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Biomedical subjects

Larry R Kaiser

Publications and source records attributed to Larry R Kaiser.

At least 19 recordsLinked to original sources

Cytokine response is lower after lung volume reduction through bilateral thoracoscopy versus sternotomy.

BACKGROUND: Lung volume reduction surgery performed through bilateral video-assisted thoracoscopy (BVATS) was associated in the National Emphysema Treatment Trial with a statistically significant reduction in intensive care unit days, failure to wean, hospital stay, and cost, and earlier recovery compared with median sternotomy. Studies comparing other minimally invasive techniques with "open" procedures, including pulmonary lobectomy, have demonstrated reduced serum proinflammatory mediators postoperatively. We measured these levels after lung volume reduction surgery through BVATS and sternotomy. METHODS: Serum cytokine levels were measured by radioimmunoassay in 9 consecutive, steroid-free patients undergoing sternotomy and lung volume reduction surgery and 6 undergoing BVATS and lung volume reduction surgery. The groups were not statistically different with respect to age, partial pressure of arterial carbon dioxide, percent forced expiratory volume in 1 second, percent residual volume, percent total lung capacity, diffusion capacity of the lung for carbon monoxide, 6-minute walk, or apical perfusion fraction. Proinflammatory interleukin 6 and interleukin 8 and antiinflammatory interleukin 10 were evaluated preoperatively and postoperatively on days 1, 4, and 5. Clinical data were prospectively collected. RESULTS: There were no major postoperative complications or deaths. Interleukin 6 levels were lower in the BVATS than the sternotomy group (p = 0.016 by repeated measures analysis of variance). Interleukin 8 levels were lower in the BVATS group at most postoperative time points, but there were no significant differences in interleukin 8 or interleukin 10 levels between the sternotomy and BVATS groups at any individual time point or by analysis of variance. CONCLUSIONS: Use of a BVATS approach to lung volume reduction surgery is associated with reduced postoperative release of proinflammatory cytokines compared with a sternotomy approach. This may account for the reduction in recovery time and some measures of postoperative morbidity seen with the BVATS approach.

Aged↗

Parasternal intercostal muscle remodeling in severe chronic obstructive pulmonary disease.

Studies in experimental animals indicate that chronic increases in neural drive to limb muscles elicit a fast-to-slow transformation of fiber-type proportions and myofibrillar proteins. Since neural drive to the parasternal intercostal muscles (parasternals) is chronically increased in patients with severe chronic obstructive pulmonary diseases (COPDs), we carried out the present study to test the hypothesis that the parasternals of COPD patients exhibit an increase in the proportions of both slow fibers and slow myosin heavy chains (MHCs). Accordingly, we obtained full thickness parasternal muscle biopsies from the third interspace of seven COPD patients (mean +/- SE age: 59 +/- 4 yr) and seven age-matched controls (AMCs). Fiber typing was done by immunohistochemistry, and MHC proportions were determined by SDS-PAGE followed by densitometry. COPD patients exhibited higher proportions of slow fibers than AMCs (73 +/- 4 vs. 51 +/- 3%; P < 0.01). Additionally, COPD patients exhibited higher proportions of slow MHC than AMCs (56 +/- 4 vs. 46 +/- 4%, P < 0.04). We conclude that the parasternal muscles of patients with severe COPD exhibit a fast-to-slow transformation in both fiber-type and MHC proportions. Previous workers have demonstrated that remodeling of the external intercostals, another rib cage inspiratory muscle, elicited by severe COPD is characterized by a slow-to-fast transformation in both fiber types and MHC isoform proportions. The physiological significance of this difference in remodeling between these two inspiratory rib cage muscles remains to be elucidated.

Biomarkers↗

Multiple variables affecting blood usage in lung transplantation.

