NEUROENDOCRINE TUMORS OF THE LUNG WITH SURGICAL RESECTION AND LYMPH NODE DISSECTION IN A TERTIARY THORACIC SURGERY CENTER.

CONTEXT: Management of neuroendocrine tumors is highly dynamic, in both diagnosis and treatment. OBJECTIVE: Surgical resection with lymph node approach offers excellent 5-years survival. DESIGN: Between 2008 and 2011 we operated with radical intent 326 lung cancers. PATIENTS AND METHODS: Cases without lymph node approach were excluded. We found 38 neuroendocrine malignancies: 12 typical carcinoids, 3 atypical carcinoids, 4 large cell neuroendocrine carcinomas (LCNEC) and 10 small-cell lung cancers (SCLC). Limits of the study are: variable lymphadenectomy technique; absence of PET - CT and EBUS-TBNA (EndoBronchial UltraSound - TransBronchial Needle Aspiration) for staging; incomplete data for disease-free survival. RESULTS: We performed 13 pneumonectomies, 22 lobectomies and 3 non-anatomical resections. There were 5 bronchoplasties. The 5-year survival difference between NSCLC (non-small-cell lung cancer - 42.9%) and SCLC (40.53% - one of the best from the literature) is not statistically significant (p=0.4780). Five-years survival was 100% for typical and atypical carcinoids - the best published. We found lymph node metastasis in 2 typical carcinoids, in 2 atypical carcinoids and in 6 SCLCs. CONCLUSIONS: For typical and atypical carcinoids, radical resection with lymphadenectomy offers 100% 5-years survival. Early-stage SCLC may benefit from radical resection; lymph node dissection is mandatory because of the well-known precocious lymphatic dissemination.

Practical use of the Virtual Cell Based Assay: Simulation of repeated exposure experiments in liver cell lines.

The Virtual Cell Based Assay (VCBA) was applied to simulate the long-term (repeat dose) toxic effects of chemicals, including substances in cosmetics and personal care products. The presented model is an extension of the original VCBA for simulation of single exposure and is implemented in a KNIME workflow. This work illustrates the steps taken to simulate the repeated dose effects of two reference compounds, caffeine and amiodarone. Using caffeine, in vitro experimental viability data in single exposure from two human liver cell lines, HepG2 and HepaRG, were measured and used to optimize the VCBA, subsequently repeated exposure simulations were run. Amiodarone was then tested and simulations were performed under repeated exposure conditions in HepaRG. The results show that the VCBA can adequately predict repeated exposure experiments in liver cell lines. The refined VCBA model can be used not only to support the design of long term in vitro experiments but also practical applications in risk assessment. Our model is a step towards the development of in silico predictive approaches to replace, refine, and reduce the in vivo repeated dose systemic toxicity studies in the assessment of human safety.

From cineradiography to biorobots: an approach for designing robots to emulate and study animal locomotion.

Robots are increasingly used as scientific tools to investigate animal locomotion. However, designing a robot that properly emulates the kinematic and dynamic properties of an animal is difficult because of the complexity of musculoskeletal systems and the limitations of current robotics technology. Here, we propose a design process that combines high-speed cineradiography, optimization, dynamic scaling, three-dimensional printing, high-end servomotors and a tailored dry-suit to construct Pleurobot: a salamander-like robot that closely mimics its biological counterpart, Pleurodeles waltl Our previous robots helped us test and confirm hypotheses on the interaction between the locomotor neuronal networks of the limbs and the spine to generate basic swimming and walking gaits. With Pleurobot, we demonstrate a design process that will enable studies of richer motor skills in salamanders. In particular, we are interested in how these richer motor skills can be obtained by extending our spinal cord models with the addition of more descending pathways and more detailed limb central pattern generator networks. Pleurobot is a dynamically scaled amphibious salamander robot with a large number of actuated degrees of freedom (DOFs: 27 in total). Because of our design process, the robot can capture most of the animal's DOFs and range of motion, especially at the limbs. We demonstrate the robot's abilities by imposing raw kinematic data, extracted from X-ray videos, to the robot's joints for basic locomotor behaviours in water and on land. The robot closely matches the behaviour of the animal in terms of relative forward speeds and lateral displacements. Ground reaction forces during walking also resemble those of the animal. Based on our results, we anticipate that future studies on richer motor skills in salamanders will highly benefit from Pleurobot's design.

