Diagnostic CT-guided online adaptive radiotherapy for locally advanced colon cancer: a prospective implementation and feasibility study.

Cytomegalovirus (CMV) is a herpes virus that usually affects immunocompromised hosts. However, there has been a recent increase in CMV-associated infections in immunocompetent hosts, with the most common sites including the gastrointestinal tract, lungs, liver, and spleen. We present a case of a 60-year-old male patient who presented with abdominal pain and diarrhea with radiological findings including circumferential mural thickening in the rectum, rectosigmoid, and descending colon with loss of haustrations in the transverse colon suggestive of colitis with toxic megacolon. A subtotal colectomy was performed, which showed gross features of inflammatory bowel disease; however, histopathological findings were suggestive of CMV colitis with typical nuclear and cytoplasmic features. The patient succumbed to death within 2 weeks postsurgery. This case emphasizes the fact that an immunocompetent host present with dreaded complications of CMV colitis, especially older patients, hence elderly age being one of the vulnerable groups.

Predicting early recurrence after hydrostatic reduction of pediatric intussusception: A nomogram and a simplified clinical score.

This study aimed to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) in detecting synchronous malignant lesions in the proximal colon in endoscopically obstructive left-sided colorectal cancer. All patients with a biopsy-proven left-sided endoscopically obstructive colorectal cancer who had a preoperative PET/CT scan and a postoperative total colonoscopy within 6 months after the index surgery between January 2015 and July 2024 at a comprehensive cancer center were enrolled into the study. The synchronous malignant lesions on PET/CT were confirmed with the pathologic examination of the subtotal/total colectomy specimen and postoperative total colonoscopy. The primary endpoint was to evaluate the diagnostic performance of PET/CT in detecting synchronous malignant lesions, and the second endpoint was to determine the ability of PET/CT to distinguish malignant lesions from advanced adenomas. Out of 90 patients, 50 (55.6%) were male with a mean age of 62.46±10.81 years. The obstructing malignant lesions detected on colonoscopy were located in the rectum, n=8 (8.9%), rectosigmoid junction, n=29 (32.2%), sigmoid colon, n=31 (34.4%), descending colon, n=16 (17.8%), and distal part of the transverse colon, n=6 (6.7%). Nine areas of abnormal fluorodeoxyglucose (FDG) uptake on PET/CT in the proximal part of the colon with a mean SUVmax value of 19.23 (range: 6.4-42) were identified in 6 patients. Four patients with synchronous lesions on PET/CT underwent a total colectomy. Two patients with synchronous lesions on PET/CT were treated with segmental resection with subsequent postoperative endoscopic submucosal dissection (ESD) for the synchronous lesion. The detection rate of PET/CT for synchronous malignant lesions was 4.4% (n=4) with a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 100%, 94.4%, 44.4%, 100%, and 94.6%, respectively. PET/CT demonstrated a high sensitivity and a high negative predictive value in detecting synchronous malignant lesions located in the proximal colon distal to the obstructing left-sided colorectal cancer. As a result, patients underwent a single-stage surgery and were spared from an unnecessary second surgical intervention.

Breast cancer metastasis to the colon is rare, occurring in less than 1% of patients with metastatic breast cancer. Invasive lobular carcinoma (ILC) exhibits a distinct tropism for the gastrointestinal tract and adnexa, often presenting with atypical imaging features that mimic primary tumors. We report a case of a 58-year-old woman with a history of right breast ILC who presented with incidental pelvic masses on ultrasound five years after mastectomy. 2-[¹⁸F]FDG PET/CT revealed multifocal hypermetabolic lesions in the transverse colon wall and bilateral adnexa. CT enterography and colonoscopy confirmed a stenotic colonic lesion with smooth mucosa. Postoperative pathology following right hemicolectomy, hysterectomy, and bilateral salpingo-oophorectomy confirmed metastatic breast carcinoma involving the right colon and bilateral adnexa. This case highlights the critical role of PET/CT in detecting occult gastrointestinal metastases in patients with ILC and underscores the importance of considering metastatic disease in the differential diagnosis of colonic lesions in this population.

