Endobronchial ultrasound in therapeutic bronchoscopy.

Endobronchial ultrasound (EBUS) has been introduced as an adjunct to diagnostic bronchoscopy as it allows evaluation of the submucosal and parabronchial structures. Its use in therapeutic bronchoscopy has not been assessed. A large observational study of the value of EBUS in therapeutic bronchoscopy is presented here. From January 1998-January 2001 all patients undergoing therapeutic bronchoscopy and EBUS were evaluated prospectively. Patient demographics, indication for bronchoscopy, interventional treatments used and changes in therapy as influenced by the use of EBUS were documented. A total 2,446 therapeutic bronchoscopies were performed. In 1,174 cases EBUS was used (29% mechanical tumour debridement, 20% airway stenting, 13% Neodymium:yttrium aluminium garnet (Nd:YAG) laser use, 23% argon plasma coagulation, 11% brachytherapy, 2% foreign body removal and 2% endoscopic abscess drainage). EBUS guided or changed therapy significantly in 43% of cases. Changes included adjustment of stent dimensions, termination of tumour debridement when nearing vessels, and referral for surgical interventions rather than endoscopic treatment. Complications associated with EBUS use were minimal. No patient undergoing EBUS guided tumour destruction experienced severe bleeding or fistula formation. In summary, endobronchial ultrasound was easily performed and changed or guided therapeutic decisions during therapeutic bronchoscopic procedures in a substantial number of cases. As this may result in better outcomes, it has become a standard adjunct in the authors practice.

Malignant transformation of the esophageal mucosa is enhanced in p27 knockout mice.

OBJECTIVE: In a previous study, we showed that experimentally induced gastroduodenal-esophageal reflux in mice treated with a carcinogen can result in Barrett esophagus and Barrett-associated adenocarcinoma. Since we have shown that most Barrett-associated adenocarcinomas in human beings have lost the tumor suppressor gene p27, we sought to determine whether cancer would be more likely to develop in p27 knockout mice than in p27 heterozygous or p27 wild type mice. METHODS: Three groups of mice were treated by esophagojejunostomy resulting in gastroduodenal-esophageal reflux and by a carcinogen (N -methyl-N -benzylnitrosamine): group I (50 wild type), group II (45 p27 heterozygous), and group III (50 p27 knockout). The mice were killed 18 to 20 weeks after operation and studied macroscopically and histopathologically. RESULTS: Barrett esophagus developed in 7 (14%) mice in group I, 4 (8.9%) mice in group II, and 13 (26%) mice in group III. Cancers developed in 30 (60%) mice in group I, 31 (68%) mice in group II, and 43 (86%) mice in group III. Ten percent of the cancers in group I were adenocarcinomas, as were 16.1% in group II, and 23.3% in group III. The difference between rates of Barrett esophagus in groups I and II compared with group III was statistically significant (P =.035), as was true of the cancer rates (P =.006). The percentage of cancers that were adenocarcinomas was highest in group III, but not significantly different from groups I and II. CONCLUSIONS: This experimental mouse model of Barrett esophagus and Barrett- associated adenocarcinoma is similar to what occurs in human beings and may be useful in developing methods to inhibit malignant transformation of Barrett esophagus.

Successful bronchoscopic placement of tracheobronchial stents without fluoroscopy.

BACKGROUND: Tracheobronchial stenting is performed increasingly often. Fluoroscopic control, which leads to significant radiation exposure for patients and staff, is recommended for the placement of metal stents. METHODS: All consecutive patients referred to two airway centers in need of airway stenting who received stents (Ultraflex; Boston Scientific, Natick, MA) underwent placement using endoscopic guidance only. All data were collected in an ongoing continuous database. RESULTS: One hundred stents were placed in 96 patients for central airway obstruction, and the data were reviewed. Stents were placed in all locations within the central airways for a variety of indications but mainly for malignant obstruction. No complications occurred, and all stents were placed satisfactorily. CONCLUSION: At centers with dedicated airway teams, Ultraflex stents can be quickly and safely inserted without the need for fluoroscopy. This saves radiation exposure to patients and to staff and may lead to a more cost-effective procedure.

