Genetic profiling of children with advanced cholestatic liver disease.

Advanced cholestatic liver disease is a leading referral to pediatric liver transplant centers. Recent advances in the genetic classification of this group of disorders promise a highly personalized management although the genetic heterogeneity also poses a diagnostic challenge. Using a next-generation sequencing-based multi-gene panel, we performed retrospective analysis of 98 pediatric patients who presented with advanced cholestatic liver disease. A likely causal mutation was identified in the majority (61%), spanning many genes including ones that have only rarely been reported to cause cholestatic liver disease, e.g. TJP2 and VIPAS39. We find no evidence to support mono-allelic phenotypic expression in the carrier parents despite the severe nature of the respective mutations, and no evidence of oligogenicity. The high-carrier frequency of the founder mutations identified in our cohort (1 in 87) suggests a minimum incidence of 1:7246, an alarmingly high disease burden that calls for the primary prevention through carrier screening.

Targeted complement inhibition and microvasculature in transplants: a therapeutic perspective.

Active complement mediators play a key role in graft-versus-host diseases, but little attention has been given to the angiogenic balance and complement modulation during allograft acceptance. The complement cascade releases the powerful proinflammatory mediators C3a and C5a anaphylatoxins, C3b, C5b opsonins and terminal membrane attack complex into tissues, which are deleterious if unchecked. Blocking complement mediators has been considered to be a promising approach in the modern drug discovery plan, and a significant number of therapeutic alternatives have been developed to dampen complement activation and protect host cells. Numerous immune cells, especially macrophages, develop both anaphylatoxin and opsonin receptors on their cell surface and their binding affects the macrophage phenotype and their angiogenic properties. This review discusses the mechanism that complement contributes to angiogenic injury, and the development of future therapeutic targets by antagonizing activated complement mediators to preserve microvasculature in rejecting the transplanted organ.

Complement and macrophage crosstalk during process of angiogenesis in tumor progression.

The complement system, which contains some of the most potent pro-inflammatory mediators in the tissue including the anaphylatoxins C3a and C5a are the vital parts of innate immunity. Complement activation seems to play a more critical role in tumor development, but little attention has been given to the angiogenic balance of the activated complement mediators and macrophage polarization during tumor progression. The tumor growth mainly supported by the infiltration of M2- tumor-associated macrophages, and high levels of C3a and C5a, whereas M1-macrophages contribute to immune-mediated tumor suppression. Macrophages express a cognate receptors for both C3a and C5a on their cell surface, and specific binding of C3a and C5a affects the functional modulation and angiogenic properties. Activation of complement mediators induce angiogenesis, favors an immunosuppressive microenvironment, and activate cancer-associated signaling pathways to assist chronic inflammation. In this review manuscript, we highlighted the specific roles of complement activation and macrophage polarization during uncontrolled angiogenesis in tumor progression, and therefore blocking of complement mediators would be an alternative therapeutic option for treating cancer.

Indocyanine Green Near-Infrared Fluorescence in Pure Laparoscopic Living Donor Hepatectomy: a Reliable Road Map for Intra-Hepatic Ducts ?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Indocyanine green near-infrared fluorescence in pure laparoscopic living donor hepatectomy: a reliable road map for intra-hepatic ducts?

Indocyanine green (ICG) near-infrared (NIR) fluorescence cholangiography (FC) has shown its usefulness to visualize the biliary ducts in open living donor hepatectomy (LDH) to check the intraoperative biliary anatomy. The fully laparoscopic LDH approach has been recently described. However, this procedure is very demanding for a possible misperception of right parenchymal transection line and the cut point of the lobar biliary ducts (BD). To explore the potential of ICG-NIR-FC method we report our experience in 11 fully laparoscopic left LDH using 5 different protocols. Protocol-A, consisted on intravenous (i.v.) ICG injection of 2.5 mg with immediate cut of the BD; -B, same dose and late cut; -C, 1 mg i.v. and late cut; -D, intra-cystic duct injection of 2.5 mg and immediate cut; -E, intra-cystic injection of 5 mg and immediate cut. Protocol-A showed fast fluorescence in the lobar artery and portal vein followed by the BD sheet ; -B showed intraductal excretion with a high parenchymal signal; -C showed a very week signal; -D failed to visualize the ducts; -E showed a good signal without parenchymal fluorescence. ICG-NIR-FC is an additional method to visualize the lobar ducts in fully laparoscopy LDH, but still insufficient for the segmental ducts.

Transhilar passage in right graft live donor liver transplantation: intrahilar anatomy and its impact on operative strategy.

