Search

We report a case of intestinal hepatoid adenocarcinoma, confirmed by albumin m-RNA in situ hybridization, with subsequent metastatic spread to the liver in a male with a long-standing history of ulcerative colitis. This novel finding strongly suggests that ulcerative colitis can lead not only to conventional adenocarcinomas but also to hepatoid adenocarcinoma and highlights the mimicry of hepatocellular carcinoma by metastatic hepatoid adenocarcinoma liver nodules.

The role of hepatitis B virus (HBV) in the course of patients with primary liver cancer who are negative for hepatitis B surface antigen has been debated. We used the polymerase chain reaction to evaluate 28 such patients for the presence of DNA and RNA sequences of the virus; 22 of these patients had associated cirrhosis. The patients were from areas with different prevalences of HBV infection (South Africa, Italy, France, and Japan).Antibodies to the surface and core antigens of HBV were detected in 10 of the 23 patients tested. HBV DNA sequences were detected in 17 of the 28 patients, including 8 of the 10 with HBV antibodies and 6 of 13 without HBV serologic markers. HBV RNA molecules were found in four of five tumors tested.Our investigation indicates that transcriptionally active HBV genomes are present in various geographic areas among patients with liver cancer who are negative for hepatitis B surface antigen. This observation is consistent with an etiologic role for the virus in the development of these tumors.

Background. Molecular targets are needed for primary liver tumours. Aims. ErbB1 and ErbB2 expression was analysed in neoplastic and surrounding tissue in surgical specimens from 52 hepatocellular carcinomas and 48 intrahepatic cholangiocarcinomas, randomly chosen from cases surgically treated in this institution. Methods. ErbB1 and ErbB2 expression were evaluated immunohistochemically, the latter by Herceptest. Gene amplification of ErbB2 was tested by chromogenic in situ hybridisation. Results. In normal/cirrhotic non-neoplastic tissue, the ErbB1 (but not ErbB2) antibody commonly stained normal hepatocytes and mature intrahepatic ducts. In neoplastic tissue, moderate/strong ErbB1 immunostaining occurred in 43/52 (85%) hepatocellular carcinomas and 39/48 (81%) intra-hepatic cholangiocarcinomas. With ErbB2 Herceptest, 0/52 (0%) hepatocellular carcinomas and 2/48 (4%) intra-hepatic cholangiocarcinomas had treatable scores of 2+/3+ (chromogenic in situ hybridisation confirmed gene amplification in the latter two cases only). Neither ErbB1 nor ErbB2 expression correlated with any of the main clinical-pathologic features or survival. Conclusions. Although not related to prognosis, ErbB1 could be a molecular target in a large percentage of patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma. Inclusion of anti-ErbB1 drugs such as ZD 1839 and c225 (and possibly also anti-ErbB2 drugs like Trastuzumab for a small subset of patients) in clinical trials is suggested. © 2003 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Science Ireland Ltd. All rights reserved.

Cytokeratin (CK) patterns and albumin messenger RNA (mRNA) are investigated in 24 patients with benign hepatic lesions (7 patients with focal nodular hyperplasia [FNH], 10 with hepatocellular adenomas [HA], 1 with biliary hamartoma, 4 with biliary cysts, 2 with cystadenomas) and in 8 patients with cystadenocarcinoma, a rare liver malignancy. The lesions and surrounding tissue of the hepatocytic components expressed CK 8 and 18 at immunohistochemistry, whereas the biliary elements evidenced CK 8 and 18 and CK 7 and 19. The albumin mRNA, as detected by in situ hybridization (ISH), revealed different distributions in the hepatocytes of FNH and HA. In the benign biliary lesions, the normal hepatocytes surrounding the tumors expressed albumin mRNA, whereas the biliary structures did not. Interestingly, in the cystadenocarcinomas, albumin mRNA was observed not only in the hepatocytes of residual parenchyma, but also in neoplastic bile duct cells lining the carcinomatous cysts; no signal was identified in the nonneoplastic biliary elements. This indicates that cystadenocarcinomas have a mixed biological phenotype and suggests they could arise either from pluripotent cells or from neoplastic cells that reacquire epigenetic features. Our results suggest two possible diagnostic applications for albumin ISH: on routine sections, it could represent an important tool for distinguishing between cystadenoma and cystadenocarcinoma; and on fine needle biopsy specimens, it could reduce uncertainty between FNH and HA.

