Investigation of some DNA repair genes association in non small cell lung cancer.

Ribonucleoside-diphosphate reductase subunit M2, also known as ribonucleotide reductase small subunit, is an enzyme that in humans is encoded by the RRM2 gene and also Ribonucleoside-diphosphate reductase large subunit is an enzyme that in humans is encoded by the RRM1 gene. RRM1 is a gene important in determining tumor phenotype, but also induced the expression of PTEN tumor suppressor gene, cell migration, invasion and metastasis formation, and play a preventive role. ERCC2 DNA repair mechanism is associated in more than 20 genes involved in the NER pathway. The aim of this study is to investigate rs13181 ERCC2 (T>G) (Lys751Gln), rs12806698 RRM1 (-269C>A) and rs6759180 (located in the 5'UTR) RRM2 (10126436G>A) gene polymorphisms by using real time PCR technique in patients with NSCLC. 193 NSCLC cases and 141 healthy control cases were included in this study. A significant difference was found between rs12806698 RRM1 genotype distributions (*p: 0.034) and were determined increases the risk of disease approximately 3.044 times AA genotype having (*p: 0.014 OR: 3.044, 95%CI: 1.205-7,688). A significant difference was found between rs6759180 RRM2 genotype distributions (*p: 0.033) and were determined increases the risk of disease approximately 3.49 times GG genotype having (p: 0,009 OR: 3, 49, %95CI:1.291-9,482). It was found significant difference in serum 8-OHdG levels between patients and controls (*p: 0001).

Association between survivin gene promoter -31G/C and -644C/T polymorphisms and non-small cell lung cancer.

Lung cancer is the most common cancer worldwide. Survivin is one of the first reported inhibitors of apoptosis proteins, which is an important family of proteins that regulate apoptosis. The survivin gene is located on human chromosome 17q25, which is composed of 142 amino acids. A common polymorphism of the survivin gene promoter -31G/C has been shown to influence cancer risk. This genetic variant has been associated with overexpression of survivin at both protein and mRNA levels in cancer cells. We examined promoter (-31G/C) genotype frequency in a patient group (N = 146), 77.4% GG, 18.5% GC, 4.1% CC, and in a control group (N = 98), 57.1% GG, 34.7% GC, 8.2% CC. These distributions were significantly different. Promoter (-644C/T) genotype frequency in the patient group was 40.4% TT, 48.6% TC, 11% CC, and in the control group it was 55.1% TT, 40.8% TC, 4.1% CC; these distributions were also significantly different. Individuals carrying the survivin 31 GC genotype and those carrying the survivin 644 CC genotype had a significantly decreased risk of having non-small cell lung cancer.

[Role of mineral elements in the immunological effects, activation nuclear transcription factor of NF-kappaB and matrix metalloproteinase].

Today chemical elements draw to themselves the increasing attention the immunological effects performance of a role of activators and inhibitors some many enzymes, active participation in inflammation processes that, undoubtedly, assumes their participation in cellular and humoral immunity. Main objective of the present review was attempt to consider a role and value of chemical elements in maintenance of a microelement homeostasis, interaction with immune system, their value in system proteolysis and regulation of antineoplastic immunity. The special attention of researchers is involved with the questions connected with ability of immune system to perceive and process pathogens with participation nuclear transcription of the factor NF-kappaB.

Very important histopathological factors in patients with resected non-small cell lung cancer: necrosis and perineural invasion.

BACKGROUND: The current staging system provides an anatomical classification of lung tumors; its secondary purpose is to allow the prognostic stratification of patients into homogeneous groups after surgery. In this work, intratumoral perineural invasion, lymphatic and blood vessel invasion together with the necrosis content of the tumor exclusive of the non-small cell cancer staging system were studied. METHODS: During a 4-year period, 152 patients operated for non-small cell lung cancer (NSCLC) at our hospital were analyzed. Mean age of patients was 55.7 +/- 10.1 years. RESULTS: Overall 5-year survival was 42.2 %. Mediastinal lymph node involvement, tumor size, incomplete resection, pneumonectomy, presence of necrosis and perineural invasion were significant prognosticators ( P = 0.03, 0.04, 0.0001, 0.046, 0.0246, < 0.0001, respectively). Multivariate analysis revealed that N status, perineural invasion, and the presence of necrosis were independent prognostic factors ( P = 0.006, P = 0.001, P = 0.001, respectively). Patients who had stage I tumor with necrosis and perineural invasion had a lower survival rate than those with stage IIIA tumor without these histopathological features ( P = 0.04). The presence of these histopathological characteristics in stage IIIA patients was a sign of a poorer prognosis ( P = 0.0001). CONCLUSIONS: Perineural invasion and the presence of necrosis independently indicated a dismal prognosis and their prognostic power is comparable to those of the TNM classification. These factors could be candidates for better survival stratification and the indicators of the need for adjuvant therapy in early stage lung cancer patients.

