[Utility of endoscopic follow-up after resection of colorectal cancer]. / Utilità di un follow-up endoscopico nei pazienti resecati per cancro del colon retto.

PURPOSE: Patients resected for colorectal cancer are at increased risk for an anastomotic recurrence, for adenomatous polyps and for a metachronous cancer. A regular colonoscopic surveillance in these patients is justified for early detection and potential resection of anastomotic recurrences, new primary cancer and adenomatous polyps. PATIENTS AND METHODS: 322 patients were observed and resected for colorectal cancer between 1970 and 1988, with complete staging agreed to be included in a follow-up program (median follow-up: 105 months). To December 1993 all the patients were submitted to colonoscopy once yearly for the first 5 years and then every 2 years. RESULTS: Anastomotic recurrence was observed in 22 of the 253 patients who underwent resection for rectal or sigmoid adenocarcinoma (8.7%). Sixteen of these patients were submitted to a second curative resection with a median survival of 35 months; the median survival was 6 months in the 6 patients who could not undergo this operation (p = 0.0018). Metachronous adenomas of the residual colon were found in 24 patients (7.4%) and metachronous cancers in 5 (1.5%) at Stage A, according to Dukes' classification. CONCLUSIONS: In patients resected for rectal or sigmoid carcinoma, a sigmoidoscopy should be performed every 6 months for the first 2 years for the early detection of anastomotic recurrences. In all cases, a colonoscopy should be performed every 5 years after surgery to detect metachronous lesions at early stage. Before surgery, a "clean colon" should always be established to detect possible synchronous lesions.

Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence.

BACKGROUND: Colorectal cancer is one of the leading causes of death from cancer in Western countries. Removal of adenomas is based on the assumption that it could lead to a reduction in the incidence of colorectal cancer, as demonstrated by the National Polyp Study in the USA. A critical issue is whether the benefit observed in clinical trials can also be observed in standard clinical practice. To address the issue, a multicentre Italian collaborative study was organised. METHODS: The study cohort comprised 1693 subjects of both sexes, aged 40-69 years, enrolled between 1980 and 1987 following a total colon examination (TCE) (that is, total colonoscopy or colonoscopy and double contrast barium enema), with removal of at least one adenoma larger than 5 mm in diameter. Exclusion criteria were genetic syndromes, previous adenomas or colorectal cancer, previous colonic resection, inflammatory bowel disease, or sessile adenomas more than 3 cm in diameter. Follow up ended in December 1996 by TCE or telephone interview, and review of the medical records, clinical files, or death certificates. Incidence ratios for colorectal cancer were compared with expected age and sex specific incidences in the Italian general population. RESULTS: Follow up data were obtained for 97.3% of cases for a total of 14 211 person/years. Mean follow up was 10.5 years. Six colorectal cancer cases (four in males, two in females) at various stages were ascertained (one at 29 months, two at five years, one at seven years, one at eight years, and one at 10 years from the index examination). The number of cancers expected in the reference population was 17.7 for an incidence ratio of 0.34 (confidence interval 0.23-0.63; p<0.01). CONCLUSIONS: Colonoscopic polypectomy substantially reduced the incidence of colorectal cancer in the cohort compared with that expected in the general population. These results are of particular relevance considering that those with adenomas are at increased risk of colorectal cancer and that this retrospective study was performed on data obtained in standard clinical practice. This observation strengthens the concept of effective population screening in view of the fact that adenomatous polyps are the most frequent neoplastic outcome of screening and their removal is associated with a decrease in the incidence of colorectal cancer.

Endoscopic follow-up in resected colorectal cancer patients.

