Cancer in Patients With Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Controls.

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. METHODS: All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. RESULTS: The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28-5.17; P < .001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58-8.22; P < .001), pancreatic cancer (HR, 6.45; 95% CI, 2.02-20.64; P = .002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76-119.47; P = .013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53-20.23; P = .20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02-3.50; P = .042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. CONCLUSIONS: Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.

Psychiatric and Educational Aspects of Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Nonexposed Individuals.

INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. METHODS: All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses ( International Classification of Disease, 10th Revision ), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. RESULTS: The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP ( P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25-2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17-1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19-2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20-1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09-2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10-3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24-2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26-2.70, P = 0.002). DISCUSSION: Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased likelihood of needing antidepressants and antipsychotics.

Cancer Risks in Attenuated and Classical Familial Adenomatous Polyposis: A Nationwide Cohort with Matched, Non-Exposed Individuals: Cancer and surgery in AFAP and FAP patients.

INTRODUCTION: Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene. FAP is usually categorized according to phenotype: classical FAP (CFAP) and attenuated FAP (AFAP); the latter is considered to have a milder disease course. We aimed to assess the risk of overall and specific cancers in CFAP and AFAP patients compared to matched, non-exposed individuals. METHODS: All known Danish FAP patients were classified as either CFAP or AFAP and assigned four matched, non-exposed individuals. The risk of overall and specific cancers, and mortality were analyzed. RESULTS: The analysis included 311 CFAP patients, 134 AFAP patients, and 1,600 non-exposed individuals. The overall cancer risk was significantly higher for both CFAP and AFAP patients than for non-exposed individuals, with hazard ratios (HR) of 4.77 (95% confidence interval (CI), 3.61-6.32; P<0.001) for CFAP and 3.22 (95% CI, 2.16-4.80; P<0.001) for AFAP. No significant difference was observed when comparing CFAP and AFAP (HR=1.48; 95% CI, 0.98-2.25; P=0.0646). The HR of colonic cancer was 2.16 (95% CI, 0.99-7.72; P=0.0522) and 2.72 (95% CI, 1.19-6.22; P=0.0177 for CFAP and AFAP), respectively compared to non-exposed and did not differ between CFAP and AFAP patients (HR=0.80; 95% CI, 0.32-2.00; P=0.6278). Mortality was significantly higher in CFAP (HR=2.96; 95% CI, 2.04-4.28; P<0.001), but not in AFAP (HR=1.40; 95% CI, 0.73-2.69; P=0.311). CONCLUSION: Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared to non-exposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients.

Validation of the Endoscopic Part of the Spigelman Classification for Evaluating Duodenal Adenomatosis in Familial Adenomatous Polyposis: A Prospective Study of Interrater and Intrarater Reliability.

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.

Colorectal Cancer in Individuals With Familial Adenomatous Polyposis, Based on Analysis of the Danish Polyposis Registry.

BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The Danish Polyposis Registry enables close monitoring of patients with FAP, reducing risk of CRC and prolonging life.

An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis.

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.

A proposed staging system and stage-specific interventions for familial adenomatous polyposis.

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.

Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study.

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.

Genotype predicting phenotype in familial adenomatous polyposis: a practical application to the choice of surgery.

PURPOSE: 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. METHODS: 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. RESULTS: 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 (P < 0.05, groups compared separately). Cumulative risks of rectal cancer after primary colectomy were 3.7%, 9.3%, and 8.3%, respectively, in the three groups (P > 0.05, groups compared separately). CONCLUSION: 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.

Colectomy and ileorectal anastomosis is still an option for selected patients with familial adenomatous polyposis.

