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Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.

Prior small reports have postulated a link between gastrointestinal polyposis and childhood and young adulthood cancer (CYAC) treatment (therapy-associated polyposis; TAP), but this remains a poorly understood phenomenon. The aim of this study was to describe the phenotypic spectrum of TAP in a multi-institutional cohort. TAP cases were identified from eight high-risk cancer centers. Cases were defined as patients with ≥10 gastrointestinal polyps without known causative germline alteration or hereditary colorectal cancer predisposition syndrome who had a history of prior treatment with chemotherapy and/or radiotherapy for CYAC. A total of 34 TAP cases were included (original CYAC: 27 Hodgkin lymphoma, three neuroblastoma, one acute myeloid leukemia, one medulloblastoma, one nephroblastoma, and one non-Hodgkin lymphoma). Gastrointestinal polyposis was first detected at a median of 27 years (interquartile range, 20–33) after CYAC treatment. A total of 12 of 34 (35%) TAP cases had ≥50 colorectal polyps. A total of 32 of 34 (94%) had >1 histologic polyp type. A total of 25 of 34 (74%) had clinical features suggestive of ≥1 colorectal cancer predisposition syndrome [e.g., attenuated familial adenomatous polyposis (FAP), serrated polyposis syndrome, extracolonic manifestations of FAP, mismatch repair–deficient colorectal cancer, or hamartomatous polyposis] including 8 of 34 (24%) with features of multiple such syndromes. TAP is an apparently acquired phenomenon that should be considered in patients who develop significant polyposis without known causative germline alteration but who have had prior treatment for a CYAC. Patients with TAP have features that may mimic various hereditary colorectal cancer syndromes, suggesting multiple concurrent biologic mechanisms, and recognition of this diagnosis may have implications for cancer risk and screening.

Supplementary Table 3 shows types of surgical resection

Supplementary Table 1 shows number of TAP cases per site

Supplementary Table 2 shows individual case-level data (clinical history, genetic testing, secondary cancers)

Current clinical dogma favors universal inpatient admission after colorectal resection particularly in the presence of an anastomosis.We evaluate the feasibility and safety of ambulatory surgery in carefully selected patients undergoing colorectal resection/anastomosis.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 (discharge24 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 discharged24 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).Of 184 abdominal colorectal surgery patients, 97 had complicated colorectal resection and/or ostomy. Of the remaining 87, 29 (33.3%) were discharged24 hours postoperatively [7 (24%) patients at 8 h]. Of these 29 AmbC patients, 4 were readmitted30 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, P0.001) while length of stay was expectedly significantly longer (109 vs 17 hours, P0.001). 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.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.

Nonspecific acute pouchitis is common in patients with ulcerative colitis who undergo IPAA, but there is disagreement about the rate at which this occurs in patients with familial adenomatous polyposis.This study aimed to define the rate at which nonspecific acute pouchitis occurs in patients with familial adenomatous polyposis.This study was conducted at a hereditary colorectal cancer center in a large academic medical center.This is a retrospective cohort study using prospectively gathered data.Patients with familial adenomatous polyposis who have had IPAA were included.Symptoms, pouchoscopy and pouch radiography, and pouch biopsy were evaluated.The primary outcomes measured were the presence of nonspecific acute pouchitis and the alternative diagnosis of pouch dysfunction.There were 250 patients with familial adenomatous polyposis who had undergone IPAA; 38 (15.2%) had been labeled as having "pouchitis": 23 men and 15 women. Median age was 55 years (range, 18-90 years). No patient had nonspecific, acute pouchitis as defined by our criteria. In 9 cases, the diagnosis was derived from benign ulcers common in ileal pouches. Stool frequency was the most common symptom associated with the "pouchitis" label, but actual causes for the frequency included poor pouch emptying, poor eating habits, poor bowel habits, and afferent limb syndrome. Median stool frequency was 9, ranging from 4 to 15 per day. Every patient had at least 1 pouch endoscopy, and the median number was 19 per patient (range, 1-21). Nine patients had pouch biopsies to rule out inflammation; all showed chronic active enteritis, a normal finding in ileal pouches.This study was limited by its retrospective nature.We could not confirm any case of nonspecific acute pouchitis in patients with familial adenomatous polyposis. Those caring for patients with familial adenomatous polyposis who have a pouch should seek causes for pouch-related symptoms other than "pouchitis." See Video Abstract at http://links.lww.com/DCR/B666.POUCHITIS AGUDA INESPECÍFICA EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: MENOS COMÚN DE LO QUE PENSAMOSANTECEDENTES:La pouchitis aguda e inespecífica es común en pacientes con colitis ulcerativa, sometidos a anastomosis de bolsa ileoanal, pero no hay acuerdo sobre la frecuencia en que se presenta en pacientes con poliposis adenomatosa familiar (PAF).OBJETIVO:Definir la frecuencia en la que se presenta pouchitis aguda inespecífica en pacientes con poliposis adenomatosa familiar.ENTORNO CLINICO:Centro de cáncer colorrectal hereditario en un gran centro médico académico.DISEÑO:Estudio de cohorte retrospectivo utilizando datos recopilados prospectivamente.PACIENTES:Pacientes con poliposis adenomatosa familiar sometidos a bolsa con anastomosis ileoanal.INTERVENCIONES:Síntomas, proctoscopia, radiografía y biopsia de bolsa ileoanal.PRINCIPALES MEDIDAS DE VALORACION:Presencia de pouchitis aguda inespecífica; diagnósticos alternos de disfunción de la bolsa ileal.RESULTADOS:De 250 pacientes con poliposis adenomatosa familiar sometidos a una anastomosis anal de la bolsa ileal; 38 (15,2%), habían sido etiquetados como "pouchitis", 23 hombres y 15 mujeres. La mediana de edad fue de 55 años (rango de 18 a 90 años). Ningún paciente tuvo pouchitis aguda inespecífica según lo definido por nuestros criterios. En 9 casos el diagnóstico se derivó de úlceras benignas frecuentes en bolsas ileales. La frecuencia de las evacuaciones fue el síntoma más común asociado con la etiqueta "pouchitis", pero las causas reales de la frecuencia, incluyeron un mal vaciado de la bolsa, malos hábitos alimenticios, malos hábitos intestinales y síndrome de asa aferente. La frecuencia media de las evacuaciones fue de 9, con un rango de 4 a 15 por día. A cada paciente se le realizó al menos una endoscopia de la bolsa: la mediana fue de 19 por paciente (rango de 1 a 21). A 9 pacientes se les realizó biopsia de bolsa para descartar inflamación: todos mostraron enteritis activa crónica, un hallazgo normal en las bolsas ileales.LIMITACIONES:Naturaleza retrospectiva del estudio.CONCLUSIONES:No pudimos confirmar ningún caso de pouchitis aguda e inespecífica en pacientes con PAF. Aquellos que atienden a pacientes con PAF con bolsa ileal, deben buscar otras causas para los síntomas relacionados con la bolsa que no sean "pouchitis". Consulte Video Resumen en http://links.lww.com/DCR/B666. (Traducción-Dr. Fidel Ruiz Healy).

