Society: SSAT

Introduction: Due to its rarity, anal adenocarcinoma (AA) does not have a standardized staging system. The tumor (T) stage of an adenocarcinoma arising from the anal canal could be based on depth of invasion, as for rectal adenocarcinoma, or on size, as in anal squamous cell carcinoma. We hypothesized that staging by adenocarcinoma histology, rather than anal location, would be most accurate in predicting survival of AA patients.

Methods: Adults with AA were identified in the Surveillance, Epidemiology, and End Results database between 2004 and 2019. Exclusion criteria were overlapping lesions of the anus/rectum, >1 lifetime diagnosis of cancer, and missing tumor size or extension. All patient stages were categorized according to the American Joint Committee on Cancer (AJCC) classifications of rectal adenocarcinoma (AJCC-rectum) and anal squamous cell carcinoma (AJCC-anus). Kaplan-Meier curves were used to determine 5-year overall (OS) and disease-specific survival (DSS) rates. Cox proportional hazard regressions, adjusting for age, gender, race, marital status, tumor grade, and treatment received, analyzed the association between prognosis and both overall and T stages.

Results: Of 424 patients, 55% were male, 63% were Caucasian, and 23% had distant metastases. Median age was 65 (interquartile ratio 53-75) years. Thirty-four percent of patients underwent chemoradiation (CRT) and abdominoperineal resection (APR), 15% CRT with local excision (LE), 26% CRT alone, 11% upfront APR, and 15% LE only. When patients were classified by AJCC-rectum staging, 36% had stage I disease, 25% stage II, and 23% stage III. Conversely, according to AJCC-anus, there were 19% stage I, 38% stage II, and 20% stage III patients. Both classifications included the same 97 patients (23%) with stage IV disease. The unadjusted 5-year DSS and OS were similar for early stages, while both classifications similarly differentiated more advanced disease (Figure 1). After adjustment, stages I and II maintained similar OS and DSS in both staging systems, while stages III and IV had significantly worse prognosis (Table 1). In contrast, when analyzing T stage alone (node-negative, non-metastatic patients), multivariable analyses demonstrated significant, incrementally lower OS and DSS for stage T1 to T4 for AJCC-rectum, but not for AJCC-anus (Table 1).

Conclusion: In this population-based cohort, neither staging system was able to accurately risk stratify stage I and II tumors, although both classifications appropriately differentiated the prognosis of more advanced disease. These observations suggest that a 3-tier localized, regional, and distant system could provide a more pragmatic option for prognostication. However, AJCC-rectum staging better discriminated between T stages, indicating that providers should consider utilizing this system in the clinical assessment of AA.

<b>Figure 1.</b> 5-year overall and disease-specific survival rates by AJCC-rectum and AJCC-anus staging systems (all patients, n=424).

Figure 1. 5-year overall and disease-specific survival rates by AJCC-rectum and AJCC-anus staging systems (all patients, n=424).

<b>Table 1.</b> Multivariable analyses of 5-year overall and disease-specific survival by AJCC-anus and AJCC-rectum staging for overall and T anal and rectal stages. All are adjusted for age, gender, race, marital status, tumor grade, and treatment received.

Table 1. Multivariable analyses of 5-year overall and disease-specific survival by AJCC-anus and AJCC-rectum staging for overall and T anal and rectal stages. All are adjusted for age, gender, race, marital status, tumor grade, and treatment received.

Introduction:
Improved oncological response of rectal cancer to neoadjuvant radiation therapy correlates with improved health outcomes. This response ranges from a complete response, or 0 on the AJCC-TRG scale, to little or no response, or a 3 on the scale. We previously demonstrated an association between increased SPATA20 expression and higher AJCC scores in a patient cohort. We hypothesize that knocking down SPATA20 in in-vitro rectal cell lines will increase their radiosensitivity.

Methods
HRT18 rectal cancer cell lines were transfected with a lentiviral construct containing small interfering RNAs (siRNA) targeting SPATA20 mRNA to create knockdown cell lines. Western blot was used for knockdown validation. Wildtype HRT18 and knockdown HRT18 cell lines were plated and irradiated with 10 Gy. Cell viability was assessed at the 48-hours interval using Annexin V/Propidium Iodide (PI) cell viability assay for both irradiated and non-irradiated controls.

Results
Decreased expression was confirmed in knockdown HRT18 cell lines compared to wildtype HRT18 using Western blot. In the non-radiated controls, Annexin V/PI demonstrated no statistical difference (p=0.63) in cell death when comparing wildtype HRT18 (28.3%) to knockdown HRT18 cell lines (30.6%). In the radiated samples on the other hand, there was a statistically significant increase (p=0.015) in cell death when comparing wildtype HRT18 (33.9%) to knockdown cell lines (52.87%). Comparing non-radiated to radiated knockdown HRT18, there was also a statistically significant increase (p=0.022) in cell death (30.6% vs 52.87%).

Conclusion
Manipulation of SPATA20 correlates with radiation response, signifying it as a possible modulator of radiosensitivity in rectal cancer. Further investigation is warranted to validate this observation in animal models and explore potential pharmacological inhibitors.

