Hepatic artery pseudoaneurysm with hemobilia following angioplasty after liver transplantation.

PubMed

Narumi, S; Osorio, R W; Freise, C E; Stock, P G; Roberts, J P; Ascher, N L

1998-12-01

A 58-yr-old female with primary biliary cirrhosis underwent an uncomplicated orthotopic liver transplantation. Elevated liver function tests 2 months post-transplantation were evaluated with Doppler ultrasound and a hepatic artery stricture was documented. The hepatic artery stenosis was treated with angioplasty. She developed hemobilia 1 d after the procedure, which was confirmed by angiography. Emergent exploratory laparotomy revealed a pseudoaneurysm at the hepatic artery anastomosis. The pseudoaneurysm was resected and the proper hepatic artery of the graft was anastomosed to the splenic artery of the host using preserved homograft. Her post-operative course was uneventful and liver function tests returned to normal quickly after the surgery. This report will discuss the unusual nature of this complication, and review the problem of hemobilia and pseudoaneurysms in liver transplant recipients.

Parvovirus B19 induced hepatic failure in an adult requiring liver transplantation

PubMed Central

Krygier, Darin S; Steinbrecher, Urs P; Petric, Martin; Erb, Siegfried R; Chung, Stephen W; Scudamore, Charles H; Buczkowski, Andrzej K; Yoshida, Eric M

2009-01-01

Parvovirus B19 induced acute hepatitis and hepatic failure have been previously reported, mainly in children. Very few cases of parvovirus induced hepatic failure have been reported in adults and fewer still have required liver transplantation. We report the case of a 55-year-old immunocompetent woman who developed fulminant hepatic failure after acute infection with Parvovirus B19 who subsequently underwent orthotopic liver transplantation. This is believed to be the first reported case in the literature in which an adult patient with fulminant hepatic failure associated with acute parvovirus B19 infection and without hematologic abnormalities has been identified prior to undergoing liver transplantation. This case suggests that Parvovirus B19 induced liver disease can affect adults, can occur in the absence of hematologic abnormalities and can be severe enough to require liver transplantation. PMID:19705505

Role of Doppler Sonography in Early Detection of Splenic Steal Syndrome.

PubMed

Li, Chaolun; Quintini, Cristiano; Hashimoto, Koji; Fung, John; Obuchowski, Nancy A; Sands, Mark J; Wang, Weiping

2016-07-01

To retrospectively investigate the role of Doppler sonography in the early detection of splenic steal syndrome. Fifty cases of splenic steal syndrome after orthotopic liver transplantation were identified. A control group was matched to the splenic steal syndrome group. Information was collected about the clinical presentation, liver enzyme levels, Doppler sonographic results, and follow-up after patients underwent splenic artery embolization. A persistent hepatic arterial diastolic reversal waveform was observed in 25 patients with splenic steal syndrome versus 0 control patients. The mean hepatic arterial resistive index (RI) values ± SD were 0.95 ± 0.09 in patients with splenic steal syndrome and 0.80 ± 0.10 in control patients (P < .0001). One week after orthotopic liver transplantation, the area under the receiver operating characteristic curve for the RI was 0.884 (95% confidence interval, 0.793-0.975; P = .001) for splenic steal syndrome diagnosis. After splenic artery embolization, there was normalization of the reversal waveform, with an average RI of 0.77 ± 0.11 (P < .0001). Dynamic changes in the hepatic arterial waveform and RI are keys to detecting splenic steal syndrome with Doppler sonography.

A point-based prediction model for cardiovascular risk in orthotopic liver transplantation: The CAR-OLT score.

PubMed

VanWagner, Lisa B; Ning, Hongyan; Whitsett, Maureen; Levitsky, Josh; Uttal, Sarah; Wilkins, John T; Abecassis, Michael M; Ladner, Daniela P; Skaro, Anton I; Lloyd-Jones, Donald M

2017-12-01

Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979). © 2017 by the American Association for the Study of Liver Diseases.

Papillary bile duct dysplasia in primary sclerosing cholangitis.

PubMed

Ludwig, J; Wahlstrom, H E; Batts, K P; Wiesner, R H

1992-06-01

A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9-year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC.

Usefulness for Predicting Cardiac Events After Orthotopic Liver Transplantation of Myocardial Perfusion Imaging and Dobutamine Stress Echocardiography Preoperatively.

PubMed

Snipelisky, David; Ray, Jordan; Vallabhajosyula, Saraschandra; Matcha, Gautam; Squier, Samuel; Lewis, Jacob; Holliday, Rex; Aggarwal, Niti; Askew, J Wells; Shapiro, Brian; Anavekar, Nandan

2017-04-01

Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation.

PubMed

Andreoli, Maria Claudia Cruz; Souza, Nádia Karina Guimarães de; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Coelho, Maria Paula Vilela; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; Almeida, Marcio Dias de; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; Santos, Oscar Pavão Dos; Santos, Bento Cardoso Dos

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27-39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery.

Predictors of renal function recovery among patients undergoing renal replacement therapy following orthotopic liver transplantation

PubMed Central

de Souza, Nádia Karina Guimarães; Ammirati, Adriano Luiz; Matsui, Thais Nemoto; Carneiro, Fabiana Dias; Ramos, Ana Claudia Mallet de Souza; Iizuca, Ilson Jorge; Afonso, Rogério Carballo; Ferraz-Neto, Ben-Hur; de Almeida, Marcio Dias; Durão, Marcelino; Batista, Marcelo Costa; Monte, Julio Cesar; Pereira, Virgílio Gonçalves; dos Santos, Oscar Pavão

2017-01-01

Renal dysfunction frequently occurs during the periods preceding and following orthotopic liver transplantation (OLT), and in many cases, renal replacement therapy (RRT) is required. Information regarding the duration of RRT and the rate of kidney function recovery after OLT is crucial for transplant program management. We evaluated a sample of 155 stable patients undergoing post-intensive care hemodialysis (HD) from a patient population of 908 adults who underwent OLT. We investigated the average time to renal function recovery (duration of RRT required) and determined the risk factors for remaining on dialysis > 90 days after OLT. Log-rank tests were used for univariate analysis, and Cox proportional hazards models were used to identify factors associated with the risk of remaining on HD. The results of our analysis showed that of the 155 patients, 28% had pre-OLT diabetes mellitus, 21% had pre-OLT hypertension, and 40% had viral hepatitis. Among the patients, the median MELD (Model for End-Stage Liver Disease) score was 27 (interquartile range [IQR] 22-35). When they were listed for liver transplantation, 32% of the patients had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD, and 50% had serum creatinine (Scr) levels > 1.5 mg/dL or were on HD at the time of OLT. Of the transplanted patients, 25% underwent pre-OLT intermittent HD, and 14% and 41% underwent continuous renal replacement therapy (CRRT) pre-OLT and post-OLT, respectively. At 90 days post-OLT, 118 (76%) patients had been taken off dialysis, and 16 (10%) patients had died while undergoing HD. The median recovery time of these post-OLT patients was 33 (IQR 27–39) days. In the multivariate analysis, fulminant hepatic failure as the cause of liver disease (p<0.001), the absence of pre-OLT hypertension (p = 0.016), a lower intraoperative fresh-frozen plasma (FFP) transfusion volume (p = 0.019) and not undergoing pre-OLT intermittent HD (p = 0.032) were associated with performing RRT for less than 90 days. Therefore, a high proportion of OLT patients showed improved renal function after OLT, and those who were diagnosed with fulminant hepatic failure, had no pre-OLT hypertension, received a lower transfused volume of intraoperative FFP and did not undergo pre-OLT intermittent HD had a higher probability of recovery. PMID:28574999

Liver transplantation: history, outcomes and perspectives

PubMed Central

Meirelles, Roberto Ferreira; Salvalaggio, Paolo; de Rezende, Marcelo Bruno; Evangelista, Andréia Silva; Guardia, Bianca Della; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Pedroso, Pamella Tung; Rocco, Rodrigo Andrey; Meira, Sérgio Paiva

2015-01-01

In 1958 Francis Moore described the orthotopic liver transplantation technique in dogs. In 1963, Starzl et al. performed the first liver transplantation. In the first five liver transplantations no patient survived more than 23 days. In 1967, stimulated by Calne who used antilymphocytic serum, Starzl began a successful series of liver transplantation. Until 1977, 200 liver transplantations were performed in the world. In that period, technical problems were overcome. Roy Calne, in 1979, used the first time cyclosporine in two patients who had undergone liver transplantation. In 1989, Starzl et al. reported a series of 1,179 consecutives patients who underwent liver transplantation and reported a survival rate between one and five years of 73% and 64%, respectively. Finally, in 1990, Starzl et al. reported successful use of tacrolimus in patents undergoing liver transplantation and who had rejection despite receiving conventional immunosuppressive treatment. Liver Transplantation Program was initiated at Hospital Israelita Albert Einstein in 1990 and so far over 1,400 transplants have been done. In 2013, 102 deceased donors liver transplantations were performed. The main indications for transplantation were hepatocellular carcinoma (38%), hepatitis C virus (33.3%) and alcohol liver cirrhosis (19.6%). Of these, 36% of patients who underwent transplantation showed biological MELD score > 30. Patient and graft survival in the first year was, 82.4% and 74.8%, respectively. A major challenge in liver transplantation field is the insufficient number of donors compared with the growing demand of transplant candidates. Thus, we emphasize that appropriated donor/receptor selection, allocation and organ preservation topics should contribute to improve the number and outcomes in liver transplantation. PMID:25993082

Infections After Orthotopic Liver Transplantation

PubMed Central

Pedersen, Mark; Seetharam, Anil

2014-01-01

Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management. PMID:25755581

Symptomatic osteonecrosis of the femoral head after adult orthotopic liver transplantation.

PubMed

Li, Hua; Zhang, Jian; He, Ji-Wen; Wang, Kun; Wang, Gen-Shu; Jiang, Nan; Fu, Bin-Sheng; Wang, Guo-Ying; Yang, Yang; Chen, Gui-Hua

2012-07-01

With the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China. A retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported. The incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up. The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

PubMed

Colavecchia, A Carmine; Cohen, David A; Harris, Jesse E; Thomas, Jeena M; Lindberg, Scott; Leveque, Christopher; Salazar, Eric

2017-12-01

Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization. This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias. During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively). The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation did not reduce intraoperative blood product requirements at a single institution. © 2017 AABB.

[Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma].

PubMed

Wu, You-min; Johlin, Frederick C; Rayhill, Stephen C; Jensen, Chris S; Jin, Xie; Mitros, Frank A

2009-08-01

To report the experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. Between January 1988 and February 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 were well without recurrence at 79, 82, 108, 128, 129 and 145 months. For patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging.

PubMed

Murakami, Takashi; Zhang, Yong; Wang, Xiaoen; Hiroshima, Yukihiko; Kasashima, Hiroaki; Yashiro, Masakazu; Hirakawa, Kosei; Miwa, Atsushi; Kiyuna, Tasuku; Matsuyama, Ryusei; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2016-05-01

Orthotopic (literally "correct place") implantation of cancer in nude mice has long been known to be superior to subcutaneous transplantation because the orthotopic tumor can metastasize. We reported previously on surgical orthotopic implantation (SOI) of gastric cancer tissue in nude mice resulting in the formation of metastases in 100% of the mice with extensive primary growth to the regional lymph nodes, liver, and lung. In contrast, when cell suspensions were used to inject gastric cancer cells orthotopically, metastases occurred in only 6.7% of the mice with local tumor formation, emphasizing the importance of orthotopically implanting intact tissue to allow full expression of metastatic potential. However, the different behavior of tumors implanted orthotopically by the two methods has not been visualized in real time. OCUM-2MD3 human gastric cancer cells labeled with the fluorescent protein Azami-Green were implanted orthotopically as cells or tissue in nude mice. Orthotopic implantation of cells resulted in local spread on the stomach. In contrast, SOI of tumor tissue of OCUM-2MD3 resulted in vessel spread of the Azami-Green-expressing cancer cells. Metastasis was also observed in the left lobe of the liver after SOI. These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Vincristine and irinotecan in children with relapsed hepatoblastoma: a single-institution experience.

PubMed

Zhang, Yu-tong; Feng, Li-hua; Zhong, Xiao-dan; Wang, Li-zhe; Chang, Jian

2015-02-01

This study was to determine the efficacy of vincristine and irinotecan in children with relapsed hepatoblastoma (HB). A total of 10 patients with relapsed HB were enrolled. Three patients were excluded. Patients received irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1, repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was performed every two cycles. The primary outcome was the rate of complete resection. Secondary outcomes were event-free survival (EFS) and overall survival (OS). Of the seven patients assessable for response, one patient with normal AFP level showed a progressive disease and withdrew. He finally died 6 months later. Four had PR, all of them underwent a second surgery and achieved complete resection. Two patients had SD, one patient relapsed 6 months after orthotopic liver transplantation and died, the other one undergoing surgery had micro margin positive, he relapsed again but alive. The rate of complete resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI, 16.39% to 37.4%), respectively. The combination of irinotecan and vincristine has a significant antitumor activity and acceptable toxicity in children with relapsed HB.

Early Spontaneous Graft Intra- and Perihepatic Hematoma after Liver Transplantation.

PubMed

Lupaşcu, Cristian; Apopei, Oana; Vlad, Nutu; Vasiluta, Ciprian; Trofin, Ana-Maria; Zabara, Mihai; Vornicu, Alexandra; Lupaşcu-Ursulescu, Corina; Nitu, Mioara; Crumpei, Felicia; Braşoveanu, Vladislav; Popescu, Irinel

2017-01-01

Hematoma of the graft is a life threatening complication of liver transplantation (LT) and there has been no overt conclusion in the literature about optimal management except in scarcely reported cases. It may be either intrahepatic or subcapsular, then again it may develop spontaneously or following parenchimal injuries or transhepatic percutaneous invasive manoeuvers. In this report we describe a rare case of large spontaneous graft intra- and perihepatic hematoma. A 62 year-old man underwent a whole graft orthotopic liver transplantation (OLT) for decompensated chronic liver disease due to alcoholic cirrhosis. The surgical procedure was uneventful. During the early postoperative course, routine Doppler ultrasound examination and CT-scan revealed an extrahepatic paracaval hematoma, 7 days after transplantation, which was stable and conservatively managed until the 18-th postoperative day, when rapidly expanding intraparenchimal hematoma involving the right hemiliver, several other perihepatic hematomas, significant right pleural effusion and hemorrhagic ascites were described. The patient was successfully treated conservatively (nonsurgically) with slow recovery of the liver allograft and discharged one month later in good general status. Celsius.

Liver transplantation in Greek children: 15 years experience

PubMed Central

Xinias, Ioannis; Mavroudi, Antigoni; Vrani, Olga; Imvrios, Georgios; Takoudas, Dimitrios; Spiroglou, Kleomenis

2010-01-01

Liver transplantation (LT) is the only available live-saving procedure for children with irreversible liver failure. This paper reports our experience from the follow-up of 16 Greek children with end-stage liver failure who underwent a LT. Over a period of 15 years, 16 pediatric liver recipients received follow up after being subjected to OLT (orthotopic liver transplantation) due to end-stage liver failure. Nine children initially presented with extrahepatic biliary atresia, 2 with acute liver failure after toxic mushroom ingestion, 2 with intrahepatic cholestasis, 2 with metabolic diseases and one with hepatoblastoma. Ten children received a liver transplant in the Organ Transplantation Unit of Aristotle University of Thessaloniki and the rest in other transplant centers. Three transplants came from a living-related donor and 13 from a deceased donor. Six children underwent immunosuppressive treatment with cyclosporine, mycophenolate mofetil and corticosteroids, and 7 with tacrolimus, mycophenolate mofetil and corticosteroids. Three out of 16 children died within the first month after the transplantation due to post-transplant complications. Three children presented with acute rejection and one with chronic organ rejection which was successfully managed. Five children presented with cytomegalovirus infection, 5 with Epstein-Barr virus, 2 with HSV1,2, 2 with ParvoB19 virus, 2 with varicella-zoster virus and one with C. Albicans infection. One child presented with upper gastrointestinal hemorrhage and one with small biliary paucity. A satisfying outcome was achieved in most cases, with good graft function, except for the patient with small biliary paucity who required re-transplantation. The long-term clinical course of liver transplanted children is good under the condition that they are attended in specialized centers. PMID:21589827

Marked elevation of hepatic transaminases in recipients of an orthotopic liver transplant from a brain-dead donor receiving extracorporeal membrane oxygenation.

