Combined liver-kidney transplantation complicated by intraoperative discovery of a bronchobiliary fistula.

Herein, we report the case of an intraoperative diagnosis of bronchobiliary fistula during combined liver-kidney transplantation because of polycystic disease. The diagnosis necessitated changes in surgical and anesthesiologic management and in the overall medical decision-making process. Emergent isolation of the affected lung was instituted to mitigate a large air leak and ensure adequate respiratory exchange, and to enable surgical repair. The kidney transplantation procedure was delayed for a few hours, enabling hemodynamic and respiratory stabilization in the intensive care unit before conditions were deemed adequate to proceed. The posttransplantation course was complicated but eventually successful, and the patient recovered both liver and kidney function. At a later evaluation, we realized that diagnosis of bronchobiliary fistula could have been made preoperatively had the chest radiograph been interpreted correctly and had the clinicians involved had a higher degree of suspicion for this complication of polycystic liver disease.

Apyrase treatment prevents ischemia-reperfusion injury in rat lung isografts.

OBJECTIVE: Endothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate. However, ectonucleoside adenosine triphosphate diphosphohydrolase expression is rapidly lost following oxidative stress, leading to the potential for adenosine triphosphate and related purigenic nucleotides to exacerbate acute solid organ inflammation and injury. We asked if administration of a soluble recombinant apyrase APT102 attenuates lung graft injury in a cold ischemia reperfusion model of rat syngeneic orthotopic lung transplantation. METHODS: Male Fisher 344 donor lungs were cold preserved in a low-potassium dextrose solution in the presence or absence of APT102 for 18 hours prior to transplantation into syngeneic male Fisher 344 recipients. Seven minutes after reperfusion, lung transplant recipients received either a bolus of APT102 or vehicle (saline solution). Four hours after reperfusion, APT102- and saline solution-treated groups were evaluated for lung graft function and inflammation. RESULTS: APT102 significantly reduced lung graft extracellular pools of adenosine triphosphate and adenosine diphosphate, improved oxygenation, and protected against pulmonary edema. Apyrase treatment was associated with attenuated neutrophil graft sequestration and less evidence of tissue inflammation as assessed by myeloperoxidase activity, expression of proinflammatory mediators, and numbers of apoptotic endothelial cells. CONCLUSIONS: Administration of a soluble recombinant apyrase promotes lung function and limits the tissue damage induced by prolonged cold storage, indicating that extracellular purigenic nucleotides play a key role in promoting ischemia-reperfusion injury following lung transplantation.

Costimulatory blockade-mediated lung allograft acceptance is abrogated by overexpression of Bcl-2 in the recipient.

Lung allografts are considered to be more immunogenic than other solid organs. Little is known about the effectiveness of immunosuppressive regimens after lung transplantation. Herein, we describe a novel model of murine vascularized orthotopic lung transplantation we used to study the effects of costimulatory blockade on lung rejection. Transplants were performed in the Balb --> B6 strain combination. Recipients were either not immunosuppressed or received perioperative CD40/CD40L and CD28/B7 costimulatory blockade. Nonimmunosupressed Balb/c --> B6 lung transplants had severe acute rejection 7 days after transplantation and CD8(+) T cells outnumbered CD4(+) T cells within the allografts. Alternatively, B6 recipients that received perioperative costimulatory blockade had minimal inflammation and there were nearly equal numbers of CD8(+) and CD4(+) T cells in these grafts. Approximately one third of graft-infiltrating CD4(+) T cells expressed Foxp3. CD4(+) T cells isolated from these grafts induced apoptosis of alloreactive CD8(+) T cells that were stimulated with donor splenocytes in vitro. In contrast with wild-type B6 recipient mice, we observed severe rejection of Balb/c lungs 7 days after transplantation into Bcl-2 transgenic B6 recipients that had received costimulatory blockade. CD8(+) T cells outnumbered CD4(+) T cells in these immunosuppressed Bcl-2 transgenic recipients and, compared with immunosuppressed wild-type B6 recipients, a lower percentage of graft-infiltrating CD4(+) T cells expressed Foxp3, and a higher percentage of graft-infiltrating CD8(+) T cells expressed intereferon-gamma. Thus, our results show that perioperative blockade of the CD40/CD40L and CD28/B7 costimulatory pathways markedly ameliorates acute rejection of lung allografts in wild type but not Bcl-2 transgenic recipients.

