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World journal of Gastroenterology 2007年第45期13卷 6090-6093页

作者： Doris Schacherer Martina Zeitoun Roland Büttner Cornelia Gelbmann Aiman Obed hans-jürgen schlitt jürgen Schlmerich Gabi I Kirchner Department of Internal MedicineⅠ University of Regensburg Regensburg 93042 Germany Department of Surgery University of Regensburg Regensburg 93042 Germany

We describe the first case of sirolimus-induced drug fever in a female liver transplant recipient, with a history of hepatitis C-induced end-stage liver cirrhosis in 1999. In 2005, six years after transplantation, she developed calcineurin inhibitor-induced renal function impairment. Immunosuppression was switched from tacrolimus to sirolimus. Two days after the intake of sirolimus, she developed daily fever spikes, but no infectious focus was found. Antibiotic therapy had no influence on the fever. After fourteen days, sirolimus was switched back to tacrolimus and the fever disappeared. In history, the patient developed ciclosporin-induced generalized seizures eleven days after liver transplantation, followed by the development of a motoric speech disorder. Magnetic resonance imaging (MRI) findings were consistent with leucoencephalopathy, therefore immunosuppressive therapy was changed from ciclosporin to tacrolimus and the neurologic symptoms improved significantly. Our case is the first reported case of sirolimus-induced drug fever. In addition, the patient showed the rare occurrence of ciclosporin-induced leukencephalopathy with seizures.

关键词： Liver transplantation Immunosuppression Side effects

Liver surgery in cirrhosis and portal hypertension

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World journal of Gastroenterology 2016年第9期22卷 2725-2735页

作者： Christina Hackl hans j schlitt Philipp Renner Sven A Lang Department of Surgery University Medical Center Regensburg

The prevalence of hepatic cirrhosis in Europe and the United States, currently 250 patients per 100000 inhabitants, is steadily increasing. Thus, we observe a significant increase in patients with cirrhosis and portal hypertension needing liver resections for primary ormetastatic lesions. However, extended liver resections in patients with underlying hepatic cirrhosis and portal hypertension still represent a medical challenge in regard to perioperative morbidity, surgical management and postoperative outcome. The Barcelona Clinic Liver Cancer classification recommends to restrict curative liver resections for hepatocellular carcinoma in cirrhotic patients to early tumor stages in patients with Child A cirrhosis not showing portal hypertension. However, during the last two decades, relevant improvements in preoperative diagnostic, perioperative hepatologic and intensive care management as well as in surgical techniques during hepatic resections have rendered even extended liver resections in higher-degree cirrhotic patients with portal hypertension possible. However, there are few standard indications for hepatic resections in cirrhotic patients and risk stratifications have to be performed in an interdisciplinary setting for each individual patient. We here review the indications, the preoperative risk-stratifications, the morbidity and the mortality of extended resections for primary and metastatic lesions in cirrhotic livers. Furthermore, we provide a review of literature on perioperative management in cirrhotic patients needing extrahepatic abdominal surgery and an overview of surgical options in the treatment of hepatic cirrhosis.

关键词： Liver resection Hepatocellular carcinoma Liver metastases Portal hypertension Cholangiocellular carcinoma Cirrhosis

Liver transplantation for malignancy:current treatment strategies and future perspectives

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World journal of Gastroenterology 2014年第18期20卷 5331-5344页

作者： Christina Hackl hans j schlitt Gabriele I Kirchner Birgit Knoppke Martin Loss Department of Surgery University Hospital Regensburg93053 RegensburgGermany Department of Internal Medicine I University Hospital Regensburg93053 RegensburgGermany Department of Pediatrics and juvenile Medicine University Hospital Regensburg93053 RegensburgGermany

