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.

Hybrid video-assisted and limited open (VALO) resection of superior sulcus tumors.

PURPOSE: To compare the postoperative recovery of patients with superior sulcus tumors (Pancoast tumors) following conventional open surgery vs. a hybrid video-assisted and limited open approach (VALO). METHODS: The subjects of this retrospective study were 20 patients we operated on to resect a Pancoast tumor. All patients received induction chemo-radiation followed by surgery, performed via either a conventional thoracotomy approach (n = 10) or the hybrid VALO approach (n = 10). In the hybrid VALO group, lobectomy and internal chest wall preparation were performed using a video technique, with rib resection and specimen removal through a limited incision. RESULTS: There was no mortality in either group. Two patients from the thoracotomy group required mechanical ventilation, but there was no major morbidity in the hybrid VALO group. The operative times were similar for the two procedures. The average length of hospital stay was shorter and the average pain scores were significantly lower in the hybrid VALO group. The incidence of chronic pain was 10 % in the hybrid VALO group vs. 50 % in the thoracotomy group. CONCLUSIONS: Hybrid VALO resection of Pancoast tumors is feasible and safe, resulting in faster patient recovery and a significantly lower incidence of severe chronic pain than open thoracotomy. We conclude that centers experienced with video-assisted lobectomy should consider hybrid VALO surgery as the procedure of choice for Pancoast tumors.

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).

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.

The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain.

PURPOSE: Brain metastases affect 25% of patients with non-small cell lung cancer (NSCLC). We hypothesized that the expression of genes in primary NSCLC tumors could predict brain metastasis and be used for identification of high-risk patients, who may benefit from prophylactic therapy. EXPERIMENTAL DESIGN: The expression of 12 genes was measured by real-time quantitative reverse transcriptase PCR in 142 frozen NSCLC tissue samples. Univariate and multivariate Cox regression analysis was used to analyze the correlation between gene expression and the occurrence of brain metastasis. Immunohistochemistry on independent samples was used to verify the findings. RESULTS: A score based on the expression levels of three genes, CDH2 (N-cadherin), KIFC1, and FALZ, was highly predictive of brain metastasis in early and advanced lung cancer. The probability of remaining brain metastasis-free at 2 years after diagnosis was 90.0+/-9.5% for patients with stage I/stage II tumors and low score compared with 62.7+/-12% for patients with high score (P<0.01). In patients with more advanced lung cancer, the brain metastasis-free survival at 24 months was 89% for patients with low score compared with only 37% in patients with high score (P<0.02). These results were confirmed by immunohistochemical detection of N-cadherin in independent cohort of primary NSCLC. CONCLUSIONS: The expression levels of three genes in primary NSCLC tumors may be used to identify patients at high risk for brain metastasis who may benefit from prophylactic therapy to the central nervous system.

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.

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.

The sequence of vessel interruption during lobectomy: does it affect the amount of blood retained in the lobe?

OBJECTIVE: In a previous study, we have shown that the sequence of vessel interruption (SVI) during lobectomy has no impact on tumor recurrence. The aim of the present study was to determine whether SVI has an impact on the amount of blood retained in the resected lobe. PATIENTS AND METHODS: A non-randomized prospective study including 30 patients undergoing lobectomy for neoplasms. Group A-1'st had all lobar arteries ligated before interruption of the lobar vein and group V-1'st had a reverse sequence. Generous exclusion criteria were used, so as to include only patients with straightforward lobectomy, attempting to isolate SVI as the only factor that could affect blood loss. Lobar weight was recorded immediately after lobectomy. All ligatures and staplers were removed; blood drained from the lobe, collected and measured, and thereafter the lobe was weighed again. RESULTS: Sixteen patients entered group A-1'st and 14 group V-1'st. The groups were similar in age, sex, body surface, histology, prior therapy, stage, FEV1%, length of operation, and number of segments resected. The amount of blood drained from the lobe was 31.4+/-13 and 34.2+/-14.8ml in group A-1'st and V-1'st, respectively. The lobar weights before and after blood drainage were 177.6+/-56.9, 141.7+/-49.1g and 201.5+/-74.2, 161.6+/-69.7g, respectively. The amount of blood divided to the lobar weight was 0.178+/-0.052 in group A-1'st and 0.177+/-0.099 in group V-1'st. All of these figures did not differ statistically. No patient required blood transfusion during or after surgery. CONCLUSIONS: In straightforward lobectomy the amount of blood retained in the resected lobe is small. This amount is not affected by the sequence of hilar vessel interruption.

