Tumor Differentiation as a Prognostic Marker in Clinically Staged T1bN0 Esophageal Adenocarcinoma.

Current guidelines recommend that clinically staged T1N0 esophageal cancers are to be referred to surgery or endoscopic resection. Using the National Cancer Database, we identified 733 individuals with clinically staged T1N0 esophageal carcinoma, who underwent upfront surgery and did not receive any prior treatment. We assessed upstaging, which was defined as ≥ T2 disease or positive lymph nodes. Poorly differentiated adenocarcinomas were associated with upstaging, whereas squamous cell carcinomas were not. Specifically, the percentage of upstaging among individuals with clinically staged T1b and poorly differentiated tumor was 33.8%. Therefore, clinically staged T1bN0 poorly differentiated esophageal adenocarcinomas are at high risk for upstaging following surgery.

Immunotherapy response modeling by ex-vivo organ culture for lung cancer.

One of the major hurdles for the advancement of cancer immunotherapy is lack of robust, accessible experimental models. We aimed to produce an ex-vivo organ culture (EVOC) model of immunotherapy for non-small cell lung cancer (NSCLC). Freshly resected early stage tumors were collected from the operating room, fragmented to clusters < 450 µm and cultured with fetal calf serum and human autologous serum. The resulting EVOC includes cancer epithelial cells within tumor tissue clusters and immune cells. Original tissue features are reflected in the EVOCs. The response to immune checkpoint inhibitors (ICI) was assessed by IFNγ gene induction. Interestingly, IFNγ EVOC induction was numerically higher when anti-CTLA4 was added to anti-PD-L1 treatment, supporting the notion that anti-CTLA4 impacts cancer partly through tumor-resident immune cells. In parallel, immunohistochemistry (IHC) for key immune-related proteins was performed on the formalin-fixed paraffin embedded (FFPE) corresponding tumors. EVOC IFNγ induction by ICI correlated with basal non-induced IFNγ, CD8, CD4 and FOXP3 mRNA levels within EVOCs and with tumor-FFPE-IHC for CD8 and granzyme B. A weaker correlation was seen with tumor-FFPE-IHC for CD3, CD4, CD68, FOXP3 and tumor-PD-L1. Tertiary lymphoid structure density was also correlated with the ICI response. Our study provides novel data about biomarkers that correlate with ICI-induced response of early stage NSCLC. Retention of the microenvironment and minimal addition of exogenous factors suggest this model to reliably represent the original tumor. The cluster-based EVOC model we describe can provide a valuable, yet simple and widely applicable tool for the study of immunotherapy in NSCLC.

Comprehensive single institute experience with melanoma TIL: Long term clinical results, toxicity profile, and prognostic factors of response.

Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) mediates objective responses in 30% to 50% of patients with metastatic melanoma according to multiple, small phase 2 trials. Here we report the long-term clinical results, intent-to-treat analysis, predictors of response and toxicity profile in a large patient cohort. A total of 179 refractory melanoma patients were enrolled in the ACT trial. TIL were administered in combination with high-dose bolus interleukin-2 following preconditioning with cyclophosphamide and fludarabine. Patients were followed-up for a median of 7.2 years. A total of 107 (60%) of 179 enrolled patients were treated. The main reason for the drop out of the study was clinical deterioration. Of 103 evaluated patients, 29 patients (28%) achieved an objective response (OR), including complete remission (8%) or partial response (20%). Sixteen pateints exhibited stable disease. Predictors of response were performance status, time of TIL in culture and CD8 frequency in the infusion product. The absolute lymphocyte count 1 and 2 weeks after TIL infusion was the most predictive parameter of response. With a medium follow-up time of 7.2 years, OR patients reached a median overall survival (OS) of 58.45 months and a median progression-free survival (PFS) of 15.43 months, as compared with nonresponders, with 6.73 months OS and 2.60 months PFS. By 6 years, 50% of OR patients were alive and 43% had no documented progression. TIL ACT can yield durable objective responses, even as salvage therapy in highly advanced metastatic melanoma patients.

Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients.

Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.

