Serhan Tanju

WWOX gene may contribute to progression of non-small-cell lung cancer (NSCLC)

Lung cancer is the most common cause of cancer-related death worldwide and, like many other cancers, is affected by different genetic, epigenetic, and environmental factors. The WW domain-containing oxidoreductase (WWOX) gene is a tumor-suppressor gene located on chromosome 16q23.3–24.1, and it has been shown that it loses its function due to alterations in genetic and epigenetic mechanisms. The aim of this study is to investigate the relationship between lung cancer and WWOX gene. Tumor tissue samples, corresponding normal tissues, and blood samples obtained from 50 lung cancer patients were involved in the study. We analyzed methylation profile by methylation-specific PCR and mutations and polymorphisms by DNA sequencing. Methylation analysis showed that promoter hypermethylation was present in 38 of 50 (76%) patients. In addition, promoter region of WWOX gene of younger patients was more frequently methylated than older patients. Using DNA sequencing, we found four genetic alterations in WWOX gene. Two of them were germline mutations (Exon 4 and 7), and two of them were polymorphic (Exon 6 and 8). We found a new mutation in exon 7 (Arg-254→Cys) which has not been described previously. The changes in the short-chain dehydrogenase domain of the protein caused by the genetic alterations may affect the function of the gene. We conclude that hypermethylation of WWOX gene promoter region and mutations in the gene might be related to lung carcinogenesis.

Oxygen uptake kinetics during cardiopulmonary exercise testing and postoperative complications in patients with lung cancer.

It is accepted that cardiopulmonary exercise testing is one of the most valuable parameters, especially peak oxygen uptake (VO(2)), for the evaluation of risk assessment in lung cancer surgery. It therefore represents an attractive way of identifying a patient at high risk for postoperative complications. However, many patients do not achieve the maximal or predictive level during an incremental exercise testing. The purpose of the current investigation was to study the value of the oxygen uptake efficiency slope (OUES), which shows exercise capacity during submaximal testing, in predicting postoperative mortality in patients with bronchogenic carcinoma scheduled for lung resection. Forty-nine patients with bronchogenic carcinoma participated in studies with exercise tests as a preoperative evaluation. The peak VO(2) was calculated for each subject by averaging values obtained during the final 10s of exercise. The following equation was used to determine OUES: VO(2)/log(10)VE. Peak VO(2) without postoperative complication was 22.8+/-3.3 ml/(kg min), however, peak VO(2) in patients with present complications was 19.1+/-4.2 ml/(kg min) (p=0.001). In addition, although the mean OUES in patients with present complications was 11.1+/-1.2, the mean OUES in the absent group was 13.3+/-2.1 (p<0.001). Although peak VO(2) is useful in evaluating selected patients with bronchogenic carcinoma, OUES is also a beneficial parameter and should be calculated and recorded with peak VO(2), a better predictor of poor surgical outcome than absolute values, and should be integrated into preoperative decision making.

Early outcomes of video-assisted thoracoscopic resection of thymus in 181 patients with myasthenia gravis: who are the candidates for the next morning discharge?

The aims of this study are to present the results of videothoracoscopic thymectomy in patients with myasthenia gravis (MG) and to predict the factors affecting the next morning discharge (NMD). This is a retrospective analysis of the prospectively recorded data of 181 consecutive myasthenic patients who underwent videothoracoscopic thymectomy from June 2002 to September 2009. Sixty-one patients (33.7%) were discharged on the next morning. Univariate and multivariate analyses were evaluated to determine the predictors for NMD. Mean calculated variables were: age (29.8 years), duration of symptoms (22.5 months), duration of surgery (51.3 min), postoperative stay (2.1) days, and visual analogue scale (2.1). No mortality occurred. Four patients were required to stay in intensive care unit (ICU) with a mean of 18.6 h. With logistic regression analysis, duration of operation (DoO) was calculated to be the only predictive factor for NMD (P=0.006). Video-assisted thoracoscopic thymectomy (VAT thymectomy) is a safe surgery procedure with a smooth postoperative period for MG. Although a detailed analysis was performed, only DoO was found to be a predictive factor for NMD in MG patients.

Association of epidermal growth factor receptor and K-Ras mutations with smoking history in non-small cell lung cancer patients

Lung cancer, a major health problem affecting the epithelial lining of the lower respiratory tract, is considered to be one of the deadliest types of cancer in males and females and it is well-known that smoking is the chief cause of lung cancer. In addition to smoking and environmental factors, genetic susceptibility may also contribute to the development of lung cancer. Previous studies have shown that certain non-small cell lung cancer (NSCLC) patients harbor gain-of-function mutations in the epidermal growth factor receptor gene (EGFR). Phosphorylated EGFR triggers the activation of intracellular signal transduction pathways, including the RAS-MAPK, PI3K-Akt and STAT pathways. However, K-Ras gene point mutations in codons 12, 13 or 61 cause the inactivation of GTPase activity which results in overstimulation of cellular growth and gives rise to neoplastic development. Our aim was to investigate the presence and association of EGFR and K-Ras mutations in 50 primary NSCLC patients with a smoking history by using real-time PCR and sequencing. EGFR mutations were detected in four patients (8%). Two of these mutations were L858R mutations and the remaining two were deletion mutations spanning between codons 746 and 750. The L858R mutation was significantly associated with smoking status (P=0.003). K-Ras codon 12 and 61 mutations were also observed in four patients. However, no association was observed between K-Ras mutations and the tumor staging, gender, histology and smoking status of the patients.

