D C Broering

University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

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Publications (169)586.56 Total impact

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    ABSTRACT: 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.
    Transplantation Proceedings 01/2014; 46(1):234–240. DOI:10.1016/j.transproceed.2013.09.026
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    ABSTRACT: Chronic allograft dysfunction is increasingly recognized as a result of multiple factors affecting the liver graft in the intermediate and long-term course after liver transplantation. Interpretation of the histological, clinical-chemical, virological and immunological findings and imaging results is difficult, since in general multiple factors may be responsible for the changes observed in these patients. During the transition period from child-to adulthood non adherence is one additional factor which has to be considered. Allograft hepatitis and toxic liver damage are encountered between 5-25%. Viral infections due to Cytomegalo- and Epstein-Barr-Virus are affecting the pediatric liver transplant population in 6-27% of patients, however there are regional differences which have to be taken into account. Disease recurrence depends on the underlying disease and may be seen in 10-100%. Special attention has to be addressed to progressive familial intrahepatic cholestasis type 1, were all patients with diarrhea will have fatty livers and steatohepatitis. Respiratory chain disorders and Niemann-Pick disease type C have a high risk of disease recurrence since they are systemic disorders. Vascular and biliary tract complications are often found together and are seen in the range of 5-10%. Donor organ related complications are rare in childhood, since hepatitis B and C affected donor organs are excluded from organ donation. The histological feature of chronic ductopenic rejection is observed in about 4%. In the transition period non-adherence is a major problem, which is responsible for late acute and even chronic rejection in at least 8% of adolescents. These data show that careful long-term follow-up investigations are mandatory in the pediatric liver transplant population. New methods such as liver elastography and donor specific antibody formation or free donor specific DNA will most probably yield better insight in processes which are almost not detectable by routine liver function tests.
    Annals of Saudi medicine 03/2013; 33(2):S27-S30.
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    ABSTRACT: In 2010, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, established a dedicated Organ Transplant Center to overcome the inadequacy in transplantation care in the region. Due to the high need for solid organ transplantation in children, this center focused on pediatric transplantation. Between 2011 and 2013, a total of 112 pediatric liver transplantations have been performed in our center, mostly from living donors (n=103, 92%). Eight percent of transplants were performed from deceased donors (n=9). Of the 112 transplants, 38.4% of children were below one year of age. There was a predominance of genetic-metabolic disorders (48.2%) as indications for transplant. Extra-hepatic biliary atresia was the indication in only 29.5% of transplant cases. End-stage liver disease of unknown origin accounted for 7.1% of cases. The actuarial recipient and graft survival are 93% and 89%, respectively. In-hospital morbidities amounted to 17% for surgical complications (n=19) and 18% for medical complications (n=20). Seven percent of recipients developed biopsy proven rejection during hospital stay. Five patients died late after discharge suddenly at home or at peripheral hospitals for unknown reasons. Overall, this newly established pediatric liver transplantation program could develop into a high-volume pediatric liver transplantation center in a short period of time due to the high need for liver transplantation in the country. In contrast to the experience in western or eastern countries, there is a high rate of indications for metabolic/genetic disorders. The early results of patient and graft survival are convincing. The long-term outcomes were compromised by an insufficient general healthcare system and cultural barriers.
    Clinical transplants 01/2013;
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    ABSTRACT: 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.
    American Journal of Transplantation 03/2012; 12(3):718-27. DOI:10.1111/j.1600-6143.2011.03827.x
