Pleural and peripheral lung lesions: comparison of US- and CT-guided biopsy.

PURPOSE: To retrospectively compare the outcome of computed tomography (CT) and ultrasonography (US) guidance when sampling a consecutive series of peripheral lung or pleural lesions. MATERIALS AND METHODS: Institutional review board approval was obtained, and the informed consent requirement was waived. From January 2000 to August 2011, 711 thoracic biopsies were performed at two institutions. Among these, 273 lesions in 273 patients (115 men, 158 women; mean age, 65 years ± 11 [standard deviation]; 86 pleural lesions; 187 pulmonary lesions) had pleural origin or were peripherally located in the lung with a small amount of pleural contact. These lesions were sampled with either CT (170 patients; mean age, 64 years ± 12; 55 pleural lesions, 115 peripheral pulmonary lesions) or US (103 patients; mean age, 67 years ± 10; 31 pleural lesions, 72 peripheral pulmonary lesions) guidance by using an 18-gauge modified Menghini needle. Procedure duration, postprocedural pneumothorax or hemorrhage, and sample adequacy were recorded. Fisher exact test, log-rank test, and Mann-Whitney U test were performed. RESULTS: No significant difference was found for patient age (P = .741), sex (P = .900), lesion size (P = .206), or lesion origin (P = .788). Median time was 556 seconds for CT-guided biopsy (25th percentile, 408 seconds; 75th percentile, 704 seconds) and 321 seconds for US-guided biopsy (25th percentile, 157 seconds; 75th percentile, 485 seconds) (P < .001). Postprocedural pneumothorax was observed in 25 of 170 (14.7%) CT-guided procedures and in six of 103 (5.8%) US-guided procedures (P = .025); hemorrhage occurred in two of 170 (1.2%) CT-guided procedures and in one of 103 (1.0%) US-guided procedures (P = .875). Technical success was achieved in 100 of 103 US-guided procedures (97.1%) and in 164 of 170 CT-guided procedures (96.5%) (P = .999). CONCLUSION: With pleural or peripheral lung lesions, US guidance is comparable to CT guidance in terms of sample accuracy, while allowing for a significant reduction in procedure time and postprocedural pneumothorax and being free from ionizing radiation.

Ipilimumab (MDX-010) in the treatment of non-small cell lung cancer.

INTRODUCTION: Non-small cell lung cancer (NSCLC) is one of the main causes of cancer-related deaths worldwide. Although new therapies have become available, innovative treatments are still needed for advanced disease. Ipilimumab , a monoclonal antibody targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), enhances the immune response against the tumor mass and has been proven effective against malignant melanoma. AREAS COVERED: The authors explored the role of ipilimumab in NSCLC using a literature review. The clinical trials involving ipilimumab for lung cancer have shown progression-free survival (PFS) benefits. The use of ipilimumab is related to unusual adverse events resulting from increased or excessive immune activity. Because ipilimumab shows unique response patterns, more suitable criteria known as immune-related response criteria (ir-RC), different from RECIST and WHO criteria, are required. EXPERT OPINION: Although NSCLC is not known as an immunogenic-mediated malignancy, in the past few years, the authors have observed an increasing interest in the development of therapies able to modulate the immune response including vaccines and non-specific immunoregulatory drugs (such as ipilimumab). Ipilimumab may become a new, powerful strategy for the management of NSCLC patients. Further investigation is needed to confirm the optimal treatment schedule and determine the potential predictors of response to the CTLA-4 blockade.

The administration of gefitinib in patients with advanced non-small-cell lung cancer after the failure of erlotinib.

PURPOSE: Recent studies have demonstrated that erlotinib therapy may be considered an option for patients with advanced non-small-cell lung cancer who experienced disease progression after treatment with gefitinib, particularly in patients in whom the disease had been stabilized for a long time prior to gefitinib therapy. The aim of this study was to evaluate the disease control rate and toxicity of gefitinib in patients whose disease progressed after erlotinib therapy. METHODS: From May 2005 to August 2006, 15 patients received a 250 mg/day dosage of gefitinib after having disease progression while taking erlotinib at a dose of 150 mg/day. RESULTS: Among patients who received erlotinib, 1 (7%) achieved a partial response (PR), and 5 (33%) achieved stable disease (SD). Among patients who received gefitinib, none achieved a PR, and 6 achieved SD (40%). Five out of 6 patients who achieved PR/SD with erlotinib also achieved SD with gefitinib; 8 out of 9 patients who achieved a progressive disease (PD) with erlotinib also achieved a PD with gefitinib. The median time to progression (TTP) and overall survival (OS) were 2.3 and 3.5 months, respectively. The TTP and OS in SD patients were 3.7 and 7.4 months, respectively. The most common toxicities of gefitinib were dry skin (grade 1-2) in 27% of patients and acneiform rashes and rashes/desquamation in 20% of patients. Diarrhea (grade 1-2) occurred in 7% of patients. CONCLUSIONS: Our data suggest that patients who achieved PR/SD with erlotinib also benefit from taking gefitinib. Conversely, gefitinib is not recommended in patients whose disease progressed after taking erlotinib.

Ultrasound-guided percutaneous injection of triamcinolone acetonide for treating capsular contracture in patients with augmented and reconstructed breast.

