of the epitope hierarchy in apoptotic tumor cells might be relevant in the induction of tumor-specific T-lymphocyte responses.

Impact of age on postoperative outcomes in 1118 gastric cancer patients undergoing surgical treatment.

BACKGROUND: The purpose of the study was to evaluate the impact of age on outcomes in gastric cancer surgery. METHODS: Patients on the hospital database who underwent gastric resection for gastric cancer during the period 1990-2005 (n = 1118) were divided into two groups: group A, patients 75 years or older (n = 249), and group B, those younger than 75 years (n = 869). RESULTS: Overall preoperative complications were diagnosed in 92 (37%) patients of group A, compared with 147 (17%) in group B (P = 0.002). Fifty-five percent of patients underwent resection with D2 or more lymph node dissection (37% [n = 93] in group A, and 60% [n = 521] in group B; P = 0.003). Postoperative overall morbidity was higher in the elderly group (29% in group A versus 23% in group B), but the difference between the two groups was not significant (P = NS). Overall postoperative surgical complications were recorded in 201 (18%) patients; 49 (20%) in the elderly cohort, compared with 147 (17%) in the younger group (P = NS). The postoperative mortality rate was 3% (n = 7) in the elderly group, compared with 3% (n = 26) in the younger cohort (P = NS). Multivariate Cox analysis showed that age was not an independent risk factor for postoperative morbidity and mortality. Overall 5-year survival was 47% in group A and 54% in group B (P = NS). CONCLUSION: Due to improved perioperative management, resection of gastric carcinoma is the treatment of choice in elderly patients. Although comorbidities were more frequent among the elderly patients, postoperative morbidity and mortality, even after extensive resections, was low. Survival rates were comparable to those in the younger patients.