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    ABSTRACT: Inadequate knowledge of the right (RHV) and accessory (IHV) hepatic 'venous drainage' territories can lead to severe postoperative venous congestion after right graft live donor liver transplantation. The purpose of our study was to define the anatomical-functional RHV and IHV drainage territories. One hundred and forty consecutive live liver donor candidates were evaluated by means of 3-D CT reconstructions and 3-D virtual hepatectomies. Three RHV/IHV drainage patterns were identified and 'risky' configurations for right graft resections were defined. Livers with 'small' IHV drainage volumes (90.1±63.2mL) had dominant type IRHV/ IHV or non-dominant type III-RHV/IHV total liver (TL) complexes. All other cases had 'large' IHV volumes (294.7±115.5mL, p<0.001) with dominant type II-RHV/IHV TL complexes. Loss of IHV drainage volume (such as with no IHV reconstruction) in these cases was associated with a 'dominance transition' from right (RHV) to middle (MHV) hepatic veins, placing the grafts at 'high risk' for venous congestion. Type II-RHV/IHV complexes with large IHV drainage volumes are at 'high risk' for venous congestion in live donor liver transplantation.
    Hepato-gastroenterology 11/2011; 58(110-111):1664-9. DOI:10.5754/hge10348
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    ABSTRACT: Some surgical centres consider palliative resection (PR) to be superior to double loop bypass (DLB) as treatment for advanced carcinoma of the pancreatic head. We performed a retrospective study with prospectively collected data at a single centre to compare PR and DLB in regard to quality of life (QoL). From January 1996 to September 2008, 196 patients were given palliative surgery for advanced pancreatic cancer at the University Hospital of Kiel. Forty-two patients underwent PR and 154 underwent DLB. These groups were compared with regard to survival, post-operative morbidity, and QoL. The EORTC QLQ-C30 was used to assess QoL before surgery, at discharge, three months after surgery, and six months after surgery. The median survival time after PR was 7.5 months (95% CI: 4.95-10.05) and after DLB was 6 months (95% CI: 4.98-7.02; log rank test: p = 0.066). There were no significant differences in mortality and morbidity rates (7.1% and 45.2% for PR; 3.9% and 38.3% for DLB, respectively). Assessment of QoL indicated that patients who underwent PR had more impairment of some functional metrics and increased symptoms compared to those who underwent DLB. There was no significant difference in survival or morbidity after PR and DLB, but patients who underwent DLB had better QoL than patients who underwent PR. Therefore, clinicians may want to reconsider the use of PR for patients with advanced pancreatic cancer.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 09/2011; 37(9):798-804. DOI:10.1016/j.ejso.2011.06.017
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    ABSTRACT: To identify transcapsular arterial neovascularization with Doppler ultrasonography (US) in pediatric patients after liver transplantation and to assess the frequency of the finding, its underlying causes, and its relevance in terms of clinical outcome. The study was approved by the local ethics committee, with waived informed consent. All pediatric patients who underwent liver transplantation between January 2000 and December 2003 were retrospectively evaluated. Patients were followed up until June 2008, by using a predefined US protocol with prospective documentation. Of 182 consecutive liver transplantations performed in 162 patients (mean age, 4.5 years; range, 0.1-18.4 years) in this period, 25 patients with a total of 27 liver transplantations underwent US examinations conducted by multiple investigators and were primarily excluded. Student t tests and χ(2) tests were performed where appropriate. The Tarone-Ware test was used to compare transplant survival times. Transcapsular arterial neovascularization was noticed in 13 of 137 patients (9.5%) and in 13 of 155 liver transplants (8.4%). The mean time until arterial neovessels appeared was 157 days after liver transplantation (median, 97 days; range, 19-477 days). Arterial neovascularization was associated with pronounced transplant malperfusion and inflammatory changes (P < .001). Patients with transcapsular arterial neovascularization had a significantly shorter mean transplant survival time (1426.4 days ± 244.5 [standard error], with 95% confidence interval: 947.23, 1905.23, vs 2526.4 days ± 92.1, with 95% confidence interval: 2345.84, 2706.97; P = .008) and a higher retransplantation rate (53.8% vs 19.7%, P = .009). Transcapsular arterial neovascularization, detected with color Doppler US, occurred in 9.5% (13 of 137) of pediatric patients and 8.4% (13 of 155) of liver transplants and was associated with underlying malperfusion and inflammation. The diagnosis of transcapsular arterial neovascularization was associated with reduced graft survival times and a high retransplantation rate. The negative prognostic value of the sign may assist in a strategy of organ allocation.
    Radiology 08/2011; 261(2):566-72. DOI:10.1148/radiol.11110138