Comparison of cell death between non-radiated and radiated samples of wildtype and knockdown HRT18 cell lines

Comparison of cell death between non-radiated and radiated samples of wildtype and knockdown HRT18 cell lines

Introduction:
Cytoreductive surgery followed by HIPEC is a treatment option for peritoneal carcinomatosis for colorectal cancer; however, there is a lack of consensus on the benefit and type of chemotherapy agent utilized. We propose a novel epigenetic agent Mithramycin A (MA), as an alternative treatment to Mitomycin C as a cytotoxic agent with enhanced capability to remodel the tumor genetic landscape.
Methods:
Utilizing two colon cancer cell lines, HT-29 and CaCO2, we performed cell proliferation assays after treatment with MA (750nM) or MC (4.48uM) incubated at 37° or 42° Celsius for 90 min. RNA Sequencing using triplicate samples of the HT-29 cell line was performed. Resultant data were organized into 50 hallmark gene sets, normalized enrichment scores, log fold changes, and adjusted p-values. The top 6 hallmark gene sets with the greatest change in expression measured by adjusted p-value were cross-referenced against the Catalog of Somatic Mutations in Cancer (COSMIC) list of 733 known cancer-associated genes and the Tumor Suppressor Gene Database (TSGD) list of 535 known tumor suppressor genes in colon cancer.
Results:
Treatment of CaCo2 and HT-29 at 42° Celsius demonstrated comparable cell viability (CaCo2: MA 48.9% vs. MC 40.9%, p=0.23) (HT-29: MA 38.1% vs. MC 25.1%, p=0.18). RNA sequencing results showed MA treatment had dramatic global effects on gene expression, with 3,523 (26.1%) genes upregulated and 4,128 (30.6%) downregulated compared to MC, which had only 369 (2.7%) upregulated and 947 (7.0%) downregulated. Compared to the COSMIC data set, the top six hallmark pathways contained 57 unique gene expressions versus control with statistical significance. Two genes whose upregulation has been previously implicated in colon cancer progression saw significant downregulation when treated with MA versus control: MYB (Log fold D= -3.45, adj p-value= 3.11x10^-5) and MYH9 (Log fold D= -3.96, adj p-value= 4.65x10^-7). Top six hallmark pathways were compared to the TSGD database and 21 genes with a significant positive log fold change were found, including CDO1 (log fold D= 5.07, adj p-value=2.01x10^-4), GPX3 (log fold D=5.44, adj p-value 5.34x10^-7), DNAJB4 (log fold D= 2.43, adj p-value= 5.44x10^-4), CDKN1C (log fold D= 1.97, adj p-value= 0.002) CDKN1A (log fold D=2.28, adj p-value= 1.88x10^-5) and CAV1 (log fold D= 3.24, adj p-value= 7.66x10^-4).
Conclusion:
While Mithramycin A shows comparable efficacy in vitro against colon cancer cell lines to Mitomycin C, MA genetically remodels tumorigenesis by epigenetic modulation. Further investigation of this novel agent is warranted as a potential agent to reduce tumor recurrence by upregulation of previously repressed tumor suppressor genes.

<b>Fig1: Volcano plot of relative expression of individual genes when treated with mithramycin A (left) or mitomycin C (right)</b>

Fig1: Volcano plot of relative expression of individual genes when treated with mithramycin A (left) or mitomycin C (right)

Introduction
The peritumoral microenvironment is known to act to suppress the immune response against cancer cells, and tumor-infiltrating lymphocytes have a crucial role in immune surveillance. Obesity leads to an imbalance in adipokines, gut dysbiosis, and endotoxemia, as well as IGF-1 activation pathways and free fatty acids release that can influence the immune microenvironment. The cross-talk between tumor cells and the immune microenvironment can be detected in the normal “healthy” mucosa surrounding cancer, according to the concept of the field of cancerization. The aim of this study is to analyze the healthy rectal mucosa surrounding rectal cancer in overweight/obese patients who underwent surgery to evaluate the potential alteration of immune surveillance mechanisms of healthy rectal mucosal
Methods
This study is a sub-analysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263). In this multicentric study, we collected healthy mucosa surrounding rectal cancer. A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8beta, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. A prospective analysis was performed with fluorescence-activated cell sorting to determine the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cell, and T reg. Immune markers of healthy rectal mucosa were compared between patients under and over the BMI 25, between infiltrated margins, and between complete response or not, respectively.
Results
A total of 213 patients with rectal cancer, whose data on body mass index were available, were analyzed: 103 in the retrospective cohort and 110 in the prospective cohort. In our study group, 88 patients were normal -weight while 125 were overweight or obese (BMI>25). Overweight patients with rectal cancer had a lower expression of HLA-ABC on the surface of their epithelial cells than those with BMI under 25 (CK+HLA-abc+ MFI (p= 0.069). In particular, in patients undergoing neoadjuvant therapy, overweight ones had a lower frequency of high expression of HLA-ABC on epithelial cells than normal-weight patients. Moreover, overweight patients had a lower infiltration of CD8beta+ T cells within the healthy mucosa surrounding the cancers than those with BMI under 25 (p=0.04). Finally, the infiltration of CD8+ T-cells in the healthy mucosa inversely correlated with BMI (rho=-0.34, p=0.03).
Conclusions
Our findings suggest that in patients with rectal cancer, those who are overweight have a lower activation of epithelial cells as antigen-presenting cells and a lower activation of cytotoxic T-cells in their healthy mucosa surrounding rectal cancer. These data could be useful to plan a tailored approach to overweight/obese patients with a rectal cancer diagnosis.

Background:
Inflammatory bowel disease and disorders of gastrointestinal motility overlap significantly in the clinical setting. While ileus is commonly seen, the mechanisms involved remain poorly understood, in part due to a lack of robust in vivo models. Prior studies have shown that serotonergic signaling plays a role in control of intestinal motility, although the precise mechanisms by which colonic and ileal motility are linked during inflammatory processes remain unclear. We hypothesize that the small intestinal dysmotility seen in a colonic inflammation model is precipitated through aberrant changes in serotonergic signaling from the inflamed colon to the small intestine.

Methods:
Four-week-old C57BL/6 mice were randomized into control and DSS groups. DSS groups received 7-day exposure to DSS (MW 40,000–50,000 kDa) ad libitum at concentrations of 2.5% and 5% in 0.5% sucrose drinking water. Mice were sacrificed on day 7. 70kda fluorescein-dextran was administered and animals were sacrificed 30 minutes later; the whole intestine was divided into 2cm sections. Sections were homogenized, and FITC-fluorescence measured in the supernatant. The small intestinal transit time was derived from the position of the geometric (Geom) center (GC) of FITC-dextran. Colon length was measured, and samples of stomach, ileum, and colon were taken. mRNA expression of interleukin 6 (IL-6), interleukin 1ß (IL1ß), and lipocalin-2 (LCN2) as well as serotonergic pathway genes tryptophan hydroxylase (Tph1), and serotonin transporter (5’HTT) were normalized to ribosomal protein large P0 (Rplp0).

