Ethical issues in solid organ transplantation: transfusion-free transplantation in Jehovah's witness patients.

PURPOSE OF REVIEW: Jehovah's Witnesses do not accept transfusion of major allogeneic blood fractions. Successful solid organ transplantation is challenging for Jehovah's Witnesses when anemia, coagulation disturbances, and difficult technical aspects co-exist, and key blood bank resources cannot be utilized. Organ availability for transplantation is limited and demand exceeds supply for all organ types. Historically, the likelihood of poor outcomes in Jehovah's Witnesses patients placed ethical limitations on transplant candidacy for this population violating the precept of maximal utilization of a limited resource. The review's purpose is to describe advancements and strategies that make Jehovah's Witnesses transplant outcomes comparable to transfusion-eligible patients and allay the ethical concerns of their candidacy. RECENT FINDINGS: Immunomodulation from allogeneic transfusion is a cause of significant postop morbidity. Blood conservation strategies have led to improved outcomes across different medical and surgical cohorts and set the stage for expanded utility in Jehovah's Witnesses with organ insufficiency.Published single-center series with descriptions of specific peri-operative strategies describe the path to major blood product avoidance. SUMMARY: Comparable outcomes in solid organ transplantation for Jehovah's Witnesses without allogeneic transfusion are possible when inclusion-exclusion criteria are respected, and blood conservation strategies employed.

Transfusion-free Strategies in Liver and Pancreatic Surgery: A Predictive Model of Blood Conservation for Transfusion Avoidance in Mainstream Populations.

OBJECTIVE: The objective of this study is to (1) describe the techniques and prove the feasibility of performing complex hepatobiliary and pancreatic surgery on a Jehovah Witness (JW) population.  (2) Describe a strategy that offsets surgical blood loss by the manipulation of circulating blood volume to create reserve whole blood upon anesthesia induction. BACKGROUND: Major liver and pancreatic resections often require operative transfusions. This limits surgical options for patients who do not accept major blood component transfusions. There is also growing recognition of the negative impact of allogenic blood transfusions. METHODS: A 23-year, single-center, retrospective review of JW patients undergoing liver and pancreatic resections was performed. We describe perioperative management and patient outcomes. Acute normovolemic hemodilution (ANH) is proposed as an important strategy for offsetting blood losses and preventing the need for blood transfusion. A quantitative mathematical formula is developed to provide guidance for its use. RESULTS: One hundred one major resections were analyzed (liver n=57, pancreas n=44). ANH was utilized in 72 patients (liver n=38, pancreas n=34) with median removal of 2 units that were returned for hemorrhage as needed or at the completion of operation. There were no perioperative mortalities. Morbidity classified as Clavien grade 3 or higher occurred in 7.0% of liver resection and 15.9% of pancreatic resection patients. CONCLUSIONS: Deliberate perioperative management makes transfusion-free liver and pancreatic resections feasible. Intraoperative whole blood removal with ANH specifically preserves red cell mass, platelets, and coagulation factors for timely reinfusion. Application of the described JW transfusion-free strategy to a broader general population could lessen blood utilization costs and morbidities.

Dynamic liver test patterns do not predict bile duct stones.

BACKGROUND: Numerous models have been developed to predict choledocholithiasis. Recent work has shown that these algorithms perform suboptimally. Identification of clinical predictors with high positive and negative predictive value would minimize adverse events associated with unnecessary diagnostic endoscopic retrograde cholangiopancreatography (ERCP) while limiting the use of expensive tests including magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) for indeterminate cases. METHODS: Consecutive unique inpatients who received their first ERCP at Los Angeles County Medical Center between January 2010 and November 2016 for suspected bile duct stones were reviewed. The primary outcome was the proportion of patients with specific combinations of liver enzyme patterns, transabdominal ultrasound, and clinical features who had stones confirmed on ERCP. As a secondary outcome, we assessed the performance of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification algorithm in our population. RESULTS: Of the 604 included patients, bile duct stones were confirmed in 410 (67.9%). Detailed assessment of liver enzyme patterns alone and in combination with clinical features and imaging findings yielded no highly predictive algorithms. Additionally, the ASGE high-risk criterion had a positive predictive value of only 68% for stones. For the 236 patients for whom MRCP was performed, this imaging modality was shown to have highest predictive value for the presence of stones on ERCP. CONCLUSION: Exhaustive exploration of various threshold values and dynamic patterns of liver enzymes combined with clinical features and basic imaging findings did not reveal an algorithm to accurately predict the presence of stones on ERCP. The ASGE risk stratification criteria were also insensitive in our population. Though desirable, there may be no "perfect" combination of clinical features that correlate with persistent bile duct stones. MRCP or EUS may be considered to avoid unnecessary ERCP and associated complications.