In 1967,Starzl et al performed the first successful liver transplantation for a patient diagnosed with *** the following,liver transplantation was considered ideal for complete tumor resection and potential cure from primary hepatic *** reports of liver transplantation for primary and metastatic liver cancer however showed disappointing results and the strategy was soon ***1996,Mazzaferro et al introduced the Milan criteria,offering liver transplantation to patients diagnosed with limited hepatocellular *** then,liver transplantation for malignant disease is an ongoing subject of preclinical and clinical *** this context,several aspects must be considered:(1)Given the shortage of deceased-donor organs,long-term overall and disease free survival should be comparable with results obtained in patients transplanted for nonmalignant disease;(2)In this regard,living-donor liver transplantation may in selected patients help to solve the ethical dilemma of optimal individual patient treatment vs organ allocation justice;and(3)Ongoing research focusing on perioperative therapy and antiproliferative immunosuppressive regimens may further reduce tumor recurrence in patients transplanted for malignant disease and thus improve overall *** present review gives an overview of current indications and future perspectives of liver transplantation for malignant disease.

关键词： Hepatocellular Fibrolamellar Carcinoma Cholangiocellular Hepatoblastoma Liver metastases

Ileo-right hemi-colonic cervical pull-up on a non-supercharged ileocolic arterial pedicle: A technical and case report

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World journal of Gastroenterology 2016年第14期22卷 3869-3874页

作者： Andreas RR Weiss Christina Hackl Yorick Soeder hans j schlitt Marc-H Dahlke Department of Surgery University Medical Center Regensburg

Esophageal reconstruction can be challenging when stomach and colon are not anatomically intact and their use as esophageal substitutes is therefore limited. Innovative individual approaches are then necessary to restore the intestinal passage. We describe a technique in which a short stump of the right hemicolon and 25 cm of ileum on a long, non-supercharged, fully mobilized ileocolic arterial pedicle were used for esophageal reconstruction to the neck. In this case, a 65 year-old male patient had accidentally indigested hydrochloric acid which caused necrosis of his upper digestive tract. An emergency esophagectomy, gastrectomy, duodenectomy, pancreatectomy and splenectomy had been performed in an outside hospital. A cervical esophagostomy and a biliodigestive anastomosis had been created and a jejunal catheter for enteral feeding had been placed. After the patient had recovered, a reconstruction of his food passage via the left and transverse colon failed for technical reasons due to an intraoperative necrotic demarcation of the colon. Our team then faced the situation that only a short stump of the right hemi-colon was left in situ when the patient was referred to our center. After intensified nutritional therapy, we reconstructed this patient's food passage with the right hemicolonapproach described herein. After treatment of a postoperative pneumonia, the patient was discharged from hospital on the 26 th postoperative day in a good clinical condition on an oral-only diet. In conclusion, individual approaches for long-segment reconstruction of the esophagus can be technically feasible in experienced hands. They do not always require arterial supercharging or free intestinal transplantation.

关键词： Esophageal cancer Esophageal trauma Esophageal reconstruction Gastric pull-up Colonic interposition

Split liver transplantation: Current developments

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World journal of Gastroenterology 2018年第47期24卷 5312-5321页

作者： Christina Hackl Katharina M Schmidt Caner Süsal Bernd Dohler Martin Zidek hans j schlitt Department of Surgery University Hospital RegensburgRegensburg 93053Germany Collaborative Transplant Study (CTS) Institute of ImmunologyHeidelberg UniversityHeidelberg 69120Germany

In 1988, Rudolf Pichlmayr pioneered split liver transplantation(SLT), enabling the transplantation of one donor liver into two recipients-one pediatric and one adult patient. In the same year, Henri Bismuth and colleagues performed the first full right/full left split procedure with two adult recipients. Both splitting techniques were rapidly adopted within the transplant community. However, a SLT is technically demanding, may cause increased perioperative complications, and may potentially transform an excellent deceased donor organ into two marginal quality grafts. Thus, crucial evaluation of donor organs suitable for splitting and careful screening of potential SLT recipients is warranted. Furthermore, the logistic background of the splitting procedure as well as the organ allocation policy must be adapted to further increase the number and the safety of SLT. Under defined circumstances, in selected patients and at experienced transplant centers, SLT outcomes can be similar to those obtained in full organ LT. Thus, SLT is an important tool to reduce the donor organ shortage and waitlist mortality, especially for pediatric patients and small adults. The present review gives an overview of technical aspects, current developments, and clinical outcomes of SLT.

