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.

Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology.

PURPOSE: Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles (M-CH) in preventing intraabdominal recurrence following curative surgery for gastric cancer. The Austrian Working Group for Stomach Cancer, a subgroup of the Austrian Working Group for Surgical Oncology, initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen. PATIENTS AND METHODS: A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were randomly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound (n = 46) or served as a surgical control group (n = 45). Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment. RESULTS: After a median observation period of 597 days (range, 72 to 1,096), a significantly higher postoperative complication rate was observed in the M-CH group (35%) compared with the control group (16%) (P < .02). In accordance with this finding, the postoperative (60 days) mortality rate was also significantly elevated in the M-CH group (11% v 2% in the control group). Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy, the protocol committee decided to stop further recruitment of patients onto this study. CONCLUSION: Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications. However, no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial.

Outcome after emergency subtotal/total colectomy compared to elective resection in patients with left-sided colorectal carcinoma.

Long term survival of 72 patients who underwent an emergency one-stage subtotal/total colectomy with primary anastomosis for obstructing carcinoma of the left colon was compared with 141 patients who underwent an elective procedure for non-obstructing carcinoma of the same location. Patients who presented with intestinal obstruction were older than electively treated patients (68.5 versus 62.1 years), postoperative mortality was higher (13.8% versus 7.8%). 5-year survival rate of patients treated by R0 emergency subtotal/total colectomy was comparable to electively R0 resected patients (69% versus 61%). There was no significant difference in survival comparing the same Dukes' stage between the two groups. One-stage procedure could be regarded as a preferred method of treatment in patients with obstructing carcinoma of the left colon, either as a subtotal/total colectomy in cases when the colonic wall is endangered or as a resection with primary colo-colonic anastomosis after on-table lavage.

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.

Comparison of Lauren's, Ming's and WHO histological classifications of gastric cancer as a prognostic factor for operated patients.

The prognostic significance of the above mentioned histological classifications is evaluated. The survival data of 259 supposedly radically resected patients is analyzed. The survival curves have been calculated according to the Kaplan-Meier method and compared with the Mantel-Cox test. The most important prognostic factors have been found and used in the stratification analysis. The diffuse type of cancer (according to Lauren) has significantly worse prognosis than the intestinal type only considering the same pT (pT3) and sex (male) or age group from 50 to 70 years. The infiltrative type of cancer (according to Ming) has a worse prognosis than expansive. The difference is insignificant even after stratification analysis. Worse prognosis of diffuse (or infiltrative) cancer is influenced more by the infiltration of regional lymph nodes than by the depth of infiltration, age or sex. WHO classification is less important as a prognostic factor. Signet ring cell type cancer has a worse prognosis considering age group 50-70 years.

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.

Prognostic value of clinical, pathological and immunohistochemical markers in stage II colon cancer patients.

BACKGROUND/AIMS: The purpose of our analysis was to determine the prognostic value of molecular markers for identifying high-risk TNM stage II colon cancer patients, the association with various clinical and pathological features, and possible relation to survival. METHODS: In 191 colon cancer patients who underwent a potentially curative resection, clinical and pathological factors (age, tumour site, histological grade of malignancy, pT stage, presence of venous, lymphatic and perineural invasion) and tumour molecular markers were analysed. Molecular markers were assessed immunohistochemically in sections of paraffin-embedded tissues. Patients were followed for a median of 8.7 years. The 5-year survival rate was estimated using the the Kaplan-Meier statistical method. RESULTS: From 1. Jan. 1994 to 31. Dec. 2000, 191 patients underwent radical resection for T3-4 N0M0 colorectal cancer without adjuvant chemotherapy. A significant decrease in survival was identified in older patients, patients with tumours pT4 and with perineural invasion. We found no significant differences in survival of patients with expression of MLH1, Cyclin D1 and reduced overexpression of E-cadherin. CONCLUSIONS: The results of our study indicate that the presence of perineural invasion, pT4 stage and the patient's age are significantly correlated with the expected survival in radically resected TNM stage II colon cancer patients, while immunohistochemical markers are not related to survival.

Interleukin-6 and lipopolysaccharide-binding protein in acute appendicitis in children.

The aim of the study was to evaluate the diagnostic accuracy of interleukin-6 (IL-6) and lipopolysaccharide-binding protein (LBP) in children with acute appendicitis (AA) and to compare this with the diagnostic accuracy of routinely used C-reactive protein (CRP) and white blood cell (WBC) count. Eighty-two consecutive children admitted to our Department because of suspected AA were enrolled in this prospective study and classified into two groups: group 1 (49 children who underwent surgery for AA) and group 2 (33 children with no surgery with diagnosis of non-specific abdominal pain or sonographic mesenteric lymphadenitis). There were no negative appendectomies during the time of the study. The patients were further classified into three subgroups: subgroup 1A (43 patients with advanced AA), subgroup 2A (11 patients with mesenteric lymphadenitis) and subgroup 2B (10 patients with non-specific abdominal pain). The perforation rate was 32.7 %. WBC count and serum CRP, IL-6 and LBP were measured on admission. Area under receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity and predictive values were evaluated. Serum IL-6 and LBP were significantly higher in group 1 than in group 2. The highest AUC for AA was that for IL-6 (0.776), followed by WBC count (0.684), CRP (0.637) and LBP (0.635). In conclusion, only IL-6, determined on admission, showed medium diagnostic accuracy, while other laboratory markers showed low diagnostic accuracy for AA in children. The new laboratory markers therefore do not significantly improve the diagnosis of AA.