Factors affecting morbidity in chronic tuberculous empyema.

BACKGROUND: Chronic empyema is not a rare complication of pulmonary tuberculosis. Various treatment modalities ranging from open drainage to pneumonectomy, depending on the status of the disease, have been used to treat this complication. However, the best strategy for this disease remains unknown. This study examined the results of different treatment strategies for chronic tuberculous empyema. METHODS: Between January 1993 and December 2002, 36 patients (29 male and 7 female) with an average age of 29.3 years (range 13 - 52 years) presented with chronic tuberculous empyema characterized by empyema cavity and persistent pleural infections that were secondary to tuberculosis. The series consisted of patients who had had tube thoracostomy and underwater drainage without complete re-expansion. All patients were treated with open drainage. Of these, 6 patients had Eloesser flap for complete drainage of pleural pus and resolution of pleural infection. RESULTS: Eloesser-flap drainage resulted in a higher morbidity compared to the open-drainage-only method ( P = 0.011). Pneumonectomy, used as a final therapeutic option, resulted in more complications postoperatively ( P = 0.034). Antituberculosis therapy lasting six months or longer reduced the morbidity rate (54 % vs. 33.3 %), but the difference was not significant. CONCLUSIONS: Our findings indicate that open drainage leads to better results compared to those of Eloesser flap in patients with chronic tuberculous empyema. Patients who underwent pneumonectomy were expected to have higher complication rates and the procedure must therefore be avoided when possible.

Pulmonary sclerosing haemangioma mimicking hydatid cyst: a case report.

We report the case of a pulmonary sclerosing haemangioma radiologically presenting as a cystic lesion. The patient was found to have specific anti-echinococcus immunoglobulin E and therefore the preoperative diagnosis was that of pulmonary hydatid cyst. A surgical resection was performed. Although rarely encountered, pulmonary sclerosing haemangioma may show radiological and serological similarities to a pulmonary hydatid cyst. Both entities necessitate complete removal of the lesion without parenchymal resection.

Thoracic surgical operations performed under local anesthesia and sedation for diagnosis and treatment.

Generally, the operative procedures for the diagnosis or treatment of mediastinal, intrathoracic and/or chest wall lesions requiring rib resection are performed under general anesthesia. Although evidence suggests that thoracoscopy can be performed under local anesthesia, no report has indicated that some major thoracic procedures can be accomplished without general anesthesia. In our study, we advocate that certain surgical procedures could be performed under local anesthesia with a performance similar to that of general anesthesia. Thirty patients underwent thoracic procedures with local anesthesia and sedation for diagnosis and treatment. Seventeen of the patients were men, and the mean age of the patients was 49.6 years (range 16 to 71 years). There were 13 diagnostic procedures, and 17 procedures were for treatment purposes. The operative procedures performed using only local anesthesia were mini-thoracotomy (n = 9), mediastinotomy (n = 4), revision of a full-thickness posterolateral thoracic incision (n = 7), resection of the chondroma (n = 4), Eloesser flap (n = 1), metastasectomy of the chest wall (n = 3), empyectomy (n = 1), and video-assisted thoracoscopy (n = 2). Severity of pain was evaluated by VAS. There were no oral or intravenous analgesic requirements in the early postoperative period. No complications attributable to the procedure were observed. Thoracic surgical procedures for diagnosis and treatment performed under local anesthesia are simple, effective, economical and comfortable for the patient.

Transcutaneous electric nerve stimulation for the treatment of postthoracotomy pain: a randomized prospective study.