PubMed

Teng-Wei, Chen; Chung-Bao, Hsieh; Chan, De-Chuan; Yu, Jyh-Cherng; Kuo, Shih-Ming; Tsai, Chien-Sung; Fan, Hsiu-Lung

2014-12-29

Hemodynamic instability can lead to failure of donor organ procurement in brain-dead donors. Extracorporeal membrane oxygenation (ECMO) has been used in non-heart-beating donors to increase the donor pool, but the use of ECMO to salvage donor organs has been rarely used. We aimed to analyze postoperative liver function test results in patients receiving orthotopic liver transplants from ECMO-supported brain-dead donors. We retrospectively reviewed the records of 43 recipients of orthotopic liver transplantation from May 2009 to June 2012. Six recipients received liver grafts from ECMO-maintained donors designated as the ECMO group (n=6). The remaining patients were assigned to the non-ECMO group (n=37). Complication and mortality rates and liver function test results on postoperative days 1, 3, 5, 7, and 14 were compared between the 2 groups. Serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase levels were significantly elevated on postoperative Day 1 in the ECMO group. There were no significant differences in the complication and overall survival rates between the 2 groups (P=0.411). Although serum transaminases markedly elevated on postoperative Day 1, ECMO successfully preserved potential liver grafts in hemodynamically unstable brain-dead donors.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation

PubMed Central

Zanaga, L.P.; Vigani, A.G.; Angerami, R.N.; Giorgetti, A.; Escanhoela, C.A.F.; Ataíde, E.C.; Boin, I.F.S.F.; Stucchi, R.S.B.

2017-01-01

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death. PMID:28076451

Left Lobe Auxiliary Liver Transplantation for End-stage Hepatitis B Liver Cirrhosis.

PubMed

Wang, S-F; Chen, X-P; Chen, Z-S; Wei, L; Dong, S-L; Guo, H; Jiang, J-P; Teng, W-H; Huang, Z-Y; Zhang, W-G

2017-06-01

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. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Percutaneous Transluminal Angioplasty of Hepatic Artery Stenosis in Patients After Orthotopic Liver Transplantation: Mid-term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarmila, Lastovickova, E-mail: jala@ikem.cz; Jan, Peregrin

2011-12-15

Purpose: This study was designed to present our experience with percutaneous treatment of hepatic artery stenosis in orthotopic liver transplant patients and to evaluate the efficacy, technical outcomes, and mid-term clinical results of the procedure. Methods: Twenty-two percutaneous transluminal angioplasties (PTAs) were performed in 19 liver transplant recipients at our institution between 1998 and 2010. Stents were placed into the hepatic/celiac artery in 16 PTAs, but balloon dilatation alone was performed in 6 because of the anatomical condition of the vessel. PTA/stenting was indicated in 17 patients because of elevated liver enzymes; 2 patients were asymptomatic. The objective of treatingmore » stenosis was prevention of long-term complications, including thrombosis. Results: Technical success was achieved in all patients. There was only one complication: dissection of the treated artery without any subsequent adverse effects. In all patients, elevated liver enzyme levels improved after treatment. No restenosis was observed in any patient during a mean follow-up of 2.6 years (1 month to 5.5 years). Conclusions: Percutaneous angioplasty/stent placement is a safe method for the treatment of hepatic artery stenosis after orthotopic liver transplantation, with a high technical success rate and promising mid-term results.« less

Liver Stiffness Measurements Using Acoustic Radiation Force Impulse in Recipients of Living-Donor and Deceased-Donor Orthotopic Liver Transplant.

PubMed

Haberal, Kemal Murat; Turnaoğlu, Hale; Özdemir, Adnan; Uslu, Nihal; Haberal Reyhan, Asuman Nihan; Moray, Gökhan; Haberal, Mehmet

2017-08-24

The aim of this study was to evaluate the diagnostic efficiency of the acoustic radiation force impulse (Siemens Medical Solutions, Erlangen, Germany) elastography in assessment of fibrosis in orthotopic liver transplant patients. We enrolled 28 orthotopic liver transplant patients (deceased and living donors), whose biopsy decision had been prospectively given clinically. Ten acoustic radiation force impulse elastographic measurements were applied before the biopsy or within 3 days after the biopsy by 2 radiologists. After the core tissue needle biopsy, specimens of all patients were analyzed according to the modified Ishak scoring system. Measurements of acoustic radiation force impulse elastography and pathology specimen results were compared. From 28 biopsies, fibrosis scores of 4 biopsies were evaluated as F0 (14.3%), 16 as F1 (57.1%), 4 as F2 (14.3%), and 4 as F3 (14.3%). Mean results of acoustic radiation force impulse measurements were calculated as 1.4 ± 0.07 in F0, 1.74 ± 0.57 in F1, 2.19 ± 0.7 in F2, and 2.18 ± 0.35 in F3. There were no significant correlations of mean acoustic radiation force impulse values between the F0 versus F1 (P = .956) and F0 versus F2 stages (P = .234). A statistically significant correlation of mean acoustic radiation force impulse values was found between the F0 and F3 fibrosis stages (P = .046). Acoustic radiation force impulse imaging is a promising screening test for detecting significant liver fibrosis (≥ F3 in modified Ishak) in living-donor or deceased-donor orthotopic liver transplant recipients.

Orthotopic Liver Transplantation for Urea Cycle Enzyme Deficiency

PubMed Central

Todo, Satoru; Starzl, Thomas E.; Tzakis, Andreas; Benkov, Keith J.; Kalousek, Frantisek; Saheki, Takeyori; Tanikawa, Kyuichi; Fenton, Wayne A.

2010-01-01

Hyperammonemia, abnormalities in plasma amino acids and abnormalities of standard liver functions were corrected by orthotopic liver transplantation in a 14-day-old boy with carbamyl phosphate synthetase-I deficiency and in a 35-yr-old man with argininosuccinic acid synthetase deficiency. The first patient had high plasma glutamine levels and no measureable citrulline, whereas citrulline values were markedly increased in Patient 2. Enzyme analysis of the original livers showed undetectable activity of carbamyl phosphate synthetase-I in Patient 1 and arginosuccinic acid synthetase in Patient 2. Both patients were comatose before surgery. Intellectual recovery of patient 1 has been slightly retarded because of a brain abscess caused by Aspergillus infection after surgery. Both patients are well at 34 and 40 mo, respectively, after surgery. Our experience has shown that orthotopic liver transplantation corrects the life-threatening metabolic abnormalities caused by deficiencies in the urea cycle enzymes carbamyl phosphate synthetase-I and arginosuccinic acid synthetase. Seven other patients–six with ornithine transcarbamylase deficiency and another with carbamyl phosphate synthetase-I deficiency–are known to have been treated elsewhere with liver transplantation 1½ yr or longer ago. Four of these seven recipients also are well, with follow-ups of 1½ to 5 yr. Thus liver transplantation corrects the metabolic abnormalities of three of the six urea cycle enzyme deficiencies, and presumably would correct all. PMID:1544622

Infections Complicating Orthotopic Liver Transplantation

PubMed Central

Schröter, Gerhard P. J.; Hoelscher, Manfred; Putnam, Charles W.; Porter, Kendrick A.; Hansbrough, John F.; Starzl, Thomas E.

2011-01-01

In 93 recipients of 102 orthotopic liver homografts, the incidence of bacteremia or fungemia exceeded 70%. The graft itself was usually an entry site for systemic infection after both immunologic and nonimmunologic parenchymal injury, especially if there was defective biliary drainage. The role of the homograft itself as the special infectious risk factor has prompted increased use of defunctionalized jejunal Roux limbs to reduce graft contamination. It has also stimulated very aggressive postoperative diagnostic efforts to rule out remedial mechanical complications of the transplant. PMID:793568

Diagnostic Value of Anti-Hepatitis C Virus (HCV) Core Immunoglobulin M in Recurrence of HCV Infection after Orthotopic Liver Transplantation†

PubMed Central

Casino, Carmela; Lilli, Daniela; Rivanera, Daniela; Comanducci, Antonella; Rossi, Massimo; Casciaro, Giovanni; Pecorella, Irene; Alfani, Dario; Mancini, Carlo

1999-01-01

The significance of anti-hepatitis C virus (HCV) core immunoglobulin M (IgM) and its relationship with genotypes, alanine aminotransferase abnormality, and histological data were studied for 18 patients who had undergone orthotopic liver transplantation due to HCV-related end-stage disease. During follow-up, IgM response seemed to be associated with the recurrence of HCV infection but did not correlate with abnormal alanine aminotransferase levels and histological data. In addition, the results of this study indicated that the detection of HCV RNA is critical for diagnosis of reinfection in liver transplantation. PMID:10405433

"Passing loop" technique: a new modification of the piggyback technique tailored to voluminous liver grafts--case report.

PubMed

Eldeen, F Z; Lee, C-F; Lee, C-S; Chan, K-M; Lee, W-C

2013-03-01

The modified piggyback technique with side-to-side cavocavostomy decreases the risk of outflow obstruction compared with the standard piggyback method. However, this modification is not ideal for recipients who receive a graft that is voluminous or bears an enlarged caudate lobe. We modified the inferior vena cava (IVC) preservation technique against deleterious complications of compression by using a passing loop. A 49-year-old woman, who underwent orthotopic liver transplantation for hepatic failure, was allocated a large-size liver. In anticipation of serious caval compression due to the voluminous grafts, we kept the suprahepatic or infrahepatic donor caval cuffs open for an anastomosis. The first anastomosis was performed between suprahepatic donor IVC cuff and recipient middle-left hepatic vein common channel; the second anastomosis was a terminolateral cavocavostomy between infrahepatic donor IVC cuff and the anterior wall of the recipient's IVC. When the liver circulation was restored, the donor retrohepatic vena cava served as a passing loop for both hepatic venous outflow and infra-diaphragmatic venous return to bypass possible IVC compression. Our technique may solve a dilemna for patients receiving voluminous liver grafts. Copyright © 2013 Elsevier Inc. All rights reserved.

Salvage with a Secondary Infrahepatic Cavocavostomy of the Occluded Modified Piggyback Anastomosis during Split Liver Transplantation: A Case Report.

PubMed

Kinaci, Erdem; Kayaalp, Cuneyt; Yilmaz, Sezai; Otan, Emrah

2014-01-01

Hepatic venous outflow obstruction following liver transplantation is rare but disastrous. Here we described a 14-year-old boy who underwent a split right lobe liver transplantation with modified (side-to-side) piggyback technique which resulted in hepatic venous outflow obstruction. When the liver graft was lifted up, the outflow drainage returned to normal but when it was placed back into the abdomen, the outflow obstruction recurred. Because reanastomosis would have resulted in hepatic reischemia, alternatively, a second infrahepatic cavocavostomy was planned without requiring hepatic reischemia. During this procedure, the first assistant hung the liver up to provide sufficient outflow and the portal inflow of the graft continued as well. We only clamped the recipient's infrahepatic vena cava and the caudal cuff of the graft cava. After the second end-to-side cavocaval anastomosis, the graft was placed in its orthotopic position and there was no outflow problem anymore. The patient tolerated the procedure well and there were no problems after three months of follow-up. A second cavocavostomy can provide an extra bypass for some hepatic venous outflow problems after piggyback anastomosis by avoiding hepatic reischemia.

Salvage with a Secondary Infrahepatic Cavocavostomy of the Occluded Modified Piggyback Anastomosis during Split Liver Transplantation: A Case Report

PubMed Central

Kinaci, Erdem; Kayaalp, Cuneyt; Yilmaz, Sezai; Otan, Emrah

2014-01-01

Hepatic venous outflow obstruction following liver transplantation is rare but disastrous. Here we described a 14-year-old boy who underwent a split right lobe liver transplantation with modified (side-to-side) piggyback technique which resulted in hepatic venous outflow obstruction. When the liver graft was lifted up, the outflow drainage returned to normal but when it was placed back into the abdomen, the outflow obstruction recurred. Because reanastomosis would have resulted in hepatic reischemia, alternatively, a second infrahepatic cavocavostomy was planned without requiring hepatic reischemia. During this procedure, the first assistant hung the liver up to provide sufficient outflow and the portal inflow of the graft continued as well. We only clamped the recipient's infrahepatic vena cava and the caudal cuff of the graft cava. After the second end-to-side cavocaval anastomosis, the graft was placed in its orthotopic position and there was no outflow problem anymore. The patient tolerated the procedure well and there were no problems after three months of follow-up. A second cavocavostomy can provide an extra bypass for some hepatic venous outflow problems after piggyback anastomosis by avoiding hepatic reischemia. PMID:24959369

Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

PubMed Central

Weng, Xiao-chuan; Zhou, Liang; Fu, Yin-yan; Zhu, Sheng-mei; He, Hui-liang; Wu, Jian

2005-01-01

Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under intravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored. The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results: Rocuronium requirement, which were (0.468±0.167) mg/(kg·h) during the paleohepatic phase, decreased significantly during the anhepatic phase to (0.303±0.134) mg/(kg·h) and returned to the initial values at the neohepatic period ((0.429±0.130) mg/(kg·h)); whereas atracuruim requirements remained unchanged during orthotopic liver transplantation. Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed, which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT. PMID:16130187

Genetically-engineered pig-to-baboon liver xenotransplantation: histopathology of xenografts and native organs.

PubMed

Ekser, Burcin; Klein, Edwin; He, Jing; Stolz, Donna B; Echeverri, Gabriel J; Long, Cassandra; Lin, Chih Che; Ezzelarab, Mohamed; Hara, Hidetaka; Veroux, Massimiliano; Ayares, David; Cooper, David K C; Gridelli, Bruno

2012-01-01

Orthotopic liver transplantation was carried out in baboons using wild-type (WT, n = 1) or genetically-engineered pigs (α1,3-galactosyltransferase gene-knockout, GTKO), n = 1; GTKO pigs transgenic for human CD46, n = 7) and a clinically-acceptable immunosuppressive regimen. Biopsies were obtained from the WT pig liver pre-Tx and at 30 min, 1, 2, 3, 4 and 5 h post-transplantation. Biopsies of genetically-engineered livers were obtained pre-Tx, 2 h after reperfusion and at necropsy (4-7 days after transplantation). Tissues were examined by light, confocal, and electron microscopy. All major native organs were also examined. The WT pig liver underwent hyperacute rejection. After genetically-engineered pig liver transplantation, hyperacute rejection did not occur. Survival was limited to 4-7 days due to repeated spontaneous bleeding in the liver and native organs (as a result of profound thrombocytopenia) which necessitated euthanasia. At 2 h, graft histology was largely normal. At necropsy, genetically-engineered pig livers showed hemorrhagic necrosis, platelet aggregation, platelet-fibrin thrombi, monocyte/macrophage margination mainly in liver sinusoids, and vascular endothelial cell hypertrophy, confirmed by confocal and electron microscopy. Immunohistochemistry showed minimal deposition of IgM, and almost absence of IgG, C3, C4d, C5b-9, and of a cellular infiltrate, suggesting that neither antibody- nor cell-mediated rejection played a major role.

[Hepatic cell transplantation: a new therapy in liver diseases].

PubMed

Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

2010-07-01

Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

Intracranial tuberculoma in a liver transplant patient: first reported case and review of the literature.

PubMed

Henderson, Corey; Meyers, Burt; Humayun Gultekin, S; Liu, Bin; Zhang, David Y

2003-01-01

A 66-year-old female who had undergone an orthotopic liver transplant two years before admission was admitted with fever and neurological symptoms of several days' duration. Following an extensive work-up, which revealed positive intracranial lesions on computed typography and magnetic resonance imaging, the patient was begun on broad spectrum antimicrobials including corticosteroids. The patient responded though the etiology of infection remained unclear. After a stereotactic biopsy was performed revealing granulomas and acid-fast bacilli, the patient was started on antituberculous medications. A review of the literature reveals that the rare occurrence of intracranial tuberculoma should be considered in an orthotopic liver transplant (OLT) patient with central nervous system pathology.

Successful Outflow Reconstruction to Salvage Traumatic Hepatic Vein-Caval Avulsion of a Normothermic Machine Ex-Situ Perfused Liver Graft

PubMed Central

Athanasopoulos, Panagiotis G.; Hadjittofi, Christopher; Dharmapala, Arinda Dinesh; Orti-Rodriguez, Rafael Jose; Ferro, Alessandra; Nasralla, David; Konstantinidou, Sofia K.; Malagó, Massimo

2016-01-01

Abstract Donor organ shortage continues to limit the availability of liver transplantation, a successful and established therapy of end-stage liver diseases. Strategies to mitigate graft shortage include the utilization of marginal livers and recently ex-situ normothermic machine perfusion devices. A 59-year-old woman with cirrhosis due to primary sclerosing cholangitis was offered an ex-situ machine perfused graft with unnoticed severe injury of the suprahepatic vasculature due to road traffic accident. Following a complex avulsion, repair and reconstruction of all donor hepatic veins as well as the suprahepatic inferior vena cava, the patient underwent a face-to-face piggy-back orthotopic liver transplantation and was discharged on the 11th postoperative day after an uncomplicated recovery. This report illustrates the operative technique to utilize an otherwise unusable organ, in the current environment of donor shortage and declining graft quality. Normothermic machine perfusion can definitely play a role in increasing the graft pool, without compromising the quality of livers who had vascular or other damage before being ex-situ perfused. Furthermore, it emphasizes the importance of promptly and thoroughly communicating organ injuries, as well as considering all reconstructive options within the level of expertise at the recipient center. PMID:27082550

Successful Outflow Reconstruction to Salvage Traumatic Hepatic Vein-Caval Avulsion of a Normothermic Machine Ex-Situ Perfused Liver Graft: Case Report and Management of Organ Pool Challenges.

