Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome.

BACKGROUND: The risk of metachronous colorectal cancer is high after surgical resection for first colon cancer in Lynch syndrome. OBJECTIVE: This study aimed to examine whether extended surgery decreases the risk of subsequent colorectal cancer and improves long-term survival. DESIGN: This was a retrospective study. SETTING: Data were collected from a nationwide registry. PATIENTS: Two hundred forty-two Lynch syndrome pathogenic variant carriers who underwent surgery for a first colon cancer from 1984 to 2009 were included. INTERVENTIONS: Patients underwent standard segmental colectomy (n = 144) or extended colectomy (n = 98) for colon cancer. Patients were followed a median of 14.6 up to 25 years. MAIN OUTCOME MEASURES: Risk of subsequent colorectal cancer in either group, overall and disease-specific survival, and operative mortality were the primary outcomes measured. RESULTS: Subtotal colectomy decreased the risk of subsequent colorectal cancer (HR, 0.20; 95% CI, 0.08-0.52; p = 0.001), compared with segmental resection. Subsequent colorectal cancer decreased in MLH1 carriers. The MSH2 carriers showed no statistical difference, possibly because of their small number. Disease-specific and overall survival within 25 years did not differ between the standard and extended surgeries (82.7% vs 87.2%, p = 0.76 and 47.2% vs 41.4%, p = 0.83). The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection and 4% and 9% after extended surgery. The cumulative risk of metachronous colorectal cancer was 7% within 25 years after subtotal colectomy with ileosigmoidal anastomosis. One patient died of postoperative septicemia within 30 days after segmental colectomy. LIMITATIONS: Data on surgical procedures were primarily collected retrospectively. CONCLUSIONS: Lynch syndrome pathogenic variant carriers may undergo subtotal colectomy to manage first colon cancer and avoid repetitive abdominal surgery and to reduce the remaining bowel to facilitate easier endoscopic surveillance. It provides no survival benefit, compared with segmental colon resection. See Video Abstract at http://links.lww.com/DCR/A319.

[Diagnosis and treatment of Lynch syndrome]. / Lynchin oireyhtymän diagnostiikka ja hoito.

Lynch syndrome (LS) refers to an autosomal dominant genetic predisposition to develop colon cancer or cancers or the uterine corpus, stomach, urinary tract, ovaries, small intestine, mammary gland or bile ducts at a young age. The predisposition to cancer is caused by a germline mutation in one of the genes of the mismatch repair (MMR) system. International recommendations suggest immunohistochemical analysis of tumor tissue from at least those having developed colorectal cancer or endometrial cancer at an age of less than 70 years. This would allow the selection of patients to be referred for gene testing as well as identification of mutation carriers, for whom a regular colonoscopy follow-up is arranged at an interval of 2 to 3 years.

Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency.

Little is known about the genetic factors that contribute to familial colorectal cancer type X (FCCX), characterized by hereditary nonpolyposis colorectal carcinoma with no mismatch repair defects. Genetic linkage analysis, exome sequencing, tumor studies, and functional investigations of 4 generations of a FCCX family led to the identification of a truncating germline mutation in RPS20, which encodes a component (S20) of the small ribosomal subunit and is a new colon cancer predisposition gene. The mutation was associated with a defect in pre-ribosomal RNA maturation. Our findings show that mutations in a gene encoding a ribosomal protein can predispose individuals to microsatellite-stable colon cancer. Evaluation of additional FCCX families for mutations in RPS20 and other ribosome-associated genes is warranted.

