Sleeve Gastrectomy as Treatment for Severe Obesity after Orthotopic Liver Transplantation

Obesity is highly prevalent in both liver transplant candidates and recipients, and can have a significant impact on perioperative morbidity and mortality and the overall cost of transplantation. Herein, we describe an obese patient who was managed sequentially with an intragastric balloon in the pre-transplant setting and a gastric sleeve following transplantation, with good long-term results. Sleeve gastrectomy is a non-malabsorptive bariatric procedure with potential benefit for liver transplant patients due to its lack of influence on the absorption of immunosuppressive agents.     

Adult Living Donor Liver Transplantation for Acute‐on‐Chronic Liver Failure in High–Model for End‐Stage Liver Disease Score Patients

The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.     

Risk Factors for End‐Stage Kidney Disease After Pediatric Liver Transplantation

Adult liver transplant (LT) recipients commonly develop advanced kidney disease. However, burden of end‐stage kidney disease (ESKD) after pediatric LT has not been well‐described. We performed a retrospective cohort study of pediatric LTs in the United States from 1990 to 2010. Multivariable Cox regression models were fit to determine risk factors for ESKD and death. Eight thousand nine hundred seventy six children received LTs. During median follow‐up of 7.8 years, 2005 (22%) subjects died (mortality rate 26.1 cases/1000 person‐years); 167 (2%) developed ESKD (incidence rate 2.2 cases/1000 person‐years). Risk factors for ESKD included older age at LT (highest risk age >15 vs. < 5 years, HR = 4.94, p < 0.001), hepatitis C (HR 2.79, p = 0.004), liver re‐transplant (HR 2.67, p < 0.001), eGFR pre‐LT < 60 versus ≥ 60 (HR 2.37, p < 0.001), hepatitis B (HR 2.25, p = 0.027), black race (HR 1.46, p = 0.046), and male sex (HR 1.44, p = 0.022). LT recipients with ESKD had increased risk of mortality (HR 2.37, p < 0.001). Among pediatric LT recipients, rate of ESKD was lower than among adults and far exceeded by rate of death, however follow‐up time in this study may underestimate lifetime burden of ESKD. Although uncommon, ESKD was highly associated with mortality. Pediatric LT recipients should be routinely monitored for kidney disease, particularly those at highest risk of ESKD.     

Mid-term Follow-up after Sleeve Gastrectomy as a Final Approach for Morbid Obesity

Background  In previous publications, we demonstrated the safety and short-term efficacy of laparoscopic sleeve gastrectomy (LSG) as a final step in the treatment of morbid obesity (MO). This study aimed to assess the mid-term efficacy of LSG. Methods  We performed a retrospective review of a prospectively collected database. Between November 2004 and January 2007, 130 consecutive patients underwent LSG as a final procedure to MO. Data including patient demographics, operative time, length of hospital stay, complications, preoperative body mass index (BMI), complications, and weight loss at 3, 6, 12, 18, and 24 months were recorded and analyzed. Results  The mean age was 45.6 (range: 12–79) years while the mean BMI was 43.2 (range: 30.2–75.4) kg/m². The mean operative time was 97 (range, 58–180) min and all operations were completed laparoscopically. The mean hospital stay was 3.2 (range, 1–19) days with zero mortality in this series. One patient (0.7%) had leakage at the stapler line, while four patients (2.8%) developed trocar site infection. Three patients (2.1%) complained of symptoms of gastroesophageal reflux disease (GERD), three patients (2.1 %) developed symptomatic gallstones, and trocar site hernia was present in one (0.7%) patient. The mean weight loss was 21, 31.2, 37.4, 39.5, and 41.7 kg at 3, 6, 12, 18, and 24 months, respectively, while the mean BMI decreased to 36.9, 32.8, 29.5, 28, and 27.1 at 3, 6, 12 18, and 24 months, respectively. Percent of excess weight loss (%EWL) was 33.1, 50.8, 62.2, 64.4, and 67.9 at 3, 6, 12, 18, and 24 months, respectively. Conclusions  LSG is a safe and effective surgical procedure for the morbidly obese up to 2 years. Excess body weight loss seems to be acceptable at 2 years postoperatively.     

