Hugo Aste

Exocrine Pancreatic Cancer, Cigarette Smoking, and Diabetes Mellitus: A Case-control Study in Northern Italy

The role of cigarette smoking and diabetes mellitus as risk factors for exocrine pancreatic cancer (PC) was investigated in a hospital based case-control study. Current smokers were at increased risk for PC (OR = 2.36, 95% CI 1.53–3.63): the magnitude of the risk was related to the lifetime amount of smoking (&khgr;2trend = 17.00; P < 0.0001). Among former smokers, after 15 years from ceasing smoking, the risk for PC dropped to the level of a lifetime non-smoker, whichever the lifetime smoking amount. Diabetes was associated with a 2.89-fold increased risk for PC (95% CI 1.71–4.86): the risk was 4.76 (95% CI 1.99–11.53) for diabetes diagnosed up to 2 years before the diagnosis of PC and dropped to 2.07 (95% CI 1.02–4.20) for diabetes diagnosed more than 5 years before PC. The risk for PC was estimated according to the treatment used to control diabetes: it was 6.49 (95% CI 2.28–18.48) for insulin treated diabetes and 2.12 (95% CI 1.16–3.87) for diabetes treated with oral hypoglycemic drugs. The risk of PC for diabetes treated for more than 5 years before the diagnosis of PC was 6.21 (95% CI 1.61–23.96) for patients treated with insulin and 1.21 (95% CI 0.50–2.92) for those treated with oral hypoglycemic drugs: the type of treatment needed to control the disease may discriminate between the diabetes that represents a consequence of cancer from the diabetes that could represent an etiological co-factor. More studies are needed to clarify whether long-lasting insulin-treated diabetes is an etiological co-factor in PC.

CA 19‐9 and CA 50 in Benign and malignant pancreatic and biliary diseases

Serum concentrations of the CA 19‐9 and CA 50 antigens were determined in 129 patients with malignant and benign biliary and pancreatic diseases. Values for the two markers were highly correlated (P < 0.001). The concentrations of CA 19‐9 and CA 50 were positive in 84.6% and 80.7% of patients with pancreatic cancer, respectively. The overall specificity of CA 19‐9 (92.4%) was slightly higher than that of CA 50 (88.5%). The sensitivity of CA 50 (91.3%) was greater than that of CA 19‐9 (73.9%) in patients with diseases of the biliary tract. Elevated concentrations of CA 19‐9 (12.9%) and CA 50 (35.2%) were also found in a number of cases with benign disease, especially in patients with obstructive jaundice. These data suggest that both CA 19‐9 and CA 50 can be useful markers of pancreatic cancer in nonjaundiced patients. The joint use of the two markers does not yield a better diagnostic resolution than the use of either one alone.

Flow cytometric DNA index in the prognosis of colorectal cancer

The authors investigated the relationship between flow cytometric DNA index (DI, defined as the ratio of the DNA content of malignant cells to that of normal cells) and other prognostic factors (grade and stage, anatomical site, age and sex) with the survival of 115 patients with colorectal cancer. Multiple biopsy specimens from 62 patients were taken during colonoscopy before surgery. Additional samples from 53 patients were obtained from paraffin‐embedded material. All patients were treated with surgery only. Fresh–frozen material gave higher incidence of DNA aneuploidy than paraffin‐embedded material (79% versus 41%). The patients with DNA diploid tumors (DI = 1) had a better overall survival than those with DNA aneuploid tumors (DI > 1). Among DNA aneuploid tumors, those with DI > 1.2 (excluding DI = 2) were worse than those with DI > 1.2 (excluding DI = 1) and DI = 2. Coxs regression analysis showed that pathologic stage was more important for prognosis than DNA index, whereas age, sex, histologic grade, and anatomic site were removed from the analysis as not relevant for prognosis. Relative risks of death (RR), in reference to patients with DI = 1 and Stages A + B (RR = 1), were RR = 1.8 for patients with carcinomas with Stage C, RR = 2.7 for patients with carcinomas with DNA near‐diploid and DNA tetraploid tumors, RR = 3.5 for those with DI > 1.2 (excluding DI = 2), and RR = 8.0 for those with Stage D. These data indicate that flow cytometrically evaluated DI values have a relevant independent power for predicting the clinical outcome of colorectal cancer patients.