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.This study aimed to investigate the surgical risk factors for desmoid formation.This was a retrospective, single-center, registry-based cohort study.This study was conducted at a single academic institution with a prospectively maintained hereditary colorectal cancer database between 1995 and 2015.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.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.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 ( p0.01).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.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.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.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.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.Hospital de atención terciaria.Todos los pacientes adultos con un nuevo diagnóstico de cáncer de colon o recto sin evidencia de enfermedad metastásica entre 2017 y 2019.Detección de anemia y programa de mejora de la calidad del tratamiento.El resultado primario fue el costo hospitalario por ingreso.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.El diseño de antes y después está sujeto a sesgos temporales y de selección.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 ).

Introduction When patients with familial adenomatous polyposis have a severely affected rectum it is usually assumed that endoscopic control is impossible or unwise. The standard approach is proctectomy with either an end ileostomy, or an ileal pouch anal anastomosis. Here we show that application of aggressive, multistage snare polypectomy to this situation can be effective and allow the patient to avoid surgery, at least in the short term. Technique Standard polypectomy using snare excision with coagulation is used, taking two or three sessions, and beginning with the largest polyps. The procedures are done with the patient under general anesthesia. Endoscopic mucosal resection technique with fluid injection to lift polyps is not necessary. Results Complete control of the rectal polyps, sustained for at least 2 years, is possible without functional sequelae. Conclusions Familial adenomatous polyposis patients with severe rectal polyposis can be offered multistage rectal polypectomy and safely avoid proctectomy.IRB and consent approval through the David G Jagelman Inherited Colorectal Cancer Registry.

Clinicians may be hesitant to prescribe biologics or immunomodulators to individuals with familial adenomatous polyposis (FAP) and comorbid inflammatory disease (CID) because of increased cancer risk. Our aim was to compare the risk of malignancy in FAP individuals with inflammatory bowel (IBD) and/or rheumatic disease that received biologics/immunomodulators to those who did not. Individuals with FAP and CID were included in the study. We compared the incidence of cancer between individuals exposed to biologics/immunomodulators compared to unexposed from the date of diagnosis of comorbid disease till last follow up or death. Hazard ratio (HR) for cancer was computed using Cox regression model and compared by exposure status to biologic/immunomodulators. 25 individuals with FAP and a comorbid inflammatory disease were identified including 9 (36%) with IBD and 16 (64%) with rheumatic disease. 14 (56%) were exposed to a biologic and or immunomodulator. Median duration of biologic/immunomodulator exposure was 48 (2-180) months. 3 (21.4%) in the exposed group compared to 1 (9.1%) in the unexposed group developed cancer with a HR for exposure of 1.92 (CI 0.2-18.5, p = 0.57). Median duration of follow up after the diagnosis of inflammatory disease was 10 (5.5-17.0) years in the exposed and 6 (3.0-15.0) years in the unexposed group. In the exposed group, 1 patient developed gastric and 2 developed colon cancer. One unexposed patient developed medullary thyroid cancer. There is a possible trend of more cancers in the group that received biologics/immunomodulators-but given the small number of patients and p-value, there may be no difference at all. This preliminary finding warrants study in a larger cohort.

Patients with an ileal pouch have a new system of defecation. The expulsive peristalsis of the rectum is replaced by the inertia of the pouch. Defecation becomes dependent on gravity and patients are prone to inefficient pouch-emptying. Several factors can impact pouch emptying and here we review a series of patients to illustrate these factors and their variable presentations.This is a retrospective, descriptive study of a series of patients who had undergone total proctocolectomy with ileal pouch anal anastomosis and presented with pouch dysfunction. Patients underwent investigations including, pouchoscopy, pouchography and anorectal physiology testing.There were 34 patients, 18 men, mean age 48.4 years. Thirty-one had a J-pouch and 3 an S-pouch. Twenty-eight had a stapled and 6 a hand-sewn anastomosis. Presenting complaints included difficulty emptying the pouch (n = 17), high stool frequency (n = 8), clinical bowel obstruction (n = 7), and nocturnal incontinence (n = 3). Diagnoses were anal stenosis (11), afferent-limb syndrome (n = 7), pouch twist (n = 4), paradoxical puborectalis contraction (n = 7), efferent-limb spasm/stenosis (n = 2), mega-pouch (n = 3), pouch prolapse (n = 1), and pouch-rectal anastomosis (n = 1). Treatments included anal dilation (n = 11), disimpaction (n = 2), biofeedback (n = 2), pouch excision (n = 2), laparotomy with lysis of adhesions (n = 6), Botox injection into puborectalis (n = 6), catheter drainage (3), and miralax (n = 11). All patients with a stenosis had some improvement after dilation, and surgery restored pouch function.Accurate diagnosis and effective treatment of pouch dysfunction is based on an appreciation of pouch physiology, correction of anatomic abnormalities that impair emptying, and management of stool consistency.

