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American Journal of Transplantation :... Mar 2024The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas...
Banff 2022 pancreas transplantation multidisciplinary report: Refinement of guidelines for T cell-mediated rejection, antibody-mediated rejection and islet pathology. Assessment of duodenal cuff biopsies and noninvasive diagnostic methods.
The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.
Topics: Pancreas Transplantation; Transplantation, Homologous; Biopsy; Isoantibodies; T-Lymphocytes
PubMed: 37871799
DOI: 10.1016/j.ajt.2023.10.011 -
Oncology Letters Aug 2023The first part of the duodenum consists of the intraperitoneal segment, called the duodenal bulb, and the retroperitoneal segment. Regarding the blood supplying the... (Review)
Review
Intracorporeal linear‑stapled gastroduodenostomy in totally laparoscopic distal gastrectomy for gastric cancer: Consideration of the intraoperative management of the duodenal wall between the transecting staple line and anastomotic staple line (Review).
The first part of the duodenum consists of the intraperitoneal segment, called the duodenal bulb, and the retroperitoneal segment. Regarding the blood supplying the duodenal bulb, which is the portion utilized in anastomosing the duodenum and remnant stomach following distal gastrectomy, the arterial pedicles branching off from the gastroduodenal artery are reported to reach the posterior wall first and then spread over the anterior wall, where they anastomose. When performing intracorporeal linear-stapled gastroduodenostomy following totally laparoscopic distal gastrectomy, the blood supply of the duodenal wall between the transecting staple line and anastomotic staple line needs to be considered because both transection of the duodenal bulb and the gastroduodenostomy are performed using an endoscopic linear stapler and the duodenal wall between the staple lines can be ischemic after the anastomosis. Since it needs to be decided intraoperatively whether this duodenal site is preserved or removed, the present review discusses the technical differences among several procedures for intracorporeal linear-stapled gastroduodenostomy, classifying them into two groups on the basis of the intraoperative management of this duodenal site. When this site is preserved, the blood supply of the duodenal wall needs to be retained with certainty. On the other hand, when this site is removed, the ischemic portion of the duodenal wall needs to be identified and removed. Furthermore, in both groups, an adequate anastomotic area needs to be secured. In conclusion, surgeons need to be familiar with the anatomical features of the duodenal bulb, including its blood perfusion and shape, when carrying out intracorporeal linear-stapled gastroduodenostomy.
PubMed: 37545615
DOI: 10.3892/ol.2023.13940 -
Diabetologia Jul 2024Protein kinase CK2 acts as a negative regulator of insulin expression in pancreatic beta cells. This action is mainly mediated by phosphorylation of the transcription...
AIMS/HYPOTHESIS
Protein kinase CK2 acts as a negative regulator of insulin expression in pancreatic beta cells. This action is mainly mediated by phosphorylation of the transcription factor pancreatic and duodenal homeobox protein 1 (PDX1). In pancreatic alpha cells, PDX1 acts in a reciprocal fashion on glucagon (GCG) expression. Therefore, we hypothesised that CK2 might positively regulate GCG expression in pancreatic alpha cells.
METHODS
We suppressed CK2 kinase activity in αTC1 cells by two pharmacological inhibitors and by the CRISPR/Cas9 technique. Subsequently, we analysed GCG expression and secretion by real-time quantitative RT-PCR, western blot, luciferase assay, ELISA and DNA pull-down assays. We additionally studied paracrine effects on GCG secretion in pseudoislets, isolated murine islets and human islets. In vivo, we examined the effect of CK2 inhibition on blood glucose levels by systemic and alpha cell-specific CK2 inhibition.
RESULTS
We found that CK2 downregulation reduces GCG secretion in the murine alpha cell line αTC1 (e.g. from 1094±124 ng/l to 459±110 ng/l) by the use of the CK2-inhibitor SGC-CK2-1. This was due to a marked decrease in Gcg gene expression through alteration of the binding of paired box protein 6 (PAX6) and transcription factor MafB to the Gcg promoter. The analysis of the underlying mechanisms revealed that both transcription factors are displaced by PDX1. Ex vivo experiments in isolated murine islets and pseudoislets further demonstrated that CK2-mediated reduction in GCG secretion was only slightly affected by the higher insulin secretion after CK2 inhibition. The kidney capsule transplantation model showed the significance of CK2 for GCG expression and secretion in vivo. Finally, CK2 downregulation also reduced the GCG secretion in islets isolated from humans.
