David M. Follette

Factors associated with false-positive staging of lung cancer by positron emission tomography

BACKGROUND Positron emission tomography imaging is gaining popularity as a noninvasive staging tool in non-small cell lung cancer. Nonmalignant processes can also affect radio-tracer uptake. This study seeks to identify factors associated with false-positive staging of mediastinal metastases. METHODS A retrospective review was performed of 100 patients with early stage non-small cell lung cancer referred for positron emission tomography scan evaluation. All had pathologic confirmation of their disease. Positron emission tomography scans, radiology records, operative reports, and pathology results were reviewed. Patients with positron emission tomography scans interpreted as positive for mediastinal involvement and negative pathology at operation were selected. RESULTS Seven patients were found to have a false-positive positron emission tomography evaluation for mediastinal metastases. All but 1 patient had a concurrent inflammatory process or an anatomic factor associated with the false positive. The sensitivity and specificity in detecting involved mediastinal nodes was 87.5% and 90.7%, respectively. The negative predictive value was 95.8%. CONCLUSIONS Although positron emission tomography has been established as an accurate modality to stage non-small cell lung cancer, false-positive evaluation of mediastinal metastases can occur in the setting of concurrent inflammatory lung diseases or for centrally located tumors. Pathologic evaluation of mediastinal disease should be pursued whenever suggested by a positive positron emission tomography scan especially in the face of those factors described.

Resection of multifocal non–small cell lung cancer when the bronchioloalveolar subtype is involved

OBJECTIVE Bronchioloalveolar lung cancer is commonly multifocal and can also present with other non-small cell types. The staging and treatment of multifocal non-small cell cancer are controversial. We evaluated the current staging of multifocal bronchioloalveolar carcinoma and the therapeutic effectiveness of resection when this tumor type is involved. METHODS We reviewed our experience between 1992 and 2000 with complete pulmonary resections for bronchioloalveolar carcinoma. Kaplan-Meier survival curves were calculated from the dates of pulmonary resection. RESULTS Among 73 patients with bronchioloalveolar carcinoma, 14 patients, 7 male and 7 female with a mean age of 65 years (51-87 years), had multifocal lesions without lymph node metastases. Follow-up was 100% for a median of 5 years (range 2.6-8.5 years). Tumor distribution was unilateral in 9 patients and bilateral in 5 patients. The multifocal nature of the disease was discovered intraoperatively in 4 patients. Nine patients had 2 lesions, 4 patients had 3 lesions, and 1 patient had innumerable discrete foci in a single lobe. Operative mortality was 0. Postoperatively, 10 patients were staged pIIIB or pIV on the basis of multiple foci of similar morphology; 4 patients had some differences in histology (implying multiple stage 1 primaries). The median survival time to death from cancer was 14 months (141 days-5.6 years). The overall 5-year survival after resection of multifocal bronchioloalveolar carcinoma was 64%. Unilateral or bilateral distribution had no impact on survival. CONCLUSIONS The current staging system is not prognostic for multifocal bronchioloalveolar carcinoma without lymph node metastases. Complete resection of multifocal non-small cell lung cancer when bronchioloalveolar carcinoma is a component may achieve survivals similar to that of stage I and II unifocal non-small cell lung cancer. When bronchioloalveolar carcinoma is believed to be one of the cell types in multifocal disease without lymph node metastases, consideration should be given to surgical resection.

Minimally invasive Ivor Lewis esophagectomy

Ivor Lewis esophagectomy consists of a laparotomy and right thoracotomy for resection of the intrathoracic esophagus. Recent advances in minimally invasive surgical technology have allowed surgeons to apply laparoscopy and thoracoscopy to perform esophagectomy. However, there have been few reports that describe a totally minimally invasive Ivor Lewis esophagectomy. We present a case of combined laparoscopic and thoracoscopic resection of the distal third esophagus with an intrathoracic esophagogastric reconstruction for esophageal carcinoma.

Selective overexpression of inflammatory molecules in hearts from brain-dead rats.