Genetic analyses of non-small cell lung cancer in Jewish Israeli patients.

BACKGROUND: The contribution of the abnormal DNA mismatch repair system to non-small cell lung cancer tumorigenesis is controversial and has not been reported in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC in the same population has not been assessed. OBJECTIVES: To assess the contribution of the DNA-MMR system to NSCLC pathogenesis by analyzing microsatellite instability, and evaluate loss of heterozygosity at 3p rates in Israeli NSCLC patients. METHODS: Paired DNA from tumorous and non-tumorous tissue was extracted, and genotyping for MSI determination was carded out using the five Bethesda markers and for determining LOH two 3p markers were used. Genotyping was performed using polymerase chain reaction amplification and size separation on an ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non-tumorous tissue were compared. RESULTS: Forty-four NSCLCs from 35 smokers and 9 non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI in at least one marker. Similarly, genotyping for LOH at chromosome 3p was performed using two markers (D3S4103, D3S1234) located at 3p14.2 I. With D3S4103, 33 of the 44 patients successfully analyzed were homozygous and therefore non-informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH. Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of these tumors showed a similar pattern when genotyped with the five consensus markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers. CONCLUSIONS: MSI using 3p markers and not the Bethesda markers occurs at a high rate and in early stages in Jewish NSCLC patients.

Metastatic Lung Lesions as a Preferred Resection Site for Immunotherapy With Tumor Infiltrating Lymphocytes.

Adoptive cell therapy with tumor infiltrating lymphocytes (TIL) yields 50% response rates in metastatic melanoma and shows promising clinical results in other solid tumors. Autologous TIL cultures are isolated from resected tumor tissue, expanded ex vivo to large numbers and reinfused to the preconditioned patient. In this prospective study, we validate the origin of the tumor biopsy and its effect on T-cell function and clinical response. One hundred forty-four patients underwent surgery and 79 patients were treated with TIL adoptive cell therapy. Cultures from lung tissue were compared with other origins. The success rate of establishing TIL culture from lung tissue was significantly higher compared with nonlung tissue (94% vs. 72%, respectively, P≤0.003). Lung-derived TIL cultures gave rise to higher cell numbers (P≤0.011) and exhibited increased in vitro antitumor reactivity. The average fold expansion for lung-derived TIL during a rapid expansion procedure was 1349±557 compared with 1061±473 for nonlung TIL (P≤0.038). Patients treated with TIL cultures of lung origin (compared with nonlung) had prolonged median overall survival (29 vs. 9.5 mo; P≤0.065). Given the remarkable advancement in minimally invasive thoracic surgery and the results of this study, we suggest efforts should be taken to resect lung metastasis rather than other sites to generate TIL cultures for clinical use.

Experience with somatostatin receptor scintigraphy in the management of pulmonary carcinoid tumors.