Little is known about the alterations of metabolic organization of the human liver tissue in chronic liver diseases. We therefore compared the distribution of the following zonal metabolic markers in 10 samples of normal liver tissue, 10 samples of fibrotic tissue, and 22 samples of cirrhotic tissue: (a) the enzymatic activities of glucose-6-phosphatase (G6P), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), nicotinamide-adenine-dinucleotide-phosphate [NAPH] dehydrogenase (ND), beta-hydroxybutyrate dehydrogenase (HBDH), and glutamate dehydrogenase (GDH); (b) the protein glutamine synthetase (GLS); and (c) albumin messenger RNA (mRNA). The normal human hepatic lobule was characterized by the periportal predominance of G6P and SDH enzymatic activities and albumin mRNAs, the perivenous predominance of ND and GDH, the restriction of GLS to a small perivenous compartment, and the predominanc of beta-HBDH at the contact of both portal tracts and centrilobular veins. In fibrosis, the overall metabolic organization of the normal liver tissue was retained. The expression of periportal markers predominated around enlarged portal tracts and that of perivenous markers around residual centrilobular veins. GLS was constantly detected at the contact of centrilobular veins. In cirrhotic nodules, no zonation was observed for most enzymatic activities or for albumin. Only G6P usually predominated at the periphery of the nodules. GLS was constantly undetectable. No difference accordingly to the etiology of the underlying disease was observed. In conclusion, the normal human hepatic lobule presents a marked metabolic zonation, preserved in fibrotic lesions, but lost in cirrhotic nodules. The alterations of the metabolic organization observed in cirrhosis might contribute to the pathogenesis of some of the metabolic disorders associated with advanced liver disease.

It has been suggested that certain clinical and morphological features can modify the outcome of Crohn's disease, particularly regarding recurrence after surgery. A series of 233 patients was followed prospectively. They underwent a resectional surgical procedure for both primary and recurrent Crohn's disease during a fifteen-year period with a minimum follow-up of eighteen months. Possible risk factors for recurrence were studied. They included duration of disease before primary surgery, the type of clinical presentation at onset (whether "Perforating" or "Non-perforating"), the initial anatomical location, the presence of microscopic disease at the resection edges, the type of surgical procedure (anastomosis vs stoma), post-operative surgical complications and the age of the patient. The duration of the disease before the initial operation was the only significant factor related to the recurrence rate.

Cysteine proteases (cathepsin B [CATB] and cathepsin L [CATL]), the serine protease urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) are thought to play an important part in cancer invasion and metastasis. The aims of this study were to measure CATB, CATL, UPA, and PAI-1 in gastric cancer (GC) and normal mucosa distant from the tumor (NORM); to evaluate whether tissue levels are related to tumor stage, grade, or histotype; to assess their prognostic relevance; and to examine UPA and PAI-1 expression immunohistochemically.Gastric cancer and NORM samples were obtained from 25 patients with gastric cancer patients undergoing surgery (17 males, 8 females; mean age, 62 years; range, 31-84 years). Antigen concentrations were measured using the enzyme-linked immunosorbent assay method. Immunohistochemistry was performed using monoclonal UPA and PAI-1 antibodies.Significantly higher antigen levels were found: (1) in GC vs. NORM (CATB, CATL, UPA, PAI-1) tissues; (2) in GC with versus without metastasis (CATB, CATL, UPA); (3) in poorly or moderately versus well differentiated GC; and (4) in diffuse versus intestinal-type GC (CATB, CATL). Urokinase-type plasminogen activator, PAI-1 and CATB levels had a significant prognostic impact. Cancer and stromal cells, showed immunoreactivity to anti-UPA and anti-PAI-1 antibodies.These results confirm the important role of CATB, CATL, UPA and PAI-1 in gastric cancer progression. Higher levels are detected in GC with metastases, poorer differentiation, and diffuse histotype, thus identifying patients with a worse prognosis.

Two cases of atypical juvenile polyposis are described in males of 9 months and 25 years-of-age. The first was associated with congenital megacolon and presented as juvenile polyps with features suggesting mild dysplasia. In the second case six histological lesions are found: I hyperplastic polyps; 2 juvenile polyps; 3 hyperplastic polyps with adenomatous areas; 4 juvenile polyps with areas of dysplastic epithelium; 5 adenomas; and 6 adenocarcinomas. On the basis of the morphological features we propose a pathogenetic sequence of focal mucosal hyperplasia to adenoma and carcinoma through stages of non-neoplastic and non premalignant polyps. Finally, the possibility that hyperplastic epithelium can in some circumstances have a greater dysplastic potential that normal colorectal mucosa is raised.

