Restorative Proctocolectomy in Ulcerative Colitis: Effect of Preoperative Immunomodulatory Therapy on Postoperative Complications and Pouch Failure.

BACKGROUND AND AIMS: Patients with ulcerative colitis are often treated with multiple immunomodulative agents to achieve remission. In refractory disease, the next option is frequently proctocolectomy with ileal pouch-anal anastomosis. No consensus exists as to whether immunomodulatory therapy at the time of ileal pouch surgery leads to any increase in postoperative complications. Our aim was to assess, in ulcerative colitis patients with restorative proctocolectomy, the effect of preoperative anti-tumor necrosis factor therapy and corticosteroids on postoperative complications and pouch failure. MATERIALS AND METHODS: A retrospective medical record review of 445 patients with ulcerative colitis who underwent proctocolectomy with ileal pouch-anal anastomosis in Helsinki University Hospital between January 2005 and June 2016. RESULTS: Anti-tumor necrosis factor agents were not associated with postoperative complications. Only high-dose corticosteroids (prednisolone ⩾20 mg or equivalent) were associated with higher incidence of anastomotic leak (12.6% vs 2.5%, P = 0.002) and wound dehiscence (4.2% vs 0%, P = 0.019), but pouch failure rate was no higher (2.1% vs 0%, P = 0.141) than in patients without corticosteroid treatment. A lower dosage of corticosteroids had no effect on early postoperative complications, but pouch failure rate was increased (4.4% vs 0%, P = 0.015). CONCLUSION: Corticosteroids, but not anti-tumor necrosis factor therapy, were associated with postoperative complications. Preoperative use of corticosteroids may increase pouch failure rate, but the risk is still minor in high-volume centers performing ileal pouch surgery.

Clinical management of 52 consecutive retro-rectal tumours treated at a tertiary referral centre.

AIM: The aim of this single-institution study was to analyse the diagnostic methods, preoperative work-up and outcomes of 52 retro-rectal tumours. METHOD: All patients treated for retro-rectal tumours from 2012 to 2017 were included. RESULTS: Out of 52 patients, 40 (77%) were women. The median age of patients at the time of surgery was 43 (19-76) years, and 30 (58%) were asymptomatic at the time of diagnosis. All tumours were visible on magnetic resonance imaging (MRI) prior to surgery. The sensitivity and specificity for predicting malignancy on preoperative imaging for retro-rectal tumours were 25% and 98%, respectively. Forty-four procedures (85%) were performed using the perineal approach. The median hospital stay was 3 (1-18) days. There was no 30-day postoperative mortality. Eleven (21%) patients developed postoperative complications, mostly surgical site infections. Twenty-nine tumours (56%) were benign tailgut cysts. Four (8%) tumours were malignant and were considered to be removed with a tumour-free resection margin. Local recurrent disease was detected on MRI in 14 (27%) patients at a median of 1.05 (range 0.78-1.77) years after primary surgery. Only the multi-lobular shape of the tumour was found to be an independent risk factor for recurrence (P = 0.030). CONCLUSION: A preoperative MRI is mandatory in order to plan the surgical strategy for retro-rectal tumours. Symptomatic, solid, large tumours should be removed because of the risk of malignancy. Minor cystic lesions with thin walls as well as asymptomatic recurrences of benign tumours are suitable to be followed conservatively.

Morbidity related to diverting ileostomy after restorative proctocolectomy in patients with ulcerative colitis.

AIM: Restorative proctocolectomy with ileal pouch-anal anastomosis is considered by many surgeons to be the standard procedure for surgical management of ulcerative colitis. There is controversy about whether or not a covering ileostomy should be constructed. The aim of this study was to evaluate the outcomes and morbidity for patients with ulcerative colitis who underwent restorative proctocolectomy with or without a diverting ileostomy. METHOD: This is a retrospective study of a consecutive series of 510 patients with ulcerative colitis who were operated on in Helsinki University Hospital between January 2005 and June 2016. A diverting ileostomy was performed in 119 patients (the stoma group) compared with 391 patients with no stoma. RESULTS: Dehydration and intestinal obstruction occurred more often in the stoma group (P < 0.0001). Clinical anastomotic leakage was more common among patients without an ileostomy (6.6% vs 1.7%, P = 0.04). However, the need for re-laparotomy because of any early complication did not differ between the groups (P = 0.58). Within 3 months, 50 patients with ileostomy (42.0%) and 51 patients without (13.0%) were readmitted (P < 0.0001). In total, 35 patients (29.3%) had a complication relating to ileostomy closure and four of them required surgery. There was no difference in the rate of fistulas, pouchitis or pouch failure between the groups. CONCLUSION: Our study shows that a diverting ileostomy is associated with considerable morbidity but it does not seem to prevent later failure of the pouch. We suggest that a diverting ileostomy should only be constructed for high-risk patients.