PubMed

Athanasopoulos, Panagiotis G; Hadjittofi, Christopher; Dharmapala, Arinda Dinesh; Orti-Rodriguez, Rafael Jose; Ferro, Alessandra; Nasralla, David; Konstantinidou, Sofia K; Malagó, Massimo

2016-04-01

Donor organ shortage continues to limit the availability of liver transplantation, a successful and established therapy of end-stage liver diseases. Strategies to mitigate graft shortage include the utilization of marginal livers and recently ex-situ normothermic machine perfusion devices. A 59-year-old woman with cirrhosis due to primary sclerosing cholangitis was offered an ex-situ machine perfused graft with unnoticed severe injury of the suprahepatic vasculature due to road traffic accident. Following a complex avulsion, repair and reconstruction of all donor hepatic veins as well as the suprahepatic inferior vena cava, the patient underwent a face-to-face piggy-back orthotopic liver transplantation and was discharged on the 11th postoperative day after an uncomplicated recovery. This report illustrates the operative technique to utilize an otherwise unusable organ, in the current environment of donor shortage and declining graft quality. Normothermic machine perfusion can definitely play a role in increasing the graft pool, without compromising the quality of livers who had vascular or other damage before being ex-situ perfused. Furthermore, it emphasizes the importance of promptly and thoroughly communicating organ injuries, as well as considering all reconstructive options within the level of expertise at the recipient center.

Liver Transplantation for Budd-Chiari Syndrome

PubMed Central

Putnam, Charles W.; Porter, Kendrick A.; Well, Richard; Reid, H. A. S.; Starzl, Thomas E.

2011-01-01

Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiarl syndrome. She Is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. PMID:781334

Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

PubMed Central

Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

2016-01-01

The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

Establishment of a reversible model of prehepatic portal hypertension in rats

PubMed Central

Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-01-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO2), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. PMID:27446299

Establishment of a reversible model of prehepatic portal hypertension in rats.

PubMed

Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-08-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

A liver-metastatic model of human primary gastric lymphoma in nude mice orthotopically constructed by using histologically intact patient specimens.

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-Wei; Zhang, Ning; Liu, Qiu-Zhen

2010-06-01

In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 100%, 94.3%, 62.6%, and 43.5%, respectively. The study successfully establishes an orthotopic liver metastatic model of human primary gastric lymphoma in nude mice. The HGBL-0304 model can completely simulate the natural clinical process of primary gastric lymphoma and provides an ideal animal model for the research on the biology of metastasis and antimetastatic experimental therapies of primary gastric lymphoma.

The Effect of Bridging Locoregional Therapy and Sociodemographics on Survival in Hepatocellular Carcinoma Patients Undergoing Orthotopic Liver Transplantation: A United Network for Organ Sharing Population Study.

PubMed

Magnetta, Michael J; Xing, Minzhi; Zhang, Di; Kim, Hyun S

2016-12-01

To investigate socioeconomic and demographic factors associated with transplantation outcomes in patients with hepatocellular carcinoma (HCC) treated with bridging locoregional therapy (LRT) before orthotopic liver transplantation (OLT). The United Network for Organ Sharing (UNOS) database was used to identify all patients in the United States with HCC who were listed for OLT between 2002 and 2013. Mean overall survival (OS) after OLT was stratified based on age, sex, ethnicity, transplant year, region, and insurance status. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazards model to assess independent prognostic factors for OS. Of the 17,291 listed patients with HCC, 14,511 underwent OLT. Mean age was 57.4 years (76.8% male). Favorable sociodemographic factors were associated with increased rates of bridging LRT before OLT and longer wait time on the transplant list and were shown to be independent prognostic factors for prolonged OS after OLT using multivariate analysis. Favorable demographic factors included patient age < 60 years, donor age < 45 years, year of diagnosis between 2008 and 2013, UNOS regions 4 and 5, Asian ethnicity, high functional status, postgraduate education, private payer insurance, and employment at the time of OLT. Patients with favorable sociodemographics had higher rates of LRT before OLT performed for HCC cure. These patients had longer transplant wait times and longer OS after OLT. Copyright © 2016 SIR. Published by Elsevier Inc. All rights reserved.

Hepatic gas gangrene following orthotopic liver transplantation: three cases treated with re-transplantation and a review of the literature.

PubMed

Doblecki-Lewis, S; Palaios, E; Bejarano, P A; Tzakis, A G; Selvaggi, G; Morris, M I

2008-07-01

Gas gangrene is a rare and devastating infectious process that can occur after liver transplantation, most often following hepatic artery thrombosis. We here report 3 cases of gas gangrene following orthotopic liver transplantation. Blood cultures were positive for Clostridium clostridiiforme in one case. In 2 other cases liver tissue from explanted specimens was positive for Enterobacter cloacae. Ultrasound demonstrated hepatic artery thrombosis and computed tomography imaging revealed diffuse liver necrosis with gas formation in each case. All 3 patients were successfully treated with a combination of antibiotics and emergent re-transplantation. We review previously published cases of gas gangrene after liver transplant and emphasize the importance of hepatic artery thrombosis in the development of this syndrome as well as the frequent involvement of non-clostridial organisms. Early diagnosis and aggressive combined medical and surgical treatment including re-transplantation are essential for successful treatment of these rare and catastrophic infections.

Extracorporeal albumin dialysis in patients with Amanita phalloides poisoning.

PubMed

Faybik, Peter; Hetz, Hubert; Baker, Amir; Bittermann, Clemens; Berlakovich, Gabriela; Werba, Alois; Krenn, Claus-Georg; Steltzer, Heinz

2003-01-01

Ingestion of Amanita phalloides is the most common cause of lethal mushroom poisoning. The relative late onset of symptoms is a distinct diagnostic feature of Amanita intoxication and also the main reason of failure for extracorporeal removal of Amanita-specific toxins from the gut and circulation. Extracorporeal albumin dialysis (ECAD) has been used on six consecutive patients admitted after A. phalloides poisoning with acute liver failure (ALF). Six patients, with mean age of 46 years (range: 9-70 years), underwent one to three ECAD treatments. The mean time from mushroom ingestion until the first ECAD treatment was 76 h. Two patients regenerated spontaneously under ECAD treatment and orthotopic liver transplantation (OLT) could be avoided. Two patients were successfully bridged to OLT and one patient died because of cerebral herniation. One patient was treated with ECAD immediately after OLT because of the graft dysfunction and survived without re-transplantation. ECAD appeared to be a successful treatment perspective in supporting liver regeneration or in sufficient bridging to OLT and also in treatment of graft dysfunction after OLT in patients with A. phalloides poisoning.

Orlistat-induced fulminant hepatic failure.

PubMed

Sall, D; Wang, J; Rashkin, M; Welch, M; Droege, C; Schauer, D

2014-12-01

Orlistat was approved by the Food and Drug Administration in 1998 and has been shown to be superior to placebo in achieving weight loss. It is generally well tolerated. However, severe liver injury has been reported. We present a case of hepatic failure in a patient taking orlistat. A 54-year-old African-American woman with hypertension presented with hepatic failure. She had noticed increasing fatigue, jaundice and confusion. She used alcohol sparingly and denied tobacco or illicit drug use, but had been taking over-the-counter orlistat for the past two months. Physical examination revealed scleral icterus, jaundice, asterixis and slow speech. Laboratory testing showed markedly abnormal liver function tests with coagulopathy. Acute viral and autoimmune serologies were negative, as was toxicology screen. Liver biopsy showed necrotic hepatic parenchyma likely secondary to drug toxicity. Based upon her clinical presentation and time course, the pattern of liver injury seen on liver biopsy and lack of an alternative plausible explanation, her liver failure was most likely associated with orlistat use. She continued to deteriorate and ultimately underwent orthotopic liver transplantation. Fourteen cases of severe liver injury associated with orlistat use have been reported, four of which are detailed in the literature. This is the second published case of liver failure associated with over-the-counter orlistat usage. Clinicians should be aware of the growing number of cases associating liver injury and orlistat use and carefully monitor their patients on this medication for signs of hepatic dysfunction. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

Role of Stereotactic Body Radiation Therapy Before Orthotopic Liver Transplantation: Retrospective Evaluation of Pathologic Response and Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mannina, Edward Michael, E-mail: emmannina@gmail.com; Cardenes, Higinia Rosa; Lasley, Foster D.

Purpose: To analyze the results of stereotactic body radiation therapy (SBRT) in patients with early-stage, localized hepatocellular carcinoma who underwent definitive orthotopic liver transplantation (OLT). Methods and Materials: The subjects of this retrospective report are 38 patients diagnosed with hepatocellular carcinoma who underwent SBRT per institutional phase 1 to 2 eligibility criteria, before definitive OLT. Pre-OLT radiographs were compared with pathologic gold standard. Analysis of treatment failures and deaths was undertaken. Results: With median follow-up of 4.8 years from OLT, 9 of 38 patients (24%) recurred, whereas 10 of 38 patients (26%) died. Kaplan-Meier estimates of 3-year overall survival and disease-free survivalmore » are 77% and 74%, respectively. Sum longest dimension of tumors was significantly associated with disease-free survival (hazard ratio 1.93, P=.026). Pathologic response rate (complete plus partial response) was 68%. Radiographic scoring criteria performed poorly; modified Response Evaluation Criteria in Solid Tumors produced highest concordance (κ = 0.224). Explants revealed viable tumor in 74% of evaluable patients. Treatment failures had statistically larger sum longest dimension of tumors (4.0 cm vs 2.8 cm, P=.014) and non–statistically significant higher rates of lymphovascular space invasion (44% vs 17%), cT2 disease (44% vs 21%), ≥pT2 disease (67% vs 34%), multifocal tumors at time of SBRT (44% vs 21%), and less robust mean α-fetoprotein response (−25 IU/mL vs −162 IU/mL). Conclusions: Stereotactic body radiation therapy before to OLT is a well-tolerated treatment providing 68% pathologic response, though 74% of explants ultimately contained viable tumor. Radiographic response criteria poorly approximate pathology. Our data suggest further stratification of patients according to initial disease burden and treatment response.« less

Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Inferior Vena Cava Thrombosis After an Orthotopic Liver Transplant

PubMed Central

Latchana, Nicholas; Dowell, Joshua D.; Taani, Jamal Al; Michaels, Anthony; Elkhammas, Elmadhi; Black, Sylvester M.

2015-01-01

Inferior vena cava thrombosis is a rare occurrence after an orthotopic liver transplant that is associated with a high rate of retransplant and mortality. There is no consensus regarding the optimal therapeutic strategy. Surgical management, including thrombectomy with revision of the cavocaval anastomosis, has been described. With the use of endovascular therapies, several minimally invasive approaches are available that are effective and avoid the high morbidity associated with reoperative surgery. We describe our successful experience using an approach after a liver transplant in which the inferior vena cava thrombosis in a patient presenting with acute renal failure, anorexia, weight loss, and fatigue using an ultrasound-accelerated, catheter-directed thrombolysis platform in conjunction with systemic anticoagulation. PMID:24918871

A 27-Year Experience With Surgical Treatment of Budd-Chiari Syndrome

PubMed Central

Orloff, Marshall J.; Daily, Pat O.; Orloff, Susan L.; Girard, Barbara; Orloff, Mark S.

2000-01-01

Objective To determine the effects of surgical portal decompression in Budd-Chiari syndrome (BCS) on survival, quality of life, shunt patency, liver function, portal hemodynamics, and hepatic morphology during periods ranging from 3.5 to 27 years. Summary Background Data Experiments in the authors’ laboratory showed that surgical portal decompression reversed the deleterious effects of BCS on the liver. This study was aimed at determining whether similar benefit could be obtained in patients with BCS. Methods From 1972 to 1999, the authors conducted prospective studies of the treatment of 60 patients with BCS who were divided into three groups: the first had occlusion confined to the hepatic veins treated by direct side-to-side portacaval shunt (SSPCS); the second had occlusion involving the inferior vena cava (IVC) treated by a portal decompressive procedure that bypassed the obstructed IVC; and the third group, who had advanced cirrhosis and hepatic decompensation and were referred too late for treatment by portal decompression, required orthotopic liver transplantation. Results In the 32 patients with BCS resulting from hepatic vein occlusion alone, SSPCS had a surgical death rate of 3%, and 94% of the patients were alive 3.5 to 27 years after surgery. All 31 survivors remained free of ascites and almost all had normal liver function. No patient with a patent shunt had encephalopathy. The SSPCS remained patent in all but one patient. Liver biopsies showed no evidence of congestion or necrosis, and 48% of the biopsies were diagnosed as normal. Mesoatrial shunt was performed in eight patients with BCS caused by IVC thrombosis. All patients survived surgery, but five subsequently developed thrombosis of the synthetic graft and died. Because of the poor results, mesoatrial shunt was abandoned. Instead, a high-flow combination shunt was introduced, consisting of SSPCS combined with a cavoatrial shunt (CAS) through a Gore-Tex graft. There were no surgical or long-term deaths among 10 patients who underwent combined SSPCS and CAS, and the shunts functioned effectively during 4 to 16 years of follow-up. Ten patients with advanced cirrhosis were referred too late to benefit from surgical portal decompression, and they were approved and listed for orthotopic liver transplantation. Three patients died of liver failure while awaiting a transplant, and four patients died after the transplant. The 1- and 5-year survival rates were 40% and 30%, respectively. Conclusions SSPCS in BCS with hepatic vein occlusion alone results in reversal of liver damage, correction of hemodynamic disturbances, prolonged survival, and good quality of life when performed early in the course of BCS. Similarly good results are obtained with combined SSPCS and CAS in patients with BCS resulting from IVC occlusion. In contrast, mesoatrial shunt has been discontinued in the authors’ program because of an unacceptable incidence of graft thrombosis and death. In patients with advanced cirrhosis from long-standing, untreated BCS, orthotopic liver transplantation is the only hope of relief and results in the salvage of some patients. The key to long survival in BCS is prompt diagnosis and treatment by portal decompression. PMID:10973384

Thyroid storm complicated by fulminant hepatic failure: case report and literature review.

PubMed

Hambleton, Catherine; Buell, Joseph; Saggi, Bob; Balart, Luis; Shores, Nathan J; Kandil, Emad

2013-11-01

Thyroid storm is a presentation of severe thyrotoxicosis that has a mortality rate of up to 20% to 30%. Fulminant hepatic failure (FHF) entails encephalopathy with severe coagulopathy in the setting of liver disease. It carries a high mortality rate, with an approximately 60% rate of overall survival for patients who undergo orthotopic liver transplantation (OLT). Fulminant hepatic failure is a rare but serious complication of thyroid storm. There have been only 6 previously reported cases of FHF with thyroid storm. We present a patient from our institution with thyroid storm and FHF. A literature review was performed to analyze the outcomes of the 6 additional cases of concomitant thyroid storm and FHF. Our patient underwent thyroidectomy followed by OLT. Her serum levels of thyroid-stimulating hormone, triiodothyronine, thyroxine, and transaminase normalized, and she was ready for discharge within 10 days of surgery. She has survived without complication. There is a 40% mortality rate for the reported patients treated medically with these conditions. Of the 7 total cases of reported FHF and thyroid storm, 2 patients died. Only 2 of the 7 patients underwent thyroidectomy and OLT--both at our institution. Both patients survived without complications. Thyroid storm and FHF each independently carry high mortality rates, and managing patients with both conditions simultaneously is an extraordinary challenge. These cases should compel clinicians to investigate liver function in hyperthyroid patients and to be wary of its rapid decline in patients who present in thyroid storm with symptoms of liver dysfunction. Patients with rapidly progressing thyroid storm and FHF should be considered for total thyroidectomy and OLT.

Obscured hemorrhagic pancreatitis after orthotopic heart transplantation complicated with acute right heart failure and hepatic dysfunction: a case report.

PubMed

Lin, Ting-Wei; Tsai, Meng-Ta; Roan, Jun-Neng; Liu, Yi-Sheng; Tsai, Hong-Ming; Luo, Chwan-Yau

2016-12-01

Pancreatitis is a serious complication after cardiac surgery and can lead to significant morbidities and mortality. The incidence of pancreatitis is even higher in patients undergoing heart transplantation than in those undergoing other cardiac surgeries. Nevertheless, the clinical presentations of pancreatitis are frequently atypical in these patients. We report a heart recipient who was complicated with acute right heart failure initially after orthotopic heart transplantation and developed devastating unanticipated hemorrhagic pancreatitis 1 month after the transplantation. This crypto-symptomatic pancreatitis was not diagnosed until massive internal bleeding and hemorrhagic shock occurred, because the typical presentations of acute pancreatitis were masked by the intra-abdominal manifestations caused by right heart failure and congestive liver dysfunction. The patient underwent a successful transarterial embolization. The causes of pancreatitis after heart transplantation include low cardiac output, immunosuppressant use and cytomegalovirus infection. The typical symptoms of pancreatitis might be not apparent in patients after heart transplantation because of their immunosuppressive status. Furthermore, in patients complicated with right heart failure after transplantation, the manifestation of pancreatitis could be even more obscure. The prompt diagnosis is highly depended on the clinician's astuteness.

