Effects of anti-erbB-2 (HER-2/neu) recombinant oncotoxin AR209 on human non-small cell lung carcinoma grown orthotopically in athymic nude mice.

The recombinant oncotoxin AR209 [e23(Fv)PE38KDEL; formerly OLX-209] was developed to treat neoplasia that expresses the c-erbB-2 (HER-2/neu) protein product p185(erbB-2). The AR209 compound contains a single-chain antibody domain specific for p185(erbB-2), coupled with a portion of the Pseudomonas exotoxin. The drug has been shown to be effective in inhibiting cells that overexpress erbB-2 due to gene amplification and in cells that do not contain amplified erbB-2 but express slightly higher levels of the protein than normal cells do. To test the efficacy of AR209 on human lung tumors, athymic nude mice were inoculated intrathoracically with a cell line derived from a poorly differentiated lung adenocarcinoma. This cell line, termed 201T, expresses moderately elevated levels of p185(erbB-2) 7.6-fold over normal bronchial epithelium. Mice treated with i.v. injections of AR209 for 5 weeks after orthotopic tumor implantation had smaller tumors and in 20% of cases showed no evidence of disease. The data from this study indicate that AR209 may be an effective treatment for patients with non-small cell lung cancers that express p185(erbB-2).

DNA ploidy pattern and tumor suppressor gene p53 expression in gallbladder carcinoma.

The relationship between p53 gene expression and DNA content in advanced gallbladder carcinoma was studied. Fifty-three cases of advanced gallbladder carcinoma (45 primary tumors and 8 metastases) were analyzed, p53 protein expression was determined by immunohistochemistry, DNA content was measured by cytophotometric techniques. Study subjects included 45 (85%) female and 8 male patients, with an overall mean age of 58.6 years. Positive staining for p53 protein was observed in 27 (51%) cases. In subserosal tumors, the expression was significantly less than that in tumors that reached the serosa (P = 0.01). Twenty-nine (55%) cases were diploid and 24 were aneuploid. Sixty-seven % of primary tumors were diploid, whereas 87% of metastases showed an aneuploid DNA content. Both diploid and aneuploid tumors were positive for the p53 protein in the same proportion, and p53 was also expressed equally in both primary and secondary tumors. In advanced gallbladder carcinoma, the expression of the p53 gene was earlier than the accumulation of abnormal quantities of chromosomal DNA in the tumor cells. The determination of these events as markers in preneoplastic lesions is warranted in gallbladder carcinogenesis.

Mutagenicity of blue rayon extracts of human bile in the Ames test.

The mutagenicity of human bile was examined in the Ames Salmonella/microsome assay. Bile samples were obtained from the gallbladders resected from patients with cholelithiasis, choledocholithiasis, gallbladder cancer, extrahepatic bile duct cancer and other diseases. For extraction of mutagenic components, the bile samples were treated with blue rayon and the adsorbed materials were assayed with Salmonella typhimurium TA98 in the presence of S9 mix. Twenty-four bile samples were tested and positive mutagenic activity was found in 14 samples. A 200-microliter bile equivalent material gave 6.3 times as many revertant colonies as the solvent control. With several samples that had undergone two cycles of blue rayon extraction, clear dose-response relationships in mutagenicity were demonstrated.

Comparison of mutagenic activity of bile between Chilean and Japanese female patients having cholelithiasis.

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p < 0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.

Preoperative chemoradiotherapy in the treatment of gallbladder cancer.

