Nucleoporins (NUPs) constitute the nuclear pore complex (NPC) and are essentially involved in nuclear transport, chromatin organization, and context-dependent gene regulation. However, the role of NUPs in neuroendocrine (tumor)biology and related diagnostic potential is poorly defined. In this study, we comparatively analyzed immunohistochemical expression patterns of NUP98 and NUP153 (sharing structural and functional similarities) across a large variety of human tissues and tumors (total N > 600), with a focus on neuroendocrine neoplasms (NENs (n = 361)). While both NUPs showed a nuclear rim accentuated staining pattern, NUP98 exhibited ubiquitous and NUP153 a striking cell- and tissue/tumor-type-dependent immunoreactivity. More specifically, NUP153 immunoreactivity was consistently detectable in neuroendocrine tissues (e.g., pancreatic islets) and retained in neuroendocrine tumors (NETs) of the pancreas, lung, appendix, and small intestine, but almost completely absent in neuroendocrine carcinomas (NECs) and non-neuroendocrine carcinomas. Loss of NUP153 staining correlated with poorer clinical outcomes in pancreatic NETs. Further analyses revealed that NUP153 messenger ribonucleic acid (mRNA) and total protein levels were not significantly different between NETs and non-neuroendocrine carcinomas, as evaluated by quantitative real-time polymerase chain reaction and targeted proteomics. Differential isoform usage was ruled out by polymerase chain reaction and sequencing as another possible explanation for the discriminative immunohistochemical findings. Finally, a high density of post-translational modifications (PTMs) within the antigen sequence could be discovered and indicated PTM-dependent detection as the likely cause of differential staining. Collectively, our findings suggest that NUP153 is a differentiation-dependent and PTM-sensitive immunohistochemical marker in NENs with diagnostic and prognostic potential. It also emphasizes the importance of orthogonal molecular analyses for correct interpretation of IHC stainings.

SHIP1-deficient mice develop severe, transmural Crohn's-like ileitis and die prematurely. Recent analysis of a human Crohn's disease (CD) cohort revealed a significant subset of patients have severely reduced levels of SHIP1 expression suggesting SHIP1 deficiency leads to CD in both rodents and humans. The mucosal inflammatory disease that causes the premature death of SHIP1[-/-] mice is a consequence of the requirement of SHIP1 expression for the survival of effector T cells in mucosal tissues. T cell specific ablation of SHIP1 expression in CD4CreSHIP1[flox/flox] mice also results in Crohn's disease-like ileitis, but less severe than in their germline SHIP1[-/-] counterparts due to the absence of a SHIP1 deficient neutrophil compartment. Consequently CD4CreSHIP1[flox/flox] mice live much longer than their SHIP1[-/-] counterparts. As Crohn's disease is associated with an increased risk of intestinal cancers in humans and that T cells are proposed to protect from occult malignancies, we hypothesized that CD4CreSHIP1[flox/flox] mice would develop malignancies originating in the gut. Here we show that CD4CreSHIP1[flox/flox] mice with ileitis develop spontaneous metastatic cancer originating in the small intestine, including widely disseminated histiocytic sarcoma and intestinal adenocarcinomas. Our findings demonstrate that T cells in the gut are essential to protect against occult intestinal cancers and that SHIP1 is essential for this function. These findings may aid our understanding of the increased susceptibility to intestinal cancer in IBD patients, and particularly since a significant subset of adult IBD patients have defective expression of SHIP1.

Pancreatic ductal adenocarcinoma has a unique tumor microbiome, and the depletion of gut bacteria or fungi using antibiotic/antifungal cocktails has been shown to decrease pancreatic tumor burden in mice. However, functional studies evaluating the role of tumor-associated microbes are few due to the limited availability of clinically relevant microbiota. Here, we describe in detail an effective workflow for the isolation of bacteria and fungi from the duodenum and tumor of pancreatic cancer patients, specifically optimized for cryopreserved, low biomass samples. Using this workflow we also isolated microbiota from normal pancreatic tissue and duodenum from organ donors, and we confirmed the presence of bacteria and fungi isolated from tissue samples with 16S and ITS sequencing analysis. Isolation and sequencing results show distinct similarities between the pancreatic and duodenal microbiomes and highlight unique bacterial strains that survive in the tumor microenvironment. As a proof of concept, we characterized a select Klebsiella oxytoca strain (UMKO1) isolated from a pancreatic tumor, using whole genome sequencing, metabolomics, and ex- vivo tumor cultures to determine its potential impact on the pancreatic tumor microenvironment. In summary, this optimized workflow allows for the isolation of a variety of bacteria and fungi from low biomass, cryopreserved pancreatic and duodenal tissues, which can then be used for functional studies characterizing clinically relevant tumor-associated microbiota.