Auxiliary partial orthotopic living donor liver transplantation with a small-for-size graft for congenital absence of the portal vein.

PubMed

Matsuura, Toshiharu; Soejima, Yuji; Taguchi, Tomoaki

2010-12-01

Congenital absence of the portal vein (CAPV) with an extrahepatic portosystemic shunt is a rare malformation; the completely absent type, Abernethy malformation type I, is especially rare. Liver transplantation for CAPV type I has been recently recognized as the only curative operation, but few reports have been published so far; meanwhile, auxiliary partial orthotopic liver transplantation (APOLT) has been proposed to be a very effective option, especially for pediatric patients. Here we present an 18-year-old adult patient with CAPV, asplenia, and an iliac shunt vessel who was managed successfully with APOLT using a small-for-size graft. To the best of our knowledge, this is the first adult patient who has experienced success with APOLT for CAPV. This is a feasible procedure: it not only fulfills the metabolic demands of the liver for adult patients but also potentially cures CAPV. Copyright © 2010 American Association for the Study of Liver Diseases.

Successful treatment of donor-derived hepatitis C viral infection in three transplant recipients from a donor at increased risk for bloodborne pathogens.

PubMed

Shah, Ashesh P; Cameron, Andrew; Singh, Pooja; Frank, Adam M; Fenkel, Jonathan M

2017-04-01

We report here the successful treatment of hepatitis C virus (HCV) transmitted from a nucleic acid testing (NAT)-negative donor to three HCV-negative recipients-two renal transplants and one liver. Both renal recipients underwent standard deceased-donor renal transplantation with immediate graft function. The liver recipient underwent standard orthotopic liver transplantation and recovered uneventfully. The donor was a 39-year-old woman with a terminal serum creatinine of 0.7 mg/dL. She was high risk for bloodborne pathogens, based upon a history of sexual contact with an HCV-infected male partner. Recipient 1 was a 45-year-old man with a history of end-stage renal disease from systemic lupus erythematosus. Recipient 2 was a 62-year-old woman with a history of end-stage renal disease caused by hypertension and insulin-dependent diabetes. Recipient 3 was a 42-year-old man with acute liver failure from acetaminophen ingestion. All recipients became HCV polymerase chain reaction positive on post-transplant follow-up. Both kidney recipients were treated with ledipasvir/sofosbuvir combination therapy for 12 weeks without side effects or rejection episodes. Recipient 3 was treated with ledipasvir/sofosbuvir in combination with ribavirin for 12 weeks without side effects. All patients achieved a sustained viral response at 12 weeks and are considered cured of HCV. The kidney recipients maintained good allograft function with a serum creatinine of 1.4 mg/dL and 1.0 mg/dL, respectively. Both renal recipients maintained normal liver function post treatment and did not develop any evidence of fibrosis. The liver recipient's liver function tests returned to normal without further incident. This case report provides evidence for the successful treatment of donor-derived HCV in transplant recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[To the issue of postreperfusion syndrome predictors in orthotopic liver transplantation (OLT)].

PubMed

Kiseleva, E A; Ushakova, I A; Kim, E F; Matveev, G P; Biriulina, N Iu; Vabishchevich, A V

2012-01-01

The aim of the study is revelation of postperfusion syndrome (pPS) predictors in orthotopic liver transplantation (OLT). Was conducted a retrospective analysis of anesthesia maintainance protocols during orthotopic liver transplantation in 261 patients aged from 6 months to 60 years. Investigated the effect of various factors on the development of PPS by the application of methods of non-parametric statistics. Significantly more frequent development of the PPS is noted in the age group from 3 to 18 years (up to 30% of patients). In recipients older than 18 years the frequency of the development of the PPS does not depend on age, with an average of 14%. The development of the PPS does not depend on the recipient sex, the nature of the pathology which served as an indication to the OTP, the initial severity of the state, type of OTP (living related donor or cadaveric transplantation, primary or re-transplantation), the transplant warm ischemia duration, use, or the lack of venous-venous bypass, metabolic status of the patient. The obtained results do not contradict to the data of foreign publications. Among parameters available for screening, predictor of PPS was not detected.

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation

PubMed Central

Taut, F J H; Schmidt, H; Zapletal, C M; Thies, J C; Grube, C; Motsch, J; Klar, E; Martin, E

2001-01-01

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P ≤ 0·02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment. PMID:11422213

Cardio-hepatic risk assessment by CMR imaging in liver transplant candidates.

PubMed

Reddy, Sahadev T; Thai, Ngoc L; Oliva, Jose; Tom, Kusum B; Dishart, Michael K; Doyle, Mark; Yamrozik, June A; Williams, Ronald B; Shah, Moneal; Wani, Adil; Singh, Anil; Maheswary, Rishi; Biederman, Robert W W

2018-03-02

The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof-of-concept study the value of a one-stop-shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one-stop-shop CMR approach. In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination. Over 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event-free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC. This study further defines the population suitable for the one-stop-shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-term survival after liver transplant for recurrent hepatocellular carcinoma with bile duct tumor thrombus: case report.

PubMed

Liu, Chao; Wang, Jie

2012-12-01

Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 μg/L, total bilirubin level was 327 μmol/L, direct bilirubin level was 261 μmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.

Initial Poor Function and Primary Nonfunction in Deceased-Donor Orthotopic Liver Transplantation Maintaining Short Cold Ischemic Time.

PubMed

Das, Somak; Swain, Sudeepta Kumar; Addala, Pavan Kumar; Balasubramaniam, Ramakrishnan; Gopakumar, C V; Zirpe, Dinesh; Renganathan, Kirubakaran; Kollu, Harsha; Patel, Darshan; Vibhute, Bipin B; Rao, Prashantha S; Krishnan, Elankumaran; Gopasetty, Mahesh; Khakhar, Anand K; Vaidya, Anil; Ramamurthy, Anand

2016-12-01

Nations with emerging deceased-donor liver transplantation programs, such as India, face problems associated with poor donor maintenance. Cold ischemic time (CIT) is typically maintained short by matching donor organ recovery and recipient hepatectomy to achieve maximum favorable outcome. We analyzed different extended criteria donor factors including donor acidosis, which may act as a surrogate marker of poor donor maintenance, to quantify the risk of primary nonfunction (PNF) or initial poor function (IPF). A single-center retrospective outcome analysis of prospectively collected data of patients undergoing deceased-donor liver transplantation over 2 years to determine the impact of different extended criteria donor factors on IPF and PNF. From March 2013 to February 2015, a total of 84 patients underwent deceased-donor liver transplantation. None developed PNF. Thirteen (15.5%) patients developed IPF. Graft macrosteatosis and donor acidosis were only related to IPF ( P = .002 and P = .032, respectively). Cold ischemic time was maintained short (81 cases ≤8 hours, maximum 11 hours) in all cases. Poor donor maintenance as evidenced by donor acidosis and graft macrosteatosis had significant impact in developing IPF when CIT is kept short. Similar study with larger sample size is required to establish extended criteria cutoff values.

Side-to-side cavo-cavostomy: a useful aid in "complicated" piggy-back liver transplantation.

PubMed

Lerut, J; Gertsch, P

1993-01-01

Piggy-back liver transplantation is a useful technical variant of orthotopic liver transplantation. Its success can, however, be compromised by severe stenosis or obstruction of the recipient's inferior vena cava at the level of the anastomosis. A technique is described--side-to-side cavocavostomy--to resolve this difficult intraoperative situation.

‘Obligate’ anaerobic Salmonella strain YB1 suppresses liver tumor growth and metastasis in nude mice

PubMed Central

Li, Chang-Xian; Yu, Bin; Shi, Lei; Geng, Wei; Lin, Qiu-Bin; Ling, Chang-Chun; Yang, Mei; Ng, Kevin T. P.; Huang, Jian-Dong; Man, Kwan

2017-01-01

The antitumor properties of bacteria have been demonstrated over the past decades. However, the efficacy is limited and unclear. Furthermore, systemic infection remains a serious concern in bacteria treatment. In this study, the effect of YB1, a rationally designed ‘obligate’ anaerobic Salmonella typhimurium strain, on liver tumor growth and metastasis in a nude mouse orthotopic liver tumor model was investigated. The orthotopic liver tumor model was established in nude mice using the hepatocellular carcinoma cell line MHCC-97L. Two weeks after orthotopic liver tumor implantation, YB1, SL7207 and saline were respectively administered through the tail vein of the mice. Longitudinal monitoring of tumor growth and metastasis was performed using Xenogen IVIS, and direct measurements of tumor volume were taken 3 weeks after treatment. In vitro, MHCC-97L and PLC cells were incubated with YB1 or SL7207 under anaerobic conditions. YB1 was observed to invade tumor cells and induce tumor cell apoptosis and death. The results revealed that all mice in the YB1 group were alive 3 weeks after YB1 injection while all mice in the SL7207 group died within 11 days of the SL7207 injection. The body weight decreased by ~9% on day 1 after YB1 injection and but subsequently recovered. Liver tumor growth and metastases were significantly inhibited following YB1 treatment. By contrast to the control group, a large number of Gr1-positive cells were detected on days 1 to 21 following YB1 treatment. Furthermore, YB1 also effectively invaded tumor cells and induced tumor cell apoptosis and death. In conclusion, YB1 suppressed liver tumor growth and metastasis in a nude mice liver tumor model. The potential mechanism may be through enhancing innate immune response and inducing tumor cell apoptosis and cell death. PMID:28123538

[Highly metastatic nude mouse model of human primary gastric lymphoma constructed by surgical orthotopic transplantation and in vivo continuous screening method].

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

2010-02-09

To develop a series of high metastatic models of human gastric malignant lymphoma in nude mice by orthotopic transplantation. Two histologically intact primary and hepatic metastatic fragments derived from surgical specimen of a patient with primary gastric lymphoma were implanted into the submucosa of stomach in nude mice. Highly metastatic and specific organ metastatic models were screened by selective orthotopic passage in nude mice. Transplantability, invasion, metastasis, morphological characteristics (light microscopy, electron microscopy and immunohistochemistry), karyotypic analysis and DNA content of orthotopically transplanted tumors were studied. Primary and hepatic metastatic fragments of primary gastric lymphoma were successfully transplanted in nude mice. Two nude mouse models of human primary gastric lymphoma, termed HGBL-0304 (hepatic metastasis model) and HGBL-0305 (high metastasis model), were developed, exhibiting different metastasis biology. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. Two models have been maintained for 45 generations by orthotopic passage in nude mice. A total of 419 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. Significant difference in metastasis biology was exhibited in four aspects of metastasis time, organ metastatic rate, the extent of hepatic metastasis and survival of cancer-bearing mice. The metastatic rates of liver, spleen, lymph nodes and peritoneal seeding in HGBL-0304 and HGBL-0305 models were 100% and 69.5%, 94.3% and 55.6%, 62.6% and 45.7%, and 43.5% and 30.5%. The onset time for metastases of liver, spleen, lymph nodes and peritoneal seeding was 2 w and 5 w, 3 w and 6 w, 2 w and 3 w, 3 w and 6 w respectively. The extent of hepatic metastasis in HGBL-0304 and HGBL-0305 models displayed diffuse involvement of the whole liver and mainly right lobe invasion of liver respectively. The mean survival time of HGBL-0304 and HGBL-0305 models was 54.3d and 106.9 d respectively. Surgical orthotopic implantation combined with in vivo selective passage screening is an effective method for establishing highly metastatic and specific organ metastatic models of human malignant lymphoma in nude mice. The study is the first time to establish hepatic metastasis and high metastasis nude mouse models of human primary gastric lymphoma with the same original patient and different potentials of invasion and metastasis.

Curative potential of GM-CSF-secreting tumor cell vaccines on established orthotopic liver tumors: mechanisms for the superior antitumor activity of live tumor cell vaccines.

PubMed

Tai, Kuo-Feng; Chen, Ding-Shinn; Hwang, Lih-Hwa

2004-01-01

In preclinical studies, tumor cells genetically engineered to secrete cytokines, hereafter referred to as tumor cell vaccines, can often generate systemic antitumor immunity. This study investigated the therapeutic effects of live or irradiated tumor cell vaccines that secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental results indicated that two doses (3 x 10(7) cells per dose) of irradiated tumor cell vaccines were therapeutically ineffective, whereas one dose (3 x 10(6) cells) of live tumor cell vaccines caused complete tumor regression. In vivo depletion of CD8+ T cells, but not natural killer cells, restored tumor formation in the live vaccine-treated animals. Additionally, the treatment of cells with live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity than the irradiated vaccines in the draining lymph nodes. The higher levels of cytokine and antigen loads could partly explain the superior antitumor activity of live tumor cell vaccines, but other unidentified mechanisms could also play a role in the early T cell activation in the lymph nodes. A protocol using multiple and higher dosages of irradiated tumor cell vaccines also caused significant regression of liver tumors. These results suggest that the GM-CSF-secreting tumor cell vaccines are highly promising for orthotopic liver tumors if higher levels of immune responses are elicited during early tumor development. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

Nutritional risk and anthropometric evaluation in pediatric liver transplantation.

PubMed

Zamberlan, Patrícia; Leone, Cláudio; Tannuri, Uenis; Carvalho, Werther Brunow de; Delgado, Artur Figueiredo

2012-12-01

To analyze the nutritional status of pediatric patients after orthotopic liver transplantation and the relationship with short-term clinical outcome. Anthropometric evaluations of 60 children and adolescents after orthotopic liver transplantation, during the first 24 hours in a tertiary pediatric intensive care unit. Nutritional status was determined from the Z score for the following indices: weight/age height/age or length/age, weight/height or weight/length, body mass index/age, arm circumference/age and triceps skinfold/age. The severity of liver disease was evaluated using one of the two models which was adequated to the patients' age: 1. Pediatric End-stage Liver Disease, 2. Model for End-Stage Liver Disease. We found 50.0% undernutrition by height/age; 27.3% by weight/age; 11.1% by weight/height or weight/ length; 10.0% by body mass index/age; 61.6% by arm circumference/age and 51.0% by triceps skinfold/age. There was no correlation between nutritional status and Pediatric End-stage Liver Disease or mortality. We found a negative correlation between arm circumference/age and length of hospitalization. Children with chronic liver diseases experience a significant degree of undernutrition, which makes nutritional support an important aspect of therapy. Despite the difficulties in assessment, anthropometric evaluation of the upper limbs is useful to evaluate nutritional status of children before or after liver transplantation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maleux, Geert; Pirenne, Jacques; Vaninbroukx, Johan

Our purpose was to assess the feasibility of orthotopic liver transplantation (OLT) in patients priorly having undergone transjugular intrahepatic portosystemic shunt (TIPS) with an expanded tetrafluoroethylene (e-PTFE)-covered endoprosthesis. In 48 patients an e- PTFE-covered endoprosthesis was inserted to treat severe complications of portal hypertension. In 36 patients the endoprosthesis was inserted during TIPS creation (de novo TIPS); in the other 12 patients the endoprosthesis was placed to repermeabilize the previously created, but occluded bare stent (revision TIPS). Eight of them (5 de novo and 3 revision cases) later underwent an OLT. The hospital records of these patients were reviewed frommore » initial admission, through TIPS, the pre-OLT period, and OLT to current postoperative status. Five de novo and 3 revision cases underwent OLT 4-279 days (mean delay: 80.8 days) after TIPS procedure. All OLT's were performed under veno-venous bypass surgery. De visu surgical inspection confirmed correct positioning of the fully patent stent graft, starting in the portal vein and ending at the junction of the hepatic vein to the inferior caval vein. No surgical difficulty was observed during proximal or distal clamping or during resection of the diseased liver. Correctly positioned e-PTFE-covered nitinol endoprostheses do not interfere with a later OLT and may not be considered as a contraindication in patients who need a TIPS as a bridge to OLT.« less

The first clinical liver transplantation of Brazil revisited.

PubMed

Bacchella, T; Machado, M C C

2004-05-01

The first clinical orthotopic liver transplantation in Brazil was performed on August 5, 1968. The patient was awake after surgery and died on the seventh postoperative day due to subdural hematoma, bronchopneumonia, renal failure, and graft rejection. The report of this case is important to understand the evolution of clinical liver transplantation in Brazil, where this procedure is now routinely carried out in many medical centers.

Overexpression of periostin and distinct mesothelin forms predict malignant progression in a rat cholangiocarcinoma model

PubMed Central

Manzanares, Miguel Á.; Campbell, Deanna J.W.; Maldonado, Gabrielle T.

