Routine diversion following delayed IPAA construction does not reduce the incidence of pouch-related sepsis or failure in patients with ulcerative colitis.

AIM: The aim of this study was to compare modified 2-stage and 3-stage IPAA construction techniques to evaluate the effect of diverting loop ileostomy following completion proctectomy and IPAA for ulcerative colitis. In addition, our overall institutional experience was reviewed to describe long-term outcomes and changes in staging trends over time. METHODS: Our institutional database was searched to identify all cases of IPAA for ulcerative colitis between 1981 and 2018. Patient, pouch and outcome characteristics were abstracted. Primary study outcomes were the incidence of primary pouch failure and pouch-related sepsis. Failure was evaluated by Kaplan-Meier estimates of survival over time. The adjusted effect of pouch stage was evaluated using multivariable Cox and logistic regression models. Exploratory analysis evaluated the effect of stage on failure in the pouch related sepsis subgroup. RESULTS: A total of 2105 patients underwent primary IPAA over the study period. The 5, 10 and 20-year pouch survival probabilities were 95.2%, 92.7% and 86.6%. The incidence of pouch related sepsis was 12.3%. Adjusted analysis demonstrated no difference in pouch failure (HR = 0.64: 95% 0.39-1.07, p = 0.09) or post-operative sepsis (aOR = 0.79: 95% CI 0.53-1.17, p = 0.24) by stage of construction. Among patients experiencing pouch sepsis, there was no difference in Kaplan-Meier estimates of pouch survival by stage (p = 0.90). CONCLUSIONS: Pouch related sepsis and IPAA failure did not differ between modified 2-stage and 3-stage construction techniques. Among the sub-group of patients experiencing pouch related sepsis, there was no difference in failure between groups. The results suggest diverting ileostomy may be safely avoided following delayed pouch reconstruction in appropriately selected patients.

Autistic traits in youth with familial adenomatous polyposis: A Dutch-Canadian case-control study.

This study investigated the neurodevelopmental impact of pathogenic adenomatous polyposis coli (APC) gene variants in patients with familial adenomatous polyposis (FAP), a cancer predisposition syndrome. We hypothesized that certain pathogenic APC variants result in behavioral-cognitive challenges. We compared 66 FAP patients (cases) and 34 unaffected siblings (controls) to explore associations between APC variants and behavioral and cognitive challenges. Our findings indicate that FAP patients exhibited higher Social Responsiveness Scale (SRS) scores, suggesting a greater prevalence of autistic traits when compared to unaffected siblings (mean 53.8 vs. 47.4, Wilcoxon p = 0.018). The distribution of SRS scores in cases suggested a bimodal pattern, potentially linked to the location of the APC variant, with scores increasing from the 5' to 3' end of the gene (Pearson's r = 0.33, p = 0.022). While we observed a trend toward lower educational attainment in cases, this difference was not statistically significant. This study is the first to explore the connection between APC variant location and neurodevelopmental traits in FAP, expanding our understanding of the genotype-phenotype correlation. Our results emphasize the importance of clinical assessment for autistic traits in FAP patients, shedding light on the potential role of APC gene variants in these behavioral and cognitive challenges.

Transabdominal IPAA Revision: Does Indication Dictate Outcome?