Perfusion with lipopolysaccharide negative blood eliminates lipopolysaccharide induced lung injury.

We investigated whether perfusion with control blood improves pulmonary functions compromised by lipopolysaccharide (LPS) infusion. This was an animal study in a research laboratory at a university hospital by using Sprague-Dawley rats (n = 19), each weighing 325 to 350 g. All animals were pretreated with a 24 hour infusion of either LPS (5 mg/kg) or vehicle, after which, excised lungs were reperfused for 2 hours with either LPS+ or control blood. Three groups were studied: (1) group S (n = 6); LPS pretreated lungs reperfused with LPS containing blood to mimic persistent sepsis, (2) group N (n = 6); LPS pretreated lungs reperfused with control blood to mimic the removal of the septic blood components, and (3) group C (n = 7); vehicle pretreated lungs reperfused with normal blood as a control. Blood gas exchange, shunt fraction (Qs/Qt), alveolar-arterial oxygen gradient (A-aDO2), and variables for lung mechanics were measured. Leukosequestration was quantified with a myeloperoxidase (MPO) assay. The PO2 (mm Hg) values at 90 min after reperfusion in groups S, N, and C were 67.8 +/- 7.0*, 85.2 +/- 9.2, and 90.1 +/- 7.5, respectively (*p < 0.05; vs. group N and C). In addition to PO2, A-aDO2 and Qs/Qt significantly deteriorated in group S. MPO activity in the lungs after LPS infusion was significantly higher than that after vehicle infusion (1.7 +/- 0.3 vs. 0.12 +/- 0.04 units/g tissue; p < 0.001). Subsequent reperfusion with LPS+ blood (group S) increased MPO activity to 3.1 +/- 0.6 (p < 0.05), but reperfusion with normal blood (group N) caused a significant decrease to 1.1 +/- 0.2 (p < 0.05). MPO activity in group C did not significantly change compared with those after vehicle infusion. Reperfusion with control blood normalized lung function compromised by pretreatment with LPS and significantly reduced leukosequestration. These results favor the possibility that the removal of LPS+ blood components may eliminate septic lung injury.

CT fluoroscopy guidance for transbronchial needle aspiration: an experience in 35 patients.

OBJECTIVE: To demonstrate the usefulness of real-time guidance with CT fluoroscopy to improve the yield of transbronchial needle aspiration (TBNA). DESIGN: Prospective, observational. SETTING: A tertiary-care, university-affiliated medical center. METHODS: From December 1998 to April 2000, 35 patients underwent CT fluoroscopy-guided TBNA. Patients with subcarinal and precarinal lymph nodes were only included if a previous attempt was nondiagnostic, as the initial yield in this setting with conventional TBNA is high. TBNA was performed using standard technique in a CT-scan suite. Needle location was confirmed with fluoroscopy without IV contrast being used. Specimens were evaluated on-site for adequacy. RESULTS: The procedure had to be aborted in three patients before TBNA could be performed. Samples were obtained in 32 patients. Samples were nondiagnostic in four patients. Adequate tissue was obtained in 28 of 32 patients (87.5%). Twenty-two patients had a specific benign or malignant diagnosis made, and 6 patients had lymphocytes only on the specimen. In follow-up, only one of these six patients proved to have a malignancy. All procedures were performed within a regular interventional CT time slot of 1 h. No TBNA side effects were noted. CONCLUSION: TBNA under CT fluoroscopic guidance is easy to perform. The yield in all accessible lymph node stations is high.

Safety of bedside percutaneous dilatational tracheostomy in obese patients in the ICU.

