Colectomy Research Articles

Contemporary perioperative outcomes after total abdominal colectomy for ulcerative colitis in a tertiary referral centre.

Colectomy for ulcerative colitis (UC) is common despite therapeutic advances. Post-operative morbidity and mortality demonstrate an association between hospital volumes and outcomes. This single-centre retrospective study examines outcomes after emergency colectomy for UC. Patient demographics, perioperative variables and outcomes were collected in Beaumont Hospital between 2010 and 2023. Univariant analysis was used to assess relationships between perioperative variables and morbidity and length of stay (LOS). A total of 115 patients underwent total abdominal colectomy with end ileostomy for UC, 8.7 (±3.8) per annum. Indications were refractory acute severe colitis (88.7%), toxic megacolon (6.1%), perforation (4.3%), or obstruction (0.9%). Over 80% of cases were performed laparoscopically. Pre-operative steroid (93%) and biologic (77.4%) use was common. Median post-operative LOS was 8 days (interquartile range 6-12). There were no 30-day mortalities, and 30-day post-operative morbidity was 38.3%. There was no association between time to colectomy ( P = 0.85) or biologic use ( P = 0.24) and morbidity. Increasing age was associated with prolonged LOS ( P = 0.01). Laparoscopic approach (7 vs. 12 days P =0.01, 36.8% vs. 45% P = 0.66) was associated with reduced LOS and morbidity. This study highlights contemporary outcomes after emergency colectomy for UC at a specialist high-volume, tertiary referral centre, and superior outcomes after laparoscopic surgery in the biologic era.

Minimally Invasive Surgery for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Robotic Versus Laparoscopic Surgical Techniques.

We aimed to evaluate outcomes of robotic versus conventional laparoscopic colorectal resections in patients with inflammatory bowel disease [IBD]. Comparative studies of robotic versus laparoscopic colorectal resections in patients with IBD were included. The primary outcome was total post-operative complication rate. Secondary outcomes included operative time, conversion to open surgery, anastomotic leaks, intra-abdominal abscess formation, ileus occurrence, surgical site infection, re-operation, re-admission rate, length of hospital stay, and 30-day mortality. Combined overall effect sizes were calculated using a random-effects model and the Newcastle-Ottawa Scale was used to assess risk of bias. Eleven non-randomized studies [n = 5566 patients] divided between those undergoing robotic [n = 365] and conventional laparoscopic [n = 5201] surgery were included. Robotic platforms were associated with a significantly lower overall post-operative complication rate compared with laparoscopic surgery [p = 0.03]. Laparoscopic surgery was associated with a significantly shorter operative time [p = 0.00001]. No difference was found in conversion rates to open surgery [p = 0.15], anastomotic leaks [p = 0.84], abscess formation [p = 0.21], paralytic ileus [p = 0.06], surgical site infections [p = 0.78], re-operation [p = 0.26], re-admission rate [p = 0.48], and 30-day mortality [p = 1.00] between the groups. Length of hospital stay was shorter following a robotic sub-total colectomy compared with conventional laparoscopy [p = 0.03]. Outcomes in the surgical management of IBD are comparable between traditional laparoscopic techniques and robotic-assisted minimally invasive surgery, demonstrating the safety and feasibility of robotic platforms. Larger studies investigating the use of robotic technology in Crohn's disease and ulcerative colitis separately may be of benefit with a specific focus on important IBD-related metrics.

