Assessing Guidelines on the Need for Colonoscopy After Initial Flexible Sigmoidoscopy in Young Patients With Outlet-Type Rectal Bleeding.

BACKGROUND: Although young-age-of-onset colorectal cancer is increasing in incidence, lack of screening leads to symptomatic presentation, often with rectal bleeding. Because most cancers in patients younger than 50 years are left-sided, flexible sigmoidoscopy is a reasonable way of investigating bleeding in these patients. OBJECTIVE: To predict which patients undergoing flexible sigmoidoscopy for outlet-type rectal bleeding need a full colonoscopy. DESIGN: Findings at colonoscopy were compared with published indications for colonoscopy after flexible sigmoidoscopy, which were as follows: 1) any number of advanced adenomas defined as a tubular adenoma of >9 mm diameter, a tubulovillous or villous adenoma of any size, or any adenoma with high-grade dysplasia; 2) 3 or more tubular adenomas of any size or histology; 3) any sessile serrated lesion; and 4) 20 or more hyperplastic polyps. SETTING: Charity Hospital with volunteer specialists. PATIENTS: Patients were included if they were younger than 57 years, had outlet-type rectal bleeding, and underwent flexible sigmoidoscopy at least to the descending colon followed by colonoscopy with biopsy of all resected lesions. INTERVENTIONS: Flexible sigmoidoscopy and colonoscopy with excision of all removable lesions. MAIN OUTCOME MEASURES: Findings at colonoscopy. RESULTS: There were 66 patients who had a colonoscopy between 5 and 811 days after sigmoidoscopy and also had complete data. There were 43 men and 23 women with a mean age of 39.5 years. Analysis of flexible sigmoidoscopy criteria for finding proximal high-risk lesions on colonoscopy showed a sensitivity of 76.9%, a specificity of 67.9%, a positive predictive value of 37%, a negative predictive value of 92.3%, and an accuracy of 69.7%. LIMITATIONS: A large number of exclusions for inadequate colonoscopy or inadequate data resulted in a reduced patient number in the study. CONCLUSIONS: Our criteria for follow-up colonoscopy based on the findings at initial flexible sigmoidoscopy in young patients with outlet-type rectal bleeding are reliable enough to be used in routine clinical practice, provided this is audited. See Video Abstract. GUA DE EVALUACIN PARA LA NECESIDAD DE COLONOSCOPIA DESPUS DE UNA SIGMOIDOSCOPIA FLEXIBLE INICIAL EN PACIENTES JVENES CON RECTORRAGIA: ANTECEDENTES:Si bien la edad de aparición temprana del cáncer colorrectal está aumentando en incidencia, la falta de pruebas de detección conduce a una presentación sintomática, a menudo con sangrado rectal. Debido a que la mayoría de los cánceres en pacientes menores de 50 años son del lado izquierdo, la sigmoidoscopia flexible es una forma razonable de investigar el sangrado en estos pacientes.OBJETIVO:Predecir qué pacientes sometidos a sigmoidoscopia flexible por rectorragia necesitan una colonoscopia completa.DISEÑO:Los resultados de la colonoscopia se compararon con las indicaciones publicadas para la colonoscopia después de una sigmoidoscopia flexible. Estos fueron: 1. Cualquier número de adenomas avanzados, definidos como un adenoma tubular > 9 mm, un adenoma tubulovelloso o velloso de cualquier tamaño, o cualquier adenoma con displasia de alto grado. 2. Tres o más adenomas tubulares de cualquier tamaño o histología. 3. Cualquier lesión serrada sésil. 4. Veinte o más pólipos hiperplásicos.ENTORNO CLINICO:Hospital de Caridad con especialistas voluntarios.PACIENTES:Menores de 57 años, con rectorragia, sometidos a sigmoidoscopia flexible al menos hasta el colon descendente, seguida de colonoscopia con biopsia de todas las lesiones resecadas.INTERVENCIONES:sigmoidoscopia flexible y colonoscopia con escisión de todas las lesiones removibles.PRINCIPALES MEDIDAS DE VALORACIÓN:Hallazgos en la colonoscopia.RESULTADOS:66 casos a los que se les realizó una colonoscopia entre 5 y 811 días después de la sigmoidoscopia, que también tenían datos completos. 43 hombres y 23 mujeres con una edad media de 39,5 años. El análisis de los criterios de sigmoidoscopia flexible para encontrar lesiones proximales de alto riesgo en la colonoscopia mostró una sensibilidad del 76,9 %, una especificidad del 67,9 %, un valor predictivo positivo del 37 %, un valor predictivo negativo del 92,3 % y una precisión del 69,7 %.LIMITACIONES:Gran número de exclusiones por colonoscopia inadecuada o datos inadecuados que causan un número reducido de pacientes en el estudio.CONCLUSIÓN:Nuestros criterios para la colonoscopia de seguimiento basados en los hallazgos de la sigmoidoscopia flexible inicial en pacientes jóvenes con rectorragia son lo suficientemente confiables para ser utilizados en la práctica clínica habitual, siempre que se audite. (Traducción- Dr. Ingrid Melo ).

A Different Way to Think About Syndromes of Hereditary Colorectal Cancer.

