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Perspective on This Article from A Randomized Placebo-Controlled Prevention Trial of Aspirin and/or Resistant Starch in Young People with Familial Adenomatous Polyposis

INTRODUCTION: In patients with familial adenomatous polyposis, the Spigelman classification is recommended for staging and risk stratification of duodenal adenomatosis. Although the classification has been used for decades, it has never been formally validated.METHODS: We included consecutive FAP patients undergoing upper gastrointestinal endoscopic surveillance and evaluated the inter- and intrarater reliability of the Spigelman classification.RESULTS: The interrater reliability of the endoscopic parameters and the Spigelman classification was good and excellent, respectively. The intrarater reliability of the endoscopic parameters and the Spigelman classification was moderate and good, respectively.DISCUSSION: The results support continued use of the Spigelman classification as the primary end point for future studies and as key endoscopic performance measure.

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Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that increases risk for colorectal cancer (CRC). We assessed changes in the incidence and prevalence of CRC, and survival times, of patients with FAP participating in the Danish follow-up study.We collected data from the Danish Polyposis Registry, a nationwide, complete registry of patients with FAP that includes clinical information, surgical procedures, follow-up findings, and pathology reports. We compared data between the periods of 1990-1999 and 2000-2017. In 2017, the registry contained 226 families with 721 individuals with FAP. Probands were defined as patients diagnosed based on bowel symptoms, without any knowledge of hereditary bowel disease. Call-up patients were defined as those found to have FAP during screening and due to a diagnosis of FAP in first-degree relatives.Although the mean incidence rate of FAP was stable from 1990-1999 (0.19/100,000/year) to 2000-2017 (0.32/100,000/year) (P = .91), the point prevalence increased from 4.86/100,000 in 1999 to 6.11/100,000 by the end of 2017 (P = .005). During 2000-2017, 25 of 72,218 CRC cases were associated with FAP (0.03%)-this was a significant decrease from 1990-1999 (26/30,005 cases; 0.09%) (P = .001). The risk of CRC was significantly higher for probands (n = 191; 61.6%) than call-up cases (n = 5; 1.9%) (P.001). All CRCs in call-up patients were detected at the diagnosis of FAP (no cases were identified in the follow-up program). The median life expectancy for call-up patients was 72.0 years (95% CI, 63.3-80.7), compared to 55.0 years for probands (95% CI, 51.2-58.8) (P.001). Therefore, the tracing and follow-up program increased life expectancy by 17.0 years for first-degree family members.The Danish Polyposis Registry enables close monitoring of patients with FAP, reducing risk of CRC and prolonging life.

Background and aim Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. Methods The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. Results 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was −13.0% for CXB+DFMO and −1.0% for CXB (p=0.69). Mean % change in adenoma burden was −40% (CXB+DFMO) vs −27% (CXB) (p=0.13). Video-based global polyp change was −0.80 for CXB+DFMO vs −0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). Conclusions CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. Trial registration number ClinicalTrials.gov number N01-CN95040.

Aim The aim of the study was to evaluate intra-operative difficulties, complications and long-term bowel function in polyposis patients undergoing conversion of an ileorectal anastomosis to an ileoanal pouch, compared with patients with a primary ileoanal pouch operation. Method A national register-based retrospective study was performed with clinical follow-up and a questionnaire on long-term bowel function. Results There were 84 patients in the study: 59 (70%) had a primary pouch operation and in 25 (30%) a secondary pouch procedure was attempted. This was abandoned, in one case, leaving 24 patients who had a successful secondary restorative proctocolectomy. The median (range) follow-up was 123 (0–359) months. There were no intra-operative difficulties in the 59 primary operations, but intra-operative difficulties were reported in nine of 25 secondary operations (P

Aim In 2003 colorectal multidisciplinary teams (MDTs) were established in all major Danish hospitals treating colorectal cancer. The aim was to improve the prognosis by multidisciplinary evaluation and decision about surgical and oncological treatment, based on medical history, clinical examination, imaging, histology and comorbidity. The present study evaluates the effect of the introduction of colorectal MDTs on 1 August 2004 in two Danish hospitals. Method A retrospective cohort study was conducted comparing the outcome during the last 3 years before introduction of MDTs with the first 2 years after (the MDT cohort). The national colorectal cancer database, with follow-up recorded by the National Patient Registry in September 2010 was used. The end-points included the incidence of preoperative radiochemotherapy offered according to the national guidelines, R0/R1/R2 resection, postoperative mortality, local recurrence, distant recurrence and over-all and disease-free survival. Results Eight hundred and eleven patients were diagnosed with primary rectal cancer in Hvidovre and Bispebjerg hospitals between 1 May 2001 and 31 August 2006. The frequency of preoperative MRI scans increased in the MDT cohort and perioperative mortality decreased. More metachronous distant metastases were found in the MDT cohort but there was no difference in overall survival. Conclusion There was an improved postoperative mortality but no other potential benefits for the patients were seen after the implementation of colorectal MDTs.

Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In case of unfavourable histology after TEM, or positive resection margins, salvage surgery can be performed. However, it is unclear if the results are equivalent to primary treatment with total mesorectal excision (TME). The aim of this retrospective study was to determine whether there is a difference in outcome between patients who underwent early salvage resection with TME after TEM, and those who underwent primary TME for rectal cancer. From 1997 to 2011, early salvage surgery with TME after TEM was performed in 25 patients in our institution. These patients were compared with 25 patients who underwent primary TME, matched according to gender, age (±2 years), cancer stage and operative procedure. Data were obtained from the patients’ charts and reviewed retrospectively. No patients received preoperative chemotherapy. Perioperative data and oncological outcome were analysed. The Mann–Whitney U-test and Fisher’s exact test were used to compare the results between the two groups. There was no significant difference between the two groups in median operating time (P = 0.39), median blood loss (P = 0.19) or intraoperative complications (P = 1.00). The 30-day mortality was 8 % (n = 2) among patients who underwent salvage TME after TEM, and no patients died in the primary TME group (P = 0.49). There was no significant difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8 %) with local recurrences among the patients with primary TME (P = 0.49). Distant metastasis occurred in one patient (4 %) after salvage TME and in 3 patients (12 %) with primary TME (P = 0.61). The median follow-up time was 25 months (3–126) for patients who underwent salvage TME and 19 months (3–73) for patients after primary TME. No difference was found in outcome between patients with rectal cancer undergoing salvage TME after TEM, those undergoing primary TME. In selected patients, TEM can therefore be chosen as a primary treatment, since failure of treatment and subsequent conventional resection appears not to compromise the outcome.

Aim Duodenal adenomatosis in familial adenomatous polyposis results in a cancer risk that increases with age. Endoscopic surveillance has been recommended, but the effect has not yet been documented. The aim of this study was to present the results of long-term duodenal surveillance and to evaluate the risk of cancer development. Method Follow up of patients in a previous study with gastroduodenoscopy in 1990–2010. Statistical analysis included the χ2 test, actuarial method and Kaplan–Meier analysis. Results Among 304 patients, 261 (86%) had more than one endoscopy. The median follow up was 14 (interquartile range, 9–17) years. The cumulative lifetime risk of duodenal adenomatosis was 88% (95% CI, 84–93), and of Spigelman stage IV was 35% (95% CI, 25–45). The Spigelman stage improved in 32 (12%) patients, remained unchanged in 88 (34%) and worsened in 116 (44%). Twenty (7%) patients had duodenal cancer at a median age of 56 (range, 44–82) years. The cumulative cancer incidence was 18% at 75 years of age (95% CI, 8–28) and increased with increasing Spigelman stage at the index endoscopy to 33% in Spigelman stage IV (P

Aim Abdominoperineal resection for rectal cancer is associated with higher rates of local recurrence and poorer survival than anterior resection. The aim of this study was to evaluate the outcome of conventional abdominoperineal resection in a large national series. Method The study was based on the Danish National Colorectal Cancer Database and included patients treated with abdominoperineal resection between 1 May 2001 and 31 December 2006. Follow up in the departments was supplemented with vital status in the Civil Registration System. The analysis included actuarial local and distant recurrence, and overall and cancer-specific survival. Risk factors for local recurrence, distant metastases, overall survival and cancer-specific survival were identified using multivariate analyses. Results A total of 1125 patients were followed up for a median of 57 (25–93) months. Intra-operative perforation was reported in 108 (10%) patients. The cumulative 5-year local recurrence rate was 11% [95% confidence interval (CI), 7–13)], overall survival was 56% (95% CI, 53–60) and cancer-specific survival was 68% (95% CI, 65–71). Multivariate analysis showed that perforation, tumour stage and nonradical surgery were independent risk factors for local recurrence; tumour fixation to other organs, perforation and tumour stage were independent risk factors for distant metastases; and risk factors for impaired overall survival and cancer-specific survival were age, tumour perforation, tumour stage, lymph node metastases and nonradical surgery. Conclusion Intra-operative perforation is a major risk factor for local and distant recurrence and survival and therefore should be avoided.

Aim The study aimed to describe genetical and clinical features of attenuated familial adenomatous polyposis (AFAP) and to propose clinical criteria and guidelines for treatment and surveillance. Method A questionnaire study was carried out of polyposis registries with data on patients with presumed AFAP, defined as having ≤100 colorectal adenomas at age ≥25. Results One hundred and ninety-six patients were included. The median number of adenomas was 25 (0–100) with a uniform distribution of colorectal adenomas and carcinomas (CRC). Age at CRC diagnosis was delayed by 15 years compared with classic FAP. Eighty-two patients had a colectomy and an ileorectal anastomosis and 5/82 (6%) had a secondary proctectomy. The location of the mutation in the APC gene was known in 69/171 (40%) tested patients. Only 15/29 (52%) of mutations in APC were found in parts of the gene usually associated with AFAP (the 5′ end, exon 9 and 3′ end). Conclusions A subset of FAP patients with a milder phenotype does exist and treatment and surveillance had to be modified accordingly. The mutation detection rate is lower than in classic FAP and mutations in AFAP patients are located throughout the APC gene. We propose the following clinical diagnostic criteria for AFAP: a dominant mode of inheritance of colorectal adenomatosis and

Item does not contain fulltext 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. 01 juni 2010

