Selective immune stimulation during induction of allograft tolerance in the rat by radical immunosuppression.

Recent investigation of a biologically active synthetic polymer, NED 137, has demonstrated its ability to induce a B cell differentiation response to certain antigens, even in the presence of T cell depletion. In this report, the effect of T cell depletion combined with NED 137, on skin allografting, is explored in the Lewis strain rat. Animals were T cell-depleted by thymectomy, total body irradiation, and syngeneic marrow repopulation. They were then challenged with skin allografts +/- NED 137 treatment. Graft survival was significantly prolonged in the T-depleted rats regardless of treatment with NED 137. The drug did not increase the immune response to donor antigen as measured by in vivo lysis of 51Cr-labeled cells. Immunization with heterologous erythrocytes produced a low level of differentiation of IgM-producing cells in the T cell-depleted skin allografted group, but in contrast the T-depleted NED 137-treated rats had a normal response to immunization. These data suggest that selective stimulation of the humoral component of the immune response is feasible at a time when T cell-mediated function has been radically suppressed, without producing adverse effects on allograft survival.

Presentation and management of bronchogenic cysts in the adult.

Bronchogenic cysts are congenital anomalies of the bronchial tree that are often asymptomatic at presentation in adults. Management of asymptomatic bronchogenic cyst in this population remains controversial. Eighteen patients with bronchogenic cysts were treated at our institution since 1975. At initial presentation, 10 patients (56 percent) were asymptomatic and 8 (44 percent) were symptomatic. Cough and pain were the most frequent symptoms. Two patients presented with potentially serious complications, one with respiratory distress from airway compression and the other with infection and airway fistulae. Chest radiographs were abnormal but nondiagnostic in 17 out of 18 (94 percent) patients. Chest computerized tomography (CT) scans were abnormal in eight of eight (100 percent) patients, but they confirmed the benign cystic nature in only five of eight (62.5 percent). Overall, considering the use of all imaging modalities and clinical suspicion, bronchogenic cyst was considered in the preoperative differential diagnosis in only 11 of 18 (61 percent) patients. Fifteen of 18 cysts were resected initially. Three of the asymptomatic patients who were followed up initially ultimately required resection because of the development of symptoms. A trend toward increased postoperative complications was noted in patients who were symptomatic at the time of surgery (27 percent vs 14 percent). In conclusion, adult patients with asymptomatic bronchogenic cyst may develop symptoms over time. Symptoms in adults can sometimes be potentially serious. Since a confident preoperative diagnosis is not always possible and because surgical complications may be more common in the symptomatic patient, we recommend surgical resection of all suspected bronchogenic cysts in operable candidates.

Lobectomy--video-assisted thoracic surgery versus muscle-sparing thoracotomy. A randomized trial.

Video-assisted thoracic surgery has been adopted by some thoracic surgeons as the preferred approach over thoracotomy for many benign and malignant diseases of the chest. However, little concrete evidence exists to support this technique as the superior approach. This randomized study was carried out to define the advantages of video-assisted lobectomy over muscle-sparing thoracotomy and lobectomy. Sixty-one patients with presumed clinical stage I non-small-cell lung cancer were entered into the study. Each patient was randomized to muscle-sparing thoracotomy and lobectomy or video-assisted lobectomy. Six patients were excluded from the study either because final pathologic results revealed nonmalignant disease (3 patients) or because an attempted video-assisted lobectomy was converted to a thoracotomy. This left 30 patients in the thoracotomy group and 25 patients in the video-assisted group. No significant differences existed between the two groups in operating time, intraoperative blood loss, duration of chest tube drainage, or length of hospital stay. Significantly more postoperative complications occurred in the thoracotomy group (p < 0.5), the majority of which were prolonged air leaks. Return to work time was not an issue because the majority of the patients were either retired or not working at the time of the operation. Only three patients had persistent postthoracotomy pain (thoracotomy, n = 2; video-assisted lobectomy, n = 1). We conclude that video-assisted lobectomy was not associated with a significant decrease in duration of chest tube drainage, length of hospital stay, postthoracotomy pain, or, in this group of patients, a faster recovery time and return to work. Video-assisted lobectomy continues to expose the patient to the risk of a major pulmonary resection being done in an essentially closed chest. These results illustrate the need for critical evaluation of video-assisted thoracic surgery before the procedure is accepted as a superior approach based on presumed and thus far unproved advantages.

