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Biomedical subjects

S J Mentzer

Publications and source records attributed to S J Mentzer.

At least 55 records · Page 3Linked to original sources

No-cut thoracoscopic lung plication: a new technique for lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery (LVRS) using a linear cutting stapler or laser ablation via median sternotomy or thoracoscopy is a current therapy for symptomatic emphysema. The primary causes of morbidity and mortality (as high as 20%) are existing comorbidities and prolonged air leaks secondary to visceral pleural division. We report a novel technique using minimally invasive techniques designed to achieve volume reduction while preserving the visceral pleura. A novel lung grasper and a knifeless stapler are used to permanently plicate lung tissue without cutting visceral pleura. STUDY DESIGN: This prospective analysis involves a consecutive series of patients who had LVRS using this method. Between May 1995 and September 1996, 32 patients underwent 50 unilateral, staged bilateral, or bilateral thoracoscopic lung plication procedures. The indications for LVRS were standard; they included severe limiting dyspnea (forced expiratory volume in one second [FEV1] = 0.68 +/- 0.05), hyperinflated lungs with flattened diaphragms on chest x-ray, and diffuse emphysema seen on chest computed tomography scan. Ventilation and perfusion scanning was used to identify potential ventilation and perfusion mismatch target areas of lung for plication. RESULTS: The right lung was plicated first in 25 of 32 patients (78%), and upper lobe plications predominated (77%). A mean of 9.3 +/- 0.8 staple firings were used for each unilateral plication procedure. There were no perioperative deaths. Two patients (4%) required axillary thoracotomies to repair air leaks. Mean chest tube duration was 6.3 +/- 0.5 days. Median hospital stay was 7 days (range 3-15). An Intensive Care Unit stay was required following 8 procedures (17%). Postoperative morbidity occurred in 18 (39%) of 46 procedures, including 5 cases of atrial fibrillation and 4 persistent (> 7 days) air leaks. A minimum 2 month followup was available for 22 patients (32 of 46 procedures), demonstrating a clear chest x-ray with significant improvement in ipsilateral diaphragmatic contour. Twelve patients had unilateral reduction, and 10 patients had bilateral reduction in either a staged (n = 7) or sequential at one operation (n = 3) fashion. Twenty-five (78%) of 32 procedures were associated with improved pulmonary function, with a mean increase in FEV1, in patients in this subgroup of procedures, of 43 +/- 7% for each ipsilateral plication at a mean followup of 3.8 +/- 0.5 months. For the entire group of 32 procedures, the mean improvement in measured FEV1 was 29 +/- 7%. Supplemental oxygen requirement was significantly reduced in 9 of 16 patients following plication. CONCLUSION: These data suggest that minimally invasive surgical techniques coupled with a no-cut lung plication can achieve significant lung volume reduction with favorable postoperative morbidity and mortality. Lung plication appears to hold promise as an alternative technique of LVRS.

Humans↗

Mediastinoscopy, thoracoscopy, and video-assisted thoracic surgery in the diagnosis and staging of lung cancer.

The intrathoracic staging of lung cancer involves assessment of the primary tumor and potential sites of metastases. Imaging studies of the chest are sensitive in detecting intrathoracic abnormalities, but specific staging information generally requires a tissue biopsy. The instruments used to obtain this information include the bronchoscope, mediastinoscope, and thoracoscope. The complementary application of these instruments can provide valuable staging information while limiting the morbidity of surgical staging.

Fiber Optic Technology↗

Malignant effusive disease of the pleura and pericardium.

Malignant pleural and pericardial effusions are a common problem in the treatment of patients with lung cancer, breast cancer, or lymphoma and may occur with any malignancy. These effusions are frequently symptomatic and, in the case of the pleural space, may be the presenting sign of cancer. In other patients, they represent markers of recurrent, disseminated, or advanced disease. Given the poor prognosis of most patients presenting with these effusions, reducing symptoms and improving quality of life are the primary goals of treatment. Permanent drainage and/or obliteration of the pleural or pericardial space are crucial to the effective management of the effusion and will provide long-term palliation. Immediate relief can be accomplished via external drainage, but definitive therapy may often also require interventional radiology, cardiology, and thoracic surgery, as well as medical and radiation oncology. The pathophysiology, diagnosis, and treatment of malignant pleural and pericardial effusions are discussed in this article.