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).

Is DNA aneuploidy a prognostic factor in gastric cancer?

Flow cytometric analysis of DNA ploidy was performed on an archival material obtained from 79 patients with gastric cancer who underwent a potentially curative (R0) stomach resection with D2 lymphadenectomy, and evaluated its relationship to conventional pathologic parameters, TNM stage and prognosis. No significant association between DNA aneuploidy and either patients' sex, depth of tumor infiltration (pT), lymph node involvement (pN), histological type according to Ming, macroscopic type according to Borrmann or tumor localization was found. However, the incidence of DNA aneuploidy was significantly lower in tumors of diffuse type according to Lauren, in tumors of signet ring cell or undifferentiated type according to WHO classification, in poorly differentiated/undifferentiated tumors and in patients younger than 50 years. We found no significant difference in survival between patients with DNA aneuploid tumors and those with DNA diploid tumors. Although the prognosis of patients with tumors of lower DNA index (DI < 1.2) tended to be better than for those of higher DNA index (DI > 1.2), the difference did not reach a statistically significant level (p = 0.09). TNM stage, depth of tumor infiltration (pT) and lymph node involvement (pN) were the only factors that significantly affected survival in univariate analysis and both pT and pN retained their independent prognostic significance in multivariate analysis.

[Management of liver injuries]. / Obskrba jetrenih povrijeda.

Evidently, the most frequent cause for surgical intervention on liver is traumatic rupture of the liver, which are often irregular or multiple. The therapy is not uniform. In noncomplicated ruptures the best management is to remove necrotic tissue by digitoklasis and individual ligation of blood vessels and bile ducts with interrupted suture. In extensive lesion, where a large part of hepatic parenchyma is devitalized, the best results are achieved by resection. The mortality largely depends on well-timed operation, whereas each delay increases the surgical risk.

[Hemangiomas of the liver]. / Hemangiomi jetre.

Hepatic tumors are mostly due to metastasizing malignant lesions of the gastrointestinal tract. Benign neoplasms of the liver occur rarely. The most common benign tumor is the hemangioma, the etiology of which is still poorly understood. Small hemangiomas are usually asymptomatic and found incidentally at operation or post mortem examination. The treatment of large localized hemangiomas is surgical resection. When this is not performable, we have recourse to local excision of the tumor with ligation of the adjacent blood vessels. Actinotherapy is an alternative method used in treatment of multiple non localized hemangiomas. Biopsy of hemangioma is a hazardous procedure, which may trigger off massive hemorrhage. The paper presents 4 of the 92 patients subjected to liver resection during 1975 and 1980.

DNA flow cytometry in gastric carcinoma: implication in patients with potentially curative resection.

BACKGROUND AND OBJECTIVES: The relevance of DNA ploidy as a prognostic factor in patients with gastric cancer is controversial. The prognostic significance of DNA ploidy and its relationship to conventional histological grading and staging of the tumor (TNM stage, Lauren, Ming and WHO classification) were evaluated. METHODS: DNA ploidy of the tumor was determined by flow cytometry on archival material from 76 patients who underwent R0, D2 stomach resection. RESULTS: DNA aneuploidy was found in 39 cases (51%). No significant association between DNA aneuploidy and either patients' sex, pT, pN, type according to Ming or Borrmann and tumor localization was found. The incidence of DNA aneuploidy was significantly lower in tumors of diffuse type according to Lauren, in signet-ring cell or undifferentiated type (WHO), in grade 3/4 tumors, and in patients younger than 50 years. We found no significant difference in survival of patients with DNA aneuploid when compared to DNA diploid tumors, although the prognosis of the patients with lower DNA index (DI < 1.2) tended to be better than that of higher DNA index (DI > 1.2). CONCLUSIONS: DNA ploidy appears to be of limited prognostic value after R0, D2 resection of stomach cancer.

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.

[Angiodysplasia - a cause of gastrointestinal bleeding]. / Angiodysplasia - uzrok za gastrointestinalno krvarenje.

Angiodysplasia is a rare cause of gastrointestinal bleeding. The lesion has a specific appearance - markedly enlarged closely grouped veins with short channels between veins and arteries. The lesion may occur on any part of the gastrointestinal tract, but it is most often located in cecum. Its clinical manifestations are predominantly seen in patients beyond the age of 55 years. Selective angiography is the most certain way of diagnosing angiodysplasia. It can be diagnosed by endoscopy too. Resection of the inflicted part is the most successful treatment. Sometimes endoscopic coagulation or embolisation lisation have good results too. Three patients with angiodysplasia - a 74-year man, a 65-year woman with angiodysplasia on cecum and a 63-year woman with angiodysplasia on jejunum are shown. The diagnostic and therapeutic problems of this rare illness are discussed.