Lung and heart-lung transplantation

This report is a brief summary on current events related to lung and heart-lung transplantation. Eleven patients have undergone transplantation of the heart and both lungs at Stanford University. The ages ranged from 22–45, the average age being about 36 years, and included were four females and seven males. The diagnosis was primary pulmonary hypertension in three and Eisenmenger syndrome-congenital heart disease with pulmonary hypertension-in eight. Eight patients are living and well, two to more than 24 months after transplantation of the heart and both lungs. All these patients were discharged and are fully rehabilitated, which is an important consideration. There have been three operative deaths, one was secondary to two previous operations that made our operation much too long, another was secondary to the use of intravenous cyclosporine, and the third was related to the poor maintenance of the donor lung. Three of the eleven patients were catheterized following the transplant from six months to a year after transplantation, and the pulmonary artery pressure and pulmonary vascular resistance were absolutely normal in all three of these individuals. Of course the plan is to go ahead with further catheter studies at yearly intervals in all of the patients. The last patient underwent transplantation in January, 1983. I think no matter how effective or how ingenious the medical staff is with artificial organs, it will be a long time before these early results of transplantation of the heart and both lungs can be matched by any types of artificial organ implants. Supported in part by a grant (HL 13108) from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, and from the Dr. Ralph and Marian Falk Foundation for Medical Research Gist of a Lecture given at the Japan Surgical Society, April 7, 1983.     

Comparison of Three Tacrolimus-Based Immunosuppressive Regimens in Lung Transplantation

Immunosuppressive therapy for solid organ transplantation has significantly evolved over the past decade. While these therapies have been found to be beneficial in abdominal organ transplantation, the efficacy of these therapies remains unclear in lung transplantation. We retrospectively compared three potent immunosuppressive regimens in our lung transplant population: Group 1 (tacrolimus/azathioprine/prednisone), Group 2 (tacrolimus/azathioprine/prednisone/daclizumab) and Group 3 (tacrolimus/mycophenolate mofetil/prednisone/daclizumab). We compared these three groups with respect to 3-year rates of acute rejection, chronic rejection, infection and survival. A total of 109 patients was followed during the course of this study. There were 32 patients in Group 1, 49 patients in Group 2 and 28 patients in Group 3. Freedom from acute rejection at 1 and 3 years were higher in Group 3 compared with Group 1 (p < 0.05). The overall incidence of infection up to 3 years after transplantation was comparable among all three groups. Freedom from chronic rejection and survival at 1 and 3 years did not differ among the three groups. In conclusion, we determined the safety and efficacy of three potent immunosuppressive regimens in lung transplantation. Addition of daclizumab and MMF to a tacrolimus-based immunosuppressive regimen decreased the incidence of acute rejection episodes without increasing any adverse events in our lung transplantation population.     

Kidney Transplantation in Previous Heart or Lung Recipients

Outcomes after heart and lung transplants have improved, and many recipients survive long enough to develop secondary renal failure, yet remain healthy enough to undergo kidney transplantation. We used national data reported to United Network for Organ Sharing (UNOS) to evaluate outcomes of 568 kidney after heart (KAH) and 210 kidney after lung (KAL) transplants performed between 1995 and 2008. Median time to kidney transplant was 100.3 months after heart, and 90.2 months after lung transplant. Renal failure was attributed to calcineurin inhibitor toxicity in most patients. Outcomes were compared with primary kidney recipients using matched controls (MC) to account for donor, recipient and graft characteristics. Although 5-year renal graft survival was lower than primary kidney recipients (61% KAH vs. 73.8% MC, p < 0.001; 62.6% KAL vs. 82.9% MC, p < 0.001), death-censored graft survival was comparable (84.9% KAH vs. 88.2% MC, p = 0.1; 87.6% KAL vs. 91.8% MC, p = 0.6). Furthermore, renal transplantation reduced the risk of death compared with dialysis by 43% for KAH and 54% for KAL recipients. Our findings that renal grafts function well and provide survival benefit in KAH and KAL recipients, but are limited in longevity by the general life expectancy of these recipients, might help inform clinical decision-making and allocation in this population.     

65例肺移植手术的临床分析

目的探讨肺移植术中供者肺的获取和术中可能遇到的特殊情况处理,以提高肺移植手术的成功率。方法65例重症呼吸衰竭,其中长期依赖呼吸机9例;病种包括肺气肿23例,肺纤维化24例,矽肺5例,肺结核2例,肺淋巴管平滑肌瘤病1例,室间隔缺损合并艾森曼格综合征4例,支气管肺囊肿4例,弥漫性细支气管炎1例和原发性肺动脉高压1例。行单肺移植术47例,双肺移植术18例。回顾性总结肺移植手术的临床经验,特别是手术中遇到的特殊情况的处理经验。结果64例供肺均获取成功。肺移植术后住院死亡11例（16.9%）,其中原发性移植肺失功3例,严重感染6例,急性排斥反应1例,肺梗死1例。术后发生并发症9例,包括术后渗血多二次开胸止血3例,肺动脉狭窄二次手术重新吻合纠正1例,支气管吻合口狭窄3例;肺梗死2例,其中1例肺叶梗死患者二次开胸手术切除。随访54例,随访时间1.0~5.6年,1年生存率达72.3%（47/65）,大部分患者生活质量良好,肺功能有极大的改善。结论提高供肺获取和受者肺移植手术技术有助于降低肺移植手术后的早期死亡率。     

