Nagoud Schukfeh

Survival with the native liver after laparoscopic versus conventional kasai portoenterostomy in infants with biliary atresia: a prospective trial.

Objective:A prospective study to compare survival with own liver in laparoscopic versus conventional Kasai portoenterostomy in patients with biliary atresia. Background:Available studies on laparoscopic versus conventional Kasai portoenterostomy focus on short-term results, include small numbers of patients and have design limitations. Methods:A consecutive series of patients underwent laparoscopic Kasai procedure from 2006 to 2007. Conventionally operated control patients consisted of a consecutive series of infants with biliary atresia operated from August 2003 to 2006. All data were ascertained prospectively using the European Biliary Atresia Registry/EBAR registration forms. Primary outcome measure was survival with own liver 6 months after Kasai without being listed for liver transplantation. An interim analysis was planned after data became available for the first 12 patients, who underwent the laparoscopic Kasai procedure. In case of a significantly different interim outcome, the follow-up period should be extended to 24 months until a final decision can be made. Results:Twelve infants underwent laparoscopic Kasai procedure without conversion or revision and there was no revision in the control group of 28 conventionally operated patients. Six months after operation, 5 of 12 laparoscopically operated patients (42%) survived with own liver, compared with 23 of 28 (82%) controls (P < 0.01). The study was stopped due to the significantly higher rate of liver transplantation after laparoscopic operation. Ten patients (83%) after laparoscopic Kasai versus 18 (64%) conventionally operated patients were transplanted after 24 months (P < 0.05) and survival rates with own liver and serum bilirubin <20 &mgr;mol/L were 1 (8%) versus 8 (29%), respectively (P < 0.05). Conclusions:This prospective study shows that the laparoscopic Kasai procedure for biliary atresia is technically feasible. However, the study was stopped after inclusion of 12 laparoscopically operated infants due to a lower survival with the native liver after laparoscopic versus conventional Kasai operation. Superior results after conventional operation were confirmed at follow-up after 24 months. Study registration ID: EBAR 9260/NCT01063699.

Normalization of serum bile acids after partial external biliary diversion indicates an excellent long-term outcome in children with progressive familial intrahepatic cholestasis.

BACKGROUND/PURPOSE The surgical treatment for patients with progressive familial intrahepatic cholestasis (PFIC) is either liver transplantation (LTX) or partial external biliary diversion (PEBD). Both procedures achieve a good short-term outcome. However, the treatment strategy for these children remains controversial because the long-term outcome after PEBD is unknown. The aim of our study was to assess the long-term outcome and complications after PEBD in our institution. METHODS We retrospectively analyzed the characteristics of all patients with PFIC undergoing PEBD in our department from 1994 to 2008. The course of serum bile acids, pruritus, and liver enzymes was assessed in a regular follow-up. RESULTS Twenty-four patients underwent PEBD. Thirteen patients (54%) improved significantly, with a normalization of serum bile acids (P < .001 vs postoperatively) and lessened pruritus (P < .05 vs preoperatively) at 12 months after PEBD. None of these patients showed progression of cholestasis during a median follow-up of 9.8 years (range, 1.6-14.3 years). Partial external biliary diversion failed to normalize bile acids in 11 patients, of whom 9 required secondary LTX at a 1-year follow-up, with a median interval of 1.9 years (range, 0.5-3.8 years). All 7 patients (100%) with liver cirrhosis at the time of PEBD and 2 of 17 patients without cirrhosis (12%) required secondary LTX (P < .001). CONCLUSIONS Clinical improvement with normalization of serum bile acids within 1 year was associated with an excellent long-term outcome in patients with PEBD. The presence of liver cirrhosis at the time of PEBD indicated an unfavorable outcome. Thus, we recommend primary LTX only in PFIC patients with liver cirrhosis.