Monocyte differentiation is controlled by MyD88 after mouse orthotopic lung transplantation.

In lung grafts, ischemia-reperfusion signals rapidly induce the recruitment and differentiation of host monocytes into macrophages and dendritic cells. The nature of ischemia-reperfusion signals are antigen independent, but have been hypothesized to initiate Toll-like receptor (TLR) and interleukin (IL)-1R-mediated signaling pathways that are thought to potentiate alloimmune responses. We wondered whether MyD88, an adaptor molecule critical for both TLR and IL-1R-mediated inflammatory responses, regulated monocyte differentiation in a mouse model of vascularized orthotopic lung transplantation. Orthotopic left lung transplants were performed in the following syngeneic combinations: CD45.1(+) B6 --> CD45.2(+) MyD88(-/-) and CD45.1(+) B6 --> CD45.2(+) B6. One day later, recipient-derived dendritic cells and macrophage numbers were assessed in the bronchiolar lavage by FACS analysis. Compared with the bronchiolar lavage of wildtype recipients, MyD88(-/-) recipients had lower numbers of dendritic cells in lung graft airways that were of recipient origin. Lower numbers of newly differentiated lung graft dendritic cells was coincident with the appearance of higher numbers of undifferentiated monocytes in the lung airways of MyD88(-/-) recipients as compared with wild-type recipients. Moreover, adoptive transfer experiments demonstrated that MyD88(-/-) monocytes were poorer at differentiating into lung dendritic cells as compared with wild-type monocytes. Taken together, these data show that MyD88 regulates graft-infiltrating monocyte differentiation and suggests a mechanism by which TLR/IL-1R-signaling pathways control adaptive responses in lung allografts through controlling monocyte fate.

Sphingosine 1-phosphate inhibits ischemia reperfusion injury following experimental lung transplantation.

Ischemia reperfusion (I/R) injury following lung transplantation is exacerbated by the destruction of the endothelial cell barrier leading to pulmonary edema and dysregulated activated lymphocyte migration. Sphingosine 1-phosphate (S1P), a G-coupled protein receptor (GPCR) agonist, has been previously shown to promote endothelial cell tight junction formation and prevent monocyte chemotaxis. We asked if S1P treatment could improve pulmonary function and attenuate I/R injury following syngeneic rat lung transplantation. In comparison to vehicle-treated recipients, S1P administered before reperfusion significantly improved recipient oxygenation following transplantation. Improved graft function was associated with reduced inflammatory signaling pathway activation along with attenuated intragraft levels of MIP-2, TNF-alpha and IL-1beta. Moreover, S1P-treated recipients had significantly less apoptotic endothelial cells, pulmonary edema and graft accumulation of neutrophils than did vehicle-treated recipients. Thus our data show that S1P improves lung tissue homeostasis following reperfusion by enhancing endothelial barrier function and blunting monocytic graft infiltration and inflammation.

A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings.

OBJECTIVE: Complement activation has been shown to play a significant role in ischemia-reperfusion injury after lung transplantation. TP-10 (soluble complement receptor 1 inhibitor) inhibits the activation of complement by inactivating C3a and C5a convertases. This was a clinical trial of TP-10 to reduce ischemia-reperfusion injury in lung transplantation. METHODS: In a randomized, double-blinded, multicenter, placebo-controlled trial, 59 patients from four lung transplant programs received TP-10 (10 mg/kg, n = 28) or placebo (n = 31) before reperfusion. This dose achieved 90% complement inhibition for 24 hours, and activity had returned toward normal by 72 hours. RESULTS: At 24 hours, 14 of 28 patients in the TP-10 group (50%) were extubated, whereas only 6 of 31 patients in the placebo group (19%) were (P = .01). The total times on the ventilator and in the intensive care unit both tended to be shorter in the TP-10 group, but these differences did not achieve statistical significance. Among patients requiring cardiopulmonary bypass (n = 5 in placebo group and n = 7 in TP-10 group), the mean duration of mechanical ventilation was reduced by 11 days in the TP-10 group (10.6 +/- 5.0 days vs 21.5 +/- 5.9 days in placebo group, P = .2). Operative deaths, incidences of infection and rejection, and length of hospital stay were not significantly different between the two groups. CONCLUSIONS: Short-term complement inhibition with TP-10 led to early extubation in a significantly higher proportion of lung transplant recipients. The effect of TP-10 was greater among patients undergoing cardiopulmonary bypass, with a large reduction in ventilator days. Complement inhibition thus significantly decreases the duration of mechanical ventilation and could be useful in improving the outcome of lung transplant recipients.