Vertical Gastric Resection (Sleeve Gastrectomy) in a Morbidly Obese Patient with Past Jejunoileal Bypass

Jejunoileal bypass (JIB) is a purely malabsorptiveoperation, which has been abandoned in the USA andWestern Europe due to occasional serious complications.We are still seeing past JIB patients who havebecome obese again over the years, but are not sufferingside-effects of the previous JIB, and are complainingof typical co-morbidities of the obesity. Wepresent a prior JIB patient who underwent a sleevegastrectomy in 2003 for recurrence of morbid obesity.The patient has been followed for another 4 years withregular laboratory tests, monitoring of weight loss,bone densitometry and possible complications.Selected morbidly obese patients who have undergonepast JIB, can be safely treated by a restrictiveprocedure, sleeve gastrectomy, to accomplish successfulweight loss without increasing the risk of possibleserious complications.     

Ex Vivo Liver Resection and Autotransplantation for End‐Stage Alveolar Echinococcosis: A Case Series

The role of autotransplantation in end‐stage hepatic alveolar echinococcosis (AE) is unclear. We aimed to present our 15‐case experience and propose selection criteria for autotransplantation. All patients were considered to have unresectable hepatic AE by conventional resection due to critical invasion to retrohepatic vena cava, hepatocaval region along with three hepatic veins, and the tertiary portal and arterial branches. All patients successfully underwent ex vivo extended right hepatectomy and autotransplantation without intraoperative mortality. The median autograft weight was 706 g (380–1000 g); operative time was 15.5 hours (11.5–20.5 hours); and anhepatic time was 283.8 minutes (180–435 min). Postoperative hospital stay was 32.3 days (12–60 days). Postoperative complication Clavien–Dindo grade IIIa or higher occurred in three patients including one death that occurred 12 days after the surgery due to acute liver failure. One patient was lost to follow‐up after the sixth month. Thirteen patients were followed for a median of 21.6 months with no relapse. This is the largest reported series of patients with end‐stage hepatic AE treated with liver autotransplantation. The technique requires neither organ donor nor postoperative immunosuppressant. The early postoperative mortality was low with acceptable morbidity. Preoperative precise assessment and strict patient selection are of utmost importance.     

Predicting End‐Stage Renal Disease After Liver Transplant

Few equations have been developed to predict end‐stage renal disease (ESRD) after deceased donor liver transplant. This retrospective observational cohort study analyzed all adult deceased donor liver transplant recipients in the Scientific Registry of Transplant Recipients (SRTR) database, 1995–2010. The prediction equation for ESRD was developed using candidate predictor variables available in SRTR after implementation of the allocation policy based on the model for end‐stage liver disease. ESRD was defined as initiation of maintenance dialysis therapy, kidney transplant or registration on the kidney transplant waiting list. We used Cox proportional hazard models to develop separate equations for assessing risk of ESRD by 6 months posttransplant and between 6 months and 5 years posttransplant. Variables in the 6‐month equation included recipient age, history of diabetes, history of dialysis before liver transplant, history of malignancy, body mass index, serum creatinine and liver donor risk index. Variables in the 6‐month to 5‐year equation included recipient race, history of diabetes, hepatitis C status, serum albumin, serum bilirubin and serum creatinine. The prediction equations have good calibration and discrimination (C statistics 0.74–0.78). We have produced risk prediction equations that can be used to aid in understanding the risk of ESRD after liver transplant.     

Left Lobe Auxiliary Liver Transplantation for End‐stage Hepatitis B Liver Cirrhosis

Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)‐related liver cirrhosis previously showed poor results, because the native liver was a significant source of HBV recurrence and the graft could be rapidly destroyed by HBV infection in an immunosuppressive condition. Four patients with HBV‐related liver cirrhosis were unable to undergo orthotopic liver transplantation because the only available grafts of left lobe were too small. Under entecavir‐based anti‐HBV treatment, they underwent ALT in which the recipient left liver was removed and the small left lobe graft was implanted in the corresponding space. The mean graft weight/recipient weight was 0.49% (range, 0.38%–0.55%). One year after transplantation, the graft sizes were increased to 273% and the remnant livers were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic graft biopsy showed no signs of tissue injury and negative immunostaining for hepatitis B surface antigen and hepatitis B core antigen. After a mean follow‐up period of 21 months, all patients live well with normal graft function. Our study suggests that ALT for HBV‐related liver cirrhosis is feasible under entecavir‐based anti‐HBV treatment. Successful application of small left livers in end‐stage liver cirrhosis may significantly increase the pool of left liver grafts for adult patients.     