Pancreaticoduodenectomy (PD) is the preferred surgical approach for resectable periampullary carcinomas. Non-pancreatic periampullary carcinomas (NPPC) demonstrate distinct biological behaviours and are generally less aggressive than pancreatic cancer. Despite over three decades of advancements, the role of laparoscopic PD (LPD) remains debated. Few studies have directly compared LPD and open PD (OPD) while accounting for tumour invasiveness, and the data specifically evaluating LPD vs OPD for NPPC are limited. Randomised controlled trials are necessary to determine whether therapeutic outcomes differ between LPD and OPD in NPPC patients.

Ampullary adenocarcinoma (AMPAC) is a rare and heterogeneous malignancy with markedly variable clinical outcomes, underscoring the urgent need for molecularly informed classification and personalized therapeutic strategies. Current AMPAC classification relies primarily on morphological and immunohistochemical criteria, which lack prognostic accuracy and fail to capture the underlying molecular and tumor microenvironment heterogeneity. In this study, we integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and clinicopathological data to elucidate the molecular architecture of AMPAC and introduced a transcriptomic-based molecular classification (AMS). The AMS categorized patients into two molecular subtypes: mesenchymal AMPAC (AMS-M) and classical AMPAC (AMS-C). The AMS-M demonstrated increased epithelial-mesenchymal transition (EMT) and stromal activation, correlating with basal-like subtypes associated with unfavorable prognosis. In contrast, AMS-C tumors exhibited metabolic and differentiation programs with relatively preserved immune infiltration. Importantly, we identified MUC16 as a pivotal biomarker specifically overexpressed in AMS-M tumors. MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.

Objective: To explore the risk factors of prolonged postoperative ileus (PPOI) after segmental jejunectomy by propensity score matching (PSM). Methods: This study was designed as a case-control study. The inclusion criteria were as follows: (1) age >18 years; (2) receipt of segmental jejunal resection; (3) postoperative pathological diagnosis of benign jejunal lesions, including small intestinal polyps, small intestinal diverticulitis, small intestinal diverticula, benign small intestinal tumors, small intestinal ulcers, small intestinal hemangioma, small intestinal vascular malformation, and ectopic pancreas of the jejunum, as well as gastrointestinal stromal tumors, lymphoma, or adenocarcinoma; and (4) complete clinical and pathological data.The exclusion criteria were as follows: (1) concomitant other malignancies; (2) combined resection of other organs; (3) emergency surgery due to intestinal obstruction, perforation, or other conditions, including intestinal bleeding, jejunal injury, jejunal rupture, acute enteritis, acute hemorrhagic necrotizing enteritis, acute intestinal obstruction, and mesenteric arterial thrombosis; (4) preoperative constipation; and (5) postoperative complications other than PPOI of Clavien-Dindo grade II or higher, or inflammatory reactions involving intra-abdominal organs, such as peritonitis, cholecystitis, or pancreatitis. According to the above criteria, clinicopathological data of patients who underwent elective segmental jejunal resection at the General Surgery Center of Beijing Friendship Hospital, Capital Medical University, between July 2013 and June 2025 were retrospectively collected. After screening, 262 patients were included and divided into the PPOI group (n = 42) and the non-PPOI group (n = 220) according to the occurrence of PPOI. Propensity score matching was performed using the nearest-neighbor matching method with a caliper value of 0.1 at a 1∶1 ratio. Logistic regression analysis was used to identify risk factors for PPOI after segmental jejunal resection. Results: Among the 262 patients who underwent elective segmental jejunal resection, PPOI occurred in 42 patients, with an incidence rate of 16.1%. After propensity score matching (PSM), 42 matched pairs of patients were successfully generated. After matching, there were no statistically significant differences between the PPOI and non-PPOI groups in terms of disease type, surgical approach, maximum lesion diameter, or anastomotic method (P>0.05). The PPOI group had significantly higher age, postoperative length of hospital stay, and postoperative C-reactive protein levels than the non-PPOI group, whereas the distance from the lesion center to the ligament of Treitz, postoperative serum potassium levels, and albumin levels were significantly lower in the PPOI group (P<0.05). Univariate analysis showed that a distance from the lesion center to the ligament of Treitz of <30 cm, postoperative serum potassium level of <3.5 mmol/L, postoperative C-reactive protein level of >85 mg/L, and postoperative albumin level of <33 g/L were associated with the occurrence of PPOI after segmental jejunal resection (P<0.05). Multivariate analysis showed that a distance from the lesion center to the ligament of Treitz of <30 cm (OR=8.481, 95%CI: 2.102-34.223, P=0.003), postoperative serum potassium level of <3.5 mmol/L (OR = 16.600, 95%CI: 3.869-71.230, P=0.011), and postoperative C-reactive protein level of >85 mg/L (OR=6.168, 95%CI: 1.514-25.128, P=0.007) were independent risk factors for PPOI after segmental jejunal resection. Conclusions: Patients undergoing proximal jejunal resection, defined as a distance from the lesion center to the ligament of Treitz of <30 cm, as well as those with postoperative hypokalemia and elevated C-reactive protein levels, are at a higher risk of developing PPOI.