Bronchoanastomotic and bronchoplastic resections in pulmonary malignancy retrospective study 2000 - 2009.

UNLABELLED: Bronchial resections are surgical procedures in which bronchial continuity is interrupted, followed by reconstruction of resected ends through terminal anastomosis or various forms of plastic procedures. The purpose of these interventions is to preserve functional lung parenchyma. These procedures are indicated in tumors with central location as an alternative to pneumonectomies, serving to preserve maximum functional lung parenchyma. MATERIAL AND METHODS: We considered bronchoanastomotic and bronchoplastic procedures performed in our clinic over the period 2000-2009, for malignancy. There were 52 bronchoanastomotic resections and 9 bronchoplastic resections of which we analysed 40 bronchoanastomotic resections and 4 bronchoplastic resections (44 cases) ± associated resection. We excluded cases with non-malignant pathology or those with incomplete data at the beginning of the study. RESULTS: The importance of the main factors involved in relation with survival was calculated. We considered the type of surgery performed, histological type, TNM stage, and characteristics of the study group (age, sex). We found statistically significant correlations between survival and histopathology of malignancy with a better survival for lung carcinoids, especially for typical carcinoid tumors. TNM stage did not significantly influence survival, but N2 nodal involvement,according to the statistics, shows a poor prognosis. Age is another statistical significant factor correlated with post operative life expectancy, patients over 65 years old having a worse postoperative survival. CONCLUSIONS: In the corresponding lung malignant pathology, bronchoanastomotic bronchoplastic resections are indicated,but one must take into account the patient's age before submission to surgery, the histopathologic type and N2 nodal involvement.

Cervico-mediastinal thyroid masses - our experience.

INTRODUCTION: Over the last decades, several definitions and classifications of cervico-mediastinal goiters and thyroid masses have been proposed. We analyze and discuss the clinical presentation, the diagnostic procedures and the surgical technique in relation to post-operative complications and results in cervico-mediastinal thyroid masses admitted in our Clinic of Thoracic Surgery over a period of 22 years (1991-2012). METHODS: We reviewed 130 patients who underwent surgery for retrosternal thyroid masses, 77 (59.23%) women and 53(40.77%) men. Mean age was of 53 years. Shortness of breath was observed in 71 (54.61%) patients as the most frequent preoperative symptom. Cervico-thoracic CT scan reveales the existence of a cervico-mediastinal mass and can appreciate the degree of intrathoracic progression, tracheal compression and dislocation, as well as the relations with other anatomical structures of the visceral mediastinum. All 130 patients were prepared for a thoracic approach, majority of the cases were operated by Prof. T. Horvat. The surgical procedure was performed by cervical approach only in most of the cases (106 cases) (Kocher type cervicotomy in 63 cases and Horvat type "en-Y" cervicotomy in 43 cases). We used a bipolar approach for large cervico-thoracic masses: cervicotomy and partial upper sternotomy in 20 cases, cervicotomy and full sternotomy in 3 cases, cervicotomy and right axillary thoracotomy in one case. RESULTS: The removal of the thyroid mass and decompression of the trachea have been achieved in all cases. Post operative results were very satisfactory, with absence of respiratory distress and with normal function of the vocal cords. No post operative mortality was encountered. CONCLUSION: The presence of a cervico-mediastinal thyroid mass with or without respiratory distress requires a surgical excision as the only treatment option. The surgical procedure represented a milestone for both anesthesiologist (difficult intubation in some cases of large goiters) and thoracic surgeon.Thyroid masses extending to the mediastinum can be excised successfully by cervical incision. Bipolar approach has an excellent outcome, achieving a safe resection, especially in large thyroid masses extending to the mediastinum with close relations to mediastinal structures.