Kidney transplantation in the Hispanic population.

Hispanic race and low socioeconomic status are established predictors of disparity in access to kidney transplantation. This single-center retrospective review was undertaken to determine whether Hispanic race predicted kidney transplant outcomes. A total of 720 patients underwent kidney transplantation from January 1, 2004 to December 31, 2013, including 398 Hispanic patients and 322 non-Hispanic patients. Hispanic patients were significantly younger (p < 0.0001), on hemodialysis for longer (p = 0.0018), had a greater percentage with public insurance (p < 0.0001), more commonly had diabetes as the cause of end-stage renal disease (p = 0.0167), and had a lower percentage of living donors (p = 0.0013) compared to non-Hispanic patients. There was no difference in one-, five-, and 10-yr graft (97%, 81%, and 61% vs. 95%, 76%, and 42% p = 0.18) or patient survival (98%, 90%, and 84% vs. 97%, 87%, and 69% p = 0.11) between the Hispanic and non-Hispanic recipients. Multivariate analysis identified increased recipient age and kidney donor profile index to be predictive of lower graft survival and increasing recipient age to be predictive of lower patient survival. In the largest single-center study on kidney transplantation outcomes in Hispanic patients, there is no difference in graft and recipient survival between Hispanic and non-Hispanic kidney transplant patients, and in multivariate analysis, Hispanic race is not a risk factor for graft or patient survival.

Surgical transgastric debridement of walled off pancreatic necrosis: an option for patients with necrotizing pancreatitis.

BACKGROUND: Transgastric debridement of walled off pancreatic necrosis (WOPN) is a surgical treatment option for patients requiring pancreatic debridement for necrotizing pancreatitis. The reported experience with surgical transgastric pancreatic debridement is limited, however, the lower incidence of postoperative pancreatic fistulae with this procedure compared to other options warrants further evaluation of this technique. METHOD: Retrospective chart review. RESULTS: Twenty-two patients underwent transgastric debridement with a cystogastrostomy for clinically symptomatic WOPN from January 1, 2005 to July 31, 2013. Eight cases were performed laparoscopically and 14 were performed by an open approach. The mean patient age was 50.9 (50.9 ± 14.5) and the median American Society of Anesthesiologist score was 3. The most common etiology for pancreatitis was gallstones and the median time from attack of pancreatitis to definitive surgical management was 60 days (range 22-300 days). Median operative time was 182 min (range 85-327 min) with 100 cc (range 20-500 cc) of blood loss. In seven patients the necrosis was infected and in 15 patients the necrosis was sterile as determined by the intraoperative culture of the necrotic material. The overall significant morbidity (Clavien type 3 or greater) was 13.6 % and the mortality was 0 %. The incidence of postoperative pancreatic fistula was 0 %. 20 patients (90 %) were symptom free during a median follow-up of 12 months. CONCLUSION: In selected patients with clinically symptomatic WOPN, surgical transgastric pancreatic debridement appears to be a safe procedure with a low morbidity and mortality. The low incidence of postoperative pancreatic fistulae warrants further evaluation.

Blood Conservation Strategies and Liver Transplantation Transfusion-Free Techniques Derived from Jehovah's Witness Surgical Cohorts.

Red blood cell and component transfusions are a frequent and widely accepted accompaniment of surgical procedures. Although the risk of specific disease transmission via allogeneic blood transfusions (ABT) is very low, the occurrence of transfusion related immune modulation (TRIM) still remains a ubiquitous concern. Recent studies have shown that ABT are linked to increased morbidity and mortality across various specialties, with negative outcomes directly correlated to number of transfusions. Blood conservation methods are therefore necessary to reduce ABT. Acute normo-volemic hemodilution (ANH) along with pre-operative blood augmentation and intraoperative cell salvage are blood conservation techniques utilized in tertiary and even quaternary (transplantation) surgery in Jehovah's Witnesses with excellent outcomes. The many hematologic complications such as anemia, thrombocytopenia and coagulopathies that occur with liver transplantation present a significant barrier when trying to avoid ABT. Despite this, living donor liver transplantation (LDLT) has been successfully performed in a transfusion-free environment, providing valuable insight into the possibilities of limiting ABT and its associated risks in all patients.

Combined surgical resection and radiofrequency ablation as treatment for metastatic ocular melanoma.

