Extended criteria donor lung reconditioning with the organ care system lung: a single institution experience

Lung transplantation is a life‐saving procedure limited by donor's availability. Lung reconditioning by ex vivo lung perfusion represents a tool to expand the donor pool. In this study, we describe our experience with the OCS? Lung to assess and recondition extended criteria lungs. From January 2014 to October 2016, of 86 on‐site donors evaluated, eight lungs have been identified as potentially treatable with OCS? Lung. We analyzed data from these donors and the recipient outcomes after transplantation. All donor lungs improved during OCS perfusion in particular regarding the PaO₂/FiO₂ ratio (from 340 mmHg in donor to 537 mmHg in OCS) leading to lung transplantation in all cases. Concerning postoperative results, primary graft dysfunction score 3 at 72 h was observed in one patient, while median mechanical ventilation time, ICU, and hospital stay were 60 h, 14 and 36 days respectively. One in‐hospital death was recorded (12.5%), while other two patients died during follow‐up leading to 1‐year survival of 62.5%. The remaining five patients are alive and in good conditions. This case series demonstrates the feasibility and value of lung reconditioning with the OCS? Lung; a prospective trial is underway to validate its role to safely increase the number of donor lungs.     

Liberalization of donor criteria in lung transplantation

Donor shortage remains a major obstacle to widespread application of lung transplantation. In region 5, including California, Nevada, New Mexico, Utah, and Arizona, the United Network of Organ Sharing (UNOS) database median waiting time for lung transplant candidates in 2000-2001 exceeded 17 months. The purpose of this study was to determine the impact of liberalization of donor criteria on median waiting time and short-term outcome of lung transplantation. From September 1999 to October 2002, 42 patients underwent lung transplantation from nonstandard donors. The donors were classified as nonstandard due to (1) infiltrate on chest radiograph (n = 33), (2) PaO2 < 300 on FiO2 1.0 and PEEP 5 (n = 3), (3) PaO2 < 100 on FiO2 0.4 and PEEP 5 (n = 3), (4) purulent sputum on bronchoscopy (n = 22), and (5) smoking history greater than 50 pack-years (n = 1). Perioperative characteristics and short-term outcome of this group was analyzed. The median waiting time for this cohort was 114 days (range, 10-1267), as compared with the national UNOS database median waiting time of 24 months between 1996 and 2001. The incidence of ischemia reperfusion injury was 2.3 per cent. None of the recipients developed pneumonia. The median ventilator support time was 2 days (range, 1-95). The median ICU stay and hospital stay were 4 days (range, 2-103) and 14 days (range, 5-194), respectively. The 3-month survival was 97.6 per cent. Selective liberalization of donor lung criteria can decrease the waiting time and is associated with favorable short-term outcome. Utilization of nonstandard lungs can expand the donor pool.     

Heterotopic heart transplantation--a means to increase donor availability

From November 1985 to August 1989, 105 patients underwent heart transplantation at our institution of whom 8 (7%) underwent heterotopic heart transplantation (HHTx). There were 7 males and 1 female with a mean age of 49 +/- 6 years (range, 41-58 years), 7 of whom had ischaemic cardiomyopathy and 1 had dilated cardiomyopathy. The indications for HHTx were gross donor/recipient size mismatch, unreliable donor heart, elevated pulmonary vascular resistance and the need for urgent transplantation or their combination. HHTx was performed as a left ventricular bypass in 6 patients and as biventricular bypass in 2 combined with various surgical procedures on the native heart in 5. There was one perioperative death with a mean follow-up of the survivors of 17 +/- 10 months (range, 6-30 months). Comparison of preoperative and postoperative (1 year) 2-D echocardiographic studies of the native heart showed haemodynamic stability of the latter with no substantial changes in left ventricular ejection fraction and cardiac index, while left ventricular end-diastolic volume tended to increase in 2 patients. In conclusion, preservation of the native heart allows recovery or growth of a graft considered unsuitable for orthotopic transplantation. Our experience confirms that HHTx may still be considered a valuable alternative to orthotopic transplantation in selected patients, thus expanding donor utilization.     

Extended criteria for living donor liver transplantation in patients with advanced hepatocellular carcinoma

Background

The purpose of this study was to evaluate the possibility of expanding the selection criteria in living donor liver transplantation (LDLT) to treat hepatocellular carcinoma (HCC).

