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The ability of the human lung to catalyze genotoxic bioactivation of constituents of diesel exhaust particle (DEP) extract (DEPE) and the identity of the lung enzymes involved in the bioactivation were investigated using human lung tissues obtained from surgical resections. Genotoxicity was determined by lung S9-catalyzed mutagenicity of DEPE constituents to Salmonella typhimurium TA98NR in the Ames test and by DEPE-induced pneumocyte DNA damage response as determined by γH2Ax expression in ex vivo tissues. S9 was prepared from lung explants treated ex vivo with either DEPE to induce pulmonary enzymes (DEPE-S9) or vehicle only (CON-S9). TA98NR served as the tester strain for the purpose of enhancing and minimizing the contribution of lung S9 and Salmonella, respectively, to DEPE bioactivation. DEPE-S9 was 2.2-fold more active than CON-S9 or rat liver S9 in DEPE bioactivation and the bioactivation was inhibited 58, 45, 22, and 16% by α-naphthoflavone, dicumarol, ketoconazole, and ticlopidine, respectively. Alveolar S9 was less active than bronchioalveolar S9 in DEPE bioactivation. DEPE and diesel exhaust particles (DEP) induced γ-pH2Ax expression in pulmonary cells. Pulmonary CYP1A1 and NQO1 were induced by DEPE treatment, with the constitutive and induced CYP1A1 distributed throughout all peripheral lung regions, whereas NQO1 was limited in distribution to bronchiolar epithelium. The results show that the human lung is highly active in catalyzing genotoxic bioactivation of diesel emission constituents and that CYP1A and NQO1 play major roles in the reaction. The findings underscore the usefulness of human lung tissues in studies of the pneumotoxicity potential of chemicals to humans., (Copyright © 2013 Wiley Periodicals, Inc.)

Catalytic activities of CYP1A1, CYP1A2 and CYP1B1, and inducibility of the activities were studied in intact human lung samples (from 23 human subjects) ex vivo. The activities [as measured by ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and 3-cyano-7-ethoxycoumarin O-deethylase (CECOD)] were present in the lungs and were induced by benzo[a]pyrene (B[a]P) and diesel exhaust particle extract (DEE) but with extensive inter-subject variability. All three activities were substantially inhibited (>or=75%) by the CYP1 inhibitor alpha-naphthoflavone, whereas only MROD and CECOD were substantially inhibited by the CYP1A2-preferential inhibitor fluvoxamine. None of the three activities was substantially inhibited by the CYP1B1-preferential inhibitor tetramethoxystilbene, indicating lack of involvement of CYP1B1 in the activities in the intact lung. CYP1A1 and CYP1A2 proteins were present in the lungs (by western blot analysis), also with extensive inter-subject variability, and were induced by B[a]P or DEE more extensively than by the combination of B[a]P and DEE (B[a]P+DEE). CYP1B1 was also present in the lungs and its level varied extensively between subjects. In contrast with CYP1A and CYP1A2 levels, CYP1B1 level was not significantly altered by B[a]P or DEE treatment and was diminished more extensively by treatment with B[a]P+DEE. The findings point to the potential usefulness of the intact lung for assessing in situ xenobiotic biotransformation reactions as well as the CYP1 specificity of the reactions ex vivo. The findings also suggest MROD and CECOD as potential markers of CYP1A2 activity in the intact lung.

Thoracic duct lymphangioma is a rare mediastinal tumor. Most patients are asymptomatic. Symptoms may include dysphagia, dyspnea, cough, or chest pain. Workup may include chest computed tomography or lymphangiography, or both. Surgery should be considered the treatment of choice. We present a 60-year-old man with a 2.4-cm mass in the retro-cardiac space to the right of the esophagus. The patient underwent a thoracoscopic resection of the mass with ligation of the thoracic duct. We conclude that video-assisted thoracoscopic surgery allows for safe evaluation and resection of mediastinal pathology.