2017-01-01

Periostin and mesothelin have each been suggested to be predictors of poor survival for patients with intrahepatic cholangiocarcinoma, although the clinical prognostic value of both of these biomarkers remains uncertain. The aim of the current study was to investigate these biomarkers for their potential to act as tumor progression factors when assessed in orthotopic tumor and three‐dimensional culture models of rat cholangiocarcinoma progression. Using our orthotopic model, we demonstrated a strong positive correlation between tumor and serum periostin and mesothelin and increasing liver tumor mass and associated peritoneal metastases that also reflected differences in cholangiocarcinoma cell aggressiveness and malignant grade. Periostin immunostaining was most prominent in the desmoplastic stroma of larger sized more aggressive liver tumors and peritoneal metastases. In comparison, mesothelin was more highly expressed in the cholangiocarcinoma cells; the slower growing more highly differentiated liver tumors exhibited a luminal cancer cell surface immunostaining for this biomarker, and the rapidly growing less differentiated liver and metastatic tumor masses largely showed cytoplasmic mesothelin immunoreactivity. Two molecular weight forms of mesothelin were identified, one at ∼40 kDa and the other, a more heavily glycosylated form, at ∼50 kDa. Increased expression of the 40‐kDa mesothelin over that of the 50 kDa form predicted increased malignant progression in both the orthotopic liver tumors and in cholangiocarcinoma cells of different malignant potential in three‐dimensional culture. Moreover, coculturing of cancer‐associated myofibroblasts with cholangiocarcinoma cells promoted overexpression of the 40‐kDa mesothelin, which correlated with enhanced malignant progression in vitro. Conclusion: Periostin and mesothelin are useful predictors of tumor progression in our rat desmoplastic cholangiocarcinoma models. This supports their relevance to human intrahepatic cholangiocarcinoma. (Hepatology Communications 2018;2:155–172) PMID:29404524

Donor miR-196a-2 polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation in a Han Chinese population.

PubMed

Xu, Xiao; Ling, Qi; Wang, Jianguo; Xie, Haiyang; Wei, Xuyong; Lu, Di; Hu, Qichao; Zhang, Xuanyu; Wu, Liming; Zhou, Lin; Zheng, Shusen

2016-02-01

Recurrence of hepatocellular carcinoma (HCC) is one of the leading causes of death after liver transplantation (LT). We aim to evaluate the association of donor and recipient single nucleotide polymorphisms (SNPs) with the risk of HCC recurrence after LT. A total of 155 adult patients who underwent primary LT for HCC were enrolled. Ten SNPs associated with HCC susceptibility were genotyped. Patients who received donor livers with the rs11614913 homozygous CC variant presented significantly higher recurrence rates of HCC (41.7 vs. 15.3%, p = 0.009) and lower cumulative tumor-free survival (p = 0.005) than those who received TT wild-type donor livers. The donor rs11614913 genetic variant was an independent risk factor for HCC recurrence (odds ratio = 2 per each C allele, p < 0.05) and could significantly improve the predictive abilities of clinical models (Milan, UCSF and Hangzhou criteria). Donor livers homozygous for rs11614913 CC were associated with a higher miR-196a expression than TT (p = 0.002). In a lentiviral infection of mouse liver and orthotopic mouse model of HCC, the liver miR-196a overexpression group showed a significantly larger tumor size than the control group (p = 0.001). There is a close association between the tumor size and expression of miR-196a in the liver (r = 0.693, p = 0.001). In conclusion, the donor miR-196a-2 rs11614913 polymorphism is associated with HCC recurrence after LT and improves the predictive value of clinical models. The overexpression of miR-196a in the liver might provide a tumor-favorable environment for the development of HCC. © 2015 UICC.

Predicting the discharge status after liver transplantation at a single center: a new approach for a new era.

PubMed

Kelly, Dympna M; Bennett, Renee; Brown, Nancy; McCoy, Judy; Boerner, Derek; Yu, Changhong; Eghtesad, Bijan; Barsoum, Wael; Fung, John J; Kattan, Michael W

2012-07-01

The aim of this study was to develop a tool for preoperatively predicting the need of a patient to attend an extended care facility after orthotopic liver transplantation (OLT). A multidisciplinary group, which included 2 transplant surgeons, 2 transplant nurses, 1 nurse manager, 2 physical therapists, 1 case manager, 1 home health care professional, 1 rehabilitation physician, and 1 statistician, met to identify preoperative factors relevant to discharge planning. The parameters that were examined as potential predictors of the discharge status were as follows: age, sex, language, Karnofsky score, OLT alone (versus a combined procedure), creatinine, bilirubin, international normalized ratio (INR), albumin, body mass index (BMI), Child-Turcotte-Pugh score, chemical Model for End-Stage Liver Disease score, renal dialysis, location before transplantation, comorbidities (encephalopathy, ascites, hydrothorax, and hepatopulmonary syndrome), diabetes mellitus (DM), cardiac ejection fraction and right ventricular systolic pressure, sex and availability of the primary caregiver, donor risk index, and donor characteristics. Between January 2004 and April 2010, 730 of 777 patients (94%) underwent only liver transplantation, and 47 patients (6%) underwent combined procedures. Five hundred nineteen patients (67%) were discharged home, 215 (28%) were discharged to a facility, and 43 (6%) died early after OLT. A multivariate logistic regression analysis identified the following parameters as significantly influencing the discharge status: a low Karnofsky score, an older age, female sex, an INR of 2.0, a creatinine level of 2.0 mg/dL, DM, a high bilirubin level, a low albumin level, a low or high BMI, and renal dialysis before OLT. The nomogram was prospectively validated with a population of 126 OLT recipients with a concordance index of 0.813. In conclusion, a new approach to improving the efficiency of hospital care is essential. We believe that this tool will aid in reducing lengths of stay and improving the experience of patients by facilitating early discharge planning. Copyright © 2012 American Association for the Study of Liver Diseases.

Unusual biliary scan appearance in a child with a transplanted liver with hepatic arterial thrombosis: a case report.

PubMed

Porn, U; Howman-Giles, R; Shun, A; Dorney, S; Uren, R

2000-02-01

A 5-year-old girl with biliary atresia and a subsequent Kasai procedure is described. She had clinical symptoms suggestive of rejection after a recent orthotopic liver transplant A hepatobiliary scan showed partial hepatic infarction and a biloma in the infarcted area.

Hypertrophic Cardiomyopathy in Liver Transplantation Patients.

PubMed

Pai, S-L; Aniskevich, S; Logvinov, I I; Matcha, G V; Palmer, W C; Blackshear, J L

2018-06-01

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder that presents with a hypertrophied nondilated left ventricle. In the absence of other known causes of cardiomyopathy, it is often associated with left ventricular outflow tract obstruction during systole, systolic anterior motion of the mitral valve, mitral regurgitation, and increased risk of sudden cardiac death. When HCM coexists with end-stage liver disease, it can be further complicated by cirrhosis-associated cardiovascular abnormalities, including hyperdynamic circulation, systolic and diastolic dysfunction, and electrophysiologic abnormalities. We retrospectively examined patient characteristics, comorbidities, preoperative echocardiogram results, sudden cardiac death risk prediction model score, and 1-year postoperative mortality of patients with HCM who underwent liver transplantation at our institution from January 1, 2000, through January 1, 2015. Of the 2,812 liver transplantations performed during the study period, we identified 15 patients with a preoperative diagnosis of HCM. When comparing the patients who did vs did not survive the first year after orthotopic liver transplantation, we identified significant differences in maximal left ventricular wall thickness (P = .004) and resting left ventricular outflow tract gradient (P = .004). Preoperative left atrium size (measured by echocardiography; P = .66) and the sudden cardiac death risk prediction model score (P = .32) were not significantly associated with 1-year survival. Preoperative left ventricular outflow tract gradient exceeding 60 mm Hg was strongly associated with death during the first year after transplant. These results suggest that the severity of HCM influences patient outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Protective effects against hepatic ischemia-reperfusion injury after rat orthotopic liver transplantation because of BCL-2 overexpression.

PubMed

Wu, Kun; Ma, Long; Xu, Ting; Qin, Zhensheng; Xia, Tianfang; Wang, Yi; Yu, Xiangyou; Pang, Liqun

2015-01-01

This study aims to investigate the protective effects and mechanism of recombinant adenovirus Ad.VSG-hBCL-2 towards ischemia/reperfusion injury in rat liver graft. Recombinant adenovirus Ad.VSG-hBCL-2 was injected into the donor rat liver of the experiment group through the portal vein, the laparotomy was performed for liver 36 h later, and the liver was save in lactated Ringer's solution at 4°C for 4 h, "two-cuff method" was used to perform the orthotopic liver transplantation. The bile secretion situations of two groups were observed 6 h after the portal vein reflow; the recipient rats were killed to detect the plasma levels of AST, ALT and LDH. And the expressions of Bcl-2 and TNF-α in liver tissue, and TUNEL assay was used to detect the apoptosis of liver tissue cells, electron microscopy was used to observe the changes of subcellular structures of liver tissue. 6 h after the surgery, the immunohistochemistry and Western Blot test showed that the Bcl-2 expression in the liver of the experiment group significantly increased than the control group, the bile secretion increased, the levels of AST, ALT and LDH were significantly lower, and the TNF-α expression increased significantly. The changes of cellular morphology of the experiment group were milder, and the apoptotic index was significantly lower than the control group. The portal vein-transfected recombinant adenovirus Ad.VSG-hBCL-2 could be effectively expressed in rat liver, and the high expressed Bcl-2 could reduce the ischemia/reperfusion injury in the transplanted liver.

Piggyback technique in adult orthotopic liver transplantation: an analysis of 1067 liver transplants at a single center

PubMed Central

Nakamura, Noboru; Vaidya, Anil; Levi, David M.; Kato, Tomoaki; Nery, Jose R.; Madariaga, Juan R.; Molina, Enrique; Ruiz, Phillip; Gyamfi, Anthony; Tzakis, Andreas G.

2006-01-01

Background. Orthotopic liver transplantation (OLT) in adult patients has traditionally been performed using conventional caval reconstruction technique (CV) with veno-venous bypass. Recently, the piggyback technique (PB) without veno-venous bypass has begun to be widely used. The aim of this study was to assess the effect of routine use of PB on OLTs in adult patients. Patients and methods. A retrospective analysis was undertaken of 1067 orthotopic cadaveric whole liver transplantations in adult patients treated between June 1994 and July 2001. PB was used as the routine procedure. Patient demographics, factors including cold ischemia time (CIT), warm ischemia time (WIT), operative time, transfusions, blood loss, and postoperative results were assessed. The effects of clinical factors on graft survival were assessed by univariate and multivariate analyses.In all, 918 transplantations (86%) were performed with PB. Blood transfusion, WIT, and usage of veno-venous bypass were less with PB. Seventy-five (8.3%) cases with PB had refractory ascites following OLT (p=NS). Five venous outflow stenosis cases (0.54%) with PB were noted (p=NS). The liver and renal function during the postoperative periods was similar. Overall 1-, 3-, and 5-year patient survival rates were 85%, 78%, and 72% with PB. Univariate analysis showed that cava reconstruction method, CIT, WIT, amount of transfusion, length of hospital stay, donor age, and tumor presence were significant factors influencing graft survival. Multivariate analysis further reinforced the fact that CIT, donor age, amount of transfusion, and hospital stay were prognostic factors for graft survival. Conclusions. PB can be performed safely in the majority of adult OLTs. Results of OLT with PB are as same as for CV. Liver function, renal function, morbidity, mortality, and patient and graft survival are similar to CV. However, amount of transfusion, WIT, and use of veno-venous bypass are less with PB. PMID:18333273

Postreperfusion hyperkalemia in liver transplantation using donation after cardiac death grafts with pathological changes.

PubMed

Zhang, Wen-Jin; Xia, Wei-Liang; Pan, Hui-Yun; Zheng, Shu-Sen

2016-10-01

With the increasing use of donation after cardiac death (DCD), especially of the graft liver with steatosis or other pathological changes, the frequency of postreperfusion hyperkalemia in liver transplantation has increased significantly. The present study aimed to determine the factors associated with developing postreperfusion hyperkalemia in liver transplantation from DCD. One hundred thirty-one consecutive adult patients who underwent orthotopic liver transplantation from DCD were retrospectively studied. Based on serum potassium within 5 minutes after reperfusion, recipients were divided into two groups: hyperkalemia and normokalemia. According to preoperative biopsy results, the DCD graft livers were classified into five categories. Univariate analysis was performed using Chi-square test to identify variables that were significantly different between two groups. Multivariate logistic regression was used to confirm the risk factors of developing hyperkalemia and postreperfusion syndrome. Correlation analysis was used to identify the relationship between the serum concentration of potassium within 5 minutes after reperfusion and the difference in mean arterial pressure values before and within 5 minutes after reperfusion. Twenty-two of 131 liver recipients had hyperkalemia episodes within 5 minutes after reperfusion. The rate of hyperkalemia was significantly higher in recipients of macrosteatotic DCD graft liver (78.6%, P<0.001) than that in recipients of non-macrosteatotic DCD graft liver. The odds ratio of developing postreperfusion hyperkalemia in recipients of macrosteatotic DCD graft liver was 51.3 (P<0.001). Macrosteatosis in the DCD graft liver was an independent risk factor of developing hyperkalemia within 5 minutes after reperfusion. The highest rate of postreperfusion syndrome also occurred in the recipients with macrosteatotic DCD graft liver (71.4%, P<0.001). A strong relationship existed between the serum potassium within 5 minutes after reperfusion and the difference in mean arterial pressure values before and within 5 minutes after reperfusion in macrosteatotic DCD graft liver recipients. Macrosteatosis in the DCD graft liver was an independent risk factor of developing hyperkalemia and postreperfusion syndrome in the recipients.

Reduced Myocardial Flow Reserve by Positron Emission Tomography Predicts Cardiovascular Events After Cardiac Transplantation.

PubMed

Konerman, Matthew C; Lazarus, John J; Weinberg, Richard L; Shah, Ravi V; Ghannam, Michael; Hummel, Scott L; Corbett, James R; Ficaro, Edward P; Aaronson, Keith D; Colvin, Monica M; Koelling, Todd M; Murthy, Venkatesh L

2018-06-01

We evaluated the diagnostic and prognostic value of quantification of myocardial flow reserve (MFR) with positron emission tomography (PET) in orthotopic heart transplant patients. We retrospectively identified orthotopic heart transplant patients who underwent rubidium-82 cardiac PET imaging. The primary outcome was the composite of cardiovascular death, acute coronary syndrome, coronary revascularization, and heart failure hospitalization. Cox regression was used to evaluate the association of MFR with the primary outcome. The relationship of MFR and cardiac allograft vasculopathy severity in patients with angiography within 1 year of PET imaging was assessed using Spearman rank correlation and logistic regression. A total of 117 patients (median age, 60 years; 71% men) were identified. Twenty-one of 62 patients (34%) who underwent angiography before PET had cardiac allograft vasculopathy. The median time from orthotopic heart transplant to PET imaging was 6.4 years (median global MFR, 2.31). After a median of 1.4 years, 22 patients (19%) experienced the primary outcome. On an unadjusted basis, global MFR (hazard ratio, 0.22 per unit increase; 95% confidence interval, 0.09-0.50; P <0.001) and stress myocardial blood flow (hazard ratio, 0.48 per unit increase; 95% confidence interval, 0.29-0.79; P =0.004) were associated with the primary outcome. Decreased MFR independently predicted the primary outcome after adjustment for other variables. In 42 patients who underwent angiography within 12 months of PET, MFR and stress myocardial blood flow were associated with moderate-severe cardiac allograft vasculopathy (International Society of Heart and Lung Transplantation grade 2-3). MFR assessed by cardiac rubidium-82 PET imaging is a predictor of cardiovascular events after orthotopic heart transplant and is associated with cardiac allograft vasculopathy severity. © 2018 American Heart Association, Inc.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities.

PubMed

Yoshiji, Hitoshi; Kuriyama, Shigeki; Noguchi, Ryuichi; Yoshii, Junichi; Ikenaka, Yasuhide; Yanase, Koji; Namisaki, Tadashi; Kitade, Mitsuteru; Yamazaki, Masaharu; Akahane, Takemi; Asada, Kiyoshi; Tsujimoto, Tatsuhito; Uemura, Masahito; Fukui, Hiroshi

2006-01-01

Recent studies have revealed that angiogenesis plays a pivotal role in carcinogenesis and tumor growth. We previously reported that the clinically used vitamin K(2) (VK) and angiotensin-converting enzyme inhibitor (ACE-I) exerted potent anti-angiogenic activities. The aim of our current study was to examine the combination effect of VK and ACE-I on hepatocarcinogenesis induced by diethyl-nitrosamine, and orthotopic hepatocellular carcinoma (HCC) growth in rats. When used individually, both VK and ACE-I at clinically comparable low doses exerted significant inhibitory effects on tumor development in the liver. A combination treatment of VK and ACE-I showed a more potent suppressive effect against hepatocarcinogenesis. Neovascularization increased during hepatocarcinogenesis, and VK and ACE-I significantly attenuated angiogenesis in the tumor. In orthotopic HCC transplantation, VK and ACE-I also showed marked suppressive effects against HCC development similar to those against hepatocarcinogenesis. In both experiments, the suppressive effects of VK and ACE-I against angiogenesis were similar in magnitude to their inhibitory effects against hepatocarcinogenesis and orthotopic HCC development. In the orthotopic model, VK and ACE-I treatment resulted in a marked increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. Since both VK and ACE-I are widely used in clinical practice without serious side effects, this combination therapy may be an effective new therapeutic strategy against hepatocarcinogenesis and HCC growth in the future.