BACKGROUND: Somatostatin receptor scintigraphy has been used widely for the evaluation of neuroendocrine tumors in the gastrointestinal tract. Its use for detecting and staging thoracic carcinoids is only sporadically reported. OBJECTIVES: To evaluate the possible roles of SRS in the management of proven or suspected pulmonary carcinoids. METHODS: We conducted a retrospective study of all patients undergoing SRS for known or suspected pulmonary carcinoids in a tertiary referral center during a 10 year period. During this period 89 patients underwent resection of pulmonary carcinoids and SRS was used for detection, staging or localization purposes in 8 of them (9%). Scans were labeled true positive, true negative, false positive, or false negative in comparison with histologic or follow-up results. RESULTS: SRS was true positive in 6/6 lung locations; true positive in 2/8, true negative in 4/8 and false positive in 2/8 lymph node locations; and true positive in 1/8, true negative in 6/8 and false negative in 1/8 distant locations. The sensitivity, specificity, positive and negative predictive values and accuracy were 90%, 83%, 83%, 91% and 87% respectively. The scans were strongly positive in the tumors and involved lymph nodes. SRS correctly localized an occult secreting pulmonary carcinoid. Granulomatous and reactive lymph nodes showed increased uptake. SRS was accurate in ruling out distant metastases. CONCLUSIONS: SRS is effective for visualizing and localizing pulmonary carcinoids. It assists in the staging of these tumors by detecting lymph node involvement and confirming or ruling out distant metastases. Inflammatory areas in the lung or lymph nodes may be falsely positive.

Cryptogenic organizing pneumonia: variety of radiologic findings.

BACKGROUND: Cryptogenic organizing pneumonia is increasingly being recognized as a major cause of diffuse infiltrative lung disease. The differential diagnosis of non-infectious diseases that resemble pneumonia should include this entity. Understanding the radiologic features of this entity will help in defining the correct diagnosis, although lung biopsy is needed to provide histopathologic confirmation. Treatment with steroids achieves an excellent response. OBJECTIVES: To present a variety of radiologic findings on high resolution computerized tomography in eight sequential patients with COP, together with clinical and pathologic correlation. METHODS: Sequential HRCT examinations of eight patients (four males) aged 53-80 years (mean 65.5 years) with pathologcally proven COP were retrospectively analyzed by a consensus of two experienced chest radiologists for the existence and distribution of airspace consolidation, ground-glass opacities, nodular thickening along bronchovascular bundles and small (<1 cm) and large (>1 cm) nodules. The distribution of radiologic findings was classified as unilateral or bilateral, located in the upper, lower or middle lobe, and central or peripheral. Also recorded was the presence or absence of mediastinal lymphadenopathy and pleural effusion. Correlation with clinical symptoms was analyzed. RESULTS: All eight patients had bilateral airspace consolidations. in two cases consolidations were limited to central fields, in four they were peripheral, and in the remaining two cases they were both central and peripheral. Small nodules were noted in six cases and large nodules in three. Ground-glass opacities were found ln four cases. All patients had enlarged lymph nodes (1-1.5 cm) in the mediastinum. Radiologic abnormalities resolved or improved after steroid treatment in all patients. CONCLUSIONS: HRCT findings of bilateral multiple heterogenic lung infiltrates and nodules associated with mild mediastinal lymphadenopathy in a patient with non-specific clinical symptoms are suggestive of COP; in such cases lung biopsy is indicated. Radiologic resolution of abnormalities correlates well with clinical improvement under adequate steroid treatment.

Major bleeding complicating deep sternal infection after cardiac surgery.

OBJECTIVES: This study was undertaken to determine the incidence and outcome of major bleeding complicating deep sternal infection after cardiac surgery, to identify predisposing factors and means of prevention, and to clarify management options. METHODS: This was a retrospective study of 10,863 consecutive patients, of whom 213 (2.18%) acquired deep sternal infection. With 43 additional referrals, the total number of patients with deep sternal infection was 280. Deep sternal infection was managed by a two-stage scheme. Major bleeding was considered to be bleeding that occurred during or after operation for deep sternal infection from the heart, great vessels, or grafts, or bleeding requiring urgent exploration. RESULTS: Fifteen patients (5.36%) had major bleeding. The incidences of deep sternal infection and bleeding were highest among patients undergoing coronary artery bypass grafting. Thirteen patients had underlying diseases (type 2 diabetes in 9 cases). Deep sternal infection was diagnosed a median of 15 days after reoperation. Bleeding originated from the right ventricle in 9 patients. In 4 patients bleeding was iatrogenic during surgery for wire removal (n = 2) or reconstruction (n = 2). In 11 it occurred 15 minutes to 15 days (median 2 days) after wire removal, as a result of shearing forces in 7 cases and of infection only in 4 cases. Three patients died immediately. The other 12 were operated on, 6 with complete cardiopulmonary bypass, 2 with femoral cannulation, and 4 without cardiopulmonary bypass. The immediate mortality was 26.7%; the overall mortality was 53.3%. The median length of hospitalization of surviving patients was 38 days. CONCLUSIONS: The probability of development of major bleeding in patients with deep sternal infection was unrelated to the primary operation. The mortality associated with this complication was high. Meticulous technique during wire removal may decrease the risk of major bleeding. The impacts of cardiopulmonary bypass and of the technique and timing of sternal reconstruction remain undetermined.