Genetic information may help preoperatively select patients with familial adenomatous polyposis for either colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis. Although complicated, the latter procedure has a low long-term risk of rectal cancer.Data were obtained from four national polyposis registries. On the basis of previously described genotype-phenotype correlations, patients were divided into three genotype groups predicting attenuated, intermediate, and severe polyposis phenotypes. Cumulative risks of secondary proctectomy and rectal cancer after primary colectomy were calculated using the Kaplan-Meier method.Four hundred and seventy-five polyposis patients with a previous colectomy were included. Cumulative risks of secondary proctectomy 20 years after primary colectomy were 10%, 39%, and 61% in the attenuated, intermediate, and severe genotype groups, respectively (P0.05, groups compared separately). Cumulative risks of rectal cancer after primary colectomy were 3.7%, 9.3%, and 8.3%, respectively, in the three groups (P0.05, groups compared separately).Mutation analysis may be used to predict the risk of secondary proctectomy after primary colectomy in familial adenomatous polyposis. Patients with severe genotypes have a high risk of reoperation after primary colectomy and will benefit from primary proctocolectomy with ileal pouch-anal anastomosis. The risk of rectal cancer after primary colectomy was not significantly different between the three groups.

Background and Aims It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. Methods Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. Results The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode. Conclusions The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.

Objectives A recent study showed less bleeding and need of transfusion after total mesorectal excision (TME) compared with conventional rectal cancer surgery. The aim of this study was to evaluate this result in more details. Patients and methods Comparison of transfusion history in rectal cancer resections in two different multicentre-studies. Two hundred and forty-six patients were operated in the period 1991–93 with a conventional technique and 311 patients were operated with TME-technique in the period 1996–98. Peri-operative data, including blood transfusion from one month before until one month after the operation, was recorded prospectively. Results The median intra-operative blood loss was 1000 ml, range 50–6000 ml, before, and 550 ml, range 10–6000 ml (P

Background Mesorectal excision for rectal cancer has resulted in local recurrence rates of 3–11 per cent compared with up to 38 per cent after conventional methods. The results of a prospective Danish study with a historical control group are presented. Methods Three hundred and eleven patients with a mobile rectal cancer had mesorectal excision with curative intent performed by certified surgeons and were followed for 3 years. Demographic, perioperative and follow-up data were recorded prospectively. A series of patients who had conventional operations for rectal cancer served as a control group. Results The cumulative 3-year local recurrence rate was 11 per cent after mesorectal excision compared with 30 per cent after conventional surgery (hazard ratio (HR) 0·33 (95 per cent confidence interval (c.i.) 0·21 to 0·52); P < 0·001). Multivariate regression analysis showed that only advanced age (HR 0·97 (95 per cent c.i. 0·94 to 1·00); P = 0·048) and tumour in the lower third of the rectum (HR 0·21 (95 per cent c.i. 0·04 to 1·97); P = 0·075) were marginal independent predictors of local recurrence after mesorectal excision. The cumulative crude 3-year survival rate was 77 per cent after mesorectal excision and 62 per cent after conventional surgery (HR 0·58 (95 per cent c.i. 0·43 to 0·77); P < 0·001). Age was the only independent predictor of death after mesorectal excision (HR 1·04 (95 per cent c.i. 1·02 to 1·07); P = 0·001). Conclusion Mesorectal excision is associated with a considerably lower risk of local recurrence and a better survival rate than conventional surgery, and is the optimum method for rectal cancer resection.

Over the last decade, a subset of familial adenomatous polyposis(FAP) patients with a milder course of disease termed attenuated familial adenomatous polyposis (AFAP) has been described. AFAP is not well-defined as a disease entity – the reports on AFAP are largely casuistic or only deal with a few kindreds – and the diagnostic criteria and methods of investigation differ markedly. The true incidence and frequency of AFAP is not known. The mutations in APC associated with AFAP have mainly been detected in three parts of the gene: in the 5′ end (the first five exons), in exon 9 and in the distal 3′ end. The main features of AFAP are 100 or less colorectal adenomas with a tendency to rectal sparing, a delay in onset of adenomatosis and bowel symptoms of 20–25 years, a delay in onset of colorectal cancer (CRC) of 10–20 years and death from CRC of 15–20 years, and although the lifetime penetrance of CRC appears to be high, CRC does not seem to develop in nearly all affected patients. A more limited expression of the extracolonic features is seen, but gastric and duodenal adenomas are frequently encountered. Colonoscopy is preferred to sigmoidoscopy, should begin at the age of 20–25 years and no upper age limit of stopping surveillance is justified. Regular esophago-gastro-duodenoscopy (EGD) is recommended. Until further research has provided us with a more substantiated knowledge about AFAP changes in current surveillance and treatment are not recommended. Prophylactic colectomy with ileorectal anastomosis (IRA) is recommended in most patients.