Hirschsprung’s Disease Diagnosis: A Comparison of Calretinin and CD56 Immunohistochemistry

Background & objectives: Hirschsprung’s disease is attributable to the congenital lack of ganglion cells in the far intestine. Rectal biopsy is deemed critical for its testing. In some instances, regular techniques fail to detect it. This study aims to evaluate the testing role of calretinin and CD56 immunohistochemistry and correlate the results to routine hematoxylin & eosin stained samples. Methods: This retrospective study was conducted in Rizgary Teaching Hospital, Erbil, Kurdistan region, Iraq. Rectal biopsies and colonic resection specimens of the clinically suspected Hirschsprung’s disease patients were collected and stained with calretinin and CD56 then their findings were compared to the hematoxylin and eosin stained sections during the period between February 2016 to October 2021. Results: Fifty patients aged from 3 days to 8 years with a male-to-female ratio of 3.6:1 were examined for rectal and colonic biopsies. Forty out of 50 cases were detected as HD by H&E staining. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy rate of calretinin were coherent with that of H&E-stained samples (100%), the likelihood ratio was 50 and the kappa test was 1, were superior to CD56 results with sensitivity (100%), specificity (90%), positive predictive value (97.5%), negative predictive value (100%), accuracy rate (98%), likelihood ratio was 27.77 and kappa test was 0.805. Conclusions: Immunohistochemical expression of calretinin is more specific and accurate than CD56 in HD diagnosis. Calretinin is a trustworthy, additional diagnostic tool for better morphological evaluation of ganglion cells and thereby assists in making a reliable diagnosis of HD.

Clinical outcomes and perioperative morbidity and mortality following segmental resections of the colon for Crohn’s colitis

IntroductionCrohn’s disease (CD) is a chronic inflammatory bowel disease of a multifactorial pathogenesis. Recently numerous genetic variants linked to an aggressive phenotype were identified, leading to a progress in therapeutic options, resulting in a decreased necessity for surgery. Nevertheless, surgery is often inevitable. The aim of the study was to evaluate possible risk factors for postoperative complications and disease recurrence specifically after colonic resections for CD.Patients and methodsA total of 241 patients who underwent colonic and ileocaecal resections for CD at our instiution between 2008 and 2018 were included. All data was extracted from clinical charts.ResultsMajor complications occurred in 23.8% of all patients. Patients after colonic resections showed a significantly higher rate of major postoperative complications compared to patients after ICR (p = < 0.0001). The most common complications after colonic resections were postoperative bleeding (22.2%), the need for revision surgery (27.4%) and ICU (17.2%) or hospital readmission (15%). As risk factors for the latter, we identified time interval between admission and surgery (p = 0.015) and the duration of the surgery (p = 0.001). Isolated distal resections had a higher risk for revision surgery and a secondary stoma (p = 0.019). Within the total study population, previous bowel resections (p = 0.037) were identified as independent risk factors for major perioperative complications.ConclusionThe results indicate that both a complex surgical site and a complex surgical procedure lead to a higher perioperative morbidity in colonic resections for Crohn’s colitis.

Surgical outcomes of very-early-onset ulcerative colitis: retrospective comparative study with older pediatric patients

PurposeThe study compares the surgical outcomes of very-early-onset ulcerative colitis (VEO-UC), which is a rare disease diagnosed in pediatric patients < 6 years, with those of older pediatric patients with ulcerative colitis (UC).MethodsA retrospective observational study of 57 pediatric patients with UC was conducted at a single center. The study compared surgical complications and postoperative growth between the two groups.ResultsOut of the 57 patients, 6 had VEO-UC, and 5 of them underwent total colectomy. Compared with the surgical cases of older patients with UC (n = 6), the rate of postoperative complications in patients with VEO-UC (n = 5) was not significantly different, except for high-output ileostomy (80% vs. 0% at 3 weeks postoperatively, p = 0.02). The rate of postoperative central venous catheter (CVC) placement at > 90 days was higher in patients with VEO-UC (100% vs. 17%, p = 0.02). The median change in the Z-score of height before and 2 years after colectomy was not significantly different between VEO-UC and older patients (1.1 vs. 0.3, p = 0.13).ConclusionWith regard to complications and outcomes, total colectomy for VEO-UC patients and that for older pediatric UC patients is comparable. However, high-output ileostomy and the long duration of CVC placement may pose management challenges.