Transition of care (TOC) in adolescents and young adults (AYAs) with chronic gastrointestinal disorders has received increased attention, especially in those with inflammatory bowel disease. AYAs with hereditary polyposis syndromes are a heterogeneous group of patients with overlapping and complex medical needs. These patients are particularly vulnerable because of the risk of loss of continuity of care and subsequent poor disease outcomes. The Pediatric Committee of the American College of Gastroenterology commissioned a report with recommendations on TOC in AYAs with hereditary polyposis syndromes. This report aims at achieving best practice by both pediatric and adult gastroenterologists despite the paucity of published evidence in this population reflected in the included PRISMA report. Therefore, the group extrapolated findings from the literature related to other chronic gastrointestinal disorders, and a high degree of expert consensus was scored for all recommendations. The report addresses TOC through identifying shared domains followed by specific recommendations in disease management, including models of care, providers and patient and socioeconomic factors relevant to TOC. Areas of strong emphasis include the need for early planning, flexibility in the transition process to maintain continuity during major surgical procedures, patient and family psychological readiness, liaison among team members addressing transition, and changing insurance coverage in this population.

Background and Aims Gastric cancer is an extracolonic manifestation of familial adenomatous polyposis (FAP) and is associated with high-risk gastric polyps. There are no known endoscopic criteria to identify these high-risk polyps. Our aim was to develop endoscopic criteria to identify high-risk polyps on endoscopy in FAP. Methods We prospectively collected 150 gastric polyps in consecutive patients undergoing surveillance EGD at the Cleveland Clinic. Pictures were taken of each polyp under narrow-band imaging and high-definition white light. In an exploratory phase, 5 endoscopists developed consensus criteria using the images to distinguish high-risk (pyloric gland adenoma, tubular adenoma, hyperplastic) from low-risk (fundic gland with low-grade or no dysplasia) polyps. In the assessment phase, endoscopists were blinded to polyp pathology and used the criteria to predict the individual polyp risk category. To measure diagnostic accuracy, we reported the mean sensitivity, specificity, and interrater agreement (κ). Results Consensus criteria were developed based on 16 low-risk and 9 high-risk polyps. The final 149 polyps consisted of 128 low-risk and 22 high-risk polyps (1 polyp was excluded from analysis). Using the criteria, the 5 endoscopists distinguished high- from low-risk polyps with a mean sensitivity and specificity of 79% (16.3%) and 78.8% (10.8%), respectively. The κ coefficient was .45, indicating moderate agreement. Conclusions We developed endoscopic criteria to distinguish between high- and low-risk polyps associated with gastric cancer in FAP. The criteria provide guidance to endoscopists in targeting high-risk polyps while surveying the stomach of patients with proximal gastric polyposis.

Recent single-institution studies have shown that colorectal cancer (CRC) in patients 70 having a left-sided CRC (< 50 vs ≥ 70; OR = 2.8; 95% CI 2.7, 2.9). The incidence of CRC in those under 50 increased over the study period due to an increase in left-sided tumors. The distribution of CRC varied with race, with African-Americans having a lower odds for left-sided CRC (OR = 0.89; 95% CI 0.87, 0.91) and Asians/Pacific Islanders having a higher odds (OR = 1.8; 95% CI 1.7, 1.9). In the < 50 age group, the incidence of CRC is increasing, with majority of these tumors left-sided. Tumor location varies with both age and race.

In the West, piecemeal endoscopic resection remains the primary treatment for large colon polyps (LCP), as most recurrences are believed to be benign and resectable with follow-up endoscopy. However, invasive malignancy at the site of prior piecemeal endoscopic mucosal resection has been reported in the Asian literature. This study aims to identify the incidence of and the risk factors for local recurrence with malignancy after endoscopic resection of LCP with high-grade dysplasia (HGD). In this retrospective cohort study, we identified patients undergoing complete endoscopic resection of LCPs (≥ 20 mm) with HGD at the Cleveland Clinic between January 2000 and December 2016. Demographic, endoscopic, and pathologic data were collected. All subsequent endoscopic and pathology reports were reviewed to identify recurrence. The cumulative incidence of malignancy at the polypectomy site was determined and univariate analysis was performed to assess risk factors. A total of 254 LCPs with HGD were resected in 229 patients. Mean polyp size was 29.2 mm. There were 138 lesions resected in piecemeal fashion and 116 en-bloc. After a median follow-up of 28.7 months for the entire cohort, local recurrence with malignancy was diagnosed in six cases. Median time to malignancy diagnosis was 28.5 months. All malignant cases occurred after piecemeal resection and none after en-bloc resection (HR 11.4; 95% CI 0.48–273). Malignancy after endoscopic resection of LCPs with HGD is uncommon and may be associated with piecemeal resection. When possible, en-bloc resection should be the goal for the management of LCPs.

Pancreas-sparing duodenectomy (PSD) offers definitive therapy for duodenal polyposis associated with familial adenomatous polyposis (FAP). We reviewed the long-term complications of PSD and evaluated the incidence of high-grade dysplasia (HGD) and cancer in the remaining upper gastrointestinal tract. Forty-seven FAP patients with duodenal polyposis undergoing PSD from 1992 to 2019 were reviewed. Long-term was defined as > 30 days from PSD. All patients were treated with an open technique, and 43 (91.5%) had Spigelman stage III or IV duodenal polyposis. Median follow-up was 107 months (IQR, 26–147). There was no 90-day mortality. Seven patients died at a median of 10.5 years (IQR, 5.4–13.3) after PSD, with one attributed to gastric cancer. Pancreatitis occurred in 10 patients (21.3%), and two required surgical intervention. Seven patients (14.9%) developed an incisional hernia, and all underwent definitive repair. Forty-one patients (87.2%) had postoperative surveillance endoscopy over a median follow-up of 111 months (IQR, 42–138). Three patients (6.4%) developed adenocarcinoma (two gastric, one jejunal), and four (8.5%) had adenomas with HGD (two gastric, two jejunal) with a median of 15 years (IQR, 9–16) from PSD. One patient with gastric adenocarcinoma and all patients with HGD or adenocarcinoma of the jejunum required surgical intervention. PSD can be performed with a low but definable risk of long-term morbidity. Risk of gastric and jejunal carcinoma rarely occurs and was diagnosed decades after PSD. This demonstrates the need for lifelong endoscopic surveillance and educates us on the risk of carcinoma in the remaining gastrointestinal tract.