Background: Colorectal cancer is the second most frequent cancer and adenomas are widely accepted as precursors to colorectal cancer. Diagnosis and removal of adenomas are recommended to reduce cancer incidence and mortality. The current diagnostic methods include sigmoidoscopy and colonoscopy. Lately, CT- and MR colonography have emerged as non-invasive methods for colon imaging. Methods: At present, CTC and MRC require bowel preparation. However, preliminary studies have been carried out without colon preparation. After the colon has been filled with air or contrast, the patient is scanned in the supine and prone positions. Data are then downloaded to a workstation for post processing and image-analysis. Results: Results have shown a high sensitivity and specificity for polyps ≥ 10 mm, comparable to the sensitivity of conventional colonoscopy and superior to double contrast barium enema. Conclusions: With the exponential development in computer processing power, CT- and MR colonography holds the promise for future colon examination with the advantages of non-invasiveness, no need for sedation, and probably no bowel preparation. major disadvantage, however, is the radiation dose during CT colonography. Future developments with the use of “intelligent” computers, better resolution and faster examinations will make CT and/or MR colonography realistic options to replace conventional diagnostic colonoscopy.

BACKGROUND AND AIMSThe choice of colorectal surgery in patients with familial adenomatous polyposis lies between the morbidity of proctocolectomy and ileum-pouch-anal anastomosis (IPAA) and the mortality from rectal cancer after total colectomy and ileorectal anastomosis (IRA). The aims of the present study were: (1) to assess the risk of dying from rectal cancer after IRA, (2) to compare the life expectancy between patients with an IRA and those with an IPAA, and (3) to investigate whether regular endoscopic examination of the rectum leads to detection of cancer at an earlier stage.METHODSClinical and pathological data on 659 patients who underwent colectomy and ileorectal anastomosis were collected from four national polyposis registries—that is, in Denmark, Finland, Sweden, and the Netherlands. Data were analysed using survival analysis methods. Decision analysis was used to compare the life expectancy between patients with an IRA and those with an IPAA.RESULTSA total of 47 patients developed rectal cancer after IRA. The risk of dying from rectal cancer was 12.5% (95% confidence interval 7.1–17.9%) by age 65. Compared with IRA, IPAA would lead to an increase in life expectancy of 1.8 years. Seventy five per cent of patients with rectal cancer had a negative rectoscopy within 12 months before the diagnosis.CONCLUSIONIRA is associated with substantial mortality due to rectal cancer. Follow up examinations of the rectum does not have sufficient preventive effect on morbidity and mortality of rectal cancer.

Desmoid tumours (DT) are rare benign tumours that do not metastasise, but tend to invade locally. DT are frequently seen in patients with familial adenomatous polyposis (FAP), and diagnosis and treatment are often difficult. Surgical trauma, genetic predisposition and hormonal factors are considered to be correlated with the development and growth of DT. In patients with FAP, 50% of the tumours are localised intra-abdominally, and 85–100% of these are mesenteric. DT frequently present as non-tender, slowly growing masses. The symptoms are abdominal pain, vomiting, diarrhoea or haematochezia. Mesenteric DT can cause small bowel obstruction or ischaemia, hydronephrosis or form fistulas. Diagnosis is obtained through biopsy and the extension is determined by a CT-scan. Surgical excision is recommended in patients with DT in the abdominal wall. First line treatment of mesenteric DT is a NSAID in combination with tamoxifen. Surgery may be considered in case of a small and well-defined DT with no signs of invasion of vital structures, and in cases of imminent bowel ischaemia or obstruction. The prognosis in mesenteric DT is serious, and improvement of the therapeutic strategy awaits current international studies.

Objective A defunctioning transanal stent may theoretically reduce the leakage rate after anterior rectal resection. We present a randomized open study with the aim of comparing the leakage rate after anterior resection with a loop ileostomy, a transanal stent, both or neither. Patients and methods Randomized open trial of 194 patients operated in 11 hospitals during September 2000 to September 2003 with anterior resection for a mobile rectal tumour, 115 men and 79 women, median age 68 years (range 37–90 years). The surgeon decided upon the use of a protective ileostomy, and after completion of the operation the patients were randomized in two groups with and without a transanal stent. Results A clinically significant leakage was diagnosed in 25 patients (13%). No significant difference was found 17 of 98 patients with a stent and 8 of 96 without (P = 0.09), or in 9 of 44 ileostomy patients with a stent and in 3 of 45 without (P = 0.07). Several leaks over a short time led to an interim analysis after inclusion of 194 of 448 planned patients. The analysis showed no significant protective effect of the stent, and more leakages in the stent group, although not statistically significant. On this basis it was decided to discontinue the study prematurely for ethical reasons. Conclusion Decompression of the anastomosis with a transanal stent does not reduce the risk of anastomotic leakage after anterior resection.

Background: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. Methods: One hundred and eight Danish HNPCC patients were compared with 870 patients with sporadic colorectal cancer. Results: The median age at CRC diagnosis was 41 years in the HNPCC group. HNPCC patients had significantly more carcinomas located to the right colon (68% against 49% in controls), more synchronous tumours (7% versus 1%). more metachronous CRC after 10 years (29% versus 5%), more localized carcinomas (62% versus 39%), and significantly higher crude cumulative 5-year survival (56% versus 30%). Conclusions: CRC in HNPCC behaves differently compared to sporadic cases concerning age of onset, frequency of multiple lesions, and location. The metastatic tendency is less than in sporadic CRC and the survival is better.

