Transabdominal robot-assisted diaphragmatic plication: a 3.5-year experience.

OBJECTIVES: Diaphragmatic paralysis, a known cause of dyspnoea, can drastically reduce breathing efficiency, diminishing quality of life. We report our 3.5-year experience with 22 consecutive patients who underwent transabdominal, robot-assisted diaphragmatic plication for diaphragmatic paralysis. METHODS: We retrospectively reviewed 22 consecutive patients who underwent this procedure by a single surgeon from 5 September 2012 to 12 May 2016. The primary outcome measure was change in dyspnoea severity, which was measured with the 5-point Medical Research Council dyspnoea scale (a score of 5 indicates breathlessness so severe, the individual is homebound). RESULTS: Of the 22 patients who underwent robotic diaphragmatic plication, 17 (77.3%) patients were male. Median body mass index was 30 kg/m2 (range 24.2-42.17 kg/m2). Most plications (13 of 22, 59.1%) were left sided; one (4.6%) was bilateral. Median operating time was 161 min (range 107-293 min), but this time was higher for the first 3 procedures (255 min, range 239-293 min). Median length of stay was 2 days, and median time to chest tube removal was 1 day. At follow-up, 20 of the 22 (91%) patients reported improved breathing and 2 reported no change. No patient reported worsened dyspnoea. The median Medical Research Council score changed from 4.0 preoperatively to 2.0 postoperatively (P = 0.001). CONCLUSIONS: Transabdominal robotic diaphragmatic plication involves small incisions but improves surgical dexterity. Surgical times are reasonable, and this surgical technique can be adopted with a quick but steep learning curve. Early results show good functional outcomes.

Vena cava filter fracture with migration to the pulmonary artery.

Inferior vena cava filter (IVCF) placement has been recommended by clinicians for patients with venous thromboembolism who are at high risk for pulmonary embolism. There are a number of complications with IVCF insertion, removal, and migration that have been reported in the literature. Although those resulting from structural failure are rare, they can also be among the most critical. We describe a 48-year-old woman with a history of hypercoagulability whose IVCF fractured during retrieval, resulting in partial embolization to the right middle lobe pulmonary artery.

Lung herniation after supraclavicular thoracic outlet decompression.

Lung herniation after first rib resection for thoracic outlet syndrome (TOS) has not been reported to our knowledge. We present a unique case of cervical lung herniation causing displacement of the brachial plexus and chronic pain in a patient who had previously undergone supraclavicular thoracic outlet decompression with first rib resection. This was successfully treated with thoracoscopic reduction and resection of the herniated lung and pleural flap closure of the defect.

Impact of video-assisted thoracoscopic surgery on benign resections for solitary pulmonary nodules.

BACKGROUND: Differentiating benign from malignant pulmonary lesions is an important part of surgical decision making. We reviewed our experience of resecting suspicious pulmonary nodules to test the hypothesis that the increased use of video-assisted thoracic surgery (VATS) has increased the resection rate of benign lesions. METHODS: A retrospective analysis was carried out on 3,217 patients who underwent resection for focal pulmonary lesions between 1995 and 2009. Resection method, computed tomography (CT) results, positron emission tomography (PET) results, and operative and pathology reports were reviewed. RESULTS: Pulmonary resection was by thoracotomy/median sternotomy in 2,632 of 3,217 (82%) patients and by VATS in 585 of 3,217 (18%). Resections performed by VATS increased from 129 of 2,150 (6%) between 1995 and 2005 to 453 of 1,067 (42.4%) between 2006 and 2009. From 2006 to 2009, 31.4% of lobectomies and 63.9% of wedge resections were performed by VATS. Benign lesions were found in 350 of 3,217 (10.8%) patients. Between 1995 and 2005 our resection rate of benign lesions was 192 of 2,150 (8.9%). From 2006 to 2009, it increased to 158 of 1,067 (14.8%), of which 85 of 456 (20.8%) were VATS and 63 of 611(10.3%) were open procedures. The benign lesion resection rate was 91 of 237 (38.3%) for VATS wedges, 49 of 134 (36.6%) for open wedges, 4 of 219 (1.8%) for VATS lobectomies, and 14 of 477 (2.9%) for open lobectomies. 257 of 456 (52.0%) of the VATS resections were wedges compared with 134 of 611 (21.9%) of the open procedures. CONCLUSIONS: There has been an increase in pulmonary resections performed by VATS. This is associated with an increase in benign lesion resections. The benign lesion resection rate for VATS was twice that of the open procedure rate. However the benign lesion resection rates for wedge resections and lobectomies were not significantly different in regard to approach. VATS has led to an increase in our overall benign lesion resection rate, which can be explained by the increased number of VATS wedge resections that are being performed.

