Ivan Zendejas

Impact of Cold Ischemia Time on Graft Survival Among ECD Transplant Recipients: A Paired Kidney Analysis

Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia times (CIT) potentially leading to discard. The effect of increased CIT on ECD kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived from the same donor transplanted to different recipients) from the SRTR registry transplanted between 1995 and 2009 (n = 17 514). To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14 230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1–3 h (p = 0.90), 4–9 h (p = 0.41), 10–14 h (p = 0.36) or ≥15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma.

The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1–19.2) for the entire cohort, 27.6 months (17.7–37.6) for curative resection, 12.9 months (6.5–19.2) for palliative chemoradiotherapy and 4.9 months (0.4–9.6) for best supportive care (P<0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology.

Liver Planning Software Accurately Predicts Postoperative Liver Volume and Measures Early Regeneration

BACKGROUND Postoperative or remnant liver volume (RLV) after hepatic resection is a critical predictor of perioperative outcomes. This study investigates whether the accuracy of liver surgical planning software for predicting postoperative RLV and assessing early regeneration. STUDY DESIGN Patients eligible for hepatic resection were approached for participation in the study from June 2008 to 2010. All patients underwent cross-sectional imaging (CT or MRI) before and early after resection. Planned remnant liver volume (pRLV) (based on the planned resection on the preoperative scan) and postoperative actual remnant liver volume (aRLV) (determined from early postoperative scan) were measured using Scout Liver software (Pathfinder Therapeutics Inc.). Differences between pRLV and aRLV were analyzed, controlling for timing of postoperative imaging. Measured total liver volume (TLV) was compared with standard equations for calculating volume. RESULTS Sixty-six patients were enrolled in the study from June 2008 to June 2010 at 3 treatment centers. Correlation was found between pRLV and aRLV (r = 0.941; p < 0.001), which improved when timing of postoperative imaging was considered (r = 0.953; p < 0.001). Relative volume deviation from pRLV to aRLV stratified cases according to timing of postoperative imaging showed evidence of measurable regeneration beginning 5 days after surgery, with stabilization at 8 days (p < 0.01). For patients at the upper and lower extremes of liver volumes, TLV was poorly estimated using standard equations (up to 50% in some cases). CONCLUSIONS Preoperative virtual planning of future liver remnant accurately predicts postoperative volume after hepatic resection. Early postoperative liver regeneration is measureable on imaging beginning at 5 days after surgery. Measuring TLV directly from CT scans rather than calculating based on equations accounts for extremes in TLV.

Combined Resection of the Liver and Pancreas for Malignancy

BACKGROUND Combined resection of both the liver and pancreas for malignancy remains a controversial procedure. To many, the need for such an extended procedure implies an extent of disease that is usually not amenable to surgical control, and the extent of the procedure exposes the patients to substantial operative risks. The purpose of this study was to assess our results with combined resection of the liver and pancreas. STUDY DESIGN Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included 26 pancreaticoduodenectomies (PD) and 14 distal pancreatic resections. Liver resections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections. RESULTS There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy. Mean hospital stay was 14 days (range 7 to 42 days). Median follow-up was 30 months (range 3 to 76 months). Patients undergoing resection for neuroendocrine tumors had a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p = 0.01). CONCLUSIONS Combined resection of the liver and pancreas can be performed safely. The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindication to resection in selected patients.