Familial adenomatous polyposis is an autosomal dominant disease that includes early development of up to thousands of colorectal adenomas and several extracolonic manifestations. All untreated patients will develop colorectal adenocarcinoma. The treatment of choice is colectomy and ileorectal anastomosis, but restorative proctocolectomy may be considered in selected cases. Polyposis patients treated with ileorectal anastomosis should be followed for life, with regular proctosigmoidoscopy and destruction of new adenomas. Furthermore, regular gastroduodenoscopy should be carried out because of frequent occurrence of premalignant duodenal adenomas. The prognosis is good after prophylactic colectomy in patients without carcinoma. All first degree relatives of affected family members should be examined regularly with proctosigmoidoscopy from the age of ten, and prophylaxis should be organised using a national or regional polyposis register. The recent detection of a specific gene for familial adenomatous polyposis is a long step forward, and several problems may be solved by increasing international cooperation.

Based on the Danish Polyposis Register epidemiological calculations on familial adenomatous polyposis (FAP) were carried out. The mean annual incidence was 1.85 x 10(-6) during the years 1971-1992, and the prevalence increasing to about 32 x 10(-6) at the end of 1992. FAP patients constituted a decreased percentage of all Danish patients with colorectal cancer (0.07% in 1980-1992). The completeness of registration was 97% in 1983-1992. The results are similar to Finnish estimates based on the same direct method of calculation, and as both series are based on almost complete national polyposis registration in well-registered populations we regard our results to be close to the true incidence rate.

In order to evaluate the prevalence of duodenal adenomas in familial adenomatous polyposis (FAP) and the risk of carcinoma development, a multicenter study was initiated in Denmark, Finland, Holland, Norway and Sweden, which have national polyposis registers with an almost complete registration. Patients aged 20 years or more are being examined with biennial gastroduodenoscopy during 1990–2000. Multiple duodenal biopsies are examined by one pathologist from each country, and the endoscopic and histological criteria of Spigelman have been adopted. At the end of August 1992, 312 patients with a median age of 37 years (range 20–86) had completed their first endoscopy. The duodenum was examined in 310 patients, of whom 199 (64%) had duodenal adenomas. Twenty-two patients (11% of all patients with duodenal adenomas) had no endoscopically visible polyps. One patient had an asymptomatic adenocarcinoma. The Spigelman stage worsened significantly (P

A de-functioning loop ileostomy (LI) reduces the consequences of anastomotic leak following low anterior resection, but its construction as well as its closure can be associated with complications. The aim of the present study was to identify risk factors for postoperative complications and particularly to determine if operation performed by trainees carry a higher risk of complications than operation performed by experienced surgeons.This was a retrospective single-centre analysis of the medical records of 159 consecutive patients who underwent LI closure following low anterior resection for rectal cancer in the period from January 2002 to December 2008.Postoperative complications developed in 32 patients (20.1%). Surgical complications occurred in 27 patients (17%) including small bowel obstruction in five (3%), anastomotic leak in four (2.5%), wound infection in eight (5%) and incisional hernia in eight (5%). There was no postoperative mortality. Univariate analysis showed that an increased rate of complications was associated with female gender (p = 0.02), small bowel resection at closure (p = 0.009) and a long interval between construction and closure of the loop ileostomy (p = 0.049).Closure of an LI is associated with a low mortality, but a relatively high rate of complications. Operation performed by trainees was not associated with an increased complication rate. More complications were seen in patients who underwent small bowel resection and those who had delayed ileostomy closure.not relevantnot relevant.

Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In patients with unfavourable post-TEM histology, salvage surgery can be performed. The aim of this study was to evaluate the results of early radical surgery after TEM for rectal cancer.From 1997 to 2010, 86 TEM procedures were performed in 79 patients due to rectal cancer. Early salvage surgery was performed in 25 patients. Data were obtained from the patients' charts and reviewed retrospectively. Perioperative data and oncological outcome were analysed.No patients received preoperative chemotherapy. The median time to salvage surgery was 37 days. Five patients underwent laparoscopic surgery. The median operative time was 165 min (range: 101-341 min, 95% confidence interval (CI): 156-214 min) and the median blood loss 275 ml (range: 0-1,275 ml, 95% CI: 232-530 ml). The 30-day mortality was 8% (95% CI: 1-19%, n = 2). Intraoperative perforation occurred in 20% (95% CI: 3-37%, n = 5). The median number of harvested lymph nodes was 12 (range: 3-25, 95% CI: 9-14) and the median circumferential resection margin (CRM) was 10 mm (range: 0-20 mm, 95% CI: 5-12 mm). Only one patient (4%, 95%CI: 1-12%) had a positive CRM. The median follow-up time was 25 months (range: 3-80 months). There was no local recurrence. Distant metastasis occurred in 4% (95% CI: 1-12%, n = 1).Early salvage surgery after TEM seems to be safe despite a high risk of specimen perforation during the operation.not relevant.not relevant.