The passage through the hilar plate during right graft live donor liver transplantation (LDLT) can have dangerous consequences for both donors and recipients. The purpose of our study was to delineate hilar transection and biliary reconstruction strategies in right graft LDLT, with special consideration of central and peripheral hilar anatomical variants. A total of 71 consecutive donors underwent preoperative three-dimensional (3D) CT reconstructions and virtual 3D hepatectomies. A three-modal hilar passage strategy was applied, and its impact on operative strategy analyzed. In 68.4% of cases, type I and II anatomical configurations allowed for an en block hilar transection with simple anastomotic reconstructions. In 23.6% of cases, donors had "difficult" type II and types III/IV hilar bile duct anatomy that required stepwise hilar transections and complex graft biliary reconstructions. Morbidity rates for our early (A) and recent (B) experience periods were 67% and 39%, respectively. (1) Our two-level classification and 3D imaging technique allowed for donor-individualized transhilar passage. (2) A stepwise transhilar passage was favored in types III and IV inside the right-sided hilar corridor. (3) Reconstruction techniques showed no ameliorating effect on early/late biliary morbidity rates.

Drainage of esophageal leakage using endoscopic vacuum therapy: a prospective pilot study.

BACKGROUND AND STUDY AIMS: Major leakage from an esophageal anastomosis is a life-threatening surgical complication. Endoscopically guided endoluminal vacuum therapy using polyurethane sponges is a new method for treating such leakage. PATIENTS AND METHODS: Between June 2007 and June 2009, five patients (mean age 68 years) who developed anastomotic leakage after esophageal surgery were prospectively evaluated. After endoscopic diagnosis of a major leakage, polyurethane sponges were endoscopically positioned in the wound cavity of the anastomosis. Continuous suction was applied via drainage tubes fixed to the sponges. Initially sponges were endoscopically changed three times per week. RESULTS: In all five patients treatment was successful. Median time to reduce levels of inflammation markers by 50 % was 10 days for white blood cell (WBC) count and 7 days for C-reactive protein (CRP). The smallest initial wound cavity size was 42 cm (3) and the largest was 157 cm (3). The median duration of drainage was 28 days, with a median of 9 sponge changes and a median time to total cavity closure of 42 days. Two patients needed anastomotic dilation by Savary-Miller bougienage due to stenosis found on further follow-up. One of these patients died of acute severe hemorrhage from an aortoanastomotic fistula after the dilation procedure. CONCLUSIONS: Endoscopically assisted vacuum therapy is a well-tolerated and effective therapeutic option for treatment of major esophageal leaks after surgery. Additional surgery was avoided in all cases. However, the occurrence of a delayed aortoesophageal fistula calls for careful further investigation of this new technique.

Effectiveness of Rex shunt in children with portal hypertension following liver transplantation or with primary portal hypertension.

Portal vein thrombosis can occur as a result of primary anomalies, after liver transplantation, and for other reasons. It may result in severe complications secondary to portal hypertension, such as bleeding from esophageal or gastric varices, hypersplenism, or impaired somatic growth. In this retrospective study, we analyzed the outcome of 25 children who underwent a Rex shunt procedure. The following venous grafts were used as the shunt: the autologous internal or external jugular vein (n = 17) or a cryopreserved graft (n = 5); in three patients the umbilical vein was recanalized. The median follow up time was 109 months (range 18 days-146 months). The best results were achieved in patients in whom an autologous jugular vein segment was used as a vascular graft for the Rex shunt (shunt patency of 88%). In patients with a functioning shunt no further lower or upper gastrointestinal bleeding occurred. And in the entire study population hypersplenism syndrome improved after surgery. In our large cohort of pediatric patients, the Rex shunt has shown to be an effective method to eliminate portal hypertension and to revascularize the liver and thereby prevents the possible consequences of long-term portosystemic shunting.

ABO-Incompatible Kidney Transplantation: Low Rates of Infectious Complications and Excellent Patient Survival.

BACKGROUND: A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS: We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS: A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS: In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.

Major hepatectomy for colorectal metastases: is preoperative portal occlusion an oncological risk factor?