Background Precursor colonic polyps of varied subtypes correlate with the known neoplastic pathways. When patients present with synchronous pre-malignant polyps of multiple histologies, multiple genetic mechanisms are likely to be active, potentially resulting in a more unstable, tumourigenic mucosa. Methods We hypothesized that patients with a combination of sessile serrated adenomas/polyps (SSA/Ps), hyperplastic (HP) polyps and adenomas would be at highest risk of developing dysplasia/cancer compared to SSA/Ps alone, due to the synergistic effect of multiple active carcinogenic pathways. A prospective colonoscopy database was examined for patients with a history of SSA/P. Patients were placed into four groups based on patterns of polyp histology as follows: (i) only SSA/Ps; (ii) SSA/P + HP; (iii) SSA/Ps + adenomas; and (iv) SSA/Ps + HP + adenomas. These groups were compared in terms of the numbers, size, location and histology of polyps and personal or family history of colorectal cancer. Results A total of 374 patients were included. The average age was 70 years (range 21-88), and 43% were male. There was a trend towards the most aggressive neoplastic pattern in group 4, associated with a tendency to larger SSA/Ps, more villous architecture in the adenomas and more high-grade dysplasia in both types of polyps. It was also associated with multiplicity of both SSA/Ps and adenomas. No SSA/Ps existing in the absence of adenomas had cytological dysplasia. Conclusion The combination of SSA/Ps, HP and adenomas in the colorectal epithelium seems to be a marker for aggressive carcinogenesis and suggests that accurate and effective surveillance is important to manage this risk.

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. 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. 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. High-risk advanced adenomas are predominantly left sided. This focuses attention on the rectum and left colon where carcinogenesis is strong in the young.

Juvenile polyposis syndrome (JPS) patients can have a significantly high burden of polyposis. Patient who undergoes prophylactic colectomy for polyps not amenable to endoscopic treatments requires close clinical surveillance to negate risk of malignancy from interval polyposis.

Familial adenomatous polyposis affects primarily the colon but can also involve other locations within the gastrointestinal tract, including the duodenum. The aim of this study was to describe a single center experience with pancreas-sparing duodenectomy for familial adenomatous polyposis and to compare outcomes with pancreatoduodenectomy performed for duodenal polyp disease.A retrospective review of a prospectively maintained database identified patients who had undergone pancreas-sparing duodenectomy during the period 2001 to 2016. This population was matched 1:1 with a cohort of patients undergoing pancreatoduodenectomy for duodenal adenomas, both sporadic and familial, during the same time period. Baseline demographics and perioperative (short- and long-term) outcomes were compared.A total of 88 patients were included; 44 in each group. The pancreas-sparing duodenectomy cohort was younger (52.6 vs 64.3 years; P.001) and more patients had undergone prior colectomy (100% vs 32%; P.001) or additional prior abdominal surgery (27% vs 9% (P.001). Median operative times were greater for pancreatoduodenectomy (391 vs 460 min; P = .002). There was no difference in any of the early postoperative complications. There was 1 30-day mortality in the pancreatoduodenectomy group secondary to aspiration. Late acute pancreatitis was more common after pancreas-sparing duodenectomy (16% vs 0%; P = .012) and exocrine pancreatic insufficiency was more common after pancreatoduodenectomy (30% vs 11%; P = .034).Pancreas-sparing duodenectomy is a reasonable option for duodenal cancer prophylaxis in familial adenomatous polyposis with high-risk features. The perioperative safety profile is comparable to pancreatoduodenectomy done for similar indications, and pancreas-sparing duodenectomy has a favorable long-term with a lesser incidence of exocrine impairment.

BACKGROUND Almost all patients with familial adenomatous polyposis undergo abdominal surgery with a risk of disease and surgery-related complications. This, the familial nature of the syndrome, and its wide-ranging manifestations make patients prone to mental health symptoms. If this is true, patients need appropriate evaluation and treatment. OBJECTIVE The purpose of this study was to record the experience of mental health symptoms in a group of unselected patients with FAP. DESIGN We conducted an observational study using an anonymized mental health symptom survey for patients affected with familial adenomatous polyposis. SETTINGS The study was conducted using the Hereditary Colorectal Cancer Registry in a tertiary referral center. PATIENTS Patients affected with familial adenomatous polyposis were included. MAIN OUTCOME MEASURES Results of the mental health survey were measured. RESULTS Seventy nine of 100 patients completed the survey; 57 endorsed ≥1 psychosocial symptom (72.2%). with a mean of 4 per patient. Nine patients (11.4%) met all 4 of the American Psychiatric Association diagnostic criteria for posttraumatic stress disorder, and 8 (10.1%) endorsed partial posttraumatic stress disorder criteria (3/4 symptoms). Patients who met all of the criteria for posttraumatic stress disorder had an average of 9.3 psychosocial symptoms each compared with 8.3 for those who met 3 of 4 and 2.2 for those who met

Our understanding of the molecular basis of colorectal neoplasia is derived from Mendelian genetics, with tumor suppressor genes contributing more to the deregulation of growth than oncogenes. In patients with hereditary syndromes, expression of one allele of a key tumor suppressor gene is absent at birth. The loss of the expression of the second allele precipitates tumorigenesis. However, there are multiple ways in which the expression of the second allele of a tumor suppressor gene is lost. Here, we review these ways and their possible effect on phenotype.