Primary signet‐ring carcinoma of the large bowel report of nine cases

Nine cases of signet‐ring carcinoma have been observed from among 800 consecutive histologic cases diagnosed as adenocarcinoma of the colon during a period of 10 years (0.9%). This group of nine patients (Group A) has been matched for sex, age, and stage with a group of 45 patients affected by oridinary carcinoma of the colon (Group B). Clinical and histologic parameters, including symptoms, primary tumor site, free interval from primary surgery, histochemical investigation of intracytoplasmic mucins, and survival, were evaluated. The results of this investigation showed no clinical differences between signet‐ring carcinoma and ordinary carcinoma, and no statistically significant results were observed regarding the frequency of local recurrence and actuarial survival.

Incidence of Barrett's adenocarcinoma in an Italian population : an endoscopic surveillance programme

Background: Barretts oesophagus is a premalignant condition leading to adenocarcinoma. The incidence of adenocarcinoma of the oesophagus and the gastro‐oesophageal junction is rapidly increasing in the USA, northern and central Europe. Data from southern Europe are still unavailable. Objective: To evaluate the incidence of oesophageal adenocarcinoma in a large cohort of Italian patients with Barretts oesophagus. Methods: A total of 344 patients (253 males and 91 females, age range 19‐75 years) with histologically proven Barretts oesophagus (length of metaplasia ≥3cm) were enrolled from November 1987 to June 1995. Endoscopic and histological examinations were scheduled at yearly intervals. Results: One hundred and eighty‐seven patients complied with the follow‐up. The mean duration of the follow‐up period was 36 months (total follow‐up 562 patient‐years; range 12‐90 months). Low grade dysplasia was found in five patients at the initial examination. During the surveillance period, dysplasia increased in frequency as well as in severity and was found exclusively in the intestinal type of Barretts oesophagus. In all, dysplastic changes were found in seven patients (five low grade and two high grade) and adenocarcinoma developed in three patients during the follow‐up. In a single case, both adenocarcinoma and specialized columnar epithelium developed without any evidence of dysplasia or intestinal metaplasia at the previous follow‐up examination. This prospective study shows an incidence of adenocarcinoma in Barretts oesophagus of 1/187 patientyears. When only patients with specialized columnar epithelium were considered, the risk of adenocarcinoma was 1/88 patient‐years. Conclusion: The present report shows that the incidence of adenocarcinoma in Italian Barretts oesophagus patients is in the range of that reported from other Western countries.

Distal hyperplastic polyps do not predict proximal adenomas: results from a multicentric study of colorectal adenomas☆☆☆★★★♢

BACKGROUND The association between distal hyperplastic polyps and proximal adenomas is still a matter of debate. We investigated this association while taking into account patient characteristics. METHODS After exclusion of patients with inflammatory bowel diseases, familial adenomatous polyposis, or any cancer, 3088 eligible consecutive subjects aged 18 to 69 years underwent total colonoscopy in four gastroenterology units. The odds ratios (OR) of having proximal adenomas according to patient characteristics (age, sex, medical center, year of endoscopy, reasons for referral, and distal findings) were estimated in univariate and multivariate analyses. RESULTS Patients with distal polyps of any type showed an adjusted OR of 2.5 (95% CI [1.9, 3.1] p < .001) of having proximal adenomas as compared with those without distal polyps. When distal adenomas and distal hyperplastic polyps were included in the multivariate model as independent factors, the presence of adenomas significantly increased the risk of proximal adenomas (OR = 2.8: 95% CI [2.2, 3.6] p < .001), whereas the presence of hyperplastic polyps did not (OR = 1.1: 95% CI [0.8, 1.5] p = .64). No association with number, size, or location of distal hyperplastic polyps was seen. CONCLUSIONS Our data show that the presence of hyperplastic polyps should not be the sole indication for total colonoscopy because they are not associated with proximal adenomas when adjusting for patient characteristics and presence of distal adenomas.