Aim Patients with hereditary non-polyposis colorectal cancer (HNPCC) seem to have a better prognosis than those with sporadic colorectal cancer (CRC). The aim was to compare survival after Stage III CC in patients with HNPCC with those having sporadic CC. Method A total of 230 patients with hereditary cancer from the Danish HNPCC Register and 3557 patients with sporadic CC from the Danish Colorectal Cancer Database, diagnosed during May 2001–December 2008, were included. HNPCC patients were classified according to mismatch repair mutation status and family pedigree. Sporadic cases had no known family history of cancer. Patient characteristics, geographical differences and survival data were analysed. Results The overall survival (OS) was better in HNPCC patients compared with sporadic CC after stratification for sex and age (P = 0.02; CI 1.04–1.7). The 5-year survival was 70% in HNPCC patients compared with 56% in sporadic CC (P

The nationwide Danish polyposis register includes all known Danish cases of familial adenomatous polyposis (FAP) and their relatives. By identifying all FAP patients born between 1920 and 1949, we found the frequency of the disease to be 1 in 13,528. By comparing the number of affected and nonaffected offspring born to affected parents during the same period we found the penetrance of the disease for inherited cases to be close to 100% at the age of 40 years. The mutation rate found by the direct method was 9 mutations per million gametes per generation and the proportion of new mutants was estimated to 25%. Fitness for patients between 15 and 29 years was found close to one, while for patients older than 30 the fitness was reduced, but increasing during the three decades (from 0.44 to 0.71) probably because treatment became more widespread and efficient. As we have used the overall fitness in the period, 0.87, to estimate the mutation rate by the indirect method, we found a lower value than by the direct method, namely 5 mutations per million gametes per generation.

BACKGROUND: Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice. OBJECTIVES: Our aim was to assess several risk factors for desmoid tumor development in an international cohort of patients with familial adenomatous polyposis and to evaluate the clinical relevance of risk factors. DESIGN: This was a retrospective cohort study. SETTING AND PATIENTS: Polyposis registries in The Netherlands, France, Denmark, Finland, and Italy provided information on familial adenomatous polyposis patients with desmoid tumors. MAIN OUTCOME MEASURES: We used univariate and multivariable analyses of data from registries in The Netherlands, France, Denmark, and Finland to test whether gender, APC mutation site, previous colorectal surgery, colorectal cancer, and family history for desmoid tumors contribute to risk of developing desmoid tumors at any location, or specifically at an intra-abdominal location. The effect of family history was tested with a generalized linear mixed model. RESULTS: Of 2260 patients with familial adenomatous polyposis from 912 families in The Netherlands, France, Denmark, and Finland, 220 patients (10%) had desmoid tumors (101 men). In 387 patients with desmoid tumors (including 167 patients from the Italian registry), the median age at diagnosis of the first desmoid tumor was 31 years (range, 4 months-74 years). Desmoid locations were intra-abdominal (53%), abdominal wall (24%), extremities (9%), and unknown sites or combinations of sites (14%). Multivariable analysis of risk factors for desmoids at any location showed surgery (OR, 2.58; P = .0004), an APC mutation 3' of codon 1444 (OR, 3.0; P < .0001), and a positive family history (P < .0001) to be independently associated with desmoid development. When only intra-abdominal location was analyzed, APC mutation site was not associated with desmoid development. LIMITATIONS: Selection bias may have occurred. CONCLUSIONS: A positive family history for desmoid tumors, abdominal surgery, and APC mutation site are significant risk factors for development of desmoid tumors. The results may have implications for determining the optimal management of FAP patients and guide future studies.

A protective loop ileostomy is used to reduce the incidence and consequences of anastomotic failure following colorectal resection. Closure of a loop ileostomy is associated with low mortality but many studies have demonstrated high morbidity rates. The aim of this review is to examine the existing evidence on the morbidity following closure of loop ileostomies and to investigate possible risk factors for complications. There is no consensus in the literature about the risk factors for complications. Counseling of the patient about the risks for complications is emphasized.

Item does not contain fulltext 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. 01 juli 2010

Total colectomy with ileorectal anastomosis (IRA) in familial adenomatous polyposis (FAP) leaves patients at risk for rectal cancer. To assess this risk, the rectal cancer incidence in 297 patients with FAP undergoing IRA since 1951 was determined in the population-based registers of Denmark, Finland and Sweden. At the same time, detailed data on 50 patients with FAP and invasive rectal cancer were obtained from 11 international polyposis registries. The cumulative incidence of rectal cancer was 13.1 per cent at 25 years. The 5-year survival rate of patients with FAP developing rectal cancer was 71 per cent. Combining both studies, the risk of dying from rectal cancer after IRA was 2.0 per cent at 15 years of follow-up. These results justify IRA as primary treatment for most patients; restorative proctocolectomy is preferred for some subgroups. The high all-cause mortality rate observed in this relatively young population necessitates lifelong surveillance of patients with FAP.

Danish rectal cancer patients previously had an inferior prognosis compared with the other Scandinavian countries. An analysis of overall and relative survival in 1994-2006 was based on the Danish Colorectal Cancer Group's national colorectal cancer databases and the Central Population Registry. The 5-year overall survival in 10,632 operated patients increased from 37% to 51% and the 5-year relative survival rose from 46% to 62%. In conclusion, the prognosis improved considerably mainly due to implementation of total mesorectal excision, improved preoperative staging and centralised surgical treatment.