OBJECTIVES: To evaluate ultrasound (US)-guided treatment of capsular contracture (CC) in patients with reconstructed/augmented breast. METHODS: Twenty-five patients with grade IV CC were treated with peri-implant US-guided injection of triamcinolone acetonide. Before/after treatment, maximum capsular thickness (MCT) was measured by ultrasound and pain assessed with visual analogue score (pain-VAS). Patients with pain relief at 1 month were considered early responders (ERs). Another injection was performed in patients without pain relief at 1 month (late responders, LRs). RESULTS: One patient (treated with chemo-radiotherapy) experienced severe pain and local reaction after the second injection, requiring surgery. Twenty-four patients had baseline MCT of 1.8 ± 0.3 mm and pain-VAS of 4.9 ± 0.5, the baseline MCT of 19 ERs (1.7 ± 0.2 mm) being significantly lower than that of 5 LRs (2.1 ± 0.2 mm) (p = 0.030). ERs had significantly reduced MCT and pain-VAS at one (1.1 ± 0.3 mm; 1.5 ± 0.5) and 6 months (1.1 ± 0.2 mm; 0.9 ± 0.7, respectively) (p < 0.001). At 1 month, LRs had a significantly reduced MCT (1.6 ± 0.1 mm, p = 0.042) but non-significantly changed pain-VAS (4.7 ± 0.2); 5 months later, MCT reached 1.0 ± 0.1 mm, pain-VAS reached 0.8 ± 0.5 (p < 0.044). Significant correlation between the relative variation of MCT and pain-VAS (1 month/baseline) was found. CONCLUSIONS: US-guided injection of triamcinolone acetonide is effective in treating grade IV CC.

[Possible connection between gastroesophageal reflux and interstitial pulmonary fibrosis in patients with systemic sclerosis]. / Correlazione tra reflusso gastroesofageo e fibrosi interstiziale polmonare in pazienti affetti da sclerosi sistemica.

Interstitial lung disease represents the main cause of morbidity and mortality in patients with systemic sclerosis. The mechanisms leading to interstitial lung disease are poorly understood and thus current strategies have little effect on this progressive and fatal disease. Therefore, it appears relevant the importance to assess the possible risk factors involved in its pathogenesis. Previous studies in vivo and in vitro suggested that pulmonary fibrosis can occur after repeated aspiration of small amounts of gastric contents over long periods of time. Recently, our group observed that patients with systemic sclerosis and pulmonary fibrosis have a more severe degree of gastroesophageal reflux with a greater number of reflux events and a higher percentage of reflux episodes reaching the proximal esophagus, causing an increasing risk of microaspiration, compared to patients with systemic sclerosis without lung involvement. Further larger controlled studies are necessary to evaluate whether or not the development of interstitial lung disease in systemic sclerosis patients can be prevented by treating gastroesophageal reflux.

Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced colorectal cancer.

BACKGROUND: Irinotecan and raltitrexed are active agents in advanced colorectal cancer (ACC) and preclinical data suggest a remarkable synergistic activity. Phase I studies demonstrated that single-agent full dose of both drugs can be administered with moderate toxicity. The aim of this phase II trial was to assess the activity and tolerability of the combination in untreated ACC. PATIENTS AND METHODS: Forty-eight patients entered the trial and received irinotecan 350 mg/m2 d.1 and raltitrexed 3 mg/m2 d.2, every three weeks. After recruitment of the first 16 patients, grade III-IV toxicity was observed in 6 patients (38%). Therefore, an amendment reduced by 15% the dose of both drugs (irinotecan 300 mg/m2, raltitrexed 2.6 mg/m2). RESULTS: A total of 290 cycles were administered (range 1-18, median number 6). According to intention-to-treat analysis, the overall response rate was 27% (95% confidence interval 16%-42%), including 3 complete responses and 10 partial responses. The median duration of response was 10 months, while median progression-free survival and overall survival were 5 and 14 months, respectively. In the first 16 patients, the main toxicities were grade III-IV diarrhea in 25% and grade III-IV neutropenia in 13%. In the subsequent 32 patients, they were grade III-IV diarrhea in 34% and grade III neutropenia in 6%. Two toxic deaths occurred. CONCLUSION: The combination irinotecan-raltitrexed is an active regimen, but the significant incidence of side-effects requires accurate patient selection and, eventually, new schedules.

Non-small cell lung cancer: from cytotoxic systemic chemotherapy to molecularly targeted therapy.

Surgery is the only method of cure in lung cancer. Seldom its application with radical intent is possible. Despite the efforts aimed at integrating all the therapeutic strategies, the overall outcome of the management of this disease remains disappointing. For this reason, in the last three decades, thousands of preclinical and clinical attempts have been realised in order to investigate any possible way to cure this disease and significant steps forward have been made on the basis of the increasing "molecular knowledge" in the so called "post-genomic era". Particularly the impressive step forward in the biological characterization of cancer as a result of genetic/epigenetic multistep process has brought in a multitude of variables with staggering classification potentialities. "Benchside" and "bedside" scientists have assembled in functional teams to move the common efforts "translationally" to bridge basic and clinical research for a mutual synergistic enhancement. This paper represents the effort of a lung cancer focused translational research team made up of molecular biologists, medical oncologists and thoracic surgeons to achieve a comprehensive, but simple, review of the current status of the shift from cytotoxic to molecularly targeted therapy in lung cancer treatment potentially useful in the planning of translational research trials.