Results:
Compared to controls, mice receiving 2.5% or 5% DSS gained less percent weight (Ctrl=24.50 vs 2.5%DSS=5.18 vs 5%DSS= -7.41; p<0.0001), had shorter colons (Ctrl=59.35mm vs 2.5%DSS=50.57mm vs 5%DSS=41.00mm; p<0.05) and showed significant upregulation of antimicrobial peptide, LCN2 (Ctrl=38.50 vs 2.5%DSS= 218.40; p<0.01) and pro-inflammatory cytokines IL6 (Ctrl=0.94 vs 2.5%DSS=4.38; p<0.05) and IL1ß (Ctrl=9.61 vs 2.5%DSS=69.95; p<0.01). DSS significantly reduced intestinal motility (Ctrl, GC=10.5 vs 2.5%DSS, GC=8 vs 5%DSS, GC=6; p<0.01). Ileal serotonergic markers showed significant alteration in DSS groups with Tph1 gene expression upregulated (Ctrl=4.01 vs 2.5%DSS=6.25; p<0.05) and serotonin transporter (5’HTT) expression downregulated (Ctrl=91.68 vs 2.5%DSS=52.04; p<0.05). However, no significant changes in key pro-inflammatory cytokines (IL6, IL1β and TNFα) were found in the terminal ileum.

Conclusions:
Colonic inflammation induced significant intestinal dysmotility that was associated with changes in the expression of genes that regulate serotonergic signaling. These findings suggest the potential for novel approaches for the control of colitis associated ileus through modulation of the serotonergic signaling system.

Background
Restorative proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) is the gold standard surgical treatment of ulcerative colitis (UC), offering complete removal of the diseased colon and effective prevention and treatment of colorectal cancer. Segmental colectomy (SC) is rarely performed, though considered in select patients such as those with quiescent disease, or elderly with comorbidities who are high risk for postoperative morbidity and poor function following IPAA surgery. We aimed to assess postoperative and long-term outcomes of SC in UC
Methods
Retrospective chart review of UC patients who underwent SC at our tertiary care center from 1999 to 2022 was performed. Primary outcomes were postoperative complication, early flare, cancer recurrence, & subsequent total abdominal colectomy (TAC)/TPC rate. Data is presented as mean (standard deviation), median [25-75 percentiles] or frequency (percent)
Results
61 patients [21 (34.4%) female] were identified. Median age at the time of diagnosis and surgery were 41.5 (30-59) and 67.7 (56.8-76.5) years, respectively. Median body mass index was 27.9 (24.6-31.7) kg/m². 36 (59%) patients had American Society of Anesthesiologists score of III. 53 (86.9%) patients had at least one comorbidity. 51 (83.6%) patients had Mayo score of 0-1 at the time of surgery. Patients underwent: Right hemicolectomy (n=30, 49.2%), left hemicolectomy (n=6, 9.8%), sigmoidectomy (n=19, 31.1%), low anterior resection (n=4, 6.6%), and segmental resection (n=2, 9.8%) for cancer (n=15, 24.6%), dysplasia/polyps (n=21, 34.4%), diverticular disease (n=13, 21.3%), stricture (n=6, 9.8%), fistula (n=3, 4.9%), bleeding (n=1, 1.6%), and megacolon (n=1, 1.6%). The median duration of operation and estimated blood loss were 168.5 (130-210) min and 100 (40-150) ml, respectively. 18 (29.5%) patients had postoperative complications, most commonly ileus (n=7, 11.5%). 7 (11.5%) patients had complications of Clavien-Dindo Class III-V. Median time to start of diet and return of bowel function were 1.5 (1-4) and 3 (2-4) days, respectively. One (1.6%) patient had anastomotic leak, while sepsis occurred in 1 (1.6%) patient. Median length of hospital stay was 5 (3-8.5) days. Early postoperative flare (within 3 months of surgery) occured in 5 (8.2%) patients. Among 36 patients with dysplasia/cancer, 1 had metachronous colon cancer and 1 developed distant recurrence at 19.5 and 23 months after surgery, respectively. 4 (6.6%) patients underwent subsequent TAC/TPC. Median follow-up time was 35.5 (5.5-63.9) months. 2-year and 5-year overall survival rates were 92% and 78.7%, respectively
Conclusion
In selected UC patients, such as elderly patients with comorbidities who have no-minimal disease activity, SC can be a safe and feasible option providing low postoperative complication, early flare, cancer recurrence and need for subsequent TAC/TPC rates

INTRODUCTION
Limited evidence exists regarding survival benefit of adjuvant chemotherapy for non-metastatic appendiceal adenocarcinoma patients, and many providers defer to colorectal adenocarcinoma guidelines for adjuvant therapy regimens. Decision-making regarding systemic therapy initiation is often based on nodal positivity, to which adequate staging is achieved via right hemicolectomy (RHC). However, treatment in the elderly patient population can present additional considerations given the potential morbidity of surgery and systemic therapy. We sought to analyze outcomes in elderly patients with node-positive appendiceal adenocarcinoma.

METHODS
Patients diagnosed with Stage III appendiceal adenocarcinoma who underwent a RHC with 12 or more examined lymph nodes were identified using the National Cancer Database (2004-2019). Elderly patients were defined as patients with age of diagnosis greater than 65 years old, while Non-elderly patients were defined as patients with age of diagnosis 65 years or younger. Propensity score matching (PSM) was performed between elderly and non-elderly patients adjusting for gender, race, Charlson-Deyo Comorbidity Index (CCI), number of positive lymph nodes, and grade. Chi-squared testing, Kaplan-Meier method with log-rank test, and Cox proportional hazards regression models were employed.