Neoplasia-related extrahepatic biliary obstruction (EHBO) is rare in dogs. An 11-year-old spayed mixed-breed dog had intermittent jaundice for several months. Imaging showed a lesion extending from the distal common bile duct to the major duodenal papilla. To relieve EHBO, transduodenal ampullectomy was performed, followed by partial duodenectomy including the papillary orifice and cholecystoduodenostomy. Histopathological examination revealed ampullary adenocarcinoma with invasion into the duodenal muscularis propria; margins were tumor-free. At >2 years after surgery, metastasis was not detected, and the dog remained clinically well. To our knowledge, this is the first report of canine ampullary carcinoma, suggesting that transduodenal ampullectomy can be useful for both palliative biliary decompression and the assessment of invasion depth to guide subsequent definitive surgery.

Small bowel tumors are rare malignancies, comprising less than 5% of all gastrointestinal (GI) cancers. The most common subtypes are adenocarcinomas, GI stromal tumors, neuroendocrine tumors, and lymphomas. Workup for these masses includes a combination of endoscopic and high-resolution imaging. Small bowel cancers are generally staged using their depth of invasion, regional lymph node involvement, and distant metastasis. While advances in medical oncology have yielded promising results, surgical resection remains central to treatment of small bowel tumors. With a shift toward minimally invasive approaches in surgery, robotic surgery has gained increasing popularity in resection of small bowel tumors.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive subtype of intestinal T-cell lymphoma with a dismal prognosis. MEITL with aberrant CD20 expression is even rarer. To date, there have been no reported cases of multiple primary malignant tumors (MPMT) composed of concurrent CD20-positive MEITL and solid tumors. We herein present a case of a 59-year-old female with concurrent small intestinal MEITL with aberrant CD20 expression and lung adenocarcinoma. The patient was admitted to hospital for abdominal pain due to intestinal perforation and underwent partial small intestinal resection. Histopathological examination confirmed MEITL with aberrant CD20 expression of the small intestine without lymph node involvement. Meanwhile, two pulmonary ground-glass opacities (GGOs) were identified and histopathological evaluation confirmed the diagnosis of lung adenocarcinoma. The patient received rituximab-based chemotherapy followed by autologous stem cell transplantation, along with surgical resection for lung adenocarcinoma. She has remained alive for more than 24 months without disease progression. Additionally, we conducted a literature review to enhance clinical awareness of this rare concurrent condition of CD20-positive MEITL and lung adenocarcinoma.