Sociodemographic Determinants of Waitlist and Posttransplant Survival Among End‐Stage Liver Disease Patients

While regional organ availability dominates discussions of distribution policy, community‐level disparities remain poorly understood. We studied micro‐geographic determinants of survival risk and their distribution across Donor Service Areas (DSAs). Scientific Registry of Transplant Recipients records for all adults waitlisted for liver transplantation 2002–2014 were reviewed. The primary exposure variables were county‐level sociodemographic risk, as measured by the Community Health Score (CHS), a previously‐validated composite index local health conditions, and distance to listing transplant center. Among 114 347 patients, the median CHS was 19.4 (range: 0–40). Compared the lowest risk counties (CHS 1–10), highest‐risk counties (CHS 31–40) had more black (14.6% vs. 5.4%), publicly insured (44.9% vs. 33.0), and remote candidates (34.0% vs. 15.1% living >100 miles away). Higher‐CHS candidates had greater waitlist mortality in Cox multivariable (HR 1.16 for CHS 31–40, 95% CI 1.11–1.21) and competing risks analysis (sHR 1.07, 95% CI 0.99–1.14). Post‐transplant survival was similar across CHS quartiles. Living >25 miles from the transplant center conferred excess mortality risk (sHR 1.08, 95% CI 1.03–1.12). Proposed distribution changes would disproportionately impact DSAs with more high‐CHS or distant candidates. Low‐income, rural and minority patients experience excess mortality while awaiting transplant, and risk disproportionately worse outcomes with reduced organ availability under current proposals.     

The Second International Consensus Summit for Sleeve Gastrectomy, March 19–21, 2009

BackgroundSleeve gastrectomy (SG) is a rapid and comparatively simple bariatric operation, which thus far shows good resolution of co-morbidities and good weight loss. The potential peri-operative complications must be recognized and treated promptly. Like other bariatric operations, there are variations in technique. Laparoscopic SG was initially performed for high-risk patients to increase the safety of a second operation. However, indications for SG have been increasing. Interaction among those performing this procedure is necessary, and the Second International Consensus Summit for SG (ICSSG) was held to evaluate techniques and results.MethodsA questionnaire was filled out by attendees at the Second ICSSG, held March 19–22, 2009, in Miami Beach, and rapid responses were recorded during the consensus part.ResultsFindings are based on 106 questionnaires representing a total of 14,776 SGs. In 86.3%, SG was intended as the sole operation. A total of 81.9% of the surgeons reported no conversions from a laparoscopic to an open SG. Mean ± SD percent excess weight loss was as follows: 1 year, 60.7 ± 15.6; 2 years, 64.7 ± 12.9; 3 years, 61.7 ± 11.4; 4 years 64.6 ± 10.5; >4 years, 48.5 ± 8.7. Bougie size was 35.6F ± 4.9F (median 34.0F, range 16F–60F). The dissection commenced 5.0 ± 1.4 cm (median 5.0 cm, range 1–10 cm) proximal to the pylorus. Staple-line was reinforced by 65.1% of the responders; of these, 50.9% over-sew, 42.1% buttress, and 7% do both. Estimated percent of fundus removed was 95.8 ± 12%; many expressed caution to avoid involving the esophagus. Post-operatively, a high leak occurred in 1.5%, a lower leak in 0.5%, hemorrhage in 1.1%, splenic injury in 0.1%, and later stenosis in 0.9%. Post-operative gastroesophageal reflux (～3 mo) was reported in 6.5% (range 0–83%). Mortality was 0.2 ± 0.9% (total 30 deaths in 14,776 patients). During the consensus part, the audience responded that there was enough evidence published to support the use of SG as a primary procedure to treat morbid obesity and indicated that it is on par with adjustable gastric banding and Roux-en-Y gastric bypass, with a yes vote at 77%.ConclusionSG for morbid obesity is very promising as a primary operation.     