Surgical Treatment of Gastro-Pulmonary Fistula Following Bariatric Surgery: Possible and Safe.

BACKGROUND: Laparoscopic sleeve gastrectomy is a common surgical management of morbid obesity. Major complication rate is 3-8%. Staple line leak is one of the most serious complications. In a small group of patients, a gastro-pulmonary fistula is formed. Endoscopic and minimally invasive measures are the first line of treatment with considerable success rate. There are very poor data in the literature what should be done in cases of failure. In this paper, we report our positive experience with definitive surgical repair. METHODS: Retrospective evaluation of 13 consecutive patients referred to the general thoracic surgery department for gastro-pulmonary fistula following sleeve gastrectomy. RESULTS: Prior to their referral, all patients underwent surgical or percutaneous drainage and multiple treatment attempts including stent insertion, pyloric dilatation, endo-clip/ring closure, endoscopic argon ablation and glue injection. Two patients underwent emergency thoracotomy for sepsis and bile empyema. One died in the early postoperative period. Eleven patients underwent semi-elective definitive surgery. Surgery included left lower lobectomy, partial diaphragmectomy and digestive system reconstruction. There was no mortality or major complications in this group. Complication rate was 45% mostly local wound infection and pneumonia. CONCLUSIONS: Gastro-pulmonary fistula is a rare devastating complication of sleeve gastrectomy. When minimally invasive measures fail, there is no place for nihilism. Surgical repair is possible and safe. The data presented herein support this treatment policy.

Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report.

BACKGROUND: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. OBJECTIVES: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009. METHODS: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009-2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method. RESULTS: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78-94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%. CONCLUSIONS: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

Neo-adjuvant Chemo-Radiation to 60 Gray Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer Patients: Evaluation of Trimodality Strategy.

BACKGROUND: Neoadjuvant chemo-radiation therapy (CRT) dosages in locally advanced non-small cell lung cancer (NSCLC) were traditionally limited to 45 Gray (Gy). OBJECTIVES: To retrospectively analyze outcomes of patients treated with 60 Gy CRT followed by surgery. METHODS: A retrospective chart review identified patients selected for CRT to 60 Gy followed by surgery between August 2012 and April 2016. Selection for surgery was based on the extent of disease, cardiopulmonary function, and response to treatment. Pathological response after neoadjuvant CRT was scored using the modified tumor regression grading. Local control (LC), disease free survival (DFS), and overall survival (OS) were estimated by the Kaplan-Meier method. RESULTS: Our cohort included 52 patients: 75% (39/52) were stage IIIA. A radiation dose of 60 Gy (range 50-62Gy) was delivered in 82.7%. Surgeries performed included: lobectomy, chest-wall resection, and pneumonectomy in 67.3%, 13.4%, and 19.2%, respectively. At median follow-up of 22.4 months, the 3 year OS was 74% (95% confidence interval [CI] 52-87%), LC was 84% (95%CI 65-93), and DFS 35% (95%CI 14-59). Grade 4-5 postoperative complications were observed in 17.3% of cases and included chest wall necrosis (5.7%), bronco-pleural fistula (7.7%), and death (3.8%). A major pathologic regression with < 10% residual tumor occurred in 68.7% of patients (36/52) and showed a trend to improved OS (P = 0.1). Pneumonectomy cases had statistically worse OS (P = 0.01). CONCLUSIONS: Major pathologic regression was observed 68.7% with 60 Gy neoadjuvant CRT with a trend to improved survival. Pneumonectomy correlated with worse survival.

Tracheostomy after cardiac surgery: timing of tracheostomy as a risk factor for mortality.