BACKGROUND: Hereditary colorectal cancer is an increasingly complex field in which the commoner syndromes are being augmented by rarer genetic presentations contributing to familial polyposis and colorectal cancer. Coming to grips with the complexity is difficult because of the phenotypic and genotypic overlap between syndromes. OBJECTIVE: This study aimed to describe a new way of thinking about syndromes of hereditary colorectal cancer based on their embryonic tissue of origin. DATA SOURCES: Articles were searched through PubMed and MEDLINE. STUDY SELECTION: The terms "hereditary colorectal cancer," "syndromes of hereditary colorectal cancer," and "hereditary polyposis" were used to direct the search. RESULTS: Primarily endoderm-derived syndromes were different from mesoderm-derived syndromes in their genetics, molecular biology, histology, and clinical course. LIMITATIONS: There is considerable phenotypic and genotypic overlap between syndromes, even when considering embryonic tissue of origin. CONCLUSIONS: Thinking about hereditary syndromes of colorectal cancer from the perspective of embryonic tissue of origin provides a fresh look at phenotype and genotype that opens new areas of exploration. UNA FORMA DIFERENTE DE PENSAR SOBRE LOS SNDROMES DEL CNCER COLORRECTAL HEREDITARIO: ANTECEDENTES:El cáncer colorrectal hereditario es un campo cada vez más complejo donde los síndromes más comunes se ven aumentados por presentaciones genéticas más raras que contribuyen a la poliposis familiar y al cáncer colorrectal. Hacer frente a esta complejidad resulta difícil debido a la superposición fenotípica y genotípica entre los síndromes.OBJETIVO:En este artículo, describimos una nueva forma de pensar sobre los síndromes de cáncer colorrectal hereditario en función del origen de su tejido embrionario.FUENTES DE DATOS:Se realizaron búsquedas de artículos en Pubmed y Medline.SELECCIÓN DE ESTUDIOS:Se utilizaron los términos "cáncer colorrectal hereditario", "síndromes de cáncer colorrectal hereditario", "poliposis hereditaria" para dirigir la búsqueda.RESULTADOS:Principalmente los síndromes derivados del endodermo fueron diferentes a los síndromes derivados del mesodermo en su genética, biología molecular, histología y curso clínico.LIMITACIONES:Existe una superposición fenotípica y genotípica considerable entre los síndromes, incluso cuando se considera el tejido de origen embrionario.CONCLUSIÓN:Pensar en los síndromes hereditarios del cáncer colorrectal desde la perspectiva del tejido embrionario de origen proporciona una nueva mirada al fenotipo y al genotipo que abre nuevas áreas de exploración. (Traducción-Dr Osvaldo Gauto ).

Role of Microbiome in the Outcomes Following Surgical Repair of Perianal Fistula: Prospective Cohort Study Design and Preliminary Results.

BACKGROUND: Anal fistulae are common, predominantly cryptoglandular, and almost invariably require surgical treatment. Recurrences are common for procedures other than fistulotomy regardless of technique and adequacy of repair. Growing evidence supports the pivotal role of specific intestinal bacteria in anastomotic failures after bowel resection. Anal crypts harbor colonic microbiota suggesting that similar mechanisms to anastomotic healing might prevail after anal fistula repair and hence influence healing. This study aims at assessing the potential role of the intestinal microbiome in the clinical outcomes after surgical repair of cryptoglandular anal fistula. METHODS: This is a pilot prospective cohort study enrolling patients with anal fistula undergoing endoanal advancement flap. For microbiome analysis, stool samples are taken via rectal swab before the procedure; additionally, a portion of the fistula is collected intraoperatively after fistulectomy. Samples from groups with treatment failure are compared to samples from patients who healed after surgical repair. Alpha and beta diversities and differential abundance of microbial taxa are determined and compared between groups with DADA2 analytical pipeline. RESULTS: Five patients have been enrolled to date (one female, four male). At median follow-up of 6 months (2-11), one patient experienced disease recurrence at 3 months. DNA from the 5 rectal swab and tissue samples was extracted, showing increased relative abundance of Enterococcus faecalis in samples from the patient who developed a recurrent fistula but not in those without recurrence. CONCLUSION: These very preliminary data suggest that intestinal microbiome may represent a crucial determinant of the surgical outcomes after anal fistula surgery.

Feasibility and Safety of Ambulatory Surgery as the Next Management Paradigm in Colorectal Resection Surgery.

BACKGROUND: Current clinical dogma favors universal inpatient admission after colorectal resection particularly in the presence of an anastomosis. OBJECTIVE: We evaluate the feasibility and safety of ambulatory surgery in carefully selected patients undergoing colorectal resection/anastomosis. METHODS: Between October 2020 and October 2021, all patients undergoing colorectal resection/anastomosis meeting specific criteria {no major comorbidity [American Society of Anesthesiologist (ASA) <4], not on therapeutic anticoagulation, compliant patient/family} were counseled preoperatively for ambulatory surgery (discharge <24 h postsurgery). Complicated surgery (ileoanal pouch, enterocutaneous fistula repair, reoperative pelvic surgery, multiple resections) and/or ostomy creation (loop/end ileostomy, Hartmann's, abdominoperineal resection) were exclusions. Discharge was at 6 to 8 hours postoperatively if all predetermined factors (no ostomy teaching needed, ambulating comfortably, tolerating diet, stable vitals, and blood-work) were met and patients were willing, or was postponed to the next day at patient request. All discharged patients received phone checks the next day with the option also given for voluntary readmission if inpatient care was preferred by patient. Patients discharged <24 hours postop (AmbC) were compared to those staying on as inpatients admitted (InpC) and also to a comparable historical (October 2019-October 2020) group when ambulatory surgery was not offered (HistC). RESULTS: Of 184 abdominal colorectal surgery patients, 97 had complicated colorectal resection and/or ostomy. Of the remaining 87, 29 (33.3%) were discharged <24 hours postoperatively [7 (24%) patients at 8 h]. Of these 29 AmbC patients, 4 were readmitted <30 days (ileus: 1, rectal bleeding: 2, nausea/vomiting: 1), 1 readmission was on first postdischarge day, none were voluntary post phone-check. AmbC and InpC (n=58) had similar age, sex, race, body mass index, and comorbidity. InpC had greater estimated blood loss (109 vs 34 mL, P <0.001) while length of stay was expectedly significantly longer (109 vs 17 hours, P <0.001). There was no mortality in either group. AmbC and InpC had similar readmission, reoperation, anastomotic leak, ileus, and surgical site infection. Mean length of stay for HistC was 83 hours. AmbC and HistC had similar age, sex, race, body mass index, and ASA class. Complications including readmission, reoperation, anastomotic leak, ileus, and surgical site infection were also similar for AmbC and HistC. CONCLUSIONS: With careful patient selection, preoperative education, perioperative management, and postoperative follow-up, ambulatory surgery is feasible in up to a third of patients undergoing colorectal resection/anastomosis and can be performed with comparable safety to the time-honored practice of routine inpatient hospitalization. Refinements in inclusion/exclusion criteria and postoperative outpatient follow-up will allow a paradigm shift in how such patients are managed, which has huge implications for patient experience, care-giver workload and health care finances.

