Improved outcome of patients with colorectal cancer: the Ljubljana University Medical Centre experience.

BACKGROUND/AIMS: Analysis of outcome in patients undergoing resection for colorectal carcinoma. METHODS: Between 1/1/1991 and 31/12/2000, 1,478 patients with a colon and rectal carcinoma underwent a potentially curative resection. The results were analyzed for two groups of patients given different treatment regimens during two consecutive 5-year periods. The 5-year survival rate was estimated by the Kaplan-Meier method. RESULTS: Over a period of 10 years, 1,478 patients were treated by resection. The 5-year survival rate for R0 resected patients with stage I and stage III colon cancer in the period 1996-2000 was significantly higher than for patients operated on between 1991 and 1995 (stage I: 86 vs. 70%; stage III: 58 vs. 40%). Similarly, the 5-year survival rate for R0 resected patients with stage III rectal cancer between 1996 and 2000 was significantly better than that for patients operated on during the early period (58 vs. 31%). CONCLUSIONS: Patients who underwent R0 resection for colorectal cancer during the period 1995-2000 showed a significantly improved 5-year survival rate compared to those operated on between 1991 and 1995. Improved survival in these patients is to a great extent attributable to improvements in clinical practice combining surgery and adjuvant therapy.

Lymph node metastases in gastric cancer: correlation between new and old UICC TNM classification.

The 5th edition of TNM classification (1997) grades lymph node involvement in gastric cancer by the number of metastatic lymph nodes. Their prognostic significance as defined by the new (5th edn., 1997) and old (4th edn., 1987) TNM classification was evaluated and survival in pN categories between both versions was compared. It was demonstrated in our analysis that comparison of old and new TNM systems is possible. Categories pN1 and pN2 contain patients selected by different criteria in both versions of TNM classification but with similar survival probabilities. Anatomic location of lymph nodes as described in the 4th edn. and number of involved nodes in the 5th edn. of TNM classification have about the same prognostic value in categories pN1 and pN2. The advantage of the 5th edn. is the identification of a group of patients (pN3, >15 involved lymph nodes) with significantly poor prognosis, which, in our series, includes 15% of R0 resected patients with lymph node metastases.

Emergency colorectal surgery: our results and complications.

BACKGROUND: Emergency surgery for obstruction, perforation and massive bleeding represent 10%-40% of all colorectal operations. METHODS: Retrospective analysis of a series of 170 patients operated on in the period from 1.1.1988 to 31.12.1993. RESULTS: 170 (12.5%) of 1363 patients with colorectal pathology needed urgent surgery: 121 (71.2%) for obstruction, 39 (22.9%) for perforation and 10 (5.9%) for massive bleeding, with mortality rate 17.6% (30 patients). 116 (68.2%) underwent one-stage procedure with mortality rate 9.5% (11 patients), 36 (21.2%) patients underwent two-stage procedure with mortality rate 27.8% (10 patients) and 18 (10.6%) patients other procedures. 115 (67.7%) of 170 patients had malignant disease; 92/115 (80.0%) underwent one-stage procedure with mortality rate 10.9% (10 patients), 7 (6.1%) patients two-stage procedure with mortality rate 14.3% (1 patient) and 16 (13.9%) other palliative procedures (by bass, stoma). CONCLUSION: We believe one-stage procedure is the method of choice for the most colorectal emergencies.

Treatment results of colorectal cancer--10-years series of UMC Ljubljana (1991 - 2000).

UNLABELLED: In Slovenia the incidence of colorectal cancer is growing rapidly. In 1998 1022 new cases were registered. Our study compares results of two groups of patients with colorectal cancer. Patients and methods. In the period from 1.1.1991 to 31.12.2000 1478 patients with a colorectal carcinoma underwent potentially curative resection. We divided them in two groups, one operated in the first 5-years and second in later 5-years period. 5-years survival was estimated with Kaplan-Meier statistical analysis. Patients who died within 30 days after the operation were censored. Differences in survival curves between both groups were assessed by the log rank test. RESULTS: We resected 1478 /1599 (92,4%) patients. There was 913 (61,7%) patients resected with colon cancer and 528 (35,8%) with rectal cancer and 37 (2,5%) with sinhronius tumors. R0 resection was performed in 1174 (79,4%) patients, R1 in 29 (2,0%), and R2 in 273 (18,5%) patients. Postoperative mortality rate in resected patients was 5,48% (81/1478), in the group with paliative operations was 17,35% (21/121). Overall five-years survival rate was 54,9% (56,18% for colon cancer and 52,4% for rectal cancer Five-years survival rate for the patients with radical resection (R0) was 66,54% for colon cancer and 59,47% for rectal cancer. CONCLUSION: 5-years survival for R0-resected patients with colon cancer was in the last period from 1996 to 2000 statistically significantly better compared with the period from 1991 to 1995 (76% vs 60%) in stage I (p = 0,04048) and in stage III (p = 0,01842). 5-years survival for R0-resected patients with rectal cancer was significantly better in the same period (63% vs 55%) (p = 0,03627) in stage III (p = 0,01663).

Mutations in the hMLH1 gene in Slovenian patients with gastric carcinoma.

Alterations of multiple oncogenes and tumor suppressor genes, together with genetic instability, are responsible for carcinogenesis in gastric cancer. The microsatellite mutator phenotype is the cause of many somatic frameshift and point mutations in non-coding repetitive sequences and in coding regions associated with cell proliferation and apoptosis. Genetic mutations in hMLH1 and transcriptional silencing of its promoter by hypermethylation lead to the inactivation of the mismatch repair system. In our study, we screened for mutations the hMLH1 gene in patients expressing the microsatellite instability genotype by using single-strand conformational polymorphism analysis and direct sequencing. Seven changes were identified; of these, three (A92P, E433Q, and K618A) were germline mutations and the other four (IVS5 453 + 79 A > G, I219V, 1039 - 7 del (T)(n), and IVS15 1668 - 19 A > G) germline polymorphisms. A92P and E433Q are novel, previously unidentified mutations. In addition, we found a rather complex distribution of mutations and polymorphisms in individual patients and in two cases also a methylated hMLH1 promoter.

Assessment of differential expression of oncogenes in gastric adenocarcinoma by fluorescent multiplex RT-PCR assay.

We screened samples of tumour and peripheral normal tissue for differential expression of oncogenes by using an approach of detecting the differences in expression of a number of oncogenes simultaneously. Total RNA was isolated from 29 pairs of normal and tumour tissue samples from patients with gastric adenocarcinoma. Seven pairs of primers for oncogenes most probably associated with the process of carcinogenesis in stomach including cyclin E, c-erbB-3, HGR, c-met, TDGF/cripto, FGF-4, and EGF were used for the construction of fluorescent multiplex RT-PCR. Sense primers were 5' end-labelled with a fluorescent dye. 5-7 gastric oncogenes were simultaneously analysed for overexpression. Multiplex reverse transcription with a set of unlabeled primers was followed by a PCR reaction by adding the corresponding set of fluorescent labelled PCR-primers. Expression of oncogenes was compared to GAPDH internal standard. Multiplex fluorescent RT-PCR results were analysed by capillary electrophoresis on ABI-PRISM 310 Genetic Analyzer. Differential expression of oncogene mRNAs in tumour and normal tissue was assessed by comparison of oncogene/GAPDH ratios in tumours and their peripheral normal mucosa. Our results show, that in most patients, comparing to normal tissue, we could estimate overexpression of at least one oncogene in a sample.