[Renal failure in patients with liver transplant: incidence and predisposing factors].

PubMed

Gerona, S; Laudano, O; Macías, S; San Román, E; Galdame, O; Torres, O; Sorkin, E; Ciardullo, M; de Santibañes, E; Mastai, R

1997-01-01

Renal failure is a common finding in patients undergoing orthotopic liver transplantation. The aim of the present study was to evaluate the incidence, prognostic value of pre, intra and postoperative factors and severity of renal dysfunction in patients who undergo liver transplantation. Therefore, the records of 38 consecutive adult patients were reviewed. Renal failure was defined arbitrarily as an increase in creatinine (> 1.5 mg/dl) and/or blood urea (> 80 mg/dl). Three patients were excluded of the final analysis (1 acute liver failure and 2 with a survival lower than 72 hs.) Twenty one of the 35 patients has renal failure after orthotopic liver transplantation. Six of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 15 patients within the hospitalization (40 +/- 10 days) (Mean +/- SD). In he overall series, liver function, evaluated by Child-Pugh classification, a higher blood-related requirements and cyclosporine levels were observed more in those who experienced renal failure than those who did not (p < 0.05). Early renal failure was related with preoperative (liver function) and intraoperative (blood requirements) factors and several causes (nephrotoxic drugs and graft failure) other than cyclosporine were present in patients who developed late renal impairment. No mortality. No mortality was associated with renal failure. We conclude that renal failure a) is a common finding after liver transplantation, b) the pathogenesis of this complication is multifactorial and, c) in not related with a poor outcome.

Management of end stage liver disease (ESLD): what is the current role of orthotopic liver transplantation (OLT)?

PubMed

Miró, José M; Laguno, Montserrat; Moreno, Asuncion; Rimola, Antonio

2006-01-01

Liver disease due to chronic hepatitis B and C is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classical opportunistic complications of severe immunodeficiency have declined dramatically. Orthotopic liver transplantation (OLT) is the only therapeutic option for patients with end-stage liver disease (ESLD). Accumulated experience in North America and Europe in the last 5 years indicates that 3-year survival in selected HIV-infected recipients of liver transplants was similar to that of HIV-negative recipients. So, HIV infection by itself is not therefore a contraindication for liver transplantation. As survival of HIV-infected patients with ESLD is shorter than non-HIV-infected population, the evaluation for OLT should be made after the first liver decompensation. The current selection criteria for HIV-positive transplant candidates include: no history of opportunistic infections or HIV-related neoplasms, CD4 cell count > 100 cells/mm(3), and plasma HIV viral load suppressible with antiretroviral treatment. For drug abusers, a 2-year abstinence from heroin and cocaine is required, although patients can be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretrovirals and immunosuppressive drugs, and the management of relapse of HCV infection. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. Currently, HCV re-infection is the main cause for concern.

Laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder: technique and clinical outcomes.

PubMed

Shao, Pengfei; Li, Pu; Ju, Xiaobing; Qin, Chao; Li, Jie; Lv, Qiang; Meng, Xiaoxin; Yin, Changjun

2015-02-01

To study the feasibility and safety of laparoscopic radical cystectomy with intracorporeal orthotopic ileal neobladder and to evaluate the role of endoscopic stapling in neobladder construction. Fifty-five patients with bladder cancer who underwent laparoscopic radical cystectomy were retrospectively examined. Extended pelvic lymph node dissection was performed before cystectomy. An ileal segment of 50 cm was harvested to construct a U-shaped reservoir. The bottom of the reservoir was anastomosed with the posterior urethra. Twenty-five patients underwent neobladder construction by manual suturing and 30 patients by endoscopic stapler suturing. The mean operative time was 346 minutes, and mean neobladder construction time was 230 minutes. The median estimated blood loss was 500 mL, and 17 patients received intraoperative transfusion. Postoperative complications included 2 cases of urine leakage, 7 cases of pyelonephritis, 4 cases of incomplete bowel obstruction, 1 case of anastomotic stricture, and 1 case of death. Endoscopic stapler suturing for neobladder construction took significantly less time than manual suturing. However, neobladder stones were found in 2 patients who underwent operation using endoscopic suturing, and the stones were removed cystoscopically. The functional outcomes of the 2 constructive methods were comparable. Laparoscopic radical cystectomy with intracorporeal orthotopic neobladder is safe and feasible for experienced laparoscopic surgeons. Application of endoscopic stapler simplifies the surgical procedure while increasing the risk of neobladder stone formation. Copyright © 2015 Elsevier Inc. All rights reserved.

Liver transplantation for severe hepatic trauma: Experience from a single center

PubMed Central

Delis, Spiros G; Bakoyiannis, Andreas; Selvaggi, Gennaro; Weppler, Debbie; Levi, David; Tzakis, Andreas G

2009-01-01

Liver transplantation has been reported in the literature as an extreme intervention in cases of severe and complicated hepatic trauma. The main indications for liver transplant in such cases were uncontrollable bleeding and postoperative hepatic insufficiency. We here describe four cases of orthotopic liver transplantation after penetrating or blunt liver trauma. The indications were liver failure, extended liver necrosis, liver gangrene and multiple episodes of gastrointestinal bleeding related to portal hypertension, respectively. One patient died due to postoperative cerebral edema. The other three patients recovered well and remain on immunosuppression. Liver transplantation should be considered as a saving procedure in severe hepatic trauma, when all other treatment modalities fail. PMID:19340909

Vascular invasion is a prognostic indicator in hepatoblastoma.

PubMed

Shi, Yan; Commander, Sarah J; Masand, Prakash M; Heczey, Andras; Goss, John A; Vasudevan, Sanjeev A

2017-06-01

The data regarding vascular invasion as a prognostic factor in hepatoblastoma (HB) are conflicted. The purpose of this study is to examine the relationship between vascular invasion and outcomes. This is a retrospective review of patients <18 years old who underwent resection for hepatoblastoma from 1998 to 2015. Pathology reports were used to identify patients who had pathologic vascular invasion (VI), and those who did not (NVI). Sixty-six children were identified with a median age at diagnosis of 21months (interquartile range: 10-33months). Pathologic vascular invasion was present in 42/66 (64%) patients. A significant difference (P=0.02) in 3-year overall survival (3YOS) was detected between NVI (95%) and VI (61%). Recurrent disease was present in 8/66 (12%) patients. A marginally significant difference (P=0.08) was found in 3-year recurrence free survival (3YRFS) between NVI (94%) and the VI (76%) groups. Patients with NVI had no metastatic disease, had a lower recurrence rate, universally responded to neoadjuvant chemotherapy, and were less likely to have small cell undifferentiated histology. Twenty-one children underwent orthotopic liver transplant (OLT), with no difference in 3YROS or 3YRFS. Pathologic vascular invasion is associated with significantly worse 3YOS in HB, and lack of vascular invasion was associated with more favorable disease characteristics. The presence of pathologic vascular invasion did not confer a worse outcome in patients treated with liver transplantation in this cohort of patients. Retrospective review. Level III. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic Portal Vein Thrombosis After Liver Transplantation in a Child Treated by a Combined Minimally Invasive Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco Cesar, E-mail: fcarnevale@uol.com.br; Santos, Aline Cristine Barbosa; Zurstrassen, Charles Edouard

Portal vein thrombosis (PVT) after orthotopic liver transplantation is an infrequent complication, and when it is present surgical treatment is considered for traditional management. Percutaneous transhepatic portal vein angioplasty has been described as an option to treat PVT with a lower morbidity than conventional surgical treatments. This article describes a case of chronic PVT in a child after a living donor liver transplantation managed by percutaneous transhepatic and surgical approaches.

Epsilon-Aminocaproic Acid Has No Association With Thromboembolic Complications, Renal Failure, or Mortality After Liver Transplantation.

PubMed

Nicolau-Raducu, Ramona; Ku, Timothy C; Ganier, Donald R; Evans, Brian M; Koveleskie, Joseph; Daly, William J; Fish, Brian; Cohen, Ari J; Reichman, Trevor W; Bohorquez, Humberto E; Bruce, David S; Carmody, Ian C; Loss, George E; Gitman, Marina; Marshall, Thomas; Nossaman, Bobby D

2016-08-01

To examine the role of epsilon-aminocaproic acid (EACA) administered after reperfusion of the donor liver in the incidences of thromboembolic events and acute kidney injury within 30 days after orthotopic liver transplantation. One-year survival rates between the EACA-treated and EACA-nontreated groups also were examined. Retrospective, observational, cohort study design. Single-center, university hospital. The study included 708 adult liver transplantations performed from 2008 to 2013. None. EACA administration was not associated with incidences of intracardiac thrombosis/pulmonary embolism (1.3%) or intraoperative death (0.6%). Logistic regression (n = 708) revealed 2 independent risk factors associated with myocardial ischemia (age and pre-transplant vasopressor use) and 8 risk factors associated with the need for post-transplant dialysis (age, female sex, redo orthotopic liver transplantation, preoperative sodium level, pre-transplant acute kidney injury or dialysis, platelet transfusion, and re-exploration within the first week after transplant); EACA was not identified as a risk factor for either outcome. One-year survival rates were similar between groups: 92% in EACA-treated group versus 93% in the EACA-nontreated group. The antifibrinolytic, EACA, was not associated with an increased incidence of thromboembolic complications or postoperative acute kidney injury, and it did not alter 1-year survival after liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

GSK3β and VDAC Involvement in ER Stress and Apoptosis Modulation during Orthotopic Liver Transplantation

PubMed Central

Zaouali, Mohamed Amine; Panisello, Arnau; Lopez, Alexandre; Castro, Carlos; Folch, Emma; Carbonell, Teresa; Rolo, Anabela; Palmeira, Carlos Marques; Garcia-Gil, Agustin; Adam, René; Roselló-Catafau, Joan

2017-01-01

We investigated the involvement of glycogen synthase kinase-3β (GSK3β) and the voltage-dependent anion channel (VDAC) in livers subjected to cold ischemia–reperfusion injury (I/R) associated with orthotopic liver transplantation (OLT). Rat livers were preserved in University of Wisconsin (UW) and Institute Georges Lopez (IGL-1) solution, the latter enriched or not with trimetazidine, and then subjected to OLT. Transaminase (ALT) and HMGB1 protein levels, glutamate dehydrogenase (GLDH), and oxidative stress (MDA) were measured. The AKT protein kinase and its direct substrates, GSK3β and VDAC, as well as caspases 3, 9, and cytochrome C and reticulum endoplasmic stress-related proteins (GRP78, pPERK, ATF4, and CHOP), were determined by Western blot. IGL-1+TMZ significantly reduced liver injury. We also observed a significant phosphorylation of AKT, which in turn induced the phosphorylation and inhibition of GSK3β. In addition, TMZ protected the mitochondria since, in comparison with IGL-1 alone, we found reductions in VDAC phosphorylation, apoptosis, and GLDH release. All these results were correlated with decreased ER stress. Addition of TMZ to IGL-1 solution increased the tolerance of the liver graft to I/R injury through inhibition of GSK3β and VDAC, contributing to ER stress reduction and cell death prevention. PMID:28282906

Supercooling Preservation Of The Rat Liver For Transplantation

PubMed Central

Bruinsma, Bote G.; Berendsen, Tim A.; Izamis, Maria-Louisa; Yeh, Heidi; Yarmush, Martin L.; Uygun, Korkut

2015-01-01

The current standard for liver preservation is limited in duration. Employing a novel subzero preservation technique that includes supercooling and machine perfusion can significantly improve preservation and prolong storage times. By loading rat livers with cryoprotectants to prevent both intra- and extracellular ice formation and protect against hypothermic injury, livers can be cooled to −6 °C without freezing and kept viable for up to 96 hours. Here, we describe the procedures of loading cryoprotectants by means of subnormothermic machine perfusion (SNMP), controlled cooling to a supercooled state, followed by SNMP recovery and orthotopic liver transplantation. PMID:25692985

17β-Estradiol protects the liver against cold ischemia/reperfusion injury through the Akt kinase pathway.

PubMed

Yang, Xiaohua; Qin, Lei; Liu, Jianxia; Tian, Liping; Qian, Haixin

2012-12-01

Hepatic ischemia-reperfusion (IR) injury occurs during liver resection and transplantation. Recent studies have shown that 17β-estradiol (E2) can protect the heart and liver against warm IR. The present study focused on the cytoprotective effects of E2 on cold IR injury to the liver. Sprague-Dawley male rats were randomly divided into three groups: sham, IR, and IR plus E2. The model of rat orthotopic liver transplantation was used. The rats in the IR plus E2 group were intraperitoneally injected with E2 (100 μg/kg/d) for 7 d before surgery. The sham and IR group received the same quantity of saline. The donor livers were then orthotopically transplanted into rats after cold ischemia preservation for 4 h at 4°C lactated Ringer's solution. After 6 h reperfusion, liver function, bile flow volume, hepatocyte apoptosis, and activation of Akt, glycogen synthase kinase-3β, and Bcl-2-associated death promoter were assessed. The survival rate of the rats was also investigated. The administration of E2 significantly prolonged the survival of liver grafts by improving liver function and decreasing hepatocyte apoptosis. Rats undergoing E2 demonstrated a greater level activation of Akt in the liver compared with the IR group. In addition, E2 also inhibited the activities of glycogen synthase kinase-3β, Bcl-2-associated death promoter, and caspase-3-induced by IR injury. E2 pretreatment attenuated the hepatocellular damage caused by hepatic cold IR injury through the Akt pathway. Estrogen therapy might be important in clinical settings associated with cold IR injury during liver transplantation. Copyright © 2012 Elsevier Inc. All rights reserved.

Liver transplantation from hepatitis B surface antigen positive donors: a safe way to expand the donor pool.

PubMed

Loggi, Elisabetta; Micco, Lorenzo; Ercolani, Giorgio; Cucchetti, Alessandro; Bihl, Florian K; Grazi, Gian Luca; Gitto, Stefano; Bontadini, Andrea; Bernardi, Mauro; Grossi, Paolo; Costa, Alessandro Nanni; Pinna, Antonio Daniele; Brander, Christian; Andreone, Pietro

2012-03-01

The main limitation of orthotopic liver transplantation (OLT) is the scarcity of available donor organs. A possibility to increase the organ pool is to use grafts from hepatitis B virus surface antigen (HBsAg) positive donors, but few data are currently available in this setting. We assessed the clinical, serovirological, and immunological outcomes of liver transplant from HBsAg positive donors in a single centre study. From 2005 to 2009 10 patients underwent OLT from HBsAg positive donors, for HBV-related disease (n=6) or HBV-unrelated disease (n=4). The median follow-up was 42 months (range 12-60). All recipients were HBcAb positive and were given antiviral prophylaxis. Patients transplanted for HBV-related disease never cleared HBsAg. Two HBsAg negative patients never tested positive for HBsAg, whereas the others experienced an HBsAg appearance, followed by spontaneous production of anti-HBs, allowing HBsAg clearance. No patient ever had any sign of HBV hepatitis. HBV replication was effectively controlled by antiviral therapy. The immunologic sub-study showed that a most robust anti-HBV specific T cell response was associated with the control of HBV infection. OLT from HBsAg positive donors seems to be a safe procedure in the era of highly effective antiviral therapy. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Liver transplantation in man: morphometric analysis of the parenchymal alterations following cold ischaemia and warm ischaemia/reperfusion

PubMed Central

VIZZOTTO, LAURA; VERTEMATI, MAURIZIO; DEGNA, CARLO TOMMASINI; ASENI, PAOLO

2001-01-01

Ischaemia and reperfusion phases represent critical events during liver transplantation. The purpose of this study was to describe morphological alterations of both vascular and parenchymal compartments after ischaemia and reperfusion and to evaluate the possible relationship between morphometric parameters and biochemical/clinical data. Three needle biopsies were drawn from 20 patients who underwent orthotopic liver transplantation. The first biopsy was taken before flushing with preservation solution, and the second and the third to evaluate respectively the effects of cold ischaemia and of warm ischaemia/reperfusion. Biopsies were examined by an image analyser and morphometric parameters related to the liver parenchyma were evaluated. At the second biopsy we observed a decrease of the endothelium volume fraction while the same parameter referred to the sinusoidal lumen achieved a peak value. The hepatocytes showed a lower surface parenchymal/vascular sides ratio. This parameter was reversed at the end of the reperfusion phase; furthermore the third biopsy revealed endothelial swelling and a decreased volume fraction of the sinusoidal lumen. The results quantify the damage to the sinusoidal bed which, as already known, is one of the main targets of cold ischaemia; warm ischaemia and reperfusion accentuate endothelial damage. The end of transplantation is characterised by damage chiefly to parenchymal cells. Hepatocytes show a rearrangement of their surface sides, probably related to the alterations of the sinusoidal bed. In addition, the fluctuations of morphometric parameters during ischaemia/reperfusion correlate positively with biochemical data and clinical course of the patients. PMID:11430699

[Orthotopic liver transplantation in adult patients with cadaveric grafts. Experience of the Fundeni Center of General Surgery and Liver Transplantation].

