Prognostic role of pericardial fluid cytology in cardiac tamponade associated with non-small cell lung cancer

BACKGROUND ANd STUDY OBJECTIVES: Cardiac tamponade is a life-threatening complication of non-small cell lung cancer (NSCLC). Malignant pericardial effusion signifies advanced disease, but the significance of a negative pericardial fluid cytology in patients with advanced lung cancer is still controversial. The differential diagnosis of cytology-negative pericardial effusion is difficult and sometimes impossible. The purpose of this study is to determine the prognostic role of pericardial fluid cytology in patients with NSCLC and cardiac tamponade. DESIGN: Retrospective review of patients with concurrent NSCLC and cardiac tamponade over a 10-year period. METHODS AND RESULTS: Eighty-two patients were included in this study. Pericardial fluid cytology was positive in 60 patients and negative in 22 patients. The overall median survival was 74.5 days, and 1-year survival was 7.3%, with no survival difference between the two groups (p = 0.2506). However, there was a significant survival difference after different treatment strategies. Patients receiving systemic chemotherapy survived longer than those receiving local therapy (p<0.001), and these patients, in turn, survived longer than those receiving supportive treatment (p<0.001). CONCLUSIONS: When patients have concurrent advanced NSCLC and cardiac tamponade, the most likely cause of the pericardial effusion is the cancer itself, regardless of the results of the cytologic examination. Our results suggest that systemic chemotherapy might prolong survival in such patients, but further prospective, randomized study is necessary.     

Prognosis and recurrent patterns in bronchioloalveolar carcinoma

STUDY OBJECTIVE: Bronchioloalveolar carcinoma (BAC) is an uncommon pulmonary neoplasm with various radiologic and clinical presentations. In this article, we analyze the initial radiologic findings, TNM stagings, surgical types, and radiologic features of recurrence, and correlate them with patient survival. DESIGN: A retrospective review of 93 patients who underwent resection for BAC from February 1989 to May 1999. PATIENTS: There were a total of 153 patients with BAC diagnosed during this period. Among them, 60 patients (39.2%) had diffuse disease and received medical therapy only, and the remaining 93 patients (60.8%), who had localized disease, underwent surgical resection. Patients who received surgical resection were enrolled in this study. MEASUREMENTS: Data regarding demographics, presentation symptoms, initial radiologic features, surgical type, tumor staging, recurrence status, radiologic patterns of recurrence, and survival were obtained from all patients. RESULTS: Female patients were significantly younger than male patients. Patients who were female, nonsmoking, undergoing curative surgery, lobectomy, or bilobectomy, and with early tumor staging and no nodal involvement had a better prognosis. Patients with a right lung tumor had a longer survival than those with a left lung tumor, with borderline significance. Among those who suffered from recurrent diseases, a second resection yielded a better survival. Multivariate analysis showed curative surgery, initial surgical type, recurrence status, radiologic patterns of recurrence, and duration from surgical resection to recurrence all had a significant impact on survival. CONCLUSIONS: Those patients with localized, early-stage BAC who underwent curative surgery had a better survival. Patients with localized recurrence after the initial surgery warranted a second resection. Those with a diffuse radiologic pattern of recurrence and/or early recurrence had a worse prognosis.     

A phase II trial of vinorelbine and cisplatin in previously untreated inoperable non--small-cell lung cancer

Weekly vinorelbine injection with cisplatin had been used in treatment of non-small-cell lung cancer. We performed a phase II trial to evaluate the efficacy and toxicity of a new schedule of vinorelbine and cisplatin in patients with previously untreated, inoperable (stage IIIB or stage IV) non-small-cell lung cancer. From April 1996 to May 1997, 52 patients were enrolled for study, and 50 patients were eligible and evaluable for both response and toxicity assessment. Therapy consisted of vinorelbine, 30 mg/m2, intravenously on days 1 and 5 of a 21-day cycle, and cisplatin 100 mg/m2 (reduced to 80 mg/m2 after the first seven patients) given on day 1. A total of 211 treatment courses were administered; the median number of cycles administered per patient was 4.5 (range: 1-6), the median dose intensity for vinorelbine was 16.9 mg/m2/week (84.4%), whereas that of cisplatin was 22.8 mg/m2/week (84.7%). Twenty-five patients responded to therapy for an overall response rate of 50%; one patient attained a complete response (2%). The main toxicities were vomiting, myelosuppression, and diarrhea, which included World Health Organization grade 3 or 4 nausea/vomiting (58% patients), anemia (41% patients), neutropenia (12% patients), and diarrhea (14%). The median duration of responses was 9 months. The median time to disease progression was 6.8 months (range 0.4-18.1 months). Median survival was 13 months, and 54% of patients were alive at 1 year. We conclude that this new schedule of vinorelbine and cisplatin achieves a high response with acceptable toxicity profile in patients with advanced non-small-cell lung cancer.     