BACKGROUND: Following IPAA failure, select patients are eligible for IPAA revision. Presently, there is limited evidence describing long-term revision outcomes and predictors of revision failure. This represents an important knowledge gap when selecting and counseling patients. OBJECTIVE: This study aimed to define long-term IPAA survival outcomes after transabdominal IPAA revision and identify preoperative clinical factors associated with revision failure. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at a tertiary referral center. PATIENTS: This study included all patients who underwent revisional IPAA surgery between 1982 and 2017 for pouch failure. INTERVENTION: Transabdominal IPAA revision was included. MAIN OUTCOME MEASURES: The primary outcome was pouch failure, defined as pouch excision or permanent pouch diversion, after IPAA revision. RESULTS: A total of 159 patients (64.2% women) were included with a median age of 36 years (interquartile range, 28.5-46.5) at revision. Eighty percent of patients had a primary diagnosis of ulcerative colitis. The most common indication for revision was leak/pelvic sepsis, representing 41% of the cohort, followed by pouch-vaginal fistula (22.2%), mechanical factors (20.4%), and poor pouch function (14.6%). During the study period, 56 patients (35.2%) experienced pouch failure. The 3-year pouch survival probability was 82.3% (95% CI, 75.5%-87.5%), 5-year pouch survival probability was 77.2% (95% CI, 69.8%-83.0%), and 10-year pouch survival probability was 70.6% (95% CI, 62.6%-77.2%). Compared to mechanical factors, pouch failure was significantly associated with pelvic sepsis (HR, 4.25; 95% CI, 1.50-12.0) and pouch-vaginal fistula (HR, 4.37; 95% CI, 1.47-12.99). No significant association was found between revision failure and previous revision, redo ileoanal anastomosis, or new pouch construction. LIMITATIONS: This study is limited by its retrospective design. CONCLUSIONS: Revisional IPAA can be undertaken with favorable long-term outcomes at high-volume centers. Consideration should be given to indication for revision when counseling patients regarding the risk of failure. Further research on risk stratifying patients before revision is required. See Video Abstract at http://links.lww.com/DCR/B966 . REVISIN DE LA ANASTOMOSIS ANAL DE LA BOLSA ILEAL TRANSABDOMINAL LA INDICACIN DICTA EL RESULTADO: ANTECEDENTES:Después de la falla en la anastomosis del reservorio ileoanal, los pacientes seleccionados son elegibles para la revisión de la anastomosis del reservorio ileoanal. Actualmente, hay evidencias limitadas que describen los resultados de la revisión a largo plazo y los predictores del fracaso de la revisión. Esto representa un importante vacío de investigación a la hora de seleccionar y asesorar a los pacientes.OBJETIVO:Definir los resultados de supervivencia a largo plazo de la IPAA después de la revisión de la anastomosis del reservorio ileoanal transabdominal e identificar los factores clínicos preoperatorios asociados con el fracaso de la revisión.DISEÑO:Este fue un estudio de cohorte retrospectivo.ENTORNO CLINICO:Este estudio se realizó en un centro de referencia terciario.PARTICIPANTES:Todos los pacientes que se sometieron a una cirugía de revisión de la anastomosis ileoanal del reservorio entre 1982 y 2017, por falla del reservorio.INTERVENCIÓN:Revisión de la anastomosis de reservorio ileoanal transabdominal.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario es el fracaso del reservorio, definido como escisión del reservorio o derivación permanente del reservorio, después de la revisión de la anastomosis del reservorio ileoanal.RESULTADOS:Se incluyeron un total de 159 pacientes (64,2% mujeres) con una mediana de edad a la revisión de 36 años (RIC: 28,5-46,5). El ochenta por ciento tenía un diagnóstico primario de colitis ulcerosa. La indicación más común para la revisión fue la fuga/sepsis pélvica, que representó el 41 % de la cohorte, seguida de la fístula vaginal del reservorio (22,2 %), factores mecánicos (20,4 %) y mala función del reservorio 14,6 %. Durante el período de estudio, 56 pacientes (35,2 %) experimentaron fallas en la bolsa. Las probabilidades de supervivencia de la bolsa a los 3, 5 y 10 años fueron del 82,3% (IC del 95%: 75,5%-87,5%), del 77,2% (IC del 95%: 69,8%-83,0%) y del 70,6% (IC del 95%: 62,6%- 77,2%), respectivamente. En comparación con los factores mecánicos, la falla de la bolsa se asoció significativamente con sepsis pélvica (HR = 4,25, IC del 95 %: 1,50 a 12,0) y fístula vaginal de la bolsa (HR = 4,37, IC del 95 %: 1,47 a 12,99). No hubo una asociación significativa entre el fracaso de la revisión y la revisión previa, el rehacer la anastomosis ileoanal o la construcción de una nueva bolsa.LIMITACIONES:El estudio está limitado por su diseño retrospectivo.CONCLUSIONES:La revisión de la anastomosis del reservorio ileoanal se puede realizar con resultados favorables a largo plazo en centros de alto volumen. Se debe considerar la indicación de revisión al asesorar a los pacientes sobre el riesgo de fracaso. Se requiere investigación adicional sobre la estratificación del riesgo de los pacientes antes de la revisión. Consulte Video Resumen en http://links.lww.com/DCR/B966 . (Traducción - Dr. Fidel Ruiz Healy ).

Short-term and Long-term Outcomes Following Pelvic Pouch Excision: The Mount Sinai Hospital Experience.

