Postmenopausal bleeding and vaginal nodules as the first presenting sign of adenocarcinoma of the gallbladder.

Vaginal submucosal nodules were observed in a 67-year-old woman, with ultrasonographic features of an advanced uterine neoplasm. On biopsy, light microscopy suggested that the lesions might be metastatic foci from an extragenital cancer, with a prevalent tubular growth pattern. Parallel immunohistochemical reactions revealed a diffuse, strong CA 19-9 positivity in both the cell membrane and cytoplasm. Subsequently, high serum levels of such tumor marker were also found, and an extragenital cancer was suspected of pancreatic or biliary origin. A mass in the gallbladder fossa was then detected by computed tomography and a primary gallbladder adenocarcinoma was confirmed on ultrasound-guided biopsy.

Cisapride and dexamethasone in the prevention of delayed emesis after cisplatin administration.

Management of delayed emesis (DE) remains unsatisfactory, and only 50% of the patients achieve complete protection. Cisapride is a strong prokinetic gastrointestinal drug that could have a role in the prevention of DE. We enrolled 31 adult naive outpatients who were scheduled to receive cisplatin chemotherapy at doses of > or = 75 mg/m2. All patients received the same prophylactic treatment for acute emesis (20 mg dexamethasone and 8 mg ondansetron i.v.) and, as preventive therapy for DE, oral cisapride, 10 mg every 8 h on days 2-4, combined with dexamethasone i.m., 8 mg twice daily on days 2 and 3, and 4 mg twice daily on day 4. All patients were evaluable for activity. Complete protection from acute vomiting was 80.7%, from nausea 71% and from nausea/vomiting 64.5%. The overall protection from DE (days 2-4) was 74.1% for vomiting, 64.5% for nausea and 58% for nausea/vomiting. In our study the combination of cisapride and dexamethasone was effective, giving 58% of complete protection from DE, and it is therefore worthy of further studies.

Hepatotoxicity of camptothecin derivatives in a primary culture system of rat hepatocytes.

The topoisomerase I inhibitors are a new class of antineoplastic agents currently under clinical development. Among these compounds there are some camptothecin (CPT) derivatives with improved toxicity profiles and antitumor activity: irinotecan (CPT-11) and topotecan (TPT), particularly active against colon, lung and ovarian cancer. The aim of this study was to evaluate the cytotoxicity of CPT, CPT-11, its metabolite SN38 and TPT in a primary culture system of rat hepatocytes. Cytotoxicity was evaluated by measuring the leakage of lactate dehydrogenase (LDH) into the medium and by assessing cell viability in terms of tetrazolium salts (MTT) reduction by mitochondrial dehydrogenase activity. Our results showed that cytotoxicity was limited in the case of short drug exposure. There was a significant and time-dependent increase in LDH leakage and a significant time- and dose-dependent decrease in MTT reduction after 3 h of incubation (p<0.01). In the treatments with doses related to peak plasma levels, CPT-11 was less responsible for the observed in vitro hepatotoxicity than its metabolite SN38; TPT had lower LDH leakage compared to SN38 and CPT-11 but showed significant and early (3 h) decrease in MTT reduction: this may mean a different mechanism of cellular damage. These results demonstrate that CPT derivatives are directly toxic to liver cells in a distinct time- and dose-related response.

Prognostic significance of the estrogen-regulated proteins, cathepsin-D and pS2, in breast cancer.

The evaluation of prognostic factors for breast cancers is important for therapeutic decisions both at the time of surgery and during postoperative surveillance. Cathepsin-D (cath-D) is an estrogen inducible aspartyl protease. Studies have demonstrated two biological activities, at an acidic PH, of the protein: a mitogenic and a proteolytic activity; both the growth promoting activity and the extracellular proteolytic activity suggest that cathepsin D (cath-D) may have prognostic significance in breast cancer. Measurement of cath-D in breast tissue, in fact, is highly significant in predicting recurrence as well as disease free interval and overall survival. The pS2 is a small cysteine-rich protein specifically expressed under estrogen transcriptional control. Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis and response to tamoxifen: appropriate adjuvant therapy can be selected on the pS2 status of the tumor; patients with pS2 expression had better overall survival and a longer survival time after the first recurrence than those without pS2 expression. For these reasons, these two new prognostic markers could be suggested as habit factors in breast cancer.

The erbB 2 oncogene and chemotherapy: a mini-review.

The erbB 2 gene, also known as Her-2/neu, is an oncogene that encodes a transmembrane glycoprotein receptor. When overexpressed erbB 2 is an indicator of poor prognosis in a number of cancers. Recent studies show that erbB 2 expression plays a role in the prediction of responsiveness to adjuvant treatment: tumors that had an overexpression of the oncogene were less responsive to treatment than those with a normal amount. Some studies on this oncogene have examined the production of anti-erbB 2 monoclonal antibodies and evaluated the combined effect of monoclonal antibody and chemotherapeutics.

Intraperitoneal chemotherapy with mitoxanthrone in ovarian cancer.

AIMS AND BACKGROUND: Ovarian carcinoma remains confined to the peritoneal cavity for the greater part of its natural history, so intraperitoneal (i.p.) administration of chemotherapy could result in greater total drug exposure of the tumor and minimize systemic antiblastic drug side effects. The aim of this study was to evaluate the therapeutic efficacy and toxic effects of intraperitoneal mitoxanthrone in patients affected by ovarian carcinoma with macroscopic absence of disease or minimal residual disease. METHODS: Ten patients were enrolled (stage II and III) who had been previously treated with neoadjuvant systemic chemotherapy (CDDP or CBDCA + CTX) and radical surgery resulting in macroscopic absence of disease or minimal residual disease (< 1 cm). Mitoxanthrone (25 mg/m2) was instilled in 2 liters of normal saline every four weeks for 2-4 cycles. RESULTS: A total of 26 courses was administered; two patients discontinued i.p. therapy, one for chemoperitonitis and another for bowel perforation requiring catheter removal. Of the 10 patients receiving i.p. chemotherapy, 7 are alive at 5 years from radical surgery, and 3 had relapses at 13, 14 and 57 months, respectively, from radical surgery. CONCLUSIONS: Intraperitoneal mitoxanthrone appears to be an effective second-line therapy in ovarian cancer; it is well tolerated as far as toxic effects are concerned, allowing cost reduction and improved patient compliance. For those cases requiring a limited number of peritoneal accesses traditional percutaneous systems have a more favorable cost/benefit ratio.