The number of identified lymph nodes (LNs) is an essential element in the pathologist's rapport on colorectal resection specimens with carcinoma (CRSC). A considerable number of papers discuss the acceptable minimum number of identified LNs to secure a correct LN status (LNS). Details as to the most appropriate grossing technique for LN detection are, however, largely lacking. In this paper the influence of the time invested by the pathologist in the pursuit of LN is investigated.The material comprised 150 CRSCs. The usual gross examination was extended by 15 minutes in an effort to identify additional LNs. Provided this careful analysis failed to produce 12 LNs and all detected LNs were benign (pNx), the specimen was re-sampled for an additional 15-minute period. Data were correlated with a baseline material comprising 100 CRSCs.The intensified search for LNs increased the average number of LNs pr. specimen from 9.1 to 14.9. The number of cases with pNx was reduced from 54% to 18%. Re-sampling performed on 25 specimens resulted in the detection of another 61 LNs in 21 cases, ranging from 1 to 8 LN pr. specimen (median 2), whereby pNx was converted to pN0 in eight cases. In another four cases, additional LNs were not detected. Re-sampling did not uncover metastatic disease.This intensified effort in the Department of Pathology resulted in a more reliable LNS.

Colorectal carcinoma is one of the most prevalent malignancies in Western countries. Lymph node status is a significant prognosticator. The chance of identifying node-positivity is positively correlated with the number of lymph nodes (LN) identified. The present paper discusses various variables that may influence the detection of LNs, including patient- as well as surgeon- and pathologist-related issues. The pathologist-related variable most probably shapes the yield the most. Introduction of guidelines focusing on the most appropriate technique may secure better and more consistent results, and the pathologist's commitment is crucial in this respect.

The treatment of rectum cancer depends on the tumour stage, and until 2005 treatment included preoperative radiation therapy for the T3 and T4 cancer stages. An exact preoperative assessment of the cancer stage is therefore essential. In Denmark rectal Magnetic Resonance Imaging (MRI) is used as a standard procedure in preoperative evaluation, sometimes supplemented by transrectal ultrasound (TRUS). The purpose of this study was to determine the accuracy of preoperative MRI in tumour stage evaluation in order to correctly select the patients who will benefit from preoperative radiation therapy.The MRI reports from 173 patients (98 male, 75 female, mean age 71 years) who underwent surgery for rectum cancer at Hvidovre Hospital, Copenhagen during the 2002-2005-period were evaluated. The T-stage of the MRI report was compared to the histological T-stage of the resected tumour.The overall accuracy of T-staging was 58% (n = 100) of which 41% T2 tumours (n = 18), 78% T3 tumours (n = 78) and 33% T4 tumours (n = 4) were correctly staged. In all, 29% of cancers were overstaged (n = 50) (100% of T1 tumours, 59% of T2 tumours, 7% of T3 tumours). A total of 13% of the cancers were understaged (15% of T3 tumours, 67% of T4 tumours). The selection of patients for preoperative radiation therapy had a sensitivity and specificity of 83% and 48%, respectively.The overall accuracy of 58% indicates that MR imaging in the early learning phases was not an optimal method for the preoperative T-staging of rectal cancer. In particular, the low specificity of MRI in selecting the patients who will benefit from preoperative radiation can result in overtreatment and increased morbidity.

Udgivelsesdato: 2009-Jul-15 Background: In 1995 an analysis showed an inferior prognosis after rectal cancer in Denmark compared with the other Scandinavian countries. The Danish Colorectal Cancer Group was estasblished with the aim to improve the prognosis, and in this study we present a survival analysis of patients treated in 1994-2006. Method: The study was based on the National Rectal Cancer Registry and the National Colorectal Cancer Database, supplemented with data from the Central Population Registry. The analysis included actuarial overall and relative survival. Results: A total of 10 632 patients were operated on. The overall 5-year survival increased from 0.37 in 1994 to 0.51 per cent in 2006; the improvement was greater in men (20 percentpoints) than in women (10 percentpoints), and greatest in stage III (20 percentpoints). The relative 5-year survival increased from 0.46 to 0.62, including an improvement of 23% points in men and 9% points in women, and greatest in stage III (22% points). Conclusions: The prognosis has improved substantially, probably mainly due to initiatives taken by the Danish Colorectal Cancer Group, among which implementation of TME, improved staging and centralised treatment are considered most important.

OBJECTIVE: Preoperative radiotherapy has been shown to enable a fixed rectal cancer to become resectable which in turn may result in long-time survival. In this study, we analysed the outcome of long-course preoperative radiotherapy in fixed rectal cancer in a national cohort including all Danish patients registered with primary inoperable rectal cancer and treated in the period May 2001 to December 2005.METHOD: The study was based on surgical and demographic data from a continuously updated and validated national database. In addition, retrospective data were retrieved from all departments of radiotherapy concerning technique of radiotherapy, dose and fractionation and use of concomitant chemotherapy. Outcome was determined by actuarial analysis of local control, disease-free survival and overall survival.RESULTS: A total of 258 patients with fixed rectal cancer received long-course radiotherapy (> 45 Gy). The median age at diagnosis was 66 years (range: 32-85) and 185 (72%) patients were male. The resectability rate was 80%, and a R0 resection was obtained in 148 patients (57% of all patients and 61% of those operated). The 5-year local recurrence rate for all patients was 5% (95% CI: 3-7%), and the actuarial distant recurrence rate was 41% (95% CI: 35-47%). The cumulative 5-year disease-free survival was 27% (95% CI: 22-32%) and overall 5-year survival was 34% (95% CI: 29-39%).CONCLUSIONS: This study is the first population-based report on outcome of preoperative long-course radiotherapy in a large unselected patient group with clinically fixed rectal cancer. Most patients could be resected with the intention of cure and one in three was alive after 5 years.