Background: Thoracic surgery is associated with a high morbidity and mortality rate in the elderly patient population. Appropriate management of thoracic diseases is often avoided because of the inherent risks associated with the access thoracotomy. The purpose of this study was to evaluate the perioperative outcomes of octogenarians who underwent video-assisted thoracic surgery (VATS) for a variety of thoracic conditions., Methods: A retrospective chart review was done on all patients who were between 80 and 90 years of age and underwent elective VATS between January 1995 and August 2001., Results: A total of 162 consecutive VATS procedures were performed in 157 patients. Comorbid conditions consistent with their advanced age included chronic obstructive pulmonary disease, hypertension, coronary artery disease, and diabetes. The procedures included 96 lung resections (53 lobectomies, 42 wedge/segment resections), 46 pleurectomies, 8 decortications, 8 mediastinal biopsies, 3 pericardial windows, and 1 drainage of hemothorax. The pathology included 76 primary lung cancers, 35 metastatic diseases, 37 benign conditions, 9 nesotheliomas, and 3 carcinoid tumors. The average operative time and length of hospital stay after surgery were 51 min and 2.6 days, respectively. There were 3 (1.9%) mortalities, 2 from cardiac complications and 1 from pneumonia. Two (1.2%) patients required reexploration for bleeding. Four (2.5%) cases were converted to open thoracotomy thirteen (8.0%) cases had an air leak, of which 11 were managed on an outpatient basis with a Heimlich valve. They were discharged from the hospital an average of 3.3 days postoperatively., Conclusion: With VATS, surgical therapy can be offered to octogenarians with a low morbidity and mortality rate, as well as a short hospital stay.

The inducibility of cytochrome P4501A1 gene (CYP1A1) expression was examined in human lung samples from 27 subjects, using an explant culture system and semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. CYP1A1 transcripts were present in all of the lung specimens and were induced by the prototypic inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and benzo[a]pyrene (B[a]P), and by the atypical inducers pyridine, nicotine, and omeprazole. 2-Hydroxypyridine was a better inducer than pyridine, implicating metabolites in CYP1A1 induction by the parent compound. The prototypical inducers were the most effective inducers in many samples but were ineffective in some samples in which the atypical compounds were effective inducers. Cytochrome P4501A2 (CYP1A2) transcripts were also detected in most of the lung specimens and were inducible in some specimens. The results show the suitability of the explant culture system for examining the inducibility of human pulmonary CYP1A1 and CYP1A2, indicate the heterogeneity in individual sensitivity to the induction, and underscore the need to include atypical inducers in studies of CYP1A inducibility in humans.

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S(9) fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S(9) fractions from the tissues catalyzed the bioactivation of benzo[a]pyrene (B[a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.

A video-assisted thoracic surgery approach to en bloc resection of lung cancer invading the chest wall is described. Using a minimally invasive surgical approach combined with neoadjuvant external beam radiotherapy, complete resection of an upper lobe carcinoma invading two rib segments was performed in a manner that permitted complete resection with curative intent and allowed for rapid recovery.

Objective: To evaluate the outcomes from a new surgical technique for lobectomy., Patients: Two hundred fifty consecutive patients with an average age of 67.3 years underwent simultaneously stapled lobectomy., Methods: Video-assisted thoracic surgical non-rib spreading lobectomy (VNSSL) is a new technique that has been evolving for approximately 6.5 years. During 1990, we began using video-assisted thoracic surgery (VATS) for simple, benign diseases. Throughout 1991, VATS was applied to malignant problems, ie, mediastinal masses, staging of lymph nodes, malignant effusions, and coin lesions. As experience was acquired, more complex procedures were attempted, such as lobectomy. On September 9, 1991, our first VATS lobectomy, using anatomic hilar dissection and lymph node sampling, was performed for primary carcinoma of the lung. One year later, we performed our first VNSSL using simultaneous stapling., Results: Currently, 400 VNSSLs have been performed. In this entire series, there have been no surgical mortality, bronchopleural fistulas, port implantations, or transfusions. Bronchial stumps have averaged 4 mm in length, and all have been microscopically negative for neoplasm. In order to evaluate long-term survival for primary carcinoma of the lung in patients with an adequate duration of follow-up, the first 250 consecutive VNSSLs have been reviewed. There were 120 male and 130 female patients ranging in age from 20 to 92 years old who had 62 right upper lobe, 20 right middle lobe, 58 right lower lobe, 63 left upper lobe, and 33 left lower lobe lobectomies, and 14 bilobectomies. The lesions consisted of 214 primary carcinomas, 8 metastatic lesions, and 28 benign problems. Seven to 18 lymph nodes could be resected during staging of the primary neoplasms. The tumors ranged in size from 1 to 9 cm, and operating times averaged 78.6 min. Hospitalization averaged 2.83 days. No patient was admitted to the ICU. Intensive monitoring or narcotic analgesia were not needed. No epidural or intercostal anesthesia was used. Complications were infrequent and minor. Most patients returned to preoperative levels of physical activity within 7 to 10 days. Overall survival at a mean of 34 months, when all stages of neoplasms were combined, is 83%. For stage I, overall survival is 92%. The cost of VNSSL is approximately 50% less than the traditional open thoracotomy., Conclusions: VNSSL is an oncologic technique that has been clinically rewarding and economically beneficial for patients with malignant lesions. Long-term survival for primary carcinoma currently exceeds reports being published for the traditional open thoracotomy. Scientific reasons for this extraordinary survival are emerging. Complications, surgical mortality, pain, and length of stay have all been reduced. Patient recovery, comfort, and satisfaction have been extraordinary.