Methods

From October 2000 to December 2010, we retrospectively analyzed 71 patients who had undergone LDLT beyond the Milan criteria (MC), among the entire cohort of 199 HCC patients. We evaluated the tumor biology as well as overall and disease-free survival (DFS), seeking to identify risk factors for recurrence. The median follow-up was 37 months (range 5-124).

Results

Among the 71 patients beyond the MC were 18 recurrences and 30 deaths. Their 5-year overall and DFS rates were 52.3% and 67.7%, respectively. On multivariate analysis, tumor diameter, tumor number, and E-S grade significantly influenced overall and DFS. According to our new criteria (size ≤7 cm, number ≤7), 86% of our patients would be included compared with 64% using MC. Five-year DFS and overall survival rates according to our criteria were comparable with the MC: 86.8% and 72.3% versus 86.8% and 73.4%, respectively.

Conclusion

Our criteria appear to achieve useful cut-off values beyond the MC.     

Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation

BACKGROUND: Currently the most important limitation in lung transplantation is donor availability. Although liberalization of donor criteria may aid in expanding the donor pool, the long-term effects of the use of "marginal" or "extended" donors remains unexplored. METHODS: In this study, we included all patients who underwent lung transplantation from January 1996 to December 1999 at Loyola University Medical Center. We categorized patients as either receiving lungs from an "ideal" donor or an "extended" donor. Extended donors were defined as having any 1 of the following criteria: donor age > 55 years, tobacco history > 20 pack years, presence of infiltrate on chest x-ray, donor ventilator time > 5 days, or donor use of inhaled drugs (cocaine or marijuana). We then compared the 2 groups with regard to short-term (operating room [OR] complications, intensive care unit [ICU] complications) and long-term outcomes (1-year pulmonary function and survival). RESULTS: Sixty-one (54%) patients received lungs from ideal donors and 52 (46%) patients received lungs from extended donors as defined above. We observed no significant differences between the 2 groups in OR complications (cardiopulmonary bypass, bleeding complications, life-threatening arrhythmias) or ICU complications (pneumonia, airway dehiscence, reoperation within 30 days related to transplantation). In addition, the 2 groups had similar median intubation times (21 hours in the ideal donor group and 20 hours in the extended donor group; p = n.s.), hospital length of stay (14+/-12 days in the ideal donor group and 12+/-8 days in the extended donor group; p = n.s.), and hospital survival (80% and 88% in the ideal and extended donor groups, respectively). One-year follow-up revealed similar pulmonary function (forced expiratory volume in 1 sec [FEV(1)] = 2.4 liters and 2.4 liters in the recipients of bilateral ideal and extended donors, respectively, and FEV(1) = 1.9 liters and 1.5 liters in the recipients of single ideal and extended donors) and survival (72% and 79% in the ideal and extended donor groups, respectively; p = n.s.) between the 2 groups. CONCLUSIONS: Liberalization of donor criteria does not affect outcome in the first year after lung transplantation. By liberalizing donor criteria, we can expand the donor pool while assessing other possible mechanisms to increase donor availability.     

Extended reverse dorsal metacarpal artery flap: clinical experience and donor site morbidity.

Extended reverse dorsal metacarpal artery (RDMA) flaps use the skin from the dorsum of the hand to cover defects of the long fingers up to the distal phalanx. The authors present a series of 12 patients who underwent closure of defects of the long fingers with these flaps. As relevant literature is scarce, special emphasis was put on donor site morbidity. Active and passive total range of motion (TRM) and pinch grip strength of the finger neighbouring the reconstructed one were evaluated and compared to the corresponding finger of the contralateral hand. The donor site was furthermore evaluated for cosmetic appearance and pain. There was no statistically significant difference for active and passive TRM. The difference for pinch grip reached statistical significance (p=0.04). Subjective evaluation of pain and cosmetic appearance by the patients revealed a mean pain value of 1.25 on a visual analogue scale (0=no pain, 10=maximal imaginable pain) and a mean estimation of cosmetic appearance of 8 (visual analogue scale, 0=worst cosmetic result, 10=best cosmetic result). In conclusion, compared to other flaps, the extended RDMA flap is a fast, secure and single-stage procedure for defect coverage on the long fingers with low donor site morbidity.     