Promoter-specific alterations of APC are a rare cause for mutation-negative familial adenomatous polyposis.

n familial adenomatous polyposis (FAP), 20% of classical and 70% of attenuated/atypical (AFAP) cases remain mutation-negative after routine testing; yet, allelic expression imbalance may suggest an APC alteration. Our aim was to determine the proportion of families attributable to genetic or epigenetic changes in the APC promoter region. We studied 51 unrelated families/cases (26 with classical FAP and 25 with AFAP) with no point mutations in the exons and exon/intron borders and no rearrangements by multiplex ligation-dependent probe amplification (MLPA, P043-B1). Promoter-specific events of APC were addressed by targeted resequencing, MLPA (P043-C1), methylation-specific MLPA, and Sanger sequencing of promoter regions. A novel 132-kb deletion encompassing the APC promoter 1B and upstream sequence occurred in a classical FAP family with allele-specific APC expression. No promoter-specific point mutations or hypermethylation were present in any family. In conclusion, promoter-specific alterations are a rare cause for mutation-negative FAP (1/51, 2%). The frequency and clinical correlations of promoter 1B deletions are poorly defined. This investigation provides frequencies of 1/26 (4%) for classical FAP, 0/25 (0%) for AFAP, and 1/7 (14%) for families with allele-specific expression of APC. Clinically, promoter 1B deletions may associate with classical FAP without extracolonic manifestations.

Distinct molecular profiles in Lynch syndrome-associated and sporadic ovarian carcinomas.

Ovarian carcinoma in Lynch syndrome (LS) is associated with unexpectedly high survival; yet, beyond DNA mismatch repair (MMR) defects, the developmental mechanisms are unknown. We used established (genetic) and new (epigenetic) classifiers of ovarian cancer to explore similarities and differences between LS-associated and sporadic diseases. To this end, all available ovarian carcinomas (n = 20) from MMR gene mutation carriers ascertained through a nation-wide registry and 87 sporadic ovarian carcinomas of the main histological types were molecularly profiled. LS-ovarian carcinomas were mostly of nonserous histology (12 endometrioid, seven clear cell and one serous), diagnosed at a mean age of 45.7 years, and associated with a 10-year survival of 87%. Among LS-ovarian carcinomas, 19/20 (95%) were MMR-deficient vs. 11/87 (13%) among sporadic cases (p < 0.0001). In a striking contrast to the sporadic cases, the expression of p53 was normal and KRAS/BRAF mutations absent in all LS-ovarian carcinomas. PIK3CA mutations, suggested to be a favorable prognostic factor, occurred with a frequency of 6/20 (30%), which was comparable to sporadic tumors of endometrioid or clear cell type. Tumor suppressor genes were more frequently methylated and LINE-1 hypomethylation less common in LS-ovarian carcinomas compared to their sporadic counterparts. The patterns of genetic and epigenetic alterations reflected the origin as LS vs. sporadic cases on one hand and the histological type on the other hand. In conclusion, the significant molecular differences observed between LS-associated and sporadic ovarian carcinomas help explain the different behavior of these tumors and emphasize the need for tailored clinical management.

Tumor-independent Detection of Inherited Mismatch Repair Deficiency for the Diagnosis of Lynch Syndrome with High Specificity and Sensitivity.

Lynch syndrome (LS) is the most common hereditary cancer syndrome. Early diagnosis improves prognosis and reduces health care costs, through existing cancer surveillance methods. The problem is finding and diagnosing the cancer predisposing genetic condition. The current workup involves a complex array of tests that combines family cancer history and clinical phenotypes with tumor characteristics and sequencing data, followed by a challenging task to interpret the found variant(s). On the basis of the knowledge that an inherited mismatch repair (MMR) deficiency is a hallmark of LS, we have developed and validated a functional MMR test, DiagMMR, that detects inherited MMR deficiency directly from healthy tissue without need of tumor and variant information. The validation included 119 skin biopsies collected from clinically pathogenic MMR variant carriers (MSH2, MSH6) and controls, and was followed by a small clinical pilot study. The repair reaction was performed on proteins extracted from primary fibroblasts and the interpretation was based on the MMR capability of the sample in relation to cutoff, which distinguishes MMR proficient (non-LS) from MMR deficient (LS) function. The results were compared with the reference standard (germline NGS). The test was shown to have exceptional specificity (100%) with high sensitivity (89%) and accuracy (97%). The ability to efficiently distinguish LS carriers from controls was further shown with a high area under the receiving operating characteristic (AUROC) value (0.97). This test offers an excellent tool for detecting inherited MMR deficiency linked to MSH2 or MSH6 and can be used alone or with conventional tests to recognize genetically predisposed individuals. Significance: Clinical validation of DiagMMR shows high accuracy in distinguishing individuals with hereditary MSH2 or MSH6 MMR deficiency (i.e., LS). The method presented overcomes challenges faced by the complexity of current methods and can be used alone or with conventional tests to improve the ability to recognize genetically predisposed individuals.

Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases.

INTRODUCTION: Breast carcinoma is the most common cancer in women, but its incidence is not increased in Lynch syndrome (LS) and studies on DNA mismatch repair deficiency (MMR) in LS-associated breast cancers have arrived at conflicting results. This study aimed to settle the question as to whether breast carcinoma belongs to the LS tumor spectrum. METHODS: MMR status and epigenetic profiles were determined for all available breast carcinomas identified among 200 LS families from a nation-wide registry (23 tumors from mutation carriers and 18 from non-carriers). Sporadic breast carcinomas (n = 49) and other cancers (n = 105) from MMR gene mutation carriers were studied for comparison. RESULTS: The proportion of breast carcinomas that were MMR-deficient based on absent MMR protein, presence of microsatellite instability, or both was significantly (P = 0.00016) higher among breast carcinomas from mutation carriers (13/20, 65%) compared to non-carriers (0/14, 0%). While the average age at breast carcinoma diagnosis was similar in carriers (56 years) and non-carriers (54 years), it was lower for MMR-deficient versus proficient tumors in mutation carriers (53 years versus 61 years, P = 0.027). Among mutation carriers, absent MMR protein was less frequent in breast carcinoma (65%) than in any of seven other tumor types studied (75% to 100%). Tumor suppressor promoter methylation patterns were organ-specific and similar between breast carcinomas from mutation carriers and non-carriers. CONCLUSIONS: Breast carcinoma from MMR gene mutation carriers resembles common breast carcinoma in many respects (for example, general clinicopathological and epigenetic profiles). MMR status makes a distinction: over half are MMR-deficient typical of LS spectrum tumors, while the remaining subset which is MMR-proficient may develop differently. The results are important for appropriate surveillance in mutation carriers and may be relevant for LS diagnosis in selected cases.

Effect of aspirin or resistant starch on colorectal neoplasia in the Lynch syndrome.

BACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. METHODS: In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome. RESULTS: Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. CONCLUSIONS: The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)

Survival in women with MMR mutations and ovarian cancer: a multicentre study in Lynch syndrome kindreds.

BACKGROUND: Women with a germline mutation in one of the MMR genes MLH1, MSH2 or MSH6 reportedly have 4-12% lifetime risk of ovarian cancer, but there is limited knowledge on survival. Prophylactic bilateral salpingo-oophorectomy (PBSO) has been suggested for preventing this condition. AIM: The purpose of this retrospective multicentre study was to describe survival in carriers of pathogenic mutations in one of the MMR genes, and who had contracted ovarian cancer. METHODS: Women who had ovarian cancer, and who tested positive for or were obligate carriers of an MMR mutation, were included from 11 European centres for hereditary cancer. Most women had not attended for gynaecological screening. Crude and disease specific survival was calculated by the Kaplan-Meier algorithm. RESULTS: Among the 144 women included, 81.5% had FIGO stage 1 or 2 at diagnosis. 10 year ovarian cancer specific survival independent of staging was 80.6%, compared to less than 40% that is reported both in population based series and in BRCA mutation carriers. Disease specific 30 year survival for ovarian cancer was 71.5%, and for all hereditary non-polyposis colon cancer (HNPCC)/Lynch syndrome related cancers including ovarian cancer it was 47.3%. CONCLUSIONS: In the series examined, infiltrating ovarian cancer in Lynch syndrome had a better prognosis than infiltrating ovarian cancer in BRCA1/2 mutation carriers or in the general population. Lifetime risk of ovarian cancer of about 10% and a risk of dying of ovarian cancer of 20% gave a lifetime risk of dying of ovarian cancer of about 2% in female MMR mutation carriers.