The impact of thoracoscopy on the management of pleural disease.

STUDY OBJECTIVE: To describe the diagnostic efficacy, morbidity, and patient outcome of thoracoscopy; to quantify the direct impact of thoracoscopy on clinical management; and to determine preoperative variables associated with finding malignancy at thoracoscopy to aid patient selection. DESIGN: Retrospective chart review of consecutive cases of thoracoscopy for pleural disease. SETTING: Single tertiary medical center. PATIENTS: One hundred eighty-two consecutive patients who underwent thoracoscopy for pleural disease over a 5-year period (from 1987 through 1992). MEASUREMENTS AND RESULTS: Final diagnoses were 98 (54%) malignant, 58 (32%) benign, and 26 (14%) idiopathic. Thoracoscopy had a diagnostic sensitivity of 95% for malignancy and 100% for benign disease. Malignancy was shown by thoracoscopy in 27 of 41 (66%) patients who had a preoperative nondiagnostic closed pleural biopsy, and in 24 of 35 (69%) patients who had at least 2 preoperative negative pleural cytologic specimens. Chart review by preestablished criteria showed information obtained from thoracoscopy directly influenced treatment in 155 (85%) patients. Thirty-seven (20%) patients, however, had at least one perioperative complication (15% major, 8% minor). Ten (6%) patients died during the same hospitalization in which a thoracoscopy was performed, although none died within 48 h. There was one thoracoscopy-related death. Sixty-two (34%) patients died within 6 months of thoracoscopy (death by all causes). Forty-seven (48%) patients who had intrathoracic malignancy present at thoracoscopy died within 6 months. Patients found to have malignant pleural disease by thoracoscopy were more likely to have a preoperative history of a malignancy (p = 0.001). Age more than 50 years was associated with finding malignancy at thoracoscopy (p = 0.04). A combined lymphocytic and hemorrhagic effusion was associated with malignancy (p = 0.004). Preoperative pleural data showed that idiopathic effusions had a significantly lower median lactate dehydrogenase (LDH) value (192, which was normal) compared with malignant or benign effusions. CONCLUSIONS: (1) Thoracoscopy increases yield for malignant and benign disease when thoracentesis and closed pleural biopsy are nondiagnostic. (2) Thoracoscopy directly affects clinical management in 85% of patients. (3) Significant complications can occur in patients receiving tertiary care. (4) For the evaluation of suspected malignant pleural disease, thoracoscopy has its greatest diagnostic yield in older patients who have a history of malignancy and who present with a lymphocytic, hemorrhagic, high LDH effusion.

Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement.

OBJECTIVE: Provide explicit expert-based consensus recommendations for the management of adults with primary and secondary spontaneous pneumothoraces in an emergency department and inpatient hospital setting. The use of opinion was made explicit by employing a structured questionnaire, appropriateness scores, and consensus scores with a Delphi technique. The guideline was designed to be relevant to physicians who make management decisions for the care of patients with pneumothorax. OPTIONS: Decisions for observation, chest tube placement, surgical interventions, and radiographic imaging. OUTCOMES: Effectiveness of pneumothorax resolution, duration of and patient tolerance of care, and pneumothorax recurrence. EVIDENCE: Literature review from 1967 to January 1999 and Delphi questionnaire submitted in three iterations to a multidisciplinary physician panel. VALUES: The guideline development group determined by consensus the relevant outcomes to be considered in developing the Delphi questionnaire. BENEFITS, HARMS, AND COSTS: The type and magnitude of benefits, harms, and costs expected for patients from guideline implementation. RECOMMENDATIONS: Management decisions vary between patients with primary or secondary pneumothoraces, with observation of small pneumothoraces being appropriate only for primary pneumothoraces. The level of consensus varies regarding the specific interventions indicated, but agreement exists for the general principles of care. VALIDATION: Recommendations were peer reviewed by physician experts and were reviewed by the American College of Chest Physicians (ACCP) Health and Science Policy Committee. IMPLEMENTATION: The guideline recommendations will be published in printed and electronic form with distribution of synopses for patients and health care providers. Contents of the guideline will be incorporated into continuing medical education programs. SPONSORS: The ACCP.