Hypertensive late hemothorax following left pneumonectomy.

INTRODUCTION: Lung cancer is an extremely serious disease, in most cases the onset of symptoms comes in late stages of the disease. Local and distant tumor development limits the surgical indication, many times the surgical act being a heroic one. Out of all pulmonary resections pneumonectomies are real challenges as possible postoperatory complications can be life-threatening. MATERIALS AND METHOD: We present the case of a 66 year-old female patient at the time of surgery, diagnosed with locally advanced adenocarcinoma of the left lung (lower lobe tumor invading the upper lobe), who sustained left pneumonectomy with mediastinal lymphadenectomy in March 2012. Immediate postoperative evolution was favorable" gradual reduction of the residual cavity, with left shift of the mediastinum€" basically a normal post-pneumonectomy course. RESULTS: Upon imagistic control at one year postoperatively the following was observed: the residual cavity had increased in size under the pressure of a fluid which instead of diminishing in quantity was present in a significantly higher volume than on previous postoperative examinations. The general consensus was that we are dealing with pleural metastases which were producing excess pleural fluid. The evolution of the patient and subsequent surgical interventions have demonstrated that the first impression is not always the truth. CONCLUSION: There are cases, like the one presented, which seem without therapeutic solution. Upon careful analysis, dubled by perseverance, these cases benefit from spectacular results which break down grim hypotheses previously formed. Associated pathology can create in these cases an unbalance in the organism, which will negatively influence local postoperative evolution.

Impact of adjuvant chemotherapy in stage IB non-small-cell lung cancer: an analysis of 112 consecutively treated patients.

PURPOSE: The impact of adjuvant chemotherapy (CT) in the management of radically resected stage IB non-small cell lung cancer (NSCLC) is highly debated. The aim of this study was to evaluate the outcome of this category of patients treated at our institution. METHODS: We retrospectively analysed the survival data of patients with pathologic stage IB NSCLC, who received at least 1 cycle of adjuvant CT. CT was planned to be platinum based and to be delivered for 6 cycles. RESULTS: One hundred and twelve consecutively treated patients were evaluated. PATIENT CHARACTERISTICS: median age 60 years, median tumor diameter 4 cm, 87% underwent lobectomy and 13% pneumonectomy, 58% had visceral pleural involvement (VPI). After a median follow up of 46 months, the estimated 5-year disease-free (DFS) and overall survival (OS) rates were 68% and 77%, respectively. The mean number of CT cycles was 5.2 (range 3-6), with 82% of patients receiving ≥ 5 cycles. The median cisplatin dose intensity (DI) was 22 mg/m(2)/week, and the relative DI was 85%. Median total cisplatin (CDDP) dose/patient was 416 mg/m(2). A total of 31 (27.6%) relapses were recorded, of which 81% were distant. Multivariate analysis showed no significant interaction between overall survival and the following variables: gender, type of surgery, histology, tumor volume, VPI. CONCLUSION: Our results compare favorably with the historical data evaluating the outcome of stage IB patients treated by surgery alone in a customary medical setting. Overall, our data support the use of adjuvant CT in stage IB NSCLC patients.

[Minimally invasive surgery in the treatment of malignant pleuro-pericardial effusions]. / Chirurgia miniinvaziva în tratamentul pleuro-pericarditelor maligne.