Use of cyclosporine in lung transplantation.

Prior to the cyclosporine (CsA) era, there were no long-term survivors from lung transplantation as the immunosuppressive drugs made patients very susceptible to opportunistic infections and anastomotic complications. CsA is a calcineurin inhibitor that binds to cyclophilins and inhibits transcription of interleukin 2 in T cells, thereby preventing proliferation of activated T cells. The initial immunosuppressive regimen at our institution includes CsA, azathioprine, and steroids. Blood levels of CsA (whole blood, TDx assay) are maintained between 250 and 350 ng/mL for 0 to 6 months, 200 to 300 ng/mL for 6 to 12 months, and around 200 ng/mL beyond 12 months following lung transplantation. Nephrotoxicity, hypertension, susceptibility to infections, and malignancy are some of the serious side effects of CsA that limit its therapeutic usefulness. Acute rejection is relatively common with this regimen, and about 60% of all lung transplant recipients are treated for an episode of acute rejection within the first 12 months after lung transplantation. Acute rejection is a probable risk factor for chronic rejection, and obliterative bronchiolitis develops in about 50% of the patients who survive 5 years. Treatment of chronic rejection continues to be a challenge in lung transplantation. CsA and tacrolimus seem to have equivalent results in lung transplantation, although a few patients may benefit from the use of tacrolimus.

Chronic obstructive pulmonary disease. 10: Bullectomy, lung volume reduction surgery, and transplantation for patients with chronic obstructive pulmonary disease.

There are currently three surgical treatments for emphysema: bullectomy, lung transplantation, and lung volume reduction surgery (LVRS). Unfortunately, most emphysema patients are poor candidates for any surgical intervention. A meticulous selection process is favoured in which indications and contraindications are considered and the best solution is devised for each patient. Patients with giant bullae filling half the thoracic volume and compressing relatively normal adjacent parenchyma are offered bullectomy; those with hyperinflation, heterogeneous distribution of destruction, forced expiratory volume in 1 second (FEV(1)) >20%, and a normal carbon dioxide tension (PCO(2)) are offered LVRS; and patients with diffuse disease, lower FEV(1), hypercapnia, and associated pulmonary hypertension are directed towards transplantation. Using these criteria, few patients are serious candidates for surgical procedures. Combinations of LVRS and lung transplantation, either simultaneously or sequentially, are possible but rarely necessary.

Lymphoproliferative disease after lung transplantation: comparison of presentation and outcome of early and late cases.