Flow cytometric DNA ploidy in colorectal adenomas and family history of colorectal cancer

Flow cytometric DNA ploidy of colorectal adenomas resected from 34 patients and the corresponding patient family history in first‐degree relatives were evaluated. The samples with at least two separate G0‐G1 peaks were defined as DNA aneuploid. The correlation between DNA ploidy and family history was evaluated using two‐by‐two contingency tables. This correlation was highly statistically significant: seven of nine patients (78%) with positive family histories, and five of 25 (20%) with negative family history had adenomas with DNA aneuploid stemlines (P = 0.0068). The overall DNA aneuploidy incidence was 12 in 34 cases (35.2%). The combined information of DNA aneuploidy and positive family history of colorectal cancer in patients with colorectal adenomas may help to better understand the process of colon carcinogenesis and to identify patients who have a higher risk for developing a malignancy.

Novel germline APC variants in patients with multiple adenomas

Chain‐terminating germline APC mutations are responsible for adenomatous polyposis coli (APC). In the present work, we tested the hypothesis that germline APC mutations may be present in some patients with a milder phenotype, i.e., multiple synchronous colorectal adenomas. Eighteen patients with 3 or more colorectal adenomas at endoscopy (within a 6‐month period) were ascertained from a series of subjects undergoing endoscopic examination. Their blood DNAs were analysed for the presence of germline mutations in the APC coding region by single‐strand polymorphism analysis. Ten unrelated polyp‐free subjects and 101 unrelated APC patients were used as controls in the molecular analyses. Five of the eighteen patients carried novel germline APC variants or rare polymorphisms. These were various in site (from the splice acceptor site of intron 7 to the end of exon 15) and type (splice‐site, missense, and chain‐terminating mutations). Only one of ten polyp‐free individuals carried a silent APC variant and none of these variants was found in the 101 APC controls. A first‐ or second‐degree family history of colorectal cancer was reported by 4 of the 5 patients carrying a germline APC variant. In conclusion, novel APC germline variants were detected in patients with multiple synchronous adenomas. This suggests that the development of sporadic adenomas, in some instances, is associated with the presence of minor germline variants of the APC gene and that the spectrum of germline APC functional mutations may be larger than previously thought. Genes Chromosomes Cancer 22:257–267, 1998.

CA 19-9 assay in patients with extrahepatic cholestatic jaundice.

Serum concentrations of the CA 19-9 tumour marker were determined in 35 patients with histologically proven bilio-pancreatic malignancies associated with obstructive jaundice and in 35 patients with benign extrahepatic jaundice due to choledocholithiasis. At a cut-off level of 37 U/ml the sensitivity of this assay was 82.8%, but the specificity was very low (45.7%). Thus CA 19-9 can not be employed to differentiate between malignant and benign extrahepatic jaundice. Serial samples of CA 19-9 were achieved in 7 patients with benign and in 6 patients with malignant biliary obstruction, before and after the disappearance of jaundice. Serum concentrations of this tumour-antigen returned to normal concurrently with the bilirubin values only in patients with benign obstruction, remaining unchanged in all cases of malignancies. The data suggest that patients with extrahepatic jaundice should be evaluated by other examinations or by collecting serial samples for this assay.

Esophageal dilation in malignant dysphagia

Esophageal dilation by means of guided Neoplex (Medoc) tubes in 38 patients with malignant obstruction of the esophagus was analyzed. Peroral dilation proved to be a simple, well‐tolerated primary procedure in the management of malignant strictures. Most patients have a temporary improvement of dysphagic symptoms, but the benefit appears to decrease progressively in successive dilatatory sessions. Dilations were more difficult, with a 10% perforation rate, in previously radiated patients. Esophageal dilations may play a complementary role in addition to other palliative techniques in the management of malignant dysphagia.