Oncological results of extended resection for locally advanced rectal cancer: the value of postirradiation MRI in predicting local recurrence.

AIM: The primary purpose of this study was to analyse the overall survival and local recurrence rate after extended resection of locally advanced rectal cancer. The second aim was to determine the ability of the response to radiological irradiation to predict R0 resection. METHOD: A retrospective study was performed of 94 consecutive patients with locally advanced rectal cancer operated on at the Helsinki University Hospital, Helsinki, Finland between 2005 and 2013. Data were collected from patient records. All patients were treated with an en bloc resection. Sixty-two patients received preoperative long-term chemoradiotherapy. RESULTS: The 30-day mortality was 3.2%. Local recurrence occurred in 10 (10.6%) patients. The cumulative 1-, 3- and 5-year overall survival to each year was 89.4%, 68.3% and 51.8%. The most important prognostic factor for both local recurrence (P = 0.006) and survival (P = 0.003) was an R0 resection. A poor or no response seen on posttreatment MRI predicted local recurrence (P = 0.045) and decreased disease-free survival in patients treated curatively (P = 0.052). The histological tumour regression grade was not associated with local recurrence or survival. CONCLUSION: Multivisceral resection offers a 5-year survival of over 50% and local control of advanced rectal cancer in nearly 90% of carefully selected patients.

Comparison of proctocolectomy and ileal pouch-anal anastomosis to colectomy and ileorectal anastomosis in familial adenomatous polyposis.

Prophylactic surgical options for familial adenomatous polyposis (FAP) are either colectomy and ileorectal anastomosis (IRA) or proctocolectomy and ileal pouch-anal anastomosis (IPAA). The aim of this study was to analyse the short-term and long-term outcomes of these two operative techniques. All patients with FAP in Finland have been prospectively recorded in a database since 1963 were retrospectively reviewed in this analysis. Altogether 140 (61%) colectomies with IRA and 88 (39%) proctocolectomies with IPAA have been performed. Complications occurred in 28 (21%) patients after IRA and in 26 (30%) patients after IPAA. There were 15 (11%) severe complications for IRA and 5 (6%) for IPAA. Twenty-one (15%) patients of the IRA group ended up in conventional ileostomy whereas 3 (3.4%) patients of the IPAA group had their ileal reservoir converted to an ileostomy (p = 0.01). Cumulative survival for IRA was lower than for the IPAA (p = 0.03), but if accounting only for operations made after the IPAA era had commenced, there was no significant difference. IPAA was associated with improved long-term survival without an increase in postoperative complications. The risk of death after colectomy and IRA seemed to be predominantly related to the remaining risk of rectal cancer. Therefore, we favour proctocolectomy with IPAA as the prophylactic surgical procedure for FAP with intermediate or severe polyposis.

Identification of 33 candidate oncogenes by screening for base-specific mutations.

BACKGROUND: Genes with recurrent codon-specific somatic mutations are likely drivers of tumorigenesis and potential therapeutic targets. Hypermutable cancers may represent a sensitive system for generation and selection of oncogenic mutations. METHODS: We utilised exome-sequencing data on 25 sporadic microsatellite-instable (MSI) colorectal cancers (CRCs) and searched for base-specific somatic mutation hotspots. RESULTS: We identified novel mutation hotspots in 33 genes. Fourteen genes displayed mutations in the validation set of 254 MSI CRCs: ANTXR1, MORC2, CEP135, CRYBB1, GALNT9, KRT82, PI15, SLC36A1, CNTF, GLDC, MBTPS1, OR9Q2, R3HDM1 and TTPAL. A database search found examples of the hotspot mutations in multiple cancer types. CONCLUSIONS: This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets.

Risk of cancer and secondary proctectomy after colectomy and ileorectal anastomosis in familial adenomatous polyposis.

