Combination of microsatellite instability and BRAF mutation status for subtyping colorectal cancer.

BACKGROUND: The objective of the study was to examine the role of microsatellite instability (MSI) and BRAF(V600E)mutation in colorectal cancer (CRC) by categorising patients into more detailed subtypes based on tumour characteristics. METHODS: Tumour samples from 762 population-based patients with sporadic CRC were analysed for MSI and BRAF(V600E) by immunohistochemistry. Patient survival was followed-up for a median of 5.2 years. RESULTS: Compared with microsatellite stable (MSS) CRC, MSI was prognostic for better disease-free survival (DFS; 5 years: 85.8% vs 75.3%, 10 years: 85.8% vs 72.9%, P=0.027; HR 0.49, CI 0.30-0.80, P=0.005) and disease-specific survival (DSS; 5 years: 83.2% vs 70.5%; 10 years: 83.2 vs 65.0%, P=0.004). Compared with BRAF wild type, BRAF(V600E) was a risk for poor survival (overall survival; 5 years: 62.3% vs 51.6%, P=0.014; HR 1.43, CI 1.07-1.90, P=0.009), especially in rectal cancer (for DSS, HR: 10.60, CI: 3.04-36.92, P<0.001). The MSS/BRAF(V600E) subtype was a risk for poor DSS (HR: 1.88, CI: 1.06-3.31, P=0.030), but MSI/BRAF(V600E) was a prognostic factor for DFS (HR: 0.42, CI: 0.18-0.96, P=0.039). Among stage I-II patients, the MSS/BRAF(V600E) subtype was independently associated with poor DSS (HR: 5.32, CI: 1.74-16.31, P=0.003). CONCLUSIONS: Microsatellite instable tumours were associated with better prognosis compared with MSS. BRAF(V600E) was associated with poor prognosis unless it occurred together with MSI. The MSI/BRAF(V600E) subtype was a favourable prognostic factor compared with the MSS/BRAF wild-type subtype. BRAF(V600E) rectal tumours showed particularly poor prognosis. The MSS/BRAF(V600E) subtype was associated with increased disease-specific mortality even in stage I-II CRC.

Epidemiologic aspects of complete rectal prolapse.

BACKGROUND AND AIMS: This study was undertaken to find out the incidence of rectal prolapse. MATERIAL AND METHODS: Ninety-nine patients operated on for rectal prolapse at Jyväskylä Central Hospital were studied. Patients operated between 1988 and 1998 were studied retrospectively from hospital records using chart review and thirty-five patients operated on between 1999 and 2002 were studied prospectively using our proctologic database. RESULTS: The annual incidence of diagnosed complete rectal prolapse in the district of Central Finland was mean 2.5 (range, 0.79-6.08) per 100 000 population. There were ten men (10 percent) and 89 women (90 percent). Median age of the patients was 69 (range, 21-91) years. Forty-eight percent of the patients had concomitant cardiovascular disease and 15 percent psychiatric illness. Anal incontinence affecting quality of life was seen in 64 percent and constipation in 72 percent of patients. Constipation tended to be more attributed to difficult evacuation (72 percent) than to impaired bowel action (18 percent). CONCLUSION: The annual incidence of rectal prolapse is 2.5 per 100 000 population. Rectal prolapse is associated with anal incontinence and constipation in majority of patients.

Laparoscopic repair of rectal prolapse: surgical technique.

Technical features of laparoscopic rectopexy include complete rectal mobilization without division of the lateral stalks to avoid parasympathetic denervation and postoperative problems with defecation. Suture rectopexy is equally effective as posterior mesh rectopexy in preventing recurrences and eliminates the use of foreign material which is sometimes associated with intense fibrosis, sepsis and increased constipation. According to two randomised studies constipation seems to be less after resection rectopexy than suture or posterior mesh rectopexy alone perhaps by eliminating possible kinking at the rectosigmoid region by falling of the redundant sigmoid colon in the pouch of Douglas. Randomized studies are, however, needed to validate the need for colonic resection and to determine its optimal extent in patients who suffer from rectal prolapse, constipation and slow transit.

