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Desmoid disease results when the wnt signaling pathway in fibroblasts is constantly active. It is characterized by enlarging tumors and sclerosing sheets of tissue. In patients with familial adenomatous polyposis (FAP) this can happen in the abdomen, the abdominal wall and in extra-abdominal sites. This review describes the clinical sequelae of desmoid disease in patients with FAP and their management. While abdominal wall desmoids cause symptoms due to their increasing size and prominence, they can be resected with a recurrence rate of about 30%. Intra-abdominal desmoid disease often involves the small bowel mesentery and cannot be resected without enterectomy. Various medical options are available for their management but none are predictably successful. A staging system has been developed that predicts mortality and allows rational treatment choices. Specific complications such as obstruction of the ureter and small bowel, small bowel perforation with abscess and fistula, and hemorrhage may need surgical management. Most FAP patients with desmoid disease can live in equilibrium with the desmoids. The keys are to mitigate symptoms while avoiding toxic or dangerous therapy.

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.

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.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.This is a retrospective study.Patients from a single-institution tertiary care center were studied.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.There were no interventions.Oncologic outcomes were analyzed according to the presence of mucinous histology.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% (p0.0001) and 5-year overall survival was 54.7% versus 80.3% (p0.0001) 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 (p0.001). 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.This is a retrospective study without genetic information.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.

Colonoscopy in patients with diverticulosis can be technically challenging and limited data exist relating to the risk of post-colonoscopy diverticulitis. Our aim was to evaluate the incidence, management, and outcomes of acute diverticulitis following colonoscopy. Study design is retrospective cohort study. Data were gathered by conducting an automated search of the electronic patient database using current procedural terminology and ICD-9 codes. Patients who underwent a colonoscopy from 2003 to 2012 were reviewed to find patients who developed acute diverticulitis within 30 days after colonoscopy. Patient demographics and colonoscopy-related outcomes were documented, which include interval between colonoscopy and diverticulitis, colonoscopy indication, simultaneous colonoscopic interventions, and follow-up after colonoscopy. From 236,377 colonoscopies performed during the study period, 68 patients (mean age 56 years) developed post-colonoscopy diverticulitis (0.029%; 2.9 per 10,000 colonoscopies). Incomplete colonoscopies were more frequent among patients with a history of previous diverticulitis [n = 10 (29%) vs. n = 3 (9%), p = 0.03]. Mean time to develop diverticulitis after colonoscopy was 12 ± 8 days, and 30 (44%) patients required hospitalization. 34 (50%) patients had a history of diverticulitis prior to colonoscopy. Among those patients, 14 underwent colonoscopy with an indication of surveillance for previous disease. When colonoscopy was performed within 6 weeks of a diverticulitis attack, surgical intervention was required more often when compared with colonoscopies performed after 6 weeks of an acute attack [n = 6 (100%) vs. n = 10 (36%), p = 0.006]. 6 (9%) out of 68 patients received emergency surgical treatment. 15 (24%) out of 62 patients who had non-surgical treatment initially underwent an elective sigmoidectomy at a later date. Recurrent diverticulitis developed in 16 (23%) patients after post-colonoscopy diverticulitis. Post-colonoscopy diverticulitis is a rare, but potentially serious complication. Although a rare entity, possibility of this complication should be kept in mind in patients presenting with symptoms after colonoscopy.

Background Surgical technique constantly evolves in response to the pressure of progress. Ileal pouch anal anastomosis (IPAA) is a good example. We analyzed the effect of changes in practice on the technique of IPAA and its outcomes. Methods Patients undergoing primary IPAA at this institution were divided into three groups by date of IPAA: those operated from 1983-1993, 1994-2004, and 2005 – 2015. Demographics, patient comorbidity, surgical techniques, post-operative outcomes, pouch function and quality of life were analyzed. Results 4525 patients had a primary IPAA. With each decade, increasing numbers of surgeons were involved (decade I=8, II=16, III=31), patients tended to be sicker (higher ASA score) and 3-staged pouches became more common. After an initial popularity of the S pouch, J pouches became dominant and a mucosectomy rate of 12% was standard. Laparoscopic technique blossomed in the last decade. 90 day postoperative morbidity by decade was 38.3% vs. 50% vs. 48% (p

