We found no benefit to therapy directed by pulmonary-artery catheter over standard care in elderly, high-risk surgical patients requiring intensive care.

CSP #221 is a randomized multiinstitutional clinical trial to assess the efficacy of 10 d of perioperative total parenteral nutrition (TPN) in reducing morbidity and mortality in malnourished patients undergoing intraperitoneal and/or intrathoracic operations. In this paper a detailed protocol for the clinical efficacy trial is presented primarily as a reference document for use in interpretation of the results of the clinical trial. It is also anticipated, however, that review of this protocol may be useful to other investigators planning future clinical nutrition intervention trials.

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 x 10(9) plaque-forming units (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.

It is widely believed that the presence of a malignancy causes increased energy expenditure in the cancer patient. To test this hypothesis, resting energy expenditure (REE) was measured by bedside indirect calorimetry in 200 heterogeneous hospitalized cancer patients. Measured resting energy expenditure (REE-M) was compared with expected energy expenditure (REE-P) as defined by the Harris-Benedict formula. The study population consisted of 77 males and 123 females with a variety of tumor types: 44% with gastrointestinal malignancy, 29% with gynecologic malignancy, and 19% with a malignancy of genitourinary origin. Patients were classified as hypometabolic (REE less than 90% of predicted), normometabolic (90-110% of predicted) or hypermetabolic (greater than 110% of predicted). Fifty-nine per cent of patients exhibited aberrant energy expenditure outside the normal range. Thirty-three per cent were hypometabolic (79.2% REE-P), 41% were normometabolic (99.5% REE-P), and 26% were hypermetabolic (121.9% REE-P) (p less than 0.001). Aberrations in REE were not due to age, height, weight, sex, nutritional status (% weight loss, visceral protein status), tumor burden (no gross tumor, local, or disseminated disease), or presence of liver metastasis. Hypermetabolic patients had significantly longer duration of disease (p less than 0.04) than normometabolic patients (32.8 vs. 12.8 months), indicating that the duration of a malignancy may have a major impact upon energy metabolism. Cancer patients exhibit major aberrations in energy metabolism, but are not uniformly hypermetabolic. Energy expenditure cannot be accurately predicted in cancer patients using standard predictive formulae.

Cancer cachexia, a common finding in patients with gastrointestinal (GI) malignancy, is frequently attributed to tumor‐induced aberrations in host energy expenditure. To characterize the frequency and severity of aberrations in energy expenditure in GI cancer patients, and to identify the potential influence of tumor characteristics in this group, the authors measured resting energy expenditure (REE) by indirect calorimetry in 173 patients and compared REE to predicted energy expenditure (PEE) from the Harris‐Benedict formulae based on current body weight. Fifty‐eight percent of patients had abnormal REE (normal REE = ±10% PEE); 36% (62 of 173) were hypometabolic (REE <90% PEE), and 22% (39 of 173) were hypermetabolic (REE >110% PEE). Host and tumor factors were compared between metabolic groups to identify potential determinants of abnormal energy expenditure. Differences between groups cannot be explained by differences in patient age, sex, body size, nutritional status, tumor burden, or duration of disease. Resting energy expenditure does not correlate with percent of weight loss, serum albumin, or duration of disease. Analysis by tumor site reveals patients with pancreatic or hepatobiliary tumors to be predominantly hypometabolic; gastric cancer patients tend to be hypermetabolic, whereas patients with colorectal or esophageal neoplasms are more evenly distributed across metabolic groups, the largest portion being normometabolic (X2 = 20.7, P <0.02). The majority of GI cancer patients have abnormal REE which is unpredictable and not uniformly hypermetabolic. The determinants of these abnormalities do not appear to be age, sex, body size, nutritional status or tumor burden. Primary tumor site is a major determinant of energy expenditure in GI cancer patients. Cancer 53:1265‐1273, 1984.