PURPOSE: The risk of rectal cancer after colectomy and ileorectal anastomosis may be reduced in the last decades, as patients with severe polyposis now have an ileoanal pouch. We have reevaluated the risk of rectal cancer and proctectomy for all causes according to the year of operation. METHODS: On the basis of the year of operation in 776 patients with ileorectal anastomosis and 471 pouch patients in Denmark, Finland, Holland, and Sweden, the "pouch period" was defined to start in 1990. Ileorectal anastomosis follow-up data was captured by May 31, 2006. The cumulative risk of rectal cancer and proctectomy was compared before and after 1990 by Kaplan-Meier analysis. RESULTS: In the prepouch period 56/576 patients (10 percent) developed rectal cancer, vs. 4/200 (2 percent) in the pouch period. Neither the cumulative risk of rectal cancer (p = 0.07) nor the cumulative risk of proctectomy (p = 0.17) changed. However, in females the cumulative risk of rectal cancer (p = 0.04) and of proctectomy (p = 0.03) were lower in the pouch period. CONCLUSIONS: Since the introduction of the ileoanal pouch rectal cancer has decreased after ileorectal anastomosis, but only statistically significant in females. This indicates that ileorectal anastomosis may still be justified in selected patients with mild adenomatosis, especially in young females.

Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis.

Almost all patients affected by Familial Adenomatous polyposis (FAP) will develop foregut as well as hindgut polyps, and following prophylactic colectomy duodenal cancer constitutes one of the leading causes of death in screened populations. Without prophylactic colectomy, FAP patients predictably develop colorectal cancer, but the lifetime risk of upper gastrointestinal cancer is lower, estimated at approximately 5%. Management of the upper gastrointestinal cancer risk is one of the greatest challenges facing clinicians involved in the care of Polyposis families, and with improved survival following prophylactic colectomy, the burden of foregut disease (particularly duodenal adenomatosis) will increase. Until recently, the value of upper gastrointestinal surveillance in FAP populations has been contentious, but with improved understanding of the natural history coupled with developments in surgery, interventional endoscopy and medical therapy, treatment algorithms for duodenal adenomatosis in FAP are becoming clearer.

Local involvement of the lower urinary tract in primary colorectal cancer - outcome after en-bloc resection.

UNLABELLED: Invasion of urinary organs due to advanced colorectal cancer can comprise a surgical challenge in achieving negative resection margins. The aim of the study was to asses the outcome of patients with colorectal cancer invading the lower urinary organs. MATERIAL AND METHODS: This is a cohort study that retrospectively evaluated the surgical and pathological findings after the resection of colorectal cancer with adjacent urological organs due to advanced colorectal cancer. Patients with primary colorectal cancer invading urological organs where primary resection was attempted were included. RESULTS: The study included 31 patients who underwent surgery in our department between 1997 and 2012. Median age was 65 years (range 44-77 years). Seventeen patients underwent partial cystectomy, one had partial prostatectomy performed, eight patients underwent cystoprostatectomy, two had cystectomy performed and three had prostatectomy performed. Overall morbidity rate was 71% (95% Confidence Interval (CI): 55-84%, n=22). The 30-day mortality rate was 10% (95% CI: 0-23%, n=3). Twentyseven of 31 patients had free resection margins. Four of 28 patients developed distant metastasis (14%, 95% CI: 4-29%), 11% developed local recurrence (95% CI: 0-25%, n=3). Median follow-up was 41 months (range 0-150 months). Histopathological examination revealed tumour invasion in 52% (95% CI: 35-69%, n=15) of the resected urological organs. The overall five-year survival rate was 70%. The five-year survival rate in the radical resection group was 74%. CONCLUSIONS: En-bloc resection of colorectal cancer with adjacent urological organs has a high morbidity rate. However it is still possible to achieve negative resection margins in most cases.

Mutation analysis of the adenomatous polyposis coli (APC) gene in Danish patients with familial adenomatous polyposis (FAP).

Development of one hundred or more adenomas in the colon and rectum is diagnostic for the dominantly inherited, autosomal disease Familial Adenomatous Polyposis (FAP). It is possible to identify a mutation in the Adenomatous Polyposis Coli (APC) gene in approximately 80% of the patients, and almost 1,000 different pathogenic mutations have been identified in the APC gene up till now. We report 12 novel and 24' previously described germline APC mutations from 48 unrelated Danish families. Four families with the mutation localized in the 3' region of the gene showed great variance in phenotypic presentation.