Alternative paratracheal lymph node dissection in left-sided hilar lung cancer patients: comparing the number of lymph nodes dissected to the number of lymph nodes dissected in right-sided mediastinal dissections

OBJECTIVE Removing or sampling lymph nodes from the bilateral paratracheal area through a left thoracotomy is not a standard procedure in patients with lung cancer. The aim of this study was to evaluate the feasibility of a technique without ductus arteriosus division and mobilization of the aortic arch and to compare the number of lymph nodes resected in left-sided dissections to the number of lymph nodes removed in right-sided mediastinal dissections that are routinely performed in clinical practice. METHODS A total of 93 patients with hilar lung cancer were evaluated. A prospective study was conducted on 51 patients with primary left-sided hilar lung cancer, who underwent left thoracotomy and paratracheal lymphadenectomy between January 2008 and January 2010. The number of nodes dissected in these patients was compared with the number of nodes dissected in 42 patients with right-sided hilar lung cancer by right-sided mediastinal dissection within the same period. RESULTS The mean number of resected nodes in the bilateral paratracheal area via left thoracotomy was 8.4 (2-18 nodes). The distribution from 4R-4L-2L-2R was as follows: 3.3-2.5-0.5-2.1, respectively. Six patients (11.7%) were diagnosed with occult N2, and two (3.9%) of these patients also had N3 disease concomitantly. The number of dissected nodes from the ipsilateral station 2 via right-sided versus left-sided thoracotomy was 1.6 versus 0.5 (p=0.000), whereas the number of dissected nodes from ipsilateral station 4 via right-sided versus left-sided thoracotomy was 3.3 versus 2.5, respectively (p=0.1). The number of dissected nodes from the contralateral station 2 via right-sided versus left-sided thoracotomy was 0.2 versus 2.1 (p=0.000), whereas those numbers from the contralateral station 4 via right-sided versus left-sided thoracotomy were 1.0 versus 3.3, respectively (p=0.000). CONCLUSIONS Lymphadenectomy of the paratracheal area via left thoracotomy without ductus arteriosus division and mobilization of the aortic arch is technically feasible. From these data, regardless of approach, more lymph nodes are obtained from the right paratracheal space; this appears to be due to the fact that there are more right-sided paratracheal lymph nodes.

An unusual intrapleural foreign body: ignored aspiration

A 54-year-old male patient was admitted to our department with fever, dyspnea and chest pain. Left pleural effusion and destroyed left lower lobe was noticed in his computerized chest tomography. After chest tube drainage, massive hemoptysis developed. An emergency thoracotomy was performed. A bronchopleural fistula, destroyed left lower lobe and the head of an oat were detected in the pleural space. Left lower lobectomy and perioperative pneumoperitoneum were performed. The patient had an uneventful postoperative (p.o.) course and was discharged on p.o. day 6. We present this case because of the rarity and to emphasize the clinical presentation. The physicians should be aware of life threatening complications of oat head aspiration.

Reimplantation of the Left Lung 17 Years After a Bronchial Rupture

We describe a 37-year-old female patient who had a major vehicle accident 17 years ago. A chest tube had been inserted through the left side of the chest to treat pneumothorax. She was readmitted to the hospital with dyspnea 17 years later. Her examinations, including fiberoptic bronchoscopy, revealed total atelectasis of the left lung with a blind-ending left main bronchus. Anastomosis of the left distal main bronchus to left main bronchus was performed. She had no complications and was discharged on postoperative day 8. Follow-up demonstrated a perfectly functioning left lung with nuclear and tomographic investigations performed on the first postoperative year.

Sleeve resection of the right main bronchus for postlobectomy broncho-pleural fistula

In this case report we present a novel treatment for bronchial fistula after lobectomy. The patient had right upper lobectomy for T1 N0 M0 peripheral adenocarcinoma and he had been reexplored 4 days later for massive air leak in another chest surgery department. After the reoperation the bronchial fistula persisted and the patient was admitted to our department. Nineteen days after the reoperation, bronchoscopy confirmed that the bronchial stump was totally opened. A sleeve resection to the right main broncus including the fistulous stump of right upper lobe was performed.

Life-threatening hemoptysis in a child: the only symptom.

An 8-year-old girl was evaluated for hemoptysis, 50 mL/day, which lasted for 3 days. Computed thoracic tomography detected a mass lesion in the right lower lobe. During rigid bronchoscopic examination, exanguinating hemoptysis occurred, and a Fogarty balloon catheter was placed in the right intermediate bronchus. Thoracotomy revealed a 2 x 2-cm mass in the right lower lobe. Common basal segmentectomy was performed. Pathological frozen-section analysis confirmed the diagnosis of perforated hydatid cyst.

Transcaval invasion of right atrium by thymoma: resection via transient cava-pulmonary shunt

Transcaval extension of the thymoma to the right atrium has very rarely been reported, and cardiopulmonary bypass is recommended for successful resection. An invasive thymoma with intravascular invasion of the superior vena cava, and the left innominate vein extending into the right atrium was presented. Intra-atrial extension was resected through a transient external shunt from the inferior vena cava to the main pulmonary artery. We discussed the feasibility of this surgical technique and possible advantages of cardiopulmonary bypass avoidance.