BACKGROUND: Few studies have reported surgical outcomes following pouch excision and fewer have described the long-term sequelae. Given the debate regarding optimal surgical management following pouch failure, an accurate estimation of the morbidity associated with this procedure addresses a critical knowledge gap. OBJECTIVE: The objective of this study was to review our institutional experience with pouch excision with a focus on indications, short-term outcomes, and long-term reintervention rates. DESIGN: This was a retrospective cohort study. SETTING: This study was conducted at Mount Sinai Hospital, Toronto, Ontario Canada. PARTICIPANTS: Adult patients registered in the prospectively maintained IBD database with a diagnosis of pelvic pouch failure between 1991 and 2018 were selected. INTERVENTION: The patients had undergone pelvic pouch excision was measured. MAIN OUTCOMES AND MEASURES: Indications for excision, incidence of short-term and long-term complications, and long-term surgical reintervention were the primary outcomes. In addition, multivariable logistic regression models were fitted to identify predictors of chronic perineal wound complications and the effect of preoperative diversion. The positive predictive value of a clinical suspicion of Crohn's disease of the pouch was also evaluated. RESULTS: One hundred forty cases were identified. Fifty-nine percent of patients experienced short-term complications and 49.3% experienced delayed morbidity. Overall, one-third of patients required long-term reoperation related to perineal wound, stoma, and hernia complications. On multivariable regression, immunosuppression was associated with increased odds of perineal wound complications, and preoperative diversion was not associated with perineal wound healing. Crohn's disease was suspected in 24 patients preoperatively but confirmed on histopathology in only 6 patients. LIMITATIONS: This is a retrospective chart review of a single institution's experience, whereby complication rates may be underestimates of the true event rates. CONCLUSIONS: Pouch excision is associated with high postoperative morbidity and long-term reintervention due to nonhealing perineal wounds, stoma complications, and hernias. Further study is required to clarify risk reduction strategies to limit perineal wound complications and the appropriate selection of patients for diversion alone vs pouch excision in IPAA failure. See Video Abstract at http://links.lww.com/DCR/B348. RESULTADOS A CORTO Y LARGO PLAZO DESPUÉS DE LA EXTIRPACIÓN DE LA BOLSA PéLVICA: LA EXPERIENCIA DEL HOSPITAL MOUNT SINAÍ: Pocos estudios han informado resultados quirúrgicos después de la escisión de bolsa pélvica (reservorio ileoanal) y menos han descrito las secuelas a largo plazo. Dado el debate sobre el manejo quirúrgico óptimo después de la falla de la bolsa, una estimación precisa de la morbilidad asociada con este procedimiento aborda una brecha crítica de conocimiento.El objetivo de este estudio fue revisar nuestra experiencia institucional con la extirpación de la bolsa con un enfoque en las indicaciones, los resultados a corto plazo y las tasas de reintervención a largo plazo.Estudio de cohorte retrospectivo.Hospital Mt Sinaí, Toronto, Ontario, Canadá.Pacientes adultos registrados en la base de datos de EII mantenida prospectivamente con un diagnóstico de falla de la bolsa pélvica entre 1991 y 2018.Escisión de bolsa pélvica.Las indicaciones para la escisión, la incidencia de complicaciones a corto y largo plazo y la reintervención quirúrgica a largo plazo fueron los resultados primarios valorados. Además, se ajustaron modelos de regresión logística multivariable para identificar predictores de complicaciones de la herida perineal crónica y el efecto de la derivación preoperatoria. También se evaluó el valor predictivo positivo de una sospecha clínica de enfermedad de Crohn de la bolsa.Se identificaron 140 casos. El 59% de los pacientes desarrollaron complicaciones a corto plazo y el 49,3% con morbilidad tardía. En general, 1/3 de los pacientes requirieron una reoperación a largo plazo relacionada con complicaciones de herida perineal, estoma y hernia. En la regresión multivariable, la inmunosupresión se asoció con mayores probabilidades de complicaciones de la herida perineal y la derivación preoperatoria no se asoció con la cicatrización de la herida perineal. La enfermedad de Crohn se sospechó en 24 pacientes antes de la operación, pero se confirmó por histopatología en solo 6 pacientes.Revisión retrospectiva del cuadro de la experiencia de una sola institución por la cual las tasas de complicaciones pueden ser subestimadas de las tasas de eventos reales.La escisión de la bolsa se asocia con una alta morbilidad postoperatoria y una reintervención a largo plazo debido a complicaciones de heridas perineales, complicaciones del estoma y hernias. Se requieren más estudios para aclarar las estrategias de reducción de riesgos para limitar las complicaciones de la herida perineal y la selección adecuada de pacientes para la derivación sola versus la escisión de la bolsa en caso de falla de reservorio ileoanal. Consulte Video Resumen en http://links.lww.com/DCR/B348.

The impact of health anxiety on perceptions of personal and children's health in parents with Lynch syndrome.

This study examined the differences in perceptions of one's health and one's child's health between parents with Lynch syndrome (LS) characterized with high versus low health anxiety. Twenty-one parents completed semistructured telephone interviews about their perceptions of their own health and the health of their children. Qualitative content analysis using a template coding approach examined the differences between parents with high and low health anxiety. Findings revealed that the most prevalent difference emerged on perceptions of personal health, showing individuals with high health anxiety reported more extreme worries, were more hypervigilant about physical symptoms, experienced the emotional and psychological consequences of LS as more negative and severe, and engaged in more dysfunctional coping strategies than those with low health anxiety. Unexpectedly, with regards to perceptions of their children, parents in the high and low health anxiety groups exhibited similar worries. However, high health anxiety parents reported using dysfunctional coping about their children's health more frequently than those with low health anxiety. The findings suggest that health anxiety is of clinical significance for individuals with LS. Accurately identifying and treating health anxiety among this population may be one avenue to reduce the distress experienced by LS carriers.