BACKGROUND: This study investigates oncological risks and benefits of portal occlusion (PO) in major resection for colorectal liver metastases (CLM). METHODS: Between 1995 and 2004, 107 patients were scheduled for major hepatectomy for CLM. Of these, 53 patients were selected for PO due to insufficient future liver remnant (FLR), and 54 patients had straightforward hepatectomy. Associations of clinicopathologic factors with resectability, and outcome after PO were analyzed. RESULTS: 21 of 53 patients (39.6%) after PO were unresectable. These patients had a significant smaller volume of the FLR than the 32 resected patients after PO (P = .029). In total, 17 patients (80.9%) did not undergo resection due to cancer progression. Among these, 11 patients (52.4%) exhibited either a progression of known metastases located in the occluded lobes, or new metastases in the nonoccluded portion of the liver. In another 4 individuals (19%), the decision against resection resulted from insufficient hypertrophy of the FLR. Following major hepatectomy, the 5-year survival was 43.66%. Although there was a significantly higher rate of extended hepatectomies versus formal hepatectomies (P < .001), more bilobar distributed metastases versus unilobar manifestations (P = .015), and a smaller resection margin (P = .01) in patients who had PO, no adverse effect on mortality, morbidity, recurrence and survival was observed. CONCLUSION: Unresectability after PO is a major problem that warrants multidisciplinary improvements, and randomization to resection with or without PO remains ethically problematic. However, following adequate patient selection, PO may provide a significant survival benefit for patients with prior unresectable CLM.

Sofosbuvir-Based Therapy for Genotype 4 HCV Recurrence Post-Liver Transplant Treatment-Experienced Patients.

Background and Aim. This is an open label prospective cohort study conducted at a tertiary care hospital. The primary endpoint is SVR12 in patients treated with sofosbuvir-based therapy in post-liver transplant patients with genotype 4 HCV recurrence. Methodology. Thirty-six treatment-experienced liver transplant patients with HCV recurrence received sofosbuvir and ribavirin ± peginterferon. Results. We report here safety and efficacy data on 36 patients who completed the follow-up period. Mean age was 56 years, and the cohort included 24 males and one patient had cirrhosis. Mean baseline HCV RNA was 6.2 log10 IU/mL. The majority of patients had ≥ stage 2 fibrosis. Twenty-eight patients were treated with pegylated interferon plus ribavirin in addition to sofosbuvir for 12 weeks and the remaining were treated with sofosbuvir plus ribavirin only for 24 weeks. By week 4, only four (11.1%) patients had detectable HCV RNA. Of the 36 patients, 2 (5.5%) relapsed and one died (2.75%). Conclusion. Our results suggest that sofosbuvir + ribavirin ± pegylated interferon can be utilized successfully to treat liver transplant patients with HCV recurrence.

Radioembolization using yttrium-90 microspheres as bridging and downstaging treatment for unresectable hepatocellular carcinoma before liver transplantation: initial single-center experience.

INTRODUCTION: HCC is the sixth most common malignancy worldwide and is the third most common cause of cancer related mortality. Moreover, the incidence of HCC is increasing. Surgical treatments for HCC including resection and/or transplantation provide the best curative outcomes in early stages. Unfortunately, many patients present at an advanced stage. Currently, locoregional therapies have an emerging role in the management of HCC for bridging to liver transplantation and for downstaging the disease to within transplant criteria. Radioembolization is among commonly used locoregional therapies. OBJECTIVE: To describe our initial experience with the use of Therasphere® as bridging or downstaging modality before liver transplantation, including our institutional indications, technique and outcome. MATERIALS AND METHODS: We retrospectively examined our database for liver transplantation after the use of Therasphere®. Nine patients were identified and reported. RESULTS: They were 5 females and 4 males. Their current age range is 40-72 years with a mean of 53.8 ± 9.5 years. Three patients had Therasphere® as downstaging treatment to our institutional transplantation criteria. Our institution is using UCSF criteria as a cut off limit for liver transplantation as primary treatment modality. The other 6 patients had Therasphere® as bridging for liver transplantation especially when other modalities are not possible. None of these lesions were treated by any other locoregional treatment before or after Therasphere®. Follow-up after liver transplantation ranged between 3.7 and 60.1 months (mean of 15.8 ± 17.7 months). All patients are still living, no retransplantation was done and none of them showed evidence of disease recurrence (100% graft, patient and disease free survival). CONCLUSION: Our initial experience showed that Therasphere® is a promising therapeutic tool for both downstaging and bridging of HCC before liver transplant.

Spontaneous clearance of hepatitis C genotype 4 after liver retransplantation.