IPAA Is More "Desmoidogenic" Than Ileorectal Anastomosis in Familial Adenomatous Polyposis.

BACKGROUND: Desmoid disease is a leading cause of morbidity and mortality in patients with familial adenomatous polyposis. Abdominal desmoid disease usually follows total proctocolectomy with IPAA or total abdominal colectomy with ileorectal anastomosis. Sex, extraintestinal manifestations, and a 3'-mutation location have been identified as risk factors, but surgical risk factors are poorly understood. We hypothesized that pouch construction creates a higher risk of desmoid formation due to the increased stretch of the small-bowel mesentery. OBJECTIVE: This study aimed to investigate the surgical risk factors for desmoid formation. DESIGN: This was a retrospective, single-center, registry-based cohort study. SETTINGS: This study was conducted at a single academic institution with a prospectively maintained hereditary colorectal cancer database between 1995 and 2015. PATIENTS: All patients with familial polyposis (total 345) who underwent either proctocolectomy with a pouch or colectomy with an ileorectal anastomosis during the study period and met inclusion criteria were selected. MAIN OUTCOME MEASURES: The development of symptomatic abdominal desmoid disease was the primary end point. Associations between desmoid formation and resection type, surgical approach, and other patient factors were analyzed. RESULTS: A total of 172 (49%) patients underwent proctocolectomy/ileoanal pouch, whereas 173 (51%) underwent total colectomy/ileorectal anastomosis. Overall, 100 (28.9%) developed symptomatic desmoids after surgery. On univariable analysis, open surgery and pouch surgery were associated with desmoid development, along with extracolonic manifestations, family history of desmoids, mutation location, and a high desmoid risk score. On multivarible analysis, proctocolectomy with pouch was most strongly associated with desmoid disease ( p < 0.01). LIMITATIONS: This study was limited by its retrospective nature, the lack of uniform desmoid screening, and the variable duration of follow-up. Unanalyzed confounding factors include polyposis severity and number of surgeries. CONCLUSIONS: Patients with polyposis who underwent total proctocolectomy with pouch by any approach had significantly greater risk of developing desmoid disease than total colectomy with ileorectal anastomosis, even when accounting for other risk factors. See Video Abstract at http://links.lww.com/DCR/B822 .RESULTADOS DE LOS PACIENTES SOMETIDOS A RESECCIÓN INTESTINAL ELECTIVA ANTES Y DESPUÉS DE LA IMPLEMENTACIÓN DE UN PROGRAMA DE DETECCIÓN Y TRATAMIENTO DE ANEMIA. ANTECEDENTES: Se sabe que los pacientes anémicos que se someten a una cirugía electiva de cáncer colorrectal tienen tasas significativamente más altas de complicaciones posoperatorias y peores resultados. OBJETIVO: Mejorar las tasas de detección y tratamiento de la anemia en pacientes sometidos a resecciones electivas de colon y recto a través de una iniciativa de mejora de calidad. DISEO: Comparamos una cohorte histórica de pacientes antes de la implementación de nuestro programa de detección de anemia y mejora de la calidad del tratamiento con una cohorte prospectiva después de la implementación. ENTORNO CLINICO: Hospital de atención terciaria. PACIENTES: Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019. INTERVENCIONES: Detección de anemia y programa de mejora de la calidad del tratamiento. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue el costo hospitalario por ingreso. RESULTADOS: Un total de 84 pacientes se sometieron a resección electiva de colon o recto antes de la implementación de nuestro proyecto de mejora de calidad de la anemia y 88 pacientes se sometieron a cirugía después. En la cohorte previa a la implementación, 44/84 (55,9 %) presentaban anemia en comparación con 47/99 (54,7 %) en la cohorte posterior a la implementación. Las tasas de detección (25 % a 86,4 %) y tratamiento (27,8 % a 63,8 %) aumentaron significativamente en la cohorte posterior a la implementación. El costo total medio por admisión se redujo significativamente en la cohorte posterior a la implementación (costo medio $16 827 vs. $25 796, p = 0,004); esta reducción significativa se observó incluso después de ajustar los factores de confusión relevantes (proporción de medias: 0,74, IC del 95 %: 0,65 a 0,85). El vínculo mecánico entre el tratamiento de la anemia y la reducción de costos sigue siendo desconocido. No hubo diferencias significativas en las tasas de transfusión de sangre, complicaciones o mortalidad entre los grupos. LIMITACIONES: El diseño de antes y después está sujeto a sesgos temporales y de selección. CONCLUSIONES: Demostramos la implementación exitosa de un programa de detección y tratamiento de anemia. Este programa se asoció con un costo por admisión significativamente reducido. Este trabajo demuestra el valor y los beneficios posibles de la implementación de un programa de detección y tratamiento de la anemia. Consulte Video Resumen en http://links.lww.com/DCR/C15 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

Using chatbots to screen for heritable cancer syndromes in patients undergoing routine colonoscopy.

