Garrett L. Walsh

Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer

A retroviral vector containing the wild–type p53 gene under control of a β–actin promoter was produced to mediate transfer of wild–type p53 into human non–small cell lung cancers by direct injection. Nine patients whose conventional treatments failed were entered into the study. No clinically significant vector–related toxic effects were noted up to five months after treatment. In situ hybridization and DNA polymerase chain reaction showed vector–p53 sequences in posttreatment biopsies. Apoptosis (programmed cell death) was more frequent in posttreatment biopsies than in pretreatment biopsies. Tumor regression was noted in three patients, and tumor growth stabilized in three other patients.

Adenovirus-Mediated p53 Gene Transfer in Sequence With Cisplatin to Tumors of Patients With Non–Small-Cell Lung Cancer

PURPOSE To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Survival in early-stage non-small cell lung cancer

The duration of survival in early-stage lung cancer (stages I and II) varies between reports in the literature. Several reasons account for this: patient population heterogeneity, inconsistent staging, anatomic variability, dissimilar tumor morphology, and unpredictable tumor biology. This report addresses some of the issues in early-stage non-small cell lung cancer that relate to variability between estimates of survival in end stage reporting. We review several large series since the introduction of the International Staging System in 1986 and other selected, contemporary reports that address end results in patients with pathologic stage I or stage II lung cancer. Overall survival for patients with pathologic stage I disease is 64.6% (range, 55% to 72%) and 41.2% for patients with stage II disease (range, 29% to 51%). Reducing morphologic differences by placing patients in groups based on the TNM subset and refinement in categorization by matching TNM subsets based on histology and other factors can improve considerably homogeneity and enhance prognostic predictability. The development of more accurate measures for predicting prognosis may serve to clarify the roles of primary and adjuvant treatment, particularly in those patients with early-stage disease associated with poor prognostic factors in whom the potential for long-term survival is reduced.

Surgical Management of Renal Cell Carcinoma With Inferior Vena Cava Tumor Thrombus

BACKGROUND The optimal management of patients with renal cell carcinoma with inferior vena cava tumor thrombus remains unresolved. Traditional approaches have included resection with or without the use of cardiopulmonary bypass. Chemotherapy has played a minor role except for biotherapeutic agents used for metastatic disease. METHODS From January 1989 to January 1996, 37 patients with renal cell carcinoma and inferior vena cava tumor thrombus underwent surgical resection. The 27 men and 10 women had a median age of 57 years (range, 29 to 78 years). Thirty-six patients presented with symptoms; 21 had hematuria. Distant metastases were present in 12 patients. Tumor thrombi extended to the infrahepatic inferior vena cava (n = 16), the intrahepatic inferior vena cava (n = 16), the suprahepatic inferior vena cava (n = 3), and into the right atrium (n = 2). All tumors were resected by inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of the vena cavotomy. Cardiopulmonary bypass was necessary in only 2 patients with intraatrial thrombus. RESULTS Complications occurred in 11 patients, and 1 patient died 2 days postoperatively of a myocardial infarction (mortality, 2.7%). Twenty patients are alive; overall 2- and 5-year survival rates were 61.7% and 33.6%, respectively. For patients without lymph node or distant metastases (stage IIIa), 2- and 5-year survival rates were 74% and 45%, respectively. The presence of distant metastatic disease (stage IV) at the time of operation did not have a significant adverse effect on survival, as reflected by 2- and 5-year survival rates of 62.5% and 31.3%, respectively. Lymph node metastases (stage IIIc) adversely affected survival as there were no long-term survivors. CONCLUSIONS Resection of an intracaval tumor thrombus arising from renal cell carcinoma can be performed safely and can result in prolonged survival even in the presence of metastatic disease. In our experience, extracorporeal circulatory support was required only when the tumor thrombus extended into the heart.

Treatment outcomes of resected esophageal cancer.

ObjectiveTo assess the evolution of treatment and outcome for resected esophageal cancer at a single institution. Summary Background DataStrategies for optimizing the treatment of resected esophageal cancer continue to evolve over time. The outcomes of these evolving treatments in the context of improved diagnostic staging and changing epidemiology have not been carefully analyzed in a single institution. MethodsOne thousand ninety-seven consecutive patients with primary esophageal cancer underwent surgery during the period 1970 to 2001. Nine hundred ninety-four patients underwent curative esophagectomy and were analyzed for changing demographics. Eight hundred seventy-nine patients who did not have systemic metastases and survived the perioperative period were assessed by multivariate analysis for factors associated with long-term survival. ResultsDuring the study period the overall median survival increased from 17 to 34 months, and combined hospital and 30-day mortality decreased from 12% to 6%. The R0 resection rate increased from 78 to 94%, and adenocarcinoma replaced squamous cell carcinoma as the predominant histology (83% vs. 17%). No change in survival with time was noted for patients treated with surgery alone having the same postoperative pathologic stage (pTNM). An increased proportion of patients had preoperative chemoradiation in the last 4 years of the study (59% vs. 2%). Preoperative chemoradiation was associated with a longer survival and increased likelihood of achieving a complete resection. Multivariate analysis showed that long-term survival was associated with a complete resection and the preoperative staging strategy used, while the use of preoperative chemoradiation was the most significant factor associated with ability to achieve an R0 esophageal resection. ConclusionsThis study shows favorable trends in the survival of patients with resected esophageal cancer over time. The increased use of preoperative chemoradiation, better preoperative staging, and other time-dependent factors may have contributed to the observed increase in survival.

Outpatient management of malignant pleural effusion by a chronic indwelling pleural catheter

BACKGROUND Previous studies have shown that a chronic indwelling pleural catheter (PC) safely and effectively relieved dyspnea, maintained quality of life, and reduced hospitalization in patients with malignant pleural effusions. Outpatient management of malignant pleural effusion with a PC may reduce length of stay and early (7-day) charges compared with inpatient management with chest tube and sclerosis. METHODS A retrospective review of consecutive PC patients (n = 100; 60 outpatient, 40 inpatient) were treated from July 1, 1994 to September 2, 1998 and compared with 68 consecutive inpatients treated with chest tube and sclerosis between January 1, 1994 and December 31, 1997. Hospital charges were obtained from date of insertion (day 0) through day 7. RESULTS Demographics were similar in both groups. Pretreatment cytology was positive in 126 of 168 patients (75%), negative in 21 (12.5%), and unknown in 21 (12.5%). Primary histology included lung (n = 61, 36%), breast (n = 39, 23%), lymphoma (n = 12, 7%), or other (n = 56, 34%). Median survival was 3.4 months and did not differ significantly between treatment groups. Overall median length of stay was 7.0 days for inpatient chest tube and inpatient PC versus 0.0 days for outpatient Pleurx. No mortality occurred related to the PC. Eighty-one percent (81/100) of PC patients had no complications. One or more complications occurred in 19 patients (19%). Patients treated with outpatient PC (n = 60) had early (7-day) mean charges of

Is follow-up of lung cancer patients after resection medically indicated and cost-effective?

3,391 +/-

Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: Correlation with pulmonary dose-volume histogram parameters

1,753 compared with inpatient PC (n = 40,

Management of Primary Pulmonary Artery Sarcomas

11,188 +/-

Proposed revision of the esophageal cancer staging system to accommodate pathologic response (PP) following preoperative chemoradiation (CRT)

7,964) or inpatient chest tube (n = 68,