Retrospective study in a single unit: outcomes of delays in reversal of loop ileostomy

Background: Formation of loop ileostomy is common after anterior resection to reduce the sequalae of an anastomosis leak. Delays to reversal of ileostomy is associated with complications. Methods: Retrospective study between 1 July 2017 to 30 June 2023. Patients were included: &gt;18 years old, loop ileostomy formed as part of anterior resection surgery (benign and malignant). Exclusion criteria: loop ileostomy performed during other colonic resections, patients with inflammatory bowel disease, de-functioning ileostomy for obstructions. Primary outcome measures included complications associated with delayed closure of loop ileostomy and readmissions after reversal surgery. Secondary measures included reasons for delay to surgery, complications prior to reversal surgery, and morbidity and mortality associated with it. Results: 135 patients were included. 85.9% of patients experienced delays in reversal surgery. Those without delays in surgery had higher rate of stoma-related complications (p=0.002). Delays were due to a long waitlist (p&lt;0.01) and adjuvant chemotherapy (p=0.598). There were no significant differences in the delays to surgery during COVID pandemic. Delays were associated with higher rate of wound infection (6.04%), post-operative ileus (12.07%), anastomotic leak (1.72%), and Clostridium difficile (C. diff) infection (3.45%). Handsewn end to end anastomosis was associated with higher proportion of post-operative ileus compared to the stapled side to side anastomosis group. Conclusions: Reversal of ileostomy within 6 months of index surgery after adjuvant therapy could potentially reduce post-operative complications, and alleviate the burden on our healthcare system in the long run. A stapled side to side anastomosis should also be considered.

Never too late: Lynch syndrome diagnosed at the age of 71

Lynch syndrome is an autosomal dominantly inherited disease characterized by a mutation in one of the deoxyribonucleic acid mismatch repair genes. In consequence of this defect, patients have higher risk of developing early colorectal and endometrial cancer (among others types of cancer). This syndrome accounts for 3% of all colorectal cancers and 10% to 19% of colorectal cancers diagnosed before the age of 50. Total abdominal colectomy is the best treatment for patients with Lynch syndrome who develop colorectal cancer.

Acute Necrotizing Pancreatitis Complicated With Sinistral Portal Hypertension And Mechanical Obstruction Of The Colon: A Case Report.

Acute necrotizing pancreatitis (ANP) is often associated with acute necrotic collection (ANC) or walled-off necrosis (WON). Due to the close anatomical connection between the pancreas, the spleen, and the transverse colon, necrotizing pancreatitis is often combined with spleen or colon involvement. Gastrointestinal dysfunction usually caused by pancreatitis leads to paralytic intestinal obstruction. However, pancreatitis combined with mechanical colonic obstruction is extremely rare. It can easily be misdiagnosed as malignant intestinal obstruction, and diagnosing the cause of intestinal obstruction becomes more critical when accompanied by Sinistral portal hypertension (SPH). Surgical resection is the primary method for the previous occurrence of colonic complications. In this case report, upon admission, a 37-year-old patient was diagnosed with acute necrotizing pancreatitis with sinistral portal hypertension. On the 6th day after admission, the patient developed a sudden colonic obstruction. After identifying the cause, the patient underwent a transanal decompression tube and minimally invasive necrosectomy, avoiding colon resection. In acute necrotizing pancreatitis combined with colonic mechanical obstruction, it is essential to clarify the etiology, and focus treatment on clearing the peripancreatic necrotic tissue, non-surgical treatment to deal with colonic obstruction is feasible, and the principle of individualized treatment should be used throughout the disease.

Impact of institutional volume on short- and long-term outcomes after laparoscopic colectomy.