BACKGROUND: A few publications have reported on the role of variables affecting blood component usage during lung transplantation. METHODS: Transfusion records for lung transplantation patients at the Hospital of the University of Pennsylvania (November 1991 to July 2004) were reviewed. Bivariate analyses and regression models were used to correlate usage of packed red blood cells (RBC), fresh-frozen plasma (FFP) and platelets (PLT) with variables such as disease, number of pulmonary lobes (1 or 2), cardiopulmonary bypass (CPB) status and time on bypass. RESULTS: Among 376 patients examined during the study period, blood product usage (in units) was significantly higher in double- than in single-lung recipients (RBC, 5.76 vs 1.21; FFP, 5.55 vs 1.10; PLT, 1.15 vs 0.16; p < 0.001). Patients on CPB also used significantly more units (RBC, 8.28 vs 1.45; FFP, 9.70 vs 0.73; PLT, 1.86 vs 0.14; p < 0.001), correlating with time on bypass. Patients transplanted for Eisenmenger syndrome (ES) and cystic fibrosis (CF) received significantly more blood products than those transplanted for other diseases (RBC, ES = 17.91 vs CF = 7.31 vs all others <2.00; FFP, ES = 19.18 vs CF = 5.72 vs others <2.00; PLT, ES = 4.73 vs CF = 1.22 vs others <0.40; p < 0.001). A regression model identified variables predictive of blood product usage, including the number of lungs transplanted, CPB status, disease and patient age. CONCLUSIONS: Patients receiving double-lung transplantations, on CPB, or transplanted for ES and CF exhibited a very highly statistically significant demand (p < 0.001) for more blood products. Additional selected variables differentially predicted usage. These data will help transplant surgeons and transfusion medicine specialists better anticipate and prepare blood products for use in lung transplantation.

Adult↗

Blockade of TNF-alpha decreases both inflammation and efficacy of intrapulmonary Ad.IFNbeta immunotherapy in an orthotopic model of bronchogenic lung cancer.

Adenoviral immuno-gene therapy using interferon-beta has been effective in an orthotopic model of lung cancer. However, pulmonary inflammation induced by adenoviral (Ad) vectors will almost certainly limit the maximally tolerated dose. On the other hand, the strong innate immune response generated by the vector may be helpful in initiating the adaptive immune response required for efficacy. The goals of this study were to develop an effective approach to inhibit Ad.IFNbeta-mediated acute pulmonary inflammation and to determine whether this reduction of Ad-mediated inflammation decreased the therapeutic efficacy of Ad.IFNbeta in a mouse model of bronchioloalveolar cancer. Our data show that anti-TNF-alpha antibodies can blunt the innate pulmonary immune response induced by Ad vectors, even in sensitized animals. However, this effect also inhibited the ability of the animal to generate anti-tumor immune responses and reduced survival in an orthotopic lung cancer model responsive to Ad.IFNbeta treatment. Interestingly, in a flank model of tumor using a cell line derived from the lung tumor, TNF-alpha blockade did not inhibit efficacy. These data suggest that the innate immune response to adenovirus in the lung may be important in immuno-gene therapy of lung cancer. Therapeutic application of anti-inflammatory therapy in immuno-gene therapy strategies should thus be undertaken with caution.

Adenoviridae↗

Outcomes after 151 extended transcervical thymectomies for myasthenia gravis.

BACKGROUND: The ideal operative technique for thymectomy in myasthenia gravis (MG) remains controversial. We present the largest series of extended transcervical thymectomy to provide outcomes data to compare with transsternal procedures. METHODS: A retrospective chart review/interview was made of 164 patients operated upon from 1992 to 2004. Complete remission (CR) was defined as asymptomatic off medication for 6 months or asymptomatic on low-dose single-drug therapy (< or = 10 mg/d prednisone or < or = 150 mg/d azathioprine). A modified Osserman classification based upon the Myasthenia Gravis Foundation of America quantitative disease severity score was employed. RESULTS: The overall complication rate was 7.3%, and nearly all procedures were outpatient. Mean age at surgery was 43 years, and mean preoperative Osserman class was 2.3 (21% class 1; 39% class 2; 28% class 3; 12% class 4). Mean length of follow-up was 53 months. Mean postoperative Osserman class was 1.0. Nineteen percent of patients failed to improve. The crude cumulative CR rate was 37% (n = 58). Kaplan-Meier estimates of CR were 43% and 45% at 3 and 6 years, respectively. On multivariate analysis, only preoperative disease severity was significantly (inversely) associated with Kaplan-Meier CR rates. Longer-term follow-up (83 months) of only the earlier patients shows preserved CR rates (46%). CONCLUSIONS: This largest series of extended transcervical thymectomy for MG confirms that the 5-year Kaplan-Meier CR rate is comparable with that obtained after transsternal procedures. Patients with less severe disease have higher CR rates. Complete responses are durable, as the CR rate remains stable with extended follow-up.