OBJECTIVES: The optimal timing for tracheostomy after cardiac surgery in patients undergoing prolonged ventilation is controversial. The aim of this study was to assess the effect of tracheostomy timing on short- and long-term mortality of these patients. DESIGN: Retrospective study of prospectively collected data. SETTING: Cardiac surgical intensive care unit (ICU) in a tertiary-care, university-affiliated hospital. PARTICIPANTS: All patients undergoing tracheostomy after cardiac surgery between September 2004 and March 2013 were included. INTERVENTIONS: The authors compared the outcome in 2 groups of patients according to the timing of tracheostomy: Group I, early-intermediate tracheostomy (0-14 days) and Group II, late tracheostomy (≥15 days). MEASUREMENTS AND MAIN RESULTS: During the study period, 6,069 patients underwent cardiac surgery; among them, 199 patients (3.26%) received a tracheostomy. There were 90 patients in Group I and 109 patients in Group II. There was no significant difference in the severity of the patients' illness between the groups. The mortality rate at 3 months, 6 months, 1 year, and 2 years was 37%, 48%, 56%, and 58% in Group I, respectively, and 58%, 70%, 74%, and 77% in Group II, respectively (p< 0.01). CONCLUSIONS: Early-intermediate (0-14 days) tracheostomy after cardiac surgery in patients requiring prolonged mechanical ventilation was associated with reduced mortality compared with late tracheostomy (≥15 days).

Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery.

OBJECTIVE: We hypothesized that driver mutations in epidermal growth factor receptor (EGFR) are associated with decreased pathologic response to neoadjuvant chemoradiation (NA-ChRT) in locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: Patients with Stage IIB-IIIA NSCLC treated with NA-ChRT, completion surgery, and underwent molecular profile testing were identified in a lung cancer database. Pathologic response was quantified using: (i) major pathologic response (MPR), (ii) complete pathologic response (pCR), and (iii) mean residual viable tumor cells (MRTC). Two groups were formed based on the presence or absence of driver mutations. Clinical and pathological correlations between the groups were studied. RESULTS: Forty-seven patients underwent tumor molecular profile testing, NA-ChRT, and completion surgery. Compared to the no-driver mutation group, the driver mutation group had lower MPR (23% vs 71%, p = 0.003), pCR (0% vs 26%, p = 0.02), and higher MRTC (43.4% vs 15.8%, p = 0.009). Univariate analysis showed an increased MPR rate for smokers, squamous cell histology, ChRT-surgery interval >65 days, and no-driver mutations. Multivariate analysis showed that only no-driver mutations (OR 0.39, p = 0.02) remained significant for MPR. PD-L1 status did not affect MPR. At 2 years, the driver mutation group had lower rates of local control (Hazard ration [HR] 0.67, p = 0.17) and disease-free survival (HR 0.5, p = 0.001). Overall survival was similar for both groups (HR = 1.04, p = 0.86). CONCLUSION: Following 60 Gray NA-ChRT, tumors with a driver mutation had lower MPR and pCR rates than tumors without a driver mutation. PD-L1 was not associated with tumor regression. ADVANCES IN KNOWLEDGE: Patients with resectable LA-NSCLC and an EGFR driver mutation treated with neoadjuvant-ChRT and completion surgery have reduced pathologic regression, lower local control rates, and shorter disease-free survival than patients without a driver mutation. Evaluation of molecular testing should be introduced in LA-NSCLC intended for prognostication and treatment decisions.

Thoracic endometriosis syndrome is strongly associated with severe pelvic endometriosis and infertility.

STUDY OBJECTIVE: To evaluate the clinical and surgical features of thoracic endometriosis syndrome (TES) represented by catamenial pneumothorax and pelvic endometriosis and to describe their association with infertility. DESIGN: Retrospective clinical study (Canadian Task Force classification: II-2). SETTING: Academic tertiary referral endometriosis center. PATIENTS: Seven patients who had undergone surgery because of thoracic and pelvic endometriosis between 2004 and 2010. INTERVENTIONS: Thoracic and pelvic exploration and treatment and fertility treatment. MEASUREMENTS AND MAIN RESULTS: Concurrently, thoracic and pelvic endometriosis, and subsequent fertility were determined during long-term follow-up after combined surgical and pharmacologic interventions. The most frequent thoracic finding was diaphragmatic implants. Except for 1 patient with recurrent pleurodesis at 1 month after video-assisted thoracoscopy, no patients experienced recurrence of thoracic symptoms during a median (range) follow-up of 31.4 (1-61) months. Severe pelvic endometriosis was diagnosed in 6 patients with notable urologic and gastrointestinal tract involvement. Only 1 patient with catamenial pneumothorax had no macroscopic pelvic lesions. There was a considerable delay between the onset of pelvic symptoms and diagnosis. Median postoperative follow-up was 31.5 (7-84) months. Most patients who tried to conceive had primary infertility. CONCLUSION: Thoracic endometriosis syndrome, represented by catamenial pneumothorax, was strongly associated with severe pelvic endometriosis and a high rate of infertility. Inasmuch as many patients with thoracic endometriosis syndrome are treated by thoracic surgeons using video-assisted thoracoscopy, it is desirable to involve an experienced gynecologist who can diagnose and treat concurrent pelvic endometriosis.