The impact of institutional volume on postoperative outcomes after laparoscopic colectomy is still being debated. This study aimed to investigate whether differences in postoperative outcomes of laparoscopic colon resection exist between high- and low-volume centers. Data were reviewed for 1360 patients who underwent laparoscopic colectomy for colon cancer between 2016 and 2022. Patients were divided according to whether they were treated at a high-volume center (≥100 colorectal surgeries annually; n = 947) or a low-volume center (<100 colorectal surgeries annually; n = 413). Propensity score matching was applied to balance covariates and minimize selection biases that could affect outcomes. Finally, 406 patients from each group were matched. After matching, patients from high-volume centers showed a higher number of retrieved lymph nodes (19 vs. 17, p < .001) and more frequent involvement of expert surgeons (98.3% vs. 88.4%, p < .001). Postoperative complication rates were similar between groups (p = .488). No significant differences between high- and low-volume centers were seen in relapse-free survival (88.8% each, p = .716) or overall survival (85.7% vs. 82.8%, p = .480). The present study suggests that in appropriately educated organizations, relatively safe procedures and good prognosis may be obtained for laparoscopic colectomy cases, regardless of institutional volume.

Is extended venous thromboprophylaxis required in patients undergoing ileal pouch procedure for ulcerative colitis?

Venous thromboembolic events (VTEs) are relatively common adverse surgical complications. Extended VTE prophylaxis for 4 weeks is recommended after colorectal cancer surgery, but its use in inflammatory bowel disease surgery lacks high-quality evidence. This retrospective study aimed to assess and characterize VTEs within the first 30 days after ileal pouch-anal anastomosis (IPAA) procedures and subtotal colectomies (STCs) for ulcerative colitis (UC). All patients who underwent IPAA for UC between 1 January 2017 and 31 December 2021 were included. VTE rates after IPAA, in-hospital or at-home occurrences, utilization of in-hospital thromboprophylaxis, and prescribed anticoagulant treatment were evaluated. Retrospectively, the same variables were analysed if patients of the cohort underwent STC before the IPAA construction. In all, 204 patients underwent IPAA (61.8% men, 73% laparoscopic), with an average hospital stay of 6.8 days. Among them, 116 patients underwent STC prior to IPAA. Thirteen patients (6.3%) experienced VTEs after IPAA, with 76.9% (10/13) of cases occurring during hospitalization and under adequate thromboprophylaxis. The VTE rate after STC was 10.3% (12/116), with 58.2% (7/12) occurring in hospital and under appropriate thromboprophylaxis. No reoperations or mortality were attributed to thrombotic events. The type and duration of anticoagulant treatment varied considerably. The VTE rate after IPAA for UC was 6.3%, with the majority of events occurring in hospital and under adequate thromboprophylaxis. These findings suggest that routine use of extended VTE prophylaxis in our cohort may not be supported. Further research is needed to clarify the optimal VTE prophylaxis strategy for inflammatory bowel disease surgery.

A270 RISK FACTORS FOR COLORECTAL NEOPLASIA DEVELOPMENT IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: A CASE-CONTROL STUDY