No long-term pouch studies have included follow-up30 years or an analysis in patients80 years old.This study aimed to investigate pouch function and pouch failure in patients with a pouch in situ30 years and in patients80 years old.This is a retrospective review.This study was conducted at an IBD referral center.Adult patients with ulcerative colitis who underwent an IPAA between 1983 and 1990 were selected.The primary outcomes measured were pouch function and pouch failure rates.Data collection included diagnosis, age at IPAA, indication for IPAA, medications at IPAA, pathology at the time of IPAA, postoperative morbidity, functional outcomes, quality of life, pouch excision or ileostomy and indication, and date of last follow-up. All living patients were contacted in April 2020 to retrieve functional data and pouch failure rates.A total of 566 patients had a pouch constructed between 1983 and 1990; of the 145 at most recent contact, 75 had their pouch in situ ≥30 years and 14 were ≥80 years old. Mean age at diagnosis was 25.8 years (10.6 SD), age at surgery was 34.7 years (11.3 SD), and age at last follow-up was 60.5 years (13.2 SD). At a median of 30 years (IQR, 21-32), 145 patients responded to the functional survey. Significantly increased rates of urgency (always, mostly, sometimes: 71.5% vs 23.5%) and seepage during the day (71.4% vs 22.4%) were observed in patients ≥80 years. In patients ≥80 years with a pouch in situ ≥30 years, urgency and incontinence were sometimes experienced by nearly 50% and pouch failure occurred in one third of patients. The overall rate of pouch failure was 19.4% (n = 110) at a median follow-up of 15 years; risk factors were female sex, 3-stage approach, and pelvic sepsis.A retrospective database was used.Patients with IPAA maintain good pouch function even after 30 years and in patients over the age of 80 years. Pouch function declines with time and failure rates increase over time. See Video Abstract at http://links.lww.com/DCR/B684.Función De La Bolsa Ileal En El Tiempo Y En Pacientes De Edad Avanzada.No se han efectuado estudios en pacientes con bolsa a largo plazo que incluyan un seguimiento por treinta años o más y en pacientes mayores de 80 años.Investigar la funcionalidad o la falla de la bolsa en pacientes bolsa in situ por mas de treinta años y en pacientes mayors de 80 años.Revisión retrospective.Centro de referencia de Enfermedad Inflamatoria Intestinal.Pacientes adultos con diagnóstico de colitis ulcerative sometidos a anastomosis bolsa ileal anal (IPAA) entre 1983 y 1990.Indices de efectividad y disfunción de la bolsa ileal.Recopilación de la información incluyendo diagnóstico, edad del procedimiento (IPAA), indicaciones para IPAA, medicamentos para IPAA, patología en el transcurso del IPAA, morbilidad postoperatoria, resultados funcionales, calidad de vida, excisión de la bolsa o ileostomía y su indicación y fecha de seguimiento mas reciente. Se contactaron a todos los pacientes vivos en abril de 202 para recuperar la información de los índices de funcionalidad o disfunción de la bolsa.Se les construyó una bolsa a un total de 566 pacientes entre 1983 y 1990; de los 145 mas recientemente contactados, 75 permanecían con su bolsa in situ ≥ 30 años y 14 eran mayores de 80 años. La edad media en el momento de diagnóstico fue de 25.8 años (con desviación estándar de 10.6, sd), edad al momento de la cirugía fue de 34.7 años (11.3sd), y la edad en el último seguimiento de 60.5 años (13.2,sd). A una media de 30 años (IQR: 21,32), 145 pacientes respondieron al cuestionario de funcionalidad. En pacientes mayores de 80 años se observaron tasas aumentadas de urgencia (siempre, la mayor parte de las veces, algunas veces: 71.5% vs 23.5%) y fuga durante el día (71.4% versus 22.4%). En pacientes mayores de 80 años con una bolsa in situ durante 30 años o más, experimentaron urgencia e incontinencia en cerca del 50% y disfunción de la bolsa en un tercio de los pacientes. La tasa global de fallo de la bolsa fue de 19.4% (n = 110) en un seguimiento a 15 años; los factores de riesgo asociados fueron: sexo femenino, abordaje de tres tiempos y sepsis pélvica.Información retrospective.Los pacientes con IPAA continúan con una función adecuada de la bolsa aún después de 30 años de efectuada así como en pacientes mayores de 80 años. La funcionalidad de la bolsa disminuye con el tiempo y las tasa de falla aumentan de igual forma con el tiempo. Consulte Video Resumen en http://links.lww.com/DCR/B684. (Traducción- Dr. Miguel Esquivel-Herrera).

Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and onlyBackground Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only 10-19% having a penetrance of 40-60%. Interpretation Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding National Health and Medical Research Council, Australia. Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.