Routine ligation of the inferior mesenteric vein (IMV) during laparoscopic left hemicolectomy is widely practiced but may predispose patients to venous congestion, ischemia, and anastomotic complications, especially in patients with a long remnant sigmoid colon. IMV preservation remains underutilized due to technical difficulty and the absence of standardized guidance. This video article presents a structured, step-by-step technique for laparoscopic left hemicolectomy with D3 lymphadenectomy and IMV preservation in a 64-year-old male with distal transverse colon adenocarcinoma. Key elements include meticulous IMV skeletonization with selective tributary ligation, targeted left colic artery division, and extracorporeal functional end-to-end anastomosis. The patient recovered uneventfully and was discharged on postoperative day 3. A 6-month colonoscopy confirmed a well-healed anastomosis without congestion or stricture. IMV-preserving left hemicolectomy is safe, oncologically sound, and technically reproducible. Maintaining venous drainage may reduce anastomotic congestion and support optimal healing, offering meaningful value in selected patients.

ABSTRACTMonomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL) is a rare primary intestinal T‐cell lymphoma newly defined in the 2016 WHO classification, characterized by rapid progression and a poor prognosis. Fistula formation caused by intestinal lymphoma is extremely uncommon, and no previous reports have described MEITL presenting with a jejunocolic fistula. An 83‐year‐old woman presented with a 20‐kg weight loss and generalized fatigue over the preceding year. Laboratory tests revealed hypoalbuminemia and elevated inflammatory markers. Computed tomography demonstrated wall thickening of the jejunum and descending colon, suggesting possible continuity between the two segments. Colonoscopy revealed a circumferential ulcerative lesion at the splenic flexure, and proximal to this lesion, another lumen extending in a direction different from the colonic lumen was observed. Biopsy confirmed a diagnosis of MEITL. Positron emission tomography–computed tomography (PET–CT) showed abnormal FDG uptake from the jejunum to the transverse colon, and the disease was classified as Lugano Stage II. Due to tumor location and the patient's poor general condition, both surgery and chemotherapy were considered infeasible, and best supportive care was chosen. The patient died on hospital Day 33. Jejunocolic fistula caused by MEITL is exceptionally rare. To our knowledge, this is the first reported case in which the fistulous opening was directly visualized endoscopically and a histopathological diagnosis was established by biopsy during life. This case highlights that, in patients with marked weight loss and hypoalbuminemia, gastrointestinal fistula formation should raise suspicion for malignant lymphoma, including MEITL, and that careful endoscopic examination and biopsy may contribute to early diagnosis.

Adequate bowel perfusion is essential for anastomotic healing in colorectal surgery. Indocyanine green (ICG) fluorescence angiography (FA) is currently considered the gold standard for intraoperative perfusion assessment. Laser speckle contrast imaging (LSCI) is an emerging, dye-free technology that enables real-time evaluation of microvascular blood flow. The aim of this study is to assess the feasibility of LSCI in elective colorectal surgery and to compare its performance with ICG-FA for intraoperative evaluation of bowel perfusion. A prospective study was conducted including consecutive patients undergoing elective laparoscopic colorectal surgery between September 2025 and March 2026. Bowel perfusion was assessed intraoperatively using both LSCI and ICG-FA. The primary endpoint was feasibility of LSCI, while the secondary endpoint was concordance between these two technologies in determining the bowel section line. Twenty-two patients were included: 7 right hemicolectomies, 11 left hemicolectomies, and 4 anterior rectal resections. LSCI and ICG-FA were successfully performed in all cases (100%). Overall concordance between LSCI and ICG-FA was 86.2%. Concordance was 100% for ileum and 57.1% for transverse colon in right hemicolectomy, 100% in left hemicolectomy and 75% in anterior resection of the rectum. Two postoperative complications were observed, both following anterior resection of the rectum: one patient developed postoperative ileus (Clavien-Dindo I), and one patient developed abdominal pain, fever of unknown origin, and intra-abdominal fluid collection requiring revision surgery, which did not reveal an anastomotic leak (Clavien-Dindo III-b). Mean hospital stay was 6 ± 4days. LSCI appears to be a feasible tool for intraoperative assessment of bowel perfusion, demonstrating high concordance with ICG-FA. Its dye-free and real-time capabilities make it a promising adjunct to ICG-FA. Larger prospective, multicentre, randomized studies are warranted to further define the clinical impact of LSCI in evaluating bowel vascularization and its potential role in improving surgical outcomes.