[Ectopic pregnancy as a presenting symptom for lung cancer].

This article describes a rare presentation of squamous cell carcinoma of the lung, mimicking an ectopic pregnancy secreting beta-hCG protein in a 47 year old female smoker, who was treated with Methotrexate and subsequently curettage, tubectomy and right ovariectomy, because of suspected hydatidiform mole. This document presents a rare and chaotic case of lung cancer and reviews the differential diagnosis of an increased level of the beta-hCG marker and the therapeutic approach to these cases.

Nonsteroidal antiinflammatory medications: efficient and safe treatment following video-assisted pleurodesis for spontaneous pneumothorax.

BACKGROUND: Recurrent spontaneous pneumothorax is widely treated by video-assisted thoracoscopic (VATS) bullectomy and pleurodesis. Treatment of postoperative pain with nonsteroidal antiinflammatory drugs (NSAIDs) is controversial as many surgeons believe that it reduces the efficacy of pleurodesis and increases the pneumothorax recurrence rate. METHODS: In this retrospective study, we reviewed the hospital records for patients following VATS pleurodesis for recurrent spontaneous pneumothorax. The patients were divided into two groups: (1) NSAID group: patients were treated with NSAIDs for more than a week following surgery and (2) control group: patients did not receive NSAIDs. Data regarding short- and long-term outcomes were compared. RESULTS: The study cohort included 105 patients: 48 in the NSAID group and 57 in the control group. During the early postoperative period the average daily requirement of narcotic analgesia and the incidence of narcotic-related side effects were lower in the NSAIDs group. No difference was found in the long-term recurrence rate: two of 48 (4%) in the NSAID group and three of 57 (5%) in the control group. There was one case of early recurrence in the NSAID group. Both groups had similar length of stay with no cases of mortality or major morbidity. CONCLUSIONS: NSAIDs for postsurgical pleurodesis pain obviates the need for narcotics without increasing the pneumothorax recurrence rate. Prospective randomized controlled studies are needed to further investigate this issue.

Stromal-MDM2 Promotes Lung Cancer Cell Invasion through Tumor-Host Feedback Signaling.

Tumor-host interactions play a major role in malignancies' initiation and progression. We have reported in the past that tumor cells attenuate genotoxic stress-induced p53 activation in neighboring stromal cells. Herein, we aim to further elucidate cancer cells' impact on signaling within lung cancer stroma. Primary cancer-associated fibroblasts were grown from resected human lung tumors. Lung cancer lines as well as fresh cultures of resected human lung cancers were used to produce conditioned medium (CM) or cocultured with stromal cells. Invasiveness of cancer cells was evaluated by transwell assays, and in vivo tumor growth was tested in Athymic nude mice. We found CM of a large variety of cancer cell lines as well as ex vivo-cultured lung cancers to rapidly induce protein levels of stromal-MDM2. CM of nontransformed cells had no such effect. Mdm2 induction occurred through enhanced translation, was mTORC1-dependent, and correlated with activation of AKT and p70 S6 Kinase. AKT or MDM2 knockdown in fibroblasts reduced the invasion of neighboring cancer cells, independently of stromal-p53. MDM2 overexpression in fibroblasts enhanced cancer cells' invasion and growth of inoculated tumors in mice. Our results indicate that stromal-MDM2 participates in a p53-independent cancer-host feedback mechanism. Soluble cancer-originated signals induce enhanced translation of stromal-MDM2 through AKT/mTORC1 signaling, which in turn enhances the neighboring cancer cells' invasion ability. The role of these tumor-host interactions needs to be further explored. IMPLICATIONS: We uncovered a novel tumor-stroma signaling loop, which is a potentially new therapeutic target in lung cancer and possibly in additional types of cancer.