BACKGROUND: Hereditary colorectal cancer (HCRC) syndromes account for 10% of colorectal cancers but remain underdiagnosed. This feasibility project tested the utility of an artificial intelligence-based chatbot deployed to patients scheduled for colonoscopy to identify HCRC risk factors, educate participants about HCRC and obtain consent to genetic testing as an extension of genetic counselling of appropriate subjects. Genetic counsellor (GC) and genetic counselling assistant (GCA) time spent per subject was also measured. METHODS: Patients scheduled for colonoscopy at Cleveland Clinic were invited via electronic medical record patient portal or letter prior to colonoscopy with a link to a chatbot administering the Colon Cancer Risk Assessment Tool (CCRAT) to screen for HCRC syndromes. Those with ≥1 positive response to a CCRAT question received chatbot-deployed genetic education and the option to receive genetic testing. An order for a 55-gene pan-cancer panel was placed for those consenting, and the subject had blood drawn on the day of colonoscopy. Results were disclosed by a GC or GCA by telephone. Subject demographics, progression through the chat, responses to CCRAT, personal and family history, genetic test results and communication with the subject were recorded. Descriptive statistics and two-tailed unpaired t-test and Fisher's exact test were used. RESULTS: 506/4254 (11.9%) initiated and 487 (96.2%) completed the chat with the chatbot. 215 (44.1%) answered 'yes' to ≥1 CCRAT question and all completed pretest education. 129/181 (71.3%) subjects who consented completed testing, and 12 (9.3%) were found to have a germline pathogenic variant. Per subject, the GC spent a mean of 14.3 (SD 7.3) and the GCA a mean of 19.2 (SD 9.8) minutes. CONCLUSION: The use of a chatbot in this setting was a novel and feasible method, with the potential of increasing genetic screening and testing in individuals at risk of HCRC syndromes.

Redo IPAA After a Failed Pouch In Patients With Crohn's Disease: Is It Worth Trying?

BACKGROUND: In selected patients with ulcerative colitis and pelvic pouch failure, redo pouch is an option. However, it is unknown whether selected patients with Crohn's disease should be offered a chance to avoid permanent diversion after failure of IPAA. OBJECTIVE: The objective was to compare the outcomes of redo pouch for ulcerative colitis and Crohn's disease. DESIGN: This was a retrospective analysis of a prospectively maintained pouch database (1983-2017). SETTINGS: The setting was the Cleveland Clinic. PATIENTS: This study included patients who underwent redo pouch with a primary surgical specimen diagnosis of ulcerative or Crohn's colitis at the time of initial pouch. MAIN OUTCOME MEASURES: Pouch failure was defined as either pouch excision or indefinite pouch diversion. Patient characteristics, perioperative and functional outcomes, pouch survival, and quality of life were compared according to the diagnosis. RESULTS: Of 422 patients, 392 had ulcerative colitis and 30 had Crohn's disease. Age and sex were comparable. The most common indications for redo pouch included anastomotic separation and fistulas (220 (56.1%) in ulcerative colitis and 21 (70%) in Crohn's disease). The majority of redo pouches required mucosectomy with handsewn anastomosis (310 (79%) in ulcerative colitis and 30 (100%) in Crohn's disease; p = 0.23). A new pouch was constructed in 160 patients (41%) with ulcerative colitis and repair of old pouch in 231 patients (59%) compared with 25 (83%) in Crohn's disease, who had creation of new pouch; only in 5 (17%) was the old pouch re-anastomosed. Stool frequency, seepage, and fecal urgency were comparable between groups. Cumulative 5-year pouch survival was longer in ulcerative colitis versus Crohn's disease (88% vs 55%; p = 0.008). Major causes of redo failure in Crohn's disease were pouch fistulas and/or strictures occurring after ileostomy closure. These were more common in Crohn's disease than in ulcerative colitis (p < 0.001). LIMITATIONS: This was a retrospective design. CONCLUSIONS: Redo pouch can be offered to selected patients with colonic Crohn's disease diagnosed at the time of their primary pouch. See Video Abstract at http://links.lww.com/DCR/B206. REHACER LA ANASTOMOSIS ILEOANAL CON RESERVORIO DESPUéS DE UN RESERVORIO ILEAL FALLIDO EN PACIENTES CON ENFERMEDAD DE CROHN: ¿VALE LA PENA INTENTARLO?: En pacientes seleccionados con colitis ulcerativa y falla del reservorio pélvico, rehacer el reservorio es una opción. Sin embargo, se desconoce si en los pacientes seleccionados con enfermedad de Crohn se debería ofrecer la oportunidad de evitar la derivación permanente después de la falla de la anastomosis ileoanal con reservorio ileal.El objetivo fue comparar los resultados de reservorios re-hechos en colitis ulcerosa y la enfermedad de Crohn.El escenario fue la Cleveland Clinic.Análisis retrospectivo de una base de datos de reservorios ileales mantenida prospectivamente (1983-2017).Este estudio incluyó a pacientes que se sometieron a cirugía para rehacer el reservorio ileal con un diagnóstico en el espécimen quirúrgico primario de colitis ulcerosa o de Crohn en el momento del reservorio inicial.La falla del reservorio se definió como la escisión del reservorio o la derivación indefinida del reservorio. Las características del paciente, los resultados perioperatorios y funcionales, la supervivencia del reservorio y la calidad de vida se compararon de acuerdo con el diagnóstico.De 422 pacientes, 392 tenían colitis ulcerativa y 30 tenían enfermedad de Crohn. La edad y el género fueron comparables. Las indicaciones más comunes para rehacer el reservorio incluyeron dehiscencia anastomótica y fístulas [220 (56,1%) en colitis ulcerosa y 21 (70%) en la enfermedad de Crohn]. La mayoría de los reservorios rehechos requirieron mucosectomía con anastomosis manual [310 (79%) en colitis ulcerosa y 30 (100%) en la enfermedad de Crohn, p = 0.23]. Se construyó un nuevo reservorio en 160 (41%) pacientes con colitis ulcerativa y se reparó el reservorio antiguo en 231 (59%) pacientes, en comparación con 25 (83%) en la enfermedad de Crohn, que requirieron creación de un nuevo reservorio, y solo 5 (17%) donde el reservorio antiguo se volvió a anastomosar. La frecuencia de las evacuaciones, el manchado fecal y la urgencia fecal fueron comparables entre grupos. La supervivencia acumulada del reservorio a 5 años fue mayor en la colitis ulcerativa frente a la enfermedad de Crohn (88% frente a 55%, p = 0.008). Las principales causas de falla del reservorio rehecho en la enfermedad de Crohn fueron las fístulas del reservorio y / o las estenosis que ocurrieron después del cierre de ileostomía. Estas fueron más comunes en la enfermedad de Crohn que en la colitis ulcerativa (p <0.001).Este fue un diseño retrospectivo.Rehacer el reservorio ileal se puede ofrecer a pacientes seleccionados con enfermedad de Crohn colónica diagnosticada en el momento de su reservorio primario. Consulte Video Resumen en http://links.lww.com/DCR/B206. (Traducción-Dr Jorge Silva Velazco).

