Phase II study of gemcitabine and cisplatin in patients with advanced or metastatic bladder cancer: long-term follow-up of a 3-week regimen.

BACKGROUND: Bladder cancer is the fifth most common cancer among men and the seventh among women. At diagnosis, at least 25% of bladder cancer tumors are locally or systemically advanced. Systemic chemotherapy is the only current modality for advanced or metastatic transitional cell carcinoma of the bladder. Recently, a phase III randomized study has demonstrated that the regimen with gemcitabine (GMC) and cisplatin (CDDP) had a survival advantage similar to the standard M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin), with a better safety profile. AIM: It was the aim of this study to evaluate the tumor response rate, the median time to progression, the median survival and toxicity in a 21-day schedule with GMC and CDDP in patients with advanced/metastatic bladder cancer. PATIENTS AND METHODS: From September 1998 to December 2000, 27 patients with advanced/metastatic transitional cell carcinoma were enrolled. All patients received 1,200 mg/m(2) GMC administered as a 30-min intravenous infusion on days 1 and 8, and 75 mg/m(2) CDDP as a 1-hour infusion on day 2. Cycles were repeated every 21 days. The patients had a median age of 59.8 years (range 39-75) and an Eastern Cooperative Oncology Group performance status of 0-2. RESULTS: Twenty-five patients were valuable for toxic effects, length of survival and tumor response. The statistical analysis was performed in May 2004. Mean and median follow-up were 20.23 and 13.2 months (range 2-68), respectively. The overall remission rate (complete response + partial response) was 48% (95% CI 28.4-67.6%). The median time to progression was 9 months (range 2-56). The median duration of survival for all patients was 13.2 months (range 2-68+), with 1-year and 23-month survival rates of 60 and 20%, respectively. There was no grade 4 toxicity or treatment-related death. Grade 3 anemia was observed in 4 patients (16%) and grade 3 thrombocytopenia occurred in 6 patients (24%). No grade 3-4 nausea/vomiting or neutropenia was observed. CONCLUSION: GMC and CDDP is an active schedule with a good safety profile in a 21-day regimen. It may be a valid alternative to the standard 28-day regimen due to its high tumor response and survival with a low incidence of toxicity, especially in pretreated and metastatic patients.

[Esophageal leiomyoma: ultrasonographic endoscopic diagnosis]. / Leiomioma dell'esofago: diagnosi ecoendoscopica.

Leiomyoma is the most frequent benign neoplasia of the esophagus. It is generally diagnosed, accidentally during a radiologic examination (filling defect with clear and regular margins) or endoscopically (sessile, hemispheric, covered by pink mucosa). Recently, to the above conventional exams, endoscopic ultrasonography has been added allowing to identify the single layers of the esophageal wall, thus furnishing useful informations on the morpho-structural characteristics of the leiomyoma. From October '94 to May '96, at the Endoscopy Service of the Institute of Oncology of the University of Messina, 12 patients, 8 males and 4 females, ranging from 39 to 69 years of age (median age 55.4) underwent EUS for suspect leiomyoma. An Olympus EU-M20 echoendoscope was used with a radial scan transducer of 12 Mhz. In 8 patients the leiomyoma was located in the III mid-esophagus, while in 4 patients the III inferior portion was interested. The Authors observed lesions ranging in size from 0.5 to 2.5 cm. In their experience, a suspect of leiomyoma represents a good indication for an endoscopic ultrasonography, which shows high sensitivity and specificity.

Helicobacter pylori: a comparison of some diagnostic methods.

We evaluated the performances of three methods (urease-test, cytology and culture) for the detection of Helicobacter pylori infection Fifty-five patients, 28 men and 27 women (ages, 19-77 years) were included in the study. Helicobacter pylori have been detected by urease-test in 41 patients (74.5%), by culture in 39 patients (70.9%), by cytology in 32 patients (58.1%). Urease-test and culture are direct and specific methods in diagnosing Helicobacter pylori infection.

[Sedation in endoscopic diagnosis: rationale of the use of specific benzodiazepine antagonists]. / Sedazione in diagnostica endoscopica: rationale d'uso degli antagonisti specifici delle benzodiazepine.