Drainage↗

Immunoblastic lymphoma of donor origin in the allograft after lung transplantation.

Posttransplant lymphoproliferative disorders (PTLD) are EBV-associated lymphoid neoplasms that are caused by the uncontrolled growth of EBV-infected B lymphocytes. The clinical presentation of PTLD can range from benign polygonal lymphoproliferative disorders to aggressive monoclonal immunoblastic lymphomas. In this report, we describe a seronegative lung transplant recipient who developed an immunoblastic lymphoma 4 months after lung transplantation from a seropositive donor. The neoplastic cells expressed B lymphocyte markers (CD19+, CD20+, sIgM+, kappa+) as well as the EBV antigen EBNA-2. A cell line with similar cytologic features spontaneously grew from in vitro cultures of the patient's peripheral blood mononuclear cells. The cell line and the lymphoma were EBV+, expressed a similar spectrum of B cell surface proteins, and had the donor's HLA haplotype. Analysis of immunoglobulin gene rearrangements and viral terminal repeat sequences revealed that the cell line and the tumor represented distinct B cell clones. Cultured peripheral blood mononuclear cells were restimulated in vitro with the EBV transformed cell line and tested for cytolytic activity. The host T cells demonstrated high levels of cytolytic activity against the tumor cell line that was abrogated by the addition of a anti-monomorphic HLA class I monoclonal antibody (mAb) (W6/32). These studies indicate that cells of donor origin can persist in the transplanted organ and may lead to an EBV-associated posttransplant lymphoma.

Antibodies, Monoclonal↗

Chest wall invasive non-small cell lung cancer: patterns of failure and implications for a revised staging system.

BACKGROUND: To assess outcomes and patterns of failure for chest wall invasive non-small cell lung cancer (T3 or IIIA NSCLC), data were acquired prospectively on 47 consecutive patients at a single institution over 6 years. METHODS: Preresectional stagings included bone scan, head and chest/abdominal computed tomography, and mediastinoscopy. There were 25 superior sulcus tumors (radiation and/or chemotherapy followed by resection) and 22 other chest wall invasive NSCLCs (resection alone). RESULTS: There were no perioperative deaths. Seventeen patients (36%) had an operative complication (median length of stay increased from 7 to 12 days; p < 0.05). A complete pathologic resection was achieved for 44 of 47 patients (94%). The median survival was 38 months (actuarial 2- and 5-year survival rates of 62% and 50%, respectively). Median lengths of survival for superior sulcus and other chest wall tumors were 36 and > 60 months, respectively. Significant univariate predictors of decreased overall and cancer-free survival were poor performance status, positive margins, and positive lymph nodes. Recurrence was observed in 22 of 47 patients (46%) at a median of 8 months (range 2-24); patterns of failure were in the ipsilateral chest (n = 2; 4%) and at a distant site (n = 15; 32%) or both (n = 5; 11%). CONCLUSIONS: The operative risk for chest wall invasive NSCLC is acceptable, even after neoadjuvant therapy, allowing for a 94% complete resection rate. The survival of this subset of stage IIIA patients may warrant a reappraisal of the international staging system.

Adult↗

Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias.

BACKGROUND: Data were acquired prospectively on 136 consecutive patients undergoing pneumonectomy for cancer from 1988 to 1993, to define factors that increase the risk of major morbidity and postoperative cardiac dysrhythmias. METHODS: There were 81 patients (60%) with non-small cell lung cancer (standard pneumonectomy) and 55 patients (40%) with malignant pleural mesothelioma (extrapleural pneumonectomy). RESULTS: Four perioperative deaths occurred (3%) with no identifiable associated risk factors. Twenty-three patients (17%) had a major complication with an increase in the median length of stay from 7 to 11 days (p < 0.01). Age greater than 65 years, right-sided procedures, and dysrhythmias were associated with an increased risk of a major complication (p < 0.05). Thirty-two patients (24%) had supraventricular dysrhythmias, which occurred on postoperative days 1 to 2 (n = 8), 3 to 4 (n = 13), 5 to 6 (n = 6), and 7 to 12 (n = 5). The median length of stay increased from 8 to 11 days with dysrhythmias (p < 0.05). Factors associated with an increased risk of dysrhythmias included age greater than 65 years, intrapericardial or extrapleural pneumonectomy, right-sided procedure, and any major complication. CONCLUSIONS: Pneumonectomy can be performed safely in selected patients with cancer. Supraventricular dysrhythmia was the most common complication noted with a peak incidence at 3 to 4 days after resection.