BACKGROUND: Post-transplantation lymphoproliferative disease (PTLD) after lung transplantation has not been fully characterized. In previous studies, the incidence has varied substantially, and most cases have been reported during the first year after transplantation. The purpose of this study was to review our center's experience with PTLD and to analyze the pattern of disease and determinants of outcome. METHODS: Among 494 adult lung (n = 491) or heart-lung (n = 3) recipients, 30 cases of PTLD were retrospectively identified. The cases were classified by site(s) of involvement, histology and time of onset (early, < or =1 year, and late, >1 year after transplantation). The outcome of each case was ascertained, and risk factors for death were analyzed in a multivariate model. RESULTS: PTLD was identified in 30 (6.1%) of the recipients during 1,687 patient-years (median 2.8 years) of follow-up. The incidence density was 1.8 cases per 100 patient-years. Fourteen cases were diagnosed during the first year after transplantation, and 16 cases in subsequent years. The incidence density was significantly higher in the first year than in later years (3.3 cases/100 patient-years versus 1.3 cases/100 patient years; p <.008). Presentation in the thorax and involvement of the allograft were significantly more common in the early cases (thorax: 12 of 14, 86%; allograft: 9 of 14, 64%) than in the late cases (thorax: 2 of 16, 12%; allograft: 2 of 16, 12%). There was no difference in survival after the diagnosis of PTLD between the early and late cases, but survival time after diagnosis was significantly longer in cases with, than those without, allograft involvement (median 2.6 years vs 0.2 year, respectively; log rank p = 0.007). The presentation and pattern of organ involvement of PTLD after lung transplantation is related to the time of onset. CONCLUSIONS: Disease in the thorax and involvement of the allograft are common in the first year after transplantation, but other sites, especially the gastrointestinal tract, predominate later. PTLD that is confined to the allograft appears to have a somewhat better prognosis than disease that involves other sites.

Outcome of bilateral lung volume reduction in patients with emphysema potentially eligible for lung transplantation.

OBJECTIVE: Between January 1993 and May 1998, we performed 200 consecutive bilateral lung volume reduction operations. After initial assessment, 99 of these patients were eligible for lung volume reduction and potentially eligible for immediate or eventual lung transplantation on the basis of age and absence of contraindications. All chose to proceed with lung volume reduction surgery. The outcomes of these 99 patients are reviewed to assess the consequences of proceeding with lung volume reduction surgery on patients potentially eligible for lung transplantation. METHODS: A retrospective study was performed with the use of a prospectively assembled computer database. RESULTS: The 61 men and 38 women were 55 +/- 7 years old at evaluation for lung volume reduction. Mean values for first second expired volume, total lung capacity, and residual volume were 24% +/- 8%, 141% +/- 19%, and 294% +/- 54% predicted. There were 4 operative deaths and 17 late deaths. Two-year and 5-year survival after evaluation for lung volume reduction are 92% and 75%. The 32 patients who have been listed for transplantation after lung volume reduction include 15 who have undergone transplantation, 14 who remain on the list, and 3 who have been removed from the list. All 15 transplant recipients survived transplantation and 3 have subsequently died of rejection or late infection. The 12 living recipients have a median post-transplantation follow-up of 1.7 years. The age at transplantation was 58 +/- 5 years with transplantation occurring 3.8 +/- 1.1 years after lung volume reduction. Sixteen of 99 patients underwent lower lobe volume reduction with an increased rate of listing (63%, P =.008) and transplantation (38%, P =.003) compared with patients undergoing upper lobe volume reduction. Patients listed for transplantation were younger, more impaired, and experienced less benefit from lung volume reduction than patients not yet listed for transplantation. CONCLUSIONS: The preliminary use of lung volume reduction in patients potentially suitable for transplantation does not appear to jeopardize the chances for subsequent successful transplantation.

Lipid-mediated ex vivo gene transfer of viral interleukin 10 in rat lung allotransplantation.