A new technique for pulmonary lobectomy has been utilized for malignant lesions. Eighty-five consecutive patients with pulmonary neoplasms underwent a VATS non-rib spread Simultaneously Stapled Lobectomy. There were 34 males and 51 females with 61 adeno, 21 squamous, 2 large cell and 1 carcinoid tumor who underwent 18 left upper, 13 left lower, 20 right upper, 7 right middle and 27 right lower lobectomies. Forty-one mediastinoscopies were negative. Patients with positive mediastinoscopies were not selected for curative resection. At VATS exploration, 10 patients had positive nodes. All resected nodes were negative in the other patients. Every bronchoscopy was negative. Operating times averaged 84.5 minutes. No patient received a transfusion. Lesions ranged from 1 cm to 8 cms with an average size of 3.62 cms. Post-operative length of stay averaged 3.38 days. There was no surgical mortality, no hemorrhage, no transfusion and no conversion to an open case in the entire series. No bronchial, vascular or broncho vascular fistula occurred. Complications were minor from which all patients recovered completely. Survival seems similar to patients resected by traditional open techniques.

Background: This study was performed to evaluate and determine the validity and benefits of video-assisted thoracic surgical simultaneously stapled pulmonary lobectomy without rib spreading., Methods: Between September 1992 and August 1995, 100 consecutive video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading were performed., Results: Forty-five male and 55 female patients had 24 right upper, 8 right middle, 29 right lower, 24 left upper, 15 left lower lobectomies for 66 adenocarcinomas, 20 squamous cell carcinomas, 4 large cell carcinomas, 8 benign lesions, and 2 metastatic lesions. Seventy-six patients had negative nodes. Nine patients had positive nodes. Every bronchoscopy was visually and cytologically negative. Forty-nine cervical mediastinoscopies were negative. Operating time for the series averaged 90.3 minutes. Hospitalization averaged 3.5 days for the entire group, but was 2.6 days for the last 20 patients. Lesions ranged from 1.5 to 8 cm, averaging 3.4 cm. There was no surgical mortality, no hemorrhage, no transfusion, and no urgent conversion to an open procedure. No bronchial fistula, vascular fistula, or bronchovascular fistula has occurred. Complications included 6 air leaks, 2 cerebrovascular accidents, 1 infected chest tube site, 2 cases of pneumonitis, and 1 subcutaneous emphysema., Conclusions: Video-assisted thoracic surgical simultaneously stapled lobectomy without rib spreading is a safe operation that can be combined with lymph node sampling. At this early stage, therapeutic outcomes (survival) for resected neoplasms appear similar to results obtained from traditional open techniques.

Seeding of carcinoma has always been of concern to surgeons. Recent reports have focused on possible implantation of tumor in the small wounds of minimally invasive procedures, i.e. VATS. A patient is presented who had a conventional open lobectomy for carcinoma and later developed tumor in the traditional thoracotomy wound. Although seeding or tumor implantation is accepted by thoracic surgeons, the exact mechanism of tumor implantation has never been scientifically explained or documented. Possibly, a rare and necessary pattern of genetic mutations could be responsible for this infrequent but serious problem.