Respiratory virus-induced dysregulation of T-regulatory cells leads to chronic rejection.

BACKGROUND: Lower respiratory viral infections predispose to bronchiolitis obliterans syndrome (BOS). In addition, there is emerging evidence to support the role of autoimmunity in the pathogenesis of BOS. Because CD4(+)CD25(+)Foxp3(+) regulatory T-cells (Treg) control autoimmunity, we tested the hypothesis that respiratory virus-induced Treg dysfunction leads to BOS. METHODS: Treg frequency was monitored using flow cytometry. Apoptosis, cytokines, and antibodies were analyzed using annexin V assay, LUMINEX, and enzyme-linked immunosorbent assay, respectively. Murine studies were performed using the orthotopic tracheal transplant model. RESULTS: (A) Human studies: Treg troughs (decrease >50% of baseline) were found in 13 (43.3%) of 30 lung transplant recipients. Treg isolated during troughs revealed increased apoptosis (37.8%). Patients with Treg troughs had increased prevalence of antibodies to self-antigens collagen type I (23.1% vs 5.8% pretrough), collagen V (7.7% vs 0%), and k-alpha tubulin (30.7% vs 11.7%, p < 0.01) at 6 months post-trough. Increased number of Treg troughs correlated with more rapid onset of BOS. (B) Murine studies: Infection of tracheal transplant recipients with murine parainfleunza sendai virus led to increased Treg apoptosis (50.5%) in the draining lymph nodes. Vaccination against sendai virus prior to transplant abrogated apoptosis of Treg. In vitro, sendai virus-infected, but not naive, tracheal epithelial cells demonstrated upregulation of FasL (>3.5-fold) and induction of co-cultured Treg apoptosis (5.6-fold increase). CONCLUSIONS: Respiratory viral infections cause Treg apoptosis which leads to the development of de novo autoimmunity that may play a role in the pathogenesis of BOS.

Pneumothorax, bullous disease, and emphysema.

This article addresses several distinct but related pulmonary conditions that are commonly referred to general thoracic surgeons for decision making and management. The management of various types of pneumothorax is reviewed, with particular attention to the selection of the appropriate level of surgical intervention. The related entities of bullous lung disease and diffuse emphysema are discussed, with a focus on the identification of appropriate circumstances for surgical intervention. The summarized work and the treatment recommendations are supported with an extensive bibliography of important work in this area.

Recurrent subcutaneous air of the face and neck.

Subcutaneous air of the face and neck can be seen after trauma to the lungs, airway, and esophagus. We present a case of a 29-year-old with recurrent subcutaneous air of the face and neck with minimal pneumomediastinum. In this report, we discuss the workup of this patient and review the literature regarding self-inflicted causes.

Immunological link between primary graft dysfunction and chronic lung allograft rejection.