CARBAMAZEPINE SUPPRESSES CALPAIN-MEDIATED AUTOPHAGY IMPAIRMENT AFTER ISCHEMIA/REPERFUSION IN MOUSE LIVERS

Onset of the mitochondrial permeability transition (MPT) plays a causative role in ischemia/reperfusion (I/R) injury. Current therapeutic strategies for reducing reperfusion injury remain disappointing. Autophagy is a lysosome-mediated, catabolic process that timely eliminates abnormal or damaged cellular constituents and organelles such as dysfunctional mitochondria. I/R induces calcium overloading and calpain activation, leading to degradation of key autophagy-related proteins (Atg). Carbamazepine (CBZ), an FDA-approved anticonvulsant drug, has recently been reported to increase autophagy. We investigated the effects of CBZ on hepatic I/R injury. Hepatocytes and livers from male C57BL/6 mice were subjected to simulated in vitro, as well as in vivo I/R, respectively. Cell death, intracellular calcium, calpain activity, changes in autophagy-related proteins (Atg), autophagic flux, MPT and mitochondrial membrane potential after I/R were analyzed in the presence and absence of 20 μM CBZ. CBZ significantly increased hepatocyte viability after reperfusion. Confocal microscopy revealed that CBZ prevented calcium overloading, the onset of the MPT and mitochondrial depolarization. Immunoblotting and fluorometric analysis showed that CBZ blocked calpain activation, depletion of Atg7 and Beclin-1 and loss of autophagic flux after reperfusion. Intravital multiphoton imaging of anesthetized mice demonstrated that CBZ substantially reversed autophagic defects and mitochondrial dysfunction after I/R in vivo. In conclusion, CBZ prevents calcium overloading and calpain activation, which, in turn, suppresses Atg7 and Beclin-1 depletion, defective autophagy, onset of the MPT and cell death after I/R.

Mitochondrial Dysfunction and Autophagy in Hepatic Ischemia/Reperfusion Injury

Ischemia/reperfusion (I/R) injury remains a major complication of liver resection, transplantation, and hemorrhagic shock. Although the mechanisms that contribute to hepatic I/R are complex and diverse involving the interaction of cell injury in hepatocytes, immune cells, and endothelium, mitochondrial dysfunction is a cardinal event culminating in hepatic reperfusion injury. Mitochondrial autophagy, so-called mitophagy, is a key cellular process that regulates mitochondrial homeostasis and eliminates damaged mitochondria in a timely manner. Growing evidence accumulates that I/R injury is attributed to defective mitophagy. This review aims to summarize the current understanding of autophagy and its role in hepatic I/R injury and highlight the various therapeutic approaches that have been studied to ameliorate injury.

Duplicate Gallbladder Arising from the Left Hepatic Duct: Report of a Case

Gallbladder duplication is a rare congenital biliary anomaly with different morphologies depending on events at embryogenesis. This case report describes a symptomatic duplicate gallbladder arising from the left intrahepatic duct 10 years after an open cholecystectomy: this is the rarest form of gallbladder duplication. The symptoms resolved following a second open cholecystectomy. This case illustrates the importance of preoperative imaging, intraoperative cholangiography, and a high index of suspicion of anomalous gallbladder anatomy in the diagnosis and management of this rare condition. We discuss the classification of anomalous gallbladder anatomy and review previous cases, to propose a modification of the common classification scheme.

Ureteral stent placement and BK viremia in kidney transplant recipients

BK virus (BKV) infection is an important cause of kidney transplant dysfunction. A possible association of double‐J ureteral stent placement and BK viremia has been suggested in previous studies; however, risk factors for BK are incompletely understood. We aimed to determine if stent placement is an independent risk factor for BK viremia.

Kidney transplantation from small pediatric donors: does recipient body mass index matter?

Background. The influence of recipient body mass index (BMI) on pediatric-donor kidney transplant outcomes is unclear. We aimed to determine graft survival and functional outcomes of pediatric-donor kidneys compared with adult kidneys stratified by recipient BMI group. Methods. Scientific Registry of Transplant Recipients data for recipients from 1996 to 2010 were reviewed. Donors were categorized by transplant type, pediatric single kidney transplant (SKT, n=3712), en bloc kidney transplant (EBK, n=1517), or adult standard criteria donor (SCD, n=66,741). Recipients were stratified by BMI tertiles (<24, 24–29, and >29 kg/m2). Results. SKT and EBK from donors ⩽40 kg conferred similar risks of adjusted death-censored graft survival relative to SCDs regardless of recipient BMI except for EBK transplants in recipients with BMI <24 where the effect was protective (adjusted hazard ratio [aHR] 0.71, 95% confidence interval [CI] 0.56–0.94). SKT from donors ⩽20 kg conferred worse death-censored graft survival in recipients with BMI <24 (aHR 1.3, 95% CI 1.0–1.6) and BMI >29 (aHR 1.5, 95% CI 1.1–2.0); however, most of the risk appeared early, and the effect was abrogated with reanalysis conditional on 1-year graft survival. Compared with SCDs, 1-year glomerular filtration rates of SKT from donors ⩽20 kg were significantly higher when transplanted into recipients with BMI <24 (P<0.01) and similar in the other BMI groups. Conclusion. Increasing recipient BMI is not a clear risk factor for outcomes or graft function after transplantation with small pediatric-donor kidneys.