Transimission of donor lymphocytes in clinical lung transplantation

Passenger mononuclear cells in organ grafts are known to influence the alloimmune response to the graft. To assess their relevance in clinical lung transplantation, we studied the amount, distribution, cell types, and surface marker expression of mononuclear cells in human donor lungs. Two major compartments of mononuclear cells could be differentiated: lymph nodes containing resting T and B lymphocytes, and the lung tissue itself, containing mainly activated lymphocytes as well as monocytes/macrophages. Tissue-associated mononuclear cells make up 20–40x10⁹ cells per lung, about 30–50 % of which are lymphocytes. Tissue-associated lymphocytes are predominantly T and NK cells; most of the T cells are CD8⁺ CD45R0⁺ and express HLA-DR. Strong expression of the adhesion molecules LFA-1 and ICAM-1 is present on infiltrating cells as well as on resident cells of the organ. Moreover, the lymphocytes inside the lung tissue are functionally highly active, with a strong stimulatory as well as alloreactive potency. Thus, large numbers of allogeneic mononuclear cells and particularly large numbers of functionally active lymphocytes are obviously transmitted by human lung allografts. The immunological in vivo relevance of these cells after lung transplantation may include allostimulation and graft-versus-host activity, but also beneficial immunomodulatory effects.     

Extended resection for lung cancer invading mediastinal organs.

We analyzed 49 patients with non-small-cell lung cancer invading mediastinal organs such as the left atrium (15), superior vena cava (13), trachea (11), aorta (5), thoracic vertebral body (4) and esophagus (1). Lung resection included lobectomy (37), pneumonectomy (8) and limited resection (4). Twenty-seven patients underwent carina- or bronchoplasty. Complete resection was possible in 35 patients. Operative mortality was 12% and overall 5-year survival was 13%. Median survival time was 519 days. Factors significantly affecting survival were the completeness of resection, node status, and histological type. Five-year survival was 18% with complete resection and 0% with incomplete resection (p < 0.0001). Five-year survival for patients with squamous cell carcinoma was 36% and for those with other types of lung cancer, 0% (p < 0.02). Five-year survival for patients classified pathologically as N0 or N1 was 36% and, for those classified as N2 or N3, 0% (p < 0.05). We concluded that aggressive resection for lung cancer invading the mediastinal organs involves a high mortality rate, making selectivity important. Patients undergoing complete resection, classified as N0 or N1, and having squamouse cell carcinoma may benefit most from surgery.     

Ascites after liver transplantation--a mystery.

Ascites after liver transplantation, although uncommon, presents a serious clinical dilemma. The hemodynamic changes that support the development of ascites before liver transplantation are resolved after transplant; therefore, persistent ascites (PA) after liver transplantation is unexpected and poorly characterized. The aim of this study was to define the clinical factors associated with PA after liver transplantation. This was a retrospective case-control analysis of patients who underwent liver transplantation at the University of Pennsylvania. PA occurring for more than 3 months after liver transplantation was confirmed by imaging studies. PA was correlated with multiple recipient and donor variables, including etiology of liver disease, preoperative ascites, prior portosystemic shunt (PS), donor age, and cold ischemic (CI) time. There were 2 groups: group 1, cases with PA transplanted from November 1990 to July 2001, and group 2, consecutive, control subjects who underwent liver transplantation between September 1999 and December 2001. Both groups were followed to censoring, May 2002, or death. Twenty-five from group 1 had ascites after liver transplantation after a median follow-up of 2.6 years. In group 1 vs group 2 (n = 106), there was a male predominance 80% vs 61% (P =.10) with similar age 52 years; chronic hepatitis C virus (HCV) was diagnosed in 88% vs 44% (P <.0001); preoperative ascites and ascites refractory to treatment were more prevalent in group 1 (P =.0004 and P =.02, respectively), and CI was higher in group 1, (8.5 hours vs 6.3 hours, P =.002). Eight of the 25 (group 1) had portal hypertension with median portosystemic gradient 16.5 mm Hg (range, 16-24). PS was performed in 7 of 25 cases, which resulted in partial resolution of ascites. The development of PA after liver transplantation is multifactorial; HCV, refractory ascites before liver transplantation, and prolonged CI contribute to PA after liver transplantation.     

