Pleural lavage cytology: Where do we stand?

Although a malignant pleural effusion is considered a manifestation of an advanced stage disease not amenable to curative resection in patients with non-small cell lung cancer, the same is not true in the case of the presence of malignant cells in the pleural cavity without an accompanying effusion, discovered incidentally during the operation with pleural lavage cytology (PLC). PLC is a diagnostic technique used to detect tumor cells and translate this finding to a prognostic index. Various reports have attempted to utilize the results of PLC and draw inferences regarding the origins of malignant cells in the pleural cavity, the association of these results with various disease characteristics and, most importantly, their impact on disease recurrence and survival. However, due to non-consistent techniques and protocols used to acquire the samples for cytological evaluation and assess their significance, results are inhomogeneous. Nevertheless, the entrance of malignant cells in the pleural cavity follows the rules posed by the natural disease process when discovered before pulmonary resection takes place, while surgical manipulations certainly play an important role in the case malignant cells are checked over after pulmonary resection. In addition, although the prognostic significance of a positive PLC result is indisputable and significantly decreases long-term survival in the majority of studies, this factor has not yet been incorporated into the TNM staging system. Lastly, some authors have advocated the use of some form of adjuvant treatment for those patients found with positive PLC results, based on the assumption that a curative resection followed by multiple pleural washings will not remove the entirety of the population of malignant cells present in the pleural space. (C) 2013 Published by Elsevier Ireland Ltd

Postresectional pulmonary oxidative stress in lung cancer patients. The role of one-lung ventilation

Objective: The authors conducted a prospective analysis in order to investigate through lipid peroxidation metabolites the generation of oxygen free radicals after one-lung ventilation (OLV). Methods: From 2001 to 2003, 212 patients were prospectively studied for lung reexpansion/reperfusion injury. They were classified in six groups. Group A, non-OLV lobectomy group; B, OLV pneumonectonny group; C-E, OLV lobectomy of 60, 90, and 120 min duration, respectively; F, normal subjects as baseline group. Preoperative, intraoperative and postoperative strict blood sampling protocol was followed. Malondialdehyde (MDA) plasma levels were measured. The recorded values were analyzed and statistically compared between groups and within each one. Results: Comparison of groups C-E (OLV) to A other documented significant (P < 0.001) increase of MDA levels during lung reexpansion and for the following 12 h. The magnitude of oxidative stress was related to OLV duration (group E > D > C, all P < 0.001). The removal of cancer-associated parenchyma led to MDA level decrease postoperatively (P < 0.001) especially after pneumonectomy (A vs. B, P < 0.001). Conclusions: (1) Lung reexpansion provoked severe oxidative stress. (2) The degree of the amount of generated oxygen free radicals was associated to the duration of OLV. (3) Patients with lung cancer had a higher production of oxygen free radicals than normal population. (4)Tumor resection removes a large oxidative burden from the organism. (5) Mechanical ventilation and surgical trauma are weak free radical generators. (6) Manipulated lung tissue is also a source of oxygen free radicals, not only intraoperatively but also for several hours later. (c) 2005 Elsevier B.V. All rights reserved

A Phase II study of paclitaxel-ifosfamide-cisplatin combination in advanced nonsmall cell lung carcinoma