The location of premalignant colorectal polyps under age 50: a further rationale for screening sigmoidoscopy.

PURPOSE: The incidence of colorectal cancer (CRC) among young adults has been dramatically rising, with guidelines for screening recently adjusted to start at age 45. However, knowledge of the precursor lesions is limited. We recently reported that 83% of CRC diagnosed under age 50 are left sided. Our aim was to analyze the location and histology of benign colorectal lesions found in a cohort of patients younger than 50, documenting the presence of advanced histology. METHODS: We used the database in the Department of Pathology to retrospectively review the location and histology of all benign colorectal neoplasms in patients under age 50 submitted to pathology examination during 2006-2016. RESULTS: A total of 8364 lesions were examined from 4773 patients, and 3534 (65.5%) of the patients had only one polyp and the rest had multiple. Mean age was 41.9 years (range 16-49) while 3843 (72.8%) of the patients were between the ages of 40 and 49. In total, 4570/8364 lesions (54.6%) were distal to the splenic flexure. The most common pathology was tubular adenoma (63.7%), then hyperplastic polyps (16.6%), sessile serrated lesions (SSLs) (13.1%), and tubulovillous adenomas (6.3%). Tubulovillous adenomas, villous lesions, advanced adenomas, and adenomas with high-grade dysplasia were all predominantly left sided (left colon and rectum = 77.6%, 85%, 78.3%, and 87.6% respectively). Of the SSLs, 71.5% were in the right colon while 16.6% of hyperplastic lesions were right sided. CONCLUSIONS: High-risk advanced adenomas are predominantly left sided. This focuses attention on the rectum and left colon where carcinogenesis is strong in the young.

Prognostic Implications of Pathological Response to Neoadjuvant Chemoradiation in Pathologic Stage III Rectal Cancer.

OBJECTIVE: To evaluate the independent prognostic ability of the American Joint Committee on Cancer (AJCC) tumor regression scores within pathologic stage II and III rectal cancers. BACKGROUND: Response to neoadjuvant chemoradiation (nCRT) has been debated as a biologic surrogate for tumor biology and prognosis in rectal cancer. AJCC regression scores have been shown to correlate with prognosis. METHODS: Patient demographics, tumor characteristics, and AJCC scores (0 = complete response; 1 = isolated tumor cells remaining; 2 = residual cancer outgrown by fibrosis; 3 = extensive residual cancer) were assessed from 545 rectal cancer patients treated by nCRT followed by surgery at a single institution. Patients were classified as responders (score 0-2) or nonresponders (score 3). Survival analyses were performed using Cox proportional hazards models. RESULTS: Of 545 cases, 123 and 182 were pathologic stage II and III, respectively. Median follow-up was 4.9 years. AJCC regression scores were not independently prognostic within stage II cancers. However, AJCC scores were strongly associated with prognosis within stage III cancers (nonresponse 5-year overall survival [OS] 27% vs 67%, P < 0.001). Stage III responders (N = 139, 76.4%) had similar outcomes to stage II (5-year OS 67% vs 74%, P = 0.89). Conversely, stage III nonresponders (N = 43, 23.6%) approached stage IV outcomes (5-year OS 27% vs 18%, P = 0.09). On multivariable analysis, nonresponse (hazard ratio 3.2, 95% confidence interval 1.7-6.2), along with positive margin, abdominoperineal resection, and no adjuvant chemotherapy administration were independently associated with worse OS. CONCLUSIONS: AJCC response score after nCRT is a novel prognostic factor in pathologic stage III rectal cancer and may guide surveillance and adjuvant therapy decisions.

Spigelman stage IV duodenal polyposis does not precede most duodenal cancer cases in patients with familial adenomatous polyposis.

BACKGROUND AND AIMS: The greatest known risk factor for duodenal cancer in familial adenomatous polyposis (FAP) is Spigelman stage (SS) IV duodenal polyposis. Endoscopic surveillance is recommended in FAP patients with SS 0 to IV, and prophylactic duodenectomy should be considered in SS IV. Cancer occurs in patients without SS IV polyposis. We assessed the relationship of SS and other factors with duodenal cancer in FAP. METHODS: We performed a case-control study on 18 FAP patients with duodenal cancer and 85 randomly selected FAP control subjects with similar age characteristics. Demographic, clinical, and endoscopic features were compared using univariate and logistic regression analyses to assess factors associated with duodenal cancer. RESULTS: Fifty-three percent of cases had no SS IV history. SS components positively associated with cancer included duodenal polyp size (77% vs 47%, P = .015), and high-grade dysplasia (HGD; 29% vs 6%, P = .003) but not polyp number or histology. In the papilla, the frequency of tubulovillous or villous histology (80% vs 22%, P < .001) and HGD (30% vs 4%, P = .010) was greater in cases than control subjects. CONCLUSIONS: SS IV polyposis was absent in half of FAP patients with duodenal cancer. Only 2 of 4 SS components (large duodenal polyp size and HGD) were positively associated with duodenal cancer. Advanced pathology of the papilla appears to be an important feature. Revision of SS to emphasize these findings should be considered to better estimate cancer risk.

Endoscopic and histologic features associated with gastric cancer in familial adenomatous polyposis.