BACKGROUND: Insufficient relief of postthoracotomy pain is a major cause of increased rates of postoperative complications including inadequate coughing, mucous plugging, hypoxia, compromised ventilation or even bacterial lung infection. We aimed to assess the efficacy of transcutaneous electric nerve stimulation (TENS) in patients with postthoracotomy pain. METHODS: Forty patients scheduled to undergo posterolateral thoracotomy were randomly allocated to receive either TENS or patient-controlled intravenous morphine. Postoperative pain was evaluated using a visual analogue scale (VAS) and the Prince Henry pain scale. Pulmonary function was evaluated and an intergroup comparison was done. RESULTS: On the first three days following surgery, the VAS intensity of the TENS group did not differ significantly from that of the morphine group ( P > 0.05), and on the first two days following thoracotomy, the Prince Henry scale of the TENS group was not statistically significantly different. However, the VAS intensity was significantly lower than that of the control group on the fourth ( P = 0.044), fifth ( P = 0.016), sixth ( P = 0.009), seventh ( P = 0.008), eighth ( P = 0.004), ninth ( P = 0.002), tenth ( P = 0.001), fifteenth ( P = 0.002), thirtieth ( P < 0.001), forty-fifth ( P < 0.001) and sixtieth ( P < 0.001) days. The Prince Henry scale of the TENS group was found to be significantly diminished from the 3rd to the 60th day. TENS significantly reduced the analgesic requirements from day 5 to 60 ( P < 0.01). No noticeable side effect was observed in the TENS group during the study period. CONCLUSION: This study demonstrated that TENS provided a better pain relief and comfort compared to PCA from the fourth postoperative day onwards, and this pain-reducing effect continued for at least two months postoperatively.

Is lobe-specific lymph node dissection appropriate in lung cancer patients undergoing routine mediastinoscopy?

BACKGROUND: The extent and the necessity of lymph node dissection has yet to be defined after resectional surgery for lung cancer. We aimed to analyze the lobe-specific extent of lymph node positivity in patients who underwent preoperative mediastinoscopy as a routine strategy. METHODS: A total of 280 patients with non-small cell lung cancer with negative mediastinoscopy were operated on in our center between January 1997 and June 2003. Hilar and mediastinal lymphadenectomy was performed in every patient. RESULTS: The most commonly involved lymph nodes were found to be paratracheal station lymph nodes (n = 83; 96.5 %) for right upper lobe tumors, subcarinal station lymph nodes (n = 52; 88.1 %) for right lower lobe carcinomas, aorticopulmonary lymph nodes (n = 62; 92.5 %) for left upper lobe and subcarinal station lymph nodes (n = 49; 96.0 %) for left lower lobe tumors. In the patients with right upper lobe, right lower lobe and left lower lobe tumors, the presence of a tumor at these stations was found to be an indicator for poor prognosis ( P = 0.033, P = 0.0038 and P = 0.0016, respectively). Patients with multiple station N2 disease did not survive beyond 3 years. CONCLUSIONS: In patients who underwent routine mediastinoscopy, lobe-specific lymph node dissection could be recommended. Patients with multilevel N2 involvement did not seem to benefit from resectional surgery.

Chylomediastinum following tracheal surgery.

Chylomediastinum is a rare but serious complication following thoracic procedures. A 70-year-old woman underwent tracheal resection through median sternotomy. Sternal dehiscence and chylous drainage appeared on the second postoperative week. Oral intake was stopped and total parenteral nutrition was started. Drainage stopped after two weeks. The region was ligated with a purse string suture during revision of sternotomy. A minimal lymph leakage was determined on control Tc-99 lymphoscintigraphy, which indicated injury of the thoracic duct. The patient has been problem-free for 9 months.

Pulmonary malacoplakia.

We report a case of a 76-year-old man with bilateral pulmonary and pleural nodules and type 2 diabetes mellitus. Laboratory investigations revealed no sign of immunodeficiency. Pleural, pulmonary and diaphragmatic biopsies were taken through a mini-thoracotomy. Pathology showed Michaelis-Gutmann inclusion bodies and diagnosis of malacoplakia was made. Malacoplakia masquerading as bilateral tumour masses was thought to be noteworthy especially in an immunocompetent patient.

Prediction of morbidity after lung resection in patients with lung cancer using fuzzy logic.

BACKGROUND: Preoperative evaluation of patients with potentially resectable non-small cell lung cancer aims to estimate the risk of planned surgery. Evidence of several factors that identify patients at risk for complications from thoracotomy is controversial. The aim of this study was to introduce and implement in medical practice a fuzzy system used in risk assessment of pulmonary resection for lung cancer. METHODS: Ninety-one consecutive patients who underwent pulmonary resection for lung cancer were investigated. The overall complication rate was 39.6 % (a total of 63 complications were seen in 36 patients). A fuzzy logic model was created with 9 input (presence of chest pain, weight loss, clinical T stage of the tumor, FEV 1, serum protein, preoperative arterial partial oxygen pressure and cigarette smoking, erythrocyte sedimentation rate and peripheral blood leukocyte count) and two output classes (high-risk and low-risk groups). The fuzzy classifier's performance was tested. RESULTS: The model was able to predict correctly the occurrence of complications in 22 out of 29 patients in the high-risk group with a sensitivity of 76 %, while 9 out of the 52 patients from the low-risk group developed complications (17 %). CONCLUSION: The fuzzy classification system provides an accurate tool to predict complications of resections in patients with non-small cell lung cancer.