INTRODUCTION: Malignant pleuro-pericardial effusions (MPPEs) are a common problem in the treatment of patients with cancer and may occur with any malignancy. METHODS: Between 01.01.1998 -31.12.2008 we conducted a retrospective study. During this period of time 46 patients were diagnosed and treated for malignant pleuro-pericardial effusions in Clinic of Thoracic Surgery under Prof. Teodor Horvat coordination (from SUUMC). RESULTS: In this study a total of 42 MPPEs have been approached through minimally invasive procedures (36 patients underwent thoracoscopic procedures and 6 patients were subjected to VATS). In our study, the pulmonary cancers were the most frequent primary cancers who caused MPPEs (22 cases). The thoracoscopic pleuro-pericardial window was the most frequent and efficient procedure used for pericardial drainage (34 cases). Effective control of the recurent malignant pleural and pericardial effusions was made most frequent through postoperative pleural bleomycin instillation (22 cases) and through thoracoscopic insufflation of talc in 14 cases. CONCLUSIONS: The minimally invasive thoracic surgery is a safe and efficient method for diagnosis and treatment of pleuro-pericardial effusions.

[Hydatid cyst of anterior mediastinum]. / Chistul hidatic al mediastinului anterior.

INTRODUCTION: Echinococcosis is endemic in Romania. Hydatid cyst can develop in any segment or organ, but the most frequent locations are liver and lung. Mediastinal hydatid lesions are extremly rare and only a few cases exists in the medical literature. MATERIAL AND METHOD: Between 1994 and 2011 Thoracic Surgery Clinic, UMF "Carol Davila" there were 3 patients diagnosed and surgical trated for hydatid cyst of mediastinum. The patients were 2 men and 1 woman aged of 20, 37 and 52 years. All hydatid cysts were located in the anterior mediastinum and all were solitary lesions when diagnosed. RESULTS: In 1 case the positive diagnosis was made preoperatively, in the other 2 the diagnosis was intraoperative. The approach was through thoracotomy. One cyst was complicated (nonviable thymic hydatid cyst), treated by ideal cystectomy, and 2 cysts were viable. There was 1 postoperative complication: gaseous cerebral embolism remitted after medical treatment, caused by the intraoperative use of H2O2 as scolicide agent. CONCLUSIONS: Although very rare, anterior mediastinal hydatid cysts must be considered in every patient with anterior mediastinal mass. Complete surgical excision is the treatment of choice; surgery followed by parasiticide therapy provides complete cure.

[Neurogenic tumors of the posterior mediastinum]. / Tmorile neurogene ale mediastinului posterior.

The posterior mediastinum is the potential space along each side of the vertebral column and adjacent proximal portions of the ribs--the paravertebral sulci. From the posterior mediastinal tumors, the most commonly encountered are the neurogenic tumors (75%), the remaining 25% are represented by a heterogenous group of rare tumors including teratoma, lymphoma, sarcoma and other lesions arising outside the mediastinum and projecting into the posterior compartment. Surgical excision, by thoracotomy or miniinvasive techniques, is the first line of treatment in the posterior mediastinal tumors. Tumors with extension into the spinal canal (dumbbell tumors), accounting for nearly 10% of the posterior mediastinal tumors, require a multidisciplinary approach: thoracic surgeon and neurosurgeon. We present the experience of the "Carol Davila" University of Medicine and Pharmacy Thoracic Surgery Clinic in the surgery of neurogenic posterior mediastinal tumors throughout a 9 year period (2001 - 2010). 42 cases admitted and operated in this period are being analysed.

[Solitary pulmonary nodule--150 resected cases]. / Nodulul pulmonar solitar--150 de cazuri operate.

Solitary pulmonary nodule represents a radiological entity with unknown prevalence in general population. As definition, solitary pulmonary nodule has 3 cm diameter or less and is surrounded by lung parenchyma, with no other abnormalities on the same chest X-ray or CT scan film. The differential diagnosis of the solitary pulmonary nodule includes over 100 conditions and the most frequent is lung cancer. Identification and correct management of the solitary pulmonary nodule opposes early detection and treatment of the lung cancer and the uselessness of a surgical procedure on a benign disease which needs no treatment. After analyzing 150 solitary pulmonary nodules resected and after comparing the results with the literature, given the fact that 48.66% of the nodules are malignant and 52.66% of the nodules have the maximum accepted dimensions (3 cm), the authors proposed an algorithm for solitary pulmonary nodule management adapted to Romania's accessibility to diagnostic procedures. As conclusion, the surgical resection of an indeterminate solitary pulmonary nodule (not certified as benign at CT scan or by biopsy) has an absolute indication and curative intention.