BACKGROUND AND AIMS: Gastric cancer (GC) is a newly described cancer risk in Western patients with familial adenomatous polyposis (FAP). Little is known about clinical, endoscopic, and pathologic features associated with FAP-related GC. We compared these features in FAP patients with and without GC. METHODS: FAP patients were identified through the David G. Jagelman Inherited Colorectal Cancer Registries Cologene database. FAP patients with GC and randomly selected FAP patients without GC who had undergone at least 2 EGDs were analyzed. Demographic, clinical, endoscopic, and pathologic features were compared. RESULTS: Ten FAP patients with GC were identified, and 40 age-matched FAP control subjects were selected. No demographic differences were noted between patients and control subjects. All GC cases arose in the proximal stomach among gastric polyposis, with only 2 endoscopically visible. The prevalence of gastric polyposis was similar (100% vs 93%). Endoscopic features associated with GC included a carpeting of gastric polyps (100% vs 22.5%), solitary polyps >20 mm (100% vs 0%), and a polypoid mound of polyps (80% vs 0%; all P < .001). GC patients had a higher prevalence of gastric adenomas (30% vs 5%, P = .048) and polyps with high-grade dysplasia, including fundic gland polyps (50% vs 10%, P = .01) and pyloric gland adenomas (20% vs 0%, P = .037). CONCLUSIONS: We identified endoscopic features and advanced pathology present in the stomachs of Western patients with FAP who developed GC. Upper GI surveillance in FAP should include the stomach and awareness of features associated with GC. Optimal approaches to treatment of gastric polyposis and methods of identification of early GC precursors in FAP are needed.

A Changing Spectrum of Colorectal Cancer Biology With Age: Implications for the Young Patient.

BACKGROUND: The methylator pathway of colorectal carcinogenesis, characterized by CpG island hypermethylation and BRAF mutations, accounts for ≈25% of colorectal cancers. Because these cancers tend to be right sided and because DNA methylation in the right colon increases with age, we expect an increasing proportion of right-sided cancer over time. Conversely, we expect young patients (age <50 y) to have less methylated and fewer right-sided cancers OBJECTIVE:: The purpose of this study was to analyze the distribution and genetic traits of colorectal cancer from different age groups. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted at a high-volume tertiary referral center. PATIENTS: Patient samples included those from our colorectal cancer biobank of resected colorectal cancer specimens. MAIN OUTCOME MEASURES: Tumor CpG island hypermethylation, microsatellite instability, and mutations in KRAS and BRAF oncogenes were analyzed in resected specimens and stratified by age and tumor location. Comparisons included age >50 or <50 years and decade of diagnosis (≤50, 51-60, 61-70, 71-80, and >81 y). Patients with IBD or hereditary syndromes were excluded. RESULTS: A total of 497 colorectal cancers were analyzed (266 men and 231 women); 57 patients (11.5%) were ≤50 years of age. No young cancers (0/57) were hypermethylated compared with 97 (22%) of 440 cancers of patients aged >50 years (p < 0.001). An increasing percentage of tumors were CpG island phenotype high with each decade of age at diagnosis. No cancers in patients <50 years of age were microsatellite unstable compared with 91 (23.6%) of 346 for those >50 years of age. No young cancers contained a BRAF mutation compared with 46 (10.6%) of 434 in older cancers (p < 0.001). KRAS mutations were less common in young cancers compared with older cancers (13/57 (22.8%) vs 126/410 (30.7%); p < 0.01). Eleven (19.3%) of 57 young cancers were proximal compared with 228 (51.8%) of 440 (p < 0.001) older cancers. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The lack of CpG island methylator phenotype tumors in young patients is consistent with the dominant left-sided cancer distribution seen in the young and focuses efforts to understand and prevent cancer in this age group on causes of chromosomal instability. See Video Abstract at http://links.lww.com/DCR/A709.

Appendix orifice polyps: a study of 691 lesions at a single institution.

PURPOSE: Data on the management of appendix orifice lesions are limited. We present our experience on the management of appendix orifice lesions focusing on the range of size, histology, treatment, and outcomes for polyps at the appendix orifice. METHODS: Retrospective descriptive study at a tertiary referral center. PATIENTS: Those having appendix orifice lesion removed and sent for histology between 2000 and 2017. INTERVENTIONS(S): Polypectomy, surgery. MAIN OUTCOME MEASURES: Polyp size, shape, histology, treatment. RESULTS: In total, 691 patients matched our inclusion criteria. Screening was the most common indication for colonoscopy (49.1%). Mean size was 10.1 mm. The most common excision method was cold biopsy forceps (36.3%), followed by hot snare (9.3%), cold snare (8.5%), jumbo cold forceps (6.7%), hot biopsy (6.8%), and endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) (4%). Recurrence was seen in 19/184 (10.3%) patients. Index polyps ≥ 10 mm had a significantly higher risk of recurrence compared to those ≤ 5 mm (odds ratio 3.2 95% CI 1.1-9.2, p = 0.027). None of the patients had complications. Surgery was performed in 45/691 (6.5%). Polyps > 5 mm (41/45) were more likely to require surgery than polyps ≤ 5 mm (4/45 6.67%), p < 0.001. LIMITATIONS: Retrospective study. CONCLUSION: Appendix orifice polyps can usually be managed by conventional endoscopic polypectomy methods without the need for ESD.

Distribution of colorectal cancer in young African Americans: implications for the choice of screening test.

BACKGROUND: We recently reported on a left-sided predominance of colorectal cancers in the young (under age 50). Given the predilection of young African Americans for the disease, we wondered if there may be a difference in the biology of colorectal carcinogenesis between this group and Caucasians. OBJECTIVE: Compare the distribution of colorectal cancer in African American patients and Caucasians under age 50, and describe implications for screening in these groups. PATIENTS: Colorectal cancer patients diagnosed under the age of 50 between the years 2000 and 2016. All races other than African American and Caucasian and all patients with hereditary colon cancer or inflammatory bowel disease were excluded. OUTCOME MEASURES: race, age at diagnosis (5 subgroups: < 20, 20-29, 30-39, 40-44, and 45-49 years) and cancer location; right (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure), left (descending colon and sigmoid colon), or rectal. RESULTS: 759 patients were included; 695 (91.6%) were Caucasian and 64 (8.4%) were African American. Most cases were diagnosed between ages 40 and 49 (African American = 75%, Caucasian = 69.5%). Rectal cancer was most common in both races, although significantly more common in Caucasian than in African American patients (64.2% vs 39.1%). Right colon cancer was more commonly found in African Americans (37.5%) compared with Caucasians (18%) (p = 0.0002). The ratio of rectal to right-sided colon cancer in African Americans was 1:1 compared with 3.6:1 in Caucasians. LIMITATIONS: Relatively low number of African American patients CONCLUSION: The high rate of right-sided cancer in young African American patients means that they should be screened with colonoscopy. The increased incidence of right-sided cancers may represent a different biology of carcinogenesis in African Americans and deserves further study.