INTRODUCCION El Registro de Cancer Colorrectal Hereditario es uno de los registros mas antiguos y mas grandes de su tipo. Incluye a los pacientes con todos los sindromes hereditarios de cancer colorrectal, utilizando los tres enfoques basicos, la atencion al paciente, la educacion y la investigacion. Este articulo resume la estructura y funcion del registro, y da ejemplos de sus contribuciones al manejo de los pacientes afectados. ACTIVIDAD En el ano 2016 el registro atendio a mas de 1000 familias con poliposis adenomatosa familiar, 224 familias con sindrome de Lynch, 61 con poliposis asociada a MYH y 146 con poliposis hamartomatosa. En el ano 2016 hubo 1009 visitas de pacientes con 80 nuevos pacientes y 879 endoscopias. Se realizaron mas de 60 cirugias. RESUMEN Se describe el enfoque de “Cleveland Clinic” para el cancer colorrectal hereditario. Esto es multidisciplinario, involucrando varias especialidades y asi como servicios de asesoramiento genetico y de salud mental dentro del registro.

Patients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.

Colorectal cancer is the end result of an accumulation of destabilizing mutations and other genetic events, which occur in clones of colonocytes over many years. While each colorectal cancer is genetically unique, there are at least three distinct mechanisms by which the process occurs. The commonest is chromosomal instability, producing microsatellite stable, aneuploid cancers. The second is DNA promoter methylation that underlies CpG island methylation phenotype cancers, either microsatellite stable or unstable, and the third is loss of DNA mismatch repair, causing microsatellite unstable, diploid cancers. Cancers arising from these three mechanisms are biologically different and the differences have clinical implications.

Severity of Clostridium difficile infection (CDI) varies from one patient to another. We aimed to test the hypothesis that surgical patients would suffer more severe CDIs than medical patients. Patients receiving in-hospital medical or surgical treatment for any underlying disease from 2007 to 2012, who developed CDI, were divided into two groups: “Medical group” and “Surgical group.” Demographics, disease characteristics, and outcomes including mortality and recurrence were compared. Of 3231 patients with CDI evaluated, 1984 (61.4%) and 1247 (38.6%) were medical and surgical patients, respectively. Surgical patients had more severe CDIs than medical. However, the long-term effects of CDI were worse in medical patients, with more and quicker deaths. Recurrence was comparable between groups. Surgical patients were more frequently male, older, and obese; had higher white blood cells but lower levels of hemoglobin, hematocrit, and prealbumin; and had a higher rate of severe CDI. Conversely, medical patients had fewer in-hospital days, CDI appeared earlier, and had greater 30-day mortality and total number of deaths, with death after CDI occurring earlier. Although surgical patients tend to have a stormier clinical course related to CDI, overall they do better than medical patients. Future studies focusing on modifiable risk factors for each group are needed.

In the current study, we aimed to compare peri- and postoperative 30-day outcomes of patients undergoing laparoscopic versus open total colectomy with ileorectal anastomosis in a case-matched design using data procedure-targeted database. Patients who underwent elective total colectomy with ileorectal anastomosis in 2012 and 2013 were identified from the American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into two groups according to the type of surgical approach (laparoscopic and open). Laparoscopic and open groups were matched (1:1) based on age, gender, diagnosis, body mass index, and American Society of Anesthesiologists classification. Comorbidities, perioperative, and short-term (30-day) postoperative outcomes were compared between the matched groups. We identified 1442 patients—549 in the laparoscopic group and 893 patients in the open group. After case matching, there were 326 patients in each group. There were 48 (14.7%) patients who had conversion in the laparoscopic group. The open group had a higher proportion of patients with ascites [0 (0%) vs. 7 (2.1%) p = 0.015], preoperative weight loss [26 (8.0%) vs. 45 (13.8%) p = 0.018], and contaminated wound classifications [Clean/Contaminated 261 (80%) vs. 240 (74%), Contaminated 55 (16.9%) vs. 54 (16.6%), and Dirty/Infected 8 (2.5%) vs. 28 (8.6%), (p = 0.003)]. The laparoscopic group had a significantly longer operative time (242 ± 98 vs. 202 ± 116 min, p