Adult↗

Laryngeal mask airway for therapeutic fiberoptic bronchoscopic procedures.

These cases illustrate the advantages of the laryngeal mask as compared with an endotracheal tube or oxygen face mask for selected patients undergoing therapeutic bronchoscopic procedures. The advantages include a larger internal diameter allowing easier passage of instruments, reduced work of breathing, lack of discomfort associated with insertion, access to the vocal cords and upper trachea unimpeded by the presence of an endotracheal tube, and capnographic and volume monitoring of respiration. The LMA is thus a valuable alternative for airway management in pulmonary compromised patients undergoing therapeutic bronchoscopic procedures.

Adult↗

Hybridoma screening for cell adhesion molecules using multiple parallel comparisons in conditions of flow.

Cell adhesion is a complex biophysical process that plays a central role in immunophysiology. Because of the complex force-energy relationships involved, insights into the mechanism of cell adhesion largely depend on comparative measurements. In this report, we describe a comparative approach to the measurement of cell adhesion under conditions of flow. The assay system perfuses fluorescently labeled lymphocytes over a cell monolayer in commercially available multiwell culture plates. The fluorescently labeled cells demonstrate a reproducible flow pattern within the well. Videomicroscopic recordings of cell movement have demonstrated rolling behavior over a wide range of cell velocities. This technique permits the measurement of cell adhesion over a variety of flow velocities, time courses, and treatment conditions. The ability to vary treatment conditions and provide multiple parallel conditions suggests the utility of this approach in the development of monoclonal antibodies (MAb) recognizing cell adhesion molecules.

Animals↗

Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma. Results in 120 consecutive patients.

OBJECTIVE: The authors examine the feasibility and efficacy of trimodality therapy in the treatment of malignant pleural mesothelioma and identify prognostic factors. BACKGROUND: Mesothelioma is a rare, uniformly fatal disease that has increased in incidence in recent decades. Single and bimodality therapies do not improve survival. METHODS: From 1980 to 1995, 120 patients underwent treatment for pathologically confirmed malignant mesothelioma at Brigham and Women's Hospital and Dana-Farber Cancer Institute (Boston, MA). Initial patient evaluation was performed by a multimodality team. Patients meeting selection criteria and with resectable disease identified by computed tomography scan or magnetic resonance imaging underwent extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. RESULTS: The cohort included 27 women and 93 men with a mean age of 56 years. Operative mortality rate was 5.0%, with a major morbidity rate of 22%. Overall survival rates were 45% at 2 years and 22% at 5 years. Two and 5-year survival rates were 65% and 27%, respectively, for patients with epithelial cell type, and 20% and 0%, respectively, for patients with sarcomatous or mixed histology tumors. Nodal involvement was a significant negative prognostic factor. Patients who were node negative with epithelial histology had 2- and 5-year survival rates of 74% and 39%, respectively. Involvement of margins at time of resection did not affect survival, except in the case of full-thickness, transdiaphragmatic invasion. Classification on the basis of a revised staging system stratified median survivals, which were 22, 17, and 11 months for stages I, II, and III, respectively (p = 0.04). CONCLUSIONS: Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.

Combined Modality Therapy↗

Sarcoidlike reaction in patients with malignancy.