RESULTS
1475 patients were identified, with 58.2% (858) elderly patients and 41.8% (617) non-elderly patients. Elderly patients were more likely to present with a CCI ≥ 2 (9.7% v. 3.8%, p<0.001). Tumor grade or mucinous histology were similar between the groups. Elderly patients were less likely to receive chemotherapy (68.6% v. 85.3%, p<0.001) or multi-agent chemotherapy (48.4% v. 74.3%, p<0.001). On unadjusted Kaplan Meier analyses, elderly patients receiving single-agent chemotherapy had similar median survival (54.1 mo, 95% CI 11.5-31.6) compared to multi-agent (59.8 mo, 95% CI 49.0-70.6), while both conferred survival advantage compared to no chemotherapy (19.4 mo, 95% CI 13.0-25.7) (Figure 1A). On multivariate analyses after PSM, single-agent (HR 0.46) and multi-agent (HR 0.41) chemotherapy regimens conferred a survival advantage compared to elderly patients who did not receive chemotherapy. There was no survival advantage between single-agent versus multi-agent (p=0.55). Greater than 3 positive lymph nodes (HR 1.73) and grade (Grade 2 HR 2.32, Grade 3 HR 2.90, Grade 4 HR 4.02) were associated with decreased survival.

CONCLUSIONS
Elderly patients presenting with stage III appendiceal adenocarcinoma confer a survival benefit from adjuvant chemotherapy after right hemicolectomy, regardless of histological grade or CCI score. However, multiagent chemotherapeutic regimens demonstrate a diminished survival advantage, and toxicities of these regimens may outweigh benefit in elderly patients.

<b>FIGURE 1. </b>Kaplan Meier survival curves of Elderly (A) and Non-Elderly (B) appendiceal adenocarcinoma patients stratified by adjuvant chemotherapeutic regimens

FIGURE 1. Kaplan Meier survival curves of Elderly (A) and Non-Elderly (B) appendiceal adenocarcinoma patients stratified by adjuvant chemotherapeutic regimens

<b>TABLE 1. </b>Cox regression multivariable analysis of factors affecting survival after propensity score matching for elderly appendiceal adenocarcinoma patients

TABLE 1. Cox regression multivariable analysis of factors affecting survival after propensity score matching for elderly appendiceal adenocarcinoma patients

Background: The Patient Reported Outcomes after Pouch Surgery (PROPS) Delphi consensus study identified a list of seven bowel symptoms and seven consequences that were utilized to develop and validate the Ileoanal Pouch Syndrome Severity Index score. The aim of the present study was to develop a meaningful measure of bowel function that accounts for the possibility of patients perceiving the same symptoms differently over time.

Methods: Patients who had a proctocolectomy with ileoanal pouch for ulcerative colitis ≥ 12 months of restored intestinal continuity were recruited by a combination of mail/email to patients treated at 11 high volume IBD centers, and online advertisements through the Crohn’s and Colitis Foundation social media pages. After obtaining consent, questionnaires regarding bowel function were administered. Participants were asked to rate how “bothersome” each symptom was on a scale of 1-9. Participants also reported on quality of life. Individual question score values were designated to form the “Ileoanal Pouch Syndrome Distress Inventory”. Validity was tested by receiver operating characteristic (ROC) curve analyzing the association between distress inventory score and quality of life. Convergent validity was assessed by comparing scores to the LARS, FIQoL, MSK bowel function score, and Wexner incontinence score. Lastly, clinical validity was assessed by comparing scores between patients based on the absence of key clinical variables.

Results: Questionnaires were completed by 676 patients eligible for inclusion. Weighted scores based on symptom bother scores were computed on the basis of the questionnaire results. The range of possible scores was 0 to 64 (Interquartile range 12-38). As scores increased, the percentage of patients reporting good quality of life decreased and the percentage of patients reporting poor quality of life increased (Figure 1). The distress index score was then used to predict poor quality of life, where the ROC curve showed an area under the curve of 0.87. This is compared to an area under the curve of 0.85 using the IPS severity index score. The score showed excellent convergent validity with all tested bowel function scores (p<0.001) and was highly correlated with long term outcomes such as pouchitis, cuffitis, and other pouch complications.

Conclusions: This study developed a patient-centered scoring system that utilizes patients perception of how bothersome various symptoms are, and then correlates these reported perceptions with quality of life. This tool will ideally allow clinicians to follow individual patients as they potentially accommodate to their symptoms and learn to cope over time, even if the actual frequency/severity of symptoms remains unchanged, which may allow for a more detailed understanding of how various interventions affect the quality of life of patients with pouches.

Background: Pouch failure after restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) occurs in up to 15% of cases. A redo pouch procedure can be offered to maintain intestinal continuity after pouch failure, but little is known on quality of life (QoL) after redo pouch. We aimed to describe long-term QoL and functional outcomes after redo pouch.
Methods: We retrospectively analyzed our prospectively collected pouch registry for redo IPAA procedures, and identified patients who had completed at least one Cleveland Global Quality of Life (CGQL) questionnaire after redo pouch.
Results: Out of 532 patients, CGQL were available for 375 (70%): 212 (57%) females, median age at redo pouch 40 (IQR 28 – 48) years. Diagnosis at index pouch was ulcerative colitis in 325 (87%) cases, indeterminate colitis in 13 (3%), Crohn’s disease in 15 (4%), familial adenomatous polyposis in 21 (6%). The median interval between index and redo pouch was 4 (2 – 6) years. The indication for redo pouch was septic complication in 230 (61%) cases, mechanical complication in 114 (31%), functional complication in 19 (5%), and dysplasia or cancer in 11 (3%). A handsewn anastomosis was performed in 72% cases. After redo pouch, 351 (95%) had their stoma closed, while 18 (5%) never had stoma closure due to complications, and 5 (1%) due to patient preference. The median interval between redo pouch and latest CGQL was 4 (1 – 9) years. The overall CGQL score (0 – 1) was 0.7 (0.5 – 0.8), with median quality of life 7 (5 – 9), quality of health 7 (5 – 8) and quality of energy 6.5 (5 – 8). There were no differences in CGQL scores in patients who had a redo pouch due to septic complications versus other indications. The median number of bowel movements was 6 (5 – 8) during the daytime, 2 (1 – 3) during the nighttime, for a total of 8 (6 – 10) bowel movements per 24 hours. Dietary restrictions were reported by 50% patients, social restrictions by 34%, work restrictions by 38%, and sexual restrictions by 37% (Figure 1). Urgency occurring daily or most days was reported by 24% patients, incontinence by 10%. Consistency of stool was reported as liquid by 76% of patients. Seepage during the day was experience by 52% of patients, nocturnally in 68%, with 53% of patients reporting daytime pad use, and 61% at night. Median happiness with surgery was 8 (5 – 10): 80% patients would undergo surgery again, and 84% patients would recommend it to other people. During follow-up, 84 (22.5%) pouch failures occurred.
Conclusion: A redo pouch procedure allows a majority of patients to maintain intestinal continuity with good quality of life. Most patients would undergo redo pouch again and recommend it to others. Before redo pouch, patients need to be counselled regarding function expectations in regards to stool frequency and consistency, urgency, incontinence, seepage, and overall success rates.