p53 immunoreactivity in Barrett's metaplasia, dysplasia, and carcinoma.

Barrett's esophagus is a metaplastic condition with an unpredictable potential for neoplasia. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of some carcinomas. These mutations frequently result in intranuclear protein accumulation, which can be detected immunohistochemically. This study was undertaken to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. Twenty-eight esophageal resection specimens were studied. Barrett's mucosa was present in each specimen, low-grade dysplasia in 27, high-grade dysplasia in 26, intramucosal cancer in 18, and submucosal cancer in 5. Immunohistochemical staining with the monoclonal antibody Pab1801 was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimens of Barrett's mucosa or low-grade dysplasia. p53 immunoreactivity was found only in specimens of high-grade dysplasia, intramucosal cancer, and submucosal cancer. Sixty-nine percent (18/26) of these specimens exhibited mutated p53; 18 of 26 specimens of high-grade dysplasia (69%), 12 of 18 intramucosal cancer specimens (67%), and two of five submucosal cancer specimens (40%) expressed mutated p53. When p53 staining was observed, the spectrum of neoplastic changes (high-grade dysplasia, intramucosal cancer, submucosal cancer) within the specimen was positive. We conclude that (1) p53 immunoreactivity in Barrett's esophagus is a frequent, but not inclusive, marker for high-grade dysplasia, intramucosal cancer, and submucosal cancer and (2) immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.

Prognostic significance of flow cytometry in non-small-cell lung cancer.

To clarify the value of deoxyribonucleic acid (DNA) ploidy analysis, we prospectively studied single-parameter flow cytometric findings of fresh tissue from 272 patients with primary non-small-cell lung cancer from whom adequate tissue from the lung cancer was available. The mean age of the patients was 65.5 years; 65.8% were men. Histologic types were as follows: adenocarcinoma, 107 (39.3%); squamous cell, 100 (36.8%); large cell, 56 (20.6%); adenosquamous, 8 (2.9%); and giant cell, 1 (0.4%). Histologic grades were as follows: I (well differentiated), 15 (5.5%); II, 100 (36.8%); and III, 157 (57.7%). American Joint Committee on Cancer stages were as follows: I, 151 (55.5%); II, 38 (14%); III, 74 (27.2%); and IV, 9 (3.3%). Survivals at 1 year and 3 years were 74.2% +/- 2.8% and 52.4% +/- 4.8%, respectively. For non-squamous cell lung cancer, multivariate analyses with the Cox proportional hazards regression model for survival showed (1) that increasing American Joint Committee on Cancer stage (p < 0.001), male gender (p = 0.02), and histologic grades II and III (p = 0.04) were of independent (negative) prognostic significance and (2) that the presence and absence of DNA aneuploidy (p = 0.91), the classification of DNA histogram (p = 0.81), the DNA index (p = 0.46), and the results of cell cycle analysis in tumors with no aneuploidy (S phase, p = 0.23; S + G2M, p = 0.62) were of no prognostic significance. For squamous cell lung cancer, multivariate analyses showed that increasing American Joint Committee on Cancer stage (p = 0.003) and increasing DNA index (p = 0.009) were of independent (negative) prognostic significance.