Abstract Background Patients with inflammatory bowel disease (IBD) and concomitant primary sclerosing cholangitis (PSC-IBD) have a 25-year cumulative risk of up to 50% to develop colorectal neoplasia (CRN). Mucosal inflammation is an important driver of CRN development in IBD, but it is unknown whether this also applies to PSC-IBD patients. Aims We aimed to assess the impact of active mucosal inflammation per colonic segment and endoscopic remission on CRN risk. Methods This is a single-center case-control study, including cases with PSC-IBD with CRN, and controls with PSC-IBD without CRN. Exclusion criteria were a CRN diagnosis prior to IBD or PSC diagnosis, familial CRC syndromes, and insufficient endoscopic follow-up (ampersand:003C2 available colonoscopy reports, and for cases, ampersand:003C2 available endoscopy reports before CRN diagnosis). Data was collected on demographics, IBD and PSC disease characteristics, and IBD medication use. Data from all available colonoscopy and sigmoidoscopy reports between 2002 and 2023, including endoscopic and histologic disease severity, disease extent, and CRN lesions, was collected. The primary outcome was a diagnosis of CRN, secondary outcomes included CRN grade and location, inflammatory burden per colonic segment harboring CRN, and colonic surgery. Results We included 247 PSC-IBD patients (163 ulcerative colitis, 80 Crohn’s disease) with a median follow-up of 6.3 years (IQR: 4.1-12.6) and 6 endoscopic procedures (IQR: 4.0-8.0). Median disease duration was 19 years for IBD (IQR: 11.0-26.0) and 13 years for PSC (IQR: 7.0-18.0). In 50 cases a total of 113 CRN lesions were observed, of which 11 (10%) were advanced CRN (aCRN; HGD or CRC). 23 patients (45%) were diagnosed with ampersand:003E 1 lesion while 45 lesions (40%) were identified in the right-sided colon, 27 (24%) in the transverse colon, 28 (25%) in the left-sided colon, and 10 (9%) in the rectum (3 lesions unknown). Endoscopic remission was observed in 24 cases (48%) during the 2 endoscopies prior to lesion detection vs. in 83 controls (42%) for their last 2 endoscopies. Of all CRN lesions, 39 (35%) were found in a colonic segment with confirmed previous endoscopic and/or histologic inflammation during the 1-2 endoscopies prior to lesion detection (31 low-grade and 8 aCRN). Of the 32 patients who underwent (sub)total colectomy or proctocolectomy, 20 (63%) had an indication due to CRN diagnosis. Mortality was 13% (n=32) during follow-up. Conclusions The risk for CRN and associated colectomy is high in PSC-IBD. Active mucosal inflammation preceded CRN in the affected colonic segment in only 35% of the lesions. Future expansion and additional analysis of our cohort will focus on the impact of persistent endoscopic remission and impact of biologic therapy on CRN risk in PSC-IBD. Funding Agencies None

SF-CORNER (splenic flexure colorectal cancer): an international survey of operative approaches and outcomes for cancers of the splenic flexure.

The optimum surgical approach to splenic flexure cancers (SFCs) remains uncertain. The aim of this survey was to explore the opinions of an international surgical community on the management and outcomes of SFC. A questionnaire was constructed comprising five sections (information about respondents; definition and prognosis of SFC; operative approach; approach in specific scenarios; outcomes) and circulated through an international dissemination committee and social media. The survey received 576 responses over 4 weeks across 50 countries. There was no consensus regarding the definition of the splenic flexure, whilst the proportion of respondents who did and did not think that patients with SFC had a worse outcome was equal. The overall preferred operative approach was left hemicolectomy [203 (35.2%)], followed by segmental resection [167 (29%)], extended right hemicolectomy [126 (21.9%)] and subtotal colectomy [7 (12%)]. The stated pedicles for ligation varied between resection types and also within the same resection. One hundred and sixty-six (28.8%) respondents thought a segmental resection was associated with the worst survival and 190 (33%) thought it was associated with the best quality of life. This survey confirms a lack of consensus across all aspects SFC treatment. The differing approaches described are likely to represent different beliefs around the variable anatomy of this region and the associated lymphatic drainage. Future studies are required to address such inconsistencies and identify the optimum surgical strategy, whilst also incorporating quality-of-life metrics and patient-reported outcomes. A one-size-fits-all approach is probably not appropriate with SFC, and a more bespoke approach is required.

Comparing the short-term clinical outcomes and therapeutic effects of different colectomies in patients with refractory slow-transit constipation in eastern countries: a network meta-analysis.