Figure 1. Functional outcomes at latest Cleveland Global Quality of Life questionnaire after redo pouch

Figure 1. Functional outcomes at latest Cleveland Global Quality of Life questionnaire after redo pouch

Background: Patients undergoing ileocolic resection are often concerned about the risk of needing a stoma. We lack accurate tools to inform patients about their risk of a stoma during the peri-operative period. Our aim was to develop a clinical applicable tool using patient, disease, and surgical factors available pre-operatively to estimate the need for a stoma among patients undergoing ileocolic resection.
Methods: We identified all patients undergoing an ileocolic resection between 2000 and 2019, inclusive at our high-volume center. We recorded patient characteristics, imaging findings, surgical details, and post-operative outcomes using our institutional IBD database and through chart review. The outcome of interest was the need for a stoma either intra-operatively or post-operatively. We generated a prognostic model using a logistic regression model with multiple imputation for missing data to identify risk factors, and internally validated the model via bootstrapping.
Results: Employing data from 936 consecutive ileocolic resections, of which 13% received a stoma, we identified the following risk factors: age, sex, disease phenotype, pre-operative anaemia, malnutrition, preoperative biologics, preoperative steroids, ASA 3 or 4, open surgery, and simultaneous resection of another intestinal segment. After applying optimism adjustment, the model demonstrated good discrimination (C-index 0.782), and excellent calibration (calibration slope 1.001, calibration-in-the-large 0.0006; see Figure 1 for calibration plot). We exported our model into an excel spreadsheet for single predictions and batch predictions for clinical use and external validation.
Conclusions: Our stoma prediction tool is able to accurately predict the need for a stoma among patients undergoing an ileocolic resection and may assist with patient counselling and informed decision making. Our tool requires external validation to ensure generalizability.

Background: When children with Crohn’s disease (CD) have medically refractory disease, a diverting ostomy may be needed. As part of an antibiotic stewardship study, we sought to determine risk of ostomy in a large pediatric cohort.

Methods: We identified pediatric patients (≤21 years old) diagnosed with CD and enrolled in ImproveCareNow Network (ICN), a multicenter, multidisciplinary pediatric inflammatory bowel disease quality improvement collaborative. Patients within 90 days of CD diagnosis (2007-2018), and with ≥3 visits, were identified. The registry includes prospectively collected data from outpatient pediatric gastroenterology visits. We gathered data on demographics (age, sex, race, insurance), medications used, and presence of ostomy. Insurance was categorized as commercial insurance (with or without public insurance) or non-commercial (public or no insurance). Disease behavior uses Paris phenotype classification (B1-non-stricturing/non-penetrating, B2-stricturing, B3-penetrating, B2/B3-stricturing/penetrating, PFC-perianal fistulizing complications). Primary outcome was creation of ostomy from onset of CD diagnosis in those with and without PFC. Descriptive data and logistic regression were performed with p<0.05 considered significant.

Results: Of 5,720 patients from 80 ICN sites (median age 13.5yr, 40.5% female, 18.7% non-White, 78% commercial insurance), 1,023 (30.7%) had PFC without differences by sex (p=0.70), age at diagnosis (p=0.19), race (p=0.14), or insurance (p=0.27). Ostomies were not more common with PFC (2.9%vs.2.3%; p=0.21) and antibiotic treatment of PFC was not different among those with an ostomy (21.1%vs.26.9%; p=0.6) or by insurance (p=0.50).

Although no differences phenotype classification by race (p=0.77), B2/B3 phenotypes were more common in those without commercial insurance (18.6%vs.13.1%; p=0.001), older age at CD diagnosis (p<0.001) and in male patients (p=0.013). Ostomies were more common among those without commercial insurance (3.8%vs.2.3%; p=0.010), among Hispanic patients (5.3%vs.2.4%; p=0.008) and among Non-White patients (3.5%vs.2.3%; p=0.027). Ostomies were not associated with age at CD diagnosis (<10yr, 1.9%; 10-17yr, 2.6%; ≥17yr, 2.4%; p=0.44), or sex (male 2.2%, female 2.8%; p=0.17). Ostomies were more common among patients with aggressive phenotype: B1,1.8%; B2,5.3%; B3,6.2%; B2/B3,10.1% (p<0.001). After controlling for disease severity, age, sex, presence of PFC, and medications (Table), White patients with and without commercial insurance were least likely to need an ostomy (OR 0.42, p=0.009, OR 0.37, p=0.029).

Conclusion: Ostomies for CD are more commonly done in children without commercial insurance, in Non-White patients, and with an aggressive disease phenotype. These disparities are unexplained by antibiotic use or presence of PFC.