Strongyloides hyperinfection syndrome following simultaneous heart and kidney transplantation

We report a case of Strongyloides hyperinfection syndrome (SHS) causing death in a patient approximately 1 month following simultaneous heart and kidney transplantation (HKTx). The patient was a 61-year-old Caucasian male who had lived in Florida. He underwent four-vessel coronary artery bypass grafting for coronary artery disease in 1992 with myocardial infarctions and percutaneous coronary interventions. He also had insulin-dependent diabetes mellitus with retinopathy and nephropathy, requiring hemodialysis. His preoperative status was NYHA IV with an ejection fraction of 30–35% and pulmonary hypertension (85/30 mmHg). He underwent HKTx for ischemic cardiomyopathy and end-stage renal disease. His immunosuppressive protocol consisted of antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. Acyclovir and trimethoprim/sulfamethoxazole were given as prophylaxis per transplant protocol. Postoperatively the patient developed delayed kidney allograft function and required hemodialysis. His respiratory condition gradually deteriorated with worsening pulmonary edema despite adequate hemodialysis and right ventricular biopsy negative for rejection. Severe leukocytosis (WBC 12 100–45 300) persisted after the operation despite various therapies. On postoperative day (POD) 27 the patient developed dehiscence at the kidney transplant incision site because of a noninfectious wound seroma and underwent primary surgical repair. In addition, at that time, it was noted that a CMV DNA-PCR performed on the patient was positive for 3700 copies/ml. Acyclovir was discontinued and the patient was started on ganciclovir intravenously. Subsequently, CMV DNA-PCR was decreased to 1000 copies/ml on POD 32, and 375 copies/ ml on POD 35. On POD 28, a chest CT was obtained because of worsening oxygenation, which showed extensive infiltrates consistent with acute respiratory distress syndrome (ARDS). The patient was intubated and underwent bronchoscopy with bronchoalveolar lavage and transbronchial biopsies, which were nonrevealing. In addition, transthoracic echocardiogram was performed on POD 28, which demonstrated preserved left ventricular ejection fraction of 60–65%, moderate right ventricular systolic dysfunction, severe right atrial enlargement and severe tricuspid regurgitation. Three days later, on POD 31, the patient was noted to have hemoptysis and repeat bronchoscopy revealed diffuse hemorrhage. High dose corticosteroids were begun for worsening ARDS and the patient received CMV hyperimmune globulin because of concerns for possible CMV pneumonia. Despite high level mechanical ventilation, the patient’s oxygenation worsened necessitating the addition of nitric oxide. The patient progressively deteriorated with hypotension refractory to pressor support and increasing difficulty with oxygenation. On POD 36, the patient died. Throughout the clinical course, he never developed acute rejection of the transplanted organs as evidenced by multiple biopsies (heart biopsies on POD 6, 13, 20, 28, renal biopsy on POD 8). The postmortem examination revealed Strongyloides stercoralis larvae in the alveoli with accompanying severe bilateral lobar pneumonia and diffuse intra-alveolar hemorrhage (Fig. 1a). Autopsy specimens also revealed numerous S. stercoralis larvae in the transplanted heart and kidney, esophagus, stomach, and small and large bowel, many of them infiltrating through the mucosa and sub-mucosa and some reaching the lymphatic and blood vessels. Strongyloides hyperinfection syndrome is an augmentation of the life cycle, which is medically important because it can lead to overwhelming and disseminated infection in immunocompromised patients including solid organ transplant recipients and carries the potential for high mortality rates (about 70%) [1,2]. In solid organ transplant patients increased corticosteroid dosages is the most frequent risk factor for development of SHS [3,4] and have been associated with the development of the hyperinfection syndrome and dissemination of the organism [5,6]. Meanwhile, not only the reactivation and dissemination of S. stercoralis in recipients but also transmissions of S. stercoralis from deceased donors may be serious problems [7]. There were some reports regarding SHS acquired from the donor in kidney[8], intestinal [7], pancreatic transplantation [9]. Donors and recipients in endemic areas, a history of other helminthic infections,