PURPOSE: To determine the radiologic features, pathogenesis, and prognostic importance of sarcoidlike reaction in patients with malignancy. MATERIALS AND METHODS: Radiographs and computed tomographic (CT) scans of the chests of 10 patients with known malignancy and either concurrent or subsequent development of noncaseating granulomas (NCG) were reviewed and correlated with histopathologic reports and pertinent clinical data. RESULTS: Ten patients with malignancy were found to have either mediastinal or hilar lymph node enlargement (n = 4) or parenchymal lung disease (n = 6). The presumptive diagnosis was metastatic disease. In eight of 10 histopathologic specimens, no tumor was found, but innumerable NCGs were present. They were thought to be consistent with sarcoidlike reaction. In the other two specimens, only a small focus of tumor cells was found amidst innumerable NCGs. On CT scans of the chests, parenchymal lung disease took the form of either ground-glass attenuation (n = 1) or nodules following perivascular and peribronchial distributions (n = 5). CONCLUSION: Lymph node enlargement and parenchymal lung nodules may not indicate metastatic disease. Sampling of all abnormal areas may be helpful in staging the disease and in treating and determining the prognosis of patients. Likewise, the discovery of NCG does not necessarily indicate sarcoidosis and may represent sarcoidlike reaction.

Adult↗

LFA-1 and L-selectin regulation of recirculating lymphocyte tethering and rolling on lung microvascular endothelium.

Recirculating lymphocytes migrate into areas of lung inflammation by binding to microvascular endothelium and transmigrating into extravascular tissue. In this report, we examined the multiple-step paradigm using a unique system: recirculating lymphocytes from sheep peripheral lymphatics adhering to activated lung microvascular endothelium in conditions of physiologic flow. Video microscopy demonstrated that recirculating lymphocytes formed abrupt adhesions, without requisite rolling, on the lung microvascular endothelial cells. Lymphocyte velocity was unchanged within 100 ms of the development of firm adhesions. To dissect the adhesion mechanism, the lymphocytes were pretreated with anti-LFA-1 or anti-L-selectin monoclonal antibody (mAb). Both mAb decreased the incidence of firm adhesions. The mechanism of this inhibition was investigated using time-lapse topographic reconstructions of cell movement after pretreatment with mAb. Time-lapse analysis of the movement of lymphocytes pretreated with anti-LFA-1 mAb suggested that abortive adhesion was manifested by a characteristic saltatory movement and a sustained reduction in cell velocity (rolling) to <25 microns/s. In contrast, abortive adhesions of lymphocytes pretreated with anti-L-selectin mAb demonstrated transient arrest (tethering) but minimal rolling before resumption of baseline velocity in the flow stream. These observations provide insights into selectin and integrin regulation of lymphocyte transmigration into the lung. Further, the results of mAb inhibition suggest that the mechanism of lymphocyte migration may have some unique features not observed in studies of neutrophil transmigration.

Animals↗

Video-assisted thoracic surgery in the elderly. A review of 307 cases.

STUDY OBJECTIVE: The objective of the study was to investigate the impact of video-assisted thoracic surgery (VATS) on age-related morbidity and mortality for thoracic surgical procedures. DESIGN: Prospective data were collected on 896 consecutive VATS procedures from July 1991 to June 1994. Daily in-hospital, postoperative data collection by a full-time thoracic surgical nurse and postdischarge follow-up in a thoracic surgery clinic at 1 and 6 weeks were done. PATIENTS: On 296 patients aged 65 or older, 307 procedures were performed. One hundred nine procedures were performed on patients between 65 and 69 years, 110 on patients between 70 and 74 years, 55 on patients between 75 and 79 years, and 33 on those between 80 and 90 years. MEASUREMENTS AND RESULTS: The population was divided into four cohorts of 5-year age spans for analysis. Comparison was made with Fisher's Exact Test. Overall, 61% of the 307 procedures were for pulmonary disease. There were 32 anatomic lung resections (VATS lobectomies or segmentectomies), 156 extra-anatomic lung resections (thoracoscopic wedge or bullectomy), 78 procedures for pleural disease (25%), 27 mediastinal dissections (9%), and 14 pericardial windows (5%). There was a trend toward a lower mean FEV1 with increasing age. There were 3 deaths; overall mortality was less than 1%. There were 4 conversions to open thoracotomy (1%). Complications occurred with 45 procedures (15% morbidity). Twenty-two operations (7%) were associated with major complications adding to the length of stay and 27 procedures (9%) had minor complications. Median length of stay after VATS was 4 days for patients aged 65 to 79 years and 5 days for those aged 80 to 90 years. Morbidity and mortality were unrelated to age. CONCLUSIONS: The 30-day operative mortality is superior to previous reports of standard thoracotomy. Morbidity is low and length of hospital stay appears improved. VATS techniques may be safer than open thoracotomy in the aged. Age alone should not be a contraindication to operative intervention.