Gallbladder cancer is generally associated with a poor prognosis, with local recurrence being the main pattern of failure. In an attempt to improve on the present status of management, we evaluated a prospective Phase II study involving preoperative 5-fluorouracil and radiation. Among 27 eligible patients with a potentially resectable gallbladder cancer detected after cholecystectomy, 18 were treated with preoperative radiation (4500 cGy; 180 cGy/fraction, 5 days/week) concurrent with a continuous infusion of 5-fluorouracil (350 mg/m2/day, days 1-5 and 21-25). Toxicity included leukopenia (8 patients) and thrombocytopenia (7 patients). Delay in surgery due to hematological toxicity was seen in 6 patients. Of the 18 patients, 15 underwent a reoperation. Resection was performed in 13 (86%). Pathologic findings after reoperation revealed residual tumor in both liver and lymph nodes in 3 patients. At a median follow-up of 24 months, 7 patients are alive. Among the patients who died after curative resection, local recurrence was demonstrated in only 1. This is the first report concerning preoperative chemoradiation in gallbladder cancer. To assess its effect on survival, a prospective randomized trial will be necessary.

Peritoneal pseudomyxoma in a child with a gallbladder Peutz-Jeghers-like hamartomatous polyp: a case report.

A 2-year, 6-month-old boy with peritoneal pseudomyxoma had a hamartomatous Peutz-Jeghers-like polyp in the gallbladder. The morphological pattern of the polyp was very characteristic of what is usually considered an hamartomatous polyp. The patient presently reported has no clinical characteristics of Peutz-Jeghers syndrome. The peritoneal pseudomyxoma creates differential diagnostic problems with well-differentiated mucinous adenocarcinoma.

Gallbladder cancer in a high risk area: morphological features and spread patterns.

BACKGROUND/AIMS: Gallbladder carcinoma is one of the most frequent malignant tumors in Chile. The aim of this paper is to show our experiences in gallbladder carcinoma. METHODOLOGY: Six-hundred-sixty-nine cases of gallbladder carcinoma were included in this prospective study; 557 females (83.5%) and 112 males (16.5%). In 466 cases (70%), diagnosis was carried out in the cholecystectomy sample, 45 cases were partial cholecystectomies and 158 cases were metastases of gallbladder carcinoma. RESULTS: Ninety-eight per cent of the cases were adenocarcinomas, and in 85% of the cases gallstones were observed. Thirty-seven per cent of the primary tumors were macroscopically inapparent. One-hundred-thirty-one cases (29%) were early carcinomas and 323 cases (71%) were advanced carcinomas. A relationship between differentiation grade and infiltration level (p=0.0001) was observed. Lymph-node metastasis was found in 18.5%, 4.5% and 3.3% in the first, second and third lymph-node barriers respectively. Muscular tumors presented no lymph-node metastasis, while in serosal tumors lymph node metastasis reached 62% (p=0.04). Hepatic tumor infiltration was observed in 11%, 19% and 38% of muscular, subserosal and serosal tumors. CONCLUSIONS: The high frequency of inapparent carcinomas, gallstones and inflammatory changes of the vesicular wall are elements that make the pre-operative diagnosis of gallbladder carcinoma difficult. Differentiation grade and infiltration level are the most reliable prognostic factors in gallbladder carcinoma. Lymph-node metastasis or liver tumor infiltration are infrequent in early gallbladder carcinoma.

[The sea blue histiocyte syndrome: a case report]. / Sindrome del histiocito azul marino: caso clínico.

A young pregnant woman presented with splenomegaly and a hemorrhagic syndrome. A persistent alteration of several coagulation tests was demonstrated. Large foamy pigmented macrophages were shown by bone marrow aspiration. The histopathologic findings are consistent with the sea blue histiocyte syndrome, a benign type of lipid storage disease.

[Malignant histiocytosis in children]. / Histiocitosis maligna en el niño.

A case of malignant histiocytosis in a two year old boy is reported. His main clinical features were fever, lymphadenopathy, hepatomegaly and splenomegaly. Lymph node biopsy showed a sinusoidal type of lymph node infiltration, histiocytes of malignant aspect and erythrophagocytosis. Liver infiltration with tumoral cells was demonstrated by needle biopsy. The clinical evolution was rapidly progressive and after six months of chemotherapy he died of intercurrent respiratory infection.

Pilonidal disease: 25 cases treated by the Dufourmentel technique.