Carbon dioxide, Hypoxia and Low pH Lead to Overexpression of c-myc and HMGB-1 Oncogenes in Neuroblastoma Cells

PURPOSE It has been reported that CO (2) gas, used to establish a pneumoperitoneum during laparoscopy, affects the behavior of tumor cells. The proto-oncogenes C-MYC and HMGB-1 mediate aggressive behavior of neuroblastomas. We studied whether exposure to CO (2), hypoxia or acidosis affects the expression of C-MYC and HMGB-1 in neuroblastoma cells. METHODS SH-SY5Y cells were incubated with 100% CO (2), 95% helium/5% CO (2) or pH 6.2 for 2 h. The expression of C-MYC and HMGB-1 was measured by Western blot test immediately, 3 h and 6 h after incubation. Additionally, we measured apoptosis after incubation using fluorometric measurements of caspase 3 and 7 activity. RESULTS C-myc (160+/-26%, p=0.007 and 138+/-16% vs. control, p=0.04) and HMGB-1 proteins (140+/-13% and 136+/-11%, both p=0.037) were found to be significantly upregulated 6 h after incubation with CO (2) and helium. There was early upregulation of both oncogenes 3 h after CO (2) incubation (251+/-79%, p=0.04 and 292+/-136, p=0.037). Correspondingly, pH 6.2 led to significant overexpression. Levels of apoptosis were reduced. CONCLUSIONS Exposures mimicking conditions of CO (2) pneumoperitoneum lead to significant overexpression of C-MYC and HMGB-1 in neuroblastoma cells with decreased apoptosis. These results point to a negative influence and potentially increased malignancy of tumor cells.

Detection of hepatotropic viruses has no impact on the prognosis after Kasai procedure

BACKGROUND/PURPOSE A viral origin of biliary atresia (BA) is discussed, and several studies have demonstrated different viral strains in liver biopsies of patients undergoing Kasai portoenterostomy. We hypothesized that the presence of hepatotropic viruses in patients undergoing portoenterostomy contributes to the progression of the disease and negatively affect the outcome. METHODS Liver biopsies were prospectively taken from 70 patients undergoing portoenterostomy in our department from April 1996 to April 2004. Samples were screened by polymerase chain reaction for all common hepatic viruses. Primary outcome parameter was survival with the native liver. Secondary parameters were postoperative serum activity of liver enzymes and serum bilirubin levels at different time points. Patients underwent regular follow-up until October 2008. RESULTS Twenty-eight patients (40%) were positive for 1 or more hepatotropic viruses. Four patients were lost to follow-up. In the remaining 66 patients, there was no significant difference in survival with their native liver between virus-positive and virus-negative patients. After a mean follow-up of 7.7 years (range, 4.6-16.1 years), 15 (23%) of 66 patients still lived with their native liver. There was no difference in liver enzymes, C-reactive protein, or bilirubin at any time point between both groups. CONCLUSION A significant number of our patients tested positive for hepatotropic viruses in liver biopsies at the time of the Kasai procedure, but the presence of virus had no influence on the course of BA. This suggests that the ongoing inflammatory process of BA leading to liver cirrhosis in most Kasai-treated patients is not affected by hepatotropic viruses. Our data question the necessity to aggressively screen for and treat viral infections in patients with BA.

Dysplastic kidney and not renal agenesis is the commonly associated anomaly in infants with seminal vesicle cyst

To determine whether the association of seminal vesicle cyst (SVC) and renal anomaly in young children correlates with previously reported cases of SVCs in adolescent and adult patients, as congenital SVCs, although rare, are frequently described in association with ipsilateral renal agenesis, mainly in adolescent and adult patients, whereas reports on SVCs in younger children are sparse.

First Case Studies of Successful ABO-Incompatible Living-Related Liver Transplantation in Infants in Germany