Predicting brain metastasis in early stage non-small cell lung cancer patients by gene expression profiling.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-death due to early metastatic spread, in many cases primarily to the brain. Organ-specific pattern of spread of disease might be driven by the activity of a specific signaling pathway within the primary tumors. We aimed to identify an expression signature of genes and the relevant signaling associated with the development of brain metastasis (BM) after surgical resection of NSCLC. METHODS: Rapidly frozen NSCLC surgical specimens were procured from tumor banks. RNA was extracted and analyzed by RNA-sequencing (Illumina HiSeq 2500). Clinical parameters and gene expression were examined for differentiating between patients with BM, patients with metastases to sites other than brain, and patients who did not develop metastatic disease at a clinically significant follow up. Principal component analysis and pathway enrichments studies were done. RESULTS: A total of 91 patients were included in this study, 32 of which developed BM. Stage of disease at diagnosis (P=0.004) and level of differentiation (P=0.007) were significantly different between BM and control group. We identified a set of 22 genes which correlated specifically with BM, and not with metastasis to other sites. This set achieved 93.4% accuracy (95% CI: 86.2-97.5%), 96.6% specificity and 87.5% sensitivity of correctly identifying BM patients in a leave-one-out internal validation analysis. The oxidative phosphorylation pathway was strongly correlated with BM risk. CONCLUSIONS: Expression level of a small set of genes from primary tumors was found to predict BM development, distinctly from metastasis to other organs. These genes and the correlated oxidative phosphorylation pathway require further validation as potentially clinically useful predictors of BM and possibly as novel therapeutic targets for BM prevention.

The human tumor microbiome is composed of tumor type-specific intracellular bacteria.

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients' smoking status, and the response to immunotherapy.

Comparative effectiveness of intensity modulated radiation therapy to 3-dimensional conformal radiation in locally advanced lung cancer: pathological and clinical outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy. METHODS: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT. RESULTS: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72). CONCLUSION: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes. ADVANCES IN KNOWLEDGE: This study validates the real-world effectiveness of IMRT compared to 3DCRT.

Lobectomy on ECMO as a Life-Saving Procedure following Necrotizing Pneumonia in a Toddler: A Case Study.

Necrotizing pneumonia is a severe form of pneumonia that is mainly treated with conservative treatment, including antibiotics. We report a unique case of necrotizing pneumonia due to group A streptococcus infection in an 18-month-old boy who required extracorporeal membrane oxygenation (ECMO) support. Following surgical lobectomy, the child was weaned off ECMO and recovered uneventfully.

Detection of Lung Cancer and EGFR Mutation by Electronic Nose System.

INTRODUCTION: Early detection of lung cancer (LC) has been well established as a significant key point in patient survival and prognosis. New highly sensitive nanoarray sensors for exhaled volatile organic compounds that have been developed and coupled with powerful statistical programs may be used when diseases such as LC are suspected. Detection of genetic aberration mutation by nanoarray sensors is the next target. METHODS: Breath samples were taken from patients who were evaluated for suspicious pulmonary lesions. Patients were classified as those with benign nodules, as patients with LC with or without the EGFR mutation, and according to their smoking status. Breath prints were recognized by nanomaterial-based sensor array, and pattern recognition methods were used. RESULTS: A total of 119 patients participated in this study, 30 patients with benign nodules and 89 patients with LC (16 with early disease and 73 with advanced disease). Patients with LC who harbored the EGFR mutation (n = 19) could be discriminated from those with wild-type EGFR (n = 34) with an accuracy of 83%, sensitivity of 79%, and specificity of 85%. Discrimination of early LC from benign nodules had 87% accuracy and positive and negative predictive values of 87.7 and 87.5% respectively. Moderate discrimination (accuracy of 76%) was found between LC of heavy smokers and that of never-smokers or distant past light smokers. CONCLUSIONS: Breath analysis could discriminate patients with LC who harbor the EGFR mutation from those with wild-type EGFR and those with benign pulmonary nodules from those patients with early LC. A positive breath print for the EGFR mutation may be used in treatment decisions if tissue sampling does not provide adequate material for definitive mutation analysis.

