Unexpected Neoplasms in Lungs Explanted From Lung Transplant Recipients: A Single-Center Experience and Review of Literature.

INTRODUCTION: Lung transplantation is a common treatment for various indications, but undiagnosed neoplasms are found in 0.5% to 2.4% of explanted lungs. We report the largest single-institution series of patients with unexpected neoplasms in explanted lungs and compare rates of undiagnosed malignancies before and after the 2005 Lung Allocation Score (LAS) update. METHODS: We reviewed the medical records of patients who underwent lung transplantation at the Cleveland Clinic from 1990 to 2014. In cases of neoplasm discovered on explant, tumor type, pathological stage, recurrence, and date of death were recorded. RESULTS: From January 1, 1990 to June 30, 2014, 1303 patients underwent lung transplantation at the Cleveland Clinic. The overall mean smoking history was 35 pack-years, and 25 undiagnosed lung malignancies were found upon explant in 24 transplant recipients (1.84%). In the post-LAS era (ie, 2005 onward), 20/812 lung transplant recipients had 21 incidental neoplasms in their explanted lungs (2.5%). Seventeen of these 25 tumors occurred in patients with interstitial lung disease; 8 occurred in patients with centrilobular emphysema. Eight tumors recurred (6 in patients with interstitial lung disease and 2 in patients with emphysema). The most common histological tumor types were adenocarcinomas (n = 14) and squamous cell carcinomas (n = 7). CONCLUSIONS: Unexpected neoplasms were found in 1.84% of lung transplant recipients' explanted lungs, with a slightly higher incidence (2.46%) in the post-LAS era. Neoplasms were more common in patients with interstitial lung diseases than in patients with centrilobular emphysema. Explanted lungs should be pathologically examined for evidence of tumor foci because this can impact post-transplantation management.

Case-matched comparison of perioperative outcomes after surgical treatment of sigmoid diverticulitis in solid organ transplant recipients versus immunocompetent patients.

AIM: To compare the perioperative outcomes following surgery for sigmoid diverticulitis in transplant recipients and immunocompetent patients. METHOD: Solid organ transplant recipients operated on for sigmoid diverticulitis from 1995 to 2010 were case-matched to immunocompetent patients based on surgical procedure, American Society of Anesthesiologists classification, Hinchey score, elective vs urgent surgery, age ± 10 years and year of surgery ± 5 years. Demographics, clinical presentation and perioperative outcomes were assessed. RESULTS: Of 5329 consecutive patients undergoing heart, lung, kidney and liver transplantation since 1995, 51 (0.6%) underwent surgery for diverticulitis between 1995 and 2010 with 14% mortality and 45% morbidity. Urgent surgery in 37/51 patients [Hartmann's procedure 28, sigmoidectomy with diverting ileostomy 8, loop ileostomy 1 (9 cases within 2 months after transplantation)] was associated with significantly increased postoperative mortality (19%vs 0%, P = 0.01), increased morbidity (51%vs 24%, P = 0.03) and longer mean hospital stay (19 vs 13 days, P = 0.1) when compared with immunocompetent patients. Four patients undergoing urgent surgery had suffered previous episodes of diverticulitis treated nonoperatively. Elective surgery was associated with no mortality in 14 transplant recipients (nine sigmoidectomy with diverting ileostomy, five sigmoidectomy without diversion) or in immunocompetent controls. Following elective procedures, transplant recipients had similar morbidity and increased hospital stay (29% and 9.6 vs 6.5 days, P = 0.2, respectively). Permanent stoma rates and postoperative morbidity after stoma takedown were comparable in the two groups. All living patients except one (kidney) retained their graft function. CONCLUSIONS: Urgent surgery for sigmoid diverticulitis in transplant recipients is associated with worse postoperative outcomes when compared with immunocompetent patients, unlike elective surgery. Future studies will need to clarify the role of early surgery after the first diverticulitis episode.

Lung transplantation in a recipient with novel 2009 H1N1 influenza: lessons learned.

Immunosuppressed patients are at an increased risk for severe disease from influenza A (H1N1). We report a case of a patient who died of septic complications from H1N1 acquired at the time of single lung transplant.

Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area.

