Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma.

PURPOSE: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels. PATIENTS AND METHODS: Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. RESULTS: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. CONCLUSION: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.

Fine needle aspiration of metastatic epithelioid angiosarcoma: a report of 2 cases.

BACKGROUND: Epithelioid angiosarcomas (EAs) are uncommon mesenchymal tumors occurring in the thyroid, deep-seated soft tissues, parenchymal organs and, more rarely, superficial soft tissues of the head and neck. Due to their cytologic and immunocytochemical presentation on fine needle aspiration cytology (FNAC) samples, these neoplasms may closely mimic a number of different tumors, potentially causing an erroneous cytopathologic diagnosis unless immunophenotypical markers of vascular differentiation are sought in the cellular material. CASES: A 68-year-old man with a 1-year history of total thyroidectomy for EA presented with a suspicious right neck node and underwent FNA. A 63-year-old woman with a history of recurring multiple scalp nodules diagnosed as EA ultimately developed small multiple, bilateral lymph nodes in the neck and underwent FNA. In both cases a cytopathologic diagnosis of metastatic EA was made. CONCLUSION: The cytopathologic diagnosis of EA is a challenge. Knowledge of the clinical history is of great help in diagnosing metastatic lesions. The cytopathologicpicture of metastases is a useful way for cytopathologists to gain confidence with presentaton of this rare entity in primary sites on FNAC samples. Cytopathologic hints of vascular differentiation should be sought in the cytopathologic material when a diagnosis of EA is entertained.

Efficacy of a haemostatic matrix for the management of bleeding in patients undergoing liver resection: results from 237 cases.

BACKGROUND: The haemostatic matrix (FloSeal) is a topical agent that provides effective haemostasis in a range of surgical applications. We evaluated this sealant for intraoperative haemostatic effectiveness in an observational series of patients undergoing surgery for the resection of primary and metastatic liver tumours. METHODS: A haemostatic matrix was applied directly to areas of bleeding. The severity of bleeding before and after application was graded on a 5-point scale (0 = no bleeding, 1 = oozing, 2 = moderate blood flow, 3 = heavy blood flow, 4 = spurting blood). The time to complete haemostasis was also recorded. RESULTS: 105 women (age 61 +/- 9 years) and 132 men (age 61 +/- 12 years) were included in this study. One hundred and seventeen patients (49.36%) had pre-operative coagulopathy resulting from co-existent cirrhosis (67 Child-Pugh Class A; 50 Child-Pugh Class B). Prior to administration of a haemostatic matrix, 93 bleeding sites (24.8%) had a bleeding severity score of 2, 269 bleeding sites (71.7%) had a score of 3 and 13 bleeding sites (3.5%) had a score of 4. Following administration of the haemostatic matrix, bleeding stopped completely (score of 0) at 367 (97.9%) of the 375 sites and was reduced to a score of 1 at the remaining 8 sites (2.1%), of which only 2 were in patients with coagulopathy. The mean time to achieve haemostasis in the overall population was 2.9 +/- 1 min; this was significantly increased in patients with coagulopathy versus noncoagulopathic patients (4 +/- 1 vs. 2 +/- 1 min, p < 0.001). CONCLUSIONS: In this prospective, uncontrolled study of 237 consecutive patients undergoing major hepatic surgery to remove primary or metastatic tumours, application of a haemostatic matrix provided rapid and effective intraoperative control of mild to severe bleeding from the liver edge, even in patients with prolonged bleeding times resulting from cirrhosis. This preliminary evidence warrants a randomised, controlled clinical trial with a larger sample size.

Ultrasound contrast media in the study of salivary gland tumors.

BACKGROUND: The aims of the present study were: to assess standard ultrasound and color-Doppler patterns for the study and characterization of salivary gland tumors; to define the improvement in the color-Doppler ultrasound image after injection of a signal amplifier (Levovist); to compare morphological and vascular aspects of the neoplasm with data obtained during postoperative histopathological analysis. MATERIALS AND METHODS: We used color-Doppler ultrasound before and after injection of the contrast medium to study 56 patients (32 males and 24 females) between the ages of 28 and 77 years old, presenting nodular pathology of the salivary glands. Only patients with less than optimal results of the basic color-Doppler examination (grade of vascularization 0-1) were included in the study. The data were then compared with the final histological results. RESULTS: According to B-mode ultrasonography, all neoplasms were hypoechogenous; 8 showed irregular margins and, of these, 6 were carcinomas. We did not obtain significant data regarding size and echostructure. In 10 cases, we observed the presence of multiple locoregional formations in the lymph nodes. Patients were selected on the basis of unsatisfactory color-Doppler examination results; following injection of the contrast medium, we were able to visualize an increased number of vascular signals in 40 out of 56 patients, compared to the basic examination. This enabled us to better assess the vascular map of the neoplasms, as well as more easily trace the vascular blood flow and perform a better extrapolation of the quantitative and semi-quantitative data. This study demonstrated the importance of the vascular pattern, which is predictive of a malignant lesion when it is high-grade with multiple vascular poles and irregular vascular distribution. Furthermore, certain semi-quantitative parameters proved to be important, particularly the velocity of the systolic peak (SP), the cut-off of which was approximately 25 cm/s. The resistance index (RI) and pulsality index (PI) did not prove significant and showed overlapping values. CONCLUSION: We observed that the contrast medium was useful in characterizing lesions, of the salivary glands by allowing for a more precise vascular map of the lesions, as well as greater diagnostic accuracy in tracing the vascular blood flow and calculating quantitative and semiquantitative data.