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    ABSTRACT: Invasive aspergillosis is one of the most severe complications after liver transplantation characterised by early dissemination of disease and high mortality. Recent data show that the prognosis is diminishing even further when Aspergillus terreus, a strain resistant to standard treatment with amphotericin, is isolated. We report a high risk liver transplant recipient with multiple co-morbidities including renal failure and allograft dysfunction in whom pulmonary aspergillosis due to A. terreus was successfully treated by the echinocandin antifungal agent caspofungin.
    Mycoses 07/2011; 54(4):e220-2. DOI:10.1111/j.1439-0507.2009.01829.x
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    ABSTRACT: The aim of this analysis was to provide an update on the current trend in living donor liver transplantation (LDLT) for adult recipients in the model of end stage liver disease (MELD) era in Germany and to encourage a wider implementation of LDLT. We descriptively analysed the data of LDLTs in Germany from 15 December 2006 to 31 December 2009 using a multi-center retrospective analysis via a questionnaire and data provided by Eurotransplant. Ten German centers performed LDLTs in adults. Eighty four transplantations in 50 male recipients and 34 female recipients were performed during the review period, ranging from 1 to 16 LDLTs per center. Hepatocellular carcinoma in cirrhosis (15/84) was the most common transplantation indication. The recipient mean lab-MELD score was 15 (±8). Six re-transplantations were necessary after initial LDLTs. The 1-year patient survival was 81%. We obtained data of 79/84 donors. The incidence of complications was 30.4% (n = 24). There were no grade 5 complications according to the Clavien classification. LDLT is an established treatment option that may reduce the waiting time, provides high quality split liver grafts and should be advocated in the MELD era to reduce organ shortage and 'death on the waiting list'.
    Transplant International 06/2011; 24(9):904-11. DOI:10.1111/j.1432-2277.2011.01283.x
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    ABSTRACT: Organ donor shortage for infant liver transplant recipients has lead to an increase in splitting and living donation. For cases in which even transplantation of the left lateral graft (Couinaud's segments II + III) results in a "large for size situation" with an estimated graft body weight ratio (GBWR) of >4%, monosegmental liver transplantation was developed. This, however, bears complications because of greater parenchymal surface and suboptimal vascular flow. We exclusively use the left lateral graft from living donors or split grafts. Temporary abdominal closure is attempted in cases of increased pressure. We report of 41 pediatric transplants in 38 children ≤10 kg. Within this group, there were 23 cases with a GBWR of ≥4, and 15 cases with a GBWR <4. There was no statistical difference in vascular or biliary complications. Despite a more frequent rate of temporary abdominal closure, we did not find a higher rate of intra-abdominal infections. Overall, patient and graft survival was excellent in both groups (one death, three re-transplants). We noticed, however, that the ventro-dorsal diameter of the graft appears to be more relevant to potential graft necrosis than the actual graft size. In conclusion, the usage of monosegmental grafts seems unnecessary if transplantation of left lateral grafts is performed by an experienced multidisciplinary team, and temporary abdominal closure is favored in cases of increased abdominal pressure.
    Transplant International 06/2011; 24(8):797-804. DOI:10.1111/j.1432-2277.2011.01277.x
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    ABSTRACT: Clinicopathologic stage is still the main parameter to evaluate the prognosis of newly diagnosed colorectal cancer (CRC) patients. Although molecular markers have been suggested for follow up of treated CRC patients, their complete clinical application is still under evaluation. To evaluate the association of immune-related genes with CRC prognosis and survival, a total of 19 single nucleotide polymorphisms (SNPs) were genotyped in 614 German patients within the Kiel cohort (POPGEN). A promoter variant (rs1800872) in the Interleukin-10 (IL-10) gene was associated with an increased lymph node metastasis involvement [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.03-4.2, for carriers of the TT genotype]. More importantly, among 582 followed up patients the SNP rs3775291 in the toll-like receptor 3 (TLR-3) gene was associated with CRC specific survival (150 events). Patients carrying the TT genotype had a 93% increased risk of death compared with the CC carriers [hazard ratio (HR) = 1.93, 95% CI 1.14-3.28]. The observed effect of the TLR-3 variant was restricted to stage II patients (HR = 4.14, 95% CI 1.24-13.84) and to patients who did not receive adjuvant therapy (HR = 3.2, 95% CI 1.4-7.7). Our results may provide additional candidates for risk assessment in stage II CRC patients for treatment decision. Further validation of the presented findings is warranted.
    European journal of cancer (Oxford, England: 1990) 05/2011; 47(8):1203-10. DOI:10.1016/j.ejca.2010.12.011