De novo mutations in familial adenomatous polyposis (FAP).

Familial Adenomatous Polyposis (FAP) results from a germline mutation in the APC gene. A new mutation rate of 4-9 x 10(-6) mutations/gametes/generation has been reported. In other familial cancer syndromes a bias for paternal origin of new mutations has been described. This bias is probably due to a larger number of cell divisions during spermatogenesis compared to oogenesis; giving a larger susceptibility for mutagenesis. We report here a molecular genetic analysis of 26 FAP patients with putative de novo APC mutations. In 15 families the novel origin of the mutations was confirmed by haplotyping and sequencing. Analysis of 10 of these mutations, in which the parental origin could be established, gave a 6 : 4 distribution in favour of maternal origin. This is in agreement with a 1 : 1 distribution and does not indicate an expected paternal bias. Moreover, no parental age effect was identified. We propose that APC germline mutations are not premeiotic events but more likely arise during the meiosis. This would give an equal susceptibility for mutagenesis during spermatogenesis and oogenesis, respectively. The model is in concordance with the previously established difference between APC somatic mutations, as being a mitotic event and APC germline mutations, as being a meiotic event. The confirmation of 15 de novo mutations by a molecular genetic approach is in fine agreement with previous results based on clinical records.

Attenuated familial adenomatous polyposis (AFAP). A review of the literature.

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.

VEGF concentrations in tumour arteries and veins from patients with rectal cancer.

This pilot study investigated the hypothesis that the tumour itself is the source of the elevated vascular endothelial growth factor (VEGF) concentrations which are often observed in peripheral blood from patients with rectal cancer. Twenty-four consecutive patients with primary rectal cancer were included. Blood samples were drawn preoperatively from peripheral veins (I) and intraoperatively from peripheral veins (II), tumour arteries (III), and tumour veins (IV). In the four compartments, VEGF concentrations were measured in serum, EDTA plasma, and supernatants from lysed whole blood. Additionally, automated complete white cell and platelet counts were performed. In serum and EDTA plasma, no significant differences in VEGF concentrations were observed (p = 0.1 and p = 0.5), respectively) between tumour arteries and tumour veins. However, in supernatants from lysed blood, VEGF concentrations were significantly (p = 0.03) lower in venous blood than in arterial blood. Unexpectedly, a 16% reduction (p < 0.0001) in the number of neutrophils was observed during transit of the arterial blood through the rectal tumours, while none of the other types of leukocytes or platelets was significantly reduced in numbers during the same passage. These findings indicate that the tumour itself is not the only source of elevated VEGF concentrations in peripheral blood from patients with rectal cancer. A consistent finding was that a large number of neutrophils disappeared from the blood during passage through the rectal tumour. However, the significance and fate of the migrating neutrophils cells are unknown and should be investigated further.

[Familial adenomatous polyposis]. / Familiær adenomatøs polypose.

Familial adenomatous polyposis (FAP) is an autosomally dominant disease characterized by early development of up to thousands of colorectal adenomas and colorectal carcinoma in untreated patients. Extra-colonic manifestations include duodenal adenomatosis and desmoid development. Due to identification of gene carriers by DNA analysis or endoscopy the prognosis is good after early colectomy, but life-long surveillance of the rectum and the duodenum is necessary. The Danish Polyposis Register coordinates prophylactic examination and treatment in the families, and serves as basis for research.

Relatively high incidence of complications after loop ileostomy reversal.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSION: 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. FUNDING: not relevant TRIAL REGISTRATION: not relevant.

The outcome of rectal cancer after early salvage surgery following transanal endoscopic microsurgery seems promising.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSION: Early salvage surgery after TEM seems to be safe despite a high risk of specimen perforation during the operation. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.