PURPOSE: Ocular melanoma is a rare disease with a strong predilection for the liver. Systemic and locoregional treatments for metastatic ocular melanoma have had disappointing results, with an average survival of 5-7 months. Resection and/or radiofrequency ablation (RFA) of liver lesions were attempted to improve the patient outcomes. METHODS: Eight patients with liver metastasis from ocular melanoma underwent surgery and/or RFA at the University of Southern California, University Hospital from 1 January 2001 to 31 December 2009. Their charts were retrospectively reviewed. RESULTS: All patients had undergone eye enucleation as the primary treatment. Four patients had all metastatic liver lesions addressed: one patient underwent left lateral segmentectomy and three patients had combinations of left lateral segmentectomies, wedge resections and RFA of two to four lesions. Two patients underwent surgical biopsies for diagnosis, one patient was unresectable and one patient underwent RFA of a dominant lesion. The median survival was 36 months. The median survival of patients who underwent surgery alone or in conjunction with RFA to address all liver lesions was 46 months. CONCLUSIONS: There are few reports of RFA for metastatic ocular melanoma. RFA of liver lesions in addition to resection can perhaps lead to improved survival and may play a critical role in the future management of this disease.

Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome.

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End-Stage Liver Disease-based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post-LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT.

Review of Oncology and Transplant Literature for the Management of Hepatic and Pancreatic Resections in Jehovah's Witnesses.

Jehovah's Witnesses undergoing liver or pancreas surgery represent a unique medical and ethical challenge. For hepatic and pancreatic malignancies, resections are currently the only curative treatment. These surgeries pose a risk for significant blood loss, for which blood transfusions are traditionally given. However, blood transfusions are considered unacceptable to many Jehovah's Witnesses patients. As the technology of surgery as well as development of new products continue to evolve, transfusion-less surgery modalities have been utilized for Jehovah's Witnesses. The use of these transfusion-less techniques is not yet standardized for hepatic and pancreatic resections. We aimed to review both oncology and transplant medical literature on pancreatic and hepatic resection to develop guidelines for the management Jehovah's Witnesses patients.

Ischemic mass effect from biliary surgical clips.

Migrating surgical clips in the hepatic hilum are known causes of biliary stricture or obstruction, most often due to direct intraluminal obstruction or secondary stone formation. Two cases are reported on patients with previous cholecystectomies presenting with delayed symptoms of biliary tract stricture. Both patients were successfully treated with a resection of the strictured area and a Roux-en-Y hepatico-jejunostomy. Resected specimens grossly demonstrated surgical clips adjacent to the stricture, but not directly within the lumen, suggestive of an ischemic mass effect, which was supported by histology. In addition to the direct intraluminal obstruction and lithogenic effects of migratory surgical clips, "clipomas" due to an ischemic mass effect can also lead to biliary tract strictures.

High seroprevalence of anti-HTLV-I/II antibodies among solid organ donors necessitates confirmatory testing.

BACKGROUND: Human T-cell lymphotrophic virus (HTLV) type I has been linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I associated myelopathy (HAM). Transmission of HTLV by blood and organ transplantation has been documented, with some infections leading to clinical disease. Organ donors are tested for anti-HTLV antibodies and donor suitability is determined primarily by results from enzyme immunoassays (EIA). Confirmatory testing is not routinely performed, and the number of false positive organ donors is unknown. METHODS: In order to investigate the contemporary seroprevalence of anti-HTLV I/II antibodies among solid organ donors and determine the number of false positive samples, we tested 1,408 specimens from prospective organ donors in 2002 and 2003. All specimens were tested for anti-HTLV antibodies by a commercial EIA. Repeatedly reactive specimens underwent confirmatory testing using a commercial Western blot. RESULTS: There were 22 repeatedly EIA reactive donor specimens (1.56%). Five specimens did not undergo further testing because of case shutdown or insufficient sample quantity. HTLV I/II western blot confirmed six positives, whereas five were negative and six were indeterminate. The majority of confirmed specimens were positive for antibodies to HTLV-II. CONCLUSIONS: Our data shows that 29% of initially reactive specimens were false positives. With the increasing demand for organs, the unnecessary rejection of organs that are falsely positive for HTLV antibodies becomes of tremendous importance and stresses the need for timely confirmatory testing for HTLV.

Prevalence of antibodies to Trypanosoma cruzi among solid organ donors in Southern California: a population at risk.