Phase II randomized trial of tri-weekly versus days 1 and 8 weekly docetaxel as a second-line treatment of advanced non-small cell lung cancer

BACKGROUND: For orientals, titrating doses of docetaxel (60-66 mg/m(2)) have shown equal effectiveness and fewer side effects as a second-line chemotherapy for patients with advanced non-small cell lung cancer (NSCLC). Under such doses, there were no comparative data between classic tri-weekly and Days 1 and 8 weekly schedules. METHODS: This Phase II randomized prospective study was designed to compare the toxicity profile, efficacy and quality-of-life (QOL) between these two schedules of docetaxel in the treatment of previously treated patients with advanced NSCLC. Fifty patients were randomized to docetaxel arm A (66 mg/m(2) Day 1) and B (33 mg/m(2) Days 1 and 8) given every 3 weeks. RESULTS: The overall response rates (ORRs) were 12 and 24% in arm A and B, respectively (P = 0.46), and disease control rates were 52 and 48%. The median time-to-progression (TTP) was 11.3 and 12.7 weeks and median survivals were 33.4 and 27.6 weeks, respectively. Both arms have same 1 year (36%) and 2 year survivals (12%). Arm A had significantly higher neutropenia but less compromised QOL. In this study, the response of second-line chemotherapy was significantly better in the group that was response to front-line chemotherapy (P = 0.032). CONCLUSIONS: While Days 1 and 8 weekly docetaxel schedules show higher ORR and less hematological toxicity, there is no advantage to tri-week schedule in terms of TTP and survival, but more compromised QOL.     

Modified devascularization surgery for isolated gastric varices assessed by endoscopic ultrasonography

Background This study aimed to assess the role of endoscopic ultrasonography (EUS) in the surgical management of isolated gastric varices (IGV), and to report the authors experience in the treatment of IGV with modified devascularization surgery.Methods In this study, 26 cirrhotic patients with IGV were treated with devascularization surgery for variceal hemorrhage. Preoperatively, percutaneous transhepatic portography (PTP) and EUS were used to determine the mode of therapy for IGV. Fundectomy was performed for 14 patients with fundic IGV, whereas 12 patients with cardiac IGV underwent proximal gastrectomy.Results A significantly higher proportion of patients with cardiac varices showed grade 3 IGV on preoperative EUS than those who had fundic varices (p < 0.05). No major complications were observed during or after the operation, and only one patient died of prolonged shock and massive transfusion. Postoperatively, gastric varices had been eradicated completely in 25 of 26 patients, as determined by EUS study. During a mean follow-up period of 50 months, two patients had recurrent varices without bleeding, as demonstrated by EUS. The overall 5-year survival rate for the fundic IGV group was 67.9%, whereas that for the cardiac IGV group was 64.3% (p > 0.05).Conclusions This study showed that devascularization surgery is highly effective for the prevention of recurrent bleeding from IGV and provides an alternative treatment method. Preoperatively, EUS is very helpful in detailed devascularization of patients with specific IGV, and may be used also for postoperative follow-up evaluation.     

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

Cyclooxygenase-2 (COX-2) expression is increased in breast cancer and surgery has been shown to increase the growth of metastatic tumours. We investigated the effect of selective COX-2 inhibition on the growth of metastases in either an experimental metastasis model or following excision of a murine primary breast tumour. 50,000 4T1 mammary carcinoma cells were injected into the mammary fat pad of female BALB/c mice. When the mean TD reached 8+/-0.4 mm, tumours were excised and the mice were randomised into two groups (n=12 per group) to receive daily intraperitoneal injections of the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days. Alternatively, experimental metastases were established by tail-vein injection of 50,000 4T1 cells. Mice received either the selective COX-2 inhibitor, SC-236 or drug vehicle for 14 days (n=12 per group). SC-236 treatment significantly reduced tumour burden, the number and size of spontaneous metastases following primary tumour excision. SC-236 treatment also reduced tumour burden, the number and size of experimental metastases. Immunohistochemical staining demonstrated that COX-2 inhibition reduced microvessel density and increased apoptosis within both spontaneous and experimental metastases. These data clearly demonstrate that the selective COX-2 inhibitor, SC-236, has potent antimetastatic activity against both spontaneous metastases arising following primary tumour excision and experimental metastases.     