Surgical treatment has been widely used in patients with refractory slow transit constipation (RSTC). The aim of this network meta-analysis (NMA) was to compare the effects of different colectomies on short-term postoperative complications and quality of life in patients with RSTC. Electronic literature searches were performed in the PubMed, Web of Science, EMBASE, WANFANG DATA, and Cochrane Central Register of controlled trials databases and were searched up to December 2022. Selected to compare the short-term clinical outcomes and quality of life of the treatment of RSTC. A random-effects Bayesian NMA was conducted to assess and rank the effectiveness of different surgical modalities. This study included a total of six non-randomized controlled trials involving 336 subjects. It was found that subtotal colectomy with cecorectal anastomosis (CRA) demonstrated superior effectiveness in several aspects, including reduced hospital stay (MD 0.06; 95% CI [0.02, 1.96]), shorter operative time (MD 4.75; 95% CI [0.28, 14.07]), lower constipation index (MD 0.61; 95% CI [0.04, 1.71]), improved quality of life (MD 4.42; 95% CI [0.48, 4.42]). Additionally, in terms of short-term clinical outcomes, subtotal colectomy with ileosigmoidal anastomosis (SC-ISA) procedure ranked the highest in reducing small bowel obstruction (OR 0.24; 95% CI [0.02, 0.49]), alleviating abdominal pain (OR 0.53; 95% CI [0.05, 1.14]), minimizing abdominal distension (OR 0.33; 95% CI [0.02, 0.65]), and reducing incision infection rates (OR 0.17; 95% CI [0.01, 0.33]). Furthermore, SC-ISA ranked as the best approach in terms of patient satisfaction (OR 0.66; 95% CI [0.02, 1.46]). Based on our research findings, we recommend that CRA be considered as the preferred treatment approach for patients diagnosed with RSTC.

Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer.

A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects. We trained a new machine learning model, referred to as the colon oxaliplatin signature (COLOXIS) model, for predicting response to oxaliplatin-containing regimens. We examined whether COLOXIS was predictive of oxaliplatin benefits in the CC adjuvant setting among 1,065 patients treated with 5-fluorouracil plus leucovorin (FULV; n = 421) or FULV + oxaliplatin (FOLFOX; n = 644) from NSABP C-07 and C-08 phase III trials. The COLOXIS model dichotomizes patients into COLOXIS+ (oxaliplatin responder) and COLOXIS- (nonresponder) groups. Eight-year recurrence-free survival was used to evaluate oxaliplatin benefits within each of the groups, and the predictive value of the COLOXIS model was assessed using the P value associated with the interaction term (int P) between the model prediction and the treatment effect. Among 1,065 patients, 526 were predicted as COLOXIS+ and 539 as COLOXIS-. The COLOXIS+ prediction was associated with prognosis for FULV-treated patients (hazard ratio [HR], 1.52 [95% CI, 1.07 to 2.15]; P = .017). The model was predictive of oxaliplatin benefits: COLOXIS+ patients benefited from oxaliplatin (HR, 0.65 [95% CI, 0.48 to 0.89]; P = .0065; int P = .03), but COLOXIS- patients did not (COLOXIS- HR, 1.08 [95% CI, 0.77 to 1.52]; P = .65). The COLOXIS model is predictive of oxaliplatin benefits in the CC adjuvant setting. The results provide evidence supporting a change in CC adjuvant therapy: reserve oxaliplatin only for COLOXIS+ patients, but further investigation is warranted.

Intratumoral metastasis of sigmoid colon cancer to chromophobe renal cell carcinoma: a case report

We herein report an extremely rare case of intratumoral metastasis of colon cancer to chromophobe renal cell carcinoma. A 71-year-old woman was diagnosed with lung metastasis of sigmoid colon cancer and underwent sigmoid colon resection with D3 lymph node dissection. Preoperative contrast-enhanced computed tomography (CT) revealed a left renal tumor; however, colon resection was prioritized, and the renal tumor was placed under observation. Two years later, CT revealed enlargement of the left renal tumor, and laparoscopic partial left nephrectomy was performed 1 month later. Histopathologic examination showed that the resected renal tumor was a chromophobe renal cell carcinoma with intratumoral metastasis of colon cancer to the renal tumor center, and adjuvant chemotherapy with bevacizumab plus SOX (L-OHP + S-1) was initiated. Because of severe chemotherapy-induced fatigue and nausea, the patient was switched to bevacizumab + S-1. However, the patient’s nausea did not improve after this change, and postoperative adjuvant chemotherapy was discontinued at the patient’s request 4 months after the partial nephrectomy. Two months after discontinuation of chemotherapy, CT showed no renal recurrence; however, increased lung metastases and a new bone metastasis in the left sciatic bone were observed. Palliative treatment was then initiated because of severe adverse events that made it difficult to continue treatment. In patients who have multiple cancers and an increase in renal tumor size, the possibility of intratumoral metastasis to the renal tumor should be considered.