To investigate the genetic factor in the development of colorectal cancer, a cohort study was undertaken of parents of patients with this disease. All 1,524 patients, who were diagnosed with colorectal cancer in Denmark in 1982-84 and were below the age of 60 years, were selected from the National Cancer Register. The parents of these patients were identified from the public population registers. The index persons had a total of 1,478 eligible mothers, of whom 96% were successfully traced, and a total of 1,414 eligible fathers, of whom 96% were traced. These parents were sought in the Cancer Register for cancer cases diagnosed in the period January 1, 1943 to December 31, 1986. The incidence rates for the Danish population were used to estimate the expected numbers of colorectal cancer cases among the parents. Both the mothers and the fathers exhibited an increased risk of colorectal cancer. The standardized incidence ratios were 1.62 (95% CI 1.31-2.01) and 1.87 (95% CI 1.54-2.27), respectively. In a previous study we found that spouses of patients with colorectal cancer in Denmark did not have an increased risk of this disease. The increased risk found in the present study among the parents of patients therefore indicates that a possible genetic factor is present in the aetiology of colorectal cancer, and that it is of importance in the general population.

Familial adenomatous polyposis (FAP) includes early development of up to thousands of colorectal adenomas and of colorectal adenocarcinoma in all untreated cases. Moreover, a variety of extracolonic manifestations are seen. Proctosigmoidoscopy is used for screening; when adenomas are found, the diagnostic evaluation includes colonoscopy and gastroduodenoscopy. Screening of first degree relatives should start at the age of 10 years, using proctosigmoidoscopy at regular intervals. The recent detection of a specific FAP gene at chromosome 5 and of congenital retinal pigmentations will allow an early preclinical diagnosis in the future. A centralized registration of FAP has resulted in an improved prognosis, and the establishment of international groups will contribute to increased research of this disease.

Background Only a few small studies have evaluated risk factors related to early death following emergency surgery for colonic cancer. The aim of this study was to identify risk factors for death within 30 days after such surgery. Methods Some 2157 patients who underwent emergency treatment for colonic cancer from May 2001 to December 2005 were identified from the national colorectal cancer registry. Thirty-day mortality rates were calculated and risk factors for early death were identified using logistic regression analysis. Results The overall 30-day mortality rate was 22·1 per cent. The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11·7 (95 per cent confidence interval 8·8 to 15·5). Such complications occurred in 24·4 per cent of patients, of whom 57·8 per cent died. Other independent risk factors were age at least 71 years, male sex, American Society of Anesthesiologists grade III or more, palliative outcome, tumour perforation, splenectomy and adverse intraoperative surgical events. Postoperative surgical complications were noted in 20·4 per cent of the patients but had no statistically significant influence on mortality. Conclusion Emergency surgery for colonic cancer is still associated with an increased risk of death. There is a need for a system providing increased safety in the perioperative period.

Over the last 25 years restorative proctocolectomy with an ileoanal pouch has been the gold standard in the surgical treatment of ulcerative colitis and in selected patients with familial adenomatous polyposis. We present a study of the course, complications and long-term functional results.A prospective cohort analysis and a questionnaire in 178 consecutive patients operated since 1987 in Hvidovre Hospital.Postoperative complications were seen in 38 patients (21%), but only few were serious: anastomotic leakage in 2 (1%), pelvic abscess in 4 (2%) and complications after ileostomy closure in 2 (1%). The late complications comprised reoperation for intestinal bowel obstruction in 10 (6%), pouch fistula in 6 (3%), pouchitis in 22 (12%), and anastomotic stricture in 8 (5%). Three patients (2%) had the pouch removed. After a median observation period of 7 years (range 1-19) the patients had a median of 7 bowel movements per 24 hours (range 3-15), and 2/3 were totally continent day and night. 88% were satisfied with the results.Our results are similar to those in the literature, probably because the preoperative evaluation, operation, postoperative course and long-term follow-up were managed by few specialists in ileoanal pouch surgery. In our opinion restorative proctocolectomy with an ileoanal pouch is still the gold standard for patients with ulcerative colitis and for selected patients with familial adenomatous polyposis.

On the basis of the literature about anastomotic leakage after anterior resection for rectal cancer a review is presented of the frequency, potential risk factors and consequences of leakage. The risk factors are evaluated according to the level of scientific evidence of the individual background articles, and based upon the best documented risk factors recommendations are proposed for prophylactic measures against anastomotic leakage. Furthermore, proposals for future research in the area are presented.

Item does not contain fulltext BACKGROUND: Familial adenomatous polyposis (FAP) is a well-described inherited syndrome, which is responsible for