Introduction Misconceptions exist about the proper way to use draining setons in the management of anal fistulas. This technical note lays out the principles for their use. Technique Insertion of draining setons is a prerequisite to successful management of anal fistulas. The correct technique involves identification of the correct track and internal opening and drainage of the track with a silastic seton. This sets the stage for definitive repair after the inflammation subsides. Results Three cases are presented to illustrate common errors made during the insertion of draining setons. Conclusions Appropriate seton drainage of an anorectal fistula is an important part of the ultimate repair. Correct use of setons minimizes symptoms from the seton itself and optimizes its effectiveness.

Recent single-institution studies have shown that colorectal cancer (CRC) in patients50 is predominantly left-sided. The aims of this study were to 1 compare the incidence of left-sided CRC in patients under and over 50, 2 investigate this trend over time, and 3 examine whether racial differences exist in the anatomical distribution of CRC.We used the Nationwide Inpatient Sample to identify all patients with colon or rectal cancer who underwent a resection from 2000 to 2014. Logistic regression models were used to determine the odds of a patient having a left-sided CRC based on age and race.A total of 1,547,589 patients underwent resection, with a mean age of 68.6. Overall, 65.1% of patients50 had a left-sided CRC compared with 47.2% of patients ≥ 50 (OR = 2.1; 95% CI 2.0, 2.1). The difference was greater as patients became older with 39.9% of patients70 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 the50 age group, the incidence of CRC is increasing, with majority of these tumors left-sided. Tumor location varies with both age and race.

Perianal symptoms occur in up to 50% of patients with Crohn's disease in other parts of the gastrointestinal tract, and in 5% of patients it is the first manifestation of the disease. The perianal area is often under stress in patients with Crohn's disease, because of the diarrhea, and the fecal urgency, frequency, and incontinence caused by proximal disease. Symptomatic perianal disease can therefore be due to the effects of the stress on an otherwise normal anus, or the result of Crohn's disease in the low rectum and/or perianal tissues themselves. This key distinction should drive the investigation and management of anal and perianal symptoms in patients with Crohn's disease. In this review, the evaluation and management of the various manifestations of Crohn's disease in the perineum and perianal tissues will be described.

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. Compare the distribution of colorectal cancer in African American patients and Caucasians under age 50, and describe implications for screening in these groups. 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

Introduction Patients undergoing an IPAA experience a completely different physiology of defecation than when they had a rectum. The new "normal" is poorly appreciated and incompletely understood, and the lack of understanding has implications for pouch function. This technical note lays out the physiology of defecation with an ileal pouch and its implications for patients and surgeons. Technique An intestinal pouch acts as a reservoir because the united antegrade and retrograde peristaltic loops produce no evacuatory pressure. Defecation occurs by gravity. Efficient defecation results in fewer stools, but inefficient defecation may cause stool frequency, incontinence, obstruction, constipation, and pouch inflammation. The technical aspects of pouch construction that impact emptying include a long efferent limb of an S-pouch, any degree of twist in the pouch body, afferent limb syndrome, and anal stenosis. Results Constructing a pouch with no twists and with an open anus, maintaining liquid stool, and encouraging unhurried defecation can improve pouch function. Conclusions Understanding pouch physiology is important in optimizing pouch function and maintaining patient expectations.