Addressing Morbid Obesity as a Barrier to Renal Transplantation With Laparoscopic Sleeve Gastrectomy

Morbid obesity is a barrier to renal transplantation and is inadequately addressed by medical therapy. We present results of a prospective evaluation of laparoscopic sleeve gastrectomy (LSG) for patients failing to achieve significant weight loss with medical therapy. Over a 25‐month period, 52 obese renal transplant candidates meeting NIH guidelines for metabolic surgery underwent LSG. Mean age was 50.0 ± 10.0 years with an average preoperative BMI of 43.0 ± 5.4 kg/m² (range 35.8–67.7 kg/m²). Follow‐up after LSG was 220 ± 152 days (range 26–733 days) with last BMI of 36.3 ± 5.3 kg/m² (range 29.2–49.8 kg/m²) with 29 (55.8%) patients achieving goal BMI of <35 kg/m² at 92 ± 92 days (range 13–420 days). The mean percentage of excess weight loss (%EWL) was 32.1 ± 17.6% (range 6.7–93.8%). A segmented regression model was used to compare medical therapy versus LSG. This revealed a statistically significant increase in the BMI reduction rate (0.3 kg/m²/month versus 1.1 kg/m²/month, p < 0.0001). Patients also experienced a 40.9% decrease in anti‐hypertensive medications (p < 0.001) and a 49.7% decrease in total daily insulin dose (p < 0.001). LSG is a safe and effective means for addressing obesity in kidney transplant candidates in the context of a multidisciplinary approach.     

The Diagnostic Conundrum and Liver Transplantation Outcome for Combined Hepatocellular‐Cholangiocarcinoma

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) is a rare primary liver malignancy with mixed hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) histological features. It is almost impossible to obtain an accurate, preoperative noninvasive diagnosis of cHCC‐CC with tumor markers or cross‐sectional abdominal imaging due to the mixed histological features. Despite these difficulties, accurate cHCC‐CC diagnosis remains an important goal with prognostic significance. In our study, we retrospectively reviewed the tumor markers: AFP and CA 19‐9, and cross‐sectional liver imaging, in light of liver explant findings, to identify and characterize cHCC‐CC features followed by liver transplantation (LT) outcome analysis. The results from this 12 patient cohort failed to identify characteristic features for cHCC‐CC. None of the imaging features helped to identify the cHCC‐CC tumor and they mimicked either HCC or CC, depending on the degree of glandular differentiation expressed histologically. In our cHCC‐CC LT recipients, the 1‐, 3‐ and 5‐year cumulative survival probabilities were 79%, 66% and 16%, respectively with a 5‐year survival comparable to or better than LT for intrahepatic CC but poorer than LT for HCC following the Milan criteria. Conceivably explained by its cholangiocarcinoma component the LT outcome for this rare and hard to diagnose tumor appears poor.     

Risk of End‐Stage Renal Disease Among Liver Transplant Recipients With Pretransplant Renal Dysfunction

Guidelines recommend restricting simultaneous liver–kidney (SLK) transplant to candidates with prolonged dialysis or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² for 90 days. However, few studies exist to support the latter recommendation. Using Scientific Registry of Transplant Recipients and Medicare dialysis data, we assembled a cohort of 4997 liver transplant recipients from February 27, 2002–January 1, 2008. Serial eGFRs were calculated from serum creatinines submitted with MELD reports. We categorized recipients by eGFR patterns in the 90 days pretransplant: Group 1 (eGFR always >30), Group 2 (eGFR fluctuated), Group 3 (eGFR always <30) and Group 4 (short‐term dialysis). For Group 2, we characterized fluctuations in renal function using time‐weighted mean eGFR. Among liver‐alone recipients in Group 3, the rate of end‐stage renal disease (ESRD) by 3 years was 31%, versus <10% for other groups (p < 0.001). In multivariable Cox regression, eGFR Group, diabetes (HR 2.65, p < 0.001) and black race (HR 1.83, p = 0.02) were associated with ESRD. Among liver‐alone recipients in Group 2, only diabetics with time‐weighted mean eGFR <30 had a substantial ESRD risk (25.6%). In summary, among liver transplant candidates not on prolonged dialysis, SLK should be considered for those whose eGFR is always <30 and diabetic candidates whose weighted mean eGFR is <30 for 90 days.     

