Familial aggregation of tumors in the three-year experience of a population-based colorectal cancer registry.

The familial occurrence of tumors has been investigated in 389 subjects with colorectal cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1984-1986, in the Local Health District, for malignancies of the large bowel. Among first-degree relatives of the registered patients there were 89 cases of colorectal cancer as opposed to 19 in a hospital-based control group matched for age and sex [odds ratio (OR), 7.5, P less than 0.001]. This excess of neoplasms among relatives was particularly evident in siblings (60 versus 7, OR 14.7, P less than 0.001) but it was observed also in parents (27 versus 12, OR 4.2, P less than 0.01). Besides colorectal cancer there was no significant excess of other types of tumor in case families, whereas lung tumors tended to be more frequent in control relatives (32 versus 17). Almost half of the registered patients (182 out of 389) had one or more cases of cancer of any sites among relatives; similarly, in 68 there were one or more relatives affected by (or deceased for) colorectal cancer. Moreover, in 27 patients (7.0%) there were at least three cancers of any sites among relatives and in 15 the excess (two or more) was limited to neoplasms of the large bowel. In patients without or with only one neoplasm among relatives, cancers were mainly located in the left colon; however, cancer of the right colon became relatively more frequent in patients with two or more tumors in close relatives. In conclusion, the present study suggests that in approximately 15-20% of patients registered for colorectal cancer one or more first-degree relatives are affected by neoplasms of the large bowel. This familial occurrence of intestinal malignancies (but not of tumors of other organs) strongly suggests a genetic susceptibility to colorectal cancer in a fraction of these patients. Moreover, in a further subgroup of individuals (approximately 5% of all cases) the familial aggregation of two or more cases of colorectal cancer among relatives (besides the proband) and the frequent location of tumors in the right colon make the diagnosis of Lynch syndrome extremely probable.

Descriptive epidemiology of colorectal cancer in Italy: the 6-year experience of a specialised registry.

The Colorectal Cancer Registry of Modena recorded 838 malignancies of the large bowel between 1984 and 1989. Crude Incidence rates were 59.5 new cases per 100,000 per year in men and 47.4 in women (age-standardised values 33.1 and 20.6, respectively). 35 incident cases (4.2%) had multiple colorectal tumours, whereas 42 (5.1%) had extraintestinal malignancies (mainly breast, endometrium and stomach). Although 90.5% of the patients underwent surgery, this was "curative" in 634 (77.6% of the total), while 105 individuals (12.8%) had palliative operations; 78 patients (9.5%) were not operated, mainly because of metastatic disease or poor clinical condition. Finally, emergency operations--due to intestinal obstruction, perforation or massive bleeding--were carried out in 46 patients (6.1%). A total of 659 tumours (79%) were accurately staged. Among first-degree relatives of the registered patients a significant excess of cases of colorectal cancer was found in each year of the study. 5-year survival was evaluated in 132 (out of 140) patients registered in 1984 and followed-up until 1989. Overall 5-year survival was 37%, but rose to 43% when only colorectal cancer related deaths were taken into consideration. As expected, survival was strongly influenced by stage (P < 0.0001 by log-rank test). In conclusion, this study confirms previously reported data about incidence and mortality rates for colorectal cancer in northern Italy. The particular approach--limited to the large bowel--allowed the evaluation of the frequency of multiple tumours and of the marked aggregation of cancer among first-degree relatives. Finally, survival figures are comparable to those of many other studies and confirm that the clinical outcome of this neoplasm remains unfavourable in more than 50% of the affected patients.

[Acute cholestatic hepatitis caused by propafenone. Report of a case and review of the literature]. / Epatite acuta colestatica da propafenone. Descrizione di un caso e revisione della letteratura.

A case of acute cholestatic hepatitis associated with use of propafenone is reported. Hepatitis developed 3 weeks after the beginning of administration of this drug. The close time relationship between the administration of the antiarrhythmic drug and the acute onset of the liver damage, the exclusion of hepatobiliary disease and the rapid normalisation of biochemical parameters following withdrawal of the drug strongly suggest that propafenone was involved in the pathogenesis of this syndrome. Meticulous taking of patient history and clinical assessment are mandatory for the early identification of drug-induced hepatotoxicity and avoidance of more severe types of reactions, such as liver failure.

Incidence and familial occurrence of colorectal cancer and polyps in a health-care district of northern Italy.