[Treatment of pseudomyxoma peritonei is developing]. / Peritoneumin pseudomyksooman hoito kehittyy.

In pseudomyxoma peritonei a mucinous tumor of the appendix spreads into the abdominal cavity. Cytologic picture of the tumor may be benign, malignant or intermediary. The symptoms were previously relieved by repeated resections of the tumor mass, whereby even the most benign form of the disease progressed slowly. A method has now emerged in which radical-aimed surgery is combined with intraperitoneal lavage with a warmed solution of a cytotoxic agent. This treatment is associated with a morbidity of 33 to 56% and a mortality of 0 to 18%. Controlled studies have not been carried out on the novel treatment.

Large genomic rearrangements and germline epimutations in Lynch syndrome.

In one-third of families fulfilling the Amsterdam criteria for hereditary nonpolyposis colorectal cancer/Lynch syndrome, and a majority of those not fulfilling these criteria point mutations in DNA mismatch repair (MMR) genes are not found. The role of large genomic rearrangements and germline epimutations in MLH1, MSH2 and MSH6 was evaluated in 2 such cohorts. All 45 index patients were mutation-negative by genomic sequencing and testing for a prevalent population-specific founder mutation, and selectively lacked MMR protein expression in tumor tissue. Eleven patients ("research cohort") represented 11 mutation-negative families among 81 verified or putative Lynch syndrome families from the nation-wide Hereditary Colorectal Cancer Registry of Finland. Thirty-four patients from 33 families ("clinic-based cohort") represented suspected Lynch syndrome patients tested for MMR gene mutations in a diagnostic laboratory during 2004-2007. Multiplex ligation-dependent probe amplification (MLPA) and methylation-specific (MS)-MLPA were used to detect rearrangements and epimutations, respectively. Large genomic deletions occurred in 12/45 patients (27%), being present in 3/25 (12%), 9/16 (56%) and 0/4 (0%) among index patients lacking MLH1, MSH2 or MSH6 expression, respectively. Germline epimutations of MLH1, one of which coexisted with a genomic deletion, occurred in 2 patients (4%) and were accompanied by monoallelic expression in mRNA. Large genomic deletions (mainly MSH2) and germline epimutations (MLH1) together explain a significant fraction of point mutation-negative families suspected of Lynch syndrome and are associated with characteristic clinical and family features. Our findings have important implications in the diagnosis and management of such families.

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.

Primary sclerosing cholangitis: outcome of patients undergoing restorative proctocolecetomy for ulcerative colitis.

PURPOSE: The prevalence of primary sclerosing cholangitis (PSC) among patients with ulcerative colitis needing proctocolectomy is about 12%. The study aim was to evaluate the progression of the liver disease after surgery. METHODS: PSC progression in 68 patients with UC after restorative proctocolectomy was evaluated after a median follow-up of 11 years (range 0 to 21). Magnetic resonance imaging (MRI) of the liver, histological examination of a core needle liver specimen, and liver function tests were used in addition to clinical history. RESULTS: Of the 68 patients, 30 participated in follow-up examinations. Ductal changes in MRI suggesting a diagnosis of PSC occurred in 21 (72%) of them. One carcinoma of the gallbladder was found in MRI. Histopathologic changes suggesting PSC were observable in 15 (50%) patients. Compared to stage in peroperative biopsies taken at proctocolectomy, PSC stage increased in four (13%) patients, decreased in 15 (50%), and remained unchanged in 11 (37%). Immunohistochemical staining for cytoceratin-7 in hepatocytes was positive in nine (30%) indicating cholestasis. After IPAA surgery, five patients underwent liver transplantation at 1, 1, 5, 6, and 11 years, respectively. Of the 68, six patients have, to date, developed cholangiocarcinoma. CONCLUSIONS: Progression of PSC in patients with minor ductal changes at the time of restorative proctocolectomy is unlikely. Those patients with more advanced disease at surgery are at risk for disease progression and liver transplantation. We lack accurate diagnostic methods to detect premalignant changes of the biliary epithelium.