Diffuse bullous disease of the lungs remains an unrelentless, debilitating, terminal disease. Intensive medical therapy can give transient relief of symptoms. Thoracotomy and resection has not always been successful and can be associated with an increased mortality and morbidity. Eight patients with end-stage bullous disease, unresponsive to medical therapy and not considered to be candidates for a thoracotomy, underwent unilateral video-assisted thoracic surgical ablation of bullae using the Argon Beam Coagulator. Six men and 2 women ranging in age from 28 to 71 years reported a decrease in dyspnea. Three patients restudied had an increase in forced expiratory volume in 1 second of 34%. Postoperatively, 7 patients had an air leak, pneumonia developed in 2 patients, and 3 patients had massive subcutaneous emphysema after parietal pleurectomy. Hospitalization averaged 13.6 days. All patients made a complete recovery, and each was subjectively improved. Steroid use decreased, oxygen requirements decreased, dyspneic episodes decreased, infections decreased, and endurance increased. In 3 patients with a limited follow-up evaluated postoperatively, video-assisted thoracic surgery and the Argon Beam Coagulator seemed to be beneficial for treating advanced, generalized bullous disease.

A simple method for placing specimens in a protective bag during video-assisted thoracic surgery has been developed. The equipment is readily available, and the technique is easy to perform.

Forty patients with malignant pulmonary disease underwent evaluation, staging, and a biopsy or resection by means of video-assisted thoracic surgery. There were 20 men and 20 women whose ages ranged from 27 to 82 years. Eight patients had a wedge resection for metastatic carcinoma, three a lobectomy for primary carcinoma, six exploration of the thorax, five biopsy of the aortopulmonary window, and eighteen a sublobar resection for primary carcinoma of the lung. There was no mortality. Three patients had air leaks that lasted an average of 8 days. Video-assisted thoracic surgery seems to be useful for more precise staging of carcinoma of the lung, and, in some patients, resectional operations can be performed.

Video-assisted thoracic surgery is a new modality that allows visualization of and access to the intrathoracic organs without making a thoracotomy incision. One hundred consecutive patients underwent 113 thoracic procedures using this technique. Eight wedge resections for metastatic lesions, 6 pericardial windows, 1 bronchogenic cystectomy, 4 explorations of the aortopulmonary window, 1 decortication, 5 pleural scleroses, 8 bullous ablations, 25 lung biopsies, 19 wedge resections for carcinoma, 9 explorations of the thorax, 3 lobectomies, 1 esophageal cystectomy, 14 wedge resections for benign lesions, 4 pleurectomies, 1 excision of a neurogenic tumor, 3 mediastinal explorations, and 1 imaged axillary dissection were performed. There was no mortality. Ten patients had complications from which they recovered completely. Patients undergoing video-assisted thoracic operations seem to have reduced postoperative pain, shorter hospitalization, and quicker recovery times. Currently, this new modality appears to have beneficial value for patients; however, only further experience will determine its true merits.

Imaged thoracic surgery is a new modality that is rapidly gaining acceptance from thoracic surgeons. Procedures that traditionally required a thoracotomy can now be done successfully using this technique in some patients. Three patients with primary carcinoma of the lung have undergone lobectomy using imaged thoracic surgery.

Imaged thoracoscopic surgery is a technique utilized to operate on the intrathoracic organs without making a formal thoracotomy incision. Eleven patients underwent lung biopsy with this procedure and each had markedly reduced postoperative pain. Each patient resumed preoperative activity levels within one week of discharge from the hospital. Besides thoracotomy and thoracoscopy, imaged thoracoscopic surgery provides another option for approaching the intrathoracic organs.

Previously, intrathoracic organs have been approached by either thoracotomy or thoracoscopy. A technique, imaged thoracoscopic surgery, using video optics and projection of images on a screen provides another option for the thoracic surgeon. Two patients with mediastinal cysts, one bronchogenic and one esophageal, underwent surgical removal using imaged thoracoscopic surgery. Postoperative pain was markedly reduced, hospitalization shortened, and recovery accelerated. Numerous complex surgical procedures can be performed using imaged thoracoscopic surgery.

Since the advent of video optics, with the projection of images on a screen, a new option has been added to the armamentarium of the thoracic surgeon: video-endoscopic thoracic surgery. A case report of a 33-year-old woman demonstrates the successful new procedure.