STUDY OBJECTIVE: To examine the safety of bedside percutaneous dilatational tracheostomy in obese patients. DESIGN: Case series of consecutive obese patients (body mass index > or = 27 kg/m(2)) with acute respiratory failure in a medical, cardiac, or surgical ICU unit who required tracheostomy for failure to wean and continued mechanical ventilatory support. RESULTS: Thirteen obese patients were identified and consented to the procedure. Bedside percutaneous dilatational tracheostomy was successfully performed in the ICU for all 13 patients. Procedural complications were limited to paratracheal tracheostomy tube placement in one patient, with immediate identification and appropriate correction. Postprocedural complications were limited to a cuff leak in one patient. CONCLUSION: Bedside percutaneous tracheostomy can be safely performed in obese patients.

Barrett's esophagus and associated adenocarcinoma in a mouse surgical model.

BACKGROUND: The development of Barrett's esophagus (BE) and Barrett's associated adenocarcinoma (BAA) in the rat after experimental inducement of esophageal reflux of gastric, bile, and pancreatic juice has been reported by others. The purpose of this study was to determine whether similar results could be demonstrated in the mouse model. MATERIALS AND METHODS: One hundred eight Swiss-Webster mice were used in this study and were divided into three groups: Group I, 37 mice with esophagojejunostomy; Group II, 39 mice with esophagojejunostomy and the carcinogen N-methyl-N-benzylnitrosamine (MBN); and Group III, 32 mice with MBN alone. The animals were sacrificed after 19 weeks. Macroscopic and histopathologic examinations were performed. RESULTS: One hundred mice survived and were available for pathologic study. Macroscopic evidence suggested esophagitis in 60.6% of mice in Group I, 62.8% of mice in Group II, and 9% of mice in Group III and suggested tumor in 3% of mice in Group I, 51.4% of mice in Group II, and 53.1% of mice in Group III. Histopathologic analysis disclosed BE in 42.4% of mice in Group I, 20% of mice in Group II, and 12.5% of mice in Group III. Cancer was present in 12.2% of mice in Group I, 54.3% of mice in Group II, and 46.9% of mice in Group III. Adenocarcinoma with or without squamous cell carcinoma was present in 6.1% of mice in Group I, 37.1% of mice in Group II, and 12.5% of mice in Group III. CONCLUSIONS: Esophagojejunostomy plus MBN in the mouse results in BE, BAA, or both in 57.1% of animals, consistent with findings in the rat model after similar interventions.

Heat shock protein suppresses the senescent lung cytokine response to acute endotoxemia.

BACKGROUND: Previous reports demonstrate that heat shock protein (HSP) can alter the pulmonary inflammatory cascade. We wished to determine if this mechanism is active in the senescent mouse. METHODS: A dose-response and time-response curve for sodium arsenite (SA) induction of HSP was constructed. Eight 25-month-old B6C3F1 mice were given either 1, 2, 4, or 6 mg/kg SA. At 4 hours, the lungs were harvested and assayed for HSP by Western blot. Next, 8 mice were given 4 mg/kg SA and the lungs harvested at either 1, 2, 4, or 6 hours after injection and assayed for HSP. Next, 12 mice were prepared: Half received 4 mg/kg SA and 4 hours later, all received 0.5 mg/kg lipopolysaccharide (LPS). After 4 hours, lungs were harvested and Interleukin-1beta mRNA was assayed by Northern blot and semi-quantified by densitometry. RESULTS: The optimum SA dose was determined to be 4 mg/kg. The maximum HSP production was at 4 hours. Mice receiving LPS only showed a marked increase (3-fold) in IL-1 message compared with the mice pretreated with SA. CONCLUSIONS: These data suggest that in the senescent as in the mature mouse lung, HSP downregulates the inflammatory cascade in response to LPS.

Reliable 18-hour lung preservation with University of Wisconsin solution. An ex vivo rat model with a pulsatile perfusion system.