关键词： Liver transplantation organ shortage in situ split extended right lobe left lateral lobe living donor

Current developments in pediatric liver transplantation

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World journal of Hepatology 2015年第11期7卷 1509-1520页

作者： Christina Hackl hans j schlitt Martin Loss Birgit Knoppke Michael Melter Department of Surgery University Hospital Regensburg KUNO-Children’s University Hospital Regensburg

In 1953, the pioneer of human orthotopic liver transplantation(LT), Thomas E Starzl, was the first to attempt an orthotopic liver transplant into a 3 years old patient suffering from biliary atresia. Thus, the first LT in humans was attempted in a disease, which, up until today, remains the main indication for pediatric LT(p LT). During the last sixty years, refinements in diagnostics and surgical technique, the introduction of new immunosuppressive medications and improvements in perioperative pediatric care have established LT as routine procedure for childhood acute and chronic liver failure as well as inherited liver diseases. In contrast to adult recipients, p LT differs greatly in indications for LT, allocation practice, surgical technique, immunosuppression and postoperative life-long aftercare. Many aspects are focus of ongoing preclinical and clinical research. The present review gives an overview of current developments and the clinical outcome of p LT, with a focus on alternatives to full-size deceased-donor organ transplantation.

关键词： Pediatric liver transplantation Deceasedorgan donation Living donor liver transplantation Splitliver transplantation Biliary atresia

Therapeutic options for peritoneal metastasis arising from colorectal cancer

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World journal of Gastrointestinal Pharmacology and Therapeutics 2016年第3期7卷 343-352页

作者： Gabriel Glockzin hans j schlitt Pompiliu Piso Department of Surgery Staedtisches Klinikum Muenchen GmbH Department of Surgery University Hospital Regensburg Department of Surgery Hospital of the Order of St. John of God

Peritoneal metastasis is a common sign of advanced tumor stage, tumor progression or tumor recurrence in patients with colorectal cancer. Due to the improvement of systemic chemotherapy, the development of targeted therapy and the introduction of additive treatment options such as cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC), the therapeutic approach to peritoneal metastatic colorectal cancer(pm CRC) has changed over recent decades, and patient survival has improved. Moreover, in contrast to palliative systemic chemotherapy or best supportive care, the inclusion of CRS and HIPEC as inherent components of a multidisciplinary treatment regimen provides a therapeutic approach with curative intent. Although CRS and HIPEC are increasingly accepted as the standard of care for selected patients and have become part of numerous national and international guidelines, the individual role, optimal timing and ideal sequence of the different systemic, local and surgical treatment options remains a matter of debate. Ongoing and future randomized controlled clinical trials may help clarify the impact of the different components, allow for further improvement of patient selection and support the standar-dization of oncologic treatment regimens for pm CRC. The addition of further therapeutic options such as neo-adjuvant intraperitoneal chemotherapy or pressurized intraperitoneal aerosol chemotherapy, should be investig-ated to optimize therapeutic regimens and further improve the oncological outcome.

关键词： Peritoneal metastasis Colorectal cancer Systemic chemotherapy Intraperitoneal chemotherapy Cytoreductive surgery

Patients without hepatocellular carcinoma progression after transarterial chemoembolization benefit from liver transplantation

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World journal of Gastroenterology 2007年第5期13卷 761-767页

作者： Aiman Obed Alexander Beham Kerstin Püllmann Heinz Becker hans j schlitt Thomas Lorf Department of Surgery University of Regensburg Regensburg 93053Germany 不详 Department of Surgery University of Goettingen Goettingen 37073 Germany