Web-Based Model for Predicting Time to Surgery in Young Patients with Familial Adenomatous Polyposis: An Internally Validated Study.

INTRODUCTION: The timing of prophylactic colorectal surgery in patients with familial adenomatous polyposis (FAP) is based on the immediacy of the colorectal cancer risk. The ability to predict the need for surgery may help patients and their families plan in the context of life events and CRC risk. We created a model to predict the likelihood of surgery within 2 and 5 years of first colonoscopy at our institution. METHODS: A single institution hereditary colorectal syndrome (Cologene™) database was interrogated for all patients with FAP having a deleterious APC mutation. Patients with first colonoscopy after age 30 and before year 2000 were excluded. Cox regression analysis was done to assess multiple factors associated with surgery, followed by stepwise Cox regression analysis to select an optimal model. Receiver operator curve (ROC) analysis was performed to assess the model. RESULTS: A total of 211 (53% female) patients were included. Forty-five percent underwent surgery after an average of 3.8 years of surveillance. The final model was created based on initial clinical characteristics (age, gender, BMI, family history of desmoids, genotype-phenotype correlation), initial colonoscopic characteristics (number of polyps, polyp size, presence of high-grade dysplasia); and on clinical events (chemoprevention and polypectomy). AUC was 0.87 and 0.84 to predict surgery within 2 and 5 years, respectively. The final model can be accessed at this website: http://app.calculoid.com/#/calculator/29638 . CONCLUSION: This web-based tool allows clinicians to stratify patients' likelihood of colorectal surgery within 2 and 5 years of their initial examination, based on clinical and endoscopic features, and using the philosophy of care guiding practice at this institution.

The Relationship Between Clavien-Dindo Morbidity Classification and Oncologic Outcomes After Colorectal Cancer Resection.

BACKGROUND: Limited data on the relationship between postoperative complications (POCs) after colorectal cancer resection and oncologic outcomes are available. We hypothesized that the increased severity of POCs is associated with progressively worse oncologic outcomes. METHODS: Patients with pathological stages I-III colorectal adenocarcinoma undergoing elective curative resection in a single institution between 2000 and 2012 were identified from a prospectively collected database. The severity of POCs was determined using the Clavien-Dindo classification, and oncologic outcomes were assessed. RESULTS: Of 2266 patients, 669 (30%) had at least one POC. POCs were not associated with pathologic stage (p = 0.58) or use of adjuvant therapy (p = 0.19). With a mean follow-up of 5.3 years, POCs were associated with decreased 5-year overall survival (OS) (60% vs. 77%, p < 0.001), disease-free survival (DFS) (53% vs. 70%, p < 0.001), cancer-specific survival (CSS) (81% vs. 87%, p < 0.001), and increased overall recurrence rates (19% vs. 15%, p = 0.008). Increasing Clavien-Dindo scores from I to IV was significantly associated with progressively decreasing OS (71, 64, 60, 22%, p < 0.001), DFS (65, 58, 51, 19%, p < 0.001), CSS (88, 77, 79, 74%, p < 0.001), and increasing recurrence rates (12, 20, 26, 18%, p = 0.002). Multivariate analysis confirmed POCs as an independent factor associated with decreased OS [hazard ratio (HR) 0.63, 95% CI 0.52-0.76], DFS (HR 0.64, 95% CI 0.54-0.76), CSS (HR 0.73, 95% CI 0.56-0.97), and increased recurrence rates (HR 1.36, 95% CI 1.02-1.80). CONCLUSIONS: POCs are associated with adverse oncologic outcomes, with increasing effect with higher Clavien-Dindo score. Efforts to reduce both the incidence and severity of complications should result in improved oncologic outcomes.

Natural history of colonic polyposis in young patients with familial adenomatous polyposis.

BACKGROUND AND AIMS: Proctocolectomy prevents colorectal cancer in familial adenomatous polyposis (FAP). Colorectal polyp progression is one of the indications for surgery. No data exist regarding the natural history of colorectal polyposis in young patients with FAP. This study examined the rate of polyposis progression and factors associated with it. METHODS: Patients with FAP <30 years old who had undergone ≥2 colonoscopies since 2000 were identified. Rate of polyposis progression was calculated by review of polyp counts obtained from baseline and last colonoscopy, accounting for any polyps removed during the observation period. Endoscopic and non-endoscopic factors affecting the rate of polyposis progression were evaluated. Multivariate analysis was performed to identify factors associated with rate of polyposis progression. RESULTS: One hundred sixty-eight patients (52% female; median age, 13.5 years) were included. Median rate of polyposis progression was 25.4 polyps/year (interquartile range, 9.5-69.8). Highest median rate of polyposis progression (89 polyps/year) was associated with mutation in codon 1309. The rate of polyposis progression was independently associated with the location of mutation in the adenomatous polyposis coli gene, the number of polyps at the initial colonoscopy, and exposure to chemoprevention. Of the 39.9% of patients who underwent surgery, an increase in polyp number was the most common indication (53.7%). CONCLUSIONS: The rate of polyposis progression in young patients with FAP varies with a median of about 25 new polyps per year. Progression is associated with distinct factors, which can be used in discussion with patients regarding the need for and timing of prophylactic colorectal surgery.

Left-Sided Dominance of Early-Onset Colorectal Cancers: A Rationale for Screening Flexible Sigmoidoscopy in the Young.

