A data-driven patient blood management strategy in liver transplantation.

BACKGROUND AND OBJECTIVES: Blood utilization during liver transplant has decreased, but remains highly variable due to many complex surgical and physiologic factors. Previous models attempted to predict utilization using preoperative variables to stratify cases into two usage groups, usually using entire blood units for measurement. We sought to develop a practical predictive model using specific transfusion volumes (in ml) to develop a data-driven patient blood management strategy. MATERIALS AND METHODS: This is a retrospective evaluation of primary liver transplants at a single institution from 2013 to 2015. Multivariable analysis of preoperative recipient and donor factors was used to develop a model predictive of intraoperative red-blood-cell (pRBC) use. RESULTS: Of 256 adult liver transplants, 207 patients had complete transfusion volume data for analysis. The median intraoperative allogeneic pRBC transfusion volume was 1250 ml, and the average was 1563 ± 1543 ml. Preoperative haemoglobin, spontaneous bacterial peritonitis, preoperative haemodialysis and preoperative international normalized ratio together yielded the strongest model predicting pRBC usage. When it predicted <1250 ml of pRBCs, all cases with 0 ml transfused were captured and only 8·6% of the time >1250 ml were used. This prediction had a sensitivity of 0·91 and a specificity of 0·89. If predicted usage was >2000 ml, 75% of the time blood loss exceeded 2000 ml. CONCLUSION: Patients likely to require low or high pRBC transfusion volumes were identified with excellent accuracy using this predictive model at our institution. This model may help predict bleeding risk for each patient and facilitate optimized blood ordering.

A high plasma: red blood cell transfusion ratio during liver transplantation is associated with decreased blood utilization.

BACKGROUND: During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. METHODS: This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. RESULTS: A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. CONCLUSION: In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions.

Use of NanoICE for Procurement Achieves Better Cooling of Liver Grafts.

BACKGROUND: Rapid cooling at procurement after cross-clamping has been the cornerstone of organ preservation. NanoICE is a new form of ice that has emerged in the food industry and is providing more efficient cooling and preservation than regular ice. We hypothesize that the use of NanoICE will accelerate the cooling process of the allograft and will be able to maintain a steady low temperature without causing any significant histologic damage. METHODS: In this randomized pilot study, 14 pigs were used to study the liver core/surface cooling in a non-survival organ procurement operation. Animals were randomly assigned to 1 of 2 groups, each arm involving 7 pigs: (1) crushed-iced normal saline cooling method (control group) and (2) NanoICE cooling method (study group). Surface and core temperatures were measured with temperature probes, and liver biopsies were obtained before cross-clamping and 15 hours after preservation to assess for any evidence and degree of freezing injury. RESULTS: NanoICE was able to reduce and sustain lower core temperatures at 30 minutes, 60 minutes, and 15 hours, compared with crushed ice. The degree of histologic damage (reflecting cold injury) at 15 hours after flushing was not significantly different between the 2 methods. CONCLUSIONS: NanoICE cools the deeper liver parenchyma more quickly and sustains a cooler temperature than regular crushed ice without causing significantly histologic damage. Future research should focus on whether the effect of NanoICE has any impact on graft function and survival.

Sporadic Retroperitoneal Hemangioblastoma: Report of a Case and Review of the Literature.

We report a case of sporadic isolated hemangioblastoma arising from the retroperitoneum and provide a review of the scarce literature regarding this very rare tumor. Furthermore, we thoroughly describe the pathologic features and the broad differential diagnosis that should always be included in the study of any retroperitoneal soft tissue mass to arrive at the final diagnosis.

Landscape of Kidney Transplantation in Patients With Compensated Liver Disease: Results of a Survey of Transplant Surgeons in the United States.

BACKGROUND: The therapeutic options that provide the best long-term outcome for patients who have a combination of end-stage renal disease and compensated cirrhosis are unknown. METHODS: Given the paucity of data and the lack of clinical guidance in this area, a national survey was conducted in the form of an e-mail-based questionnaire addressed to the transplantation surgeons registered with the American Society of Transplant Surgeons. RESULTS: Of the 818 surgeons invited to participate in the survey, 167 (20%) responded. Twenty-one (12.6%) respondents indicated that their program performed <50 kidney transplantations per year, 49 (29.3%) reported performing 50 to 100 kidney transplantations per year, and the majority, 97 (58.1%) of respondents, performed >100 kidney transplantations per year. The majority, 116 (69.5%), believed that compensated cirrhotic patients with end-stage renal disease could be considered for renal transplantation alone, 45 (26.9%) respondents believed that compensated cirrhotic patients on dialysis could only be considered for simultaneous liver-kidney transplantation, and 6 (3.6%) believed that this population of patients was not suitable for kidney transplantation alone. CONCLUSIONS: Our findings suggest that there is a substantial heterogeneity of opinion among transplantation surgeons towards transplantation options for compensated cirrhotic patients. Further data is needed to define best practices and clinical guidelines.