BACKGROUND Inflammatory processes that occur before, during, and after surgery may contribute to damage of transplanted hearts and their ability to withstand acute and chronic rejection. METHODS We determined the expression of mRNA for 10 inflammatory indicator molecules in hearts from brain-dead animals in which stable circulation was maintained. To produce brain death in male rats (n = 11), we inflated an intracranial balloon with saline (245 microl +/- 27 microl) to produce apnea and areflexia. Mean arterial pressure was maintained at 80 +/- 2 mm Hg for 6 hours. Controls (n = 11) received a burr hole but no balloon (mean arterial pressure, 94 +/- 1 mm Hg). We measured expression of each indicator molecule mRNA relative to expression of glyceraldehyde-3-phosphate dehydrogenase mRNA using reverse-transcriptase polymerase chain reaction. RESULTS Relative expression of intercellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1beta, and interleukin-6 mRNAs differed significantly (2.4 -4.6 times higher) between brain-dead and control hearts (p < 0.05; group t-test). CONCLUSION Increases in the inflammatory cytokine, interleukin-1beta, whose mRNA also increased, may mediate the overexpression of the adhesion molecule and interleukin-6 mRNAs. The data suggest that endothelial cells become inflamed during brain death, even when the circulation is stable, which may lead to leukocyte-endothelial interactions during brain death or after graft transplantation.

Tamponade in patients undergoing cardiac surgery: A clinical-echocardiographic diagnosis

The purpose of this study was to evaluate the sensitivity of current echocardiographic criteria in detecting cardiac tamponade in the patient who has undergone cardiovascular surgery. Because the current echocardiographic criteria for tamponade were initially developed and studied predominantly in patients with medical problems, relatively less information is available in patients who have undergone cardiac surgery. Of 848 consecutive patients who underwent cardiovascular surgery, patients were selected for the study if they had clinical or hemodynamic deterioration and had undergone an echocardiogram just before a successful pericardiocentesis or a surgical evacuation of pericardial blood or clot. The echocardiograms were evaluated for evidence of chamber collapse, cardiac motion, Doppler flow variations, and the location and width of pericardial separation. Fourteen patients were identified who met the inclusion criteria (clinical or hemodynamic deterioration, recent echocardiogram, and successful intervention) for cardiac tamponade. The clinical and hemodynamic findings were hypotension (13 patients), low cardiac output (7), low urine output (3), cardiopulmonary arrest (1), elevated central venous pressure (1), and shortness of breath (1). In these patients current echocardiographic criteria were seen infrequently: chamber collapse in the right atrium (6 of 14 patients) and right ventricle (4 of 14); Doppler flow variation (2 of 5); and swinging heart (0 of 15), whereas increased pericardial separation (> or = 10 mm) was seen in all (14 of 14) the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A Phase II Study of Paclitaxel, Carboplatin, and Radiation with or without Surgery for Esophageal Cancer

Background: Cisplatin-based chemoradiotherapy (CRT) has been a standard treatment for patients with locally advanced esophageal cancer. However, cisplatin is associated with significant toxicity. We conducted a phase II clinical trial of concurrent paclitaxel, carboplatin, and radiation with or without surgery as an alternative to the standard cisplatin-based CRT for localized and metastatic esophageal cancer. Methods: Fifty patients with esophageal cancer were enrolled: 16 patients with stage II, eight patients with stage III, and 26 patients with stage IV disease. Two thirds (67%) of patients had adenocarcinoma and one third (33%) with squamous histology. Patients with resectable disease were treated with paclitaxel 30 mg/m2, twice weekly for 10 doses, carboplatin AUC (area under the curve) 1.5 weekly for five doses; and concurrent radiation, 1.8 Gy/day, for a total of 45 Gy, followed by esophagectomy. Without surgery, patients received an additional dose each of paclitaxel and carboplatin with concurrent radiation for a total of 50.4 Gy, followed by two consolidation cycles of paclitaxel (200 mg/m2) and carboplatin (AUC 6). Results: During CRT, common stage III/IV toxicities included nausea/emesis (19%), esophagitis (9%), and neutropenia (4%). For consolidation chemotherapy, neutropenia (23%), neuropathy (8%) and nausea/emesis (4%) were the most common stage III/IV side effects. After CRT, 26% had a complete response, 17% had a partial response, and 41% had stable disease. Ninety-one percent of patients had clinical improvement of dysphagia. With a median follow-up of 32 months, the median survival was 12 months for patients with metastatic disease, 44 months for localized disease treated with esophagectomy, and >44 months for localized disease treated with definitive CRT. Conclusions: The regimen of paclitaxel, carboplatin, and radiation with or without surgery is well tolerated with promising efficacy for patients with esophageal cancer.