Patient-physician relationships, health self-efficacy, and gynecologic cancer screening among women with Lynch syndrome.

BACKGROUND: Lynch syndrome, a hereditary cancer syndrome, predisposes women to colorectal, endometrial, and ovarian cancer. Current guidelines recommend that women with Lynch syndrome undergo risk-reducing gynecological surgery to reduce their chances of developing endometrial or ovarian cancer. Little is known about how women with Lynch syndrome perceive gynecological cancer screening, or the psychosocial factors associated with screening attitudes and behaviour. METHODS: This study used a cross-sectional, quantitative design. Using self-report questionnaire data from a sample of women with Lynch syndrome (N = 50) who had not undergone risk-reducing surgery, the current study sought to: 1) describe the gynecological cancer screening behaviours of women with Lynch syndrome, as well participant-reported sources of information about Lynch syndrome; 2) examine the extent to which women believe gynecological cancer screening is effective and provides them with reassurance and; 3) assess to what extent relationships with one's family physician were associated with gynecological cancer screening, perceptions about screening, and health self-efficacy. Data were analyzed using descriptive statistics and Spearman rank-ordered correlations. RESULTS: Data analyses showed that transvaginal ultrasound was the most common screening behaviour (57%) followed by pelvic ultrasound (47%). Only 22% of participants underwent endometrial biopsy. Patient-physician relationships were related to greater health self-efficacy to manage Lynch syndrome and greater perceived effectiveness of gynecological screening. However, health self-efficacy and better patient-physician relationships were not associated with increased engagement in gynecological cancer screening. CONCLUSIONS: The data suggest that feeling efficacious about managing one's Lynch syndrome and screening is related to positive interactions and communication with one's family physician. While this is encouraging, future research should examine educating both family physicians and patients about current guidelines for Lynch syndrome gynecological screening recommendations.

Symptom Severity and Quality of Life Among Long-term Colorectal Cancer Survivors Compared With Matched Control Subjects: A Population-Based Study.

BACKGROUND: Data are lacking regarding physical functioning, psychological well-being, and quality of life among colorectal cancer survivors >10 years postdiagnosis. OBJECTIVE: The purpose of this study was to examine self-reported physical functioning, quality of life, and psychological well-being in long-term colorectal cancer survivors compared with age- and sex-matched unaffected control subjects. DESIGN: Participants completed a cross-sectional survey. SETTINGS: The colorectal cancer survivors and unaffected control subjects were recruited from the Ontario Familial Colorectal Cancer Registry. PATIENTS: A population-based sample of colorectal cancer survivors (N = 296) and their age- and sex-matched unaffected control subjects (N = 255) were included. Survivors were, on average, 15 years postdiagnosis. MAIN OUTCOME MEASURES: Quality of life was measured with the Functional Assessment of Cancer Therapy-General scale, bowel dysfunction with the Memorial Sloan-Kettering Cancer Center scale, urinary dysfunction with the International Consultation on Incontinence Questionnaire-Short Form, fatigue with the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and depression with the Center for Epidemiologic Studies-Depression scale. RESULTS: In linear mixed-model analyses adjusting for income, education, race, and comorbid medical conditions, survivors reported good emotional, functional, physical, and overall quality of life, comparable to control subjects. Fatigue and urinary functioning did not differ significantly between survivors and control subjects. Survivors reported significantly higher social quality of life and lower depression compared with unaffected control subjects. The only area where survivors reported significantly worse deficits was in bowel dysfunction, but the magnitude of differences was relatively small. LIMITATIONS: Generalizability is limited by moderately low participation rates. Findings are likely biased toward healthy participants. No baseline assessment was available to examine change in outcomes over time. CONCLUSIONS: Long-term colorectal cancer survivors appear to have comparable quality of life and, in some areas, better well-being than their unaffected peers. Bowel dysfunction may continue to be an ongoing issue even 15 years after colorectal cancer diagnosis. Overall quality of life can be expected to be good in this group of older survivors. See Video Abstract at http://links.lww.com/DCR/A476.

Rates and Predictors of Endoscopic and Clinical Recurrence After Primary Ileocolic Resection for Crohn's Disease.