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    ABSTRACT: A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; P(genotype) = 1.2 × 10(-5) ; P(allelic) = 1.6 × 10(-6) ) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; P(genotype) = 0.0085; P(allelic) = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; P(genotype) = 0.040; P(allelic) = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. CONCLUSION: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.
    Hepatology 01/2011; 53(1):86-95. DOI:10.1002/hep.24017
  • Zeitschrift für Gastroenterologie 01/2011; 49(01). DOI:10.1055/s-0030-1269579
  • Zeitschrift für Gastroenterologie 01/2011; 49(01). DOI:10.1055/s-0030-1269631
  • Zeitschrift für Gastroenterologie 01/2011; 49(01). DOI:10.1055/s-0030-1269524
  • Zeitschrift für Gastroenterologie 01/2011; 49(01). DOI:10.1055/s-0030-1269592
  • Zeitschrift für Gastroenterologie 01/2011; 49(01). DOI:10.1055/s-0030-1269617
  • Zeitschrift für Gastroenterologie 01/2011; 49(01). DOI:10.1055/s-0030-1269629
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    ABSTRACT: Die Dünndarmtransplantation (DTx) ist eine noch junge Technik, die bei Patienten mit Kurzdarmsyndrom und Komplikationen der totalen parenteralen Ernährung (TPN) indiziert ist. Das International Intestinal Transplant Registry (IITR) erfasste bis 2005 weltweit bislang 989 DTx bei 923 Patienten in 61 registrierten Transplantationszentren. Ein Meilenstein in der Dünndarmtransplantation war die Einführung des Immunsuppressivums Tacrolimus, das gegenüber dem Ciclosporin eine effektivere Kontrolle von Transplantatabstoßungen ermöglichte. Mit der Etablierung von Tacrolimus als Basisimmunsuppressivum stieg die Anzahl der Dünndarmtransplantationen stetig an und erreichte 2001 erstmals 100 DTx pro Jahr. Von den bislang 989 Transplantationen erfolgten 43,8% als isolierte DTx, 39,0% als kombinierte Leber- und DTx (LDTx) und 17,2% als multiviszerale Transplantation (MTx).
    12/2010: pages 493-508;
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    ABSTRACT: Genome-wide association studies have mapped loci that are associated with serum levels of bilirubin. Bilirubin is a major component of gallstones so we investigated whether these variants predict gallstone bilirubin content and overall risk for gallstones. Loci that were identified in a meta-analysis to attain a genome-wide significance level of a P value less than 1.0×10(-7) (UGT1A1, SLCO1B1, LST-3TM12, SLCO1A2) were analyzed in 1018 individuals with known gallstone composition. Gallstone risk was analyzed in 2606 German choleystecomized individuals and 1121 controls and was replicated in 210 cases and 496 controls from South America. By using the presence of bilirubin as a phenotype, variants rs6742078 (UGT1A1; P = .003), rs4149056 (SLCO1B1; P = .003), and rs4149000 (SLCO1A2; P = .015) were associated with gallstone composition. In regression analyses, only UGT1A1 and SLCO1B1 were independently retained in the model. UGT1A1 (rs6742078; P = .018) was associated with overall gallstone risk. In a sex-stratified analysis, only male carriers of rs6742078 had an increased risk for gallstone disease (P = 2.1×10(-7); odds ratio(recessive), 2.34; P(women) = .47). The sex-specific association of rs6742078 was confirmed in samples from South America (P(men) = .046; odds ratio(recessive), 2.19; P(women) = .96). The UGT1A1 Gilbert syndrome variant rs6742078 is associated with gallstone disease in men; further studies are required regarding the sex-specific physiology of bilirubin and bile acid metabolism. Variants of ABCG8 and UGT1A1 are the 2 major risk factors for overall gallstone disease, they contribute a population attributable risk of 21.2% among men.
    Gastroenterology 12/2010; 139(6):1942-1951.e2. DOI:10.1053/j.gastro.2010.09.003

Publication Stats

3k Citations
586.56 Total Impact Points

Institutions

  • 2007–2012
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
  • 2011
    • King Faisal Specialist Hospital and Research Centre
      • Department of Surgery
      Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia
    • Universität Bern
      • Department of Clinical Pharmacology and Visceral Research
      Bern, BE, Switzerland
  • 2008–2011
    • Christian-Albrechts-Universität zu Kiel
      Kiel, Schleswig-Holstein, Germany
    • Universitätsklinikum Schleswig - Holstein
      • Klinik für Allgemeine Pädiatrie (Kiel)
      Kiel, Schleswig-Holstein, Germany
  • 2009
    • Universitätsklinikum Freiburg
      Freiburg an der Elbe, Lower Saxony, Germany
  • 2000–2007
    • University Medical Center Hamburg - Eppendorf
      • • Department of Medical Psychology
      • • Department of Hepatobiliary and Transplant Surgery
      Hamburg, Hamburg, Germany
  • 1997–2005
    • University of Hamburg
      • • Department of Hepatobiliary and Transplant Surgery
      • • Department of General, Visceral and Thoracic Surgery Department and Clinic
      Hamburg, Hamburg, Germany