Impact of the expanded criteria donor allocation system on candidates for and recipients of expanded criteria donor kidneys

BACKGROUND: A national policy to allocate kidneys from expanded criteria donors (ECD) took effect October 31, 2002. METHODS: To assess its impact, we analyzed data from the Scientific Registry of Transplant Recipients for ECD kidney candidates and recipients between November 1999 and October 2005. RESULTS: The likelihood of being listed for ECD transplant, of receiving any transplant, and of receiving an ECD transplant were assessed using logistic regression models. As of October 31, 2005, 42.6% of candidates were listed with an ECD designation (range by donation service area [DSA], 1.9% to 94.9%). ECD-listed candidates were likely to be older, diabetic, and sensitized. By October 31, 2005, candidates listed for ECD as of November 1, 2002 were 41% more likely to receive any kidney transplant than those not ECD-listed. Among ECD-listed recipients, 30.1% received an ECD transplant and 69.9% a non-ECD transplant. Recipients more likely to receive an ECD transplant were significantly older and in DSAs where a high percentage of ECD transplants were performed and/or a low percentage of candidates were ECD-listed. CONCLUSIONS: A large, regionally variable fraction of candidates are opting to receive ECD offers. Listing with an ECD designation increases the likelihood of transplantation in selected populations. Selective listing of ECD candidates is associated with a higher likelihood of receiving an ECD transplant.     

Reliable thirty-hour lung preservation by donor lung hyperinflation.

We examined the hypothesis that the degree of inflation of the lungs at the time of harvest may have an important role in postpreservation function. Lungs of donor dogs randomly assigned to groups 1 (n = 5) and 2 (n = 5) were ventilated with large tidal volumes (tidal volume, 25 ml/kg; positive end-expiratory pressure, 5 cm H2O; respiratory rate, 12 breaths/min, inspired oxygen fraction 1.0) and were inflated to 30 cm H2O for 15 seconds before pulmonary artery flush and again immediately before tracheal crossclamping. In group 3 (n = 5) donor lungs were normally ventilated (tidal volume, 12.5 ml/kg, positive end-expiratory pressure 0 cm H2O; respiratory rate 12 breaths/min, inspired oxygen fraction, 1.0) and were not hyperinflated before pulmonary artery flushing; the trachea was crossclamped at end-inspiration. In groups 1 and 3 a large bolus (25 micrograms/kg) of prostaglandin E1 was injected into the pulmonary artery before flushing and was also added to the pulmonary artery flush solution (500 micrograms/L). A rapid (approximately 50 seconds), high-volume mm Hg), hypothermic (4 degrees C) pulmonary artery flush was performed in all hypothermic (4 degrees C) pulmonary artery flush was performed in all groups with modified Euro-Collins solution. Heart-lung blocks were stored at 4 degrees C for approximately 29 hours before left single lung allografting. An inflatable cuff was placed around the recipient right pulmonary artery, allowing independent study of the transplanted lung. Hyperinflated lungs harvested with or without prostaglandin E1 provided equivalently excellent early posttransplant function (arterial oxygen tension [mean +/- standard deviation]: group 1; 503 +/- 45, vs group 2; 529 +/- 150 mm Hg; inspired oxygen fraction 1.0). Mean arterial oxygen tension was significantly lower in group 3 (116 +/- 78 mm Hg) than in either groups 1 or 2 (p < 0.0002 for either comparison). Copious reperfusion pulmonary edema was a constant feature in group 3 but was not seen in groups 1 and 2. All 10 recipients in groups 1 and 2 survived the 3-day assessment period without difficulty; two of the five recipients in group 3 died during initial unilateral perfusion of the transplanted lung. Donor hyperventilation and inflation to 30 cm H2O before hypothermic storage can help provide excellent posttransplantation lung function after 30-hour preservation, with or without prostaglandin E1 pretreatment. We speculate that this improvement may be due to effects of increased lung volume on pulmonary vascular tone and/or surfactant metabolism.     