Rates of Adverse Events in Patients With Ulcerative Colitis Undergoing Colectomy During Treatment With Tofacitinib vs Biologics: A Multicenter Observational Study.

Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics. A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints. Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00). Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy.

Abstract B008: The polyclonal path towards malignant transformation in familial adenomatous polyposis

Abstract The widely accepted paradigm that cancer initiation is a monoclonal event has not been definitively resolved. This is largely due to the limitations of experimental systems to study cancer initiation, a definitively transient step in tumorigenesis. Individuals with familial adenomatous polyposis (FAP) possess a germline APC mutation, leading to hundreds of colonic polyps in adolescence and an eventual 100% lifetime risk of colorectal cancer. As such, total colectomies are performed once polyp burden becomes unmanageable and provide the resected colons from FAP donors provide a source of histologically normal mucosa, benign and dysplastic polyps, and, on rare occasions, adenocarcinomas, and serve as an exemplary model disease to understand human tumorigenesis. Through whole genome sequencing of 123 independent samples from six patients, we reveal the polyclonal origins of tumorigenesis in FAP. We characterize and contrast the genomic landscape and relative timing of driver mutation acquisition across normal to dysplastic and invasive colon tissue and compare this with multi-region sequencing data from sporadic colorectal cancers (CRC). We find that only early sporadic CRC drivers are common across the more heterogeneous premalignant stages. Selection, as assessed based on the ratio of nonsynonymous to synonymous mutations (dN/dS), is higher in benign than dysplastic FAP lesions and in sporadic adenomas relative to carcinomas. Phylogenetic reconstruction and pairwise sample comparisons reveal extensive heterogeneity and subclonal sharing within a patient’s benign and dysplastic lesions. Using a mechanistic mathematical model, we infer polyclonality for 90-100% of benign and 53-83% of dysplastic samples. Based on these findings, we propose a conceptual framework for the polyclonal origin of intestinal malignancies where inconsequential mutations, arising during colon formation in utero, are present across the colon and are valuable markers to uncover polyclonal ancestry. Citation Format: Ryan O. Schenck, Aziz Khan, Aaron M. Horning, Edward D. Esplin, HTAN Consortia, William J. Greenleaf, James M. Ford, Michael P. Snyder, Christina Curtis. The polyclonal path towards malignant transformation in familial adenomatous polyposis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B008.

Abstract B004: PISCA-box: A user-friendly interface for Phylogenetic Inference using Somatic Chromosomal Alterations (PISCA)