Background mutation frequency in microsatellite-unstable colorectal cancer.

Microsatellite instability (MSI) is observed in approximately 12% of colorectal cancers. Genes containing a mononucleotide microsatellite in the coding sequence are particularly prone to inactivation in MSI tumorigenesis, and much work has been conducted to identify genes with high repetitive tract mutation rates in these tumors. Much less attention has been paid to background mutation frequencies, and no work has focused on nontranscribed regions. Here, we studied 114 nontranscribed intergenic A/T and C/G repeats 6 to 10 bp in length, located distant from known genes, to examine background mutation frequencies in MSI colorectal cancers. A strong correlation with tract length was observed, and mutation frequencies of up to 87% were observed in 8 to 10 bp tracts. Subsequently, to compare the background mutation rate in transcribed and nontranscribed noncoding repeats, we screened nine randomly selected intronic C/G8 repeats. In addition, the coding repeats of seven suggested MSI target genes, and nine previously published intronic A8 and G8 repeats were analyzed. Intronic repeats seemed to mutate less frequently than nontranscribed intergenic repeats. Our results show that strand slippage mutations in mismatch repair-deficient cells are as abundant in short intergenic repeats as in many proposed MSI target genes. However, under mismatch repair deficiency, strand slippage mutations in transcribed sequences seem to be repaired more efficiently than in intergenic nontranscribed sequences. The mechanisms causing these differences are not yet understood and should be a subject for further studies. For MSI target gene identification, repeats in transcribed sequences seem to be the most appropriate reference group for coding region repeat mutations.

[Colonic carcinoma]. / Koolonkarsinooma.

Colonic carcinoma is the third most common cancer in Finland. Cardinal symptoms include a change in bowel function and rectal hemorrhage. The first line treatment of this cancer, both localized and metastatic, is surgery. Before surgery, the patient is subjected to colonoscopy and computed tomography scanning of the body, and the concentration of carcinoembryonic antigen in serum is determined. The surgical operation aspires to a local radicality by excising the part of colon bearing the tumor along with the corresponding mesocolon. If metastases are detected in the mesenteric lymph nodes or elsewhere, use of chemotherapy is considered postoperatively.

[Rectal cancer]. / Peräsuolen syöpä.

The most common symptom of rectal cancer is bleeding. The average diagnostic delay is half a year. Colonoscopy, magnetic resonance imaging of the pelvis and computed tomography scanning of the body are carried out before the operation to assess the extent, and the level of carcinoembryonic antigen is determined from the serum. In cancers grown through the intestinal wall or spread to the mesorectal lymph nodes, local radiotherapy is applied preoperationally. The surgical operation involves total mesorectal excision with low-rectal anastomosis. Cytotoxic chemotherapy of a disseminated cancer will improve the quality of life.

ARLTS1 germline variants and the risk for breast, prostate, and colorectal cancer.