BACKGROUND AND AIMS: The utility of postoperative medical prophylaxis (POMP) and the treatment of mild endoscopic recurrence remain controversial. METHODS: This study is a retrospective review of patients undergoing a primary ileocolic resection for CD at a single academic center. Endoscopic recurrence (ER) was defined using the Rutgeerts score (RS), and clinical recurrence (CR) was defined as symptoms of CD with endoscopic or radiologic evidence of neo-terminal ileal disease. RESULTS: There were 171 patients who met inclusion criteria. The cumulative probability of ER (RS ≥ i-1) at 1, 2, and 5 years was 29, 51, and 77 %, respectively. The only independent predictors of ER were the absence of POMP (HR 1.50; P = 0.03) and penetrating disease behavior (HR 1.50; P = 0.05). The cumulative probability of CR at 1, 2, and 5 years was 8, 13, and 27 %, respectively. There was a higher rate of clinical recurrence in patients with RS-2 compared to RS-1 on the initial postoperative endoscopy (HR 2.50; P = 0.02). In 11 patients not exposed to POMP with i-1 on initial endoscopy, only 2 patients (18 %) progressed endoscopically during the study period while 5 patients (45 %) regressed to i-0 on subsequent endoscopy without treatment. CONCLUSIONS: Postoperative medical prophylaxis decreased the likelihood of ER while certain phenotypes of CD appear to increase the risk of developing ER and CR. There may be a role for watchful waiting in patients with mild endoscopic recurrence on the initial postoperative endoscopy.

Genetic testing for Lynch syndrome in the province of Ontario.

BACKGROUND: In November 2001, genetic testing for Lynch syndrome (LS) was introduced by the Ministry of Health and Long-Term Care (MOH) in Ontario for individuals at high risk for LS cancers according to either tumor immunohistochemistry staining or their family history. This article describes the outcomes of the program and makes recommendations for improving it and informing other public health care programs. METHODS: Subjects were referred for molecular testing of the mismatch repair (MMR) genes MutL homolog 1, MutS homolog 2, and MutS homolog 6 if they met 1 of 7 MOH criteria. Testing was conducted from January 2001 to March 2015 at the Molecular Diagnostic Laboratory of Mount Sinai Hospital in Toronto. RESULTS: A total of 1452 subjects were tested. Of the 662 subjects referred for testing because their tumor was immunodeficient for 1 or more of the MMR genes, 251 (37.9%) carried a germline mutation. In addition, 597 subjects were tested for a known family mutation, and 298 (49.9%) were positive; 189 of these 298 subjects (63.4%) were affected with cancer at the time of testing. An additional 193 subjects were referred because of a family history of LS, and 34 of these (17.6%) had a mutation identified. CONCLUSIONS: These results indicate that the provincial criteria are useful in identifying LS carriers after an MMR-deficient tumor is identified. Placing greater emphasis on testing unaffected relatives in families with a known mutation may identify more unaffected carriers and facilitate primary prevention in those individuals. Cancer 2016;122:1672-9. © 2016 American Cancer Society.

Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium.

OBJECTIVES: Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data. METHODS: The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates. RESULTS: Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73%) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8-25), and 11 of 18 (61%) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9-25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11-33). Two CRC and two SBC were detected during surveillance within 6-11 months and 9-16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed. CONCLUSIONS: The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3-5 and 8 years, respectively.

Is there a role for prophylactic colectomy in Lynch syndrome patients with inflammatory bowel disease?

PURPOSE: Lynch syndrome and chronic inflammatory bowel disease are two important risk factors for colorectal cancer. It is unclear whether Lynch syndrome patients with inflammatory bowel disease are at sufficiently increased risk for colorectal cancer to warrant prophylactic colectomy. This study aims to identify all cases of Lynch syndrome and concurrent inflammatory bowel disease in a large familial gastrointestinal cancer registry, define incidence of colorectal cancer, and characterize mismatch repair protein gene mutation status and inflammatory bowel disease-associated colorectal cancer risk factors. METHODS: We retrospectively identified and collected clinical data for all cases with confirmed diagnoses of Lynch syndrome and inflammatory bowel disease in the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital in Toronto, Canada. RESULTS: Twelve cases of confirmed Lynch syndrome, and concurrent inflammatory bowel disease were identified. Four cases developed colorectal cancer. An additional five cases had colectomy; one was performed for severe colitis, and four were performed for low-grade dysplasia. None of these surgical specimens contained malignancy or high-grade dysplasia. CONCLUSIONS: The presentation of Lynch syndrome with inflammatory bowel disease is uncommon and not well described in the literature. This small but important series of twelve cases is the largest reported to date. In this series, patients with Lynch syndrome and concurrent inflammatory bowel disease do not appear to have sufficiently increased risk for colorectal cancer to recommend prophylactic surgery. Therefore, the decision to surgery should continue to be guided by surgical indications for each disease. Further evaluation of this important area will require multi-institutional input.

Physician trust moderates the relationship between intolerance of uncertainty and cancer worry interference among women with Lynch syndrome.