The coincidence of mediastinal tuberculosis lymphadenitis in lung cancer patients.

Mediastinal lymph node enlargement in operable non-small cell lung cancer is of clinical importance since it indicates the high possibility of nodal metastasis. The coincidence of tuberculosis and lung cancer is detected by the mediastinal lymph node staging of lung cancer patients. In our study, we retrospectively re-evaluated the records of patients who had been hospitalized with the diagnosis of lung cancer for the past 10 years. The mean age was 58 +/- 10 years (ranging from 39 to 72). A tuberculous lymphadenitis was detected in 16 of the 315 (5.1%) patients in one and/or multiple stations by either mediastinoscopy or thoracotomy. Inferior paratracheal lymph nodes (4R-4L) were the most frequently affected. None of the patients had a history of primary tuberculosis infection. The cell type was squamous cell carcinoma in ten patients (62.5%) and adenocarcinoma in six patients (37.5%). The tumour was located in the right lung in nine patients (56.2%). The most frequently involved site was the right upper lobe (n = 13, 81.2%). N2 disease was detected in six patients (37.5%). Our study showed that 5.1% of lung patients had tuberculous lymphadenitis coincidentally. The diagnosis and treatment of this latent disease could be considered as important, especially in lung cancer patients who would potentially receive radiotherapy or chemotherapy which alters the immune system. However, the real value of this finding needs further study.

Emergency surgery for massive haemoptysis.

BACKGROUND: Massive haemoptysis (600 ml in 24 hours) results in considerable mortality and deserves appropriate management. Since it is life threatening, lung resection remains the surgical treatment of choice in unrelenting haemoptysis. MATERIAL AND METHODS: We retrospectively reviewed all patients (n = 29) who were referred to our clinic between January 1994 to September 2001 with massive haemoptysis (> 600 ml/24 h). All patients had uncontrollable haemorrhage and/or failure of conservative treatment. After initial resuscitation, assuring adequate airway and providing adequate intravenous access, emergency thoracotomy was performed in all patients following rigid bronchoscopy (n = 27) in order to localize the bleeding. RESULTS: The most common underlying cause of the massive haemoptysis was pulmonary tuberculosis (n = 10) followed by emphysema in 4, lung cancer in 3, collagenous vascular disease in 2 and aspergilloma in one patient. Seventeen lobectomies (58.6%), 5 pneumonectomies (17.2%), 3 segmentectomies and 3 bilobectomies were done whereas physiological lung exclusion was performed in one patient. Haemoptysis could be controlled in all patients. Rate of operative morbidity and hospital mortality were 27.5% and 11.5% respectively. We recorded one patient with recurrent haemoptysis who was treated by completion pneumonectomy. CONCLUSION: Despite the debate over definition of massive haemoptysis and indication for surgery in these patients, emergency pulmonary resection provides an effective treatment with acceptable morbidity and mortality in patients with massive haemoptysis.

Simultaneous bilateral spontaneous pneumothorax report of 12 cases and review of the literature.

Simultaneous bilateral spontaneous pneumothorax (SBSP) is a very rare condition, mainly seen in patients with underlying lung disease. Up to now, there are 65 patients who have been published. Twelve consecutive patients who presented with SBSP as definitive diagnosis were recruited for this study. They represented 1 % of all patients with spontaneous pneumothorax. All patients had immediate bilateral chest tubes on admission. Five of the 12 patients (42%) had no underlying lung disease. In 7 patients, SBSP was secondary to pulmonary metastases, histiocytosis X, undefined interstitial pulmonary disease, tuberculosis, pneumonia and chronic obstructive pulmonary disease. None of the patients died during hospitalization. Eleven patients were treated with chemical pleurodesis, whereas thoracotomy and pleurectomy were necessary in 7 patients. Reexpansion of the lungs was achieved in all patients. Immediate bilateral chest tube insertion and pleurodesis are of major importance in the treatment of SBSP although a subset of patients needed surgical pleurectomy. Combination of these treatments provides successful and uneventful treatment of the disease.

Antibiotic prophylaxis in elective thoracic surgery: cefuroxime versus cefepime.