Progression of Hepatic Adenoma to Carcinoma in the Setting of Hepatoportal Sclerosis in HIV Patient: Case Report and Review of the Literature.

We report a case of hepatic adenoma progression to carcinoma in the setting of hepatoportal sclerosis in an HIV+ patient and provide a review of the scarce literature regarding hepatoportal sclerosis in HIV patients. We describe the clinical presentation, diagnostic workup, and management. This is the first case report in the literature of progression of hepatic adenoma to carcinoma in hepatoportal sclerosis in an HIV patient. This case also highlights the broad differential diagnosis that should always be included in the study of any liver disease in this patient population, including the performance of invasive and aggressive tests to arrive at the final diagnosis.

Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Serum alkaline phosphatase and bilirubin are early surrogate markers for ischemic cholangiopathy and graft failure in liver transplantation from donation after circulatory death.

Liver transplantation with the use of donation after circulatory death (DCD) is associated with ischemic cholangiopathy (IC) often leading to graft loss. We hypothesized that serial postoperative analysis of alkaline phosphatase and bilirubin might identify patients who would later on develop ischemic cholangiopathy and/or graft loss, allowing early recognition and potentially retransplantation. The University of Washington DCD experience totals 89 DCD liver transplantations performed from 2003 to 2011 with Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively; 84/89 patients transplanted with DCD livers lived ≥ 60 days after transplantation and were analyzed. Serum bilirubin and alkaline phosphatase levels at 1 week, 2 week, 1 month, and 2 months after transplantation were analyzed. Two-month serum bilirubin and alkaline phosphatase proved to have the strongest associations with development of IC and graft failure. Two-month alkaline phosphatase of <100 U/L had a negative predictive value of 97% for development of IC. Two-month alkaline phosphatase demonstrated an inflection starting at >300 U/L strongly associated with development of IC (P < .0001). Serum bilirubin at 2 months was most strongly associated with graft failure within the 1st year with a strong inflection point at 2.5 mg/dL (P = .0001). All jaundiced recipients at 60 days after transplantation (bilirubin >2.5 mg/dL) developed graft failure within the 1st year (P < .0001). Use of these early surrogate markers could facilitate prioritization and early retransplantation for DCD liver recipients with allografts destined for failure.

Differential rates of ischemic cholangiopathy and graft survival associated with induction therapy in DCD liver transplantation.

Transplantation utilizing donation after circulatory death (DCD) donors is associated with ischemic cholangiopathy (IC) and graft loss. The University of Washington (UW) DCD experience totals 89 DCD liver transplants performed between 2003 and 2011. Overall outcome after DCD liver transplantation at UW demonstrates Kaplan-Meier estimated 5-year patient and graft survival rates of 81.6% and 75.6%, respectively, with the great majority of patient and graft losses occurring in the first-year posttransplant from IC. Our program has almost exclusively utilized either anti-thymocyte globulin (ATG) or basiliximab induction (86/89) for DCD liver transplantations. Analysis of the differential effect of induction agent on graft survival demonstrated graft survival of 96.9% at 1 year for ATG versus 75.9% for basiliximab (p = 0.013). The improved survival did not appear to be from a lower rate of rejection (21.9% vs. 22.2%) but rather a differential rate of IC, 35.2% for basiliximab versus 12.5% for ATG (p = 0.011). Multivariable analysis demonstrated induction agent to be independently associated with graft survival and IC free graft survival when analyzed against variables including donor age, fWIT, donor cold ischemia time and transplant era.

A symptomatic de novo pheochromocytoma 23 years after liver transplantation: a case report and review of the literature.

We report a case of subacute onset of headaches and tremors with a newly discovered adrenal pheochromocytoma 23 years after an orthotopic liver transplantation and provide a review of the scarce literature regarding endocrine malignancies in liver transplant recipients. We describe the clinical presentation, diagnostic work-up, and management. This is the second case report in the literature of a de novo pheochromocytoma after solid organ transplantation. It shows that new-onset common symptoms in transplant recipients are always challenging and deserve a very thorough work-up until the cause of the symptoms is elucidated. A broad differential diagnosis should always be included in the study of any abnormalities in this patient population.