Aged↗

Characterization of a hypoxia-responsive adhesion molecule for leukocytes on human endothelial cells.

Decreased oxygen tension is one important component of ischemic episodes, which are characterized by leukocyte accumulation at the site of infarction. We have reported recently that cultured endothelial and muscle RD cells transferred from pO2 of 120 torr to pO2 of 50 torr for 3 h dramatically increased their adhesiveness for lymphocytes and neutrophils. In the present study, we identify and characterize a new endothelial cell adhesion molecule that mediates hypoxia-induced adhesion to leukocytes. We have generated a mAb, HAL 1/13, that recognizes a cell surface epitope common to both RD and endothelial cells and inhibits lymphocyte and neutrophil adhesion to muscle and endothelial cell monolayers under normoxic conditions in a dose-dependent manner. The contribution of the HAL 1/13 ligand to leukocyte adhesion significantly increased (more than twofold) when the muscle or endothelial cells had been exposed previously to a hypoxic environment. HAL 1/13 mAb completely abolished the enhancing effect of hypoxia on RD and endothelial cell adhesiveness for leukocytes. HAL 1/13 mAb immunoprecipitated a protein with Mr approximately 85,000 Da from cell surface-iodinated muscle and endothelial cells. The Mr, CD cluster dendrogram analysis, and lack of induction by IL-1 of HAL 1/13 distinguish it from most other known endothelial cell adhesion molecules. We suggest that this hypoxia-sensitive adhesion receptor on mesenchymal cells participates in neutrophil adhesion and consequent diapedesis during hypoxia-associated pathologic conditions.

Antibodies, Monoclonal↗

Cytogenetic and histologic findings in 17 pulmonary chondroid hamartomas: evidence for a pathogenetic relationship with lipomas and leiomyomas.

Pulmonary chondroid hamartomas (PCH) are benign tumors that contain mesenchymal and epithelial components. In this series, we identified clonal chromosome aberrations in mesenchymal cells from 10 of 17 PCH. Chromosome band 12q15 was rearranged most frequently (N = 4), and one case had a t(12;14)(q15;q24) that was identical cytogenetically to the characteristic translocation in uterine leiomyomas. Histologic review revealed diverse mesenchymal populations, including undifferentiated cells, cartilage, adipose tissue, and smooth muscle, in most of the PCH. These findings suggest that PCH result from neoplastic transformation of a primitive mesenchymal cell that differentiates along chondroid, adipose, and smooth muscle pathways.

Adult↗

In situ fluorescence labeling of sheep lung microvascular endothelium.

Endothelial cells are intimately involved in a variety of biological processes such as inflammatory disorders, wound healing, and tumor invasion. The finding of endothelial heterogeneity in various tissues has led to major efforts to isolate and culture microvascular endothelial cells in human and animal tissue. In this report we have used phosphatidyl ethanolamine (PE)-labeled liposomes to fluorescently label the sheep lung microvasculature in situ. Using normotensive perfusion pressure, the PE-labeled liposomes did not extravasate into extravascular lung tissue. Mechanical and enzymatic digestion of the lung tissue demonstrated that the PE-labeled liposomes provided a stable label of the vascular lining cells during ex vivo processing. After digestion, the overwhelming majority of the fluorescent label appeared in cellular aggregates. Approximately 80% of these cells demonstrated an in vitro phenotype consistent with microvascular endothelium. A novel monoclonal antibody selective for sheep endothelial cells was developed to confirm the presence of lung endothelium in the fluorescently labeled cellular aggregates. We conclude that in situ fluorescence labeling of vascular lining cells provides an anatomic marker for relevant vascular lining cells and an opportunity to study these cells in vitro.

Animals↗

Hybridoma screening using an amplified fluorescence microassay to quantify immunoglobulin concentration.

