Anacleto Peracchia

Role of follow-up in management of local recurrences of colorectal cancer

PURPOSE: This prospective, randomized, single-center study was designed to evaluate the influence of follow-up on detection and resectability of local recurrences and on survival after radical surgery for colorectal cancer. METHODS: Between 1987 and 1990, 207 consecutive patients who underwent curative resections for primary untreated large-bowel carcinoma were randomly assigned to a conventional follow-up group (Group A; n=103) and to an intense follow-up group (Group B; n=104). All the patients were followed up prospectively, and the outcome was known for all of them at five years. Patients in Group A were seen at six-month intervals for one year, and once a year thereafter. Patients in Group B were checked every three months during the first two years, at six-month intervals for the next three years, and once a year thereafter. RESULTS: Of the 103 patients in Group A, local recurrence was detected in 20; 9 (13 percent) of these patients had colon cancer, and 11 (29 percent) had rectal cancer. Of the 104 patients in Group B, local recurrence was detected in 26; 12 (16 percent) of these patients had colon cancer, and 14 (45 percent) had rectal cancer. Twelve cases (60 percent) of local recurrence in Group A and 24 cases (92 percent) in Group B were detected at scheduled visits (P<0.05). Local recurrences were detected earlier in patients of Group B (10.3±2.7vs. 20.2±6.1 months;P<0.0003). Curative re-resection was possible in 2 patients (10 percent) in Group A, 1 with colon cancer and 1 with rectal cancer, and in 17 patients (65 percent) in Group B, 6 with colon cancer and 11 with rectal cancer (P<0.01). Of the Group B patients who had curative re-resections of local recurrence, 8 (47 percent) were disease-free and long-term survivors as of the last follow-up, and 2 (11.7 percent) were alive, but with a new recurrence. The 2 patients in Group A who had curative re-resections died as a result of cancer. The five-year survival rate in Group A was 58.3 percent and in Group B was 73.1 percent. The difference is statistically significant (P < 0.02). CONCLUSIONS: Our data support use of an intense follow-up plan after primary resection of large-bowel cancer, at least in patients with rectal cancer.

Curative surgery for colorectal cancer: Long-term results and life expectancy in the elderly

PURPOSE: The long-term prognosis after curative surgery for colorectal cancer was evaluated in relation to age and life expectancy as a possible basis for assessing the risk to benefit ratios in the elderly. METHODS: Data relating to 1,256 patients operated on from 1976 to 1994 were stored in a computer database prospectively from 1987. Patients were subdivided into four age groups (A=<60 years; B=60–69; C=70–79; D=≥80). Distribution of general contraindications to curative surgery was examined. In the 869 patients who underwent curative treatment (A=206; B=256; C=289; D=118), distribution of tumor stage and elective/emergency surgery and the operative mortality rate were evaluated. Crude and age-corrected survival curves were calculated in 794 patients. The median crude survival of each group was related by gender and tumor stage to demographic life expectancy, assuming as “relative median survival index” the ratio between the two values. RESULTS: General contraindications to curative surgery increased significantly with age. The operative mortality rate was higher in Group D than in Groups A, B, plus C over the total series (P<0.001) and in both elective (P<0.001) and emergency surgery (P<0.05). Intergroup analysis of long-term survival rates showed significant differences between “crude” (P=0.0057) but not age-corrected (P=0.66) curves. The relative median survival index increased with age, up to approximately 1 in the local stages of Groups C and D. CONCLUSIONS: To evaluate long-term results, elderly patients should be compared with unaffected, same-age subjects. Because the risks may be very high, the surgical policy in the elderly should be carefully weighed and related to life expectancy and actual results.