Traditional serrated adenoma (TSA) is the least common of the currently recognized serrated colorectal polyps and, thus, elucidating its pathogenesis, spectrum of morphological features and biological risk has been challenging. Most TSAs harbour either KRAS or BRAF mutations and may progress to adenocarcinoma via distinct carcinogenic pathways. TSAs with KRAS mutation are more commonly located in the distal colorectum, whereas BRAF-mutant TSAs typically arise proximal to the transverse colon, may be associated with a background sessile serrated lesion and represent putative precursors of biologically aggressive BRAF-mutant, mismatch repair-proficient colorectal carcinomas. This review summarizes the evolution of the concept of TSA as a distinct pathological entity and its relationship to other neoplasms within the serrated neoplastic pathway. The molecular and histopathological characteristics of TSAs are outlined, with particular emphasis on the classification of lesions with mixed morphology, including those associated with non-dysplastic serrated components and those showing progression to severe dysplasia, with the hope of improving their recognition. Although further studies are required to validate the proposed terminology, consistent classification of these lesions is essential to improve recognition and to advance understanding of this uncommon pathway to colorectal carcinoma.

Capsule colonoscopy (CC) and pan-intestinal capsule endoscopy ("panendoscopy") require effective bowel cleansing; however, evidence on ultra-low-volume regimens is lacking. This study compared the efficacy of 1 L polyethylene glycol with ascorbic acid (PEG-Asc) vs sodium picosulfate with magnesium citrate (SPMC) in CC and panendoscopy procedures. In this prospective, single-center, researcher-blinded, randomized trial, 220 consecutive adult outpatients referred for CC or panendoscopy were assigned 1:1 to receive split-dose PEG-Asc or SPMC. Primary outcomes were adequate bowel cleansing and procedure completion, while secondary outcomes included tolerability and clinically relevant endoscopic findings. Adequate bowel cleansing was achieved in 70.0% of the PEG-Asc group vs 47.1% of the SPMC group ( P = 0.001). PEG-Asc achieved higher rates of excellent segmental cleansing in the right (32.6% vs 9.4%; P < 0.001) and transverse colon (38.8% vs 15.6%; P < 0.001). Overall completion rates were similar between regimens (PEG-Asc 68.9% vs SPMC 66.7%; P = 0.742), but with CC procedures achieving 62.7% and panendoscopy 87.2% ( P = 0.004). Tolerability was higher with SPMC, reflected by fewer reports of nausea (27.6% vs 42.2%; P = 0.035) and vomiting (9.2% vs 24.4%; P = 0.005), and a greater proportion of patients rating the preparation as "easy" (34.7% vs 21.1%; P = 0.039). Clinically relevant findings, including polyps ≥6 mm, were similar across both groups. PEG-Asc provides superior bowel cleansing for CC and panendoscopy, whereas SPMC is better tolerated. These findings support PEG-Asc as the first-line ultra-low-volume bowel preparation for capsule-based procedures.

In right-sided colon cancer surgery, ileocolic artery stump length may reflect the extent of mesenteric resection and lymph node harvest. This study evaluated the association between postoperative stump length measured on CT, lymph node yield, and recurrence or progression within 24 months. This single-center retrospective study included 64 patients who underwent right or extended right hemicolectomy for right-sided colon adenocarcinoma between 2016 and 2024. Right-sided tumors were defined as those located in the cecum, ascending colon, hepatic flexure, or proximal transverse colon. Only primary surgical cases were included. Ileocolic artery stump length was measured on contrast-enhanced CT scans performed approximately 12 months postoperatively (± 1 month) by two independent radiologists. A Random Forest regression model using stump length as the only predictor variable was developed to estimate lymph node yield. Model performance was assessed using 10-fold cross-validation with R² and mean squared error (MSE). Exploratory recurrence/progression analysis used logistic regression with natural cubic splines. Mean stump length was 2.03cm (range 1.0-4.5cm), and median lymph node yield was 17 (range 10-55). Adequate nodal evaluation (≥ 12 nodes) was achieved in 85.9% of patients. The model demonstrated a consistent inverse relationship between stump length and lymph node yield (R² = 0.78; MSE = 0.16). Exploratory analysis suggested a non-significant trend toward higher recurrence or progression with longer stumps. Longer ileocolic artery stumps were associated with reduced lymph node yield, suggesting stump length may reflect the extent of mesenteric resection. External validation is required before clinical application.