BACKGROUND Rectal cuff and anal transitional zone neoplasia is an increasing challenge in patients with familial adenomatous polyposis who have undergone restorative proctocolectomy. Its real incidence, range of severity, and treatment efficacy are poorly documented. OBJECTIVE We sought to document the evolution of rectal cuff and anal transitional zone neoplasia and describe its management. DESIGN This is a retrospective cohort study collecting prospectively recorded data. SETTINGS This study involved a hereditary colorectal cancer group in a large academic medical center. PATIENTS All patients undergoing primary restorative proctocolectomy at this institution were included. INTERVENTIONS Surveillance pouchoscopy and treatment of rectal cuff/anal transitional zone neoplasia were performed. MAIN OUTCOME MEASURES The primary outcomes measured were the presence and the severity of rectal cuff/anal transitional zone neoplasia. Excision by cautery, snare, mucosectomy, or redo pouch was evaluated. RESULTS A total of 165 patients were included: 52% were male (86/165) with a median age at restorative proctocolectomy of 31.0 years (SD 12.8). In 117 of 165, the proctocolectomy was their first operation and, in 48 of 165, it followed a colectomy. Of the patients, 83% (137/165) had stapled anastomosis; 17% had mucosectomy with handsewn anastomosis; and 14% (23/165) were treated with sulindac at some point during their surveillance. Median follow-up was 10.1 years (interquartile range, 4.5-17.2) and the median number of pouchoscopies per patient was 4 (interquartile range, 2-8). Seventy-eight of 165 (47.3%) developed rectal cuff/anal transitional zone adenomas, more in the stapled group (52.3%; 72/137) than in the handsewn group (21.4%; 6/28; p < 0.005). Median time to adenoma was 4.5 years (interquartile range, 2.4-8.9). Three patients developed cancer under surveillance, and, in 3 other patients, cancers developed when screenings lapsed. Five patients developed symptomatic anal stenosis secondary to repeated surgeries (median, 9 procedures; range, 2-10). LIMITATIONS There was no quality-of-life measurement in patients who developed rectal cuff/anal transitional zone neoplasia. CONCLUSIONS Rectal cuff/anal transitional zone adenomas are more common than previously reported. Mild polyposis can be controlled endoscopically, but repeated procedures in a higher stage are associated with risk of anal stenosis. Compliance with surveillance is essential to avoid cancer. See Video Abstract at http://links.lww.com/DCR/B594. INCIDENCIA Y TRATAMIENTO DE LA NEOPLASIA DEL REMANENTE RECTAL Y DE LA ZONA DE TRANSICIN ANAL EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR ANTECEDENTES:La neoplasia del remanente rectal y de la zona de transicion anal presenta un desafio mayor en pacientes con poliposis adenomatosa familiar tratados con una proctocolectomia restaurativa. Su incidencia real, el espectro de la gravedad y la eficacia del tratamiento estan mal documentados.OBJETIVO:Buscamos documentar la evolucion de la neoplasia del remanente rectal y de la zona de transicion anal y describir su tratamiento.DISENO:Estudio de cohorte retrospectivo que recabo datos registrados prospectivamente.AMBITO:Un grupo con cancer colorrectal hereditario de un importante centro medico academico.PACIENTES:Todos los pacientes operados por primera vez de proctocolectomia restaurativa en nuestra institucion.INTERVENCIONES:Endoscopia del pouch para vigilancia y tratamiento de la neoplasia del remanente rectal / zona de transicion anal.PRINCIPALES VARIABLES ANALIZADAS:La presencia y la gravedad de la neoplasia del remanente rectal / zona de transicion anal. Reseccion con cauterio, asa, mucosectomia o rehacer el pouch.RESULTADOS:Se incluyeron un total de 165 pacientes: 52% eran hombres (86/165) con una mediana de edad al momento de la proctocolectomia restaurativa de 31,0 anos (DE 12,8). En 117/165 la proctocolectomia fue su primera cirugia y en 48/165 fue posterior a una colectomia. En 83% (137/165) tenia una anastomosis con engrapadora, 17% tenia mucosectomia y anastomosis con sutura manual (HS). El 14% de los pacientes (23/165) fueron tratados con sulindac en algun momento durante su vigilancia. La mediana de seguimiento fue de 10,1 anos (IQR: 4,5, 17,2) y la mediana del numero de endoscopias del pouch por paciente fue de 4. (IQR: 2, 8) 78/165 (47,3%) desarrollaron adenomas en la zona de transicion anal /remanente rectal, mayor en el grupo con engrapadaora (52,3%; 72/137) comparado con el grupo con sutura manual (21,4%; 6/28) (p

Rupture of a superior mesenteric artery pseudoaneurysm is a rare but potentially lethal complication in patients with familial adenomatous polyposis and desmoid disease.We report our experience in the management of such patients with a rare but significant and life-threatening condition.This is a descriptive study of a small series of patients.Data were obtained from their medical charts and from the Cologene Database of the David G. Jagelman Polyposis Registry in the Sanford R. Weiss, M.D., Center for Hereditary Colorectal Cancer at the Cleveland Clinic Foundation.Of 227 patients with mesenteric desmoid disease, there were 4 cases of superior mesenteric artery pseudoaneurysm rupture.We reviewed the patients with mesenteric desmoid tumors in our desmoid registry. The registry is approved by the institutional review board of the Cleveland Clinic.The patients were young (aged from 22 to 28 y at presentation), with otherwise minimal comorbidities. Two patients had a previous proctocolectomy and J-pouch, and 2 had a total colectomy and ileorectal anastomosis. Two patients had preemptive endoluminal stenting and fared better than the 2 who had damage control embolization. One patient died and, in the others, recovery was prolonged and complicated. Two of the 4 patients have ended up with a reasonable quality of life.We acknowledge that this is a rare complication of an uncommon disease and, as such, any case series will be limited by small numbers; therefore, a tailored approach is warranted when managing such complex patients.We advocate an increased awareness of the possibility of visceral pseudoaneurysms in patients with familial adenomatous polyposis who have desmoid disease encasing the superior mesenteric artery. See Video Abstract at http://links.lww.com/DCR/A914.

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.

Colorectal cancer (CRC) is common and at least 80% of cases are sporadic, without any significant family history. Prognostication and treatment have been relatively empirical for what has become increasingly identified as a genetically heterogeneous disease. There are three main genetic pathways in sporadic CRC: the chromosomal instability pathway, the microsatellite instability pathway and the CpG island methylator phenotype pathway. There is significant overlap between these complex molecular pathways and this limits the clinical application of CRC genetics. Recent Australian and New Zealand guidelines recommend routine testing of mismatch repair (MMR) status for new cases of CRC and selective KRAS and BRAF testing on the basis of diagnostic, prognostic and therapeutic implications. It is important that all clinicians treating CRC have an understanding of the importance of and basis for identifying key genetic features of CRC. It is likely that in the future better molecular characterization such as that allowed by the consensus molecular subtype classification will allow improved prognostication and targeted therapy in order to deliver more personalized treatment for CRC.

The prognostic association between mesorectal grading and oncological outcome in patients undergoing resection for rectal adenocarcinoma is controversial. The aim of this retrospective chart review was to determine the individual impact of mesorectal grading on rectal cancer outcomes.We compared oncological outcomes in patients with complete, near-complete and incomplete mesorectum who underwent rectal excision with curative intent from 2009 to 2014 for Stage cI-III rectal adenocarcinoma. We also assessed the independent association of mesorectal grading and oncological outcome using multivariate models including other relevant variables.Out of 505 patients (339 men, median age of 60 years), 347 (69%) underwent a restorative procedure. There were 452 (89.5%), 33 (6.5%) and 20 (4%) patients with a complete, near-complete and incomplete mesorectum, respectively. Local recurrence was seen in 2.4% (n = 12) patients after a mean follow-up of 3.1 ± 1.7 years. Unadjusted 3-year Kaplan-Meier analysis by mesorectal grade showed decreased rates of overall, disease-free and cancer-specific survival and increased rates of overall and distant recurrence with a near-complete mesorectum, while local recurrence was increased in cases of an incomplete mesorectum (all P 0.05). On multivariate analyses, a near-complete mesorectum was independently associated with decreased cancer-specific survival (hazard ratio 0.26, 95% CI 0.1-0.7; P = 0.007). There were no associations between mesorectal grading and overall survival, disease-free survival, overall recurrence or distant recurrence (all P 0.05).Mesorectal grading is independently associated with oncological outcome. It provides unique information for optimizing surgical quality in rectal cancer.