Frequency and characteristics of early gastric cancer (egc) were evaluated in a retrospective study of 511 surgical specimens of gastric carcinoma. We observed a total of 46 egc in 40 patients. The predominant macroscopic type was IIc, followed by I and III. On the basis of histological appearance, 25 egc were of intestinal type and 15 of diffuse type. Seventy-six per cent of egc were localized at the lesser curvature of the stomach and in particular at the pyloric antrum. Twenty-two egc were limited to the muscosal layer. no relationship was observed between macroscopic type or histological characters, and tumour staging. As Italy can be considered a high-risk country for gastric carcinoma and because this disease is in many respects similar to that observed in Japan, it seems possible to obtain a reduction of the death rate for gastric cancer by increasing, as in Japan, the number of cancers diagnosed in the early phase.

Endoscopic ultrasonography (US) enables high-resolution imaging of the stomach and can demonstrate the different layers of the gastric wall. It has therefore been proposed for use in evaluating the extension of gastric neoplasms. It was performed in nine patients with primary gastric non-Hodgkin lymphoma and in 36 with gastric carcinoma. The US and pathologic findings were correlated in three surgical specimens of gastric lymphoma. Three different US patterns were found in gastric lymphomas: a polypoid pattern (two cases), localized (two cases) or extended (five cases) hypoechoic infiltration, and thickening with superficial ulcerations. Infiltration was confined to the second and third layers of the gastric wall in six cases and was transmural in three. The study of the gastric lymphoma specimens confirmed the accuracy of US in demonstrating the extent of infiltration. Gastric carcinomas had a more echogenic pattern and a different trend of diffusion, with no extended longitudinal hypoechoic infiltration of the superficial layers or extended hypoechoic transmural infiltration.

Eleven small primary liver lesions detected in four cirrhotic patients are reported in detail. Some lesions showed the histopathological features of macroregenerative nodules (MRN) containing foci of cellular and structural atypia or of hepatocellular carcinoma (HCC). Other lesions showed the histological abnormalities of the early developmental stage of HCC without a background of MRN. Finally one lesion is described with an equivocal background between benign and malignant, containing a focus of carcinoma. All lesions presented suggest the presence of different pathways in the morphogenesis of human HCC.

Clinical, histological, histochemical and ultrastructural characteristics of eight cases of carcinoid tumors of the non-antral portion of the stomach are presented. Four cases with multiple polypoid lesions are accompanied by an increased level of gastrin. A normal level of gastrin was present in the other four cases with isolated tumor and a normal component of endocrine cells in the uninvolved mucosa. In the first group with multiple lesions, the histological and histochemical analysis of the endocrine cells revealed a wide range of appearances: a) "simple hyperplasia", b) "nodular hyperplasia", and c) carcinoid tumor. These aspects suggested a different pathogenesis for the carcinoid tumors of the non-antral portion of the stomach with possible therapeutical implications.

The frequency and the pathological findings of 125 early gastric cancers (ECGs), and particularly of small and minute lesions, were evaluated in a retrospective study of 839 surgical specimens of gastric carcinoma. Sixty two ECGs were believed to have risen from gastric epithelium, 27 from areas of intestinal metaplasia, and 3 from cardio-pyloric mucosa. The remaining lesions showed mixed histological patterns. The most frequent macroscopic type was IIc (24.8%) followed by IIb (16.8%), I (16.8%), and III (14.4%). In 63 cases (50.4%) the cancer was limited to the mucosa. In all specimens, and particularly in small and minute lesions, the surrounding mucosa was accurately analyzed to detect any lesions, from which the cancer could have developed. Intestinal ECGs, especially if protruded, seem to arise from areas of intestinal metaplasia or of chronic atrophic gastritis. Rarely ECGs seem to stem from polypoid lesions both hyperplastic and adenomatous. On the contrary, most important seems to be the role of ulcerative lesions, since in 14 cases of our series, carcinomatous foci were observed within the regenerative epithelium covering the crater. No correlation was found between histologic type, size, staging, and frequency of node metastasis; this suggests the existence of ECGs with different biologic behaviour.

We have reviewed 415 cases of colon-rectum carcinoma in order to establish the most important prognostic anatomical features. Furthermore, we have examined the associated adenomatous polyps, and the possible relationships between anatomical and histological aspects and Dukes stage of carcinoma. We have searched for some useful parameters to decide whether 5 centimeters between neoplasia and resection line is the correct surgical treatment.