CONCLUSIONS/INTERPRETATION
These novel findings not only indicate an important function of protein kinase CK2 for proper GCG expression but also demonstrate that CK2 may be a promising target for the development of novel glucose-lowering drugs.
Topics: Casein Kinase II; Animals; Glucagon; Mice; Humans; Glucagon-Secreting Cells; Homeodomain Proteins; Trans-Activators; Male; Cell Line; Insulin
PubMed: 38503901
DOI: 10.1007/s00125-024-06128-1 -
VideoGIE : An Official Video Journal of... Sep 2023Video 1Case presentation.
Video 1Case presentation.
PubMed: 37719945
DOI: 10.1016/j.vgie.2023.05.014 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Oct 2023Internal hernias involve the herniation of intestines through mesenteric or peritoneal defects in the gastrointestinal system. Etiologically, they are generally... (Observational Study)
Observational Study
BACKGROUND
Internal hernias involve the herniation of intestines through mesenteric or peritoneal defects in the gastrointestinal system. Etiologically, they are generally classified as congenital or acquired. Internal hernias often present with non-specific symptoms. Despite the increased use of computed tomography (CT), discrepancies between imaging findings and diagnostic accuracy continue to pose challenges for clinicians. This study aims to compare the outcomes of patients presenting to the emergency department with abdominal pain and receiving a preliminary internal hernia diagnosis through CT, followed by laparotomy.
METHODS
Our research is a retrospective, observational, and descriptive study. It includes patients presenting to the emergency department with abdominal pain, who were provisionally diagnosed with internal hernia based on CT. Patient data recorded age, gen-der, CT-identified internal hernia type, surgery, diagnoses, hospitalization status, duration of hospital stay, bowel resection, mortality, and blood parameters. The Welch classification was used to categorize internal hernia types, with eight types examined.
RESULTS
Among 112 patients with a preliminary internal hernia diagnosis based on abdominal CT, the median age was 52 years. Of these, 46 were female and 66 were male. Among all patients, 87 were admitted to the hospital for observation and surgery, while 25 were discharged after emergency department. Paraduodenal hernias were the most common provisional diagnosis (48 cases). Among these patients, 45 were discharged after symptom relief and were advised for elective re-evaluation. The exact diagnosis for these pa-tients remains unknown. Post-surgery, the diagnosis of internal hernia was confirmed in 32 cases. Among them, 15 were female and 17 were male, with a median age of 52. The median hospital stay for patients diagnosed with internal hernia was 5 days. Although acquired hernias exhibited higher resection and mortality rates, no statistically significant difference was found. Thirty-five cases received dif-ferent diagnoses: 19 had brid ileus, five had volvulus, six had acute appendicitis, one had duodenal perforation, three had gynecological malignancies, and one had renal malignancy.
CONCLUSION
Although internal hernias are rare, early diagnosis and treatment are very important due to the high risk of death. The study findings indicate that increased CT utilization leads to earlier diagnosis and treatment, resulting in improved prognosis for patients. This study holds one of the largest case series in the literature. It provides a novel perspective by evaluating radiologically-diagnosed cases, confirming diagnoses post-surgery, and comparing conditions that mimic internal hernias, thereby making a valuable contribution to the literature.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Hernia, Abdominal; Intestinal Obstruction; Internal Hernia; Abdominal Pain
PubMed: 37791450
DOI: 10.14744/tjtes.2023.36037 -
PloS One 2023Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune...
BACKGROUND
Small bowel adenocarcinoma (SBA) is a rare malignancy of the small intestine associated with late stage diagnosis and poor survival outcome. High expression of immune cells and immune checkpoint biomarkers especially programmed cell death ligand-1 (PD-L1) have been shown to significantly impact disease progression. We have analysed the expression of a subset of immune cell and immune checkpoint biomarkers in a cohort of SBA patients and assessed their impact on progression-free survival (PFS) and overall survival (OS).