BACKGROUND: Infection is one of the major morbidity factors after thoracic surgery. Although different prophylactic regimens have been used to prevent this complication, the ideal prophylactic agent, dose and duration of administration remain unknown. METHODS: All patients included underwent elective lung resection. 102 selected patients consecutively scheduled for major thoracic surgery were enrolled in this study and randomized into either the cefuroxime group (n = 50) or the cefepime group (n = 52). RESULTS: Twelve pathologic bacterium strains were isolated in the cefepime group, whereas only 5 pathogenic strains were isolated in the cefuroxime group; the difference was statistically significant (p = 0.04). Two empyemas (3.8 %) in the cefepime group were noted, while the cefuroxime group showed no cases of empyema (p = 0.16). Overall infection rate (pneumonia + bronchopneumonia + empyema) were 14.0 % and 26.7 % in the cefuroxime and the cefepime groups, respectively (p = 0.12). Using chest radiography, pulmonary infiltration was found to be more frequent in the cefuroxime group (p=0.002). CONCLUSION: Cefuroxime as a prophylactic agent in major thoracic surgical operations was marginally more effective than cefepime, and presented an additional cost advantage.

The value of mediastinoscopy in preoperative evaluation of mediastinal involvement in non-small-cell lung cancer patients with clinical NO disease.

BACKGROUND: The efficacy of mediastinal lymph node examination using cervical mediastinoscopy in operable non-small cell lung cancer patients without radiological nodal involvement on computerized tomography (CT) has been elusive. METHODS: The value of mediastinoscopy as a staging modality for assessing the mediastinal lymph node status was evaluated in 79 patients with presumed resectable non-small-cell lung cancer (NSCLC) with mediastinal nodes smaller than 1 cm (NO) form the CT scan. Sixty-one patients who did not have nodal involvement at mediastinoscopy and had complete medical records underwent complete resection. RESULTS: Negative predictive value (NPV) of the CT scan according to mediastinoscopy was 92.4 %. Histopathological examination of the surgical specimen showed the NPV of mediastinoscopy to be 93.4 %. Only 4 patients (3 patients with N2, 1 patient with N3 disease) were not correctly staged using CT scanning and mediastinoscopy. According to the pathological examination, the NPV of CT was found to be lower (76.5 %) in patients with adenocarcinoma, but the difference was not statistically significant (p > 0.128) CONCLUSION: Although the likelihood of surgical-pathological N2 is slightly higher in patients with adenocarcinoma, radiological examination of patients with cNO NSCLC disease can be as accurate as mediastinoscopy in appropriately staging mediastinal lymph node involvement.

Aprotinin reduces postoperative bleeding and the need for blood products in thoracic surgery: results of a randomized double-blind study.

OBJECTIVE: Bleeding complications have been a major concern in certain thoracic surgery operations, especially decortication and pulmonary resection for inflammatory pulmonary infection. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood consumption. METHODS: Use of blood products (packed red cells, whole blood), chest tube drainage, analgesic requirement, chest tube duration for the patients undergoing major thoracic operations were recorded. In a double blind randomized fashion, patients were assigned to two groups receiving aprotinin (n=51) at a loading dose of 10(6) kallikrein inhibitory units (KIU) followed by an infusion of the same dose during chest closure or receiving placebo (n=52). On a daily basis, red-cell percentages of total fluid from drainage bottles were recorded and using the blood hematocrit level of the patient of the day before, the corrected value for the patient's blood volume equivalent of daily drainage was calculated. RESULTS: There was a significant reduction in perioperative use of donor blood (0.98+/-0.92 vs. 0.45+/-0.32 unit; P=0.0026), and total chest tube drainage (corrected value for the corresponding blood volume) (28.2+/-36.9 vs. 76.9+/-53.3 ml, P=0.0004) (mean+/-standard deviation) in the aprotinin group. However, aprotinin did not reduce postoperative transfusion or decrease in hematocrit level due to thoracic operations. In high transfusion-risk thoracic surgery patients (patients who underwent decortication, pulmonary resection for inflammatory lung disease and chest wall resection), the perioperative transfusion was only 0.50+/-1.08 units in aprotinin group, compared with 1.94+/-0.52 units in control group (P=0.003). Postoperative transfusion was also reduced in aprotinin administrated group (0.53+/-0.56 vs. 1.38+/-0.97 units; P=0.02). The mean total blood loss was decreased to nearly one third of the blood loss of the control group (41+/-28 ml vs. 121+/-68 ml; P=0.001). CONCLUSION: Aprotinin significantly reduced perioperative transfusion requirement and postoperative bleeding during major thoracic operations. Aprotinin decreased perioperative transfusion needs. Moreover, patients who were at risk of greater blood loss during and after certain thoracic operations had a greater potential to benefit from prophylactic perioperative aprotinin treatment.