The sequence of vessel interruption during lobectomy for non-small cell lung cancer: is it indeed important?

OBJECTIVE: During pulmonary resections for non-small cell lung cancer, the pulmonary vein is traditionally interrupted first to prevent seeding of malignant cells and consequently decrease metastatic implantation. This hypothesis was never confirmed scientifically. The aim of the present study was to determine whether the sequence of vessel interruption during lobectomy (lobar vein or lobar artery first) affects disease recurrence. METHODS: A historical prospective study was performed of 279 consecutive patients with complete follow-up, who survived lobectomy for non-small cell lung cancer during 1992 to 1998, in a single center. Pre-, intra-, and postoperative variables were collected from the medical records; recurrence and vital status were obtained from follow-up files, central population registry, and personal confirmation, updated to December 2000. Comparison of recurrence rates by sequence of ligation and other independent variables was assessed by univariate and multivariate logistic regression analyses. RESULTS: A total of 133 patients (48%) had vein interruption before the artery (V-first) and 146 (52%) had artery interruption first (A-first). The distribution of demographic, clinical, and other characteristics was similar between the 2 groups, except for the operated side and performing surgeons. The morbidity, blood requirement, and length of stay were equal for both groups. The total recurrence rate (A-first, 53%; V-first, 51%) was similar. Multivariate analysis (controlling for the effect of the performing surgeon) revealed elevated risk for recurrence among patients with high disease stage (odds ratio = 2.54), male gender (odds ratio = 1.59), intraoperative lung manipulation (odds ratio = 2.72), and blood transfusion (odds ratio = 1.49). Sequence of vessel interruption was not found as a risk factor for recurrence (odds ratio = 1.29; 95% 0.73 to 2.29, P =.4). CONCLUSIONS: Our results did not show that sequence of vessel interruption during lobectomy plays a role in tumor recurrence. A prospective study with randomization in selection of method as well as surgeons for each patient is needed to confirm these results.

Transsternal transpericardial closure of a postlobectomy bronchopleural fistula.

We report a case of chronic empyema and bronchopleural fistula after lobectomy for tuberculosis. The patient had undergone four different surgical procedures to correct his bronchopleural fistula during an interval of seven years. Finally, he had a successful closure of the fistula using the transsternal transpericardial approach.

[Video-assisted thoracoscopic lobectomy--preliminary experience].

BACKGROUND: Video-assisted thoracoscopic surgery has become routine worldwide. On the basis of accumulating experience and technologic improvements, more complex operations can be performed. Until recently, thoracoscopic lobectomy has not been performed in Israel. GOALS: To describe the initial experience with thoracoscopic lobectomy in Sheba Medical Center, and discuss the advantages, disadvantages and indications for its use. MATERIAL & METHODS: From June 2000 to January 2001, five patients (3 male, 2 female) 22-72 year-old underwent thoracoscopic lobectomy. Four had malignant neoplasms (3 lung primary) and one a benign process. Preparations for surgery, anesthesia and monitoring were standard as for open lobectomy. Surgery was done through 3 ports and a 5-7 cm auxiliary thoracotomy. The majority of the operation was performed with staplers. In patients with lung tumors the regional lymph nodes were sampled. Pulmonary function tests were evaluated prior to surgery and in the immediate postoperative period. RESULTS: Lobectomy was completed in all patients according to preoperative planning without conversion to open thoracotomy. Operative time was 120-160 minutes. Blood transfusion was not required in any patient during or after the lobectomy. There was no operative mortality and only two minor complications in one patient. Narcotic requirement did not exceed 40 mg of morphine in any patient. Pulmonary function tests revealed a smaller than expected decrease compared to open thoracotomy. The cosmetic results were excellent. CONCLUSIONS: Thoracoscopic lobectomy is feasible in Israel too. It is an acceptable alternative for patients needing this operation. Thoracoscopic lobectomy causes less surgical trauma, better functional result and expectance for lowered mortality and morbidity. Its main disadvantage is its high cost.