The early identification of antibody-secreting hybridomas significantly reduces the time and resources devoted to unproductive colonies. To quantify the immunoglobulin concentration in hybridoma supernatants within 2 weeks of fusion, we used immunomagnetic microspheres to capture immunoglobulin in the hybridoma culture supernatant. The captured immunoglobulin was detected using a goat anti-mouse second antibody liked to beta-galactosidase. With data transformation to correct for the nonlinear accumulation of the fluorescent reaction product, the enzymatic hydrolysis of fluorescein digalactoside permitted the reliable detection of less than 10 pg of immunoglobulin per milliliter. To determine the value of quantifying immunoglobulin concentration within 2 weeks of fusion, the amplified fluorescence microassay was applied to the evaluation of 3 consecutive fusions and more than 1200 growing hybridoma colonies. Using antibody concentrations greater than 10 ng/ml as a threshold for routine subculture, the selection of hybridoma colonies based on antibody secretion was threefold more efficient than selection based on colony growth alone. These results suggest the utility of the early determination of immunoglobulin concentration in the selection of hybridoma colonies.

Animals↗

Thoracoscopy and video-assisted thoracic surgery in the treatment of lung cancer.

The contemporary surgical repertoire for the evaluation and treatment of patients with lung cancer includes the bronchoscope, mediastinoscope, thoracoscope, and standard surgical instrumentation. The recent advances in video optics and the development of endoscopic instruments have significantly expanded the surgical options for patients with lung cancer. Thoracoscopy, or the more inclusive term of video-assisted thoracic surgery (VATS), has been characterized as "minimally invasive" surgery. Thoracoscopy and VATS have decreased operative trauma and facilitated surgical staging prior to neoadjuvant therapy. An ancillary benefit to diminished surgical morbidity is shorter hospital stays with a concomitant reduction in costs to the patient and health-care system. These advantages make VATS ideal for elderly patients or patients with significant comorbidity.

Humans↗

The safety and versatility of video-thoracoscopy: a prospective analysis of 895 consecutive cases.

BACKGROUND: The application of video-endoscopy to general thoracic surgery is radically changing the approach to many benign and malignant diseases of the chest. Since July 1991, we have performed 794 purely thoracoscopic and 101 video-assisted thoracic surgical (VATS) procedures on 860 patients. STUDY DESIGN: Comprehensive, prospectively acquired data examining the specific indications for and outcomes of this new technique were prospectively entered into a thoracic surgical database. Preoperative, intraoperative, postoperative, and outcome variables were studied for the entire group as well as three high-risk cohorts: age over 70 years (n = 198), forced expiratory volume in one second (FEV1) of less than 1 L (n = 46), and Karnofsky performance index of less than 8 (n = 61). RESULTS: The 895 cases involved 449 men and 446 women of ages 15 to 89 years (mean 56 +/- 16 years standard deviation). The indications for surgery were diagnostic in 501 cases (56 percent), therapeutic in 244 cases (27 percent), and both diagnostic and therapeutic in an additional 150 cases (17 percent). The specific procedures performed were operations on the lung (569 cases), pleura (196 cases), esophagus (42 cases), mediastinum (51 cases), and pericardium (37 cases). Fifty-seven percent of the procedures were for a malignant process and 43 percent were for benign or infectious pathology. There were nine deaths for a series operative mortality rate of 1.0 percent. Thirteen patients (1.4 percent) required conversion to a limited thoracotomy for technical reasons. There were 127 complications in 121 patients yielding a morbidity rate in all patients of 14 percent. Mortality rates in the elderly, poor lung function, and depressed performance index cohorts were 1.5, 2.1, and 9.8 percent, respectively. Morbidity rates in these high-risk populations were 19, 30, and 18 percent, respectively. The median postoperative length of stay was three days after closed thoracoscopy and five days after VATS resection. CONCLUSIONS: These data underscore the flexibility, safety, efficacy, and potential for cost savings of videoscopic surgery in patients with thoracic diseases. The ability to perform excisional biopsy improves diagnostic specificity and sensitivity to nearly 100 percent. Video-assisted thoracic surgical techniques also offer a minimally invasive procedure with acceptable risk to patients heretofore inoperable by standard thoracotomy.

Adolescent↗