Stage II esophageal carcinoma: the significance of T and N.

OBJECTIVE: Stage II esophageal carcinomas are a heterogeneous group of uncommon malignant tumors that include both node-negative (IIA; T2 N0 M0 and T3 N0 M0) and node-positive (IIB; T1 N1 M0 and T2 N1 M0) carcinomas. The purpose of this study was to evaluate this heterogeneity and to identify predictors of improved survival. RESULTS: Ninety-four of 345 patients undergoing esophageal resection at the Cleveland Clinic Foundation between 1985 and 1994 had stage 11 carcinomas; 70 stage IIA (24 T2 N0 M0 and 46 T3 N0 M0) and 24 stage IIB (9 T1 N1 M0 and 15 T2 N1 M0). Pathologic stage and T and N status were the only identifiable predictors of survival. Stage IIA survival was significantly better than stage IIB (p = 0.01). T2 N0 M0 survival was not different from T1 N0 M0 survival (p = 0.83). T3 N0 M0 survival was significantly worse than T1 N0 M0 (p = 0.03) and intermediate between T2 N0 M0 survival (p = 0.06) and T1 N1 M0 and T2 N1 M0 survivals (p = 0.07). T1 N1 M0 and T2 N1 M0 survival was not significantly different from T3 N1 M0 survival (p = 0.63). CONCLUSIONS: (1) N1 disease is the principal predictor of reduced survival and N1 is independent of T. Therefore the distinction between T1 N1 M0, T2 N1 M0, and T3 N1 M0 carcinomas is not warranted. (2) N0 disease is the principal predictor of improved survival but N0 is not independent of T. T1 N0 M0 and T2 N0 M0 survivals are similar and therefore distinction between these subgroups is not warranted. T3 N0 M0 survival is intermediate between T1 N0 M0 and T2 N0 M0 carcinomas and between T1 N1 M0, T2 N1 M0, and T3 N1 M0 carcinomas. Therefore stratification by T for N0 carcinomas is warranted.

Diagnostic yield and therapeutic impact of flexible bronchoscopy in lung transplant recipients.

BACKGROUND: Bronchoalveolar lavage and transbronchial biopsy are often used for definitive diagnosis of lung rejection and infection in lung transplant recipients. Although protected specimen brushing is of value in nosocomial bacterial pneumonia, its role in lung transplant recipients had not been widely reported. The aim of the study is to review the diagnostic yield and therapeutic impact of flexible bronchoscopy with the use of a combination of bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy in lung transplant recipients. METHODS: We reviewed flexible bronchoscopy data in 83 transplant recipients between February 1990 and March 1995. Only those with bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy were included in the analysis. There were 282 bronchoscopies performed for clinically suspected lung rejection or infection (clinical bronchoscopy) and 38 bronchoscopies for follow-up of a previously detected histologic abnormality (follow-up bronchoscopy). RESULTS: The total yields for rejection and infection for clinical and follow-up bronchoscopies were 67.4% and 58.9%, respectively. Acute rejection was detected with transbronchial biopsy in 26.2% and 34.2% of clinical and follow-up bronchoscopies, respectively. Cytomegalovirus pneumonitis was detected with transbronchial biopsy in 4.0% and 11.4% of clinical and follow-up bronchoscopies, respectively. Overall, bacteria was the most common cause of lower respiratory tract infection. When used together, protected specimen brushing and bronchoalveolar lavage were complementary techniques for detection of bacterial lower respiratory tract infection with a significantly higher proportion detected with protected specimen brushing ( > or = 10(3) colony forming units/ml) compared with bronchoalveolar lavage ( > or = 10(5) colony forming units/ml) (p < 0.001). Complications were hemorrhage (1.9%), pneumothorax (2.5%) and transient hypoxemia (10.5%). The results had an impact on management of rejection and infection in 57.8% of clinical and 39.5% of follow-up bronchoscopies. CONCLUSIONS: We conclude that bronchoscopy, with the use of a combination of bronchoalveolar lavage, protected specimen brushing, and transbronchial biopsy, is safe with a high diagnostic yield and therapeutic impact for treating lung transplant recipients.