Lung Transplantation in Japan

The first successful living-donor lobar lung transplant (LDLLT) in Japan was performed at Okayama University in October 1998 after a long period of waiting for the legalization of thoracic organ transplantation. By May 2003, a further 41 lung transplants had been performed; 28 from living donors and 13 from cadaveric donors. The indications for a lung transplant are very specialized in Japan, the most common being primary pulmonary hypertension. Although the number of lung transplants is still small, survival in Japan, at 72% after 4 years, is better than the world average. Because the number of available cadaveric donors for lung transplantation is limited, at less than 5 per year, LDLLT is a realistic option for properly selected candidates.     

One and One-Half Year Experience with Unilateral and Bilateral Lung Transplantation

Lung transplantation has now become an established form of treatment for end-stage pulmonary parenchymal and vascular diseases. Despite its wide acceptance, technical aspects are still in discussion. We report on the initiation of our own lung transplant program and the technical changes we have performed during our first 1 1/2-year experience. During that period of time, we have performed 26 lung transplantations (16 single lung [SLTX] and 10 bilateral lung transplantations [BLTX]). Three-month survival for the whole group was 74% (69% for the SLTX group and 77% for the BLTX group). No instance of bronchial dehiscence was observed; however, there were eight cases of bronchial stenosis: six were managed by silicone stent insertion, one by bronchoplastic correction, and one by retransplantation. Changes in the technique of the bronchial anastomosis together with the addition of prednisone to the immediate postoperative immunosuppressive regime resulted in almost complete avoidance of these problems.     

Geographic Disparities in Access to Lung Transplantation Before and After Implementation of the Lung Allocation Score

The 62 lung transplant centers in the United States are unevenly distributed. We examined whether remote dwelling (distance from one's primary residence to the nearest lung transplant center) or rural dwelling (as opposed to urban) influences patients’ access to lung transplantation, and whether such relationships changed following introduction of the lung allocation score (LAS) in May 2005. Between July 2001 and February 2009, 14 015 patients were listed for lung transplantation and 7923 (56.5%) were transplanted. Americans lived a median of 90.3 miles (IQR: 45.3–159.4) from the closest transplant center. Distance from a lung transplant center was inversely associated with the hazard of being listed before LAS implementation (adjusted HR for 100 miles = 0.87 [0.83–0.90]) and afterward (0.81 [0.78–0.85]); LAS implementation did not modify this relationship (p = 0.38). Once waitlisted, distance from the closest center was not associated with time to transplantation, and among those transplanted, distance was not associated with survival. Similar results were identified for rural, as opposed to urban, residence. We conclude that geographic disparaties exist in access to lung transplantation in the United States. These are mediated by listing practices rather than by transplantation rates, and were not mitigated by LAS implementation.     

Long-Term Outcomes of Cadaveric Lobar Lung Transplantation: An Important Surgical Option

Background: Cadaveric lobar lung transplantation (L-LTx) is developed to overcome donor–recipient size mismatch. Controversial short- and long-term outcomes following L-LTx have been reported compared to full-sized lung transplantation (F-LTx). This study reports long-term outcomes after L-LTx.Methods: We reviewed patients undergoing lung transplantation (LTx) between 2000 and 2016. The decision to perform L-LTx was made based mainly on donor–recipient height discrepancy and visual assessment of donor lungs. Predicted donor–recipient total lung capacity (TLC) ratio was calculated more recently. Primary outcome was overall survival.Results: In all, 370 bilateral LTx were performed during the study period, among those 250 (67%) underwent F-LTx and 120 (32%) underwent L-LTx, respectively. One- and 5-year survival rates were 85% vs. 90% and 53% vs. 63% for L-LTx and F-LTx, respectively (p = 0.16). Chronic lung allograft dysfunction (CLAD)-free survival at 5 years was 48% in L-LTx vs. 51% in F-LTx recipients (p = 0.89), respectively. Age, intraoperative extracorporeal membrane oxygenation (ECMO) use, intensive care unit (ICU) stay, and postoperative renal replacement therapy (RRT) were significant prognostic factors for survival using multivariate analysis.Conclusions: Overall survival and CLAD-free survival following L-LTx were comparable to F-LTx. Given the ongoing donor organ shortage, cadaveric L-LTx remains as an important resource in LTx.     

Lung transplant in a recipient with tracheal bronchus

We describe the intraoperative surgical management of tracheal bronchus encountered in a lung transplant recipient.     