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. 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. 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

ObjectiveThe plasma-based methylated SEPTIN9 (mSEPT9) is a colorectal cancer (CRC) screening test for adults aged 50–75 years who are at average risk for CRC and have refused colonoscopy or faecal-based screening tests. The applicability of mSEPT9 for high-risk persons with Lynch syndrome (LS), the most common hereditary CRC condition, has not been assessed. This study sought preliminary evidence for the utility of mSEPT9 for CRC detection in LS.DesignFirstly, SEPT9 methylation was measured in LS-associated CRC, advanced adenoma, and subject-matched normal colorectal mucosa tissues by pyrosequencing. Secondly, to detect mSEPT9 as circulating tumor DNA, the plasma-based mSEPT9 test was retrospectively evaluated in LS subjects using the Epi proColon 2.0 CE assay adapted for 1mL plasma using the “1/1 algorithm”. LS case groups included 20 peri-surgical cases with acolonoscopy-based diagnosis of CRC (stages I-IV), 13 post-surgical metastatic CRC, and 17 pre-diagnosis cases. The control group comprised 31 cancer-free LS subjects.ResultsDifferential hypermethylation was found in 97.3% (36/37) of primary CRC and 90.0% (18/20) of advanced adenomas, showing LS-associated neoplasia frequently produce the mSEPT9 biomarker. Sensitivity of plasma mSEPT9 to detect CRC was 70.0% (95% CI, 48%-88%)in cases with a colonoscopy-based CRC diagnosis and 92.3% (95% CI, 64%-100%) inpost-surgical metastatic cases. In pre-diagnosis cases, plasma mSEPT9 was detected within two months prior to colonoscopy-based CRC diagnosis in 3/5 cases. Specificity in controls was 100% (95% CI 89%-100%).ConclusionThese preliminary findings suggest mSEPT9 may demonstrate similar diagnostic performance characteristics in LS as in the average-risk population, warranting a well-powered prospective case–control study.

Colorectal cancer (CRC) results from a series of complex, multistep genetic and molecular events causing uncontrolled cell growth. The underlying changes within the cells define distinct but somewhat overlapping tumor phenotypes. There are at least three well-defined pathways leading to CRC: chromosomal instability, microsatellite instability, and DNA hypermethylation. These pathways are present in cancers that develop via somatic mutations or within hereditary syndromes. The changes are manifest in both sporadic cancers and in hereditary syndromes. A relatively small proportion of CRCs develop as a consequence of a highly penetrant germline mutation in one gene, resulting in a familial cancer syndrome. The tumors that develop in these syndromes then follow the same evolutionary paths as sporadic tumors, but the risk for cancer is greatly elevated, forms at an early age, and is associated with multiple and metachronous colorectal and extracolonic cancers. The hereditary CRC syndromes are broadly classified as polyposis (adenomatous, hamartomatous, or mixed) or nonpolyposis syndromes (including hereditary nonpolyposis CRC, Lynch syndrome, and familial CRC type X). Each of these syndromes is associated with specific gene mutations that determine the clinical phenotype and define the cancer risk. This chapter provides an overview of the underlying changes in colorectal carcinogenesis and the hereditary CRC syndromes.

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.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.This was a retrospective cohort study.The study was conducted at a tertiary referral center.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.Age at which polyps were first diagnosed, location and size of polyps, demographics, and family history were measured.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% were2 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.No measurement of methylation or BRAF mutations in polyps or normal mucosa and a lack of subclassification of hyperplastic polyps limited this study.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.