Patients resected for colorectal cancer are at risk for anastomotic recurrence, for adenomatous polyps and for metachronous cancer. The present retrospective study was conducted to evaluate the incidence of neoplasms of the colon, both metachronous or recurrent, in 322 patients. They were observed and resected for colorectal cancer between 1970 and 1988, with complete staging, and all agreed to be included in a follow-up program (median followup: 105 months). All the patients were submitted to colonoscopy once yearly for the first 5 years and then every 2 years. Anastomotic recurrence was observed in 22 of the 253 patients who underwent resection for rectal or sigmoid adenocarcinoma (8.7%). Sixteen of these patients were submitted to a second curative resection with a median survival of 35 months; the median survival was 6 months in the 6 patients who could not undergo this operation (p=0.0018). Metachronous adenomas of the residual colon were found in 24 patients and metachronous cancers in 5 at Stage A, according to Dukes' classification. In conclusion, a regular colonoscopic surveillance in patients resected for colorectal cancer is justified for early detection and potential resection of anastomotic recurrences, new primary cancer and adenomatous polyps. In patients resected for rectal or sigmoid carcinoma, a sigmoidoscopy should be performed every 6 months for the first 2 years for the early detection of anastomotic recurrences. In all cases, a colonoscopy should be performed every 5 years after surgery to detect metachronous lesions. Before surgery, a "clean colon" should always be established to detect possible synchronous lesions.

[Helicobacter pylori and gastric cancer]. / Helicobacter pylori e cancro gastrico.

Several unresolved issues still cast doubts on the epidemiological data which point to an association between infection from Helicobacter pylori (Hp) and gastric cancer. These are: a) the male/female ratio of gastric cancer ranges from 4 to 1.5 in all studies, whereas the prevalence of Hp infection is the same in both sexes; b) the prevalence of Hp infection is as high as 90% in several developing countries where the frequency of gastric cancer is very low; c) the acquisition of the infection at a young age, considered very important with regard to the risk for cancer, varies from 4.2% to 83% in several countries in which the mortality for stomach cancer is, on the average, 10/100,000; d) the incidence of cancer in patients with a duodenal ulcer is half of that of the general population but Hp infects up to 100% of these patients. In the sequence of events that lead to gastric cancer, Hp appears to play a role only in the very initial steps, as a causative agent of chronic inflammation. The further events which lead to cancer are multifactorial, involving environmental agents and the host response. It is therefore inappropriate to consider Hp a direct carcinogen for humans. This also applies to specific strains of the bacterium such as the ones expressing the cagA gene. In a study we conducted in an area with a low incidence of gastric cancer (Latina), the prevalence of Hp infection was equal to 78.6% and, among the positives, 81% resulted cagA positive. This data, if compared with a similar research that took place in another area with a high incidence of gastric cancer (San Marino) where the prevalence of Hp infection was 51% and cagA 69%, further demonstrates the inconsistency of associating Hp and cancer of the stomach.

Helicobacter pylori and gastric cancer: what is the real risk?

Some epidemiological data point to an association between infection from Helicobacter pylori (Hp) and gastric cancer, although several unresolved issues still cast doubts on the real weight of this association. These issues are as follows: the male-to-female ratio of gastric cancer ranges from 4:1 to 1.5:1 in all studies, whereas the prevalence of Hp infection is the same in both sexes; the prevalence of Hp infection is as high as 90% in several developing countries where the frequency of gastric cancer is very low; the acquisition of the infection at a young age, considered very important with regard to the risk for cancer, varies from 4.2% to 83% in several countries in which the mortality for stomach cancer is approximately 10 in 100,000; and the incidence of cancer in patients with a duodenal ulcer is half that of the general population, but Hp infects up to 100% of these patients. In the sequence of events that leads to gastric cancer, Hp appears to play a role only in the very initial steps, as a causative agent of chronic inflammation. The further events that cause gastric atrophy, intestinal metaplasia, dysplasia, and cancer are multifactorial, involving environmental agents and the host response. It is therefore inappropriate to consider Hp a direct carcinogen for humans. This also applies to specific strains of the bacterium such as the cagA gene. In fact, Hp infection is widespread in humans, and only a small minority will ever be affected by peptic ulcer and cancer.

Gastric cancer and Helicobacter pylori: biologic and epidemiologic inconsistencies.