BACKGROUND: Primary graft dysfunction (PGD) in the immediate post-lung transplant period strongly increases the risk of chronic rejection (broncholitis obliterans syndrome). Here, we hypothesized that PGD-induced inflammation augments alloimmunity, thereby predisposing to broncholitis obliterans syndrome. METHODS: Primary graft dysfunction and broncholitis obliterans syndrome were diagnosed according to the established International Society for Heart and Lung Transplantation criteria. Anti-human leukocyte antigen (HLA) alloantibodies were analyzed using Flow-PRA. Donor HLA class II-specific T cells were analyzed using interferon (IFN)-gamma ELISPOT. Serum levels of 25 cytokines and chemokines were measured using LUMINEX. RESULTS: Of the 127 subjects, 29 (22.8%) had no PGD (grade 0), 42 (33.2%) had PGD-1, 36 (28.3%) had PGD-2, and 20 (15.7%) had PGD-3. Patients with PGD grades 1 to 3 (PGD(1-3)) had elevated proinflammatory mediators MCP-1, IP-10, interleukin (IL)-1 beta, IL-2, IFN-gamma, and IL-12 in the sera during the early posttransplant period compared with patients with PGD grade 0 (PGD(0)). On serial analysis, PGD(1-3) patients revealed increased development of de novo anti-HLA-II (5 years: 52.2% versus PGD(0) 13.5%, p = 0.008). However, no difference was found in anti-HLA-I alloantibody development (PGD(1-3) patients 48% versus PGD(0) 39.6%, p = 0.6). Furthermore, PGD(1-3) patients had increased frequency of donor HLA class II-specific CD4(+) T cells [(91.4 +/- 19.37) x 10(-6) versus (23.6 +/- 15.93) x 10(-6), p = 0.003]. CONCLUSIONS: Primary graft dysfunction induces proinflammatory cytokines that can upregulate donor HLA-II antigens on the allograft. Increased donor HLA-II expression along with PGD-induced allograft inflammation promotes the development of donor specific alloimmunity. This provides an important mechanistic link between early posttransplant lung allograft injury and reported association with broncholitis obliterans syndrome.

Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

BACKGROUND: Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. METHODS: Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. RESULTS: Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. CONCLUSIONS: Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

Respiratory viral infection in obliterative airway disease after orthotopic tracheal transplantation.

BACKGROUND: The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model. METHODS: Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation. RESULTS: Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection. CONCLUSIONS: Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.

IL-12 p80 is an innate epithelial cell effector that mediates chronic allograft dysfunction.

RATIONALE: Bronchiolitis obliterans syndrome is the leading cause of chronic lung allograft dysfunction. We have demonstrated that respiratory viral infection is a bronchiolitis obliterans syndrome risk factor and virus-dependent injury induces expression of innate airway epithelial genes belonging to the interleukin (IL)-12 family. Thus, we hypothesized that epithelial cell IL-12 family members could mediate lung allograft dysfunction. OBJECTIVES: We used mouse and human allograft specimens to evaluate the role of epithelial cell IL-12 family members in allograft dysfunction associated with and without viral infection. METHODS: Murine and human IL-12 family members were characterized and manipulated in allografts and then correlated with epithelial cell injury, immune cell accumulation, and collagen deposition. RESULTS: In a mouse model of lung transplantation, concurrent viral infection and allogeneic transplantation increased epithelial injury and this was followed by exaggerated accumulation of macrophages and collagen deposition. This virus-driven allograft dysfunction was associated with an epithelial innate response manifested by a synergistic increase in the production of the macrophage chemoattractant IL-12 p80 (p80), but not IL-12 or IL-23. Blockade or overexpression of donor epithelial p80 resulted in a corresponding abrogation or enhancement of macrophage accumulation and allograft dysfunction. We extended these findings to human recipients with viral infection and transplant bronchitis and again observed excessive epithelial p80 expression that correlated with increased macrophage accumulation. CONCLUSIONS: These experiments support a role for an enhanced epithelial innate response as a central process in allograft dysfunction and identify the macrophage chemoattractant p80 as an innate epithelial effector of disease progression.

Animal models for bronchiolitis obliterans syndrome following human lung transplantation.

Lung transplantation is the only viable treatment option that can improve survival and enhance the quality of life of patients with end-stage lung diseases such as emphysema, cystic fibrosis, idiopathic pulmonary fibrosis, and primary pulmonary hypertension. However, the long-term survival of lung allografts is still limited by the development of bronchiolitis obliterans syndrome (BOS), an irreversible condition unresponsive to therapy. BOS is the most significant cause of long-term morbidity and mortality after lung transplantation. Over the past decade, several animal models have been developed to investigate BOS. These are valuable to elucidate the immunologic and pathologic mechanisms that lead to BOS and to test treatment options for BOS. In this review, we discuss the advantages and disadvantages of different animal models and highlight work that has been done with each model.