OBJECTIVES: A common experimental model is necessary to assess therapeutic intervention in lung preservation. This study was designed to establish lung preservation in an ex vivo rat model that would enable post-storage lung function to be stably evaluated during the 2 hours following reperfusion. SUBJECTS AND METHODS: Lungs isolated from Sprague-Dawley rats (n = 36) were flushed and stored in University of Wisconsin solution at 4 degrees C for the following periods: Group 1: no storage (n = 12); Group 2: 4 hours (n = 8); Group 3: 18 hours (n = 8); and Group 4: 24 hours (n = 8). After storage in University of Wisconsin solution, all lungs were reperfused with homologous venous blood exsanguinated from donor rats using a pulsatile perfusion system. Pulmonary variables, including lung airway resistance, dynamic lung compliance, total pulmonary vascular resistance, and blood gas analysis, were assessed during reperfusion. RESULTS: All lungs stored for 24 hours failed within 1 hour of reperfusion. Lungs stored for up to 18 hours survived 2-hour reperfusion. pO2 in groups 1 to 3 (87.1 +/- 3.5, 89.7 +/- 2.4, and 80.6 +/- 6.4, pO2 mmHg at 30 minutes) was similar during reperfusion, but that in group 4 (49.5 +/- 4.6 mmHg, at 30 minutes) deteriorated within 30 minutes after reperfusion onset. Lung airway resistance, dynamic lung compliance, and shunt fraction also deteriorated in group 4, whereas these variables were similar in groups 1, 2, and 3 during reperfusion. CONCLUSIONS: These results indicate that this experimental model provided a reliable evaluation of preserved lung function after 18-hour cold storage. Any therapeutic intervention for extending storage periods or ameliorating post-storage lung function is easily tested using this system.

Calcium channel blocker enhances lung preservation.

BACKGROUND: The standard program for lung transplantation employs PGE1 pretreatment for donor lungs, but its efficacy remains controversial. Calcium channel blocker has been reported more effective for reducing potassium-induced vasoconstriction. We investigate the efficacy of calcium channel blocker in the initial lung flush using rat lung transplant model. METHODS: The excised rat lungs (n = 30) were flushed with either University of Wisconsin solution (UWS) with a prior injection of 50 microg/kg PGE1 into the pulmonary artery (UWS + PGE1; n = 7), UWS only (UWS; n = 7), or UWS containing 10(-6) M nifedipine (UWS + Nif; n = 8). After storage (4 degrees C) for 24 hours, all lungs were reperfused for 2 hours using an isolated, pulsatile blood perfused lung model. Control lungs (n = 8) were reperfused immediately after harvest. Blood gas analysis and shunt fraction, lung airway resistance, dynamic lung compliance, and pulmonary vascular resistance were assessed. RESULTS: The pO2 at 30 minutes after reperfusion in the control, UWS, UWS + PGE1, and UWS + Nif group were 88.0 +/- 3.2, 49.6 +/- 2.2, 52.0 +/- 2.4, 85.1 +/- 2.1 (mmHg), respectively. Until 30 minutes after reperfusion, the pO2 in UWS and UWS + PGE1 group were significantly lower than those in UWS + Nif group (p < .001). Shunt fraction, lung airway resistance, and dynamic lung compliance also demonstrated the superiority of UWS + Nif group. CONCLUSIONS: The early graft function after storage was significantly enhanced in lungs flushed with UWS containing nifedipine. Calcium channel blocker is more effective than PGE1 in reducing the potassium-induced vasoconstriction. Optimal composition of the flush may require both calcium channel blocker for pulmonary vasodilation and PGE1 for pulmonary protection by non-vasodilatory mechanisms.

Does PGE1 attenuate potassium-induced vasoconstriction in initial pulmonary artery flush on lung preservation?

The standard clinical protocol for lung transplantation employs cold single pulmonary artery flush with Euro-Collins solution or the University of Wisconsin solution. Prostaglandin E1 (PGE1) is usually given by direct injection into the pulmonary artery to reduce pulmonary vasoconstriction caused by these intracellular, high-potassium solutions, however, the efficacy of PGE1 on lung preservation remains controversial. In this study we demonstrated that vasodilator effects of PGE1 were markedly reduced under a high-potassium condition, and that potassium-induced pulmonary vasoconstriction were inhibited by calcium channel blocker nifedipine. There are three therapeutic options in the cold single pulmonary artery flush for optimal lung transplantation, including the use of a higher dose of PGE1, use of the calcium channel blocker instead of PGE1, or the use of the extracellular, low-potassium solution such as low-potassium dextran solution for initial pulmonary artery flush before the lung harvest.