Primary colonic Epstein-Barr virus-positive inflammatory follicular dendritic cell sarcoma (EBV+ iFDCS) is a rare, poorly characterized neoplasm. This study aims to delineate its clinicopathological features and thereby facilitate accurate diagnosis. This study retrospectively analyzed 14 cases of primary colonic EBV+iFDCS and conducted a systematic review of 18 additional cases from the literature. The median age was 51 years (range, 35-68 years), with 10 females and 4 males. All cases were confined to the colon, with the transverse colon as the most common site (50%, 7/14), followed by the descending colon (28.6%, 4/14), sigmoid colon (14.3%, 2/14), and ascending colon (7.1%, 1/14). The vast majority of cases (85.7%, 12/14) were asymptomatic and were incidentally detected during routine physical examinations. Endoscopically, the tumors presented as either pedunculated polyps (9 cases) or sessile polypoid lesions (5 cases) with surface congestion. Their histology was characterized by mucosal erosion, prominent superficial perpendicular vessels, and secondary lymphoid follicular (SLF)hyperplasia. Neoplastic spindle cells were arranged in scattered and fascicular patterns within a background of plasma cells and small lymphocytes. Morphological subtypes comprised classic/lymphoma-like mixed type (64.3%, 9/14) and lymphoma-like type (35.7%, 5/14). Tumor cells expressed multiple FDC markers (CD21, CD23, CD35), co-expressed SMA (100%, 13/13) and CD56 (100%, 12/12), while SSTR2 was typically negative or only weakly expressed. The microenvironment was characterized by a B-cell predominance. EBV-encoded RNA was detected in perivascular and interfollicular tumor cells, with positivity also in germinal center FDCs. Clonality assays were negative in all but two cases (one case each with TCR rearrangement and IG rearrangement). All patients were underwent endoscopic submucosal resection, with no recurrence or major complications. Primary colonic EBV+iFDCS is a distinct, low-grade malignant neoplasm that typically presents as polyp or polypoid lesion. Its hallmark histologic features include a characteristic arrangement of vessels and SLFs in a prominent lymphocytic background. The tumor exhibits a dual immunophenotype, expressing markers of both FDCs and follicular reticular cells. Because the disease follows an indolent clinical course with a favorable prognosis, accurate diagnosis is essential to avoid overtreatment.

Although laparoscopic surgery for colon cancer offers advantages over open surgery, such as minimal invasion and faster recovery, the transverse colon presents unique challenges due to its special anatomical location and complex vascular and lymphatic drainage. This study aimed to identify independent risk factors and to develop a corresponding combined predictor for perioperative complications following laparoscopic radical resection of transverse colon cancer. Retrospective clinical data from 170 patients with transverse colon cancer who underwent laparoscopic colectomy at The First People's Hospital of Yongkang between January 2020 and July 2025 were analyzed. According to the Clavien-Dindo classification system, patients were divided into a complication group (Clavien-Dindo grade ≥I) and a non-complication group. Baseline demographics, surgical variables, and occurrence of perioperative complications were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for complications. The combination of these independent risk factors was then assessed as a composite predictor. Its predictive performance was evaluated using receiver operating characteristic (ROC) curve analysis. Among the cohort, 43 patients experienced complications (complication group) while 127 did not (non-complication group). Univariate logistic regression analysis revealed that age, presence or absence of comorbid diabetes mellitus, type of abdominal anastomosis, and operation time were associated with perioperative complications following laparoscopic colectomy for transverse colon cancer (p < 0.05). Multivariate logistic regression analysis revealed that comorbid diabetes mellitus (odds ratio [OR] = 4.656, 95% confidence interval [CI]: 1.715-12.640, p = 0.003), extracorporeal anastomosis (OR = 5.943, 95% CI: 2.497-14.142, p < 0.001), and an operation time exceeding 3 hours (OR = 4.520, 95% CI: 1.929-10.595, p < 0.001) were independent risk factors for perioperative complications. The area under the ROC curve (AUC) for the predictor combining these three factors was 0.825 (95% CI: 0.752-0.897, p < 0.001), demonstrating superior predictive efficacy compared to any single factor alone. Comorbid diabetes mellitus, extracorporeal anastomosis, and operation time >3 hours are independent risk factors for perioperative complications in patients undergoing laparoscopic resection of transverse colon cancer. The combination of these three risk factors shows good predictive value and holds promise for guiding targeted clinical interventions to improve patient outcomes.