BACKGROUND: Hepatitis C virus (HCV)-related cirrhosis remains the most common indication for liver transplantation worldwide. Graft reinfection with HCV is nearly universal, causing significant morbidity and mortality. Spontaneous clearance of HCV after liver transplantation and retransplantation is extremely rare. We report a case of spontaneous clearance of HCV genotype 4 that occurred shortly after 2nd liver transplantation. CASE REPORT: A 32-year-old female patient received a cadaveric liver transplant for HCV-related cirrhosis in 2007. She was not treated for HCV before transplantation. The patient developed biopsy-proven HCV recurrence with elevated transaminases and 65,553 IU/mL HCV RNA, genotype 4. She could not tolerate interferon-based treatment. The patient's condition progressively worsened and required a 2nd cadaveric liver transplantation in March 2013. Immunosuppression initially included steroids and Prograf, which was then switched to cyclosporine after the patient developed seizure. She developed acute cellular rejection which was readily treated with immunosuppression adjustment. HCV RNA became negative in April, which was confirmed in May 2013. CONCLUSIONS: Spontaneous clearance of hepatitis C rarely occurs after liver transplantation and is extremely rare after retransplantation. This finding may be explained by alterations in the host immune responses to HCV after transplantation. To our knowledge, this is the first case of spontaneous clearance of HCV genotype 4 after liver retransplantation.

Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation.

BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and interferon (IFN)-gamma are mediators of acute graft rejection after liver transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective role and correlate with graft acceptance. To test the hypothesis that infants aged <1 year have an immunological advantage with regard to graft acceptance because of a partially immature immune system with a physiological balance toward a Th2 cytokine profile, we conducted the present study. METHODS: We compared the T helper serum cytokine profiles in 105 infants and children after liver transplantation with or without acute graft rejection and analyzed the normal age-distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS: The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1 to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence of acute rejection in infants 0 to 12 months of age compared with children >1 year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1 cytokine concentrations and decreasing Th2 cytokine concentrations were found with increasing age. Patients with acute rejection had significantly higher values of Th1 cytokines compared with nonrejecting subjects, who had significantly higher concentrations of Th2 cytokines. A longitudinal analysis of serum cytokines from patients showed that changes of the cytokine patterns in the follow-up did not differ significantly from preoperative values, except in the 4 weeks posttransplant. CONCLUSIONS: We conclude from the data that the physiological balance toward a Th2 cytokine profile of infants in the first months of life predisposes to improved graft acceptance. Transplantation of children with biliary atresia as early as possible, avoiding Th1 stimulation by recurrent infections and vaccinations, may have a positive impact on overall tolerance.

FDG PET in the diagnosis of hilar cholangiocarcinoma.

Resectional surgery offers a curative intent and a survival benefit for patients with hilar cholangiocarcinoma, but is associated with high morbidity. Since morphological imaging cannot solve differential diagnosis preoperatively, in order to exclude patients inappropriate to this aggressive surgery, we evaluated the impact of functional imaging using fluorodeoxyglucose positron emission tomography (FDG PET) in the detection of cholangiocarcinoma and its usefulness in the differentiation from benign Klatskin tumour-mimicking lesions. Fifteen consecutive patients aged 47-78 years underwent standardized whole-body FDG PET with attenuation correction before potentially curative surgery using a conventional full-ring PET scanner with an axial field-of-view of 16.2 cm. FDG PET was evaluated visually and semiquantitatively using tumour-to-background ratios (T/B) ratios. All lesions were evaluated histopathologically. FDG PET presumed to be indicative for carcinoma was positive in 12 of 15 patients, true positive in 10 (T/B ratio, 3.2+/-1.9) and false positive in two of them (T/B ratios, 2.1 and 2.8) with Klatskin tumour-mimicking lesions. While all true positive PET results were seen in the tubular type of cholangiocarcinoma with a high amount of tumour cells and only low production of mucus, a false negative FDG PET in three patients was observed in mucinous adenocarcinoma. Additionally, FDG PET detected locoregional lymph nodes in two patients and distant metastases in a further three patients. Due to false positive results FDG PET does not allow the differentiation of benign from malignant lesions, and FDG PET should be avoided in patients with mucinous cholangiocarcinoma. However, FDG PET may have significant influence on the treatment strategy in as much as 20% of the patients, since it may detect distant metastases.

[Evaluation of potential liver living donors. Logistic and financial aspects]. / Evaluation potenzieller Leberlebendspender. Logistik und finanzieller Rahmen.

INTRODUCTION: The increasing shortage of cadaveric organs makes living-related liver transplantation a more and more important option. Safety for the donor has the highest priority, and therefore detailed and thorough evaluation is needed. MATERIALS AND METHODS: All potential donors who had been evaluated at our center from January 2001 to March 2002 ( n=100) were included in a retrospective study to analyse the qualitative, logistical, and economic aspects of the evaluation. RESULTS: Seventy-three percent of the potential donors were found to be unsuitable for living donation during the evaluation process. The main reasons were: uncompatible blood group, availability of cadaveric transplant by Eurotransplant, steatosis of more than 10% of hepatocytes in liver biopsy, insufficient liver volume, and psychosocial reasons. The expenditure for all scheduled investigations was 4,469 euro for a complete evaluation. CONCLUSION: While on the one hand, high standards of the evaluation process must be guaranteed, insufficient reimbursement on the other should not lead centers to reduce either quantity or quality of necessary examinations entered in the evaluation protocol.