An assessment of hepatitis C virus infection among health-care workers of the National Cancer Institute of Naples, Southern Italy.

BACKGROUND: As many people with chronic hepatitis C virus (HCV) infection are asymptomatic, HCV infection could spread easily among the health-care workers of the National Cancer Institute of Naples (especially before the identification of HCV and in the absence of good, effective preventative measures, e.g. sterile syringe use, gloves, protective glasses). METHODS: In order to determine whether there is a transmission risk for HCV infection from patient to health-care worker, we carried out a cross-sectional study of a cohort of National Cancer Institute health-care workers in Naples, Southern Italy. RESULTS: The chi2-test was not significant; we did not find any significant risk for HCV in the 'other untrained staff' group [odds ratio (OR) 2.2; 95% confidence interval (CI) 0.4-10.9] or in the health-care workers group (OR 1.6; 95% CI 0.4-7.0). In the health-care worker subgroups, doctors were the reference category because of the low prevalence of HCV in this subgroup (3.3%). A non-significant association was found in the professional nurses group (OR 2.7; 95% CI 0.8-8.8), as well as in the categories of technicians and biologists. CONCLUSIONS: No excessive risk was found among the health-care workers as a whole or among the different categories of personnel, confirming that health-care employees have benefited sufficiently from preventative measures.

Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Radiofrequency ablation (RFA) offers an alternative treatment in some unresectable hepatocellular carcinoma (HCC) patients with disease confined to the liver. We prospectively evaluated survival rates in patients with early-stage, unresectable HCC treated with RFA. METHODS: All patients with HCC treated with RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated. Patients were treated with RFA by using a percutaneous or open intraoperative approach with ultrasound guidance and were evaluated at regular intervals to determine disease recurrence and survival. RESULTS: A total of 194 patients (153 men [79%] and 41 women [21%]) with a median age of 66 years (range, 39-86 years) underwent RFA of 289 sonographically detectable HCC tumors. All patients were followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients, respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic. The overall complication rate was 12%. Overall survival rates at 1, 3, and 5 years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively. CONCLUSIONS: Treatment with RFA can produce significant long-term survival rates for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed in these patients with relatively low complication rates. Confirmation of these results in randomized trials should be considered.

Docetaxel plus epidoxorubicin as neoadjuvant treatment in patients with large operable or locally advanced carcinoma of the breast: a single-center, phase II study.

BACKGROUND: The objective of this study was to test the activity and toxicity of epirubicin plus docetaxel as primary chemotherapy for women with large, operable (T2; > 3 cm) or locally advanced (Stage III) breast carcinoma, including patients with inflammatory breast carcinoma. METHODS: In this single-center, open-label, single-stage, Phase II trial, epirubicin (75 mg/m(2); intravenous bolus) followed by docetaxel (80 mg/m(2); 1-hour intravenous infusion) was administered on Day 1 of each cycle for four cycles. RESULTS: Nine of 30 patients (30%) had inflammatory breast carcinoma. Twenty-three patients (76.7%; 95% confidence interval, 57.7-90.1) had a clinical objective response that was complete in 6 patients (20%). Twenty-seven patients (90%) underwent surgery that was conservative in 5 patients (16.7%). Pathologic response evaluation revealed four complete responses (13.3%; 95% confidence interval, 3.8-30.7). Grade 4 neutropenia was recorded in 80.0% of patients, and febrile neutropenia was recorded in one-third of patients. Anemia and thrombocytopenia were never severe. Other side effects were diarrhea (26.6%), oral mucositis (43.3%), and emesis (26.6%). CONCLUSIONS: Neoadjuvant chemotherapy with epirubicin plus docetaxel was a feasible treatment and was active in an unfavorable series of patients with locally advanced breast carcinoma, including patients with inflammatory breast carcinoma.