Trypanosoma cruzi, a parasite that causes Chagas' disease, is endemic in parts of Mexico, South America, and Central America. Transmission of T. cruzi infection by solid organ transplantation has been reported in Latin America and recently in the United States. To determine the prevalence of T. cruzi antibodies in Southern California organ donors, 404 samples from deceased organ donors between May 2002 to April 2004 were screened using a qualitative enzyme-linked immunosorbent assay (EIA) and confirmed with an immunofluorescence assay (IFA) available through the Centers for Disease Control (CDC). Six donors were initially reactive by EIA. Three donors were repeatedly reactive after repeat testing and were sent to the CDC for confirmation. One donor (0.25%) had an IFA-confirmed reactivity to anti-T. cruzi antibodies. In areas where there is a high number of immigrants from T. cruzi endemic countries, screening for anti-T. cruzi donor antibodies may be beneficial.

Impact of a transfusion-free program on non-Jehovah's Witness patients undergoing liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is associated with a large amount of blood loss. This article examines the impact of the initiation of a transfusion-free program in January 2000 for Jehovah's Witnesses (JWs) on the overall use of blood products in non-JW patients undergoing OLT. DESIGN: Retrospective review of OLT from January 1997 through December 2004. SETTING: University of Southern California University Hospital. PATIENTS: A total of 272 OLTs were performed on non-JW adults. This number includes 216 (79.4%) deceased donor and 56 (20.6%) living donor liver transplantations. Thirty-three OLTs were performed before January 2000 (ie, before the initiation of a transfusion-free program) (group 1), and 239 OLTs were performed after January 2000 (group 2). In group 2, all patients underwent OLT using cell-scavenging techniques and acute normovolemic hemodilution whenever feasible. Demographic, laboratory, and clinical data were collected and matched for severity of disease (model of end-stage liver disease [MELD] score). Transfusion records of packed red blood cells (PRBCs), platelets, and fresh frozen plasma (FFP) were obtained from the University of Southern California blood bank. RESULTS: In comparing group 2 with group 1, the mean MELD score was statistically significantly higher (P < .001), whereas the mean number of intraoperative PRBC and FFP transfusions was significantly lower (P = .03 and P = .004, respectively). The number of preoperative and postoperative PRBC, FFP, and platelet transfusions between the 2 groups was not statistically different. CONCLUSION: The development of a transfusion-free surgical program for JW patients has had a positive impact on reducing the overall blood use in non-JW patients undergoing OLT, despite the increase in MELD score.

Extended pancreatectomy with resection of the celiac axis: the modified Appleby operation.

BACKGROUND: Celiac axis invasion by central and distal pancreatic cancers has been considered a contraindication to resection. Appleby first described en-bloc celiac axis resection with total gastrectomy for locally advanced gastric cancer. We present our experience with a modification of this procedure in central pancreatic cancers involving the celiac trunk. METHODS: Three patients with central pancreatic cancers invading the celiac axis are reviewed. All patients underwent extended pancreatectomy with en-bloc resection of the celiac axis. RESULTS: Margins were grossly clear of tumor in all patients. The mean length of stay was 8.3+/-1.1 days. There was no evidence of clinically significant gastric or hepatic ischemia. All 3 patients remain disease free at 34, 14, and 14 months from surgery, respectively. COMMENTS: Extended pancreatectomy with celiac axis resection can result in prolonged survival and should be considered in central and distal pancreatic cancers invading the celiac trunk.

Gallstone-induced inflammatory fibrosis: a relentless clinical course of retained gallstones after laparoscopic cholecystectomy.

Multiple reports in the literature confirm that retained gallstones spilled during laparoscopic cholecystectomy perpetuate chronic inflammation and suppuration long after the initial operation. Two patients who had previously undergone laparoscopic cholecystectomy presented to our institution with complications of retained stones. Patient 1 presented with right upper quadrant pain and a mass involving the right hepatic lobe. Patient 2 presented with a draining right flank abscess. Both underwent exploratory laparotomy at which time multiple abscess cavities were found, many of which contained retained gallstones. Patient 1 required reoperation for recurrent abscesses 7 months after the initial procedure and has been disease free for 6 months. Patient 2 had abscess recurrence that required percutaneous drainage 1 year after the original procedure and has not had recurrence for 4 years.

Transfusion free surgery: single institution experience of 27 consecutive liver transplants in Jehovah's Witnesses.