The aim of this study was to evaluate the best clinical use of Flumazenil, a specific antagonist of benzodiazepines, during endoscopic exams. Two-hundred patients were studied: 120 were treated with Flumazenil and 80 with placebo. The patients were prepared for the endoscopic exam with local anaesthesia and i.v. Diazepam administration. Controls performed at the end of the exam and at 5, 30, 120 e 240 minutes from the administration of Flumazenil and placebo, allowed to evaluate the state of awakeness, the level of conscience and the capacity of time-space orientation. Significantly statistical differences between the two groups were obtained at 5, 30 and 120 minutes after Flumazenil administration, while both groups had retrograde amnesia. The drug was well tolerated and there were no undesiderable side effects or reactions. The Authors therefore affirm that Flumazenil, in virtue of its competitive action toward benzodiazepine receptors, interrupts sedation with immediate awakening and improvement of the state of consciousness. Such drug, thus, permits the Day Hospital performance of endoscopic procedures which otherwise would require hospitalization, at the same time allowing the surgeon to use benzodiazepines at doses more adequate for surgical necessities.

[Use of endoscopic ultrasonography in the staging of esophageal tumors]. / L'impiego dell'ecoendoscopia nello staging dei tumori esofagei.

Endoscopic Ultrasound (EUS) was performed in 15 patients with esophageal and cardial carcinoma with the aim to evaluate intramural or extraesophageal invasion and regional lymph node metastases. In 10 patients the Authors correctly evaluated the tumoral depth invasion. In 5 patients mediastinal lymph node metastases were observed. It is concluded that EUS is a useful diagnostic method in the staging of esophageal carcinoma.

Comparative prognostic value of Ki-67 and MIB-1 proliferation indices in breast cancer.

BACKGROUND: Tumor proliferation index was evaluated in 246 samples of breast carcinoma using Ki-67 and MIB-1 monoclonal antibodies on frozen and paraffin sections, respectively, with the purpose to compare the two proliferation indices from both a quantitative and prognostic point of view. MATERIALS AND METHODS: All determinations were performed with the same immunohistochemical procedure (Avidin-Biotin Complexes). The prognostic relevance of tumor proliferation index, defined by both the antibodies, was investigated in 127 patients. Ki-67 and MIB-1 median values were used to obtain two groups of patients at different risk and life-table analysis (Mantel-Cox) was performed to assess the probabilities of overall survival (OS) and relapse-free survival (RFS). The median time of observation was 61 months. RESULTS: Ki-67 and MIB-1 values were exponentially distributed with overlapping ranges varying from 2% to 90%. Ki-67 mean and median values were 16.7% and 14.0%, respectively, compared to 22.5% and 20% for MIB-1. Ki-67 and MIB-1 mean values were statistically different (t = -4.396; p < 0.001), while no difference was observed for MIB-1 mean values on frozen and paraffin sections (t = 1.35; p = n.s.). Ki-67 and MIB-1 values were statistically correlated (Spearman's coefficient = 0.75; p < 0.0001) and directly associated (agreement rate = 79.3%; p < 0.0001). Patients with tumors having a high proportion of MIB-1 positive cells showed a higher 5-year probability of relapse of disease (43.7% versus 27.6%; p = 0.02) and death (35.4% versus 15.8%; p = 0.007) than those with a low one. In parallels Ki-67 was found to be prognostically relevant for OS (32.2% versus 16.2%; p = 0.02) but not for RFS (40.7% versus 27.9%; p = 0.10). CONCLUSIONS: Such results indicate that the detection of proliferative activity on paraffin sections with MIB-1 monoclonal antibody provides in formation analogous to or even better than that obtained with Ki-67 antibody on frozen ones. Moreover, it represents a valuable tool to obtain kinetic data on "routine" histological samples and, above all, to give prognostic evaluations on the clinical outcome of breast cancer patients.

[Anesthesiological methods in acoustic neuroma surgery using the translabyrinthine approach]. / Condotta anestesiologica nella chirurgia del neurinoma dell'acustico per via translabirintica.

Removal of acoustic neuromas may often imply anesthesiological as well as surgical problems, especially in the case of large tumors (> 3 cm) which may have come into contact with vital neighbouring structures (brain stem, cerebellum). In this paper the use of two different anesthesiological methods during the translabyrinthine approach is analyzed and discussed in the light of the different needs in this type of surgery. More specifically, anesthesia maintenance was assured by constant infusion of either Propofol (4 mg/kg/h) or Isoflurane (1-1.5%). Withdrawal of curarization was also planned in order to allow the surgeon to take advantage of routine intraoperative facial nerve monitoring. Arterial pressure, CO2 and O2 were assessed at prefixed phases of the operation. Both anesthesiologic methods proved to be satisfactory during the entire surgical procedure. During dissection of the tumoral capsule, an increased heart rate (7% of the initial value) was noticed, whilst in only three patients (with tumors larger than 3.5 cm) a severe bradycardia, which did not respond to Atropine administration and which subsided spontaneously during temporary suspension of surgical manoeuvres, occurred. After this preliminary experience, the Authors believe that both techniques could have a major role in translabyrinthine acoustic tumor surgery and auspicate their further application.