Transverse colon cancer is traditionally treated with extended right hemicolectomy (EHC), which involves division of the middle colic, right colic, and ileocolic arteries, along with removal of the terminal ileum and right colon. Transverse colectomy (TC) is a limited resection removing only 10cm of bowel on either side of the tumor, along with resection of the middle colic artery and regional lymphadenectomy. This approach may contribute to the preservation of bowel function without compromising oncologic adequacy. This multicenter, randomized, phase III trial is designed to evaluate the non-inferiority of TC compared with EHC in terms of relapse-free survival among patients with Stage II/III transverse colon cancer whose main feeding artery is the middle colic artery. In total, 510 patients will be enrolled across major Japanese centers over 5years. The trial has been registered with the Japan Registry of Clinical Trials (jRCT1030240479).

BackgroundGastrojejunocolic fistulas (GJCFs) are rare complications following gastrojejunostomy and Roux‐en‐Y procedures, most often in the context of peptic ulcer disease.Case ReportA 42‐year‐old woman, with a history of cocaine addiction, underwent an gastrojejunostomy, a transgastric closure of the gastric pylorus, and a Graham patch for a perforated duodenal ulcer. She then presented with a dehisced gastrojejunal anastomosis. Resection of the dehisced anastomosis and Roux‐en‐Y reconstruction was performed. Eight months later, the patient returned to the hospital with a GJCF. A one‐stage en‐bloc GJCF resection with redo Roux‐en‐Y was performed. Six months later, a scan demonstrated a recurrent GJCF. Antrectomy and bilateral truncal vagotomy were performed to avoid recurrent gastric acid secretion. Resection of the dehisced gastrojejunal anastomosis and the segment of fistulized transverse colon was performed. A third Roux‐en‐Y reconstruction was fashioned. The patient evolved well and showed no signs of recurrent disease.DiscussionThe cornerstone treatment of GJCF is the administration of parenteral nutrition, followed by a single‐stage en‐bloc procedure. Some factors that can contribute to recurrent GJCF are retained gastric antrum syndrome, incomplete vagotomy, and noncompliance with oral antacid therapy. Despite the significant leaps in the medical management of peptic ulcer disease in recent years, surgical strategies that reduce excess gastric acid secretion should be considered in select cases.ConclusionThis case highlights that gastric antrectomy and bilateral vagotomy have not been rendered obsolete in the 21st century, particularly in patients who cannot be compliant with oral proton pump inhibitors.

Synchronous colonic volvulus is an extremely rare and life‐threatening cause of large bowel obstruction, characterized by simultaneous torsion of two separate colonic segments. Early diagnosis is challenging due to its nonspecific clinical presentation and overlapping radiological features with isolated volvulus. Delay in recognition increases the risk of ischemia, perforation, sepsis, and mortality, making rapid identification and surgical intervention critical. We present a case of a middle‐aged patient who arrived at the emergency department with progressive abdominal pain, distension, constipation, and absence of flatus. Physical examination revealed a markedly distended abdomen with diffuse tenderness, and laboratory tests demonstrated leukocytosis. Abdominal radiographs suggested large bowel obstruction, while contrast‐enhanced computed tomography (CECT) demonstrated the characteristic whirl sign at two distinct anatomical sites, consistent with synchronous volvulus of the sigmoid and transverse colon. The patient underwent emergency exploratory laparotomy, which confirmed volvulus of both affected segments with compromised vascularity. Surgical management included resection of the necrotic segments with primary anastomosis. The postoperative course was uneventful, and the patient was discharged in stable condition with scheduled follow‐up. This case highlights the importance of maintaining a high index of suspicion in patients presenting with acute large bowel obstruction, particularly when imaging demonstrates atypical or dual transition points. While sigmoid volvulus is the most common form, synchronous involvement of multiple colonic segments is exceedingly uncommon but should be considered to prevent diagnostic delay. Timely surgical intervention remains the cornerstone of management and is paramount in preventing progression to gangrene, peritonitis, and septic shock.