A phase I trial of intrapleural recombinant human interferon alpha (rHuIFN alpha 2b) in patients with malignant pleural effusions.

The use of intrapleural sclerosing agents to control reaccumulation of pleural fluid in patients with malignant effusions has been widely investigated. A phase I trial of intrapleural recombinant human interferon alpha (rHuIFN alpha 2b) was initiated to determine the toxicity and maximal tolerated dose in this group of patients. rHuIFN alpha 2b was instilled as a single dose following chest tube (15/16) or percutaneous (1/16) drainage of cytologically proven malignant effusions. Doses of rHuIFN alpha 2b were escalated from 25 x 10(6) to 200 x 10(6) U/m2 in cohorts of three to four patients. Toxicity was mild to moderate, and included chills, fever and chest pain, and resembled that produced by systemic administration of rHuIFN alpha 2b. Dose-limiting toxicity occurred at 200 x 10(6) U/m2 and consisted of hepatic enzyme elevations and renal failure. Partial control of the effusions was noted in two patients, with two additional patients having stable disease. Phase II trials of rHuIFN alpha 2b should utilize up to 150 x 10(6) U/m2 for intrapleural instillation.

Thoracoscopic lobectomy.

The various applications of video-assisted thoracic surgery (VATS) have rapidly expanded in the past 2 years to include may straightforward and technically unsophisticated procedures. We report our experience in 23 patients in which a VATS lobectomy was attempted. Preoperative staging, which included a computed tomographic scan of the head, chest, and abdomen as well as a bone scan, revealed that these patients with primary non-small cell lung carcinomas were in clinical stage I. All patients had adequate pulmonary reserve to tolerate a lobectomy. Further staging was accomplished by invasive means in all patients, and consisted of mediastinoscopy and, when indicated, mediastinotomy. Three patients were subsequently found to have N2 disease and were excluded from the study. In 15 of the remaining 20 patients, a successful VATS lobectomy was accomplished. There were no major intraoperative complications and all patients recovered uneventfully. Their mean hospital stay was 5.5 +/- 1.9 days. We conclude that VATS lobectomy is technically possible in this good-risk group of patients with early clinical stage I lung cancer. However, as with all VATS procedures, the advantages of this approach over more conventional surgical techniques need to be addressed in randomized trials. Our experience also indicates that considerable improvements are necessary, both in terms of the imaging and the instrumentation, to allow major procedures such as pulmonary lobectomy to be safely and expeditiously performed using a VATS approach.

Airway management during bilateral sequential lung transplantation for cystic fibrosis.

Bilateral sequential lung transplantation is now an accepted therapy for patients with end-stage cystic fibrosis. In our experience, the use of a standard double-lumen endotracheal tube to establish one-lung ventilation during bilateral lung transplantation has been associated with difficulty in clearing the airway of the thick, tenacious secretions characteristically seen in these patients. Intraoperatively, retained secretions have resulted in inadequate ventilation with subsequent hypercarbia, hypoxia, and the need for cardiopulmonary bypass support. We therefore changed our airway management to a single-lumen endotracheal tube combined with a bronchial blocker to establish one-lung ventilation during bilateral lung transplantation. The lumen of a single-lumen tube accommodates larger suction catheters and an adult bronchoscope, which has a larger suction port. We have used this technique in our last five transplantations, finding easier clearing of airway secretions along with markedly improved ventilation compared with management with a double-lumen tube. We recommend this technique of airway management when performing a bilateral single-lung transplantation for end-stage cystic fibrosis.

Esophageal carcinoma: esophageal ultrasound assessment of preoperative chemotherapy.

