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.

Regular-dose versus high-dose omeprazole in peptic ulcer bleeding: a prospective randomized double-blind study.

BACKGROUND: It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. METHODS: We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One-hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. RESULTS: Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled (P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. CONCLUSION: Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding.

Cost effectiveness of preoperative ultrasound in primary parathyroid surgery.

A prospective, randomized, blind study was undertaken to assess whether preoperative ultrasound (US) localization of the abnormal parathyroid glands is cost-effective in patients undergoing initial neck exploration for primary hyperparathyroidism (PHPT). Twenty-eight patients were randomly allocated into two groups. In Group I the results of preoperative US were reported to the surgeon before exploration, and in Group II he was not informed of the US results. All patients underwent bilateral neck exploration, performed by the same surgeon. The operating room time was recorded and the operating room costs calculated. They included the total costs of cervical US in Group I. The cure and morbidity rates in Group I were 100% and 14% and those in Group II 86% and 7%, respectively (P > 0.05). The mean operating room time of 97 +/- 15 min in Group I was significantly lower than that of 113 +/- 23 min in Group II (P < 0.05). The mean operating room costs, however, were almost the same in both groups being only 286 FIM higher in Group II (P > 0.4) because the costs of preoperative US, the least expensive of the localization studies, of 497 FIM negated any cost savings achieved by the reduced operating room time. We thus conclude that preoperative US before initial neck exploration for PHPT is not cost-effective.

Simultaneous thyroid operation in patients undergoing initial neck exploration for primary hyperparathyroidism.

Twenty-three (25%) out of 92 patients undergoing initial neck exploration for primary hyperparathyroidism (PHPT) also underwent a simultaneous thyroid operation. Based on a postoperative analysis a simultaneous thyroid operation was unquestionably indicated in 18 (78%) cases but in the remaining five (18%) the indications were less well proved. Six (9%) of the 66 patients subjected only to neck exploration for PHPT and four (17%) of those with a simultaneous thyroid operation had postoperative complications (P > 0.05). The patients with four incidental biopsies and an incidental lobectomy had no complications, but otherwise complications were evenly distributed among the different thyroid operations. The somewhat higher complication rate in patients undergoing simultaneous thyroid operation was related to the learning curve of the surgeon. Simultaneous thyroid operation increased the operating room costs only by 31%, and the combined operation was definitely cost effective as compared with separate parathyroid and thyroid operations. It is concluded that in experienced hands, simultaneous thyroid operation is safe, cost effective and recommendable for patients undergoing initial neck exploration for PHPT, because it avoids the expense and risk associated with neck re-exploration and can reveal unsuspected cancer.

Parathyroid re-exploration in patients with primary hyperparathyroidism.

In a prospective study fifteen consecutive patients underwent re-exploration for persistent or recurrent primary hyperparathyroidism. We aimed at definite preoperative localization of enlarged, abnormal parathyroid glands in all patients. Ultrasound guided fine needle aspirations for parathyroid hormone assay had the highest accuracy rate of 100%, those for cervical ultrasound and thallium-technetium, scintigraphy were similar, both 86%. Normocalcaemia was achieved in all patients, but five (33%) patients required more than one re-exploration. Permanent unilateral vocal cord injury occurred in two (13%) patients, but none had permanent hypocalcaemia. We conclude that the results of re-exploration are good but one third of the patients required more than one reoperation. Localization studies aiming at definite localization are mandatory before re-exploration. On the basis of our results we suggest a protocol for preoperative localization which takes into consideration both the accuracy rates and the costs of localization examinations.

Preoperative ultrasound in patients undergoing initial neck exploration for primary hyperparathyroidism.

92 patients with primary hyperparathyroidism were subjected prospectively to preoperative ultrasound to identify enlarged parathyroid glands and detect simultaneous thyroid lesions of surgical significance. The overall sensitivity and specificity rates were 62.7% and 95.7%, 85.2% and 96.8% for patients with a single adenoma, 44.3% and 88% for those with multiglandular disease, 56.8% and 95.6% for those with simultaneous thyroid disease and 20% and 100% for mediastinal glands. Ultrasound revealed a pathological thyroid gland in 26 patients (28%). The sensitivity and specificity rates were 96% and 100%. The thyroid lesion was considered clinically significant in 15 of the 92 patients (16.3%) and only in three patients (3.3%) was the diagnosis not established preoperatively. Operating room times and costs were significantly lower for patients with an accurate ultrasound scan than for those with an inaccurate scan (P < 0.001). We conclude that both the sensitivity of ultrasound for locating enlarged parathyroid glands and its yield of previously unknown thyroid lesions of surgical significance are too low to warrant preoperative ultrasound evaluation. Although our operating room expenses were significantly higher for patients with an inaccurate scan, the cost effectiveness of preoperative ultrasound cannot be proved until a prospective, randomised investigation has been carried out.

Results of surgery in primary hyperparathyroidism.

In a prospective study 92 consecutive patients with biochemically proved primary hyperparathyroidism underwent initial neck exploration at Oulu University Hospital. The incidence of multiglandular disease was 34%. 23 patients (25%) underwent a simultaneous thyroidectomy. The cure rate after initial exploration was 91.3%, ectopic parathyroid glands and multiglandular disease being the most common causes of failure. Simultaneous thyroidectomy increased somewhat but not significantly the complication risk. There was a slight tendency for serum calcium concentrations to increase during the mean follow-up of 2.3 +/- 1.5 years. Four patients with persistent hypercalcaemia underwent a successful reoperation during that time. Thus the overall cure rate was 95.6%, but 5.4% of the patients required permanent medication for hypocalcaemia. We conclude that the most common causes for failed initial exploration were ectopic parathyroid glands and multiglandular disease. The incidence of multiglandular disease was unusually high in this series. Because simultaneous thyroidectomy increased somewhat the complication risk of initial neck exploration, the indications for this additional procedure should be carefully considered. The results of parathyroid surgery were good and dependent on how many patients underwent reoperation during the follow-up. A consequence of tendency for serum calcium concentrations to increase during the follow-up could be that a definite cure cannot always be attained in cases of primary hyperparathyroidism.