Adolescent↗

Wilms' tumor arising within a mediastinal teratoma.

The majority of Wilms' tumors present in young children as an intraabdominal mass of renal origin. The use of multimodal treatment protocols according to internationally recognized treatment guidelines has resulted in extremely high cure rates even in the setting of advanced disease. By comparison, Wilms' tumors in older patients or Wilms' tumors located entirely outside the kidney are extremely rare. Because of the rarity of these tumors and the lack of established treatment guidelines specific to these lesions, older patients with atypical Wilms' tumors are at risk for under treatment and poorer outcomes. We report the case of an 18-year-old man with a Wilms' tumor arising within a mediastinal teratoma and discuss the management of this extremely rare lesion.

Adolescent↗

Anterior surgical approaches to the thoracic outlet.

OBJECTIVES: The anatomy of the thoracic outlet is complex, and the optimum surgical approach to pathologic disease at this location is controversial. Although the Dartevelle approach to the apex seems to be a safer and more direct approach, this technique has not been widely adopted in the United States. We have used this approach for pathologic disease at the thoracic outlet and modified it. Our experience is described in this article. METHODS: A retrospective review was performed on all patients who underwent an anterior approach between December 1997 and May 2003. RESULTS: There were 42 patients who underwent anterior approaches to pathologic disease at the level of the outlet. Diagnosis included apical non-small cell lung cancers (20 patients), osteosarcoma (2 patients), spinal cord compression (5 patients), solitary metastasis (4 patients), and benign lesions (11 patients). There were 22 female and 20 male patients with ages ranging from 26 to 82 years (mean age, 54.6 years). There were 25 complications in 14 patients and 1 in-hospital death. A transmanubrial approach was used in 14 patients, the standard Dartevelle technique was used in 8 patients, and a transclavicular approach with reapproximation of the clavicle was used in 20 patients. Reapproximation failed in 5 patients (3/3 patients who underwent fixation with mini-plates and 2/17 patients with sternal wires). CONCLUSIONS: The anterior approach is a useful adjunct to a thoracic surgeon's armamentarium. When a transclavicular approach is optimal, division and reapproximation of the clavicle are feasible. In our experience, reapproximation with wires is superior to plates and screws.

Adult↗

Interferon beta adenoviral gene therapy in a patient with ovarian cancer.

Background A 47-year-old woman with a history of ovarian cancer and a 6-year disease-free remission presented with dyspnea and increased abdominal girth. The patient was found to have ascites and a large left pleural effusion, both of which contained malignant cells consistent with recurrent ovarian cancer. Her disease progressed despite treatment with chemotherapeutic and hormonal agents. She was then enrolled in a phase I clinical trial of adenoviral-mediated interferon beta gene therapy. Investigations Abdominal and chest CT scans, 2-[(18)F]fluoro-2-deoxyglucose PET scan, viral cultures, interferon cytokine analysis, immunophenotyping, and tumor cytotoxicity analyses. Diagnosis Stage IV ovarian cancer with malignant ascites and pleural effusion. Management Tunneled pleural catheter and intrapleural adenoviral-mediated interferon beta gene therapy.

Adenoviridae↗

Activation of tumor-associated macrophages by the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid induces an effective CD8+ T-cell-mediated antitumor immune response in murine models of lung cancer and mesothelioma.