PubMed

Popescu, I; Ionescu, M; Tulbure, D; Ciurea, S; Băilă, S; Braşoveanu, V; Hrehoreţ, D; Sârbu-Boeţi, P; Pietrăreanu, D; Alexandrescu, S; Dorobanţu, B; Gheorghe, L; Gheorghe, C; Mihăilă, M; Boroş, M; Croitoru, M; Herlea, V

2005-01-01

We analyze the experience of the Center of General Surgery and Liver Transplantation from the Fundeni Clinical Institute (Bucharest, Romania) regarding orthotopic liver transplantation (OLT) in adult recipients, with whole liver grafts from cadaveric donors, between April 2000 (when the first successful LT was performed in Romania) and December 2004. This series includes 37 OLTs in adult recipients (16 women and 21 men, aged between 29-57 years--average 46 years). Other two LT with whole liver cadaveric grafts and two reduced-size LT were performed in children; also, in the same period, due to the acute organ shortage, other methods of LT were performed in 28 patients (21 living donor LT, 6 split LT and one "do mino" LT), that were not included in the present series. The indications for OLT were HBV cirrhosis--10, HBV+HDV cirrhosis--4, HCV cirrhosis--11, HBV+HCV cirrhosis--2, biliary cirrhosis--5, Wilson disease--2, alcoholic cirrhosis--1, non-alcoholic liver disease--1, autoimmune cirrhosis--1. With three exceptions, in which the classical transplantation technique was used, the liver was grafted following the technique described by Belghiti. Local postoperative complications occurred in 15 patients (41%) and general complications in 17 (46%); late complications were registered in 18 patients (49%) and recurrence of the initial disease in 6 patients (16%). Intrao- and postoperative mortality was 8% (3/37). There were two patients (5%) who died because of immunosuppressive drug neurotoxicity at more than 30 days following LT. Four patients (11%) died lately because of PTLD, liver venoocclusive disease, recurrent autoimmune hepatitis and liver venoocclusive disease, myocardial infarction, respectively. Thirty-four patients survived the postoperative period (92%); according to Kaplan-Meier analysis, actuarial patient-survival rate at month 31 was 75%.

Change in hepatic function, hemodynamics, and morphology after liver transplant. Physiological effect of therapy.

PubMed

Millikan, W J; Henderson, J M; Stewart, M T; Warren, W D; Marsh, J W; Galloway, J R; Jennings, H; Kawasaki, S; Dodson, T F; Perlino, C A

1989-05-01

Orthotopic liver transplantation (OLT) has become standard therapy for patients with acute hepatic necrosis and end-stage liver disease. This study measured change in hepatic function (galactose elimination capacity [GEC]), liver blood flow (low dose galactose clearance: flow), hepatic volume (CT scan; volume) and morphology after OLT. The aim was to measure the physiologic response after OLT and compare this response with that after selective shunt (SS) and sclerotherapy (ES) to determine which patients should receive specific therapy. Between January 1987 and November 1988, 37 patients underwent OLT. Operative mortality was 18%, which was similar to that of SS in Child's C cirrhotics. GEC and volume were less in transplant patients than in cirrhotics treated with SS or ES. GEC, flow, and volume normalized after OLT; GEC was preserved after ES and SS, but volume decreased. Three preoperative patterns were observed that can aid in selection of OLT candidates. Patients with chronic cirrhosis (chronic active hepatitis; cryptogenic) need OLT when GEC is less than or equal to 225 mg/min and volume is less than or equal to 50% normal. Patients with Budd-Chiari Syndrome require OLT if cirrhosis has evolved. Patients with sclerosing cholangitis and primary biliary cirrhosis qualify for transplants when complications of the portal hypertensive syndrome develop. The studies can also direct therapy for ES failures. Selective shunt is indicated in those patients with stable disease whose GEC is greater than or equal to 300 mg/min and liver volume is greater than 75% normal; OLT is indicated for cirrhotics with GEC that is less than 225 mg/min and liver volume that is less than 50% predicted normal.

Effects of N-Acetylcysteine Addition to University of Wisconsin Solution on the Rate of Ischemia-Reperfusion Injury in Adult Orthotopic Liver Transplant.

PubMed

Aliakbarian, Mohsen; Nikeghbalian, Saman; Ghaffaripour, Sina; Bahreini, Amin; Shafiee, Mohammad; Rashidi, Mohammad; Rajabnejad, Yaser

2017-08-01

One of the main concerns in liver transplant is the prolonged ischemia time, which may lead to primary graft nonfunction or delayed function. N-acetylcysteine is known as a hepato-protective agent in different studies, which may improve human hepatocyte viability in steatotic donor livers. This study investigated whether N-acetylcysteine can decrease the rate of ischemia-reperfusion syndrome and improve short-term outcome in liver transplant recipients. This was a double-blind, randomized, control clinical trial of 115 patients. Between April 2012 and January 2013, patients with orthotopic liver transplant were randomly divided into 2 groups; in 49 cases N-acetylcysteine was added to University of Wisconsin solution as the preservative liquid (experimental group), and in 66 cases standard University of Wisconsin solution was used (control group). We compared postreperfusion hypotension, inotrope requirement before and after portal reperfusion, intermittent arterial blood gas analysis and potassium measurement, pathological review of transplanted liver, in-hospital complications, morbidity, and mortality. There was no significant difference between the groups regarding time to hepatic artery reperfusion, hospital stay, vascular complications, inotrope requirement before and after portal declamping, and blood gas analysis. Hypotension after portal reperfusion was significantly more common in experimental group compared with control group (P = .005). Retransplant and in-hospital mortality were comparable between the groups. Preservation of the liver inside Univer-sity of Wisconsin solution plus N-acetylcysteine did not change the rate of ischemia reperfusion injury and short-term outcome in liver transplant recipients.

Indocyanine green plasma disappearance rate during the anhepatic phase of orthotopic liver transplantation.

PubMed

Bruegger, Lukas; Studer, Peter; Schmid, Stefan W; Pestel, Gunther; Reichen, Juerg; Seiler, Christian; Candinas, Daniel; Inderbitzin, Daniel

2008-01-01

Non-invasive pulse spectrophotometry to measure indocyanine green (ICG) elimination correlates well with the conventional invasive ICG clearance test. Nevertheless, the precision of this method remains unclear for any application, including small-for-size liver remnants. We therefore measured ICG plasma disappearance rate (PDR) during the anhepatic phase of orthotopic liver transplantation using pulse spectrophotometry. Measurements were done in 24 patients. The median PDR after exclusion of two outliers and two patients with inconstant signal was 1.55%/min (95% confidence interval [CI]=0.8-2.2). No correlation with patient age, gender, body mass, blood loss, administration of fresh frozen plasma, norepinephrine dose, postoperative albumin (serum), or difference in pre and post transplant body weight was detected. In conclusion, we found an ICG-PDR different from zero in the anhepatic phase, an overestimation that may arise in particular from a redistribution into the interstitial space. If ICG pulse spectrophotometry is used to measure functional hepatic reserve, the verified average difference from zero (1.55%/min) determined in our study needs to be taken into account.

Biliary complications after orthotopic liver transplantation from donors after cardiac death: broad spectrum of disease.

PubMed

Abou Abbass, A; Abouljoud, M; Yoshida, A; Kim, D Y; Slater, R; Hundley, J; Kazimi, M; Moonka, D

2010-11-01

Donation-after-death liver transplantation (DCD-LT) carries higher complication rates compared with donation-after-brain death liver transplantation (DBD-LT). In this report we describe our experience with biliary complications in DCD-LT with emphasis on anatomical patterns and outcomes. We performed retrospective review of patients' medical records from August 2004 to December 2008, during which time total of 26 DCD-LTs were performed. Mean follow-up was 29 months (range 3 to 51 months). Biliary complications occurred in 12 patients (46%), of whom 9 were related to DCD (35%). Four patients had more than 1 biliary complication, and 4 had concomitant arterial problems (stricture/thrombosis). Treatment of complications included: ERCP (n = 5, 3 resolved), conversion to roux (n = 5, 2 resolved), revision of roux (n = 1), percutaneous transhepatic cholangiography (n = 1), artery revision (n = 3). Three patients with casts had operative extraction of casts depicting a mummified biliary tree; histology showed casts and fibrosis and anastomotic suture material. Six patients underwent retransplantation (23%). Among retransplanted patients, 2 deaths occurred (7.7%). Our experience with DCD-LT reveals a high prevalence of biliary complications with a new and wide spectrum of clinicopathologic findings. Better strategies for prevention of these unique biliary complications are needed to better justify the added risks and costs for performance of DCD-LT. Copyright © 2010 Elsevier Inc. All rights reserved.

Cost of achieving equivalent outcomes in sicker patients after liver transplant.

PubMed

Dhar, Vikrom K; Wima, Koffi; Kim, Young; Hoehn, Richard S; Jung, Andrew D; Ertel, Audrey E; Diwan, Tayyab S; Paterno, Flavio; Shah, Shimul A

2018-03-01

We aimed to characterize variability in cost after straightforward orthotopic liver transplant (OLT). Using the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified patients who underwent OLT between 2011 and 2014. Patients meeting criteria for straightforward OLT, defined as length of stay < 14 days with discharge to home, were selected (n = 5763) and grouped into tertiles (low, medium, high) according to cost of perioperative stay. Patients undergoing straightforward OLT were of similar demographics regardless of cost. High cost patients were more likely to require preoperative hemodialysis, had higher severity of illness, and higher model for end-stage liver disease (MELD) (p < 0.01). High cost patients required greater utilization of resources including lab tests, blood transfusions, and opioids (p < 0.01). Despite having higher burden of disease and requiring increased resource utilization, high cost OLT patients with a straightforward perioperative course were shown to have identical 2-year graft and overall survival compared to lower cost patients (p = 0.82 and p = 0.63), respectively. Providing adequate perioperative care for OLT patients with higher severity of illness and disease burden requires increased cost and resource utilization; however, doing so provides these patients with long term survival equivalent to more routine patients. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Donor age does not influence 12-month outcome after orthotopic liver transplantation.

PubMed

Faber, W; Seehofer, D; Puhl, G; Guckelberger, O; Bertram, C; Neuhaus, P; Bahra, M

2011-12-01

Orthotopic liver transplantation (OLT) is the most effective treatment for patients with end-stage liver disease to date. The discrepancy between the numbers of donor livers and recipients has become a significant problem, resulting in a high patient mortality on the waiting list. Due to this, an expansion of the donor pool is necessary, for example, by accepting donor grafts from elderly donors. The aim of this study was to investigate the outcome after OLT depending on donor age. We retrospectively evaluated the outcome of 272 full-size cadaveric initial single OLTs within 12 months after OLT. The outcome was analyzed by dividing the collective into four donor age categories: donor age under 50, between 50 and 59, between 60 and 69, and 70 years or above. The outcome after OLT in these patients was retrospectively reviewed by using a prospective database. Patients positive for hepatitis C were excluded from the analysis. No increase of initial nonfunction was observed. Furthermore, no significant differences with regard to surgical complications and serum liver parameter were observed between the groups. Neither patient mortality rates nor rejection rates were different between the groups. However, ischemic-type biliary lesion rates increased significantly with donor age over 70 years (P<.05). The acceptance of liver grafts from older donors is a possible alternative to narrow the gap between donated and required organs. Safe use under optimal protocols is necessary to avoid a deterioration of post-OLT results. Copyright © 2011 Elsevier Inc. All rights reserved.

MELD score measured day 10 after orthotopic liver transplantation predicts death and re-transplantation within the first year.

PubMed

Rostved, Andreas A; Lundgren, Jens D; Hillingsø, Jens; Peters, Lars; Mocroft, Amanda; Rasmussen, Allan

2016-11-01

The impact of early allograft dysfunction on the outcome after liver transplantation is yet to be established. We explored the independent predictive value of the Model for End-Stage Liver Disease (MELD) score measured in the post-transplant period on the risk of mortality or re-transplantation. Retrospective cohort study on adults undergoing orthotopic deceased donor liver transplantation from 2004 to 2014. The MELD score was determined prior to transplantation and daily until 21 days after. The risk of mortality or re-transplantation within the first year was assessed according to quartiles of MELD using unadjusted and adjusted stepwise Cox regression analysis. We included 374 consecutive liver transplant recipients of whom 60 patients died or were re-transplanted. The pre-transplant MELD score was comparable between patients with good and poor outcome, but from day 1 the MELD score significantly diversified and was higher in the poor outcome group (MELD score quartile 4 versus quartile 1-3 at day 10: HR 5.1, 95% CI: 2.8-9.0). This association remained after adjustment for non-identical blood type, autoimmune liver disease and hepatocellular carcinoma (adjusted HR 5.3, 95% CI: 2.9-9.5 for MELD scores at day 10). The post-transplant MELD score was not associated with pre-transplant MELD score or the Eurotransplant donor risk index. Early determination of the MELD score as an indicator of early allograft dysfunction after liver transplantation was a strong independent predictor of mortality or re-transplantation and was not influenced by the quality of the donor, or preoperative recipient risk factors.

The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors.

PubMed

Chang, Chun-Jung; Tai, Kuo-Feng; Roffler, Steve; Hwang, Lih-Hwa

2004-11-15

Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

PubMed

Markowitz, Geoffrey J; Michelotti, Gregory A; Diehl, Anna Mae; Wang, Xiao-Fan

2015-04-01

Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard to immune cell prevalence and presence of mediators of immune function. To better understand the consequences of liver disease on tumor growth and the interplay with its microenvironment, we utilized two standard methods of fibrosis induction and orthotopic implantation of tumors into the inflamed and fibrotic liver to mimic the liver condition in human HCC patients. Compared to non-diseased controls, tumor growth was significantly enhanced under fibrotic conditions. The immune cells that infiltrated the tumors were also drastically different, with decreased numbers of natural killer cells but greatly increased numbers of immune-suppressive CD11b + Gr1 hi myeloid cells in both models of fibrosis. In addition, there were model-specific differences: Increased numbers of CD11b + myeloid cells and CD4 + CD25 + T cells were found in tumors in the bile duct ligation model but not in the carbon tetrachloride model. Induction of fibrosis altered the cytokine production of implanted tumor cells, which could have farreaching consequences on the immune infiltrate and its functionality. Taken together, this work demonstrates that the combination of fibrosis induction with orthotopic tumor implantation results in a markedly different tumor microenvironment and tumor growth kinetics, emphasizing the necessity for more accurate modeling of HCC progression in mice, which takes into account the drastic changes in the tissue caused by chronic liver disease.

Characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver: A report from the National Cancer Database.

PubMed

Shi, Yan; Rojas, Yesenia; Zhang, Wei; Beierle, Elizabeth A; Doski, John J; Goldfarb, Melanie; Goldin, Adam B; Gow, Kenneth W; Langer, Monica; Meyers, Rebecka L; Nuchtern, Jed G; Vasudevan, Sanjeev A

2017-04-01

To examine patient characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver (UESL) using a multi-institutional database. UESL is a rare disease (incidence is one per million). Therefore, the current literature is mostly limited to small case series. The National Cancer Database was queried for primary UESL diagnosed between 1998 and 2012. A total of 103 patients (<18 years) were identified. The 5-year overall survival of the entire group was 86%. The best outcomes were seen in children who had tumors smaller than 15 cm and were able to undergo surgical resection with or without chemotherapy. Margin status did not appear to significantly affect survival. The most common type of resection was hemihepatectomy (37%), followed by sectionectomy (10%) and trisectionectomy (10%). Orthotopic liver transplant was performed in 10 children, all of whom survived to 5 years. Surgical resection with or without chemotherapy should be the mainstay of treatment in children with UESL, and is associated with very favorable outcomes. Negative surgical margins were not associated with improved survival. Orthotopic liver transplantation may be a viable method of attaining local control in tumors, which would otherwise be unresectable. © 2016 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

Characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver: A report from the National Cancer Database

PubMed Central

Shi, Yan; Rojas, Yesenia; Zhang, Wei; Beierle, Elizabeth A.; Doski, John J.; Goldfarb, Melanie; Goldin, Adam B.; Gow, Kenneth W.; Langer, Monica; Meyers, Rebecka L.; Nuchtern, Jed G.