AIM A series study mainly from Asia suggests that ABO-incompatible (ABOi) living-related liver transplantation (LRLT) for pediatric recipients is associated with excellent short- and long-term graft and patient survival. Until now, ABOi LRLT has been rarely performed in Europe. The aim of this study was to analyze the safety and early results of an ABOi LRLT in a German high-volume pediatric liver transplant center. METHODS Six consecutive pediatric patients (four males and two females) were included in this prospective study from January, 2010 to January, 2013 with a median age of 13 months (range, 6-30 months) receiving ABOi LRLT and were matched with six patients receiving ABO-compatible LRLT in the same period. In the ABOi group, titers of IgG and IgM isoagglutinins against the donors blood group were determined at day 14 before the transplantation and from day 1 to 14 after the transplantation, and then twice a week for another 8 weeks. The titer results were determined as the reciprocal number of the highest serum dilution that caused macroscopical reaction. RESULTS The patients receiving ABOi and those receiving ABO-compatible LRLT were comparable regarding the recipients preoperative pediatric end-stage liver disease (PELD), age, gender, and technical aspects of transplantation. The median follow-up was 2.6 years (range, 1-4.5 years). At the time of operation, the mean body weight was 7.7 kg (range, 5.7-16 kg) in ABO-compatible LRLT recipients and 8.8 kg (range, 5.5-18 kg) in ABOi LRLT recipients. In each group, the median PELD score was 28 (range, 28-35), respectively. All recipients received tacrolimus plus mycophenolate mofetil-based standard immunosuppression and four ABOi transplanted patients received intravenous immunoglobulins at days 1, 3, and 5 after liver transplantation. Patient and graft survival in this group was 83%. One female patient died within 24 hours due to fulminant gram-negative sepsis. Another patient developed acute cellular rejection at the 8th postoperative day, which responded to steroid treatment. No further complications occurred. In the ABO-compatible group, patient survival was 100% and graft survival was 83%; one patient in this group received retransplantation after 4 days. During follow-up, two patients of the ABOi group had maximum alloantibody titers of four against the donors blood group; all other patients had titers below four. CONCLUSION ABOi LRLT seems to be safe without an escalation of immunosuppression and should be considered as an additional option to timely facilitate the transplantation.

Laparoscopic button cholecystostomy for progressive familial intrahepatic cholestasis in two children.

BACKGROUND Untreated, progressive familial intrahepatic cholestasis (PFIC) results in fibrosis, cirrhosis, and liver failure. It has been shown that partial external biliary diversion (PEBD) may prevent from liver transplantation in patients without cirrhosis. The aim of this study is to present a new laparoscopic technique using a button instead of a bowel conduit for PEBD. PATIENTS AND METHODS Two boys with PFIC (patient 1, 17 months; patient 2, 12 years) underwent laparoscopic button cholecystostomy using a 3-trocar technique by insertion of a 14 French MIC KEY button (Kimberly-Clark Worldwide, Inc, Draper, Utah, United States) at the gallbladder fundus secured with two absorbable purse-string sutures. Beside the suitability of the procedure, end points included course of serum bile acids, total bilirubin, liver enzymes, and pruritus at a follow-up of 6 months. RESULTS No complications related to the operation occurred. Relieve of pruritus was achieved in both the children, due to adequate bile drainage during a follow-up period of 6 months. In patient 2, a 10-mm gallstone was removed simultaneously. In patient 1, serum bile acids decreased from 12.3 to 6.6 µmol/L and in patient 2, serum bile acids decreased from 106.3 to 2.9 µmol/L. Total bilirubin, aspartate amino transferase, alanine amino transferase, and gamma-glutamyltransferase are kept in normal ranges during follow-up. Patients and parents acceptance with the button was excellent. CONCLUSION Laparoscopic button cholecystostomy is a simple, safe, and sufficient technique for PEBD in patients with PFIC. It achieves an adequate bile flow with consecutive relief of pruritus and avoids an enteric anastomosis.

Implementation of Fast-Track Pediatric Surgery in a German Nonacademic Institution without Previous Fast-Track Experience

