Thomas J. Kirby

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.

Cytomegalovirus Infection Is a Risk Factor for Invasive Aspergillosis in Lung Transplant Recipients

Invasive aspergillosis (IA) remains a major cause of morbidity and mortality following solid organ transplantation. To assess the incidence of IA following lung transplantation and to identify risk factors for its occurrence, we performed a case-control study involving 101 patients undergoing lung transplantation at our institution from 1990 to 1995 and reviewed the findings. Fourteen patients (14%) developed IA. The mean time from transplantation to diagnosis was 15 months. Nine patients died; the mean time to death from diagnosis was 13 days. Risk factors associated with developing IA included concomitant cytomegalovirus (CMV) pneumonia or viremia and culture isolation of Aspergillus species from a respiratory tract specimen after lung transplantation. Optimal strategies to prevent IA in lung transplant recipients remain to be determined, but prevention of aspergillus airway colonization and CMV viremia and disease after transplantation may be important targets for prophylactic interventions.

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.

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.

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.

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)

p53 Immunoreactivity in Barrett's metaplasia, dysplasia, and carcinoma

Barretts 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 Barretts 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. Barretts 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 Barretts 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 Barretts 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.

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.

Rare pulmonary manifestation of Ehlers-Danlos syndrome

Ehlers–Danlos syndrome (EDS) is an inherited disorder of connective tissue with multiple thoracic manifestations. We present an unusual thoracic manifestation of EDS consisting of parenchymal cysts and fibrous and fibroosseous nodules. These manifestations may be related to an abnormal attempt at repair of parenchymal or vascular tears.

Cardiopulmonary bypass (CPB) for lung transplantation

Surgeons have often been reluctant to use cardiopulmonary bypass (CPB) during single (SLTx) and double lung (DLTx) transplantation surgery because of the potential adverse sequelae of CPB including haemorrhage and activation of complement leading to sequestration of neutrophils and platelets in the pulmonary capillary bed, endothelial damage, increased capillary permeability and pulmonary oedema. To clarify the effect of CPB on lung transplant recipients, we reviewed our last four years’ experience in 74 patients of whom 30 required CPB support. Indications for CPB were mean pulmonary artery pressure of greater than 50 mmHg, haemodynamic instability, hypoxia or hypercarbia. Patients undergoing SLTx were placed on CPB via the femoral artery and vein, while those undergoing DLTx were cannulated in the standard fashion using the ascending aorta and right atrium. All patients were administered aprotinin prior to CPB. Intraoperatively and postoperatively, haemorrhage was not a major problem. The 30-day mortality in the CPB group and the non-CPB group were 20% and 4.6%, respectively which was not statistically significant (p = 0.06). We conclude that CPB during lung transplantation is a safe, effective method to support these severely ill patients and should not be avoided because of concerns over adverse sequelae of CPB on postoperative graft function.