Recently, a nonsense alteration Trp149Stop in the ARLTS1 gene was found more frequently in familial cancer cases versus sporadic cancer patients and healthy controls. Here, the role of Trp149Stop or any other ARLTS1 germline variant was evaluated on breast, prostate, and colorectal cancer risk. The whole gene was screened for germline alterations in 855 familial cancer patients. The five observed variants were further screened in 1169 non-familial cancer patients as well as in 809 healthy population controls. The Trp149Stop was found at low frequencies (0.5-1.2%) in all patient subgroups versus 1.6% in controls, and the mutant allele did not co-segregate with disease status in families with multiple affected individuals. The CC genotype in the Cys148Arg variant was slightly more common among both familial and sporadic breast (odds ratio (OR), 1.48; 95% confidence interval (CI), 1.16-1.87; P=0.001) and prostate cancer patients (OR, 1.50; 95% CI, 1.13-1.99; P=0.005) when compared to controls. A novel ARLTS1 variant Gly65Val was found at higher frequency among familial prostate cancer patients (8 of 164, 4.9%) than in controls (13 of 809, 1.6%; OR, 3.14; 95% CI, 1.28-7.70, P=0.016). However, after adjusting for multiple testing, none of these results were still significant. No association was found with any of the variants and colorectal cancer risk. Our results suggest that Trp149Stop is not a predisposition allele in breast, prostate, or colorectal cancer in the Finnish population, and, while the Gly65Val variant may increase familial prostate cancer risk and the Cys148Arg change may affect both breast and prostate cancer risk, the evidence is not strong in these data.

The risk of extra-colonic, extra-endometrial cancer in the Lynch syndrome.

Persons with the Lynch syndrome (LS) are at high risk for cancer, including cancers of the small bowel, stomach, upper urologic tract (renal pelvis and ureter), ovary, biliary tract and brain tumors, in addition to the more commonly observed colorectal and endometrial cancers. Cancer prevention strategies for these less common cancers require accurate, age-specific risk estimation. We pooled data from 4 LS research centers in a retrospective cohort study, to produce absolute incidence estimates for these cancer types, and to evaluate several potential risk modifiers. After elimination of 135 persons missing crucial information, cohort included 6,041 members of 261 families with LS-associated MLH1 or MSH2 mutations. All were either mutation carriers by test, probable mutation carriers (endometrial/colorectal cancer-affected), or first-degree relatives of these. Among mutation carriers and probable carriers, urologic tract cancer (N = 98) had an overall lifetime risk (to age 70) of 8.4% (95% CI: 6.6-10.8); risks were higher in males (p < 0.02) and members of MSH2 families (p < 0.0001). Ovarian cancer (N = 72) had an lifetime risk of 6.7% (95% CI: 5.3-9.1); risks were higher in women born after the median year of birth (p < 0.008) and in members of MSH2 families (p < 0.006). Brain tumors and cancers of the small bowel, stomach, breast and biliary tract were less common. Urologic tract cancer and ovarian cancer occur frequently enough in some LS subgroups to justify trials to evaluate promising prevention interventions. Other cancer types studied occur too infrequently to justify strenuous cancer control interventions.

Prevalence of primary sclerosing cholangitis in ulcerative colitis patients undergoing proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: This study aimed to determine the prevalence of primary sclerosing cholangitis (PSC) among patients with ulcerative colitis (UC) needing proctocolectomy. METHODS: The study sample included 441 consecutive patients who underwent proctocolectomy with ileal pouch-anal anastomosis from 1993 to 2004 at the Helsinki University Central Hospital. Liver biopsy samples were taken at operation. Patient groups with and without PSC were compared. RESULTS: PSC was present in 52 (11.8%) patients. Only 19 of these had been diagnosed before surgery; 40 patients with PSC were detected by liver biopsy at the operation, making the sensitivity of perioperative liver biopsy to diagnose PSC 83.3%. The cumulative incidence of colorectal dysplasia or cancer in the UC patients with PSC (19% after 10 years and 43% after 20 years) was not significantly different than that of UC patients without PSC (24% after 10 years and 39% after 20 years). Pouchitis occurred more often in patients with PSC (25 of 52; 48.1% versus 101 of 389, 26.0%; P = 0.001). The failure rate of ileal pouch-anal anastomosis did not significantly differ between the 2 groups. CONCLUSIONS: The prevalence of PSC among patients with UC needing proctocolectomy was higher than in patients with UC in general. Liver biopsy can be recommended as a safe adjunct at proctocolectomy for surveillance of any liver effects.