[Surgery and hyperthermic pleural perfusion--a new approach for malignancies with pleural involvement].

BACKGROUND: Malignant neoplasms involving the pleura have a poor prognosis. In some cases the main symptoms and the cause of death are due to local spread, whereas metastases, if at all, develop late. The preferred treatment of these tumors is not clear. GOALS: To evaluate whether regional therapy that includes resection, local chemotherapy and hyperthermia is feasible, safe and effective for tumors with pleural spread. MATERIAL & METHODS: Forty-three patients undergoing surgery and hyperthermic pleural perfusion were studied retrospectively. The majority had mesothelioma, or thymic malignancies with pleural spread. Twenty-five patients received previous treatment. The extent of resection was dictated by tumor type and patients condition. Perfusion was performed with a roller pump and heat exchanger plus cisplatinum in a dose of 60-200 mg. RESULTS: Intrapleural temperature exceeded 40 degrees C in all patients. There were no hemodynamic, or respiratory problems related to perfusion. There was neither intraoperative mortality nor hematologic, renal or systemic toxicity. Three patients died (7% mortality) and 14 had complications. The overall 1, 2, 3, and 5-year survival rates ware 78%, 72%, 50% and 36% respectively. The best survival was for thymoma patients--70% after 3 and 5 years, and the worst for metastatic tumors--31% 3-year survival. Among 39 patients followed-up for more than 1 year (24 alive, 15 dead), 28 (72%) were free of ipsilateral pleuro-pulmonary recurrence. CONCLUSIONS: Surgery and hyperthermic pleural perfusion is feasible and relatively safe. This method offers a good chance of complete midterm local eradication of neoplasms with pleural spread. A survival benefit over other modalities is suggested in patients with thymoma. Other drugs, alone or in combinations, should be studied.

Genetic mutation screen in early non--small-cell lung cancer (NSCLC) specimens.

BACKGROUND: Testing for genetic abnormalities in epithelial growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and potentially additional genes is a critical tool in the care of advanced NSCLC. There is conflicting evidence for the role of such tests in early NSCLC. We report a single-institute Sequenom testing for a wide range of mutations and their clinical correlations in early-resected NSCLC specimens. MATERIALS AND METHODS: Early NSCLC paraffin-embedded, formalin-fixed (FFPE) specimens were collected, DNA extracted, and using Sequenom-based matrix-assisted laser desorption/ionization-time of flight analysis, mutations in 22 oncogenes and tumor suppressor genes were evaluated. Clinical data was collected retrospectively. RESULTS: The technique was found to be feasible. Thirty-six of 96 patients (37.5%) had any genetic abnormality identified, and 8 (8.3%) had 2 or more mutations. Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR were the most common genes to appear mutated (15.6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) was the gene to be found most commonly in tumors with co-mutations. Transversions were found mostly in KRAS gene mutations and to be nonprognostic. No difference in the spectrum of mutations was found between squamous-cell and non-squamous-cell lung cancers. Ever-smokers showed a trend for worse prognosis, with a similar spectrum of mutations. CONCLUSION: Sequenom-based mutation screen is feasible using FFPE samples. More than a third of the patients were found to harbor some genetic abnormality, and 8% were found to have more than a single mutated gene. Wide-range gene screens using large sample depositories are required for further insight into the important genes at play in early NSCLC.