Laparoscopic repair of rectal prolapse: a prospective study evaluating surgical outcome and changes in symptoms and bowel function.

BACKGROUND: There have been few large series that have focused on the feasibility of the laparoscopic approach for rectal prolapse. This single-institution study prospectively examines the surgical outcome and changes in symptoms and bowel function following the laparoscopic repair of rectal prolapse. METHODS: In a selected group of 34 patients (total prolapse, 28; intussusception, six), 17 patients underwent laparoscopic-assisted resection rectopexy and 17 patients received a laparoscopic sutured rectopexy. Preoperative and postoperative evaluation at 3, 6, and 12 months included assessment of the severity of anal incontinence, constipation, changes in constipation-related symptoms, and colonic transit time. RESULTS: Median operation time was 255 min (range, 180-360) in the resection rectopexy group and 150 min (range, 90-295) in the rectopexy alone group. Median postoperative hospital stay was 5 days (range, 3-15) and median time off work was 14 days (range, 12-21) in both groups. There were no deaths. Postoperative morbidity was 24%. Incontinence improved significantly regardless of which method was used. The main determinant of constipation was excessive straining at defecation. Constipation was cured in 70% of the patients in the rectopexy group and 64% in the resection rectopexy group. Symptoms of difficult evacuation improved, but the changes were significant only after resection rectopexy. Two patients (7%) developed recurrent total prolapse during a median follow-up of 2 years (range 12-60 months). CONCLUSIONS: Laparoscopic-sutured rectopexy and laparoscopic-assisted resection rectopexy are feasible and carry an acceptable morbidity rate. They eliminate prolapse and cure incontinence in the great majority of patients. Constipation and symptoms of difficult evacuation are alleviated.

Functional outcome after laparoscopic or open Nissen fundoplication: a follow-up study.

OBJECTIVE: To compare the results of open and laparoscopic fundoplication. DESIGN: Nonrandomized controlled study with a 3-year follow-up. PATIENTS AND METHODS: Fifty-seven consecutive patients with erosive reflux esophagitis underwent laparoscopic (30 patients) or open (27 patients) fundoplication. INTERVENTIONS: Interview by an independent person. In addition, 52 patients (91%) underwent postoperative endoscopy, and 38 patients (67%) underwent esophageal 24-hour pH recording. RESULTS: Temporary dysphagia was reported by 20 patients (67%) after laparoscopic and by 11 (41%) after open fundoplication (P = .05). There were no differences between groups concerning incidence of persistent dysphagia (20% vs 18%, respectively) and mild to no reflux symptoms (97% vs 100%, respectively). In addition, bloating (50% vs 63%, respectively) and increased flatus (77% vs 78%, respectively) were equally common. Visual analog scale scores for dysphagia, bloating, and increased flatus were 0.6, 2.4, and 4.3, respectively, in the laparoscopic and 0.6, 3.5, and 3.4, respectively, in the open groups. Normal belching ability was reported by 12 patients (40%) after laparoscopic and by 20 (74%) after open fundoplication (P = .01). Visick grade 1 or 2 was reported by 21 patients (70%) after laparoscopic and by 24 (89%) after open fundoplication (P = .08). Defective fundic wrap was detected in 4 patients (13%) in the laparoscopic and in none in the open group. In addition, abnormal results of 24-hour pH recording were found in 4 patients (22%) after laparoscopic and in 2 (10.5%) after open fundoplication. CONCLUSION: From a functional point of view, both techniques were equally effective except concerning belching ability and temporary dysphagia.

Colorectal dysplasia and carcinoma in patients with ulcerative colitis and primary sclerosing cholangitis.