Combined Pancreatic Islet and Kidney Transplantation in a Child With Unstable Type 1 Diabetes and End‐Stage Renal Disease

Islet transplantation after successful kidney transplantation is a recognized treatment for adults with diabetes and end‐stage renal disease (ESRD), but has not been considered an option in the pediatric population. To our knowledge, we report the first combined islet and kidney transplant in a child. The patient was born with bilateral renal hypoplasia and was diagnosed with type 1 diabetes mellitus at age 13 months. He had erratic glycemic control and hypoglycemia unawareness. At 6 years of age, the child safely underwent simultaneous islet and live donor kidney transplantation. Although function of the islet graft was transient, the combined transplant provided significant benefits in terms of glucose control and overall growth and development. Such an approach represents a viable treatment option for pediatric patients with ESRD and unstable diabetes.     

Depression and Frailty in Patients With End‐Stage Liver Disease Referred for Transplant Evaluation

End‐stage liver disease (ESLD) patients are believed to have a high prevalence of depression, although mental health in ESLD has not been studied comprehensively. Further, the relationship between depression and severity of liver disease is unclear. Using baseline data from a large prospective cohort study (N = 500) of frailty in ESLD patients, we studied the association of frailty with depression. Frailty was assessed with the five‐component Fried Frailty Index. Patients were assigned a composite score of 0 to 5, with scores ≥3 considered frail. Depression was assessed using the 15‐question Geriatric Depression Scale, with a threshold of ≥6 indicating depression; 43.2% of patients were frail and 39.4% of patients were depressed (median score 4, range 0–15). In multivariate analysis, frailty was significantly associated with depression (odds ratio 2.78, 95% confidence interval 1.87–4.15, p < 0.001), whereas model for ESLD score was not associated with depression. After covariate adjustment, depression prevalence was 3.6 times higher in the most‐frail patients than the least‐frail patients. In conclusion, depression is common in ESLD patients and is strongly associated with frailty but not with severity of liver disease. Transplant centers should address mental health issues and frailty; targeted interventions may lower the burden of mental illness in this population.     

Liver Transplantation Outcome in Patients With Angiographically Proven Coronary Artery Disease: A Multi‐Institutional Study

Over the last decade the age of liver transplant (LT) recipients and the likelihood of coronary artery disease (CAD) in this population have increased. There are no multicenter studies that have examined the impact of CAD on LT outcomes. In this historical cohort study, we identified adult LT recipients who underwent angiography prior to transplantation at seven institutions over a 12‐year period. For each patient we recorded demographic data, recipient and donor risk factors, duration of follow‐up, the presence of angiographically proven obstructive CAD (≥50% stenosis) and post‐LT survival. Obstructive CAD was present in 151 of 630 patients, the CAD(+) group. Nonobstructive CAD was found in 479 patients, the CAD(?) group. Patient survival was similar for the CAD(+) group (adjusted HR 1.13, CI = [0.79, 1.62], p = 0.493) compared to the CAD(?) group. The CAD(+) patients were further stratified into severe (CADsev, >70% stenosis, n = 96), and moderate CAD (CADmod, 50–70% stenosis, n = 55) groups. Survival for the CADsev (adjusted HR = 1.26, CI = [0.83, 1.91], p = 0.277) and CADmod (adjusted HR = 0.93, CI = [0.52, 1.66], p = 0.797) groups were similar to the CAD(?) group. We conclude that when current CAD treatment strategies are employed prior to transplant, post‐LT survival is not significantly different between patients with and without obstructive CAD.     

Combined ''En Bloc'' Liver and Pancreas Transplantation in Patients with Liver Disease and Type 1 Diabetes Mellitus

Liver disease alters the glucose metabolism and may cause diabetes, but this condition is potentially reversible with liver transplantation (LTx). Type 1 diabetes mellitus may be coincidentally present in a LTx candidate and immunosuppressive drugs will aggravate diabetes and make its management more difficult for posttransplant. In addition, diabetes negatively influences outcome after LTx. Therefore, the question arises as to why not transplanting the pancreas in addition to the liver in selected patients suffering from both liver disease and Type 1 diabetes. We report two cases of en bloc combined liver and pancreatic transplantation, a technique originally described a decade ago in the treatment of upper abdominal malignancies but rarely used for the treatment of combined liver disease and Type 1 diabetes. Both recipients are currently liver disease-free and insulin-free more than 2 and 4 years posttransplant, respectively. Surgical, medical and immunological aspects of combined liver-pancreas transplantation are discussed in the light of the existing relevant literature.