Mediastinoscopy might not be necessary in patients with non–small cell lung cancer with mediastinal lymph nodes having a maximum standardized uptake value of less than 5.3

OBJECTIVE Accurate pretreatment staging in non-small cell lung cancer remains tantamount in formulating an appropriate treatment plan. The maximum standardized uptake value obtained with integrated fluorodeoxyglucose-positron emission tomography/computed tomography has been proposed to be a predictor of malignancy in mediastinal lymph nodes. A recent study has also suggested that accuracy of integrated fluorodeoxyglucose-positron emission tomography/computed tomography might be improved by increasing the maximum standardized uptake value used for calling a lymph node positive from 2.5 to 5.3. We tested the hypotheses that the maximum standardized uptake value is a predictor of individual lymph node metastasis in non-small cell lung cancer and that pathologic staging with mediastinoscopy might not be necessary in patients with a maximum standardized uptake value of less than 5.3 in their mediastinal lymph nodes. METHODS This is a retrospective review of 765 lymph nodes sampled from 110 patients in a single institution with biopsy-proved non-small cell lung cancer. All patients underwent integrated fluorodeoxyglucose-positron emission tomography/computed tomography before biopsy or resection of their mediastinal lymph nodes. Surgical staging was the reference standard. All N2 lymph nodes were individually assessed according to station. Data were analyzed by using the Pearson chi(2) test. RESULTS Twenty-one (19%) of 110 patients had N2 disease, and a total of 765 N2 lymph nodes were pathologically examined. The mean and median maximum standardized uptake values for N2 nodes with metastatic disease were 9.2 (95% confidence interval, 7.0-11.4) and 7.2 (range, 2.2-25.8), respectively. For benign N2 nodes, the mean and median maximum standardized uptake values were 1.5 (95% confidence interval, 1.4-1.6) and 1.0 (range, 1.0-9.6), respectively (P < .05). When integrated fluorodeoxyglucose-positron emission tomographic/computed tomographic scans were reinterpreted by using a maximum standardized uptake value of 5.3 as a cutoff for malignancy, sensitivity decreased from 93% to 81% (P = .15), specificity increased from 86% to 98% (P < .01), positive predictive value increased from 22% to 64% (P < .01), negative predictive value was unchanged at 99%, and overall accuracy of integrated positron emission tomography/computed tomography increased from 87% to 97% (P < .01). CONCLUSIONS The maximum standardized uptake value is a predictor of individual lymph node metastasis in non-small cell lung cancer. Accuracy of integrated positron emission tomography/computed tomography is significantly improved by using a maximum standardized uptake value of 5.3 to assign malignancy, thereby dramatically decreasing the number of false-positive results. More importantly, these results suggest that some patients with non-small cell lung cancer with a maximum standardized uptake value less than 5.3 in their N2 lymph nodes might be able to forego mediastinoscopy and proceed directly to thoracotomy. This represents a significant change in the current management of standardized uptake value-positive mediastinal lymph nodes in non-small cell lung cancer.

Four-Dimensional Aortic Blood Flow Patterns in Thoracic Aortic Grafts

Time-resolved cardiac gated three-directional velocity data obtained with magnetic resonance velocity-encoded phase contrast sequences were used to study blood flow patterns in thoracic aortic grafts. Twelve patients were studied, 6 with traumatic descending aortic pseudoaneurysms, 3 with atherosclerotic aneurysms, and 3 with dissecting aneurysms. All grafts had an inflow jet; outflow jet; and/or vortices proximal, in, or distal to the graft. Flow abnormalities were generally mild in the descending aortic traumatic pseudoaneurysms seen in young people. The atherosclerotic aneurysms seen in elderly patients had the most abnormal flows with multiple vortices in and outside the graft. Blood persisted up to one and a half heartbeats in some vortices and took three to five heartbeats to flow from ascending to descending aorta compared with two to three in age-matched normal subjects. Rather large energy losses, probably up to 33% of the cardiac output in our worst case, may occur in thoracic aortic grafts.

Evaluation of minimally invasive surgical staging for esophageal cancer

BACKGROUND Conventional imaging studies (computed tomography and endoscopic esophageal ultrasonography) used for preoperative evaluation of patients with esophageal cancer can be inaccurate for detection of small metastatic deposits. We evaluated the efficacy of minimally invasive surgical (MIS) staging as an additional modality for evaluation of patients with esophageal cancer. METHODS Between December 1998 and February 2001, 33 patients with esophageal cancer were evaluated for surgical resection. Conventional imaging studies demonstrated operable disease in 31 patients and equivocal findings in 2 patients. All patients then underwent MIS staging (laparoscopy, bronchoscopy, and ultrasonography of the liver). We compared the results from surgical resection and MIS staging with those from conventional imaging. RESULTS MIS staging altered the treatment plan in 12 (36%) of 33 patients; MIS staging upstaged 10 patients with operable disease and downstaged 2 patients with equivocal findings. MIS staging accurately determined resectability in 97% of patients compared with 61% of patients staged by conventional imaging. The specificity and negative predictive value for detection of unsuspected metastatic disease in MIS staging were 100% and 96%, respectively, compared with 91% and 65%, respectively, for conventional imaging studies. CONCLUSION In addition to conventional imaging studies, MIS staging should be included routinely in the preoperative work-up of patients with esophageal cancer.