Technology acquisition and credentialing controversies.

In the age of the health care financial squeeze, staying on the cutting edge of medical technology is problematic at best. Surgeons must be proactive to design, specify, and acquire highly sophisticated, functional thoracoscopic technology. Credentialing is a legal process designed to improve patient care quality and must be fair and applied to all. An area of contention is credentialing for newly designed procedures. Valid reasons for decredentialing, always a difficult issue, include personal temporary or permanent medical conditions, patient care quality issues, insufficient caseload to maintain proficiency, and personal or interpersonal relationship problems.

Pneumostasis of experimental air leaks with a new photopolymerized synthetic tissue sealant.

Air leak is a major contributor to increased length of stay and postoperative morbidity following pulmonary surgery. The effectiveness of a new photopolymerized synthetic hydrogel (FocalSeal, Focal, Inc., Lexington, MA) as a sealant for pulmonary air leaks was determined in 10 mongrel dogs (20-35 kg). The animals were anesthetized and underwent left-sided anterolateral thoracotomy with amputation of a 2 x 3-cm segment of the lung apex. Hemostasis was achieved and terminal bronchial openings of 1.5 to 3 mm with vigorous air leaks were identified. After successful injury, the dogs were randomly assigned to sealant (n = 5) or control (n = 5) groups. In treated animals, the sealant was applied by brushing the solution to the cut parenchymal surface and solidified while briefly interrupting ventilation (40-60 seconds) using visible illumination (450-550 nm) from a xenon light source. Controls received no sealant. A single chest tube was maintained at the injury site with a continuous negative pressure of 20 cm of water. All dogs were extubated and allowed to breathe spontaneously under sedation for 24 hours. Chest radiographs were taken postsurgery and presacrifice. All control animals (n = 5) showed persistent vigorous air leak for the duration of the 24-hour observation period. All treated air leaks resolved immediately, and four of five remained sealed throughout the observation period. One leak reappeared after 17 hours due to inadequate sealant thickness over a 3-mm terminal bronchus. Gross evaluation of the treatment group at the end of 24 hours demonstrated intact sealant well adherent to the parenchyma. No evidence of atelectasis or excessive edema was seen, and no sealant-related complications or toxic effects were noted. Radiologically, lungs were fully inflated. Histologic evaluation at 24 hours revealed no evidence of a strong cellular response to the synthetic sealant, and no fibrosis or adhesions were seen, the onset of the healing process was favorable, indicating good biocompatability. In conclusion, this material was found to be an effective means for sealing bronchial and parenchymal air leaks in this model and warrants clinical evaluation.

Pseudoachalasia: a report of two cases with comments on possible causes and diagnosis.

Pseudoachalasia is a rare entity with symptoms and radiographic and esophageal manometric findings that may mimic primary achalasia. Two such cases are presented, one of which was associated with gastric carcinoma and the other with carcinoma of the lung.

The successful treatment of symptomatic, refractory hepatic hydrothorax with transjugular intrahepatic portosystemic shunt.

Hepatic hydrothorax is a rare complication of portal hypertension. Conservative therapy may be successful but refractory hepatic hydrothorax is not uncommon. Management of refractory hydrothorax is usually ineffective and can result in a worsened clinical status. Transjugular intrahepatic portosystemic shunts (TIPS) lower portal pressure and have been used in the treatment of refractory ascites. The aim of this study was to determine the efficacy of TIPS in the treatment of symptomatic refractory hepatic hydrothorax. A TIPS was placed in 24 consecutive cirrhotic patients with symptomatic refractory hepatic hydrothorax. Five patients (20.8%) were Child's/Pugh class B and 19 (79.2%) were class C. All had undergone multiple thoracenteses and were hypoalbuminemic. Mean follow-up was 7.2 months (range, 0.25-49 months). Fourteen (58.3%) of 24 patients had complete relief of symptoms after shunt placement and did not require further thoracentesis. Five (20.8%) additional patients required fewer thoracenteses. Five (20.8%) patients developed worsening liver function and died within 45 days. In eight (66.7%) of 12 patients with > or = 60 days of follow-up, the serum albumin increased by a mean of 1.2 g/dL (range, 0.1-2.2 g/dL). The Child's-Pugh score improved in 7 (58.3%) of these 12 patients and two patients improved from class C to class A. These two patients no longer require liver transplantation. This study shows that TIPS can be effective in the management of symptomatic, refractory hepatic hydrothorax. Clinical and laboratory improvement may be seen and liver transplantation may become unnecessary.