[A giant thoracoabdominal tumor--hereditary multiple exostoses]. / Tumora giganta toracoabdominala. Maladia exostozanta ereditara.

Hereditary multiple exostoses (HME), also known as osteochondromatosis, is an inherited, autosomal dominant disorder in which multiple osteochondromas develop throughout the skeleton. We present the case of a 17 years old boy diagnosticated with HME with multiple prior orthopedic interventions for upper and lower limbs deformant osteochondromas. He was admitted in our service for a giant osteochondroma localized at the left thoraco-abdominal border arising from C11, C12 ribs, involving the thoracic postero-bazal wall, the abdominal posterior wall and practically the entire left retroperitoneal space. We performed the total resection of this giant tumor (2.6 kg) with postero-inferior thoracic parietectomy (10 to 12 ribs) and abdominal postero-lateral parietectomy followed by the thoraco-abdominal parietal reconstruction with a dual-mesh soft tissue patch, after the high reinsertion of the left diaphragm. The postoperative results were very good from both points of view: esthetical and functional, with preservation of the diaphragm activity and the anatomical reposition of the abdominal viscera. The paper refers to the etiopathogenesis, clinical symptoms, diagnostic, and therapeutic considerations of HME.

[Pleurotomy--an operation by the general surgeon]. / Pleurotomia -- operatie la îndemâna chirurgului generalist.

The authors present the newest data of a minimal thoracic technique: the pleurotomy. In our times this technique requires the modem chest tubes, the complete pleurotomy sets for different emergent situations. The authors presents the indications, the possible complications, their own technique of pleurotomy and the actual management of pleural drainage.

Giant laterocervical fibrosarcom.

Soft tissue sarcomas are rare tumors representing 1% of all malignancies and less than 10% concerning head and neck tumors. We are presenting the case of a 42-year-old patient that was admitted in our service for a giant laterocervical tumor (15/12/10 cm). We performed total excision of this tumor en bloc with the involved tegument; the resulting defect was covered with a split thick skin graft. The weight of the tumor was 500 g. Histopathological examination revealed an intermediate-grade fibrosarcoma. The postoperative evolution was good; radiotherapy was indicated.

Toxicity testing of herbicide norflurazon on an aquatic bioindicator species--the planarian Polycelis felina (Daly.).

Norflurazon is a bleaching, preemergence herbicide. Due to its mobility and long half-life it presents a potential for groundwater contamination. The aim of our study was to investigate toxic effects of norflurazon on non-targeted aquatic bioindicator organism, the planarian Polycelis felina (Daly.). Animals were exposed to water solutions of norflurazon in concentrations 200, 20, 2 and 0.2 microM. Mortality, locomotive and morphological changes were monitored. Histological changes were studied both on treated and control animals with light microscopy. The primary DNA damage on single planarian cells was studied using the alkaline comet assay. Three comet parameters were studied: tail length, percentage of DNA in comet tail and tail moment. The results showed that norflurazon caused mortality, locomotive, morphological and histological changes in treated animals compared to corresponding controls. The most prominent histological changes were damage of the outer mucous layer, lack of rhabdites, damage to epidermis and extensive damage to parenchyma cells. The results of alkaline comet assay indicated that norflurazon in concentrations of 2 and 0.2 microM induces significant increase of primary DNA damage in planarian cells compared to the corresponding control animals. The mean values of all three measured parameters were significantly elevated on the fourth day of the treatment compared with the first and the seventh day. Based on the results of mortality and locomotive observations, we conclude that the fourth day of the treatment represents a certain threshold within planarian metabolism followed by the beginning of detoxification and recovery. However, histological preparations and comet data statistics show results indicating that high toxicity on the seventh day of the treatment gave the results of decrease of DNA damage due to the tissue/cell damage (apoptosis) and not recovery. The present study showed the ability of norflurazon to induce a wide range of different toxicological responses in freshwater planarian Polycelis felina (Daly.).