BACKGROUND: Many clinical scenarios have been encountered by patients who developed histoplasmosis after receiving a solid organ transplant at a large transplant center in an endemic area. METHODS: Cases of posttransplantation histoplasmosis were identified by use of multiple methods, including reviews of microbiology test results, transplant databases, and billing codes. Data were obtained retrospectively. Descriptive statistics were used. RESULTS: During the 1997-2007 study period, 3436 patients received a solid organ transplant, and 38 patients were identified as having posttransplantation histoplasmosis. Of these 38 patients, 9 were excluded from our study because the diagnosis was solely clinical. Of the remaining 29 patients, 14 had posttransplantation histoplasmosis (incidence, 1 case per 1000 person-years); 14 showed histologic evidence of histoplasmosis in the recipient or donor tissue, which was encountered unexpectedly at the time of transplantation; and 1 had histoplasmosis before receiving the transplant. Of the 14 patients who developed histoplasmosis after transplantation, 5 were heart transplant recipients, 3 were lung transplant recipients, 3 were kidney transplant recipients, 1 was a liver transplant recipient, 1 was a pancreas transplant recipient, and 1 was a kidney-pancreas transplant recipient. The median time from transplantation to diagnosis was 17 months (interquartile range, 8.1-46 months), and the median time from onset of symptoms to diagnosis 3 weeks (interquartile range, 1.9-6.5 weeks). All recipients had disseminated disease. The most common treatment was amphotericin B and itraconazole. All were cured, or still on treatment, but symptom-free. Of the 14 patients who had an explanted organ or donor tissue that showed histologic evidence of histoplasmosis, 13 (93%) were lung transplant recipients, and 1 (7%) was a liver transplant recipient. None of these patients developed active histoplasmosis, but all received prophylactic treatment. Finally, 1 patient had histoplasmosis before transplantation; he was treated with itraconazole 3 months before and after transplantation, and he did well. CONCLUSIONS: In conclusion, posttransplantation histoplasmosis is rare (1 case per 1000 transplant-person-years; 95% confidence interval, 0.6-1.7), even in endemic areas. Prognosis is good but requires protracted therapy. Patients with latent infection did not develop posttransplantation histoplasmosis when prophylaxis was used.

Challenges in the diagnosis and management of Nocardia infections in lung transplant recipients.

BACKGROUND: Nocardia infection occurs in 2.1-3.5% of lung transplant recipients, and may involve cavitary nodular pulmonary lesions, soft tissue infection, or other sites of dissemination. Nocardiosis can pose challenging clinical problems in the areas of diagnosis and treatment. Diagnostic delays may occur, and adverse reactions to therapy are common. This study reviews clinical and epidemiological aspects of nocardiosis in lung transplant recipients, with special attention to pitfalls in management. Clinicians should be alert for these possibilities in order to institute prompt therapy and to achieve successful outcomes. METHODS: A retrospective cohort study was conducted of 577 lung transplant recipients from January 1991 to May 2007. Demographics, reason for transplant, recent rejection, time from transplantation, site of infection, hypogammaglobulinemia, and/or neutropenia shortly before onset, Pneumocystis jiroveci prophylaxis, Nocardia species, radiographic findings, extrapulmonary lesions, nature and duration of treatment, adverse reactions, and outcomes were recorded. RESULT: Nocardia infection occurred in 1.9% (11/577). Mean onset was 14.3 months after transplant (range 1.5-39 months). N. asteroides was isolated in 55% (6/11). Emphysema was the most common reason for transplant (7/11, 64%). Six patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis. Three patients had immune globulin G levels <400 mg/dL and 2 were neutropenic in the 3 months preceding diagnosis. Diagnosis was made by bronchoalveolar lavage (55%), skin abscess culture (18%), open lung biopsy (9%), pleural fluid (9%), and sputum culture (9%). Definitive diagnosis required a median of 9 days and a mean of 13.6 days (range 3-35 days) from the time of diagnostic sampling. Soft tissue lesions occurred in 3 and central nervous system involvement in 1 patient. Adverse reactions to therapy occurred in 9/10 (90%) of patients for whom information was available. Nocardia-related mortality occurred in 2/11 patients (18%). CONCLUSIONS: Nocardiosis occurred in 1.9% of lung transplant recipients and was associated with a mean of nearly 2 weeks to diagnosis and frequent adverse effects on therapy. TMP-SMX prophylaxis on a thrice weekly basis did not prevent all episodes of nocardiosis. Despite utilization of protocol bronchoscopies with cultures for Nocardia, this organism remains a source of clinical complexity in the lung transplant population.

Hyperlipidemia is associated with accelerated chronic kidney disease progression after lung transplantation.

Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 +/- 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 +/- 23 vs. 62 +/- 29 mL/min/1.73 m2, p = 0.01), a difference that persisted at 60 months (39 +/- 24 vs. 73 +/- 57 mL/min/1.73 m2, p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m2 (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox-proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding.

Hepatic veno-occlusive disease due to tacrolimus in a single-lung transplant patient.

Hepatic veno-occlusive disease is defined as nonthrombotic fibrous obliterative endophlebitis of small centrilobular hepatic venules. Clinically, patients present with elevated liver enzymes and a triad of jaundice, hepatomegaly and ascites. Although reported as a complication of other solid organ and stem cell transplantation, there have been no reported cases to date of veno-occlusive disease following lung transplantation. The present authors report a case of veno-occlusive disease following single-lung transplantation in a patient on a triple-drug immunosuppressive regimen composed of tacrolimus, mycophenolate mofetil and prednisone. The diagnosis was established by transjugular liver biopsy and by discontinuing tacrolimus; there was clinical regression of symptoms and serological return to baseline.