BACKGROUND Large colorectal polyps can be treated either endoscopically or by formal resection. The aim of this study was to clarify the relative advantages and disadvantages of surgical resection and colonoscopic snaring as means of treating large colorectal polyps. METHODS This is a matched cohort study, comparing cases of surgical resection of benign colorectal polyps with endoscopic resection. Cases drawn from pathology and endoscopy databases were matched for the size and site of polyps, and the groups were compared for the end points of complications, length of hospital stay and completeness of the removal of the polyp. RESULTS There were 78 patients in each group, with mean ages of 65.6 years (colonoscopy) and 66.8 years (surgery). A total of 39 of the surgery group and 47 of the colonoscopy group were men. Mean polyp size was 34.1 mm (colonoscopy) and 32.1 mm (surgery). There was an exact match for polyp location. Complications occurred in eight colonoscopy patients (10.3%) and 42 surgery patients (56.0%) (P < 0.001, chi-square). Length of hospital stay was 0 days for colonoscopy patients and 7.3 ± 4.7 days for surgery (P < 0.001). The surgery group was separated into laparoscopic (n = 35) and open (n = 43) surgery. There was no difference in complication rates (42.4 versus 53.5%, respectively) but laparoscopic had shorter length of stay (5.8 days ± 4.9 SD versus 8.4 days ± 4.3 SD). Recurrence of surgically resected polyps was zero; at last follow-up 13% of snared polyps persisted. CONCLUSION Although resection is a more certain and absolute way of treating benign polyps, endoscopic polypectomy is preferable.

MYH-associated polyposis is a recessively inherited syndrome of colorectal cancer predisposition attributed to biallelic germline mutations in the base excision repair gene MYH. Clinically it overlaps with attenuated familial adenomatous polyposis, sporadic oligopolyposis, serrated polyposis, familial colorectal cancer type X, and Lynch syndrome. There is no specific phenotypic feature of MYH-associated polyposis. We have noticed that a proportion of patients with MYH-associated polyposis presenting for yearly colonoscopy surveillance have rectums that are studded with small hyperplastic polyps.We report this as a possible unique phenotypic feature of the syndrome.This was a descriptive study.The study was conducted at a department of colorectal surgery in a tertiary referral center.Patients affected with oligopolyposis or MYH-associated polyposis presenting for endoscopic surveillance and polyp control were included.Interventions included colonoscopy or proctoscopy with excision or biopsy of mucosal lesions.The presence of rectal studding was measured.There were 49 patients, 16 with biallelic germline mutations of MYH; 10 of these had rectal studding. A sampling of rectal polyps was biopsied and all were hyperplastic. Five patients with biallelic MYH mutations had no studding, and 1 had not been prospectively examined. The studding was independent of the nature of the MYH mutation(s). The 33 patients other patients included 21 with serrated polyposis, 2 with a germline APC mutation, 1 with a PTEN mutation, 2 with mixed polyposis, 3 with oligoadenomatous polyposis and no germline mutation, and 4 patients with oligoadenomatous polyposis who had not been genetically tested. Only 1 of these (oligoadenomatous polyposis, not tested) had studding.The study was limited by its small number of biallelic MYH mutation carriers.Rectal studding may be a sign of MYH-associated polyposis and raises questions about the biology of abnormal base excision repair.

Background Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing. Methods Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry. Results There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC. Conclusion Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance.

The purpose of this study was to report our large, single-center experience of transabdominal ileal pouch-anal anastomoses (IPAA) redo surgery for a failed initial IPAA.IPAA fail from 3% to 15% of the times, mainly due to technical or inflammatory conditions. There is limited information about the surgical, functional, and quality-of-life (QOL) outcomes of redo surgery for failed IPAA, especially in large series of patients.Patients undergoing transabdominal redo surgery for failed IPAA between 1983 and 2014 were evaluated. Primary endpoints were morbidity of the surgery, the proportion of patients with a functioning pouch, frequency of defecation and incidence of incontinence, and the patients' perception of QOL.There were 502 (43% males) patients with a median age of 38 years and median body mass index 24 kg/m at the time of revision surgery. A new pouch was created in 41% of patients whereas 59% had their original pouch revised and retained. Postoperative mortality was 0% and morbidity was 53%. The short-term anastomotic leak rate was 8%. At a median follow-up of 7 years after redo surgery, 101 (n = 20%) patients had redo IPAA failure. Pelvic sepsis developing after redo ileal pouch surgery was the primary indicator of pouch failure (hazard ratio, 3.691; 95% confidence interval, 2.411-5.699; P 0.0001). Overall functional outcomes and QOL scores were acceptable.Patients with a failed ileoanal pouch may be offered redo pouch surgery with a high likelihood of success in terms of function and QOL.