Background: Rectal small cell cancer (rSCC) is an uncommon malignancy of rectum. Significant evidence to support multimodality treatment strategies is lacking. Treatment recommendations are extrapolated from studies of pulmonary and non pulmonary SCC.

Aim: To examine the National Cancer Database (NCDB) for treatment-trends of rSCC to include surgery, chemotherapy, radiation, combination therapies and their effect on survival.

Methods: Retrospective review of rSCC patients in NCDB, (2004-2018), > 18y old, stage I-III. Treatments: Group (Gp) A- Surgery alone; Gp B-Surgery+Chemo; Gp C- Surgery+ Chemo+ XRT; Gp D- Chemo alone; Gp E- XRT alone. Univariate analyses comparing variables in the 5 different treatment groups were performed. Multivariate Cox regression model and Kaplan Meier (KM) analysis was used to assess survival.

Results: 1801 patients were identified with rSCC out of 228,213 patients with rectal cancer (0.7%). Equal distribution of males and females was observed. Table 1 describes univariate analysis of variables of significance. Surgery alone arm (Gp A) had significantly more patient numbers, smaller tumor sizes, lower grades and stage than other groups. No significant differences were observed in patient education, income, distance from treatment center, type of facility (community, academic, integrated network cancer programs) in the treatment groups. Practice trends showed that use of chemotherapy alone increased over the 15 years of the study while patients receiving surgery alone declined in the last 5 years (table 1).

Unadjusted Kaplan- Meier survival curves, (Fig 1), showed an overall significant benefit of Gp A (surgery alone). However, Multivariate Cox regression with adjusted hazard ratio, showed that Gp C (surgery+chemo+XRT) had significant survival advantage over surgery alone, aHR 1.732, 95% CI (1.181-2.542) p = 0.0050. Limitations of this registry study include variation in treatment groups, lack of randomisation, physician bias, and patient choice.

Conclusion: In this observational study, multimodality treatment of surgery, radiation and chemotherapy provided survival advantage over surgery alone for rSCC. However, treatment practice-trends during 15 years (2004-2018) showed increasing use of chemotherapy and declining surgery.

<b>Table 1: Univariate Analysis of Patient, Tumor & Clinical Variables in the 5 Treatment Groups </b>

Table 1: Univariate Analysis of Patient, Tumor & Clinical Variables in the 5 Treatment Groups

<b>Figure 1: Kaplan Meier Overall Survival Curves between the 5 Treatment Groups</b>

Figure 1: Kaplan Meier Overall Survival Curves between the 5 Treatment Groups

Background: IPAA is a technically demanding procedure with many potential complications. Rediversion is often the first step in pouch salvage, but at time of rediversion it may not be clear if a patient will undergo subsequent pouch salvage surgery. The outcomes after rediversion have not previously been reported. We aimed to describe indications for rediversion, short- and long-term outcomes, in a large pouch cohort.

Methods: We queried our institutional pouch registry for patients who underwent index IPAA and subsequent rediversion at our institution from 1991–2022. Pouch patients constructed or rediverted elsewhere, or pouch salvage/excision without rediversion, were excluded. Patients were selected for pouch salvage according to surgeon discretion. Descriptive statistics and Kaplan-Meier analysis described outcomes after rediversion using EZR v1.6, 2022, Tochigi-ken, Japan.

Results: Overall, 188 patients (3.9% of 4,695 index primary pouches) were rediverted. At time of index pouch, median age 32 years, 50.5% were women. Indications for IPAA: UC (85.1%), Crohn’s (5.3%), FAP (4.3%), indeterminate colitis (1.1%) and others (4.3%).

Time from prior ileostomy closure to rediversion was 71 months (0-1381). Indications for rediversion were “Inflammatory Reasons” in 95 (50.8%): fistulae (43, 22.9%), pouchitis/cuffitis (31, 16.5%), pelvic/perianal sepsis (18, 9.6%), small bowel Crohn's (5, 2.7%); and “Non-inflammatory Reasons” in 93 (49.5%): obstruction/volvulus (50, 26.6%), functional problems (22, 11.8%), perforations (11, 5.9%), IPAA leaks (9, 4.8%), others (13, 6.9%). Rediversion was performed open in 156 (82.9%) and laparoscopic in 32 (17.1% [9.4% conversions]). Types of rediversion: loop ileostomy in 174 (92%), end-ileostomy in 12 (6.4%), and end-loop ileostomy in 3 (1.6%). The operative time was 100 minutes (16 – 495), estimate blood loss 50 mL (0-750 mL), and median length of stay was 5 days. The Clavien-Dindo ≥3 complication rate was 13.3%, readmission rate 9.6% and reoperations rate 1.6%.

After rediversion, 99 (52.7%) underwent pouch salvage, 58 (30.9%) patients had no further surgery (pouch left in situ), and 31 (16.5%) had pouch excision without attempted salvage; the reasons for pouch left in situ and pouch excision are shown in Figure 1. The 5-year pouch survival for non-inflammatory vs. inflammatory indications was 87.4% vs. 62.4% (p=0.02), respectively (Figure 2). After pouch salvage surgery (n=98), rediversion closure was achieved in 98 (100%), and subsequent median pouch survival was 280 months.

Conclusion: Overall, 4% of our pouches were rediverted, and rediversion after IPAA was a safe initial strategy to manage failing pouches, with half of the rediverted patients going on to attempted pouch salvage; salvage for non-inflammatory indications had a significantly higher pouch salvage rate than those rediverted for inflammatory complications.