BACKGROUND: The aim of this study was to evaluate the role of primary sclerosing cholangitis (PSC) as a cofactor in the dysplasia-carcinoma sequence in ulcerative colitis (UC). METHODS: Forty-five patients with UC and concomitant PSC and 45 pair-matched control patients with UC only were examined for colorectal dysplasia and carcinoma. RESULTS: The median duration of UC was 11 years in the group with UC and PSC and 15 years in the control group. Thirteen of the 45 patients (29%) with UC and PSC had colorectal neoplasia: 4, carcinoma; 2, high-grade dysplasia; and 7, low-grade dysplasia. Four of the 45 control patients (9%) had neoplastic findings: 1, carcinoma; 1, high-grade dysplasia, and 2, low-grade dysplasia (P < 0.05). CONCLUSION: The results suggest that the risk of colorectal dysplasia and carcinoma in patients with UC is increased by concomitant PSC.

Serum aminoterminal propeptide of type III procollagen (S-PIIINP) and hepatobiliary dysfunction in patients with ulcerative colitis.

The aim of the study was to estimate the usefulness of measuring the circulating concentration of serum aminoterminal propeptide of type III collagen (S-PIIINP) in screening for hepatobiliary diseases in patients with ulcerative colitis. S-PIIINP was measured in 69 patients with ulcerative colitis and normal liver biochemistry, in 14 patients with ulcerative colitis and elevated catalytic concentration of alkaline phosphatases in serum (S-ALP, EC 3.1.3.1) but without primary sclerosing cholangitis (PSC), and in 20 patients with ulcerative colitis and PSC. The median S-PIIINP was 3.1 micrograms l-1 in patients with ulcerative colitis and normal liver biochemistry, 4.3 micrograms l-1 in patients with ulcerative colitis and hepatobiliary disorder other than PSC and 8.9 micrograms l-1 in those with ulcerative colitis and PSC. When the S-PIIINP cut-off level was set at 5.0 micrograms l-1, 1% of the patients with ulcerative colitis and normal liver biochemistry, 21% of those with hepatobiliary disorder, not PSC, and 90% of the patients with PSC had S-PIIINP values above that concentration. In conclusion, S-PIIINP above 5.0 micrograms l-1 in a patient with ulcerative colitis strongly suggests concomitant PSC.

Detection of colorectal neoplasia with peanut-agglutinin (PNA)-reactive carbohydrate structures in rectal mucus.

In contrast to normal colorectal mucosa, peanut-agglutinin-(PNA)-reactive glycoconjugates are commonly expressed in most colorectal carcinomas and in some pre-malignant conditions such as adenomas and ulcerative colitis. Since enzymatically detectable galactose-beta1-3-N-acetyl-galactosamine residues are found in rectal mucus obtained from patients with carcinoma of the large bowel, it was investigated here whether PNA-reactive carbohydrate structures in rectal mucus can be exploited in the detection of colorectal neoplasia. Samples of rectal mucus obtained from 261 randomly selected patients with colorectal symptoms were applied on nitrocellulose filters. The presence of PNA-reactive glycoconjugates in mucus samples was determined by a peroxidase-conjugated PNA-overlay procedure. The results were correlated to findings from total colonoscopy/surgery and histopathology. PNA-reactive carbohydrate structures were detected in 76% of patients with carcinoma (p < 0.005), in 62% of patients with adenoma (p < 0.005), in 69% of patients with inflammatory bowel disease (p < 0.005), and in 38% of patients with hyperplastic polyps (NS), in contrast to 21% of the control subjects with macroscopically normal colorectal mucosa. These results show that PNA-reactive carbohydrate alterations in rectal mucus correlates with neoplastic and hyperproliferative conditions of the colorectal mucosa. The specificity of the PNA test for colorectal neoplasia was 76%. Therefore the use of more discriminate carbohydrate probes are needed for the pre-symptomatic detection of colorectal neoplasia.

Hereditary breast cancer in Finnish women.