The effect of preoperative chemotherapy in the treatment of esophageal carcinoma is difficult to assess because of the inadequacies of clinical staging. Endoscopic esophageal ultrasound (EUS) has been shown to be accurate in the clinical determination of depth of tumor invasion (T) and regional lymph node status (N). Therefore, EUS may be useful in assessing the effect of preoperative chemotherapy in the treatment of esophageal carcinoma. Eleven patients with operable adenocarcinoma of the esophagus or esophagogastric junction underwent staging by EUS before treatment. This was followed by two courses (10 patients) or one course (1 patient) of chemotherapy: etoposide, 120 mg/m2 for 3 days; doxorubicin hydrochloride, 20 mg/m2; and cisplatin, 100 mg/m2. Restaging by EUS was done after treatment. Ten patients then underwent resection of the tumor with lymphadenectomy. One patient was found to have metastatic disease at thoracotomy and did not undergo resection. However, tissue sampling was adequate for the determination of pathological stage. Independent pathological determinations of T and N were then obtained. On completion of chemotherapy, 9 patients (82%) had relief or reduction of preoperative symptoms, and 9 patients (82%) had either no evidence of tumor or reduction of tumor size by endoscopy. Despite this clinical and endoscopic response, no patient had EUS-documented and pathology-confirmed reduction of T. However, 2 patients had EUS-documented and pathology-confirmed progression of N. The accuracy of EUS in the determination of T was 82% and of N, 73%.(ABSTRACT TRUNCATED AT 250 WORDS)

Initial experience with video-assisted thoracoscopic lobectomy.

In the past 2 years, the development of video-assisted thoracic surgery (VATS) has allowed thoracoscopy to rapidly evolve from a primarily diagnostic tool to a therapeutic tool with potentially useful applications. As with laparoscopy, the initial enthusiasm for VATS must be tempered by the reality of technical inadequacies, complications, and results that have yet to withstand careful scientific scrutiny. The purpose of this study was to determine the technical feasibility of a VATS lobectomy. Forty-four patients with primary bronchogenic carcinoma were evaluated and accepted as potential candidates for VATS lobectomy. After complete preoperative staging, these patients were in clinical stage I. All patients had normal arterial blood gases and adequate pulmonary function (forced expiratory volume in 1 second > 1.5 L) to tolerate a lobectomy. At the time of operation, 3 patients were found to have N2 disease and were excluded from the study. In 35 of the remaining 41 patients, a successful VATS lobectomy was accomplished through two thoracoscopy ports and a non-rib-spreading 6- to 8-cm "access" thoracotomy. There were no major intraoperative complications that necessitated conversion to an open thoracotomy. Mean operative time was 153 +/- 26 minutes. All 35 patients recovered uneventfully with a mean hospital stay of 5.7 +/- 1.6 days. A VATS lobectomy is technically feasible using our approach and is potentially safe. However, major advances in thoracoscopy imaging and instrumentation are necessary before this procedure will have the potential for widespread acceptance. Also, the advantages of VATS lobectomy over accepted surgical techniques will have to be carefully documented in randomized trials.

Expression of blood group antigen A by stage I non-small cell lung carcinomas.