Glycoprotein C of herpes simplex virus type 1 is required to cause keratitis at low infectious doses in intact rabbit corneas

PURPOSE: To determine whether the herpes simplex virus type 1 (HSV-1) viral glycoprotein C (gC) plays a role in induction of keratitis in unscarified and scarified rabbit eyes. MATERIALS AND METHODS: A gC deletion mutant (DeltagC) was constructed and then rescued back to wild type (wt) for use as a control. Following ocular infection with each virus in rabbit eyes, with or without prior corneal scarification, keratitis was compared. RESULTS: At low infection doses of 2 x 10(3) and 2 x 10(4) plaque-forming units (PFU)/eye, in unscarified cornea, DeltagC produced significantly less keratitis than did wt virus (p = 0.007 and 0.03, respectively). In contrast, the keratitis induced by DeltagC was similar to that induced by the wt virus (p > 0.60) in scarified cornea. At high infection dose (2 x 10(5) PFU/eye), keratitis induced by DeltagC was similar in scarified and unscarified cornea, and the severity of disease was similar to that seen in scarified eyes at the low-dose DeltagC infections. Interestingly, although DeltagC induced keratitis with or without corneal scarification at high infection doses, the severity of disease was significantly less than that induced by wt infection. At all infection doses, keratitis induced by wt infection was similar in scarified and unscarified eyes. CONCLUSIONS: These results suggest that (1) at low infection doses, in unscarified corneas, gC is required for HSV-1 induced keratitis; (2) corneal scarification prior to infection can circumvent the need for gC at low doses, but (3) at higher doses, gC is required for wild-type levels of keratitis even in scarified cornea.     

Antibody-dependent enhancement of HSV-1 infection by anti-gK sera

We previously reported that vaccination of BALB/c mice with the baculovirus expressed HSV-1 glycoprotein K (gK) or passive transfer of gK purified IgG to naive BALB/c mice causes severe exacerbation of HSV-1 induced corneal scarring following ocular challenge. In addition, a productive chronic infection, rather than a latent infection, is found in most trigeminal ganglia. These phenomena are accompanied by a very high T(H)1+T(H)2 response in the eye (Ghiasi, H., Cai, S., Nesburn, A.B., Wechsler, S.L., 1996. Vaccination with herpes simplex virus type 1 glycoprotein K impairs clearance of virus from the trigeminal ganglia resulting in chronic infection. Virology 224, 330-333; Ghiasi, H., Cai, S., Slanina, S., Nesburn, A. B., Wechsler, S.L., 1997. Nonneutralizing antibody against the glycoprotein K of herpes simplex virus type-1 exacerbates herpes simplex virus type-1-induced corneal scarring in various virus-mouse strain combinations. Invest. Ophthalmol. Vis. Sci. 38, 1213-1221; Ghiasi, H., Hofman, F.M., Cai, S., Perng, G.C., Nesburn, A.B., Wechsler, S.L., 1999. Vaccination with different HSV-1 glycoproteins induces different patterns of ocular cytokine responses following HSV-1 challenge of vaccinated mice. Vaccine 17, 2576-2582). In the studies reported here, we investigated the hypothesis that anti-gK serum produces antibody-dependent enhancement (ADE) of ocular HSV-1 infection. We found that gK vaccinated mice had significantly higher HSV-1 titers in their eyes than gD or mock-vaccinated mice and that anti-gK sera enhanced HSV-1 infection in the macrophage cell line U937. In addition, passive transfer of anti-gK sera to naive mice 24 h prior to ocular HSV-1 challenge also increased viral replication. These results were consistent with ADE of HSV-1 by sera to gK. This suggests that the severely exacerbated corneal disease seen following HSV-1 ocular challenge of gK vaccinated mice is a result of ADE. The ability of gK sera to cause harmful ADE may impact HSV-1 vaccine development.