[Pulmonary aspergilloma successfully operated on in a patient with the pentalogy of Fallot]. / Aspergilom pulmonar operat cu succes la un purtator de pentalogie Fallot.

Fallot disease occurs in 10% of congenital heart diseases. This case showed a clinical association between Fallot disease and a pulmonary aspergilloma. A 44-years male, with a history of Fallot disease (diagnosed in childhood) and a normal life, was admitted for repeated hemoptysis during last three months. Clinical examination revealed signs of Fallot disease: cyanosis, finger clubbing. CT scan and chest X-ray revealed a cavitary image in the right upper lobe. The CT image revealed a typical aspect of cavitary aspergilloma. The patient was referred to the thoracic surgeon, a right upper lobectomy was performed, which confirmed the presence of aspergilloma. Postoperative evolution was good.

[The chronology and diagnostic round of patients operated on for bronchopulmonary cancer]. / Studiu asupra cronologiei si al circuitului diagnostic al bolnavilor operati pentru cancer bronhopulmonar.

UNLABELLED: 37 patients with certified diagnosis, operated for lung cancer (LC) in The Central Military Hospital Bucharest, during six months period (October 1st 1996-June 1st 1997). It was a retrospective study on the patients medical files. Sex distribution, postsurgical staging and histological type were studied. We calculated the following delays: 1. Between the first medical examination and the first suspicion (chest X-ray): 6 +/- 3 days; 2. Between the first medical examination and first hospital admission: 14 +/- 11 days; 3. Between the first hospital admission and the first admission in surgical units: 43 +/- 23 days; 4. Between the first admission in surgical units and surgery: 59 +/- 26 days; 5. The delay until bronchoscopy: 23 +/- 16 days; 6. The delay until the CT examination: 26 +/- 16 days; 7. Between the first medical examination and the surgery: 78 +/- 30 days. These delays were correlated with the specialty profile of the services which referred the patients: pulmonology, internal medicine, oncology or primary services. CONCLUSION: 1. Most patients come from pulmonology units (22 out of 37 patients); 2. There are significant delays until bronchoscopy and CT scan, the availability of these services is still limited; 3. The primary care medical network is still inefficient in early diagnosis of LC; 4. The overcrowding of thoracic surgery unit (scheduling for surgical intervention). All of these are arguments for developing more efficient and faster circuits of LC diagnosis, especially for high risk patients.

[Clinical study of the efficacy of albendazole treatment in human hydatidosis]. / Studiu clinic al eficientei tratamentului cu albendazol în hidatidoza umana.

A follow-up study of Albendazol effectiveness therapy in human hydatid diseases was carry out using WHO methodology. Albendazole was given at a dose of 10 mg/Kg body/day in cycles of 28 days separated by 14 days without treatment. The efficacy of chemotherapy was evaluated by clinical improvement and changes in the cyst's morphology (detachment and collapse of the cyst membrane and increased density of the cyst fluid). We performed this study in 134 patients with hydatidosis: 17 patients with pre and post surgery treatment, 50 patients with post surgery treatment and 67 patients with chemotherapy only. Albendazole was effective in the hydatid disease; the patients with complex chemotherapy treatment did not report any secondary hydatidosis during the follow-up period (max. 2 years); the patients with exclusive chemotherapy reported 79% successful response, only 21% of them remained with unchanged cyst's size, but with modified internal structure. The therapeutic response depends of the cyst's size and its visceral site.