We read with interest the paper by Rutter et al on surveillance guidelines after colonoscopic polypectomy and postcolorectal cancer resection.1 However, like all similar recognised guidelines, they do not address the issue of following up polyps found on a flexible sigmoidoscopy (FS) done to investigate rectal bleeding. With colonoscopy services in short supply in many countries, FS is often used at rectal bleeding clinics in cases where other known personal risk factors for colorectal neoplasia are absent. At FS, the finding of a normal rectum and sigmoid combined with a likely anal cause of the bleeding excludes significant left-sided neoplasia. However, the appropriate follow-up of an adenoma found in the rectum or sigmoid colon has been a topic of much study and debate, centred on the likelihood of detecting significant proximal colonic neoplasia. One of the most …

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.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.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 polyps20 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).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.

Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome associated with a substantial lifetime risk for colorectal cancer. The leading extra-colonic causes of cancer in FAP include duodenal and thyroid cancer (TC). Recent guidelines recommend annual thyroid ultrasound (TUS) screening beginning in the teenage years but the evidence to support the interval particularly in FAP patients with a normal baseline ultrasound is lacking. TUS results from FAP patients enrolled in a thyroid screening program from 2006 to 2016 and who had at least 2 TUS were reviewed. TUS findings were classified as normal, low (LR) or high risk (HR) for TC based on nodule characteristics as determined by American Thyroid Association (ATA) guidelines. We assessed the incidence of TC in patient with normal baseline TUS and factors associated with TC. 264 FAP patients were included. Baseline TUS was normal in 167, LR in 74, and HR in 24 patients. Patients were observed for a mean 4.8 years and underwent an average of 3 TUS. Patients with normal baseline TUS did not develop TC during the course of follow up of 5.1 years. TC developed in 6 patients (2.3%) all with baseline nodules; 5 in the LR group and 1 in the HR group. Factors associated with development of TC were presence of baseline nodule(s) and female sex. The development of TC in FAP patients in a TUS screening program with short term follow up is low and no FAP patient with a normal baseline TUS developed TC during observation. Annual TUS in patients with a normal baseline TUS may not be needed. Extending the screening interval to 2 years may be reasonable until nodules are detected.

Background Colorectal cancer (CRC) is a heterogeneous disease with distinct clinical subsets based on underlying genetic and epigenetic changes. DNA hypermethylation yields a unique CRC subset with a distinct phenotype and clinical behaviour, but this oncogenic pathway is not fully characterised. This study identifies and characterises miR-1247 as a novel tumour suppressor microRNA in methylated human colon cancers. Method Tumour samples from patients with hypermethylated and non-methylated colon cancer and cell lines were evaluated for miR-1247 expression and function. A murine subcutaneous xenograft model was used for in vivo functional studies. Results miR-1247 was methylated and underexpressed in methylator colon cancers. Overexpression of miR-1247 significantly inhibited cell proliferation, decreased tumour cell motility, induced apoptosis, and mitigated tumour formation capacity both in vivo and in vitro. Pharmacologic demethylation increased miR-1247 expression and produced similar anti-tumour activities. Mechanistic investigations revealed that MYCBP2, a member of the c-myc oncogene family, is a direct functional target of miR-1247. Furthermore, in CRC patients, MYCBP2 protein levels are associated with miR-1247 levels and survival. Conclusions miR-1247 acts as a tumour suppressor by inhibiting MYCBP2 in methylator colon cancer. The MYCBP2/c-myc axis may underlie the anti-tumour activities of miR-1247 and is a potential therapeutic target via demethylation agents.

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.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.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%).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.