Ulcerative colitis (UC) patients carry a 2.5-fold increased risk of colorectal cancer (CRC), yet the shared multi-scale genetic architecture remains poorly understood. We constructed an integrative framework across tissue, cellular, and variant levels to systematically dissect the pathogenic evolution of this comorbidity across spatiotemporal dimensions. We integrated GWAS data from 100,204 CRC cases and 12,160 UC patients with tissue-specific MAGMA enrichment, embryonic spatial mapping (gsMap), and multidimensional single-cell prioritization (ECLIPSER, CELLECT, scDRS). We further resolved cell-specific co-expression patterns using hdWGCNA and identified high-confidence causal variants and genes through Bayesian fine-mapping (eCAVIAR, fastenloc) and Open4Gene analysis. Genetic susceptibility for both diseases was significantly enriched in the terminal ileum and transverse colon, anchored to E16.5 embryonic gut programs. CD4 + T cells emerged as the core immune hub in UC, exhibiting profound immunometabolic polarization (Th17/IL-17 axis and Warburg effect), while progenitors were identified as the primary cellular origin for CRC malignancy. Pathological progression was characterized by a transition from chronic inflammatory stress toward p53-mediated genomic instability, epithelial-mesenchymal transition (EMT), and vascular remodeling. We prioritized Tier 1 candidate genes-ARPC5, PTGER4, CIB1, PREX1, and S100A10-as key mediators of the comorbidity association between inflammation and cancer. These findings partially support a "genetic programming-microenvironment triggering" hypothesis, where regional vulnerabilities established by embryonic developmental programs are activated by postnatal insults, though its broad applicability warrants caution. This study provides a comprehensive multi-scale molecular framework for understanding UC-CRC comorbidity, offering potential targets for risk stratification and therapeutic intervention.

Colorectal cancer is one of the most common cancers in Aotearoa New Zealand. Evidence supports that right colon cancer (RCC) and left colon cancer (LCC) represent distinct entities, with RCC associated with a poorer prognosis, despite accounting for stage. Oncogenic mutations in MMR protein expression, BRAF V600E, and RAS genes have been shown to differ significantly between RCC and LCC, influencing tumour behaviour and prognosis. Histopathologic features of RCC and LCC in patients treated between 2018 and 2023 in a centre in Aotearoa New Zealand were evaluated. RCC was defined as arising from caecum to distal transverse colon, and LCC from splenic flexure to rectosigmoid junction. The primary outcomes were the rates of deficient MMR protein expression (dMMR), BRAF V600E, and NRAS gene mutations. Secondary outcomes included tumour characteristics, lymph node status, and AJCC prognostic stage. A total of 376 patients were included, for a total of 390 tumours. RCC had a higher rate of dMMR tumours compared to LCC (50.4% vs. 13.75%; adjusted OR 6.36, 95% CI: 3.57-11.35). There were no significant differences in the rates of BRAF V600E or NRAS gene mutations between sides. RCC was more likely to be mucinous adenocarcinoma (23% RCC vs. 10% LCC; OR 2.99, 95% CI: 1.64-5.49), and to be high-grade (18.7% vs. 12.5%; OR 1.68, 95% CI: 1.03-2.92) compared to LCC. RCC was associated with a higher rate of dMMR and high-grade tumours, and a greater proportion of mucinous adenocarcinomas.

Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are recognized as interconnected immune disorders, necessitating comprehensive genetic analysis. The research employed genome-wide association study (GWAS) data pertinent to IBD and PSC. Initially, linkage disequilibrium score regression alongside SUPERGNOVA was utilized to assess their genetic correlation. The genetic overlap between these two conditions was subsequently evaluated using the conditional/conjunctional false discovery rate (cond/conjFDR) approach. Shared loci pertinent to IBD and PSC were discerned through both conjFDR and multitrait analysis of GWAS (MTAG) techniques. Finally, transcriptome-wide association studies were executed at the tissue level to investigate enriched tissues and expressed genes. A substantial overall correlation was identified at the genome-wide level between IBD (including Crohn's disease and ulcerative colitis) and PSC. Locally, correlations were prominent as both diseases exhibited enrichment across various chromosomes, with chromosome 9 being particularly noteworthy. The conditional quantile-quantile plot derived from the conjFDR analysis indicated genetic overlap between the two diseases. Using an integrated approach involving conjFDR and MTAG analyses, 15, 12, and 6 shared loci were detected for IBD, Crohn's disease, and ulcerative colitis with PSC, respectively. Furthermore, concurrent enrichment of IBD and PSC was found in seven tissues (spleen, terminal ileum of the small intestine, whole blood, lung, Epstein-Barr virus-transformed lymphocytes, transverse colon, and adipose visceral omentum). This study provides genetic evidence for the comorbidity of IBD and PSC, enhancing our understanding of the pathophysiological aspects of both diseases.

Abstract Introduction Antiphospholipid syndrome (APS) is classically defined by thrombosis in the presence of antiphospholipid antibodies (aPL). Seronegative APS is increasingly recognized as a phenotype in which clinical thrombotic behavior is indistinguishable from APS despite persistently negative standard aPL assays. Diagnostic anchoring on laboratory criteria can delay recognition. Here, we present a fulminant case where catastrophic seronegative APS coexisted with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, resulting in fatal multisystem ischemia despite aggressive immunosuppression and anticoagulation. Case Presentation A healthy 36-year-old woman, with no chronic medical illnesses but with a history of a prior unexplained first-trimester pregnancy loss, presented with acute-onset dysarthria and left-sided weakness. Imaging demonstrated right frontal hypoperfusion, but she was outside the window for thrombolytics. Within 24 hours she deteriorated with shock and respiratory failure requiring the intensive care unit (ICU). She had severe anemia, thrombocytopenia, acute kidney injury (creatinine 2.2 mg/dL), hypoalbuminemia, and markedly elevated inflammatory markers. Computed tomography (CT) imaging demonstrated diffuse anasarca, hepatic steatosis, and moderate ascites. Echocardiography showed aortic valve thickening concerning for Libman-Sacks endocarditis. Autoimmune studies showed high PR3 IgG (239 U), ANCA titer 1:640, and antinuclear antibody (ANA) 1:2560, consistent with ANCA-associated vasculitis. However, antiphospholipid antibodies were negative. Given the extent and pattern of thrombosis, seronegative APS overlap was considered. She received pulse-dose corticosteroids, eculizumab, intravenous immunoglobulin (IVIG), and rituximab. Hospital course was complicated by hyperammonemia, recurrent ileus, ischemic digital necrosis, gastrointestinal (GI) bleeding from coagulopathy, and mechanical ventilation requiring tracheostomy. She later underwent emergent laparotomy for perforated distal transverse colon with segmental resection and end colostomy. Multiple ischemic territories (stroke, peripheral tissue necrosis, mesenteric ischemia, and suspected Libman-Sacks endocarditis) were attributed to a catastrophic thrombo-inflammatory state. Anticoagulation was resumed once stable. Days later she developed hemorrhagic shock with evolving disseminated intravascular coagulation (DIC). Given ongoing thrombotic injury, inability to maintain anticoagulation, and multisystem organ failure, care was transitioned to comfort-focused goals. She died on hospital day 29. Discussion This case demonstrates that seronegative APS can produce catastrophic ischemia indistinguishable from classic APS, and ANCA vasculitis can coexist as a second autoimmune accelerator. Reliance on negative aPL serologies can mislead clinicians away from APS when escalation of immunomodulation is needed. When thrombosis is widespread and multiterritorial, especially in a patient with concurrent systemic autoimmunity, seronegative APS must remain on the differential. Recognition must be based on phenotype—not the antibody panel alone. This abstract is funded by: None