[Haemosuccus pancreaticus as a rare initial manifestation of chronic pancreatitis]. / Haemosuccus pancreaticus als seltene Erstmanifestation einer chronischen Pankreatitis.

Haemosuccus pancreaticus is an unfrequent but known cause of an upper gastrointestinal bleeding. Pathogenesis of spontaneous severe hemorrhage of the pancreatic duct includes chronic pancreatitis generated pseudocysts or aneurysms of the visceral arteries. We present two cases of severe spontaneous gastrointestinal bleeding as a first manifestation of chronic pancreatitis, in which the diagnosis chronic pancreatitis was not known and the patients denied any gastrointestinal symptoms in their medical history at the time of hemorrhage.

Rupture of the spleen associated with Enterobacter cloacae.

A 58-year-old male, with abdominal pain but no signs of sepsis, was admitted as a medical emergency. During hospitalization, spontaneous splenic rupture was diagnosed and splenectomy successfully performed. A smear revealed presence of Enterobacter cloacae on the splenic surface; histopathology demonstrated granulocytous infiltration of the spleen.

Improvement in gastrointestinal and health-related quality of life outcomes after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant recipients.

OBJECTIVE: To evaluate improvement in gastrointestinal (GI) symptoms and health-related quality of life (HRQoL) in liver transplant recipients switched from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS). METHODS: A multicenter, open-label, single-arm study was undertaken in maintenance liver transplant recipients who reported GI complications with MMF therapy. The patients were switched to equimolar doses of EC-MPS at baseline. The primary end point was the change in the Gastrointestinal Symptom Rating Scale (GSRS) total score after 6 to 8 weeks of treatment with EC-MPS. Other key assessments for GI symptoms and HRQoL included the GSRS subscores, the Gastrointestinal Quality of Life Index (GIQLI), the Psychological General Well-Being Index, and the Overall Treatment Effect (OTE). Paired t-test was used to assess the difference in the mean score changes over time. RESULTS: A total of 34 patients were enrolled and switched to equimolar doses of EC-MPS. After 6 to 8 weeks of EC-MPS treatment, mean GSRS total score improved significantly from 2.88 ± 0.66 to 2.10 ± 0.78. Mean improvement in GSRS total score (-0.77 score points; P = .001) exceeded the minimal clinically important difference. Significant improvements were observed in all GSRS subscales (P < .05), GIQLI total scores (P = .001), and GIQLI subscales "GI symptoms" (P < .001) and "physical function" (0.013). Patients who continued EC-MPS reported sustained benefits compared with patients who switched back to MMF after 6 to 8 weeks of treatment with EC-MPS. On the OTE scale, improvement in symptoms was reported in 76.5% and 61.8% of the patients as perceived by the physicians and the patients. Improvement in HRQoL was reported by 41.2% of the patients. No deaths, biopsy proven acute rejections, or graft losses were reported during the study. CONCLUSION: Conversion from MMF to EC-MPS was associated with a significant improvement in GI symptoms and HRQoL in liver transplant recipients.

Regional variation in organ donation in Saudi Arabia.

INTRODUCTION: There is marked regional variation in organ donation among the different regions of Saudi Arabia. Our aim was to study the dominating factors for these variations to improve organ donation in low-donation areas. MATERIALS AND METHODS: This study was a retrospective review of the Saudi Center for Organ Transplantation data for cadaveric organ donation from 2006 to 2012, with the number of cases reported, documented, consented, and harvested in various regions (northern, southern, eastern, western, and central). The region, number, and size of contributing intensive care units (ICUs), overall donation rate, and transplanted rate (potential donor and those harvested, respectively) were also reviewed. RESULTS: Between 2006 and 2012, a total of 512 cases were procured and analyzed from Saudi Arabia. From the central region, 393 were acquired, representing 76.7% of the total consented cases. These 393 cases came from 30 of 97 contributing ICUs (31%). The eastern region was ranked second, followed by the western region. The conversion rate for all regions followed a similar trend. CONCLUSIONS: There is marked variation with regard to organ donation in different regions throughout Saudi Arabia, from 1.9% in the southern region to 76.7% in the central region. This finding is related to the presence of a Mobile Action Donor Team in the central region. The number of potential donors and the contributing ICUs were strong predictors of the number of actual donors. We suggest that having a mobile donor team in each region will increase the number of donors by at least 3 times within the next 3 to 5 years.