BACKGROUND: Despite the risks associated with transfusion, the medical community continues to view blood as a safe and abundant product. In this article, we provide an effective strategy to accomplish orthotopic liver transplantation without transfusion. STUDY DESIGN: From June 1999 through July 2004, 27 liver transplantations were performed in Jehovah's Witness patients at the USC-University Hospital (24 adults, 3 children). Nineteen of these were living donor (LD) and eight were deceased donor (DD) liver transplants. Preoperative blood augmentation with erythropoietin and iron was achieved. At induction, all LD and six of eight DD recipients underwent acute normovolemic hemodilution (ANH), and the operation was conducted under conditions of moderate anemia. Cell scavenging techniques were used. Acute normovolemic hemodilution and salvaged blood were returned as needed during bleeding or on completion of transplantation. RESULTS: The preoperative liver disease severity score was higher in the deceased donor group. We had 100% graft and patient survivals in the LD group, and 75% in the DD recipients. Two DD recipients died. The remaining are all alive and well, with a mean followup of 965 days (range 266 to 1,979 days) in the LD group and 624 days (range 119 to 1,132 days) in the DD group. CONCLUSIONS: Preoperative blood augmentation and acute normovolemic hemodilution provide a safe cushion against operative blood loss. Elective living donor liver transplantation allows full implementation of a transfusion-free strategy in the setting of early hepatic failure, portal hypertension, and anemia. This feat is an important step toward global standardization of transfusion-free surgical practice and an important response to widespread blood shortages and transfusion risks.

Major hepatobiliary surgery during pregnancy: safety and timing.

Hepatobiliary disease, although rare, may present during pregnancy with potential complications for mother and fetus. We present two cases of choledochal cysts and one case of a hepatic adenoma diagnosed in gravid patients. All three patients had acute events or failed medical management and were successfully treated with open resection, excision, or reconstruction during the second or third trimesters of pregnancy without requiring blood transfusions or tocolytic therapy. Although conservative treatment may be indicated in select patients due to the risk of underlying disease, we recommend surgical treatment preferably in the second trimester. With diligent intra- and postoperative management, pregnant patients can safely proceed with major hepatobiliary surgery.

Recombinant human coagulation factor VIIa in Jehovah's Witness patients undergoing liver transplantation.

Indisputably, liver transplantation is among the most technically challenging operations in current practice and is compounded by significant coagulopathy and portal hypertension. Recombinant human coagulation factor VIIa (rFVIIa) is a new product that was initially described to treat bleeding in hemophilia patients. We present in this paper 10 liver transplants in Jehovah's Witness patients using this novel product at University of Southern California-University Hospital. The subject population included nine males and one female with an average age of 50 years. Six patients underwent cadaveric and four live donor liver transplantation. Surgeries were conducted following our established protocol for transfusion-free liver transplantation, which includes preoperative blood augmentation, intraoperative blood salvage, acute normovolemic hemodilution, and postoperative blood conservation. Factor rFVIIa was used at a dose of 80 microg/kg intravenously just prior to the incision in all patients, and a second intraoperative dose was used in 3 patients. All living donor liver transplantation (LDLT) recipients did well and were discharged uneventfully with normal liver functions. Two of the six cadaveric recipients died. One patient died intraoperatively from acute primary graft nonfunction, and the other died 38 hours postoperatively from severe anemia. This report suggests factor rFVIIa might have a much broader application in surgery in the control of bleeding associated with coagulopathy.

Laparoscopic Hand-Assisted Parenchymal-Sparing Resections for Presumed Side-Branch Intraductal Papillary Mucinous Neoplasms.

BACKGROUND: The diagnosis of side-branch intraductal papillary mucinous neoplasms (IMPNs) is increasingly more common, but their appropriate management is still evolving. We recently began performing laparoscopic hand-assisted enucleation or duodenal-sparing pancreatic head resection for these lesions with vigilant postoperative imaging. MATERIALS AND METHODS: Seventeen patients with pancreatic cystic lesions were included in this single-center retrospective review from January 1, 2008 to March 30, 2013. Indication for surgical intervention was growth in size of the cyst, symptoms, cyst size >3 cm, and/or presence of a mural nodule. Twelve patients underwent laparoscopic hand-assisted enucleation, and 5 patients underwent laparoscopic hand-assisted pancreatic head resection. RESULTS: The mean age of patients was 64 years old. The most common presenting symptom was abdominal pain. The indication for surgical intervention was growth in the cyst or symptoms in the majority of patients. Fourteen lesions were in the head/uncinate, two were in the pancreatic body, and one was in the tail. Final pathology was consistent with side-branch IPMN in 13 patients (1 with focal adenocarcinoma). Three patients had serous cysts, and 1 had a mucinous cyst. Three patients developed pancreatic leaks, which were controlled with intraoperative placed drains, whereas 1 patient required additional drain placement. Median time from surgery to latest follow-up imaging is over 2 years. No patients have developed recurrent cysts or adenocarcinoma. CONCLUSIONS: Duodenal-sparing pancreatic head resection or pancreatic enucleation for patients with presumed side-branch IPMN is a safe and efficacious option, in terms of both operative outcomes and postoperative recurrence risk.