To clarify the significance of blood group antigen A (BAA) expression by neoplastic cells, we studied patients who had curative resections of stage I non-small cell lung carcinomas. Immunohistochemical staining using monoclonal antibodies was used to detect BAA expression by paraffin-embedded carcinoma cells. One hundred three patients were studied; mean age was 62.6 years, and 70 (68%) were male. Histologic types were as follows: adenocarcinoma, 52 (50.5%); squamous cell, 25 (24.3%); large cell, 24 (23.3%); and adenosquamous, 2 (1.9%). Histologic grades were as follows: I, 13 (12.6%); II, 26 (25.3%); and III, 64 (62.1%). All patients had American Joint Committee on Cancer stage I tumors: 65 patients (63.1%) had T1 tumors, and 38 (36.9%) had T2 tumors. Recurrences developed in 25 (24.3%) and metachronous malignancies in 4 (3.9%). Survival was 75% +/- 4.8% at 3 years and 66.6% +/- 7.5% at 5 years. Eighty-nine patients (86.4%) were blood group A and 14 (13.6%) were AB. Ninety-five (92.2%) were secretors of BAA and 8 (7.8%) were not. The expression of BAA by neoplastic cells was not detectable in 34 (33%), trace (1% to 5% of neoplastic cells) in 10 (9.7%), 1+ (6% to 25%) in 8 (7.8%), 2+ (26% to 50%) in 12 (11.7%), 3+ (51% to 75%) in 12 (11.7%), and 4+ (76% to 100%) in 27 (26.2%). The pattern of neoplastic cell staining was homogeneous in 14 patients (20.3%) and heterogeneous in 55 (79.7%). Carcinoma recurrence, overall survival, and event-free survival were not related to secretor status, BAA expression, or pattern of staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggressive multimodality therapy for malignant pleural mesothelioma.

Nineteen patients with clinical stage I malignant pleural mesothelioma were treated with aggressive multimodality therapy. Nine patients underwent pleurectomy and decortication followed by immediate intrapleural chemotherapy with cisplatin and mitomycin C. Ten patients required pleuropneumonectomy followed within 1 week to 2 weeks by intrapleural administration of cisplatin (100 mg). Four to 8 weeks after operation, 15 patients underwent postoperative adjuvant cisplatin-based systemic chemotherapy. There were three postoperative complications (16%) requiring reoperation and one postoperative death (5%). Intrapleural chemotherapy was well tolerated with no complications. Systemic chemotherapy was poorly tolerated, and there was one chemotherapy-related death. Sixteen patients (84%) experienced good to excellent palliation. Three patients are currently alive with no evidence of recurrent disease at 10, 35, and 43 months. The median overall survival was 13 months and the median disease-free survival, 11 months. Overall and disease-free 3-year survivals were 17% and 22%, respectively. Patients with epithelial malignant pleural mesothelioma had significantly better overall survival (p = 0.037) and disease-free survival (p = 0.02) than patients with sarcomatous or biphasic malignant pleural mesothelioma. We conclude that despite major toxicity, in select patients with clinical stage I malignant pleural mesothelioma, aggressive multimodality therapy offers effective palliation and occasional long-term disease-free survival.

Normal bronchial healing without bronchial wrapping in canine lung transplantation.

The deleterious effect of steroids on bronchial healing in lung transplantation has led to the development of techniques to protect the anastomosis and to the exclusion of steroid-dependent patients from transplantation. The effect of steroids on bronchial healing was tested in a canine single-lung allotransplantation model. Twenty size-matched mongrel dogs (20 to 30 kg) underwent left lung transplantation without anastomotic wrap or direct revascularization. Postoperatively, all received daily doses of cyclosporine (15 mg/kg) and azathioprine (1 mg/kg) and were subdivided into three steroid dosage groups. Group A (n = 10) animals received 1.5 mg/kg of prednisone per day whereas groups B (n = 5) and C (n = 5) received 5.0 mg/kg of prednisone per day for 28 postoperative days. In addition, group C received prednisone (5.0 mg.kg-1.day-1) for 1 month preoperatively. In group A, 8 of 10 dogs survived 28 days without evidence of respiratory compromise, with anastomotic bursting pressure greater than 510 mm Hg. In group B, all 5 dogs survived to 28 days without evidence of respiratory compromise and with intact bronchial anastomoses (bursting pressures greater than 510 mm Hg). In group C, 3 of 5 animals survived to 28 days with intact anastomoses. Histological examination demonstrated normal bronchial healing in all anastomoses. These data suggest that preoperative steroid dependence should not be a contraindication to lung transplantation and that bronchial anastomotic wrapping with vascular tissue may not be essential.

Superficial esophageal carcinoma.