BACKGROUND: National databases show a recent significant increase in the incidence of colorectal cancer in people younger than 50. With current recommendations to begin average-risk screening at age 50, these patients do not have the opportunity to be screened. We hypothesized that most of the cancers among the young would be left sided, which would create an opportunity for screening the young by flexible sigmoidoscopy. OBJECTIVE: This study aims to analyze the anatomic distribution of sporadic colorectal cancers in patients under the age of 50. DESIGN: This is a retrospective review of a prospectively maintained database. SETTING: This study was conducted at a single high-volume tertiary referral center. PATIENTS: Patients under the age of 50 with colorectal cancer between the years 2000 and 2016 were included. Patients with IBD, familial adenomatous polyposis, Lynch syndrome, or hereditary nonpolyposis colorectal cancer were excluded. MAIN OUTCOME MEASURES: The primary outcomes measured were tumor location and stage, demographics, and family history. RESULTS: A total of 739 patients were included. Age range at diagnosis was 18 to 49 years; median age was 44 years. Five hundred thirty patients were between the ages of 40 and 49, 167 were between the ages of 30 and 39, 40 were between the ages of 20 and 29, and 2 were under 20. Two hundred thirty-one patients (32%) had a family history of colorectal cancer. The anatomic distribution of the cancers was: 485 rectum (65%), 107 sigmoid colon (15%), 19 descending colon (3%), and 128 right colon and transverse colon (17%). Therefore, 83% of the tumors were theoretically within the range of flexible sigmoidoscopy. LIMITATIONS: Referral bias favors rectal cancer. CONCLUSION: The combination of an increasing incidence of colorectal cancer in those under 50 years of age and the predominance of left-sided cancer suggests that screening by flexible sigmoidoscopy starting at age 40 in average-risk individuals may prevent cancer by finding asymptomatic lesions. See Video Abstract at http://links.lww.com/DCR/A579.

Aspects of the Natural History of Sessile Serrated Adenomas/Polyps: Risk Indicators for Carcinogenesis in the Colorectal Mucosa?

BACKGROUND: Sessile serrated adenomas/polyps are potentially premalignant colorectal lesions that are precursors to colorectal cancer arising via CpG island methylator phenotype. They are caused by the combination of a BRAF mutation and promoter hypermethylation. DNA methylation is an age-dependent phenomenon in the right colon, and we would expect the occurrence and severity of serrated neoplasia to reflect this. OBJECTIVE: The purpose of this study was to document the natural history of sessile serrated adenomas/polyps, including the ages at which they appear and the ranges of their number, size, and associated lesions. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Consecutive patients with sessile serrated adenomas/polyps removed between 2006 and 2015 were included. Patients with IBD, familial adenomatous polyposis, Lynch syndrome, serrated polyposis, and hereditary nonpolyposis colorectal cancer were excluded. MAIN OUTCOME MEASURES: Age at which polyps were first diagnosed, location and size of polyps, demographics, and family history were measured. RESULTS: A total of 440 patients had 668 sessile serrated adenomas/polyps, 257 (58%) also had ≥1 adenoma, and 28 (6%) had a history of colorectal cancer. Mean age at diagnosis was 68 ± 11 years, and 45% were men. Two hundred had had ≥1 colonoscopy before the diagnosis of the first sessile serrated adenomas/polyps. A total of 136 patients (31%) had multiple sessile serrated adenomas/polyps, including 24% synchronous and 10% metachronous. The range of total cumulative sessile serrated adenomas/polyps was from 1 to 7. A total of 554 (83%) of 668 sessile serrated adenomas/polyps were right sided; 48% were ≥1 cm diameter and 22% were >2 cm. The size of the first sessile serrated adenomas/polyps in those diagnosed under age 50 years averaged 10 mm, those between 50 and 60 years averaged 12 mm, and those between 60 and 70 years averaged 12 mm. LIMITATIONS: No measurement of methylation or BRAF mutations in polyps or normal mucosa and a lack of subclassification of hyperplastic polyps limited this study. CONCLUSIONS: The age of onset of sessile serrated adenomas/polyps varies, but the pattern is consistent with increasing methylation in the mucosa. Early negative colonoscopies predict a low risk of methylator cancers. See Video Abstract at http://links.lww.com/DCR/A736.

Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With Colorectal Cancer.

BACKGROUND: The incidence of colorectal cancer in the young (under age 40) is increasing, and this population has worse oncologic outcomes. Mucinous histology is a potential prognostic factor in colorectal cancer, but has not been evaluated specifically in young patients. OBJECTIVE: The objective of the study was to determine factors associated with poor outcome in young patients with colorectal cancer (≤40 years) and to determine relationships between mucinous histology and oncologic outcomes in this population. DESIGN: This is a retrospective study. SETTING: Patients from a single-institution tertiary care center were studied. PATIENTS: A total of 224 patients with colorectal cancer under 40 years of age diagnosed between 1990 and 2010 were included (mean age, 34.7 years; 51.3% female). 34 patients (15.2%) had mucinous histology. INTERVENTIONS(S): There were no interventions. MAIN OUTCOME MEASURES: Oncologic outcomes were analyzed according to the presence of mucinous histology. RESULTS: The mucinous and nonmucin colorectal cancer study populations were statistically similar in age, sex, tumor location, pathological stage, differentiation, and adjuvant chemotherapy use. Five-year disease-free survival was 29.1% versus 71.3% (p < 0.0001) and 5-year overall survival was 54.7% versus 80.3% (p < 0.0001) for mucinous and nonmucinous patients, respectively. Mucinous colorectal cancers recurred earlier at a median time of 36.4 months versus 94.2 months for nonmucin colorectal cancers (p < 0.001). On multivariate analysis, pathological stage (stage II HR, 3.61; 95% CI, 1.37-9.50; stage III HR, 5.27; 95% CI, 2.12-12.33), positive margins (HR, 1.95; 95% CI, 1.12-3.23), angiolymphatic invasion (HR, 2.15; 95% CI, 1.26-3.97), and mucinous histology (HR, 2.36; 95% CI, 1.44-3.96) were independently associated with worse disease-free and overall survival. LIMITATIONS: This is a retrospective study without genetic information. CONCLUSIONS: Mucinous histology is a negative prognostic factor in young patients with colorectal cancer. This is associated with early and high recurrence rates, despite use of standard neoadjuvant and adjuvant regimens. Physicians need to be aware of this association and potentially explore novel treatment options. See Video Abstract at http://links.lww.com/DCR/A575.