METHODS
25 patient samples in the form of formalin fixed, paraffin embedded (FFPE) tissue were obtained in tissue microarray (TMAs) format. Automated immunohistochemistry (IHC) staining was performed using validated antibodies for CD3, CD4, CD8, CD68, PD-L1, ICOS, IDO1 and LAG3. Slides were scanned digitally and assessed in QuPath, an open source image analysis software, for biomarker density and percentage positivity. Survival analyses were carried out using the Kaplan Meier method.
RESULTS
Varying expressions of biomarkers were recorded. High expressions of CD3, CD4 and IDO1 were significant for PFS (p = 0.043, 0.020 and 0.018 respectively). High expression of ICOS was significant for both PFS (p = 0.040) and OS (p = 0.041), while high PD-L1 expression in tumour cells was significant for OS (p = 0.033). High correlation was observed between PD-L1 and IDO1 expressions (Pearson correlation co-efficient = 1) and subsequently high IDO1 expression in tumour cells was found to be significant for PFS (p = 0.006) and OS (p = 0.034).
CONCLUSIONS
High levels of immune cells and immune checkpoint proteins have a significant impact on patient survival in SBA. These data could provide an insight into the immunotherapeutic management of patients with SBA.
Topics: Humans; B7-H1 Antigen; Adenocarcinoma; Survival Analysis; Duodenal Neoplasms; Biomarkers, Tumor; Intestine, Small; Prognosis; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment
PubMed: 37527282
DOI: 10.1371/journal.pone.0289355 -
Scientific Reports Aug 2023Enteric methane (CH) emission is one of the major greenhouse gasses originating from cattle. Iodoform has in studies been found to be a potent mitigator of rumen CH...
Enteric methane (CH) emission is one of the major greenhouse gasses originating from cattle. Iodoform has in studies been found to be a potent mitigator of rumen CH formation in vitro. This study aimed to quantify potential of iodoform as an anti-methanogenic feed additive for dairy cows and investigate effects on feed intake, milk production, feed digestibility, rumen microbiome, and animal health indicators. The experiment was conducted as a 4 × 4 Latin square design using four lactating rumen, duodenal, and ileal cannulated Danish Holstein dairy cows. The treatments consisted of four different doses of iodoform (1) 0 mg/day, (2) 320 mg/day, (3) 640 mg/day, and (4) 800 mg/day. Iodoform was supplemented intra-ruminally twice daily. Each period consisted of 7-days of adaptation, 3-days of digesta and blood sampling, and 4-days of gas exchange measurements using respiration chambers. Milk yield and dry matter intake (DMI) were recorded daily. Rumen samples were collected for microbial analyses and investigated for fermentation parameters. Blood was sampled and analyzed for metabolic and health status indicators. Dry matter intake and milk production decreased linearly by maximum of 48% and 33%, respectively, with increasing dose. Methane yield (g CH/kg DMI) decreased by maximum of 66%, while up to 125-fold increases were observed in hydrogen yield (g H/kg DMI) with increasing dose of iodoform. Total tract digestibility of DM, OM, CP, C, NDF, and starch were unaffected by treatments, but large shifts, except for NDF, were observed for ruminal to small intestinal digestion of the nutrients. Some indicators of disturbed rumen microbial activity and fermentation dynamics were observed with increasing dose, but total number of ruminal bacteria was unaffected by treatment. Serum and plasma biomarkers did not indicate negative effects of iodoform on cow health. In conclusion, iodoform was a potent mitigator of CH emission. However, DMI and milk production were negatively affected and associated with indications of depressed ruminal fermentation. Future studies might reveal if depression of milk yield and feed intake can be avoided if iodoform is continuously administered by mixing it into a total mixed ration.
Topics: Female; Cattle; Animals; Lactation; Diet; Methane; Dietary Supplements; Milk; Rumen; Fermentation; Digestion; Silage
PubMed: 37550361
DOI: 10.1038/s41598-023-38149-y -
Revista Espanola de Enfermedades... Sep 2023We present the case of a 75-year-old male admitted due to severe epigastric pain. His medical history was remarkable for chronic alcohol abuse, diabetes mellitus type 2,...