OBJECTIVE: To estimate the incidence of hereditary breast cancer seen in one Finnish hospital and to study the characteristics of the disease. DESIGN: Retrospective questionnaire and study of Finnish Cancer Registry. SETTING: University hospital, Finland. SUBJECTS: All 669 patients operated on for breast cancer 1986-90. MAIN OUTCOME MEASURES: Type of breast cancer and morbidity in hereditary compared with other forms of breast cancer. The definition of hereditary breast cancer requires that at least three first degree relatives, inclusive of the proband, have breast cancer. RESULTS: Of the 669 patients 495 answered the questionnaire. Ten patients (2%) were classified as having hereditary breast cancer. The remaining 485 patients had other types of breast cancer by definition. Of those that were not hereditary 89 (18%) were classified as having familial breast cancer. Of the 495 patients 396 (80%) were classified as sporadic. The mean age of the patients at onset of the disease was 56 years in the hereditary group, 55 years in the familial group, and 57 years in the sporadic group. One patient (10%) in the hereditary, five (6%) in the familial, and 17 patients (4%) in the sporadic group had bilateral disease. Ductal carcinoma was most common in all groups of patients with breast cancer. CONCLUSION: There were no statistical differences in this series in the age at onset, incidence of bilateral disease, stage, and histopathology among the groups, although bilateral and lobular cancer were seen more often in the group with hereditary breast cancer.

HLA antigens in ulcerative colitis and primary sclerosing cholangitis.

The aims of this study were to find out whether the alleles of the HLA class I or II region are associated with susceptibility to ulcerative colitis, and to show whether there is a difference or similarity in HLA associations between primary sclerosing cholangitis and ulcerative colitis. HLA-A, B, C and DR antigens were studied using the standard lymphocyte microcytotoxicity test in 24 Finnish patients with primary sclerosing cholangitis, 77 patients with ulcerative colitis, and 106 controls. HLA-B8 (54%) and DR3 (60%) were associated with primary sclerosing cholangitis. HLA-DR1 (46%) and DR6 (20%) seemed more common in ulcerative colitis than in controls. A positive association with Cw7 was common to both ulcerative colitis (25%) and primary sclerosing cholangitis (33%). Our results indicate that ulcerative colitis is more heterogeneous than primary sclerosing cholangitis in its HLA-DR associations.

Differences in lectin reactivities of cellular glycoconjugates between primary human colorectal carcinomas and their metastases.

Recent studies have demonstrated that colonic carcinomas consist of heterogeneous populations of cells endowed with different abilities to metastasize. Increasing evidence suggests that cell surface carbohydrates may play an important role in cancer invasion and metastasis. Therefore the binding of five fluorescein isothiocyanate-conjugated lectins to cellular glycoconjugates was analyzed immunohistochemically in paraffin-embedded tissue sections obtained from 16 colorectal carcinomas and their 25 metastases. In positive cases peanut agglutinin (galactose beta 1----3N-acetylgalactosamine), Ulex europeus' agglutinin 1 (alpha-L-fucose), Griffonia simplicifolia agglutinin 1 (galactose), Vicia villosa agglutinin (N-acetylgalactosamine), and G. simplicifolia agglutinin 2 (N-acetylglucosamine) stained apical cell membranes in carcinomatous glands and intraluminal secretions. Nine of 16 primary colorectal carcinomas showed intratumoral heterogeneous cell populations with regard to the lectin binding which resulted in areas of fluorescence-positive and fluorescence-negative carcinomatous glands. Only one liver metastasis showed this intralesional heterogeneity in lectin binding. Nineteen of 25 metastatic tumors produced cellular glycoconjugates which differed in their lectin binding profiles from those made by the majority of the cells in the respective primary colorectal carcinomas. The findings of the present work suggest that many primary colorectal carcinomas consist of phenotypically distinct subpopulations of carcinomatous cells. Most metastatic tumors appeared to result from a selective emergence of carcinoma cells producing glycoconjugates which differed in their lectin-binding profiles from those in their respective primary colorectal carcinomas.