This study investigated the extent to which intolerance of uncertainty was associated with cancer worry interference, anxiety and depression among women with Lynch syndrome (LS), and whether having greater trust in one's physician moderated those relationships. Women with confirmed LS (N = 128) were recruited from a high-risk of cancer registry and completed a one-time self-report questionnaire. Women who reported greater intolerance of uncertainty and more trust in their physician reported less cancer worry interference compared to women who had greater intolerance of uncertainty and less trust in their physician, who reported the highest worry interference, b = -1.39, t(99) = -2.27, p = .03. No moderation effect of trust in physician was found for anxiety or depression. Trust in one's physician buffered the impact of high intolerance of uncertainty on cancer worry interference, underscoring the need for supportive provider-patient relationships, particularly for LS patients.

Progression and Management of Duodenal Neoplasia in Familial Adenomatous Polyposis: A Cohort Study.

OBJECTIVE: To describe the natural history and outcomes of surveillance of duodenal neoplasia in familial adenomatous polyposis (FAP). BACKGROUND: Duodenal cancer is the most common cause of death in FAP. METHODS: Cohort study of patients prospectively enrolled in an upper endoscopic surveillance protocol from 1982 to 2012. The duodenum was assessed by side-viewing endoscopy and classified as stage 1 to 5 disease. Endoscopic and/or operative interventions were performed according to stage. RESULTS: There were 218 patients in the protocol (98 with advanced stage). They had a median of 9 endoscopies (range: 2-25) over a median of 11 years (range: 1-26). Median age at diagnosis of stage 3 disease (adenoma: 2.1-10 mm) was 41 years and stage 4 disease (adenoma >10 mm) was 45 years. Median time from first esophagogastroduodenoscopy to stage 4 disease was 22.4 years. The risk of stage 4 disease was 34.3% [95% confidence interval (CI) 23.8-43.4] at 15 years. In multivariate analysis, sex, type of colorectal surgery, years since colorectal surgery, and stage were significantly associated with risk of progression to stage 4 disease. Five of 218 (2.3%) patients developed duodenal cancer at median age of 58 years (range: 51-65). The risk of developing duodenal cancer was 2.1% (95% CI: 0-5.2) at 15 years. CONCLUSIONS: Patients with advanced duodenal polyposis progress in the severity of disease (size and degree of dysplasia); however, the rate of progression to carcinoma is slow. Aggressive endoscopic and surgical intervention, especially in the presence of large polyps and high-grade dysplasia, appears to be effective in preventing cancer deaths in FAP.

DNA Mismatch Repair Status Predicts Need for Future Colorectal Surgery for Metachronous Neoplasms in Young Individuals Undergoing Colorectal Cancer Resection.

BACKGROUND: The treatment of colorectal cancer in young patients involves both management of the incident cancer and consideration of the possibility of Lynch syndrome and the development of metachronous colorectal cancers. OBJECTIVE: This study aims to assess the prognostic role of DNA mismatch repair deficiency and extended colorectal resection for metachronous colorectal neoplasia risk in young patients with colorectal cancer. DESIGN, SETTING, AND PATIENTS: This is a retrospective review of 285 patients identified in our GI cancer registry with colorectal cancer diagnosed at 35 years or younger in the absence of polyposis. MAIN OUTCOME MEASURES: Using univariate and multivariate analysis, we assessed the prognostic role of mismatch repair deficiency and standard clinicopathologic characteristics, including the extent of resection, on the rate of developing metachronous colorectal neoplasia requiring resection. RESULTS: Mismatch repair deficiency was identified in biospecimens from 44% of patients and was significantly associated with an increased risk for metachronous colorectal neoplasia requiring resection (10-year cumulative risk, 13.5% ± 4.2%) compared with 56% of patients with mismatch repair-intact colorectal cancer (10-year cumulative risk, 5.8% ± 3.3%; p = 0.011). In multivariate analysis, mismatch repair deficiency was associated with a HR of 3.65 (95% CI, 1.44-9.21; p = 0.006) for metachronous colorectal neoplasia, whereas extended resection with ileorectal or ileosigmoid anastomosis significantly decreased the risk of metachronous colorectal neoplasia (HR, 0.21; 95% CI, 0.05-0.90; p = 0.036). LIMITATIONS: This study had a retrospective design, and, therefore, recommendations for colorectal cancer surgery and screening were not fully standardized. Quality of life after colorectal cancer surgery was not assessed. CONCLUSIONS: Young patients with colorectal cancer with molecular hallmarks of Lynch syndrome were at significantly higher risk for the development of subsequent colorectal neoplasia. This risk was significantly reduced in those who underwent extended resection compared with segmental resection.

Severity of inflammation as a risk factor for ileo-anal anastomotic leak after a pouch procedure in ulcerative colitis.