PURPOSE: The aim of our retrospective study was to review the outcome of patients undergoing colectomy with ileorectal anastomosis (IRA) due to familial adenomatous polyposis (FAP) in Finland during the last 50 years. METHODS: The cumulative risk of rectal cancer and the rate of anus preservation were analyzed. A total of 140 FAP patients with previous colectomy combined with ileorectal anastomosis were included. Kaplan-Meier analysis was performed to evaluate cumulative risks. RESULTS: Secondary proctectomy was performed for 39 (28 %) of 140 patients. The cumulative risk of secondary proctectomy was 53 % at 30 years after colectomy with IRA. A total of 17 (44 %) secondary proctectomies were performed due to cancer or suspicion of cancer, and another 17 (44 %) secondary proctectomies were performed due to uncontrollable rectal polyposis. During our study, the anus preservation rate in secondary proctectomies was 49 %. The cumulative risk of rectal cancer was 24 % at 30 years after colectomy with IRA. Therefore, the cumulative rectal cancer mortality 30 years after colectomy with IRA was 9 %. CONCLUSIONS: Proctocolectomy and ileal pouch-anal anastomosis (IPAA) should be favored as a primary operation for patients not having technical or medical contraindications for it because colectomy with IRA carried a rectal cancer risk of 13 % with a mortality of 7 % during our study, and because IPAA is likely to succeed better at earlier phase of the disease. Patients with attenuated FAP had no rectal cancer in our study, and they may form a group where IRA should still be the first choice as an exception.

Peutz-Jeghers syndrome: a systematic review and recommendations for management.

Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal dominant condition defined by the development of characteristic polyps throughout the gastrointestinal tract and mucocutaneous pigmentation. The majority of patients that meet the clinical diagnostic criteria have a causative mutation in the STK11 gene, which is located at 19p13.3. The cancer risks in this condition are substantial, particularly for breast and gastrointestinal cancer, although ascertainment and publication bias may have led to overestimates in some publications. Current surveillance protocols are controversial and not evidence-based, due to the relative rarity of the condition. Initially, endoscopies are more likely to be done to detect polyps that may be a risk for future intussusception or obstruction rather than cancers, but surveillance for the various cancers for which these patients are susceptible is an important part of their later management. This review assesses the current literature on the clinical features and management of the condition, genotype-phenotype studies, and suggested guidelines for surveillance and management of individuals with PJS. The proposed guidelines contained in this article have been produced as a consensus statement on behalf of a group of European experts who met in Mallorca in 2007 and who have produced guidelines on the clinical management of Lynch syndrome and familial adenomatous polyposis.

Recommendations to improve identification of hereditary and familial colorectal cancer in Europe.

Familial colorectal cancer (CRC) accounts for 10-15% of all CRCs. In about 5% of all cases, CRC is associated with a highly penetrant dominant inherited syndrome. The most common inherited form of non-polyposis CRC is the Lynch syndrome which is responsible for about 2-4% of all cases. Surveillance of individuals at high risk for CRC prevents the development of advanced CRC. About 1 million individuals in Western Europe are at risk for Lynch syndrome. We performed a survey to evaluate the strategies currently used to identify individuals at high risk for CRC in 14 Western European countries. Questionnaires were distributed amongst members of a European collaborative group of experts that aims to improve the prognosis of families with hereditary CRC. The survey showed that in all countries obtaining a family history followed by referral to clinical genetics centres of suspected cases was the main strategy to identify familial and hereditary CRC. In five out of seven countries with a (regional or national) CRC population screening program, attention was paid in the program to the detection of familial CRC. In only one country were special campaigns organized to increase the awareness of familial CRC among the general population. In almost all countries, the family history is assessed when a patient visits a general practitioner or hospital. However, the quality of family history taking was felt to be rather poor. Microsatellite instability testing (MSI) or immunohistochemical analysis (IHC) of CRC are usually recommended as tools to select high-risk patients for genetic testing and are performed in most countries in patients suspected of Lynch syndrome. In one country, IHC was recommended in all new cases of CRC. In most countries there are no specific programs on cancer genetics in the teaching curriculum for medical doctors. In conclusion, the outcome of this survey and the discussions within an European expert group may be used to improve the strategies to identify individuals at high risk of CRC. More attention should be given to increasing the awareness of the general population of hereditary CRC. Immunohistochemical analysis or MSI-analysis of all CRCs may be an effective tool for identifying all Lynch syndrome families. The cost-effectiveness of this approach should be further evaluated. All countries with a CRC population screening program should obtain a full family history as part of patient assessment.