Outcomes of laparoscopic-assisted transhiatal esophagectomy for adenocarcinoma of the esophagus and esophago-gastric junction.

Esophagectomy is associated with substantial morbidity and mortality, yet it is the only modality that offers the possibility of cure for esophageal and gastroesophageal junction (E-GEJ) adenocarcinoma. Several minimally invasive techniques have been developed to decrease the morbidity of the operation, but to date, the results have not led to its wide adoption in part due to their complexity. We developed a technique of laparoscopic-assisted transhiatal esophagectomy (LA-THE) with the idea of preserving some of the advantages of the minimally invasive approach while eliminating the degree of complexity and the time required to complete the operation solely using laparoscopy. The course of all patients who underwent LA-THE for E-GEJ adenocarcinoma at the University of Washington Medical Center was determined by analysis of all hospital records to determine perioperative variables, complications, and survival. Patients were also given a follow-up survey in order to assess long-term health-related quality of life (Gastrointestinal Quality of Life Index or GIQLI). Seventy-two patients underwent LA-THE between 1995 and 2007. Median age was 64 years (range, 42-83 years), and the median body mass index was 28 (range 17-35). Twenty-eight tumors (39%) were categorized as Siewert I, 41 (57%) as Siewert II, and 3 (4%) as Siewert III. Median operative time was 299min (range, 212-700min). All the resections were R-0. The median number of lymph nodes harvested was 11 (range, 2-32). Using the Dindo-Clavien classification of surgical complication, we had a total of 48 postoperative complications in 37 patients: 26 (53%) grade I, 20 (41%) grade II, 1 (2%) grade IIIb, 1 (2%) grade IVb, and 1 (2%) grade V complications. Median length of hospital stay was 9 days (range, 7-58 days). One patient (1.4%) died within 30 days. Overall, 3- and 5-year survival (calculated Kaplan-Meier) was 68% and 63%, respectively. Forty-nine patients (90% of those still alive) answered the GIQLI survey. Median follow-up was 26 months (range, 6-144 months). The mean GIQLI score was 108 (range, 74-138) from a maximum possible value of 144. Our study shows that LA-THE is feasible, safe, and effective in the treatment of adenocarcinoma of the esophagus and GEJ and should probably be considered an alternative to open esophagectomy and other minimally invasive techniques in the treatment of this disease.

Does combined multichannel intraluminal esophageal impedance and manometry predict postoperative dysphagia after laparoscopic Nissen fundoplication?

Laparoscopic Nissen fundoplication (LNF) is an effective treatment for gastroesophageal reflux disease; however, some patients develop dysphagia postoperatively. Manometry is used to evaluate disorders of peristalsis, but has not been proven useful to identify which patients may be at risk for postoperative dysphagia. Multichannel intraluminal impedance (MII) evaluates the effective clearance of a swallowed bolus through the esophagus. We hypothesized that MII combined with manometry may detect those patients most at risk of developing dysphagia after LNF. Between March 2003 and January 2007, 74 patients who agreed to participate in this study were prospectively enrolled. All patients completed a preoperative symptom questionnaire, MII/manometry, and 24-h pH monitoring. All patients underwent LNF. Symptom questionnaires were administered postoperatively at a median of 18 months (range: 6-46 months), and we defined dysphagia (both preoperatively and postoperatively) as occurring more than once a month with a severity >or=4 (0-10 Symptom Severity Index). Thirty-two patients (43%) reported preoperative dysphagia, but there was no significant difference in pH monitoring, lower esophageal sphincter pressure/relaxation, peristalsis, liquid or viscous bolus transit (MII), or bolus transit time (MII) between patients with and without preoperative dysphagia. In those patients reporting preoperative dysphagia, the severity of dysphagia improved significantly from 6.8 +/- 2 to 2.6 +/- 3.4 (P < 0.001) after LNF. Thirteen (17%) patients reported dysphagia postoperatively, 10 of whom (75%) reported some degree of preoperative dysphagia. The presence of postoperative dysphagia was significantly more common in patients with preoperative dysphagia (P= 0.01). Patients with postoperative dysphagia had similar lower esophageal sphincter pressure and relaxation, peristalsis, and esophageal clearance to those without dysphagia. Neither MII nor manometry predicts dysphagia in patients with gastroesophageal reflux disease or its occurrence after LNF. The presence of dysphagia preoperatively is the only predictor of dysphagia after LNF.