Outcome of invasive mechanical ventilation in cancer patients: Intubate or not to intubate a patient with cancer.

PURPOSE: The outcome of cancer patients who undergo mechanical ventilation has been grim. However, it has lately become more promising, creating hesitation when approaching the decision to intubate a cancer patient. Therefore, the main goal was to find some factors that could predict mortality. MATERIAL AND METHODS: Studies were selected on the basis of their information wholeness, the year done, patients' number, participating country, underlying hematological or nonhematological malignancies, ventilation duration, ICU survival, hospital survival, long term survival, disease activity, and other contributing factors. RESULTS: Twenty-two studies were included which accrued 3115 patients. The average ICU survival was 32.4%, and long-term survival was 10.2%. Over the years, the outcome of cancer patients undergoing mechanical ventilation has improved. The most important predicting factors are: The respiratory failure etiology, the performance status, the disease activity, and the SOFA score. CONCLUSIONS: The aforementioned predicting factors could be used when approaching the decision to intubate. When in doubt, we should give the benefit to the patient, proceed to intubate and reevaluate progress daily and in doing so, we would suggest to use the trends in SOFA score and weaning index to assess success or failure of invasive mechanical ventilation.

Pulmonary alveolar proteinosis: a case report and world literature review.

Pulmonary alveolar proteinosis (PAP) is a lung disorder which was first described in 1958 by Rosen et al. and is indeed rare disease with a prevalence of 0.1 per 100,000 individuals. PAP is characterized by abnormal accumulation of pulmonary surfactant in the alveolar space, which impairs gas exchange leading to a severe hypoxemia. Pulmonary surfactant is an insoluble proteinaceous material that is rich in lipids and stains positive with periodic acid-Schiff (PAS). The most common type of PAP is the so-called autoimmune or idiopathic type. It has been hypothesized that deficiency in granulocyte macrophage-colony stimulating factor (GM-CSF), as a result of the anti-GM-CSF antibody production, is strongly related to impaired surfactant recycling that leads to the accumulation of surfactant in the alveolar space. Its clinical course is variable from spontaneous remission in the best case scenario, going through the entire spectrum of disease severity, towards fatal respiratory failure. Whole lung lavage has been the gold standard therapy in PAP until the advent of GM-CSF. Although the first case was reported to be idiopathic, subsequent analysis revealed that Pneumocystis jirovecii, silica, and other inhalational toxins were able to trigger this reaction. In this study, we report the case of a 52-year-old man who developed PAP syndrome after a 2-year exposure to silica dust. Our review of the world literature that includes 363 cases reported until now, reflects the evolution of science and technology in determining different aetiologies and diagnostic tests that lead to an improved perspective in the life of these patients.

Clinical evaluation of the delivery and safety of aerosolized liposomal 9-nitro-20(s)-camptothecin in patients with advanced pulmonary malignancies.

PURPOSE: The purpose is to evaluate the feasibility and safety of aerosol administration of the topoisomerase I inhibitor, 9-nitrocamptothecin, in a liposome formulation, and to recommend a dosage for a Phase II trial for an 8-week daily treatment schedule. EXPERIMENTAL DESIGN: Patients with primary or metastatic lung cancer received aerosolized liposomal 9-nitrocamptothecin for 5 consecutive days/week for 1, 2, 4, or 6 weeks followed by 2 weeks of rest to determine feasibility. For the Phase I part, the dose was increased stepwise from 6.7 up to 26.6 micro g/kg/day Monday to Friday for 8 weeks followed by 2 weeks of rest. RESULTS: Twenty-five patients received treatment. The mean baseline forced expiratory volume in 1 second for all patients was 85% of predicted. A dose-limiting toxicity was chemical pharyngitis seen after 1 week in 2 of 2 patients at 26.6 micro g/kg/day. At 20.0 micro g/kg/day, grade 2 and 3 fatigue prompting a dose reduction was seen after 4 weeks in 2 of 4 patients. Grade 2 toxic effects included nausea/vomiting (9 patients), cough and bronchial irritation (6 patients), fatigue (5 patients), anemia (4 patients), neutropenia (2 patients), anorexia (1 patient), and skin rash around the face mask (1 patient). 9-Nitro-20(S)-camptothecin (9NC) was absorbed systemically. Partial remissions were observed in 2 patients with uterine cancer, and stabilization occurred in 3 patients with primary lung cancer. CONCLUSIONS: Aerosol administration of liposomal 9NC was found to be feasible and safe. 9NC delivered as an aerosol was detected in patient's plasma shortly after the start of treatment. The recommended dose for Phase II studies is 13.3 micro g/kg/day (equivalent to 0.5 mg/m(2)/day), which constitutes two consecutive 30-min nebulizations/day from a nebulizer reservoir with 4 mg of 9NC in 10 ml of sterile water, Monday to Friday for 8 weeks every 10 weeks.