Cyclosporine A-associated thrombotic thrombocytopenic purpura following lung transplantation.

THROMBOTIC thrombocytopenic purpura (TTP) and hemolytic uremia syndrome (HUS) are the clinical sequelae of thrombotic microangiopathy. These two disorders are often regarded as a spectrum of a disease (TTP– HUS). TTP is an uncommon but well documented complication of cyclosporine A (CsA) therapy. The clinical syndrome is characterized by the pentad of thrombocytopenia, anemia, renal impairment, neurologic involvement, and fever. TTP–HUS appears to be the result of endothelial damage. CsA may cause TTP via direct injurious effects on endothelial cells generated by numerous potential mechanisms. CsA can reduce thrombomodulin-dependent generation of activated protein C from endothelial cells, thus inducing a thrombogenic state. It may also alter both the prostacyclin to thromboxane A ratio, and change the balance between the release and inhibition of von Willebrand factor, and the delicate balance of numerous other modulators leading to thrombosis. TTP associated with CsA use has been previously reported following bone marrow, kidney, heart, and liver transplantation. We report three cases of TTP in patients receiving CsA following lung transplantation. Between October 1994 and July 1997, we performed 31 lung transplants. Three patients developed TTP (9.7%). All three patients (two bilateral, one single lung recipient) manifested the classic pentad of TTP. All patients were maintained on CsA from the time of their transplant until their TTP was diagnosed. Two patients had levels that were considered above the therapeutic range prior to the development of TTP. The first patient was a 56-year-old female who underwent bilateral lung transplantation for lymphangioleiomatosis. Postoperatively she was started on intravenous CsA to maintain a level between 300 and 400 ng/mL and was subsequently converted to oral cyclosporine (Neoral). She had a relatively uneventful postoperative course. Five months later she was readmitted with nausea, vomiting, and abdominal distention. She was diagnosed with C. difficile colitis and initially improved with treatment. She then deteriorated. Lethargy and disorientation were replaced by obtundation. Her course included anemia (schistocytes were present on peripheral blood smears), progressive renal failure, thrombocytopenia (low of 13,000), and fever. The diagnosis of TTP was entertained late in her course so CsA was continued. Her highest trough CsA level was 485 ng/mL by HPLC 8 days prior to the diagnosis of TTP. Her condition deteriorated rapidly over 72 hours and she succumbed. The second patient, a 66-year-old male, was readmitted 9 months after bilateral lung transplantation for emphysema. His early postoperative course had been complicated by several episodes of pneumonia, and on this admission he was found to have an empyema which was treated surgically. When he manifested the signs of TTP, his CsA was discontinued and he was started on FK506. He required hemodialysis and support with blood products. After approximately 1 week, total plasma exchange (TPE) was instituted and he slowly improved. After 2 weeks of improvement, the diagnosis of TTP was doubted and TPE was stopped. He then relapsed with disorientation and thrombocytopenia, and did not subsequently improve until TPE was reinstituted. It was gradually weaned off over 2 months as an outpatient and he has subsequently done well. The final patient underwent single lung transplantation for a-1 antitrypsin deficiency. In her first postoperative week, she was treated with pulse-dose steroids for suspected rejection from which she appeared to improve. She had an isolated CsA trough level of 497 ng/mL 10 days postoperatively. Forty-eight hours later she had increasing fatigue and mental status changes that required reintubation. She had a rapid deterioration in her renal function requiring dialysis. A precipitous fall in her hematocrit to 21.9%, thorombocytopenia to a low of 14,000/mm, fever, and a grand mal seizure followed. Her CsA was discontinued and FK506 was started. The patient’s peripheral blood smear showed moderate schistocytes and a bone marrow biopsy was normal except for an increased number of megakaryocytes. She received intravenous g-globulin for 10 days and a total of 35 plasma exchanges with FFP. She was weaned off TPE and was discharged in good condition with adequate renal function and a normal platelet count. Due to the relative rarity of the disease, analysis of a large group of transplant patients has not been possible. It is,