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 (age50 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.This was a retrospective cohort study.The study was conducted at a high-volume tertiary referral center.Patient samples included those from our colorectal cancer biobank of resected colorectal cancer specimens.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 age50 or50 years and decade of diagnosis (≤50, 51-60, 61-70, 71-80, and81 y). Patients with IBD or hereditary syndromes were excluded.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 aged50 years (p0.001). An increasing percentage of tumors were CpG island phenotype high with each decade of age at diagnosis. No cancers in patients50 years of age were microsatellite unstable compared with 91 (23.6%) of 346 for those50 years of age. No young cancers contained a BRAF mutation compared with 46 (10.6%) of 434 in older cancers (p0.001). KRAS mutations were less common in young cancers compared with older cancers (13/57 (22.8%) vs 126/410 (30.7%); p0.01). Eleven (19.3%) of 57 young cancers were proximal compared with 228 (51.8%) of 440 (p0.001) older cancers.This study was limited by its retrospective design.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.

Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

The recent interest in transanal, minimally invasive surgery has highlighted the importance of an in depth understanding of this complex region. We applied data from an anatomical study of the perineum to the concept of transanal minimally invasive surgery with the aim to describe more accurately anatomy relevant to this surgical technique. A consecutive series of adult patients undergoing colonoscopy were approached for consent to measure dimensions and angles of the perineum before the examination. Distances from the posterior margin of the anus to the coccyx, and the anterior margin of the anus to the posterior edge of the scrotum or introitus were measured. Then, using a pediatric proctoscope and a protractor, the anoperineal angle and the recto perineal angles were measured. The anorectal angle was derived from these measurements. Data is described using means and standard deviations. Measurements were obtained from 106 patients undergoing elective colonoscopy for average risk screening with no history of defecatory disorder. Posterior perineal length was similar in both sexes (4.5 cm ± 0.9 in women and 4.6 cm ±0.7 in men) but the anterior perineum was significantly shorter in women (2.5 ± 0.8). The mean anoperineal angle was 93° (±9), and mean rectoperineal angle was 73° (±9). These angles varied significantly between the sexes. The mean anorectal angle (derived) was 160° (±9), and did not differ significantly between the sexes. There was no correlation between the posterior perineal length and ano perineal, recto perineal, or anorectal angles. Limitations: small sample size. Anoperineal and recto perineal differ significantly between the sexes. Surgeons using transanal minimally invasive surgical techniques should expect to alter the alignment of their dissection accordingly. This study shows the magnitude of the differences that can exist. Clin. Anat. 32:68-72, 2019. © 2018 Wiley Periodicals, Inc.

We describe a simple endoscopic grading system of diverticular disease for the assessment of disease severity and prediction of outcomes.A retrospective analysis of prospectively maintained colonoscopy database was conducted. A single endoscopist prospectively graded disease severity according to the number and size of diverticula, the degree of muscular hypertrophy and rigidity of the sigmoid colon.762 patients were included in the analysis. Mean patient age was 70 years (range 37-97). Endoscopic severity of diverticulosis was predictive of the need for surgery, with 2% in the mild-moderate, 12% in the severe and 33% in the acute group (p 0001). Time to surgery showed correlation to severity grade, with mean periods of 107.5 months in the moderate group vs. 3 and 2.5 months in the severe and acute group (p 0001). The mean follow up was 11 years.Surgeons should consider using endoscopic grading as an adjunct to clinical management decisions.

It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes—people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 MLH1, 314 MSH2, 126 MSH6, 71 PMS2, and 22 EPCAM) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided P > .05). The hazard ratio per standard deviation of the PRS for colorectal cancer was 0.97 (95% confidence interval = 0.88 to 1.06; 2-sided P = .51). Whereas PRSs are predictive of colorectal cancer in the general population, they do not predict Lynch syndrome colorectal cancer.

BACKGROUND: The efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown. METHODS: We evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease. RESULTS: A total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine-sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine-sulindac as compared with sulindac (P = 0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine-sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups. CONCLUSIONS: In this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.).

Multigene panel tests for hereditary cancer syndromes are increasingly utilized in the care of colorectal cancer (CRC) and polyposis patients. However, widespread availability of panels raises a number of questions including which patients should undergo testing, which genes should be included on panels, and the settings in which panels should be ordered and interpreted. To address this knowledge gap, key questions regarding the major issues encountered in clinical evaluation of hereditary CRC and polyposis were designed by the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer Position Statement Committee and leadership. A literature search was conducted to address these questions. Recommendations were based on the best available evidence and expert opinion. This position statement addresses which genes should be included on a multigene panel for a patient with a suspected hereditary CRC or polyposis syndrome, proposes updated genetic testing criteria, discusses testing approaches for patients with mismatch repair proficient or deficient CRC, and outlines the essential elements for ordering and disclosing multigene panel test results. We acknowledge that critical gaps in access, insurance coverage, resources, and education remain barriers to high-quality, equitable care for individuals and their families at increased risk of hereditary CRC.

BackgroundHereditary 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.MethodsPatients 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.Results506/4254 (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.ConclusionThe 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.