5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is a small molecule in the flavanoid class that has antitumor activity thought to be due to ability to induce high local levels of tumor necrosis factor (TNF)-alpha that disrupt established blood vessels within tumors. The drug has completed phase 1 testing in humans and is currently in phase 2 trials in combination with chemotherapy. Although characterized as a "vascular disrupting agent," there are some studies suggesting that DMXAA also has effects on the immune system that are important for its efficacy. The goal of this study was to carefully define the immune effects of DMXAA in a series of murine lung cancer and mesothelioma cell lines with varying immunologic characteristics. We show that DMXAA efficiently activated tumor-associated macrophages to release a variety of immunostimulatory cytokines and chemokines, including TNF-alpha; IFN-inducible protein-10; interleukin-6; macrophage inflammatory protein-2; monocyte chemotactic protein-1; and regulated on activation, normal T-cell expressed, and secreted. DMXAA treatment was highly effective in both small and large flank tumors. Animals cured of tumors by DMXAA generated a systemic memory response and were resistant to tumor cell rechallenge. DMXAA treatment led to initial tumor infiltration with macrophages that was followed by an influx of CD8(+) T cells. These CD8(+) T cells were required for antitumor efficacy because tumor inhibitory activity was lost in nude mice, mice depleted of CD8(+) T cells, and perforin knockout mice, but not in CD4(+) T-cell-depleted mice. These data show that activation of tumor-associated macrophages by DMXAA is an efficient way to generate a CD8(+) T-cell-dependent antitumor immune response even in animals with relatively nonimmunogenic tumors. Given these properties, DMXAA might also be useful in boosting other forms of immunotherapy.

Angiogenesis Inhibitors↗

Long-term follow-up of patients with malignant pleural mesothelioma receiving high-dose adenovirus herpes simplex thymidine kinase/ganciclovir suicide gene therapy.

PURPOSE: Delineation of the long-term follow-up data on a series of patients with malignant mesothelioma, who received a single intrapleural dose of a nonreplicative adenoviral (Ad) vector encoding the herpes simplex virus thymidine kinase "suicide gene" (Ad.HSVtk) in combination with systemic ganciclovir. EXPERIMENTAL DESIGN: This report focuses on the 21 patients receiving "high-dose" therapy, defined by an intrapleural dose of vector (> or =1.6 x 10(13) viral particles), where transgene-encoded tk protein was reliably identified on immunohistochemical staining. In 13 patients, the vector was deleted in the E1 and E3 regions of the Ad; in the other eight patients, the vector had deletions in the Ad genes E1 and E4. Safety, immunologic responses, transgene expression, and clinical responses were evaluated. RESULTS: Both the E1/E3-deleted vector and the E1/E4-deleted vector were well tolerated and safe, although production of the E1/E4 vector was more difficult. Posttreatment antibody responses against the tumors were consistently seen. Interestingly, we observed a number of clinical responses in our patients, including two long-term (>6.5 year) survivors, both of whom were treated with the E1/E4-deleted vector. CONCLUSIONS: Intrapleural Ad.HSVtk/ganciclovir is safe and well tolerated in mesothelioma patients and resulted in long-term durable responses in two patients. Given the limited amount of gene transfer observed, we postulate that Ad.HSVtk may have been effective due to induction of antitumor immune responses. We hypothesize that approaches aiming to augment the immune effects of Ad gene transfer (i.e., with the use of cytokines) may lead to increased numbers of therapeutic responses in otherwise untreatable pleural malignancies.

Adenoviridae↗

Intrapulmonary IFN-beta gene therapy using an adenoviral vector is highly effective in a murine orthotopic model of bronchogenic adenocarcinoma of the lung.