The first year of registration of colorectal tumors in a predominantly urban population (263,546 inhabitants) of northern Italy gave us the opportunity to investigate: (a) the incidence (crude, age-specific, age-standardized) of both colorectal cancer and polyps and their localization; (b) the familial occurrence of these neoplasms; and (c) if the data could fit into the "Adenoma-Carcinoma Sequence." Crude incidence of cancer was 52.8 new cases/100,000 in 1984, with 53.4 cases in men and 52.2 cases in women. The corresponding figures for polyps were 59.6 new cases, with 83.4 in men and 37.3 cases in women. The incidence increased with age for both cancer and polyps, although the latter were more frequent until patients were in their sixties and the peak of incidence of polyps anticipated that of cancer by a 5 year period. Both cancer and polyps had a similar distribution in the large bowel, more than 60% being located in the left distal portion. There were 72 cases of colorectal cancer among the first-degree relatives of the registered patients compared with 16 in the controls (RR = 4.26, chi 2 = 27.2 p less than 0.001). An increased frequency of cases of colorectal cancer in the families was found in both the cancer group and the polyp group. In conclusion, the observed incidence of large bowel tumors was similar to that of other well-developed countries. The earlier rise and peak of age-specific incidence of polyps as compared to cancer, the similar distribution of benign and malignant neoplasms in the various intestinal tracts, and the similar familial aggregation observed both in the cancer and in the polyp groups further support the "polyp-cancer sequence" and provide us with a promising strategy for the prevention of colorectal malignancies.

Genetic transmission of colorectal cancer: exploratory data analysis from a population based registry.

Classical segregation analysis was conducted on 605 families of probands with colorectal carcinoma ascertained through the Cancer Registry of the Province of Modena in Italy. The families were classified as 28 suspected hereditary non-polyposis colorectal cancer (HNPCC) syndromes and 577 presumed non-HNPCC. In 11 of these, both parents had colorectal carcinoma, in 130 one parent was affected, and in 436 both parents were normal. In the suspected HNPCC families, segregation was compatible with dominant transmission of susceptibility to carcinoma. In families with one parent affected, the segregation frequency was almost exactly equal to the frequency of segregation in families where both parents were normal. The model of dominant transmission of susceptibility through a major gene with greatly reduced penetrance in heterozygotes fitted the data acceptably.

Evidence for the existence of different types of large bowel tumor: suggestions from the clinical data of a population-based registry.

The clinical findings of a population-based colorectal tumor registry have been analyzed to determine elements of supporting or not supporting the existence of different types of large bowel cancer. Age-specific incidence rate of the 409 registered patients rose sharply with increasing age in all segments of the large bowel; however, regarding left colon and rectum, the male: female ratio showed a marked male preponderance, more evident in the more advanced age groups. Histopathology, studied in 87% of patients, revealed adenocarcinoma as the most frequent feature; however, adenocarcinoma with concomitant adenoma (i.e., presumably arising in adenoma) was observed in 14.3% of cancers of the left colon, in 17.7% of rectal tumors, but in only 5.7% of neoplasms of the proximal colon (P less than 0.05 and P less than 0.01, respectively, vs. left colon and rectum). Some histological features (carcinoid and mucinous carcinoma) were observed in right-side tumors only. Analysis of the familial occurrence of cancer showed that a significantly larger proportion of patients with neoplasms located in proximal colonic segments had three or more first-degree relatives affected by (or deceased from) cancer of all sites. Similarly, colorectal tumors among relatives were more frequent in patients with right-side cancer. The location of the 793 polyps observed during 3 years of registration showed that more than 70% of adenomas were located beyond the splenic flexure, overlapping the distribution of cancers. In conclusion, the differences of sex ratio at different colonic subsites, the higher fraction of adenocarcinomas with adenomas in cancer of the more distal tracts of the large bowel, and the more marked familial occurrence of colorectal cancer in patients with right-side neoplasms tend to support the view that cancer of the proximal colon, cancer of the distal colon, and cancer of the rectum may actually be three different types of tumors.

Frequency of upper gastrointestinal lesions in patients with liver cirrhosis.

The frequency of gastroduodenal lesions has been investigated in 142 patients with liver cirrhosis of various degrees of severity and in 63 patients with mild liver disease (controls) in whom liver biopsy excluded nodular regeneration. Cirrhotic patients were subdivided in three groups according to the Pugh modification of the Child-Turcotte criteria. Although the frequency of peptic ulcer was not different, gastroduodenal erosions were observed more frequently in cirrhotics than in controls (29.6% vs 11.1%, P less than 0.01). The occurrence of erosions was related to the severity of the disease: in Child A and B patients their frequency was 21 and 26% respectively, but rose to 48.4 (15 of 31 vs 7 of 63 in controls, P less than 0.001) in the Child C group. Both mild and severe gastroduodenitis occurred more frequently, although not significantly, in patients with liver cirrhosis. All together one or more endoscopic lesions were observed in almost 60% of cirrhotics but only in 25.4% of controls (P less than 0.001). In conclusion, our data do not show an increased prevalence of peptic ulcer in cirrhotic patients; in contrast, liver cirrhosis is significantly associated with the endoscopic finding of gastroduodenal erosions, especially in the more advanced stages of the disease. These findings would suggest a cautious use, in cirrhotic patients, of drugs which may damage the gastroduodenal mucosa; moreover, long-term administration of antacids or of other drugs with a protective effect on gastroduodenal mucosa might be taken into consideration for Child C patients.