BACKGROUND: Recent studies suggest that viral interleukin 10 suppresses alloimmune response in transplantation and that cationic lipids are one of the most promising nonviral vehicles for gene therapy. The aim of this study was to examine the effect of ex vivo lipid-mediated viral IL10 gene transfer into rat lung allografts on subsequent rejection. METHODS: Male F344 rats (RT1lvl) underwent left lung transplantation with allografts from Brown Norway rats (RT1n). Allografts were transvascularly transfected 15 minutes after harvest with 5 mL of 1:20-diluted (group 1, n = 7) or 1:40-diluted (group 2, n = 6) GL67-pCMVievIL-10 complex. Group 3 (n = 7), serving as the control group, received 1:40-diluted GL67-pCF1-chloramphenicol acetyltransferase complex. All allografts were preserved for 3 hours at 10 degrees C before transplantation. In all groups recipients were killed on postoperative day 5. Transgene expression of viral interleukin 10 was assessed by means of both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Histologic rejection score, allograft gas exchange, exhaled nitric oxide level, and allograft cytokine mRNA expression were also assessed. RESULTS: Dose-dependent transgene expression of viral interleukin 10 was detected by means of both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Allograft gas exchange (PaO2) in groups 1 (114.06 +/- 61.1 mm Hg) and 2 (108.58 +/- 35.7 mm Hg) was significantly better than that in group 3 (66.4 +/- 8.22 mm Hg; P =.020 and P =.023, respectively). The vascular rejection score in group 1 was significantly lower than that in group 3 (P =.032, Kruskal-Wallis test). Exhaled nitric oxide levels in group 2 (5.150 +/- 6.38 ppb) were significantly lower than those in group 3 (13.517 +/- 10.4 ppb; P =.039). Allograft interleukin 2 mRNA expression levels in group 1 (1.123 +/- 0.23 relative units) were significantly lower than those in group 3 (1.753 +/- 0.71 relative units; P =.038 vs group 3). CONCLUSIONS: Lipid-mediated ex vivo viral IL10 gene transfer into rat lung allografts improved graft gas exchange, reduced histologic rejection scores, downregulated graft interleukin 2 mRNA expression, and reduced exhaled nitric oxide levels by postoperative day 5. These results suggest a therapeutic potential of graft viral IL10 gene transfer as an effective immunosuppressive strategy against lung allograft rejection.

Recipient intramuscular gene transfer of active transforming growth factor-beta1 attenuates acute lung rejection.

BACKGROUND: Gene transfer into the donor graft has been demonstrated to be feasible in reducing ischemia-reperfusion injury and rejection in lung transplantation. This study was undertaken to determine whether intramuscular gene transfer into the recipient can also reduce subsequent lung graft rejection. METHODS: Brown Norway rats served as donors and F344 rats as recipients. Recipient animals were injected with 10(10) plaque-forming units of adenovirus encoding active transforming growth factor beta1 (group I, n = 6), beta-galactosidase as adenoviral controls (group II, n = 6), or normal saline without adenovirus (group III, n = 6) into both gluteus muscles 2 days before transplantation. Gene expression was confirmed by enzyme-linked immunosorbent assay. Graft function was assessed on postoperative day 5. RESULTS: Successful gene transfection and expression were confirmed by the presence of active transforming growth factor beta1 protein in muscle and plasma. Oxygenation was significantly improved in group I (group I vs II and III, 353.6 +/- 63.0 mm Hg vs 165.7 +/- 39.9 and 119.1 +/- 41.5 mm Hg; p = 0.02 and 0.004). The muscle transfected with the transforming growth factor beta1 showed granulation tissue with fibroblast accumulation. CONCLUSIONS: Intramuscular adenovirus-mediated gene transfer of active transforming growth factor beta1 into the recipients attenuates acute lung rejection as manifested by significantly improved oxygenation in transplanted lung allografts. This intramuscular transfection approach as a cytokine therapy is feasible in transplantation and may be useful in reducing rejection as well as reperfusion injury.

Activation of human airway epithelial cells by non-HLA antibodies developed after lung transplantation: a potential etiological factor for bronchiolitis obliterans syndrome.

BACKGROUND: The main cause of morbidity and mortality after lung transplantation (LT) is bronchiolitis obliterans syndrome (BOS). Anti-HLA antibodies development after LT has been shown to play an important role in BOS pathogenesis. However, the nature of non-HLA antibodies developed after LT and their role in BOS pathogenesis have not been determined. METHODS: Sera from 16 BOS+ patients and 11 BOS- patients were collected at 12, 24, 36, and 48 months after LT. Anti-HLA class I and class II antibodies were absorbed with pooled human platelets and pooled human lymphoblastoid cell lines, respectively. Then, the presence of non-HLA antibodies against several cell lines from different origin was determined by flow cytometric analysis. Antibody-positive samples were tested for induction of proliferation and growth factor production in two selected airway epithelial cell (AEC) lines. RESULTS: Five of 16 BOS+ patients (31.2%) and 0 of 11 BOS- patients (0%) developed anti-AEC antibodies after LT (P=0.05). No reactivity against endothelial cells, lymphocytes, monocytes, or granulocytes was detected. Further analysis of two selected sera demonstrated the development of reactivity against a 60-kDa antigen expressed by 60% of AEC lines and only 12% of cell lines from other tissues. Antibody binding to this antigen induced intracellular Ca++ influx, tyrosine phosphorylation, proliferation, and up-regulation of transforming growth factor-beta and heparin-binding epidermal growth factor mRNA transcription in AECs. CONCLUSIONS: These results indicate that anti-AEC antibodies may play a role in the immunopathogenesis of BOS in the absence of anti-HLA antibodies.