BACKGROUND: The detection of superficial esophageal carcinomas by surveillance endoscopy and the downstaging of advanced carcinomas to superficial carcinomas by induction therapy have increased the number of patients with these carcinomas undergoing resection. The natural history of these carcinomas is not well defined. METHODS: To evaluate the results of surgical resection and identify predictors of improved survival, a retrospective review of (1) patients with superficial esophageal carcinoma at presentation (SECP) and (2) patients with advanced carcinomas that were downstaged to no residual carcinoma or superficial esophageal carcinoma after induction therapy (SECD) was conducted. RESULTS: There were 54 patients with SECP (19 Tis and 35 T1). Survival was significantly better for patients with Tis carcinomas (85.3% at 5 years) and patients with intramucosal T1 carcinomas (79.4%) than for patients with submucosal T1 carcinomas (16.3%) (p = 0.007 and p = 0.045, respectively). Survival at 5 years for the 49 patients without regional lymph node metastases (N0) was 65.2%, whereas none of the 5 patients with regional lymph node metastases (N1) have survived more than 3 years (p = 0.054), and 3 died of recurrent disease. There were 21 patients with SECD (13 T0, 2 Tis, and 6 T1). Survival at 4 years was 58.2%. In this group, survival was not related to depth of tumor invasion (p = 0.76) or regional lymph node status (p = 0.68). CONCLUSIONS: We conclude that (1) patients with Tis and intramucosal T1 SECP have a significantly better survival than those with submucosal T1 SECP, (2) patients with N0 SECP have a significantly better survival than those with N1 SECP, and (3) survival of patients with SECD is not related to depth of tumor invasion or regional lymph node status.

Accelerated induction therapy and resection for poor prognosis stage III non-small cell lung cancer.

BACKGROUND: Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of this study was to assess toxicity, response, and survival of an accelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer. METHODS: Forty-two surgically staged patients with poor prognosis stage III non-small cell lung cancer received 11 days of induction treatment consisting of 96 hours of continuous chemotherapy infusions of cisplatin (20 mg.m-2.day-2), 5 fluorouracil (1,000 mg.m-2.day-2), and etoposide (75 mg.m-2.day-2) concurrent with accelerated fractionation radiation therapy (1.5 Gy twice a day, to a dose of 27 Gy). Induction was followed in 4 weeks by resection. Postoperatively, a second course of continuous chemotherapy and concurrent accelerated fractionation radiation therapy (postoperative dose 13 to 36 Gy) was given. RESULTS: Despite some degree of induction toxicity in all patients there was only one induction death (2.4%). A clinical partial response was seen in 24 patients (57%). Thirty-six patients (86%) underwent thoracotomy, and resection was possible in 33 (79%). Pathologic downstaging was seen in 17 patients (40%), and 2 patients (5%) had no residual carcinoma at operation. There were 11 postoperative complications (31%) and 4 postoperative deaths (11%). Thirteen patients (31%) are alive and disease-free, 24 (57%) have persistent disease or have recurred (15 distant, 5 locoregional, 4 both), and 9 patients are alive with disease. The median survival is 21 months and the 2-year Kaplan-Meier survival is 43%, with no differences identified between stages IIIA and IIIB patients (p = 0.63). CONCLUSIONS: We conclude that accelerated induction therapy and resection in poor prognosis stage III non-small cell lung cancer (1) is toxic, with a 12% treatment mortality; (2) is effective with a 79% resection rate and 40% pathologic downstaging rate; (3) provides excellent local control; (4) may prolong survival; and (5) is of value in stage IIIB as well as stage IIIA patients.

Management of the pneumothorax and barotrauma.

Primary and secondary pneumothoraces are relatively common problems in a busy chest physician's practice. Management options are often different when dealing with primary or secondary pneumothoraces because the underlying cause is different. Thoracoscopy will have a major impact on the surgical approach used in these patients, whereas the advent of lung transplantation has led to a more cautious approach toward the use of sclerosing agents in potential lung transplant recipients.