Twenty-five patients with pilonidal disease were treated by the Dufourmentel technique between 1984 and 1989. In this series, 18 patients (72 percent) were women and 7 (28 percent) were men (mean age, 24 years); hospital stay averaged 4 days. There were no recurrences and no reports of surgical wound infection. Diagnosis was confirmed histologically in all cases.

[Regeneration of gastric mucosa after endoscopic biopsy]. / Regeneración de la mucosa gástrica después de biopsia endoscópica.

Eleven gastric mucosal defects produced by endoscopic biopsy in non-tumoral areas were histologically studied in gastrectomy specimens. The biopsies had been performed from one up to seven days before the operation. The base of each defect was formed by submucosa infiltrated by erythrocytes, fibrin and neutrophils, which were later replaced by small blood vessels, fibroblasts and collagen fibrils. The mucosa of the margins bowed down towards the base of the defect. This marginal mucosa showed dedifferentiation of the glandular epithelial cells, increased mitotic index and some cystic glandular structures lined by basophilic cells. The defect was progressively covered by a layer of flattened or cuboidal cells in which no mitoses were observed; their cytoplasm contained mucosubstances similar to those of the superficial epithelium of the remaining mucosa, either foveolar- or intestinal metaplastic-type. From this layer, simple gland-like invaginations to the underlying connective tissue were observed. The findings are consistent with the regenerative events described in experimental gastric ulcers in animals. The method employed may be useful to study specific aspects on the regeneration of the human gastric mucosa.

[Gastric cancer in the IX Region of Chile: an analysis of 233 cases]. / Cáncer gástrico en la IX Región de Chile: análisis de 233 casos.

Gastric cancer is the leading cause of mortality from malignancy in Chile. Different reports indicate a high incidence of well differentiated forms of this tumor. Among 233 endoscopically diagnosed lesions in patients from the Ninth Region of Chile, we found a high incidence of poorly differentiated tumors and a relatively high incidence of signet-ring cell carcinoma. The incidence of inoperable lesions was high.

[Gallbladder pathology in Temuco, IX Region]. / Patología de la vesícula biliar en Temuco, IX Región.

We reviewed the histological (light microscopy) findings in 1553 biopsies obtained after surgery for gallbladder disease and correlated these with demographic characteristics of patients. Cancer of the gallbladder was present in 6.1%. Women prevailed in all age and disease groups, especially in mapuches (11:1). Both for neoplastic and nonneoplastic disease the proportion of patients with mapuche surnames was lower than expected for the population in the area. 52% of neoplastic lesions were not macroscopically apparent. Seven tumors involved only the mucous layer and 2 were intraepithelial. Only 2 tumors were well differentiated. The liver was the organ most frequently invaded by gallbladder cancer.

[Study and application of the DNA pattern in oncology]. / Estudio y aplicación del patrón de ADN en oncología.

Abnormalities of DNA content are commonly observed in malignant tumors. Clinically relevant information may be obtained given the ease with which DNA pattern can be studied. Flux cytometry and photocytometry are the methods commonly used and both measure the emission of fluorescence after staining the nucleus. ADN pattern has been found to be related to prognosis in many tumors. Also, precancerous lesions and tumor heterogeneity can be analyzed by this technique.

[Nucleolar organizer regions in gastric cancer]. / Regiones del organizador nucleolar en el cáncer gástrico.

Nucleolar organizer regions may be observed by colloidal silver stains. A considerable increase in the number of regions may be observed in tumors and other pathologic processes as an index of cellular proliferation. Among 20 studies in patients with gastric carcinoma we found a significantly greater number of nucleolar organizer regions in well differentiated tumors as opposed to less differentiated ones. No difference was found in nucleolar organizer regions between seal ring cell tumors and adenocarcinoma.

[Carcinoma hepatocellular. Description of verified clinical characteristics in a region of Southern Chile]. / Hepatocarcinoma. Descripción de características clínicas verificadas en una Región del sur de Chile.