AIM： To assess the outcome of patients, who underwent transarterial chemoembolization （TACE） for hepatocellular carcinoma （HCC） and subsequently liver transplantation （OLT） irrespective of tumor size when no tumor progression was observed. METHODS： Records, imaging studies and pathology of 84 patients with HCC were reviewed. Ten patients were not treated at all, 67 patients had TACE and 35 of them were listed for OLT. Tumor progression was monitored by ultrasound and AFP level every 6 wk. Fifteen patients showed signs of tumor progression without transplantation. The remaining 20 patients underwent OLT. Further records of 7 patients with HCC seen in histological examination after OLT were included. RESULTS： The patients after TACE without tumor progression underwent transplantation and had a median survival of 92.3 too. Patients, who did not qualify for liver transplantation or had signs of tumor progression had a median survival of 8.4 mo. The patients without treatment had a median survival of 3.8 mo. Independent of International Union Against Cancer （UICC） stages, the patients without tumor progression and subsequent OLT had longer median survival. No significant difference was seen in the OLT treated patients if they did not fulfill the Milan criteria. CONCLUSION： Selection of patients for OLT based on tumor progression results in good survival. The evaluation of HCC patients should not only be based on tumor size and number of foci but also on tumor progression and growth behavior under therapy.

关键词： Liver transplantation Hepatocellularcarcinoma

Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the progression of micronodular cirrhosis in rats

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World journal of Gastroenterology 2006年第13期12卷 2016-2023页

作者： Tung-Yu Tsui Chi-Keung Lau jian Ma Gabriel Glockzin Aiman Obed hans j schlitt Sheung-Tat Fan Centre for the Study of Liver Disease and Department of Surgery the University of Hong Kong Pokfulam Hong Kong Department of Surgery University of Regensburg Medical Centre Regensburg Germany

AIM： To test the hypothesis that enhancement of the activity of heine oxygenase can interfere with processes of fibrogenesis associated with recurrent liver injury, we investigated the therapeutic potential of over-expression of heine oxygense-1 in a CCl4-induced micronodular cirrhosis model. METHODS： Recombinant adeno-associated viruses carrying rat HO-1 or GFP gene were generated, 1×10^12 vg of adeno-associated viruses were administered through portal injection at the time of the induction of liver fibrosis. RESULTS： Conditioning the rat liver with over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic activities in a stable manner. The development of micronodular cirrhosis was significantly inhibited in rAAV/HO-1-transduced animals as compared to controls. Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as compared to controls, whereas there are no significant changes in systolic blood pressure. This finding was accompanied with improved liver biochemistry, less infiltrating macrophages and less activated hepatic stellate cells （HSCs） in rAAV/ HO-1-transduced livers. CONCLUSIONS： Enhancement of HO activity in the livers suppresses the development of cirrhosis.

关键词： Cirrhosis Portal hypertension Heme oxygenase Gene therapy Adeno-associated virus

5-Fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-adenovirus receptor independent and associated with morphological changes in lipid membranes

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World journal of Gastroenterology 2006年第32期12卷 5168-5174页

作者： Chiara Cabrele Mandy Vogel Pompiliu Piso Markus Rentsch josef Schroder Karl W jauch hans j schlitt Alexander Beham Department of Surgery Clinic of the Regensburg University Franz-Josef-Strauss-Allee 11D-93053RegensburgGermany

AIM： To evaluate the mechanism underlying the effects of 5-Fluorouracil （5-FU） on adenoviral infection. METHODS： Low and high Coxsackievirus-Adenovirus Receptor （CAR） expressing human colon carcinoma cell lines were treated with 5-FU and two El-deleted adenoviral constructs, one transferring GFP （Ad/CMV- GFP） the other bax （Ad/CEA-bax）. The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU. RESULTS： Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU- treated liposomes appeared irregular and porous-like. CONCLUSION： adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy.

关键词： 5-Fluorouracil Coxsackievirus-adenovirusreceptor Adenoviral infection Gene therapy