Is Tumour Angiogenesis a Prognostic Factor in Patients with Colorectal Cancer and No Involved Nodes

OBJECTIVE To examine a possible association between tumour angiogenesis and conventional prognostic variables and to assess the prognostic value of the variables examined in patients with colorectal cancer, with no involved nodes. DESIGN Retrospective study. SETTING University hospital, Italy. SUBJECTS 119 patients who had had colorectal cancers resected for cure with no involved nodes between 1985-1990. INTERVENTIONS The three microscopic fields with the most microvessels were identified by immunohistochemical techniques. 10 high-power fields in each area were used for the microvessel count and the mean values indicated the microvessel density. MAIN OUTCOME MEASURES Correlation of microvessel density with conventional prognostic factors, recurrence rates, and survival. RESULTS There was a significant correlation between microvessel density and sex, women having a higher density than men (p < 0.05), but no significant correlations between density and recurrence rates or survival. Multivariate analysis did not indicate that microvessel density had a prognostic role. CONCLUSION Microvessel density in colorectal cancer without involved nodes does not correlate with conventional prognostic factors and provides no prognostic information.

Reduced Postoperative Morbidity after Elective Laparoscopic Cholecystectomy: Stratified Matched Case-Control Study

Abstract. To answer the question whether laparoscopic cholecystectomy (LC) or open cholecystectomy (OC) is safer in terms of complications and to what extent the “learning curve” influences the frequency of complications after LC, we conducted a matched case–control study. First, 200 patients undergoing LC (LC group A), and two groups of 200 patients undergoing LC at two different periods of the learning curve (LC groups B and C) were matched, taking into account sex, age, anesthesiologic risk, and surgical difficulties. We evaluated the frequency and grade of postoperative complications of these patients and of the last 200 patients undergoing OC before the introduction of LC, retrospectively matched with the LC groups. The total rate of complications in the OC group was 16.0% compared with 5.5% in the LC groups (p < 0.003); the difference was particularly significant for complications classified as grade I, in female patients, those younger than 70, those with low anesthesiologic risk (ASA), and those after cholecystectomy without surgical difficulties. Matched case–control analysis revealed that the complication rate in the LC group significantly decreases with experience (p < 0.01). We conclude that LC is today the treatment of choice for symptomatic cholelithiasis and is replacing OC as the gold standard against which new therapies should be compared.

Prognostic value of ploidy, cell proliferation kinetics, and conventional clinicopathologic criteria in patients with colorectal carcinoma: A prospective study

PURPOSE: The aim of this study was to obtain additional biologic determinants that may be of use in segregating into subgroups with different prognosis patients with similarly staged colorectal cancers. METHODS: Between 1989 and 1991, a prospective study of prognostic factors has been performed in a group of 98 consecutive, unselected patients who underwent curative resections for primary untreated large bowel carcinoma. The fate of all patients is known at three years after operation. Clinical and pathologic data were recorded at the time of presentation and operation, and patients have been the subjects of regular follow-up. Tumor DNA content was determined by flow cytometry, and cell proliferative activity was determined by autoradiography with tritiated thymidine labeling index (LI). RESULTS: Univariate analysis revealed that the most important predictors of survival (P<0.001) were the presence of positive lymph nodes, the presence of preoperative complications, Dukes stage, and LI. The multivariate analysis showed that Dukes stage (P<0.002) and LI(P<0.0001) were the only factors significantly related to survival. Disease-free survival was influenced significantly by Dukes stage (P<0.001), LI, according to the classification in the two groups of high and low proliferative activity, respectively, (P<0.0001), LI, calculated as a continuous variable (P<0.0002), and the presence of lymph node metastases (P<0.003). Outcome (favorable/unfavorable) was influenced significantly by Dukes stage (P<0.0001) and LI (P<0.0001). Concordance for each patient between Dukes stage and outcome was 73.1 percent and between LI, calculated as a continuous variable, and outcome was 74.1 percent. If, on the other hand, Dukes stage and LI are used together, concordance with outcome reaches 89.2 percent. CONCLUSION: We can conclude that, from a practical point of view, LI is an essential factor that must be combined with pathologic variables for a better prediction of patient outcome.

DNA content in human colon cancer and non-neoplastic adjacent mucosa.