Retrosternal thyroid goiter: 15 years experience.

BACKGROUND: Thyroidectomy for goiter is a common surgical procedure performed in most hospitals in Israel. Both general and ear, nose and throat surgeons are familiar with thyroidectomy for cervical goiters. In about 1-15% of thyroidectomies, the goiter is intrathoracic and requires somewhat different management. This topic has not been reviewed in the literature recently. OBJECTIVE: To evaluate the clinical presentation, preoperative workup, surgical complications and risk of malignancy in retrosternal goiters. METHODS: We retrospectively reviewed the records of 75 patients who underwent thyroidectomy for retrosternal goiter in the General Thoracic Surgical Department of our institution during a 15 year period, January 1990 to January 2005. RESULTS: All the patients (41 women and 34 men) were symptomatic at presentation, with choking and dyspnea being the most common complaint. Computerized tomography scan of the neck and chest were obtained before the operation in 71 patients (95%). Ten patients (13%) had a previous partial thyroidectomy. A cervical approach was used in 68 patients (91%). Seven patients (9%) required median sternotomy to complete the operation. One patient (1.3%) died from postoperative respiratory failure. Transient recurrent laryngeal nerve palsy occurred in 5 patients (7%) and permanent RLNP in 3 (4%). The incidence of transient and permanent hypoparathyroidism was 10% and 2.6% respectively. Sixty-six lesions (88%) were benign and 9 (12%) were malignant. CONCLUSIONS: Choking and dyspnea are the most common presenting symptoms of retrosternal goiter. CT scan is an important component of the preoperative evaluation and operative planning. Surgical removal of the thyroid is the treatment of choice and most patients have symptomatic improvement following the operation. Since a substernal thyroidectomy may be technically different from cervical thyroidectomy, a surgical team familiar with its unique pitfalls should perform the procedure.

[The value of FDG-PET/CT in the evaluation of patients with a pulmonary nodule and a previous malignant disease].

BACKGROUND: Patients with primary malignant disease undergoing oncological surveillance, upon completion of their treatment, are a unique population that is gradually growing. Therefore, the number of patients with a pulmonary nodule and a previous malignant disease has increased over recent years. In order to select appropriate management for these patients, a few questions should be answered: Is it a malignant lesion? Secondly, is it primary or metastatic? Is it the only one? In the past, several imaging and invasive diagnostic procedures were used to clarify theses uncertainties. However, in many cases the results were equivocal and it was difficult to establish treatment policy. In recent years PET/CT-FDG was found to be specific, sensitive and accurate in the evaluation and staging of patients with primary malignant disease. In this study we analyzed the accuracy and value of PET/CT-FDG in patients with primary malignant disease and an indeterminate pulmonary nodule. METHODS: Patients with primary malignant disease in the past and undefined pulmonary nodule/s were recruited. Computerized retrospective screening was performed. The specificity, sensitivity, positive and negative predictive value of PET/CT-FDG were calculated. The influence of the PET results on the clinical policy was evaluated. RESULTS: Forty one patients with previous malignant disease entered the study. PET/CT-FDG was positive in 15 cases. In 13 patients (87%) the FDG positive nodule was found to be malignant. In 26 patients the PET/CT was negative. In 19 (73%) diagnosis of non-malignant nodule was confirmed. The positive and negative predictive value of PET/CT-FDG for metastatic disease was 87% and 91% respectively and the accuracy 86%. CONCLUSIONS: The results of the present study demonstrate that PET/CT-FDG is a very valuable tool in the evaluation of patients with previous primary malignant disease and a pulmonary nodule. This imaging technique was able to clarify most of the thoracic surgeon's uncertainties and provided enough data to choose the optimal treatment strategy.