Vittorio Pugliese

Endoscopic retrograde forceps biopsy and brush cytology of biliary strictures: a prospective study☆☆☆★

BACKGROUND Nonsurgical pathologic confirmation of malignant bile duct strictures is desirable for defining subsequent treatment and prognosis. Endoscopic retrograde cholangiopancreatography is frequently performed in patients suspected of having pancreaticobiliary obstruction, but there exists no standardized method for defining the nature of obstructing lesions by ERCP. METHODS We prospectively evaluated the yields of endoscopic retrograde brush cytology and biopsy for the diagnosis of malignant bile duct strictures. Fluoroscopically guided endobiliary biopsy and brush cytology (52) or cytology alone (42) were performed during endoscopic retrograde cholangiopancreatography in 94 consecutive patients, 64 with malignant strictures and 30 with benign strictures. A single cytopathologist classified the results of these studies as positive or negative for malignancy. RESULTS The sensitivities of the two procedures were identical (53%) and the gain achieved by combining the two techniques (61%) was small. Specificity proved excellent for both methods. One major complication that occurred was perforation of the common hepatic duct with leakage of bile, which was managed by surgical oversewing. This complication was ascribed to biopsy and untimely removal of the nasobiliary drain by the patient herself. CONCLUSIONS This study indicates that endoscopic retrograde brush cytology alone may be sufficient in daily practice, at least in centers that have access to experienced cytopathologists. We recommend use of forceps biopsy in selected cases where brush cytology is negative.

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.

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.

Tissue sampling from the common bile duct through endoscopic retrograde cholangiopancreatography, endoscopic papillo(sphinctero)tomy and drainage in juxtapapillary malignancies

SummaryIn 22 patients with radiological evidence of a malignant stricture or an obstruction of the common bile duct, endobiliary tissue specimens were obtained through endoscopic retrograde cholangiopancreatography. An endoscopic papillo(sphinctero)tomy was necessary in 9 of the 22 patients. The following techniques were employed: (1) forceps biopsy of the papillary infundibulum and/or of the common bile duct; (2) brush cytology in the same sites as above; (3) biliary juice cytology obtained by a nasobiliary drainage tube. In 8 patients, two different sampling techniques were used. The final diagnosis was established by means of pathological evaluation of surgical or necroscopic material. The diagnostic adequacy was 100% for biopsy, 88% for brush cytology, and 62% for bile cytology. The sensitivity was 100%, 66%, and 25%, respectively, for the above techniques. From 6 cases without biliary cancer, the specificity was 100%. These data show that biopsy specimens alone provide a definitive preoperative diagnosis in most cases, provided adequate samples are obtained.

Outcome of follow-up programs in patients previously resected for colorectal cancer.

The survival of a group of 115 patients (group A) who entered a follow-up program after apparently « curative » surgery for colorectal cancer was compared with that of 62 similar patients (group B) who did not join such a program. No significant difference was found. Clinical benefits to single patients in group A, in terms of anticipated diagnosis and effective treatment of recurrences and of metachronous neoplasias, appeared to be, if any, extremely limited. In light of the high costs of intensive follow-up programs, it is concluded that their use can be justified only within controlled perspective trials aimed to evaluate their usefulness.

Mixed pleomorphic-osteoclast-like tumor of the pancreas. Light microscopical, immunohistochemical, and molecular biological studies.

SummaryThe morphological, immunohistochemical, and molecular biological features of a case of giant cell tumor of the pancreas are described. This neoplasm showed mononuclear and multinucleated tumor giant cells as well as numerous osteoclast-like cells with multiple foci of osteoid-osseous metaplasia. The pleomorphic and osteoclastic giant cells displayed extensive homologies in their immunohistochemical profiles. Neither the pleomorphic nor osteoclast-like portion of the tumor showed neither c-Ki-ras nor p53 mutation and did not express the mutated p53 protein. The results suggest that the pleomorphic and osteoclast-like components are histogenetically related and that this rare neoplasm originates from a precursor cell capable of differentiating along divergent cell type.

DNA Aneuploidy Is an Independent Factor of Poor Prognosis in Pancreatic and Peripancreatic Cancer

SummaryThe purpose of this study was to investigate the clinical significance of DNA ploidy, as assessed by flow cytometry, for pancreatic and peripancreatic cancers. Between 1988 and 1990, we examined fresh/frozen samples from 49 patients who had histologically confirmed adenocarcinomas of the bilio-pancreatic carrefour: They had 23 cancers of the pancreas, 21 of the Vaters papilla, and 5 of the common bile duct. All patients were selected among a cohort of subjects who underwent Endoscopic Retrograde Cholangio Pancreatography (ERCP) and/or surgery. No prognostic impact of age, sex, stage, and surgical treatment on survival was observed by univariate analysis. When the affected organ was considered, a statistically significant difference in survival was observed: At 88 wk, survival was 0% for pancreatic and common bile duct cancer patients, and 18.2% at 175 wk for Vaters papilla cancer patients (p=0.04). In addition, we found, irrespective of affected organ, that the patients with DNA diploid tumors had a statistically significant survival advantage as compared to those with DNA aneuploidy (p=0.02). Furthermore, the statistically significant prognostic power of DNA ploidy was confirmed when patients with tumors of the pancreas and those with tumors of the Vaters papilla were separately analyzed. Finally, multivariate analysis showed that DNA content and affected organ were the only independent prognostic factors: Relative risks of dying were 3.9 (95% confidence interval CI=1.6–9.7) for patients with pancreatic cancer and 2.5 (CI=0.7–8.8) for those with common bile duct tumor when compared to those with ampullary cancer; the relative risk for DNA aneuploid tumors, as compared to DNA diploid ones, was 2.4 (CI=1.2–5.0). In conclusion, our results indicate that abnormal nuclear DNA content in pancreatic and peripancreatic cancers is an independent and powerful, indicator of poor prognosis.

ENDODUCTAL TISSUE SAMPLING OF BILIARY STRICTURES THROUGH ENDOSCOPIC RETROGRADE CHOLANGIOPAN CREATOGRAPHY (ERCP)

Aim and background Pathological proof of malignant in biliary strictures is useful in the preoperative setting as it helps define therapeutic planning and prognosis, and reduces the length of the subsequent surgical intervention. However, it is difficult to obtain. The aim of this study was to evaluate the yield of histological and cytological examination of endobiliary samples obtained during endoscopic retrograde cholangiopancreatography (ERCP). Methods Endobiliary forceps biopsy and brush cytology were performed during ERCP examination in 52 consecutive patients, 36 with malignant and 16 with benign strictures. Results Histology and cytology turned out to have the same sensitivity (53%). The gain in sensitivity achieved by combining the two techniques was limited, reaching a value of 61%. The specificity, however, was 100% for both methods. Most of the few complications observed were due to sphincterotomy and subsided spontaneously or with medical treatment. However, one patient experienced a serious complication and chose to be treated by surgical intervention. The complication was caused by forceps biopsy. Conclusions This study shows that 1) sampling of biliary strictures during ERCP is the primary approach to tissue diagnosis; 2) brush cytology alone is sufficient in clinical practice; 3) forceps biopsy must always be used to sample intra-ampullary strictures but should be considered as a secondary step to sample strictures located more proximally, in the bile ducts, if previous cytology was negative.