BACKGROUND: Hepatocellular carcinoma is the most frequent primary tumor of the liver. It is associated to chronic liver diseases and has a high prevalence in some regions of Africa and Asia. AIM: To describe the clinical characteristics of patients with hepatocellular carcinoma, admitted to two hospitals of the IX region of southern Chile. MATERIAL AND METHODS: Prospective study of 29 consecutive patients admitted to two hospitals in Temuco, Chile. Clinical features, laboratory values and viral markers were analyzed. RESULTS: Eighteen patients were male and ages ranged from 29 to 75 years old. The most frequent presenting symptom was abdominal pain in 21 patients. Seven subjects had a history of alcoholism. Serum bilirubin values ranged from 0.1 to 15.8 mg/dl, alkaline phosphatases ranged from 171 to 3476 U/l, ASAT from 24 to 5400 U/l and alpha feto protein from 1.4 to 350 ng/ml. Two patients had a positive hepatitis B surface antigen and all had negative hepatitis C virus antibodies. Mean tumoral diameter was 9.6 cm and the most common presentation was nodular. Mean survival after the diagnosis was 6.3 months. CONCLUSIONS: These patients with hepatocellular carcinoma have a low frequency of positive viral markers and tumors of large sizes on presentation.

[Hepatocellular carcinoma. General aspects of diagnosis and treatment]. / Carcinoma hepatocelular. Aspectos generales del diagnóstico y tratamiento.

Hepatocellular carcinoma is the most frequent form of primary hepatic cancer and has a high dissemination capacity. About 90% of tumors develop over a pre-existing cirrhosis but they also may occur in a normal liver. It has a higher frequency among males and 80% of tumors have clinical manifestations. It is associated to hepatitis B and C virus infection, alcoholism, cirrhosis of any etiology, consumption of aflatoxin Bl, oriental race and familial history. Patients are staged using classifications proposed by Okuda, Child-Pugh and the performance status test. Alpha feto protein is useful for diagnosis and follow up Abdominal ultrasound, hepatic scintiscan, angiography with lipiodol, CAT scan and nuclear magnetic resonance have a high diagnostic yield. Non surgical therapeutic alternatives include intratumoral alcoholization, chemoembolization and other such as tamoxifen and monoclonal antibodies. Surgical treatment is based on hepatic resection, whose magnitude depends on hepatic function. Hepatic transplantation is a new therapeutic alternative for patients in whom resection is not feasible and have a single small tumor without metastases.

[Gallbladder cancer: anatomic and anatomo-pathologic considerations]. / Cáncer de la vesícula biliar: consideraciones anatómicas y anatomopatológicas.

Gallbladder cancer is a common neoplasia in Chile. Subclinical forms constitute 30 to 50% of all cases and poorly differentiated lesions are more common in Chile than elsewhere. Traditional grading of this neoplasia according to the degree of wall infiltration neglects important aspects such as the discontinuity of the muscular layer, heterogeneity of the subserosa, microinvasion of the mucosa and Rokitansky-Aschoff sinuses. All of these factors may influence prognosis. Surgical biopsy of liver and lymph nodes in cases without infiltration of the mucosa has revealed up to 60% rate of hepatic infiltration and a somewhat lower on for lymph nodes. We have designed a study that will evaluate the importance of all these factors in the prognosis of gallbladder cancer in our institution.

[Stomach neoplasms in the IX Region of Chile: comparison of the anatomo-pathological study of lymph node emptying in 2 periods]. / Cáncer gástrico en la IX Región de Chile. Comparación del estudio anatomopatológico de vaciamientos ganglionares linfáticos en dos periodos.

Complete resection of lymph nodes may help achieve a cure in patients with gastric cancer. In this paper we evaluate the yield of a careful search for lymph nodes in fresh tissue obtained immediately after resection. A mean of 42.5 nodes per gastric piece was obtained, which is significantly higher than that previously reported with examination of fixed tissue. The yield was higher for all node groups except the left para-cardial one.