DNA content was determined by flow cytometry in a series of 51 paired fresh tissue samples of primary colorectal carcinomas and the respective non-neoplastic adjacent mucosa in order to assess the relationship between DNA ploidy and the most commonly used prognostic factors. Aneuploidy was observed in 70.6% of the tumors and more than one aneuploid peak was present in 3.9%. Aneuploid tumor frequency was higher in left (93.3%) and right colon (64.7%) cancers than in rectal carcinomas (60.0%), and multiple aneuploid clones were detected more frequently in men than in women and in patients with advanced disease (Dukes stage D). Non-neoplastic mucosa adjacent to aneuploid tumors showed aneuploidy in 4 out of 51 samples (7.8%). The mucosa adjacent to diploid cancers had only diploid characteristics. Polidy did not correlate with histological abnormalities. These findings suggest that DNA content as determined by flow cytometry needs further study with adequate follow-up to evaluate possible correlations with relapse-free and overall survival. Furthermore the aneuploidy of non-neoplastic mucosa provides evidence for a field defect in mucosa adjacent to colorectal cancer and supports the concept that this alteration may be of influence on carcinogenesis.

Lack of allelic loss at the multiple endocrine neoplasia type 1(MEN-1) gene locus in a pancreatic ductal (non-endocrine) adenocarcinoma of a patient with the MEN-1 syndrome

The gene responsible for multiple endocrine neoplasia type I (MEN-1) syndrome has been mapped to chromosome 11q13. It appears to function as a tumour-suppressor gene analogous to that for retinoblastoma and allelic losses involving the wild-type of the MEN-1 allele have been found in parathyroid and pancreatic endocrine tumours of MEN-1 patients. No genetic information has been provided so far on non-endocrine malignancies that may occur in MEN-1 patients. A case of exocrine pancreatic adenocarcinoma presenting as the terminal event in a woman with a long standing history of MEN-1 syndrome and multiple endocrine tumours of the pancreas was investigated for possible allelic losses at the MEN-1 gene locus using restriction fragment length polymorphisms (RFLPs) closely linked to the MEN-1 gene and polymerase chain reaction (PCR) for D11S533 locus. No allelic losses were found in tumour tissue with two informative RFLPs (D11S97, D11S146) or with PCR analysis. These findings suggest that the MEN-1 gene does not confer a predisposition to develop tumours other than those that typify the syndrome.

Prevention of colorectal cancer

A significant association was found between colorectal cancer, especially of the right colon, and concomitant gallstones. This was noted especially in female patients and in those over the age of 65. The existence of such an association is of advantage in terms of secondary prevention of colorectal cancer. The possible screening methods are discussed for those gallstone patients at risk.

Cholesterol Microlithiasis: Bacteriology, Gallbladder Bile and Stone Composition

It is not known whether microcalculi possess structural differences compared with larger stones or whether they represent simply an earlier stage in stone disease. We carried out a controlled study on 10 patients affected by gallbladder cholesterol microlithiasis (CM). In all patients, samples from all parts of the stones were studied by X-ray diffraction and by infrared spectrophotometry. Bile analysis was carried out to determine cholesterol, phospholipid and total bile acid content. The cholesterol saturation indices (C.S.I.) were calculated. In all samples, bacterial bile culture was carried out. The results were compared with those of 10 patients who had undergone cholecystectomy for large cholesterol stones, and for 10 patients who had undergone abdominal surgery but without biliary pathology. Patients in these latter groups were matched with the first according to sex and age. Microcalculi proved to be layered (nucleus and external layer) in only 2 cases and larger stones in 9; cholesterol was seen to be the principal crystalline component in all cases. Traces of bilirubin were found in 7 CM and in the nuclei of 5 larger stones. These results show that the structural composition of microcalculi is similar to that of the nucleus of larger stones. No substantial differences exist, however, between the two groups of patients regarding the other parameters taken into consideration.

A critical review of classification systems for colorectal cancer

After a chronological overview of the various staging systems for colorectal cancer, presented in an effort to demonstrate the reasons for the current state of confusion, four different systems (Dukes. Astler and Coller, ACPS, TNM) were compared in 791 patients treated at some stage of their disease at Parma University’s Institute of Surgery. Life survival table analysis was used to examine survival according to each staging system. From the analysis of the staging systems commonly utilised, Dukes’system modified by Astler and Coller, emerges as the best reference model now available. The system can be fine-tuned to a certain extent, in order to improve its predictive value, by taking into account the number of lymph nodes affected by the tumour; further improvement is also foreseeable, above all by the use of genetic variables. However, no classification system can be correct, if it is not accompanied by an accurate pre-operative diagnosis and a thorough post-operative histological study.