Hereditary adenomatosis of the colon and rectum: clinical features of eight families from northern Italy.

Adenomatosis coli (or familial polyposis of the large bowel) and related syndromes are relatively rare diseases characterized by an autosomal dominant mode of inheritance. In these diseases, the entire colorectal mucosa is covered by hundreds (often innumerable) polyps of various dimensions. In addition, several extracolonic abnormalities have been reported. In the present study, we describe the clinical features of eight families from northern Italy fulfilling the diagnostic criteria of adenomatosis coli. Information was available on 123 unaffected and 30 affected family members. The most relevant findings of the study can be summarized as follows. 1) Gene frequency was calculated to be between 1:7,300 and 1:19,000. Segregation ratio in affected branches was 0.57, with a gene penetrance of nearly 60% and a male:female ratio of 1.73. 2) Extracolonic manifestations were present in all families and in 15 of 30 affected patients, the most frequent being cutaneous cysts and retinal lesions. No case fulfilling the classical criteria of Gardner syndrome was observed. 3) When the diagnosis of adenomatosis followed the appearance of symptoms, colorectal cancer had usually already developed, whereas no malignant changes were observed in individuals diagnosed in the asymptomatic stage. When colectomy with ileorectal anastomosis was the treatment of choice, polyps tended to recur in the rectal stump, and long-term endoscopic follow-up was necessary. In conclusion, adenomatosis coli may account for a definite proportion of colorectal neoplasms observed in the general population. Taking into consideration the genetic base of the disease, it follows that individuals at risk should be closely monitored for several years. Moreover, clinical investigations should not be limited to the large bowel, but should be extended to the skin, upper digestive tract, fundus oculi, bones, and probably other organs.

Clinical and pathologic prognostic indicators in colorectal cancer. A population-based study.

The institution of a colorectal Cancer Register in a health care district of Northern Italy gave the authors the opportunity to evaluate the prognostic relevance of several morphologic and clinical variables by univariate and multivariate analyses. Of the 134 patients registered in 1984, 132 were followed up until the end of 1989. Overall 5-year survival was 37%, but the figure increased to 43% when only colorectal cancer-related deaths were considered. Univariate analysis for clinical variables showed that TNM staging and age at diagnosis were significantly related to prognosis, whereas none of the other parameters were indicative of the clinical outcome. With a similar analysis, among the various morphologic variables, pattern of growth (infiltrating versus expanding) and extent of fibrosis (extensive versus little or absent) appeared to be indicators of prognosis. When the variables that were significant (stage, age, pattern of growth, and fibrosis) in the univariate analysis were entered into the Cox model of multivariate analysis, TNM staging was the only parameter that maintained an independent prognostic importance. The authors state that their results confirm the importance of stage in predicting survival for cancer of the large bowel and suggest that the possible prognostic value of clinical and morphologic variables should be investigated within each of the major TNM or Dukes' classes.

Familial occurrence of gastric cancer in the 2-year experience of a population-based registry.

The authors studied the familial occurrence of tumors in 154 individuals with gastric cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1986 through 1987 in the Local Health Care District of Modena, Italy, for cancer of the stomach. Crude and age-adjusted (world population) incidence rates of gastric cancer were 34.0 and 21.4 new cases/100,000/year, respectively, in men, and 24.5 and 10.9 in women, respectively. Among first-degree relatives of the registered patients there were 30 cases of gastric carcinoma versus 15 cases in a control group matched for age and sex (Mantel-Haenszel odds ratio [M-H OR] 3.14, P less than 0.01). This excess of gastric neoplasms was observed in siblings (17 versus 7, M-H OR 4.33, P less than 0.02) but not in parents (13 versus 8, not significant). Besides gastric cancer, there was no significant excess of other type of tumors in case families. The familial occurrence of gastric cancer tended to be more frequent in patients with "diffuse" carcinoma (52%) than in subjects with "intestinal" cancer (33%), although the difference was not statistically significant. In conclusion, the current investigation suggests that a "family history" for gastric neoplasms is usually observed in approximately 10% to 15% of the registered cases. As already described for other common malignancies, therefore, the familial occurrence of gastric carcinoma suggests the existence of a genetic susceptibility to cancer of the stomach, at least in a fraction of these patients.