Lung transplantation versus lung volume reduction as surgical therapy for emphysema.

There are currently two surgical therapies aimed at crippling, end-stage emphysema: lung transplantation and lung volume reduction surgery (LVRS). Unfortunately, most emphysema patients are poor candidates for any surgical intervention. The authors favor a meticulous selection process in which indications and contraindications are considered and the best solution is devised for each patient. Patients with ideal circumstances for LVRS--hyperinflation, heterogeneous distribution of disease, FEV1 of more than 20%, and normal PCO2--are offered LVRS. Patients with diffuse disease, low FEV1, hypercapnia, and associated pulmonary hypertension are directed toward transplantation. LVRS has not been a satisfactory option for patients with a1-antitrypsin deficiency, and we prefer a transplant in most of these patients. With these considerations, we find that few patients are serious candidates for both procedures. Combinations of lung volume reduction and lung transplantation, simultaneously or sequentially, are possible but rarely necessary.

Endobronchial transfection of naked viral interleukin-10 gene in rat lung allotransplantation.

BACKGROUND: Recent studies suggest that viral interleukin-10 (vIL-10) suppresses alloimmune response in transplantation. Tissue mRNA expression of inducible nitric oxide synthase (iNOS) and exhaled nitric oxide (NO) levels have been observed to increase in lung allograft rejection. The aims of this study were to examine the feasibility of vIL-10 gene transfer into rat lung allografts and to investigate its effect on subsequent allograft rejection. METHODS: Male Lewis rats (RT1l) underwent left lung transplantation with allografts from Brown Norway rats (RT1n). The donor rats were endobronchially transfected 2 minutes before harvest with 400 microg (group I, n = 5), 600 microg (group II, n = 5), or 800 microg (group III, n = 5) of naked pCMVievIL-10. Group IV (n = 5) animals, serving as control, received 400 microg of naked pCF1-CAT. All recipients were sacrificed on postoperative day 5. Transgene expression of vIL-10 was assessed by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. Allograft gas exchange, exhaled NO level, histologic rejection score, and mRNA expression of graft cyokines were also assessed. RESULTS: Transgene expression of lung graft vIL-10 was detected by both reverse transcriptase-polymerase chain reaction and immunohistochemistry. The iNOS mRNA expression in groups I, II, and III was significantly lower than that of group IV (p < 0.05, analysis of variance). Exhaled NO levels in groups I, II, and III were significantly lower than in group IV (p < 0.01, analysis of variance). There was no significant difference between groups with respect to gas exchange, peak airway pressure, or histologic rejection score. CONCLUSIONS: It appears that endobronchial transfection of naked vIL-10 plasmid in a rat lung allotransplant model is feasible and suppresses lung iNOS mRNA expression and exhaled NO levels. An association between iNOS upregulation and high exhaled NO levels in lung allograft resection was also noted.

Clotrimazole inhibits lung fibroblast proliferation in vitro: implications for use in the prevention and treatment of obliterative bronchiolitis after lung transplantation.