Molecular mechanisms of chronic rejection following transplantation.

Although significant advances have been made in the field of organ transplantation, chronic rejection remains a major limiting factor for prolonged graft survival. The long-term survival and function of transplanted lungs are limited by the development of bronchiolitis obliterans syndrome (BOS). The 10-yr lung graft survival rate is only 18.6%. Aside from results of several clinical studies that strongly support the concept that BOS results from alloimmune-mediated injury, little is known regarding specific immune effectors or target molecules involved in the pathogenesis of BOS. Studies from our laboratory have provided evidence for the seminal role of CD4+ T-cells in the pathogenesis of obliterative airway disease (OAD) seen in BOS. Prior to any clinically detectable lesions, there is indirect antigen presentation of mismatched major histocompatibility complex (MHC) class I antigen and production of antibodies to these MHC antigens. Both MHC and minor histocompatibility antigen disparities can result in the development of OAD in animal models and preliminary results strongly suggest that peptide vaccination strategies may prevent OAD following heterotopic tracheal transplants. Using a newly developed orthotopic tracheal transplant model, we have obtained evidence for an important and probably exclusive role for airway epithelial cell injury as a primary mechanism for the immunopathogenesis of the development of OAD.

Immune mechanisms in the pathogenesis of bronchiolitis obliterans syndrome after lung transplantation.

Lung transplantation is recognized as the only viable treatment option in a variety of end-stage pulmonary diseases. However, the long-term survival after lung transplantation is limited by the development of obliterative bronchiolitis, and its clinical correlate bronchiolitis obliterans syndrome (BOS), which is considered to represent chronic lung allograft rejection. Histopathologically, BOS is an inflammatory process that leads to fibrous scarring of the terminal and respiratory bronchioles and subsequent total occlusion of the airways. The specific etiology and pathogenesis of BOS are not well understood. The current premise is that BOS represents a common lesion in which different inflammatory insults such as ischemia-reperfusion, rejection, and infection can lead to a similar histological and clinical outcome. However, the low incidence of BOS in non-transplanted individuals and the observation that early development of BOS is predicted by the frequency and severity of acute rejection episodes indicate that alloimmune-dependent mechanisms play a crucial role in the pathogenesis of BOS. The evidence presented in this review indicates that BOS is the result of humoral and cellular immune responses developed against major histocompatibility complex molecules expressed by airway epithelial cells of the lung allograft. This process is aggravated by alloimmune-independent mechanisms such as ischemia-reperfusion and infection. Currently, treatment of BOS is frequently unsuccessful. Therefore, a better understanding of the immunopathogenesis of BOS is of paramount importance toward improving long-term patient and graft survival after lung transplantation.

Cut it out: Managing hepatic abscesses in patients with chronic granulomatous disease.

BACKGROUND: Hepatic abscesses develop in patients with chronic granulomatous disease (CGD) because the liver is a site of constant bacterial challenge. The authors investigated the roles of drainage and hepatic resection in the management of liver abscesses in CGD patients. METHODS: Medical records of CGD patients with hepatic abscesses from 1990 to 2001 were reviewed. RESULTS: There were 6 patients. Mean age of initial abscess was 7.2 years (range, 3 weeks to 18.9 years). All abscesses involved the right lobe of the liver (2 single, 4 multiple). All patients received appropriate antibiotics. Four patients were treated with one to 6 drainage procedures over one to 4 admissions before ultimately undergoing resection. The other 2 patients underwent primary resection without preliminary drainage. Of the 6 resections, 4 were nonanatomic, and 2 were anatomic. There was one major postoperative complication (bleeding) requiring reoperation. There were no recurrences after resection (mean follow-up 4.3 yr). Mean total days in hospital for the treatment of liver abscess was 49 in the preliminary drainage group and 8.5 in the primary resection group. Three patients required admission into the intensive care unit, one after a drainage procedure and 2 after resection. CONCLUSIONS: For CGD patients with hepatic abscesses, drainage procedures are associated with recurrence and prolonged hospitalization. Primary hepatic resection removing all involved tissue is safe and definitive for the management of this problem.