Given previous work showing that an adenoviral vector expressing IFN-beta (Ad.IFNbeta) was highly effective in eradicating i.p. mesothelioma tumors, the antitumor efficacy of this agent was evaluated in an orthotopic model of bronchogenic adenocarcinoma of the lung. These transgenic mice have a conditionally expressed, oncogenic K-rasG12D allele that can be activated by intratracheal administration of an adenovirus expressing Cre recombinase (Ad.Cre). K-rasG12D mutant mice were given Ad.Cre intranasally to activate the oncogene. Mice were then given 10(9) plaque-forming units of a control vector (Ad.LacZ) or Ad.IFNbeta intranasally 3 and 4 weeks later, a time when lung tumors had been established. Cells derived from K-ras-mutated lung tumors were also grown in the flanks of mice to study mechanisms of therapeutic responses. In two separate experiments, untreated tumor-bearing mice all died by day 57 (median survival, 49 days). Ad.LacZ-treated mice all died by day 71 (median survival, 65 days). In contrast, 90% to 100% of mice treated with Ad.IFNbeta were long-term survivors (>120 days; P < 0.001). In addition, immunity to re-challenge with tumor cells was induced. In vitro and flank tumor studies showed that Ad.IFNbeta induced direct tumor cell killing and that depleting natural killer or CD8+ T cells, but not CD4+ T cells, with antibodies attenuated the effect of Ad.IFNbeta. These studies, showing remarkable antitumor activity in this orthotopic lung cancer model, provide strong preclinical support for a trial of Ad.IFNbeta to treat human non-small cell lung cancer.

Adenoviridae↗

Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity.

PURPOSE: Myeloid suppressor (Gr-1(+)/CD11b(+)) cells accumulate in the spleens of tumor-bearing mice where they contribute to immunosuppression by inhibiting the function of CD8(+) T cells and by promoting tumor angiogenesis. Elimination of these myeloid suppressor cells may thus significantly improve antitumor responses and enhance effects of cancer immunotherapy, although to date few practical options exist. EXPERIMENTAL DESIGN: The effect of the chemotherapy drug gemcitabine on the number of (Gr-1(+)/CD11b(+)) cells in the spleens of animals bearing large tumors derived from five cancer lines grown in both C57Bl/6 and BALB/c mice was analyzed. Suppressive activity of splenocytes from gemcitabine-treated and control animals was measured in natural killer (NK) cell lysis and Winn assays. The impact of myeloid suppressor cell activity was determined in an immunogene therapy model using an adenovirus expressing IFN-beta. RESULTS: This study shows that the chemotherapeutic drug gemcitabine, given at a dose similar to the equivalent dose used in patients, was able to dramatically and specifically reduce the number of myeloid suppressor cells found in the spleens of animals bearing large tumors with no significant reductions in CD4(+) T cells, CD8(+) T cells, NK cells, macrophages, or B cells. The loss of myeloid suppressor cells was accompanied by an increase in the antitumor activity of CD8(+) T cells and activated NK cells. Combining gemcitabine with cytokine immunogene therapy using IFN-beta markedly enhanced antitumor efficacy. CONCLUSIONS: These results suggest that gemcitabine may be a practical strategy for the reduction of myeloid suppressor cells and should be evaluated in conjunction with a variety of immunotherapy approaches.

Adenoviridae↗

Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review.

Lung cancer is the leading cause of cancer death in the U.S. with survival restricted to a subset of those patients able to undergo surgical resection. However, even with surgery, recurrence rates range from 30% to 60%, depending on the pathologic stage. With the advent of partially effective, but potentially toxic adjuvant chemotherapy, it has become increasingly important to discover biomarkers that will identify those patients who have the highest likelihood of recurrence and who thus might benefit most from adjuvant chemotherapy. Hundreds of papers have appeared over the past several decades proposing a variety of molecular markers or proteins that may have prognostic significance in non-small cell lung cancer. This review analyzes the largest and most rigorous of these studies with the aim of compiling the most important prognostic markers in early stage non-small cell lung cancer. In this review, we focused on biomarkers primarily involved in one of three major pathways: cell cycle regulation, apoptosis, and angiogenesis. Although no single marker has yet been shown to be perfect in predicting patient outcome, a profile based on the best of these markers may prove useful in directing patient therapy. The markers with the strongest evidence as independent predictors of patient outcome include cyclin E, cyclin B1, p21, p27, p16, survivin, collagen XVIII, and vascular endothelial cell growth factor.

Apoptosis↗

Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm.

We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease (COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1; P < 0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms (P < 0.01), and a 19% increase (P < 0.05) in fibers expressing only the slow SERCA isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on diaphragm homogenates indicated that COPD diaphragms expressed only one-third the SERCA1 content noted in control diaphragms; in contrast, COPD and control diaphragms did not differ with respect to SERCA2 content. The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data (Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB. Am J Respir Crit Care Med 168: 706-713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm.