We present the case of a 75-year-old male admitted due to severe epigastric pain. His medical history was remarkable for chronic alcohol abuse, diabetes mellitus type 2, arterial hypertension, dyslipidemia. At admission he was hemodynamically stable. The initial workup showed elevated amylase, and the abdominal ultrasound excluded gallstone disease, so the diagnosis of acute pancreatitis was assumed. Despite appropriate fluid therapy, the patient developed hemodynamic instability. No signs of GIB were detected. An urgent laboratory workup revealed a new onset anemia and liver tests, including hyperbilirrubinemia. He underwent an urgent abdominal computed tomography with contrast, which showed a bleeding gastroduodenal artery (pseudoaneurysm and a hematoma adjacent to the second part of the duodenum. The patient underwent coil embolization achieving hemostasis without complications. GAD (pseudo)aneurysm is rare, accounting for 1.5% of all visceral artery aneurysms. Our patient presented with elevated pancreatic and liver enzymes, a more unique and challenging presentation since another more common differential diagnosis should be considered. The aneurysm can cause extrinsic common bile duct and main pancreatic duct pressure, which could explain the raised liver tests. Gastroenterologists should be aware of this rare and life-threatening entity, especially among patients presenting with common findings such as elevated amylase, jaundice, or altered liver tests. Hemodynamic instability is the main clue unmasking this diagnosis.
Topics: Male; Humans; Aged; Aneurysm, False; Pancreatitis; Hyperamylasemia; Acute Disease; Aneurysm; Hepatic Artery; Abdominal Pain; Amylases; Embolization, Therapeutic
PubMed: 36537340
DOI: 10.17235/reed.2022.9407/2022 -
Journal of Gastrointestinal Surgery :... Nov 2023Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy or parenchyma-sparing, local extirpation is a challenge for decision-making regarding surgery-related early and late postoperative morbidity.
METHODS
PubMed, Embase, and Cochrane Libraries were searched for studies reporting early surgery-related complications following pancreatoduodenectomy (PD) and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. Thirty-four cohort studies comprising data from 1099 patients were analyzed. In total, 654 patients underwent DPPHR and 445 patients PD for benign tumors. This review and meta-analysis does not need ethical approval.
RESULTS
Comparing DPPHRt and PD, the need for blood transfusion (OR 0.20, 95% CI 0.10-0.41, p<0.01), re-intervention for serious surgery-related complications (OR 0.48, 95% CI 0.31-0.73, p<0.001), and re-operation for severe complications (OR 0.50, 95% CI 0.26-0.95, p=0.04) were significantly less frequent following DPPHRt. Pancreatic fistula B+C (19.0 to 15.3%, p=0.99) and biliary fistula (6.3 to 4.3%; p=0.33) were in the same range following PD and DPPHRt. In-hospital mortality after DPPHRt was one of 350 patients (0.28%) and after PD eight of 445 patients (1.79%) (OR 0.32, 95% CI 0.10-1.09, p=0.07). Following DPPHRp, there was no mortality among the 192 patients.
CONCLUSION
DPPHR for benign pancreatic tumors is associated with significantly fewer surgery-related, serious, and severe postoperative complications and lower in-hospital mortality compared to PD. Tailored use of DPPHRt or DPPHRp contributes to a reduction of surgery-related complications. DPPHR has the potential to replace PD for benign tumors and premalignant cystic and neuroendocrine neoplasms of the pancreatic head.
Topics: Humans; Pancreatectomy; Pancreas; Pancreaticoduodenectomy; Pancreatic Neoplasms; Duodenum; Neuroendocrine Tumors; Pancreatic Cyst
PubMed: 37670106
DOI: 10.1007/s11605-023-05789-4 -
United European Gastroenterology Journal Nov 2023Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated.
METHODS
We searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta-analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non-users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) was also performed.
RESULTS
Twelve studies with 341,063 participants were included in this meta-analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]] = 1.42 [1.16-1.73]; hazard ratio [HR] [95% CI] = 3.23 [1.56-6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI] = 1.64 [1.49-1.80]; HR [95% CI] = 6.55 [2.01-21.33]). In the bleeding site-specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI] = 1.54 [1.30-1.84]).
CONCLUSIONS
PPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.
Topics: Humans; Proton Pump Inhibitors; Aspirin; Anti-Inflammatory Agents, Non-Steroidal; Gastrointestinal Hemorrhage; Colorectal Neoplasms
PubMed: 37553807
DOI: 10.1002/ueg2.12448