In this report we examine biologic and epidemiologic data with the aim of understanding any correlations between Helicobacter pylori infection and preneoplastic and neoplastic changes. As far as biologic data are concerned, some elements point to the role of H. pylori in the development of preneoplastic and neoplastic changes, such as intestinal metaplasia and dysplasia. The relationship with H. pylori would mainly be due to an increased cellular proliferation with the presence of immature cells in the superficial layers, susceptible to metaplastic or dysplastic modifications. The subsequent passage toward cancer is probably caused by other factors inasmuch as H. pylori is not able to colonize metaplastic or dysplastic areas and hyperproliferation remains at comparable levels, even in the absence of infection. In fact, available epidemiologic data show a high prevalence of H. pylori infection in some geographic areas with a high incidence of gastric cancer. It is also true, however, that there are several populations in which a low neoplastic risk is associated with a high prevalence of infection. We stress the methodologic weaknesses of several studies that attempt to establish a strict association between cancer and H. pylori. Therefore, epidemiologic data are still contradictory and do not permit identifying a precise role of H. pylori as a predominant causative agent in the onset of preneoplastic and neoplastic changes. We conclude that H. pylori behaves as a possible cofactor of other known damaging agents to the gastric mucosa, contributing to the risk of developing neoplastic modifications that may also be subject to individual genetic susceptibility.

The association of Helicobacter pylori infection with low levels of urea and pH in the gastric juices.

Fifty-four gastric biopsies and their relative gastric juices were analyzed for the presence of Helicobacter pylori with both cultural and microscopic methods. Thirty-one samples were positive and twenty-three were negative. These data were therefore employed as references for the subsequent comparisons. Furthermore, the gastric juices were later tested to establish the urea concentration and the pH level. In addition, the sediment obtained after centrifugation was microscopically observed for the possible presence of other bacterial flora in the sample (unstained smears). The urease test on the bioptic specimens has also been evaluated. The presence of H pylori was strictly related to urea levels of less than 15 mg/dl and pH less than 3.5. Furthermore, H pylori was generally not associated with the presence of other bacterial flora (only 1 out of 12 samples). The latter instead, was almost exclusively present in high pH samples (with the exception of one). On the basis of these results, a simple diagnostic scheme was constructed to identify carrier subjects. All patients (14/14) with urea levels of more than 15 mg/dl were found to be negative as well as those presenting a pH of more than 3.5 (7/9) or evidence of other bacteria in the juices (8/9). The remaining subjects (30/31 or 29/31, respectively) presented H pylori in the gastric juices. The final classification was 96.3% (or 94.4%) correct.

Detection of Helicobacter pylori carriers by discriminant analysis of urea and pH levels in gastric juices.

An alternative approach to the problems inherent in current methods for detecting Helicobacter pylori carriers--that of being generally time-consuming, expensive, and not sufficiently sensitive--was devised by using the urea concentration and pH levels of gastric juices. A linear discriminant analysis of these variables, measured in 54 patients submitted to digestive endoscopy for gastritis, provided a mathematical formula for assigning the subjects (previously classified by other standard methods) to groups of either positive or negative H pylori carriers. The results obtained showed a correct classification in 52 out of 54 cases with only one false negative and one false positive case.

Basophil-bound and serum immunoglobulin E directed against Helicobacter pylori in patients with chronic gastritis.

The immunoglobulin (Ig) E immune response in patients with Helicobacter pylori-associated chronic gastritis has been evaluated. Of 26 patients with H. pylori infection, 22 (84%) tested positive for basophil-bound specific IgE (determined by the histamine release test) and 18 (69%) for serum specific IgE (determined by an enzyme-linked immunosorbent assay). In contrast, only 1 of 17 persons in whom the bacterium was not detected presented cell-bound and serum specific IgE. In the 4 histamine release test--positive but enzyme-linked immunosorbent assay--negative patients, removal of antibody from the basophil surface by acid elution showed that histamine release occurred through an IgE-dependent mechanism. When normal basophils, passively sensitized with serum from IgE-positive patients, were exposed to the H. pylori antigen, a significant release was observed, confirming the class specificity of the response. Inhibition experiments with bacteria other than H. pylori showed that the IgE antibody was specifically directed against this organism. The percentage of antigen-induced histamine release did not correlate with serum specific IgE level. However, the response of basophils to antigenic challenge was proportional to IgE-dependent cellular releasability. This finding suggests that target cell sensitivity may be the most important factor in determining the entity of biological response to the antigenic challenge. The ability of H. pylori to induce a specific IgE immune response could answer key questions regarding the mechanisms inducing gastric inflammation.