Intro
Anal fistulas are classified and treated based on the position of the fistula tract relative to the anal sphincter muscles. Surgical treatment seeks to eliminate the epithelialized tract while also preserving anal sphincter function. Fistulotomy is a highly effective surgical treatment for simple anal fistulas. However, there is a lack of evidence on the use of fistulotomy in patients with ileal pouch-anal anastomosis (IPAA), generally considered a contraindication to fistulotomy. Therefore, our aim was to determine the safety, efficacy, and functional outcomes after fistulotomy used selectively in IPAA patients.
Methods
A retrospective review of all adult patients with an IPAA who underwent fistulotomy at our institution between January 1999 and August 2022 was performed. Data were collected from a prospective IPAA registry and supplemental chart review. Data included demographics, fistula characteristics, postoperative complications, recurrence, reoperations, resolution of fistula, and IPAA functional outcomes at the most recent follow-up.
Results
49 adult patients were included. The study cohort included 28 males (57%), the median age at fistulotomy was 45 years (range 23-70), median time from IPAA to fistula symptoms was 114.5 months (range, 2.6 to 450.2). Prior to fistulotomy, 24 patients (49%) had seton placement, 16 (33%) had drainage of abscess, and 5 patients (10%) had nonoperative therapy. Etiology of fistula was cryptoglandular (n=24, 49%), perianal Crohn’s (n=17, 35%), IPAA anastomosis leak (n=7, 14%), and fissure (n=3, 6%). Fistula class was superficial (n=26, 53%), intersphincteric (n=15, 31%), and low transsphincteric (n=8, 16%). Anal fistulas were evaluated with MRI in 10 (20%) and CT in 11 (22%) patients. Fistulotomies were performed in the left anterior (n=18, 37%), right anterior (n=12, 24%), left posterior (n=7, 14%), right posterior (n=7, 14%), and posterior midline (n=5, 10%). Short-term complications included bleeding (n=2, 4%), and perianal sepsis (n=1, 2%). During a median follow-up time of 36 months (range 0-135.4) after fistulotomy, long-term complications included recurrence/new fistula (n=13, 26.5%), reoperation (n=9, 18%), and keyhole deformity (n=2, 4%). Functional IPAA outcomes included seepage (n=6, 12%) and fecal incontinence (n=2, 4%); no anal stricture was reported. Three patients (6%) required a temporary fecal diversion and 2 (4%) required IPAA excision, all of whom had been diagnosed with Crohn’s. Thirty-seven (75%) of patients had complete resolution after fistulotomy with an intact functioning pouch.
Conclusion
Our data suggest that select patients with IPAA may safely undergo fistulotomy for anal fistulas that are superficial or involve minimal sphincter muscle. Pouch functional outcomes were minimally affected by fistulotomy in patients that did not have recurring fistula and abscess or Crohn’s disease.

Background: Rectal cancer surgery remains a significant technical challenge. Development and implementation of new technology offers hope for more accurate and precise surgery. To evaluate if single port robotic technology (SPR) helps achieve this goal we established an international SP robotic registry. This study reports short-term clinical and oncological outcomes from an international SPR registry for rectal cancer.

Methods: Review of a prospective international registry of SPR procedures approved for colorectal surgery under an investigational design exemption (IDE) was performed. Patients with rectal adenocarcinoma that had resection for curative intent using the SPR platform through an abdominal approach from 11/2018-9/2022 were included. Frequency statistics described patient and tumor characteristics and intraoperative, oncological and clinical outcome variables. The main outcome measure was the quality of the TME specimen. Secondary outcome measures were intraoperative conversions; R1 resection rate; 30-day postoperative morbidity and mortality.

Results:122 SPR rectal cancer cases were performed at 2 centers by 4 colorectal surgeons. 9 transanal excisions were excluded, leaving 113 cases analyzed. The cohort was 51.32% male, mean age of 59.81years (SD 11.46) and BMI 25.97 kg/m2 (SD 6.13). The most common T-stage was 3 (n=56, 49.56%), followed by 2 (n=24, 21.24%). Three-fourths had preoperative neoadjuvant chemoradiation. The cancers were a mean 2.91cm (SD 2.59) from the anorectal ring and 4.08cm (SD 1.93) in size. The procedures performed were a TATA/TaTME (n=61, 53.98%), low anterior resection (n=49, 43.36%) and abdominoperineal resection (n=3, 2,65%). The mean operating time was 168.71min (SD 56.89). There were no intraoperative complications but 2 (1.77%) conversions to laparoscopy. There was a median of 1 incision, with a mean size of 3.00cm (SD 1.64). The TME specimen was complete in 97.35% (n=110) and near complete in 2.65% (n=3). R1 rate was 3.53% with 3 distal and 1 circumferential positive margin post-operatively, there were 15 total complications, 4 major and 11 minor. There were 2 readmissions (ileus and small bowel obstruction) but no 30-day mortality.

Conclusions: This early international experience with the SPR showed it was a safe and effective technique for distal rectal cancers, with excellent specimen quality. Complications and conversion rates seen with other techniques and platforms used in rectal cancer surgery were not demonstrated. With the use of an international registry, we hope to develop a better understanding of the opportunities and limitations of SPR in rectal cancer surgery as the technology is adopted and applied more widely. While structured training and controlled trials will be required to develop best practices and define the use of the SPR, initial international registry data is encouraging.