PURPOSE: The pelvic pouch procedure (PPP) carries significant post-operative complication risks including a 4-14 % risk of ileo-anal anastomotic (IAA) leak [1-4]. The aim of this study is to evaluate the severity of disease at the distal resection margin as an independent risk factor for an IAA leak following the PPP for patients with ulcerative colitis (UC). METHODS: A retrospective matched case-control study was undertaken. The distal margin of each subject's specimen was reviewed by a blinded pathologist and the degree of inflammation was scored using a modified histological activity index (mHAI)--a 0 to 5 graded scale with HAI of 5 representing ulcerations >25 % the depth of bowel wall. RESULTS: Forty-nine patients with perioperative IAA leaks (mean 11 days ±0.92) were identified and matched for gender, age and year of surgery. The case cohort had 33 males (67 %) of mean age at time of surgery of 36.3 years (±1.42). The severity of distal inflammation did not increase the risk of IAA leak. The presence of a diverting ileostomy was associated with a decreased incidence of an IAA leak (p = 0.01). CONCLUSION: Studies with greater power will be required to evaluate the association (if any) between histological severity of UC at the distal margin of a PPP procedure and IAA leak rate. This risk factor could influence preoperative management and post-operative outcome in patients requiring the PPP.

Ileal pouch symptoms do not correlate with inflammation of the pouch.

BACKGROUND & AIMS: Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA). However, symptoms are not specific. The Pouchitis Disease Activity Index (PDAI) and the Pouchitis Activity Score (PAS) have been used to diagnose pouchitis. We evaluated the correlation between the clinical components of these scores and endoscopic and histologic findings. METHODS: We performed a cross-sectional study, analyzing data from 278 patients from Mount Sinai Hospital (Toronto, Canada) who had an IPAA. Patients underwent pouchoscopy with a biopsy, and data were collected on patients' clinical status. The PDAI and PAS were calculated for each subject. The Spearman rank correlation (ρ) statistical test was used to evaluate correlations between the PDAI scores and PAS, and between total scores and subscores. RESULTS: The total PDAI scores and PAS scores were correlated; the clinical components of each correlated with the total score (ρ = 0.59 and ρ = 0.71, respectively). However, we observed a low level of correlation between clinical and endoscopic or histologic subscores, with ρ of 0.20 and 0.10, respectively, by PDAI, and ρ of 0.19 and 0.04, respectively, by PAS. CONCLUSIONS: There is a low level of correlation between clinical and endoscopic and histologic subscores of patients with IPAA; clinical symptoms therefore might not reflect objective evidence of inflammation. These findings, along with evidence of correlation between total scores and clinical symptoms, indicate that these indices do not accurately identify patients with pouch inflammation. Further research is required to understand additional factors that contribute to clinical symptoms in the absence of objective signs of pouch inflammation.

Proctocolectomy for colorectal cancer--is the ileal pouch anal anastomosis a safe alternative to permanent ileostomy?

PURPOSE: Ileal pouch anal anastomosis (IPAA) is the procedure of choice in patients requiring surgery for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). There are few data on reconstruction with the IPAA in patients with colorectal cancer (CRC). This study assessed the outcomes of the IPAA compared to proctocolectomy and permanent ileostomy (PI) on these patients. METHODS: Between 1983 and 2013, over 2800 patients with CRC have been treated at the Mount Sinai Hospital (MSH). Demographic, surgical, pathological, and outcome data for all patients have been maintained in a database-73 patients were treated for CRC with proctocolectomy: 39 patients with IPAA and 34 patients with PI. Clinical features, pathologic findings, and survival outcomes were compared between these groups. RESULTS: Each group was similar with respect to gender, stage, and histologic grade. Patients undergoing IPAA were significantly younger. The diagnosis leading to proctocolectomy was more commonly UC or FAP in patients treated with IPAA (39/39 vs. 23/34, p = 0.001). Rectal cancer subgroups were similar in age, sex, TNM stage, T-stage, height of tumor, and histologic grade. There was no significant difference in overall or disease free survival between groups for colon or rectal primaries. Analysis using the Cochran-Armitage trend test suggests that utilization of IPAA has increased over time (p = 0.002). CONCLUSIONS: The IPAA is a viable and safe option to select for patients who would otherwise require PI. Increased experience and improved outcomes following IPAA has led to its more liberal use in selected patients.

Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease.