Calcium-Transporting ATPases↗

Comparative study of subxiphoid versus video-thoracoscopic pericardial "window".

BACKGROUND: It remains undefined whether surgical subxiphoid drainage or thoracoscopic pericardial "window" is the optimal operative approach to pericardial effusion. We hypothesized that the true window into the pleural space created by the latter might improve the duration of freedom from recurrent effusion. METHODS: We conducted a retrospective chart review of indications, preoperative and intraoperative variables, morbidity, recurrence, and survival. RESULTS: Fifty-six patients underwent the subxiphoid procedure and 15 underwent the thoracoscopic procedure. Echocardiographic evidence of tamponade was present before 8 of 10 thoracoscopic procedures (80%) and 43 of 56 subxiphoid procedures (81%) for which descriptions of hemodynamics were available. In addition, non-pericardial procedures were performed in 10 (67%) and 18 (32%) patients, respectively (p = 0.020). Anesthesia time was longer at thoracoscopy (117.1 +/- 32.4 vs 81.1 +/- 25.5 minutes; p < 0.001). Procedural morbidity was higher after thoracoscopy (4 [27%] vs 1 [2%]; p = 0.006), but was generally minor. Hospital mortality tended to be higher after the subxiphoid procedure (7 [13%] vs 0 [0%]; p = 0.332), but none of the deaths was procedure-related. Follow-up was complete for 65 patients (92%). Recurrence occurred in 1 thoracoscopy patient (8%) and 5 subxiphoid patients (10%) (p = 1.000). Mean time to recurrence by Kaplan-Meier analysis trends were longer after thoracoscopy (36.1 vs 11.4 months; p = 0.16), and multivariate analysis identified the thoracoscopic approach as an independent predictor of freedom from recurrence (relative risk, 0.41; p = 0.014). CONCLUSIONS: Operative time and minor procedural morbidity are higher with thoracoscopic pericardial window, but long-term control of effusion seemed to be better than after subxiphoid surgical drainage.

Female↗

Catamenial pneumothorax: optimal hormonal and surgical management.

OBJECTIVE: To provide further information addressing the etiology, optimal hormonal management and surgical management in catamenial pneumothorax (CP). METHODS: We retrospectively analyzed records of all female patients operated on for spontaneous pneumothorax at a university hospital between January 1993 and March 2002. RESULTS: In eight of 24 patients, pneumothoraces were timed with menses. In all, the right side was involved. Seven patients were on hormonal medications pre-operatively and six post-operatively. All six patients taking estrogen/progesterone replacement had recurrences pre-operatively and two of three had recurrences post-operatively while on these medications. No patient suffered a pneumothorax either pre- or post-operatively while taking a gonadotropin releasing hormone agonist (two and three patients, respectively). Intraoperative findings included diaphragmatic implants [5] diaphragmatic fenestrations [4], apical blebs [2] and visceral pleural implants [2]. All pathology was specifically addressed at the time of surgery. Pleural space management included mechanical pleurodesis in seven and pleurectomy with talc insufflation in 1. Follow-up ranged from 27 to 63 months with a mean of 48 months. Three patients developed post-operative recurrences. One was managed without intervention and two required additional procedures. CONCLUSION: Catamenial pneumothorax is under appreciated, representing up to one-third of women with spontaneous pneumothorax. Hormonal agents that allow for menses are ineffective. Gonadotropin releasing hormone agonists should be considered as part of the pre-operative or post-operative management in high risk patients. Our findings suggest that an additional intervention to augment pleural symphysis at the level of the diaphragm should be performed.

Adult↗

Familial massive leiomyoma with esophageal leiomyomatosis: an unusual presentation in a father and his 2 daughters.

Esophageal leiomyomatosis and leiomyoma are benign neoplastic lesions composed of proliferating smooth muscle cells. Although rare, these 2 conditions may occur simultaneously in an individual patient. Symptomatic patients often require surgical management. We describe the first reported cases of family members presenting with esophageal leiomyomatosis and concomitant massive esophageal leiomyoma.

Adolescent↗