肺移植手术中供肺保存液的研究现状

肺移植手术是治疗终末期肺部疾病的惟一有效方法，但仍然有许多相关问题须待解决。除了供肺严重缺乏外，因缺血-再灌注损伤导致的移植肺功能异常是肺移植手术患者最常见的早期死亡原因之一。保存移植肺的最佳状态对减轻肺移植术后缺血器官功能障碍至关重要。因此，寻找一种高度可靠的肺保存液，对减轻移植肺的缺血-再灌注损伤、提高肺移植术后肺功能有着十分重要的意义。现就供肺保存液的种类、灌注方式、灌注条件及其改良措施的研究现状进行综述。     

Lung donation following SARS-CoV-2 infection

There have been over 177 million cases of COVID-19 worldwide, many of whom could be organ donors. Concomitantly, there is an anticipated increase in the need for donor lungs due to expanding indications. Given that the respiratory tract is most commonly affected by COVID-19, there is an urgent need to develop donor assessment criteria while demonstrating safety and “efficacy” of lung donation following COVID-19 infection. Accordingly, we report an intentional transplant using lungs from a donor with recent, microbiologically confirmed, COVID-19 infection into a recipient suffering from COVID-19 induced ARDS and pulmonary fibrosis. In addition to the standard clinical assays, both donor and recipient lungs were analyzed using RNAscope, which confirmed that tissues were negative for SARS-CoV-2. Immunohistochemistry demonstrated colocalized KRT17+ basaloid-like epithelium and COL1A1+ fibroblasts, a marker suggestive of lung fibrosis in COVID-19 associated lung disease, in the explanted recipient lungs but absent in the donor lungs. We demonstrate that following a thorough assessment, lung donation following resolved COVID-19 infection is safe and feasible.     

Increasing Lung Allocation Scores Predict Worsened Survival Among Lung Transplant Recipients

Implemented in 2005, the lung allocation score (LAS) aims to distribute donor organs based on overall survival benefits for all potential recipients, rather than on waiting list time accrued. While prior work has shown that patients with scores greater than 46 are at increased risk of death, it is not known whether that risk is equivalent among such patients when stratified by LAS score and diagnosis. We retrospectively evaluated 5331 adult lung transplant recipients from May 2005 to February 2009 to determine the association of LAS (groups based on scores of ≤46, 47–59, 60–79 and ≥80) and posttransplant survival. When compared with patients with LAS ≤ 46, only those with LAS ≥ 60 had an increased risk of death (LAS 60–79: hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.21–1.90; LAS ≥ 80: HR, 2.03; CI, 1.61–2.55; p < 0.001) despite shorter median waiting list times. This risk persisted after adjusting for age, diagnosis, transplant center volume and donor characteristics. By specific diagnosis, an increased hazard was observed in patients with COPD with LAS ≥ 80, as well as those with IPF with LAS ≥ 60.     

Kidney Disease After Heart and Lung Transplantation

Kidney disease is a commonly recognized complication of heart and lung transplantation and is associated with increased morbidity and mortality. While the spectrum of kidney disease in this population is wide-ranging, studies indicate that between 3% and 10% of these patients will ultimately develop end-stage renal disease (ESRD). This review examines the risk factors for both acute and chronic kidney injury, with a particular emphasis on the role of calcineurin inhibitor-mediated nephrotoxicity in both these settings. Against the background of current National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, we have further considered and recommended appropriate strategies for long-term management of kidney disease-related manifestations in heart and lung transplant recipients. Specific aspects addressed include retarding progressive renal injury and minimizing nephrotoxicity, as well as treatment of hypertension, hyperlipidemia and anemia. Finally, for patients in this population with advanced kidney disease, renal replacement therapy options are discussed. Based on the impact of chronic kidney disease on outcomes in both heart and lung recipients, we advocate early referral to a nephrologist for patients displaying evidence of significant renal dysfunction.     

肝移植术后急性肺损伤的观察与分析

目的 分析肝脏移植患者术后并发急性肺损伤(AU)的危险因素，并探讨其防治措施。方法 采用回顾性调查的方法，对4例肝脏移植患者的相关资料进行分析。结果 门肺高压症、呼吸机长期使用、严重感染、全身炎性反应综合征、高凝状态、液体超载、肾功能障碍等．是肝移植术后并发急性肺损伤及急性呼吸窘迫综合征(ARDS)的危险因素。结论 肝移植术后易发生ALI，预防并减少相关危险因素的影响．对减少术后ALI及ARDS有重要意义。     

Lung Cancer after Heart Transplantation: Results from a Large Multicenter Registry

In this study we analyzed Spanish Post‐Heart‐Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post‐HT follow‐up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post‐HT. Incidence increased with age at HT from 149 per 100 000 person‐years among under‐45s to 542 among over‐64s; was 4.6 times greater among men than women; and was four times greater among pre‐HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age‐at‐diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan–Meier 2?year survival to 70% versus 16% among inoperable patients.