OBJECTIVE: Previous investigations of short-term outcomes after preoperative exposure to biological therapy in inflammatory bowel disease (IBD) were conflicting. The authors aimed to assess postoperative outcomes in patients who underwent abdominal surgery with recent exposure to anti-tumour necrosis factor therapy. DESIGN: A retrospective case-control study with detailed matching was performed for subjects with IBD with and without exposure to biologics within 180 days of abdominal surgery. Postoperative outcomes were compared between the groups. RESULTS: 473 procedures were reviewed consisting of 195 patients with exposure to biologics and 278 matched controls. There were no significant differences in most postoperative outcomes such as: length of stay, fever (≥ 38.5°C), urinary tract infection, pneumonia, bacteraemia, readmission, reoperations and mortality. On univariate analysis, procedures on biologics had more wound infections compared with controls (19% vs 11%; p=0.008), but this was not significant in multivariate analysis. Concomitant therapy with biologics and thiopurines was associated with increased frequencies of urinary tract infections (p=0.0007) and wound infections (p=0.0045). Operations performed ≤ 14 days from last biologic dose had similar rates of infections and other outcomes when compared with those performed within 15-30 days or 31-180 days. Patients with detectable preoperative infliximab levels had similar rates of wound infection compared with those with undetectable levels (3/10 vs 0/9; p=0.21). CONCLUSION: Preoperative treatment with TNF-α antagonists in patients with IBD is not associated with most early postoperative complications. A shorter time interval from last biological dose is not associated with increased postoperative complications. In most cases, surgery should not be delayed, and appropriate biological therapy may be continued perioperatively.

The NOD2insC polymorphism is associated with worse outcome following ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: Inflammatory complications after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) are common. OBJECTIVE: To investigate whether genetic factors are associated with adverse pouch outcomes such as chronic pouchitis (CP) and a Crohn's disease-like (CDL) phenotype. DESIGN: 866 patients were recruited from three centres in North America: Mount Sinai Hospital (Toronto, Ontario, Canada), the Cleveland Clinic (Cleveland, Ohio, USA) and Penn State Milton S Hershey Medical Center (Hershey, Pennsylvania, USA). DNA and clinical and demographic information were collected. Subjects were classified into post-surgical outcome groups: no chronic pouchitis (NCP), CP and CDL phenotype. RESULTS: Clinical and genetic data were available on 714 individuals. 487 (68.2%) were classified as NCP, 118 (16.5%) CP and 109 (15.3%) CDL. The presence of arthritis or arthropathy (p=0.02), primary sclerosing cholangitis (p=0.009) and duration of time from ileostomy closure to recruitment (p=0.001) were significantly associated with outcome. The NOD2insC (rs2066847) risk variant was the single nucleotide polymorphism (SNP) most significantly associated with pouch outcome (p=7.4×10(-5)). Specifically, it was associated with both CP and CDL in comparison with NCP (OR=3.2 and 4.3, respectively). Additionally, SNPs in NOX3 (rs6557421, rs12661812), DAGLB (rs836518) and NCF4 (rs8137602) were shown to be associated with pouch outcome with slightly weaker effects. A multivariable risk model combining previously identified clinical (smoking status, family history of inflammatory bowel disease), serological (anti-Saccharomyces cerevisiae antibody IgG, perinuclear antineutrophil cytoplasmic antibody and anti-CBir1) and genetic markers was constructed and resulted in an OR of 2.72 (p=8.89×10(-7)) for NCP versus CP/CDL and 3.22 (p=4.11×10(-8)) for NCP versus CDL, respectively. CONCLUSION: Genetic polymorphisms, in particular, the NOD2insC risk allele, are associated with chronic inflammatory pouch outcomes among patients with UC and IPAA.

Evaluating colonoscopy screening intervals in patients with Lynch syndrome from a large Canadian registry.

BACKGROUND: Lynch syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20 and 25 years. Recent studies have questioned the benefits of these short screening intervals in preventing colorectal cancer (CRC). Our goal is to determine how colonoscopy screening intervals impact CRC in patients with LS. METHODS: We analyzed the demographics, screening practices, and outcomes of patients with LS identified through the clinic based Familial Gastrointestinal Cancer Registry at the Zane Cohen Centre, Sinai Health System, Toronto, Canada. RESULTS: A total of 429 patients with LS were identified with median follow-up of 9.2 years; 44 developed CRC. We found a positive trend between shorter screening intervals and the number of adenomas detected during colonoscopy. Any new adenoma detected at screening decreased 10-year CRC incidence by 11.3%. For MLH1 carriers, a screening interval of 1-2 years vs 2-3 years led to a 20-year cumulative CRC risk reduction of 28% and 14% in females and males, respectively. For MSH2 carriers, this risk reduction was 29% and 17%, respectively, and for male MSH6 carriers 18%. Individuals without any adenomas detected (53.4% of LS carriers) had an increased 20-year CRC risk of 25.7% and 57.2% for women and men, respectively, compared with those diagnosed with adenomas at screening. CONCLUSIONS: The recommended colonoscopy screening interval of 1-2 years is efficient at detecting adenomas and reducing CRC risk. The observation that 53.4% of LS patients never had an adenoma warrants further investigation about a possible adenoma-free pathway.