Extended segmentectomy for small lung tumors

To identify the benefits of limited surgery on small-sized lung tumors, the following subjects are discussed: 1) an updated report from a prospective group study (January 1992-December 1994) for extended segmentectomy for small lung tumors (n = 55); 2) a histopathological study of resected adenocarcinoma specimens less than 2 cm in size (n = 94), proposed by Noguchi; and 3) lung function after limited surgery and the quality of video-assisted thoracoscopic surgery. RESULTS: 1) Among 10 deaths, 4 patients died of their disease including one with local recurrence. The survival rate at 5 years was 91%, not including 6 unrelated deaths. 2) Of 94 patients, twelve with localized bronchioalveolar tumors (type A and B), and 23 of 57 patients with active fibroblastic proliferation (type C), underwent extended segmentectomy. Those 35 patients are all free of disease. The remaining 59 patients had a 70% 5-year survival rate. 3) Forced vital capacity was maintained at 92% of the preoperative level, which was much better than 81% for patients undergoing lobectomy. Card-sized thoracotomy using a thoracoscope was carried out in 92 patients, including 21 patients who underwent segmentectomy, in a series of 175 consecutive lung cancer operations. This approach resulted in less bleeding, the same operating time, and better preservation of vital capacity. CONCLUSIONS: Extended segmentectomy for small lung tumors did not affect the prognosis, and was associated with a better quality of life postoperatively.     

Extended ganciclovir prophylaxis in lung transplantation.

BACKGROUND: Positive cytomegaloviral status of the donor or of the recipient adversely affects survival and enhances the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. The role of ganciclovir prophylaxis in cytomegalovirus infection in respect to obliterative bronchiolitis or to BOS development is not known. METHODS: From the Papworth transplant database, we identified 146 patients who received organs from cytomegalovirus-positive donors. We classified patients into 3 groups as follows: Group 1 consisted of 42 patients who underwent transplantation between 1990 and 1992 when no prophylaxis was given; Group 2 consisted of 49 patients who underwent transplantation between 1992 and 1995 when 4 weeks of IV ganciclovir was given as prophylaxis; and Group 3 consisted of 55 patients who underwent transplantation between 1995 and 1998 when cytomegalovirus prophylaxis consisted of IV (1 week) followed by oral ganciclovir for a total of 3 months. Donor management, recipient management during and after surgery, and pharmacotherapy were uniform during the study period. We used survival and regression methods to compare these groups, adjusting for the transplantation type (single lung, double lung, or heart-lung) and for HLA typing. RESULTS: We found a significant difference among all 3 groups in numbers of cytomegaloviral disease episodes in the 1st year after transplantation. The number of rejection episodes in the 3 groups during the 1st post-transplant year gradually decreased from Group 1 to Group 3. We identified no statistically significant benefit in the time to BOS occurrence or in actuarial survival. CONCLUSION: Extended prophylaxis with IV and oral ganciclovir practically abolishes cytomegaloviral disease and is related to a decreased incidence of rejection episodes. However, ganciclovir prophylaxis is not related to a decreased incidence or progression of BOS or survival.     

Expanded criteria donor grafts for deceased donor liver transplantation under the MELD system: a decision analysis.

Expanded criteria donor (ECD) liver grafts have a higher likelihood of primary graft failure (PGF) compared with standard criteria donor (SCD) grafts. Given a choice between an available ECD graft versus waiting for an SCD graft that may not always become available, what should liver transplant candidates do? The study's aim was to estimate 1-year survival comparing immediate ECD liver grafting with waiting for an SCD organ. Using UNOS data, published literature estimates, and expert opinion, we constructed a Markov decision analytic model to estimate survival while waiting for an SCD transplant and survival with immediate ECD transplant. Sensitivity analyses were performed by varying model parameters individually and simultaneously with a second-order Monte Carlo simulation. For all patients with MELD scores >20, survival was higher with immediate ECD transplant despite the additional increased risk for PGF. Survival was better with an immediate ECD transplant unless the probability of PGF exceeded 23%, 72%, and 88% for recipients with MELD scores of 11-20, 21-25, and 26-30 respectively. For patients with MELD scores >30, the survival benefit with the immediate ECD strategy persisted at even higher rates of PGF. In conclusion, our results suggest that, despite the higher risk for PGF, transplantation with an available ECD graft should be preferred over waiting for an SCD organ for patients with advanced MELD scores. At less advanced MELD scores, the survival benefit depends on the risk of PGF associated with the ECD organ.