Pulmonary actinomycosis: surgical considerations.

Pulmonary actinomycosis is a rare disease. Of 2,247 patients presenting with a radiological pulmonary opacity, 13 (0.6%) were identified with pulmonary actinomycosis in a 13 year period. Twelve of the 13 patients underwent thoracotomy and one had clinical diagnosis and subsequent medical treatment alone. Neither mortality nor major complications were observed. One patient had recurrent disease after surgery. The other surgical patients are well and free from disease at a minimum 6 month follow-up. Diagnosis of actinomycosis is frequently difficult because it often infects pre-existing cavitary disease in the lung. As a consequence, the infection may progress to stages which will not respond to medical treatment alone. Surgery then provides the best method to achieve diagnosis and ultimate treatment.

Spiral CT with multiplanar and three-dimensional reconstructions accurately predicts tracheobronchial pathology.

BACKGROUND: This study was designed to evaluate the clinical accuracy of multiplanar reconstructions and three-dimensional shaded surface displays compared with conventional transaxial computed tomography, bronchoscopy, and surgical pathologic findings. METHODS: Transaxial computed tomographic images, two-dimensional nonstandard multiplanar reconstruction images, and three-dimensional images obtained from patients with tracheobronchial disease were prospectively evaluated for the relationship to adjacent structures, lesion characterization, and surgical anatomic correlation before invasive procedures. RESULTS: Compared with conventional transaxial computed tomographic images, multiplanar reconstructions and three-dimensional shaded surface displays provided a correlative map of bronchoscopic and surgical anatomy in patients with benign and malignant tracheobronchial pathology. The longitudinal extent of abnormalities are better demonstrated on the multiplanar reconstruction and three-dimensional images, whereas the transverse extent of disease and relationships to adjacent structures were better shown on axial computed tomographic sections. CONCLUSIONS: Three-dimensional and multiplanar two-dimensional images are additive to transaxial computed tomography for evaluation of diseases involving the central airways. They are beneficial for planning invasive procedures. More importantly, they provide consistent, highly accurate measurements for routine follow-up and for future clinical trials.

Spiral CT with multiplanar and three-dimensional reconstructions accurately predicts tracheobronchial pathology.

BACKGROUND: This study was designed to evaluate the clinical accuracy of multiplanar reconstructions and three-dimensional shaded surface displays compared with conventional transaxial computed tomography, bronchoscopy, and surgical pathologic findings. METHODS: Transaxial computed tomographic images, two-dimensional nonstandard multiplanar reconstruction images, and three-dimensional images obtained from patients with tracheobronchial disease were prospectively evaluated for the relationship to adjacent structures, lesion characterization, and surgical anatomic correlation before invasive procedures. RESULTS: Compared with conventional transaxial computed tomographic images, multiplanar reconstructions and three-dimensional shaded surface displays provided a correlative map of bronchoscopic and surgical anatomy in patients with benign and malignant tracheobronchial pathology. The longitudinal extent of abnormalities are better demonstrated on the multiplanar reconstruction and three-dimensional images, whereas the transverse extent of disease and relationships to adjacent structures were better shown on axial computed tomographic sections. CONCLUSIONS: Three-dimensional and multiplanar two-dimensional images are additive to transaxial computed tomography for evaluation of diseases involving the central airways. They are beneficial for planning invasive procedures. More importantly, they provide consistent, highly accurate measurements for routine follow-up and for future clinical trials.