BACKGROUND: Immunosuppressive therapy has limited activity against the mesenchymal cell proliferation of obliterative bronchiolitis. Clotrimazole (CLT) has been shown to inhibit proliferation in normal and cancer cell lines. Here we investigate whether CLT inhibits the proliferation of lung mesenchymal cells. METHODS: Proliferation of human lung fibroblasts (MRC-5) in the presence of CLT was determined by [3H]thymidine incorporation. Messenger ribonucleic acid (mRNA) expression of platelet-derived growth factor (PDGF)-B and transforming growth factor (TGF)-beta after treatment with CLT was measured by reverse transcriptase-polymerase chain reaction. RESULTS: Treatment of MRC-5 cells with CLT resulted in a significant reduction in proliferation as assessed by DNA incorporation and cell counts compared with dimethylsulfoxide alone. There was no cytotoxic effect associated with CLT treatment. Reverse transcriptase-polymerase chain reaction demonstrated a marked decrease in PDGF-B and TGF-beta mRNA levels in cells treated with CLT compared with those treated with dimethylsulfoxide. CONCLUSION: CLT inhibits proliferation of human lung fibroblasts. This inhibitory effect is associated with decreased levels of PDGF-B and TGF-beta mRNA expression and may have value in the prevention and treatment of obliterative bronchiolitis.

Lung transplantation is warranted for stable, ventilator-dependent recipients.

BACKGROUND: Lung transplantation for patients on ventilators is a controversial use of scarce donor lungs. We have performed 500 lung transplants in 12 years and 21 of these have been in ventilator-dependent patients. METHODS: A retrospective review of patient records and computerized database was performed. Living patients were contacted to confirm their health and functional status. RESULTS: Patients included 13 men and 8 women with a mean age of 43 years. Sixteen patients were considered stable awaiting lung transplant, whereas 5 patients were unstable with acute graft failure after prior lung transplantation. Stable patients had been ventilated for a mean of 57 +/- 46 days whereas unstable patients had been supported for 10 +/- 9 days. Half of the patients required cardiopulmonary bypass support during the transplant, and there was no statistical difference in the frequency of CPB in stable and unstable patients (p = 0.61). Three hospital deaths included 0 of 16 of the stable patients and 3 of 5 of the unstable patients (p = 0.01). Long-term actuarial survival was significantly better in stable versus unstable patients (p = 0.02), with 5-year survival 40% for stable patients and 0% for unstable patients. CONCLUSIONS: Lung transplantation can be successfully conducted in stable patients who have become ventilator dependent after listing for transplantation. Acute retransplantation for early lung dysfunction is high risk and has produced poor long-term results.

Perioperative complications after living donor lobectomy.

OBJECTIVE: Clinical lung transplantation has been limited by availability of suitable cadaveric donor lungs. Living donor lobectomy provides right and left lower lobes from a pair of living donors for each recipient. We reviewed our experience with living donor lobectomy from July 1994 to February 2000. METHODS: Sixty-two donor lobectomies were performed. The hospital and outpatient records of these 62 donors were retrospectively analyzed to examine the incidence of perioperative complications. RESULTS: Twenty-four (38.7%) of 62 donors had no perioperative complications and had a median length of hospital stay of 5.0 days. Thirty-eight (61.3%) of 62 donors had postoperative complications. Twelve major complications occurred in 10 patients and included pleural effusions necessitating drainage (n = 4), bronchial stump fistulas (n = 3), bilobectomy (n = 1), hemorrhage necessitating red cell transfusion (n = 1), phrenic nerve injury (n = 1), atrial flutter ultimately necessitating electrophysiologic ablation (n = 1), and bronchial stricture necessitating dilatation (n = 1). These 38 donors had 55 minor complications including persistent air leaks (n = 9), pericarditis (n = 9), pneumonia (n = 8), arrhythmia (n = 7), transient hypotension necessitating fluid resuscitation (n = 4), atelectasis (n = 3), ileus (n = 3), subcutaneous emphysema (n = 3), urinary tract infections (n = 2), loculated pleural effusions (n = 2), transfusion (n = 2), Clostridium difficile colitis (n = 1), puncture of a saline breast implant (n = 1), and severe contact dermatitis secondary to adhesive tape (n = 1). There were no postoperative deaths and only 1 donor required surgical re-exploration. CONCLUSIONS: Living donor lobectomy can be performed with low mortality and remains an important alternative for potential recipients unable to wait for cadaveric lung allografts. However, morbidity is high and must be considered when potential living donors are being counseled.