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Biomedical subjects

W J Hwu

Publications and source records attributed to W J Hwu.

8 recordsLinked to original sources

Treatment of malignant pleural effusions with tunneled long-term drainage catheters.

PURPOSE: To assess the effectiveness of tunneled pleural catheters (TPCs) in the treatment of malignant pleural effusions (MPEs). MATERIALS AND METHODS: Twenty-eight patients with symptomatic MPEs had 31 hemithoraces treated with TPCs placed under image guidance. Chemical sclerotherapy had failed in two patients and two had symptomatic locules. Drainage was accomplished by intermittent connection to vacuum bottles. Pleurodesis was considered achieved when three consecutive outputs were scant and imaging showed no residual fluid. RESULTS: All catheters were successfully placed. Dyspnea improved in 94% (29 of 31 hemithoraces) at 48 hours and 91% (20 of 22 patients) at 30 days. Control of the MPE was achieved in 90% of hemithoraces (28/31), although five required ancillary procedures. Pleurodesis occurred in 42% (13 of 31) of hemithoraces, including both that underwent an earlier attempt at chemical sclerotherapy and one treated locule. Continued drainage without pleurodesis controlled the effusion in 48% (15 of 31). In only 7% was hospital time necessary for care related to the TPC. Early, transient catheter-related pain was common, but only three complications (in two patients) occurred. Neither of these altered patient care. CONCLUSIONS: Regardless of whether pleurodesis is achieved, TPCs provide effective long-term outpatient palliation of MPEs.

Catheters, Indwelling↗

Colonic melanoma, primary or regressed primary.

Primary melanoma originating in the gastrointestinal tract is very rare and the majority of these tumors arise in the mucosa of the anus or rectum. A case of solitary colonic melanoma in a 79-year-old man is described with a review of pertinent literature. The surgically excised neoplasm was evaluated by routine histology and immunohistochemistry stains. Pathologic examination of the excised cecal mass revealed an 8 x 5-cm tan-pink mass with a central green-black necrotic area. Histologically, there were solid sheets of S100- and HMB-45-positive pigmented cells extending from the mucosal ulcerated surface through the bowel wall. The patient had no evidence of cutaneous or ocular primary melanoma. He remained free of recurrent disease 5 years after surgical resection of the colonic melanoma. The unique pathologic features and clinical outcome support the diagnosis of primary colonic melanoma in this patient.

Aged↗

Staging work-up and post-treatment surveillance of patients with melanoma.

Strategies based on evidence are required to accurately stage and effectively follow patients with melanoma. The goal of staging is to define the extent of disease at the time of presentation to direct and assign prognosis. Patient surveillance is performed to assess treatment results and detect recurrences amenable to further treatment. Staging and surveillance require careful use of resources to be cost effective. This article addresses preoperative staging and post-treatment surveillance of patients with melanoma and outlines a method of follow-up based on available data.

Follow-Up Studies↗

Systemic chemotherapy.

The main use of systemic chemotherapy in metastatic melanoma remains palliative. Dacarbazine (dimethyl-1-triazeno imidazole-4-carboxamide [DTIC]) is the standard chemotherapy agent for advanced disease. The combination chemotherapy and biochemotherapy regimens have achieved higher response rates, but have not led to durable remission or improved survival. The field of systemic therapy remains in need of a more effective and less toxic treatment strategy.

Antineoplastic Agents↗

New approaches in the treatment of metastatic melanoma: thalidomide and temozolomide.

Although melanoma is a relatively chemoresistant malignancy, systemic chemotherapy remains the primary treatment for metastatic melanoma. The observation of vasculogenic mimicry in aggressive melanoma has prompted investigation into using an antiangiogenic agent to enhance the antitumor activity of chemotherapy in metastatic melanoma. Thalidomide (Thalomid) exhibits antiangiogenic activity and other biological modulatory effects that may provide additive or synergistic antitumor effects when given concurrently with chemotherapy. A phase I/II study of thalidomide and temozolomide in the treatment of metastatic melanoma is in progress. Preliminary results of this combination therapy have shown significant antitumor activity, including some striking responses in brain metastases.

Adult↗

A clinical-pharmacological evaluation of percutaneous isolated hepatic infusion of doxorubicin in patients with unresectable liver tumors.

A dose escalation study of hepatic arterial infusion of doxorubicin during hemodynamic isolation of the liver (the Delcath system) was conducted to: 1) study the pharmacokinetics of regional doxorubicin therapy, and 2) define therapeutic efficacy in the treatment of unresectable liver tumors. Eighteen patients with unresectable primary or metastatic tumor in the liver were treated with 57 procedures. Pharmacokinetic studies were performed on all treatments. Hepatic extraction ratio of doxorubicin remained constant at 60.3+/-12.1%. independent of the dose escalation. The calculated intrahepatic concentration of doxorubicin ranged from 30 to 88 microg/ml when the dosage of doxorubicin was escalated from 50 to 120 mg/m2. Dose-limiting systemic toxicity (grade 4 myelosuppression) was observed at 120 mg/m2. Twelve of 14 patients who received more than one treatment at 90 or 120 mg/m2 were evaluable for disease response: there were 4 partial responses, 3 minor responses, I stable disease, and 4 progressive disease. The median overall survival of responders was 23 months, and for nonresponders it was 8 months. We have demonstrated a dose-response effect of hepatic infusion of doxorubicin at 90 and 120 mg/m2 in advanced hepatic malignancies. The isolated hepatic perfusion system improves the therapeutic index of doxorubicin and provides pharmacologic justification for its use in the treatment of unresectable hepatic malignancies, especially metastatic melanoma and sarcoma.

Adult↗

Molecular basis for thymidine modulation of the efficacy and toxicity of alkylating agents.

The antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in mice previously was shown to be markedly enhanced by co-administration of thymidine. We have examined the cellular mechanisms underlying the augmentation effect of thymidine. It was found that thymidine did not increase the cytotoxicity of BCNU for B16/F10 melanoma or L1210 leukemia cells in vitro. Instead, thymidine appeared to augment the activity of tumor-specific cytotoxic T-cells in tumor-bearing mice, which specifically rejected a secondary challenge with the B16/F10 tumor. Thus, development of an antitumor immune response is facilitated by thymidine in BCNU-induced immunosuppressed mice. These preclinical studies suggested that combination therapy with alkylating agents and thymidine may be a more efficacious and less toxic anticancer therapy. The potential efficacy of the sequential administration of dacarbazine (DTIC), BCNU, and thymidine in patients with advanced malignant melanoma was investigated. As predicted from animal studies, sequential administration of DTIC, BCNU, and thymidine is a relatively nontoxic therapy for metastatic melanoma. This treatment induced durable responses in up to 35% of patients, and hence is superior to many commonly used toxic combination chemotherapies. The mechanism of action, although not well characterized, is thought to be mediated through protection of the cellular immune process, as well as organ function, from alkylating agent toxicity through modulation of DNA repair enzymes such as O(6)-alkylguanine-DNA alkyltransferase in normal tissue. Thus, thymidine is a biomodulator, which not only protects patients from hematologic, pulmonary, and hepatic toxicities associated with DTIC and BCNU chemotherapy, but also potentiates therapeutic efficacy.

Animals↗