Abstract PISCA, originally introduced by Martinez et al. in 2018, represents a pivotal Bayesian phylogenetics tool for the modeling of tumor evolution using multi-region somatic chromosomal alteration (SCA) data. PISCA takes allele-specific copy number data, typically obtained from deep genome sequencing or SNP arrays, or absolute copy number data from low-pass genome sequencing methodologies. It extends the classic BEAST1 framework and inherits a rich repertoire of evolutionary models. Importantly, PISCA leverages longitudinal sampling to estimate SCA mutational clock rates, either employing strict clock models, where mutation rates remain constant throughout the evolutionary tree, or relaxed clocks, which allow each branch or subtree to possess its distinct mutation rate. This nuanced approach empowers PISCA to account for the heterogeneous rates of mutations, a pivotal consideration in understanding tumor evolution dynamics. However, PISCA has historically posed a formidable entry barrier for wider community adoption due to platform and Java dependencies for installation, as well as the need for manual or custom-scripted XML file generation. Here we showcase PISCA-box, a user-friendly interface designed to streamline the generation and testing of XML files. Our PISCA-box Docker image works on any desktop machine to create a locally hosted webpage, where users can input SCA data, sampling dates, select clock and demographic models, and set priors for key parameters - similar to the BEAST XML generator, BEAUTi. The Docker or Singularity installation can then be used for longer analyses using high-performance computing resources. To demonstrate its practical utility, we present novel colorectal cancer data. First, we examine data from a patient with a long-standing history of inflammatory bowel disorder (IBD), a known high-risk factor for colorectal cancer. This patient had undergone surveillance colonoscopies for many years, which provided 38 samples, and subsequently an additional 118 samples were collected from a total colectomy. All were analyzed with low-coverage whole genome sequencing. We find some samples from surveillance and colectomy form lineages with overlapping copy number events, that we used to construct a phylogeny, finding a cancer-adjacent clade that appears to evolve rapidly. A second dataset of multi-region samples from a cohort of exceptional survivors of oligometastatic colorectal cancer who lived &amp;gt;60 months from metastatic diagnosis with biopsies/resections across 3-10 time points is examined and temporal models are used to estimate the ages of metastatic clades. PISCA therefore harnesses the power of longitudinal SCA data to enable a comprehensive study of SCA dynamics. We are currently expanding this framework to include fluctuating methylation clocks which PISCA-box will soon include. By providing this accessible tool, we enable researchers to readily apply Bayesian phylogenetics to real-world clinical datasets to better understand tumor evolution. Citation Format: Heather E. Grant, Rachel Alcraft, Pablo Bousquets-Muñoz, Calum Gabbutt, Alison Berner, Mehmet Yalchin, Carlo C. Maley, Trevor A. Graham, Diego Mallo. PISCA-box: A user-friendly interface for Phylogenetic Inference using Somatic Chromosomal Alterations (PISCA) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B004.

Predictors of in-hospital outcomes for diverticular bleeding patients: a retrospective analysis of National Inpatient Sample data (2016-2020).

Diverticular bleeding is the leading cause of lower gastrointestinal bleeding, affecting 3-5% of patients with diverticulosis. Current management protocols include resuscitation, diagnosis via direct visualization, computed tomography imaging, endoscopic interventions, angioembolization, and surgery when needed. However, predictive factors for outcomes and optimal interventions remain ambiguous. This retrospective cohort study analyzed data from the National Inpatient Sample (NIS) database (2016-2020) to determine predictors of adverse in-hospital outcomes in diverticular bleeding patients without perforation or abscess. Demographic and clinical data were extracted, and multivariate regression models were applied. Analysis was conducted using R statistical software (version 4.1.3), with significance set at P<0.05. A total of 28,269 patients hospitalized for diverticular bleeding were identified. Age >85 years, moderate to severe Charlson Comorbidity Index, hypovolemic shock, blood transfusion requirement, and requirement for colectomy were significantly associated with greater in-hospital mortality. Factors such as late colonoscopy timing and colon resection led to longer hospital stays, while arterial embolization was predicted by older age, Black race, hypovolemic shock, and blood transfusion. Predictors of colon resection included advanced age, presence of colon cancer, and hypovolemic shock. Our retrospective study identified significant predictors of in-hospital outcomes among patients with diverticular bleeding, informing risk stratification and management strategies. Further research is warranted to validate these findings and refine management algorithms for improved patient care. Integrating these insights into clinical practice may enhance outcomes and guide personalized interventions in diverticular bleeding management.

A severe case of checkpoint inhibitor induced proctocolitis requiring subtotal colectomy

A severe case of checkpoint inhibitor induced proctocolitis requiring subtotal colectomy