Induction of p53-regulated genes and tumor regression in lung cancer patients after intratumoral delivery of adenoviral p53 (INGN 201) and radiation therapy.

PURPOSE: We designed a prospective single arm Phase II study to evaluate the feasibility and mechanisms of apoptosis induction after Ad-p53 (INGN 201) gene transfer and radiation therapy in patients with non-small cell lung cancer. EXPERIMENTAL DESIGN: Nineteen patients with nonmetastatic non-small cell lung cancer who were not eligible for chemoradiation or surgery were treated as outpatients with radiation therapy to 60 Gy over 6 weeks in conjunction with three intratumoral injections of Ad-p53 (INGN 201) on days 1, 18, and 32. RESULTS: Seventeen of 19 patients completed all planned radiation and Ad-p53 (INGN 201) gene therapy as outpatients. The most common adverse events were grade 1 or 2 fevers (79%) and chills (53%). Three months after completion of therapy, pathologic biopsies of the primary tumor revealed no viable tumor (12 of 19 patients, 63%), viable tumor (3 of 19 patients, 16%), and not assessed (4 of 19 patients, 21%). Computed tomography and bronchoscopic findings at the primary injected tumor revealed complete response (1 of 19 patients, 5%), partial response (11 of 19 patients, 58%), stable disease (3 of 19 patients, 16%), progressive disease (2 of 19 patients, 11%), and not evaluable (2 of 19 patients, 11%). Quantitative reverse transcription-PCR analysis of the four p53 related genes [p21 (CDKN1A), FAS, BAK, and MDM2] revealed that Bak expression was increased significantly 24 h after Ad-p53 (INGN 201) injection and levels of CDKN1A and MDM2 expression were increased over the course of treatment. CONCLUSIONS: Intratumoral injection of Ad-p53 (INGN 201) in combination with radiation therapy is well tolerated and demonstrates evidence of tumor regression at the primary injected tumor. Serial biopsies of the tumor suggest that BAK gene expression is most closely related to Ad-p53 (INGN 201) gene transfer.

Diagnosis of invasive pulmonary aspergillosis using polymerase chain reaction-based detection of aspergillus in BAL.

STUDY OBJECTIVE: To assess the value of Aspergillus polymerase chain reaction (PCR) test performed on the BAL in diagnosing invasive pulmonary aspergillosis (IPA). DESIGN: Between January 1996 and 1997, we prospectively followed up 249 cancer patients with pulmonary infiltrates suggestive of pneumonia. Bronchoscopy with fungal stains, cultures, and PCR was performed on all patients. PCR was used for the detection of Aspergillus mitochondrial and alkaline protease gene DNA. The PCR products were visualized either directly on polyacrylamide gel or after Southern transfer and probing with specific probes for mitochondrial and alkaline protease DNA. RESULTS: The 249 patients consisted of 10 patients with proven IPA (tissue invasion), 22 patients with probable IPA (microbiologic culture), 18 patients with possible IPA (consistent clinical and radiologic findings), and 199 control patients with no evidence of IPA. PCR positivity was strongly associated with all forms of IPA (p < 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value of PCR were 80%, 93%, 38%, and 99%, respectively, for proven IPA, and 64%, 93%, 52%, and 96%, respectively, for probable IPA. Southern blotting analysis did not improve the diagnostic yield of the PCR test. CONCLUSION: PCR performed on BAL is associated with high specificity and negative predictive value for IPA. The low positive predictive value could be related to the transient colonizing presence of aspergilli in the respiratory tract. The sensitivity correlates with the certainty of the diagnosis based on tissue invasion.