BACKGROUND. The necessity to develop more effective chemotherapy regimens in advanced nonsmall cell lung carcinoma (NSCLC) prompted the authors to evaluate the paclitaxel-ifosfamide-cisplatin (PIC) combination, developed on the basis of high individual single-agent activity, in vitro synergism, and tolerance as determined in a previous Phase I study by the authors. PATIENTS. Eligibility criteria included advanced NSCLC (American Joint Committee on Cancer [AJCC]/International Union Against Cancer [UICC] Stage III/IV), Eastern Cooperative Oncology Group performance status (PS) less than or equal to 2, no prior chemotherapy, and unimpaired hematopoietic and organ function. Chemotherapy included, paclitaxel 175 (in the first 10 patients) or 200 mg/m(2) on Day 1, ifosfamide: 5 g/m(2) divided over Days 1 and 2, and cisplatin 100 mg/m2 divided over Days 1 and 2, recycled every 21 days. Granulocyte-colony stimulating factor was administered from Day 4 to 13 or until leukocyte count reached greater than or equal to 10,000/mu L. RESULTS, Fifty patients were entered, and all were evaluable for response and toxicity: median age, 58 years (range, 40-72), PS, 1 (range, 0-2), Gender: 44 males and 6 females, Stages ILIA, 6 patients; IIIB, 17; IV, 27; histologies: adenocarcinoma, 27 patients; squamous, 17; large cells, 5; unspecified, 1. Metastatic sites at diagnosis included lymph nodes, 33 patients; bone, 6; liver, 5; brain, 10; lung nodules, 7; adrenals, 6; other, 2. Thirty-two of 50 (64%; confidence interval, 50.7-77.3%) evaluable patients responded: 4 complete remissions, 28 partial remissions, 13 stable disease, and 5 progressive disease. The quality-of-life score improved in 37 of 50 (74%) patients. The median response duration was 7 months (range 2-34+); median time-to-progression, 8 months (range, 1-36+), median overall survival, 12 months (range, 2-36+). One-par survival was 53%. Grade 3 and 4 toxicities included neutropenia 38 of 50 patients with 21 developing Grade 4 neutropenia (less than or equal to 5 days) and 7 of these febrile neutropenia (144b); thrombocytopenia, 4 of 50 patients with 1 Grade 4 requiring platelet transfusions, 1 Grade 3 neuropathy; Grade 1-2 central nervous system toxicity due to ifosfamide was seen in 22 patients, no renal toxicity, 15 Grade 2 myalgias, 17 Grade 2 diarrhea, and 10 Grade 3 vomiting. CONCLUSIONS. The PIC combination appears highly active and tolerable in advanced NSCLC administered in the outpatient setting, Future randomized comparisons to other current standard regimens in NSCLC will be warranted. (C) 2000 American Cancer Society

A phase I-II study of docetaxel-ifosfamide-cisplatin (DIP) combination chemotherapy regimen in advanced nonsmall cell lung cancer

In an attempt to develop more effective chemotherapy regimens in advanced nonsmall cell lung cancer (NSCLC), we evaluated docetaxel-ifosfamide-cisplatin (DIP) based on our previous experience with paclitaxel-ifosfamide-cisplatin. Patients with advanced NSCLC (stages III-IV), WHO-PSless than or equal to2, no prior chemotherapy and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered in successive dose levels (DLs) and included docetaxel (80100 rng/m(2) day 1), ifosfamide (4-5 g/m(2)) and cisplatin (80100 mg/m(2)), both divided over days I and 2 every 21 days. G-CSF (lenograstin) was administered from days 4-13. Fifty-five patients were accrued (phase 1: IS; phase II: 40) and all are evaluable for response and toxicity: median age = 58 (40-72); PS = 1 (0-2); gender = 48 males, 7 females; stages IIIA = 8, 11113 = 19, IV = 28; and histologies were adenocarcinoma (29), squamous (20), large cell (6). Metastatic sites at diagnosis included lymph nodes (33), bone (8), liver (6) brain (6), lung nodules (9), adrenals (7) and soft tissue (1). The dose-limiting toxicity (DLT) was reached at DL4 (Docetaxel: 100 mg/m(2)-Ifosfamide: 5 g/m(2)-Cisplatin: 100 mg/m(2)) consisting of 2 cases of febrile neutropenia (FN), and DL3 (Docetaxel: 100 mg/m(2)-Ifosfamide: S g/m(2)-Cisplatin: 80 mg/m2) was considered as the maximum tolerated dose (MTD) and recommended for further phase 11 testing. Among evaluable patients in phase 11, 31146 (67%; Cl = 54-81%) responded; 4 were complete responses, 27 partial responses, 12 with stable disease and 3 with progressive disease. The median response duration was 7 months (2-21 +), median time to progression (TTP) 8 months (1-23 +) and median overall survival (OS) 13 months (2-23 +). The 1-year survival was 57%. Grade (Gr) 314 toxicities included neutropenia 39146 with 27 developing Gr4 ( less than or equal to7 days) and 20% FN managed successfully with broad-spectrum antibiotics, thrombacytopenia Gr3 3/46-Gr4 1/46, no Gr3 neuropathy, Gr1-2 CNS toxicity in 12, no renal toxicity, IS Gr2 myalgias, 17 Gr2 diarrhea and 10 Gr3 vomiting. In the present phase I-II study, DIP appears highly active and tolerable in advanced NSCLC in the outpatient setting. Randomized comparisons to current standard 2-drug regimens will be warranted. (C) 2002 Wiley-Liss, Inc