Background: Resection rectopexy (RR) and ventral mesh rectopexy (VMR) are widely accepted surgical options for the treatment of rectal prolapse, however reports on long-term recurrence rates and functional outcomes are lacking. The aim of our study was to investigate differences in recurrence rates and functional outcomes a decade after RR vs VMR. We hypothesized that VMR would have a lower recurrence rate and superior functional outcomes versus RR.
Methods: We retrospectively reviewed our prospectively collected database on surgery for rectal prolapse. Patients who underwent RR or VMR at our center between 2009 and 2016 were included. All patients were contacted by phone and administered three validated questionnaires: Global Quality of Life (GQoL) scale, Patient Global Impression of Change (PGIC), and Initial Measurement of Patient-reported Pelvic Floor Complaints Tool Short Form (IMPACT-SF). Data on prolapse recurrence was also collected. We compared quality of life, long-term functional outcomes and prolapse recurrence.
Results: 220 patients were included, of which 208 (94%) female; 85 (39%) underwent RR, 135 (61%) VMR. The RR group was younger (median 52 vs 60 years old, p = 0.02) and had more open procedures (20% vs 9%, p < 0.001) (Table 1). The VMR group had more combined procedures (58% vs 23%, p < 0.001). After a median follow up of 110 (IQR 94 – 146) months for RR and 113 (87 – 137) for VMR, recurrences occurred in 21 (26%) in the RR and 50 (39%) in the VMR group. The recurrence rate at 5- and 10-years was 16% and 34% for RR, and 28% and 44% for VMR (p = 0.047) (Figure 1). Median time to recurrence was 44 (18 – 80) months in the RR group and 28.5 (11 – 52.5) in the VMR group (p = 0.14). Recurrence was managed conservatively in 52% cases in the RR and 54% in the VMR group (p = 0.79). At follow up, 69 (81%) in the RR and 113 (84%) in the VMR group were still alive: of those, 36 (52%) for the RR and 67 (59%) for the VMR group consented to participate to the phone interview. GQoL, PGIC, functional outcomes, and solid and fecal incontinences rates were similar between the two groups.
Conclusion: Long-term quality of life and functional outcomes after RR and VMR were comparable. Contrary to our hypothesis, VMR was associated with a higher prolapse recurrence rate.

Figure 1. Kaplan Meier curve of prolapse recurrence after resection rectopexy versus ventral rectopexy

Figure 1. Kaplan Meier curve of prolapse recurrence after resection rectopexy versus ventral rectopexy

Table 1. Characteristics of the two groups and long term functional outcomes

Table 1. Characteristics of the two groups and long term functional outcomes

Background:
Total neoadjuvant therapy (TNT) in the treatment of locally advanced rectal cancerinvolves administration of chemoradiotherapy (CRT) and consolidation chemotherapy prior to surgery.Complete response (CR) following TNT is defined as combination of patients who underwent surgery and hadpathological complete response (pCR) with watch-and-wait (WW) patients who had a sustained clinicalcomplete response (cCR) for at least 12 months in previous studies. The aim of the current study is todetermine the predictors of CR after TNT.
Methods:
Following Institutional Review Board approval, stage 2-3 rectal cancer patients whoreceived TNT at a tertiary care center from January 2015 to December 2021 were identified retrospectively.Our TNT protocol included concurrent CRT (50-50.4 Gy in 25-28 fractions with 5-FU or Capecitabine) and 4months of consolidation chemotherapy (FOLFOX or CAPOX). Following completion of CRT and TNT, patientswere evaluated with digital rectal exam, flexible sigmoidoscopy and MRI. Patients with a cCR were offered aWW approach. Data were presented as mean (standard deviation), median [25-75 percentiles] or frequency(percent). Univariable and multivariable logistic regression models were used to identify the predictors of CR.
Results:
Total of 119 patients with rectal cancer (19 patients with stage 2, 100 with stage 3) wereincluded. Mean age was 56 (11.3) years with 47 (39.5%) patients being female. Median tumor size was 5.10[4.00-6.45] cm. Median distance from the anal verge and to the top of internal anal sphincter were 5.00 [3.2-9.0] and 1.40 [0.00-5.50] cm, respectively. Median baseline CEA was 3.1 [1.7-8.3] ng/mL. Of the 88 (73.9%)patients that underwent surgery, 20 (22.7%) had pCR. Of the 31 (26.1%) patients that underwent WW, 24(77.4%) had sustained cCR after a year. CR rate was 36.9% (44 patients). Closer distance to anal verge andthe top of internal anal sphincter, absence of extramural vascular invasion (EMVI), low baseline CEA,complete/near complete response on endoscopy, and magnetic resonance tumor regression grade (mrTRG) 1-2 were predictors of CR in the univariate analysis. In the multivariate analysis, absence of EMVI andcomplete/near complete response in endoscopy were associated with CR. Compared to MRI, endoscopy wasmore sensitive in predicting CR (76.9% vs. 65.9%). Endoscopy, when combined with MRI, was more specific inpredicting CR compared to endoscopy alone (82.6% vs. 72.5%). During a median follow-up of 18.9 months,recurrence was observed in 24 (20%) patients. Disease-free and overall survival rates were 75% and 77.2%following 2 years of completion of TNT, respectively.
Conclusions:
In this cohort of locally advanced rectal cancer patients, TNT achieved 36.9% CR.Absence of EMVI was the only independent predictor of CR at the time of diagnosis. Following TNT,endoscopy is a better predictor of CR than MRI.

Introduction: Up to two thirds of patients presenting for surgery are malnourished pre-operatively, with higher incidence amongst oncology patients. Perioperative nutritional supplementation has been proposed to improve surgical outcomes, though its effect on quality of life (QoL) has not yet been studied.
Methods: A prospective, randomized controlled feasibility trial for perioperative nutrition among patients undergoing major abdominal surgery for gastrointestinal tract cancers was conducted. Patients in the intervention group received supplements for thirty days until the day of surgery. Patients completed two QoL questionnaires (EORTC QLQ LMC-21 and FACT-G) on the day of surgery, four, and twelve weeks postoperatively. Patients were compared between groups and within groups at baseline, week 4 and 12 using t-tests. Minimal important clinical differences (MICD) were considered as a 10-point difference from baseline.
Results: 71 patients were included in this analysis, including 36 in the intervention and 35 in control. Baseline demographics were balanced between groups except for different rates of pancreas cancer (36% intervention vs 9% control) and colorectal cancer (19% intervention vs 34% control) between groups. On the day of surgery, patients in the intervention group had higher QoL (77% vs 59%, p=0.01), role functioning (88% vs 72%, p=0.045), and cognitive functioning (90% vs 79%, p=0.047). Following surgery, however, there were no significant differences in QoL according to either QoL score between groups. The rates of MICD were similar between both intervention and control groups at week 4 and 12 post-operatively and all scores returned to baseline by week 12 in both groups.
Discussion: Perioperative nutrition leads to improved QoL in those preparing for surgery; however, improvements do not appear to persist following surgery.

Christopher Griffiths

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