Fast-track concepts in pediatric surgery were established in a university hospital in consecutive studies within several years. They significantly reduced the length of hospitalization compared with German institutions without fast-track protocols. The aim of this study was to assess the implementation process of fast-track in a German nonacademic department of pediatric surgery without previous fast-track experience. All patients undergoing four types of operations (appendectomy, hypospadias repair, pyloromyotomy, and fundoplication) from February 2011 to January 2012 were included in this prospective study. Fast-track included detailed clinical pathways and specific pain treatment protocols using validated pain scales according to age. Mobilization and oral nutrition were started 2 hours postoperatively and documented with established scores. The length of hospital stay was compared with data from other hospitals with conventional treatment using information from the German reimbursement system (German diagnosis-related groups [G-DRG]) and with the hospital stay of patients from the corresponding university hospital undergoing fast-track treatment for the same procedures during the same study period. Two weeks after discharge, a questionnaire was completed by the patients/parents. A total of 143 patients with a mean age of 7.9 ± 5.0 years underwent fast-track treatment. The mean pain intensity during the immediate postoperative period was 1.7 ± 2.1 in patients < 4 years and 2.3 ± 2.1 in patients ≥ 4 years on a 10-point scale. Full mobilization was reached after a mean duration of 2.3 ± 2.0 days while full oral nutrition was completed after a mean duration of 1.8 ± 1.4 days. There were no complications associated with fast-track. The mean hospital stay was 5.8 ± 3.4 days which was not significantly different compared with G-DRG data from other hospitals without fast-track. This was in contrast to the mean hospital stay of patients from the corresponding university hospital (5.6 ± 3.0 days vs. G-DRG 6.9 ± 3.2 days, p < 0.05). After 2 weeks, patients/parents were highly satisfied with fast-track (mean score of 8.6 ± 1.4 on a 1-10-point scale) and 95.2% claimed that they would choose it again. Fast-track concepts can be applied in a nonacademic department of pediatric surgery without previous fast-track experience and with excellent patient/parent satisfaction. However, the G-DRG system interferes with concepts of early discharge of patients. Modifications of the reimbursement modalities within the German health care system seem to be mandatory.

Spectrum of pathogens in native liver, bile, and blood during pediatric liver transplantation

During LTX, there may be a risk that pathogens of the native liver are released into the systemic circulation. No investigations on incidence/spectrum of pathogens in native livers have been published. We hypothesized that pathogens are found in the native liver of a large proportion of pediatric patients during LTX and investigated the microbiology of native livers. These data may help optimize antibiotic therapy. Twenty‐two consecutive pediatric patients (median age 14 months, range, 5 months–15 yr) receiving LTX in our department from October 2010 to October 2011 were included in this prospective study. Tissue and bile were collected from the explanted liver and were cultivated on different media. All liver tissues were investigated using a broad‐range PCR (SepsiTest®). In 16 patients, blood cultures were collected post‐transplantation. Eleven patients (50%) had at least one pathogen detected; nine of these patients had an underlying diagnosis of biliary atresia. SepsiTest® was positive in seven patients. In four patients it was the only test detecting any pathogen. In detail, the positivity rate for liver tissue in all patients was 41% (n = 9); for bile 25% (n = 3); and for blood 25% (n = 4). Thirteen different pathogens (69% bacterial, 31% fungal) were isolated. A highly‐sensitive broad‐range PCR appears to be an effective method to detect pathogens in native livers of patients undergoing LTX. A high number and variety of microbes, including a high proportion of fungal pathogens, were detected.

Using pediatric liver grafts (≤6 yr) for adult recipients: A considerable option?

In LT, the common policy is to allocate pediatric liver grafts to pediatric recipients. Pediatric organs are also offered to adults if there is no pediatric recipient. However, they are rarely accepted for adult recipients. So far, there is no information available reporting outcome of LT in adult recipients using pediatric livers from donors ≤6 yr. In this study, we included nine adult recipients (seven females and two males) who received grafts from children ≤6 yr from January 2008 to December 2013. We evaluated the graft quality, the GBWR and analyzed the recipients’ perioperative course. Laboratory samples and graft perfusion were analyzed. Nine adults with a median age of 49 yr (range: 25–65) and a median weight of 60 kg (range: 48–64) underwent LT with a pediatric donor graft. Median donor age was five yr (range: 3–6). Median GBWR was 1.02 (range: 0.86–1.45). After a median follow‐up of 3.9 yr (range: 11 months–6.6 yr), patient survival was 100%; graft survival was 89%. One patient needed re‐transplantation on the second postoperative day due to PNF. Eight recipients were discharged from the ICU after 2–9 days with a regular graft function. Doppler scans revealed regular flow patterns at any time. Only if denied for pediatric recipients, the use of pediatric livers from donors ≤6 yr for adult recipients is a considerable option.