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 DESPUeS 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 pelvico, rehacer el reservorio es una opcion. Sin embargo, se desconoce si en los pacientes seleccionados con enfermedad de Crohn se deberia ofrecer la oportunidad de evitar la derivacion permanente despues 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.Analisis retrospectivo de una base de datos de reservorios ileales mantenida prospectivamente (1983-2017).Este estudio incluyo a pacientes que se sometieron a cirugia para rehacer el reservorio ileal con un diagnostico en el especimen quirurgico primario de colitis ulcerosa o de Crohn en el momento del reservorio inicial.La falla del reservorio se definio como la escision del reservorio o la derivacion indefinida del reservorio. Las caracteristicas del paciente, los resultados perioperatorios y funcionales, la supervivencia del reservorio y la calidad de vida se compararon de acuerdo con el diagnostico.De 422 pacientes, 392 tenian colitis ulcerativa y 30 tenian enfermedad de Crohn. La edad y el genero fueron comparables. Las indicaciones mas comunes para rehacer el reservorio incluyeron dehiscencia anastomotica y fistulas [220 (56,1%) en colitis ulcerosa y 21 (70%) en la enfermedad de Crohn]. La mayoria de los reservorios rehechos requirieron mucosectomia con anastomosis manual [310 (79%) en colitis ulcerosa y 30 (100%) en la enfermedad de Crohn, p = 0.23]. Se construyo un nuevo reservorio en 160 (41%) pacientes con colitis ulcerativa y se reparo el reservorio antiguo en 231 (59%) pacientes, en comparacion con 25 (83%) en la enfermedad de Crohn, que requirieron creacion de un nuevo reservorio, y solo 5 (17%) donde el reservorio antiguo se volvio 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 anos 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 fistulas del reservorio y / o las estenosis que ocurrieron despues del cierre de ileostomia. Estas fueron mas comunes en la enfermedad de Crohn que en la colitis ulcerativa (p

No formal guidelines exist for surveillance pouchoscopy following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis.All adults who had previously had IPAA for ulcerative colitis, and underwent a pouchoscopy between 1 January 2010 and 1 January 2020, were included.A total of 9398 pouchoscopy procedures were performed in 3672 patients. The majority of the examinations were diagnostic (8082, 86·0 per cent; 3260 patients) and the remainder were for routine surveillance (1316, 14·0 per cent; 412 patients). Thirteen patients (0·14 per cent of procedures) were found to have biopsy-proven neoplasia at the time of pouchoscopy; seven had low-grade dysplasia (LGD) (0·07 per cent; all located in the anal transition zone), none had high-grade dysplasia (HGD) and six (0·06 per cent) had invasive adenocarcinoma (4 in anal transition zone and 6 in pouch). Of the six patients with adenocarcinoma, four had neoplasia at the time of proctocolectomy (2 adenocarcinoma, 1 LGD, 1 HGD); all six were symptomatic with anal bleeding or pelvic pain at the time of pouchoscopy, had a negative surveillance pouchoscopy examination within 2 years of diagnosis of adenocarcinoma, had palpable masses on digital rectal examination, and had visible lesions at the time of pouchoscopy.Surveillance pouchoscopy is not recommended in asymptomatic patients because significant neoplasia following IPAA for ulcerative colitis is rare.No existen unas recomendaciones formales para vigilancia endoscópica en pacientes a los que se les ha realizado un reservorio ileoanal (ileal pouch anal anastomosis, IPAA) por una colitis ulcerosa (ulcerative colitis, UC). MÉTODOS: Se incluyeron todos los pacientes adultos a los que se les había realizado previamente un IPAA por UC y se sometieron a una endoscopia del reservorio.Se realizaron un total de 9.398 procedimientos endoscópicos en 3.672 pacientes entre el 1/1/2010 y el 1/1/2020. La mayoría de las exploraciones fueron diagnósticas (n = 8.082; 86%; 3.260 pacientes) y el resto fueron de seguimiento (n = 1.316; 14%; 412 pacientes). Se descubrió que 13 pacientes tenían una neoplasia demostrada por biopsia (0,14%) en el momento de la endoscopia; siete pacientes tenían displasia de bajo grado (low-grade displasia, LGD) (0,074%; localizada en todos los casos en la zona de transición anal), ninguno tenía displasia de alto grado (high-grade displasia, HGD) y seis (0,064%) tenían un adenocarcinoma invasivo (cuatro en la zona de transición anal) y dos en el reservorio). De los seis pacientes con adenocarcinoma, 4 tenían neoplasia en el momento de la proctocolectomía (2 adenocarcinoma, uno LGD, uno HGD). Todos estos pacientes tenían síntomas de hemorragia anal o dolor pélvico en el momento de la endoscopia, se les había practicado una endoscopia previa reciente del reservorio en los dos años anteriores, presentaban una masa palpable en la exploración digital rectal, así como lesiones visibles en la endoscopia del reservorio. CONCLUSIÓN: La vigilancia endoscópica del reservorio no se recomienda en pacientes asintomáticos porque es raro que aparezca una neoplasia después del IPAA por UC.

Background: Familial adenomatous polyposis (FAP) is a condition typically caused by pathogenic germline mutations in the APC gene. In addition to colon polyps, individuals with FAP have a substantially increased risk of developing papillary thyroid cancer (PTC). Little is known about the events underlying this association, and the prevalence of somatic "second-hit" mutations in APC is controversial. Methods: Whole-genome sequencing was performed on paired thyroid tumor and normal DNA from 12 FAP patients who developed PTC. Somatic mutation profiles were compared with clinical characteristics and previously sequenced sporadic PTC cases. Germline variant profiling was performed to assess the prevalence of variants in genes previously shown to have a role in PTC predisposition. Results: All 12 patients harbored germline mutations in APC, consistent with FAP. Seven patients also had somatic mutations in APC, and seven patients harbored somatic mutations in KMT2D, which encodes a lysine methyl transferase. Mutation of these genes is extremely rare in sporadic PTCs. Notably, only two of the tumors harbored the somatic BRAF p.V600E mutation, which is the most common driver mutation found in sporadic PTCs. Six tumors displayed a cribriform-morular variant of PTC (PTC-CMV) histology, and all six had somatic mutations in APC. Additionally, nine FAP-PTC patients had rare germline variants in genes that were previously associated with thyroid carcinoma. Conclusions: Our data indicate that FAP-associated PTCs typically have distinct mutations compared with sporadic PTCs. Roughly half of the thyroid cancers that arise in FAP patients have somatic "second-hits" in APC, which is associated with PTC-CMV histology. Somatic BRAF p.V600E variants also occur in some FAP patients, a novel finding. We speculate that in carriers of heterozygous pathogenic mutations of tumor suppressor genes such as APC, a cooperating second-hit somatic variant may occur in a different gene such as KTM2D or BRAF, leading to differences in phenotypes. The role of germline variance in genes other than APC (9 of the 12 patients in this series) needs further research.