Guidelines for the clinical management of familial adenomatous polyposis (FAP).

BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for <1% of all colorectal cancer (CRC) cases. The syndrome is characterised by the development of hundreds to thousands of adenomas in the colorectum. Almost all patients will develop CRC if they are not identified and treated at an early stage. The syndrome is inherited as an autosomal dominant trait and caused by mutations in the APC gene. Recently, a second gene has been identified that also gives rise to colonic adenomatous polyposis, although the phenotype is less severe than typical FAP. The gene is the MUTYH gene and the inheritance is autosomal recessive. In April 2006 and February 2007, a workshop was organised in Mallorca by European experts on hereditary gastrointestinal cancer aiming to establish guidelines for the clinical management of FAP and to initiate collaborative studies. Thirty-one experts from nine European countries participated in these workshops. Prior to the meeting, various participants examined the most important management issues according to the latest publications. A systematic literature search using Pubmed and reference lists of retrieved articles, and manual searches of relevant articles, was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described herein may be helpful in the appropriate management of FAP families. In order to improve the care of these families further, prospective controlled studies should be undertaken.

Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer).

Lynch syndrome (hereditary non-polyposis colorectal cancer) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. The discovery of these genes, 15 years ago, has led to the identification of large numbers of affected families. In April 2006, a workshop was organised by a group of European experts in hereditary gastrointestinal cancer (the Mallorca-group), aiming to establish guidelines for the clinical management of Lynch syndrome. 21 experts from nine European countries participated in this workshop. Prior to the meeting, various participants prepared the key management issues of debate according to the latest publications. A systematic literature search using Pubmed and the Cochrane Database of Systematic Reviews reference lists of retrieved articles and manual searches of relevant articles was performed. During the workshop, all recommendations were discussed in detail. Because most of the studies that form the basis for the recommendations were descriptive and/or retrospective in nature, many of them were based on expert opinion. The guidelines described in this manuscript may be helpful for the appropriate management of families with Lynch syndrome. Prospective controlled studies should be undertaken to improve further the care of these families.

No support for endoscopic surveillance for gastric cancer in hereditary non-polyposis colorectal cancer.

BACKGROUND: The DNA mismatch repair gene mutations underlying hereditary non-polyposis colorectal cancer syndrome (HNPCC) also predispose, besides colorectal and endometrial cancer, to gastric cancer. usually of the intestinal type. The carcinogenetic pathway behind the elevated gastric cancer risk is largely unknown. METHODS: The aim of this study was to determine whether there are any premalignant lesions to search for in gastric surveillance in HNPCC by comparing gastric histopathology between mutation-positive and mutation-negative family members. We searched for differences in occurrence of Helicobacter pylori, inflammation, atrophy, intestinal metaplasia and dysplastic changes. Upper gastrointestinal endoscopy was performed for 73 mutation-positive and 32 mutation-negative family members. RESULTS: One case of duodenal cancer was detected in the mutation-positive group, but no gastric neoplastic lesions were seen in either group. There were no differences in the occurrence of polyps, H. pylori, inflammation, activity, atrophy nor intestinal metaplasia tested with binaric, logistic, regression analysis. CONCLUSIONS: We conclude that surveillance gastroscopy may not be beneficial in HNPCC, since neither cases of early cancer nor premalignant lesions could be detected in our series of 73 mutation-positive subjects.

Surveillance improves survival of colorectal cancer in patients with hereditary nonpolyposis colorectal cancer.

Some patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome develop carcinoma despite surveillance. The aim of this study was to determine whether survival was greater in colorectal cancer (CRC) cases detected by surveillance than in patients who had disease diagnosed on the basis of symptoms. All 150 CRC cases detected in 57 HNPCC families over the last 15 years were divided into two groups depending on whether they had been included in the surveillance program (n = 35) or not (n = 115). The stage distribution of the tumors in the group that underwent surveillance (Dukes' A, 50%; B, 35%; C, 15%; D, 0%) was significantly more favorable (P < .001) than in the group without surveillance (Dukes' A, 17%; B, 50%; C, 16%; D, 17%). CRC-specific 10-year survival was 93% in the surveillance group, significantly better than the 68% in the nonsurveillance group (P < .02). The overall survival did not differ significantly between the two groups despite a tendency in favor of the surveillance group. Colonoscopic surveillance enables early detection of CRC in HNPCC and reduces CRC mortality.