2016-01-01

Abstract Objective To examine patient characteristics and outcomes in children with undifferentiated embryonal sarcoma of the liver (UESL) using a multi‐institutional database. Summary Background Data UESL is a rare disease (incidence is one per million). Therefore, the current literature is mostly limited to small case series. Methods The National Cancer Database was queried for primary UESL diagnosed between 1998 and 2012. Results A total of 103 patients (<18 years) were identified. The 5‐year overall survival of the entire group was 86%. The best outcomes were seen in children who had tumors smaller than 15 cm and were able to undergo surgical resection with or without chemotherapy. Margin status did not appear to significantly affect survival. The most common type of resection was hemihepatectomy (37%), followed by sectionectomy (10%) and trisectionectomy (10%). Orthotopic liver transplant was performed in 10 children, all of whom survived to 5 years. Conclusion Surgical resection with or without chemotherapy should be the mainstay of treatment in children with UESL, and is associated with very favorable outcomes. Negative surgical margins were not associated with improved survival. Orthotopic liver transplantation may be a viable method of attaining local control in tumors, which would otherwise be unresectable. PMID:27781381

Natural History of Cirrhosis of Liver after First Decompensation: A Prospective Study in India.

PubMed

Shah, Apurva S; Amarapurkar, Deepak N

2018-03-01

As liver cirrhosis is a dynamic condition, it is possible to improve survival in decompensated cirrhosis. Hence, we planned a prospective study to determine the natural history of cirrhosis after first decompensation. We enrolled all patients of liver cirrhosis who presented with first episode of decompensation defined by the presence of ascites, either overt or detected by Ultrasonography (UD), Gastroesophageal Variceal Bleeding (GEVB), and Hepatic Encephalopathy (HE). All patients were followed up to death/liver transplant or at least for the period of 1 year. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or Orthotopic Liver Transplantation (OLT)). In total of 110 cirrhotic patients (93 males, mean age 50 ± 11 years), the most frequent etiology was alcohol (48%), followed by nonalcoholic steatohepatitis/cryptogenic (26%), hepatitis B (10%), autoimmune hepatitis (7%), and hepatitis C (6%). The distribution of CTP classes was: 4%, 56%, and 41% in class A, B, and C, respectively. Ascites was the most common decompensation found in 88 patients (80%) followed by HE (14%) and GEVB (6%). At 1-year follow up, transplant free survival was 78%, 2 underwent OLT, 4 developed hepatocellular carcinoma, and 24 died. Cumulative incidence of failure (death or OLT) by type of decompensation after 1 year was: 22% overt ascites, 50% GEVB, 28% UD ascites, 20% HE, and 33% ascites and GEVB concomitant. Patients with UD ascites do not have a negligible mortality rate as compared to overt ascites. Patients with cirrhosis after first decompensation have better transplant free survival with treatment of etiology and complications than previously mentioned in literature.

Betel quid chewing leads to the development of unique de novo malignancies in liver transplant recipients, a retrospective single center study in Taiwan.

PubMed

Chen, Yi-Chan; Cheng, Chih-Hsien; Wang, Yu-Chao; Wu, Ting-Jun; Chou, Hong-Shiue; Chan, Kun-Ming; Lee, Wei-Chen; Lee, Chen-Fang; Soong, Ruey Shyang

2016-09-01

Orthotopic liver transplantation (OLT) is the choice of treatment not only for end-stage liver disease and acute liver failure but also for hepatocellular carcinoma (HCC). The development of de novo malignancies after liver transplantation plays an important role in late mortality; the incidence of late mortality has increased owing to improved survival. The incidence of de novo malignancies is 2.3% to 25%, which is 2 to 3 times that of malignancies in the general population. The most commonly reported de novo malignancies in solid organs are skin cancer, Karposi sarcoma, and colon cancer according to the frequency of exposure to a specific carcinogen. We hypothesized that exposure to different carcinogens would change the distribution of de novo malignancies among patients after OLT. In Taiwan, 10% of the population is exposed to a unique carcinogen, the betel quid, which is associated with a high incidence of head and neck cancer (HNC) among the Taiwanese population.From 2004 to 2014, we retrospectively reviewed 484 cases post-OLT at our institution and 16 patients with 17 de novo malignancies were identified. Most of the patients had HNC, which is in contrast to previous literature reports.Univariate and multivariate analyses identified betel quid chewing as the main leading factor for HNC in the Taiwanese population.Routine screening of the oral mucosa in patients with the habit of betel quid chewing is recommended in Taiwan for the early detection of HNC. Routine screening with aggressive treatment after diagnosis of HNC in patients with the habit of chewing betel quid, who underwent OLT, resulted in good patient prognosis.

Liver Procurement for Orthotopic Transplantation: An Analysis of the Pittsburgh Experience

PubMed Central

Van Thiel, David H.; Schade, Robert R.; Hakala, Thomas R.; Starzl, Thomas E.; Denny, Donald

2010-01-01

The incidence of prospective organ donors in the United States and the techniques which are to used to guarantee their optimal use after identification are analyzed. Attitudes of the public and health professionals toward organ donation are discussed. The organization of the Pittsburgh Organ Procurement Agency and its relationship to other such agencies is described. Finally, the presently used techniques of liver salvaging and preservation are outlined. PMID:6363261

Hepatic Arterial Infusion of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles Selectively Disrupts Redox Balance in Hepatoma cells and Reduces Growth of Orthotopic Liver Tumors in Rats

PubMed Central

Wen, Xiaodong; Reynolds, Lacy; Mulik, Rohit S.; Kim, Soo Young; Van Treuren, Tim; Nguyen, Liem H.; Zhu, Hao; Corbin, Ian R.

2015-01-01

Background & Aims Dietary intake of the natural omega-3 fatty acid docosahexaenoic acid (DHA) has been implicated in protecting patients with viral hepatitis B or C from developing hepatocellular carcinoma (HCC). Little is known about the effects of DHA on established solid tumors. Herein, we describe a low-density lipoprotein (LDL)-based nanoparticle that acts as a transporter for unesterified DHA (LDL–DHA) and demonstrates selective cytotoxicity towards HCC cells. We investigated the ability of LDL–DHA to reduce growth of orthotopic hepatomas in rats. Methods ACI rats were given intrahepatic injections of rat hepatoma cells (H4IIE); 24 tumor-bearing rats (mean tumor diameter, ~1 cm) were subject to a single hepatic artery injection of LDL nanoparticles (2 mg/kg) loaded with DHA (LDL–DHA), triolein (LDL–TO) or sham surgery controls. Tumor growth was measured by magnetic resonance imaging and other methods; tumor, liver and serum samples were collected and assessed by histochemical, immunofluorescence, biochemical and immunoblot analyses. Results Three days after administration of LDL–TO or sham surgery, the control rats had large, highly vascularized tumors that contained proliferating cells. However, rats given LDL–DHA had smaller, pale tumors that were devoid of vascular supply and greater than 80% of the tumor tissue was necrotic. Four to 6 days after injection of LDL–DHA, the tumors were 3-fold smaller than those of control rats. The liver tissue that surrounded the tumors showed no histologic or biochemical evidence of injury. Injection of LDL–DHA into the hepatic artery of rats selectively deregulated redox reactions in tumor tissues by: increasing levels of reactive oxygen species and lipid peroxidation, depleting and oxidizing glutathione and nicotinamide adenine dinucleotide phosphate, and significantly downregulating the antioxidant enzyme glutathione peroxidase-4. Remarkably, the redox balance in the surrounding liver was not disrupted. Conclusion LDL–DHA nanoparticle selectively kills hepatoma cells and reduces growth of orthotopic liver tumors in rats. It induces tumor-specific necrosis by selectively disrupting redox balance within the cancer cell. PMID:26484708

Hepatic Arterial Infusion of Low-Density Lipoprotein Docosahexaenoic Acid Nanoparticles Selectively Disrupts Redox Balance in Hepatoma Cells and Reduces Growth of Orthotopic Liver Tumors in Rats.

PubMed

Wen, Xiaodong; Reynolds, Lacy; Mulik, Rohit S; Kim, Soo Young; Van Treuren, Tim; Nguyen, Liem H; Zhu, Hao; Corbin, Ian R

2016-02-01

Dietary intake of the natural omega-3 fatty acid docosahexaenoic acid (DHA) has been implicated in protecting patients with viral hepatitis B or C from developing hepatocellular carcinoma (HCC). Little is known about the effects of DHA on established solid tumors. Here we describe a low-density lipoprotein-based nanoparticle that acts as a transporter for unesterified DHA (LDL-DHA) and demonstrates selective cytotoxicity toward HCC cells. We investigated the ability of LDL-DHA to reduce growth of orthotopic hepatomas in rats. AxC-Irish (ACI) rats were given intrahepatic injections of rat hepatoma cells (H4IIE); 24 tumor-bearing rats (mean tumor diameter, ∼1 cm) were subject to a single hepatic artery injection of LDL nanoparticles (2 mg/kg) loaded with DHA (LDL-DHA), triolein (LDL-TO), or sham surgery controls. Tumor growth was measured by magnetic resonance imaging and other methods; tumor, liver, and serum samples were collected and assessed by histochemical, immunofluorescence, biochemical, and immunoblot analyses. Three days after administration of LDL-TO or sham surgery, the control rats had large, highly vascularized tumors that contained proliferating cells. However, rats given LDL-DHA had smaller, pale tumors that were devoid of vascular supply and >80% of the tumor tissue was necrotic. Four to 6 days after injection of LDL-DHA, the tumors were 3-fold smaller than those of control rats. The liver tissue that surrounded the tumors showed no histologic or biochemical evidence of injury. Injection of LDL-DHA into the hepatic artery of rats selectively deregulated redox reactions in tumor tissues by increasing levels of reactive oxygen species and lipid peroxidation, depleting and oxidizing glutathione and nicotinamide adenine dinucleotide phosphate, and significantly down-regulating the antioxidant enzyme glutathione peroxidase-4. Remarkably, the redox balance in the surrounding liver was not disrupted. LDL-DHA nanoparticle selectively kills hepatoma cells and reduces growth of orthotopic liver tumors in rats. It induces tumor-specific necrosis by selectively disrupting redox balance within the cancer cell. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy

PubMed Central

Gao, Long; Zhang, Jian; Ma, Tengchuang; Yao, Nan; Gao, Meng; Shan, Xin; Ni, Yicheng; Shao, Haibo; Xu, Ke

2016-01-01

Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models. Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting. A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy. In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models. PMID:27285983

The Protective Effects of Trypsin Inhibitor on Hepatic Ischemia-Reperfusion Injury and Liver Graft Survival

PubMed Central

Guan, Lianyue; Liu, Hongyu; Fu, Peiyao; Li, Zhuonan; Li, Peidong; Xie, Lijuan; Xin, Mingang; Wang, Zhanpeng

2016-01-01

The aim of this study was to explore the protective effects of ulinastatin (urinary trypsin inhibitor, UTI) on liver ischemia-reperfusion injury (IRI) and graft survival. We employed mouse liver cold IRI and orthotopic liver transplantation (OLTx) models. UTI was added to lactated Ringer's (LR) solution for liver perfusion and preservation in vitro or combined with UTI injection intraperitoneally to the liver graft recipient. Our results indicated that UTI supplementation protected the liver from cold IRI in a dose-dependent manner and prolonged liver graft survival from extended cold preserved liver donors significantly. The underlying mechanism of UTI on liver IRI may be mediated by inhibition of proinflammatory cytokine release, increasing the expression of the antiapoptotic gene Bcl-2 and decreasing the expression of the proapoptosis genes of Caspase-3 and Bax, and further protects hepatocytes from apoptotic death and improves liver function. PMID:26783413

The Protective Effects of Trypsin Inhibitor on Hepatic Ischemia-Reperfusion Injury and Liver Graft Survival.

PubMed

Guan, Lianyue; Liu, Hongyu; Fu, Peiyao; Li, Zhuonan; Li, Peidong; Xie, Lijuan; Xin, Mingang; Wang, Zhanpeng; Li, Wei

2016-01-01

The aim of this study was to explore the protective effects of ulinastatin (urinary trypsin inhibitor, UTI) on liver ischemia-reperfusion injury (IRI) and graft survival. We employed mouse liver cold IRI and orthotopic liver transplantation (OLTx) models. UTI was added to lactated Ringer's (LR) solution for liver perfusion and preservation in vitro or combined with UTI injection intraperitoneally to the liver graft recipient. Our results indicated that UTI supplementation protected the liver from cold IRI in a dose-dependent manner and prolonged liver graft survival from extended cold preserved liver donors significantly. The underlying mechanism of UTI on liver IRI may be mediated by inhibition of proinflammatory cytokine release, increasing the expression of the antiapoptotic gene Bcl-2 and decreasing the expression of the proapoptosis genes of Caspase-3 and Bax, and further protects hepatocytes from apoptotic death and improves liver function.

Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-κB signaling pathway

PubMed Central

ZHANG, CHAO-BIN; TANG, YI-CHEN; XU, XUE-JUN; GUO, SHI-XIANG; WANG, HUAI-ZHI

2015-01-01

Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The present study was designed to investigate the effect of hydrogen inhalation on liver ischemia/reperfusion (I/R) injury in rats. The portal triad to the left lobe and the left middle lobe of the liver were completely occluded for 90 min. This was followed by reperfusion for 180 min. The rats subsequently underwent syngeneic orthotopic liver transplantation. Inhalation of various concentrations (1, 2 and 3%) of hydrogen gas and its administration for different durations (1, 3 and 6 h) immediately prior to the I/R injury allowed the optimal dose and duration of administration to be determined. Liver injury was evaluated through biochemical and histopathological examinations. The expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6, were measured by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction (qPCR). Liver nuclear factor κB (NF-κB) was detected by qPCR and western blot analysis. Inhalation of hydrogen gas at 2% concentration for 1 h significantly reduced the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, the expression of cytokines, including IL-6, TNF-α, early growth response protein 1 (Egr-1) and IL-1β, and morphological damage. In addition, the mRNA and protein expression levels of NF-κB, heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2) and zinc finger protein A20 (A20) in rats where only the donors received hydrogen were significantly increased compared with those in rats where both the donor and recipient, or only the recipient received hydrogen. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF-κB signaling pathway. PMID:26136944

Gas gangrene caused by clostridium perfringens involving the liver, spleen, and heart in a man 20 years after an orthotopic liver transplant: a case report.

PubMed

Kitterer, Daniel; Braun, Niko; Jehs, Margit C; Schulte, Bernhard; Alscher, M Dominik; Latus, Joerg

2014-04-01

Despite advances in immunosuppression and liver transplant in the past, mortality and morbidity caused by infections remain major problems. We present a 71-year-old man who was admitted to our internal intensive care unit with septicemia. Upon admission, he had poorly localized epigastric pain and fever of 2 days ' duration. Twenty years earlier, he had undergone an orthotopic liver transplant. Testing revealed a high C-reactive protein level, elevated liver enzymes, and an acute kidney injury. A computer tomography scan showed 2 circular, non--rim-enhancing, totally emphysematous intrahepatic lesions. Additionally, gas could be seen in the portal veins mainly, as well as in the biliary system, in the right auricle, and the splenic veins. To the best of our knowledge, he showed no malignant lesion or predisposing trauma. Empirically, treatment with broad-spectrum antibiotics was begun, and the patient was transferred to the operating suite. When surgery began, blood cultures revealed the presence of gram-positive bacilli, which were identified as Clostridium perfringens. Seven hours after the surgery, the patient developed asystole and died. In septic patients presenting with severe hemolysis, Clostridium perfringens infection must be considered in the absence of a malignant lesion or a predisposing trauma; a previous episode of gastroenteritis might be a predisposing trauma by impairing the barrier of the intestinal flora, leading to Clostridium perfringens infection.

Use of the Viatorr Expanded Polytetrafluoroethylene-Covered Stent-Graft for Transjugular Intrahepatic Portosystemic Shunt Creation in Children: Initial Clinical Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mermuys, Koen; Maleux, Geert, E-mail: geert.maleux@uzleuven.be; Heye, Sam

2008-07-15

Four children, three boys and one girl, with a median age of 9 years 8 months, underwent transjugular intrahepatic portosystemic shunt creation with an expanded polytetrafluoroethylene (e-PTFE)-covered nitinol stent. The stent-graft was successfully placed in all four patients without any complication. Clinical and biochemical improvement was noted in all four patients during follow-up. Radiological follow-up with use of duplex ultrasound showed a recurrent stenosis of the shunt 180 days after stent-graft implantation in one patient. This was treated with placement of an additional stent-graft, re-expanding completely the recurrent stenosis. In the other three patients, the stent-graft remained fully patent untilmore » the end of the study or until orthotopic liver transplantation. These preliminary results suggest that use of the Viatorr ePTFE-covered stent-graft in children is safe and feasible, with potentially the same high patency rate and improved clinical outcome as reported in adult patients.« less

Solving the Mystery: Hyalinized cyst wall containing organism- like structures in a Lung Transplant Donor.

PubMed

Bini Viotti, Julia; Loebe, Matthias; Brozzi, Nicolas; Pinto, Andre; Simkins, Jacques; Cloke, Christina M; Camargo, Jose F; Salama, Sam; Abbo, Lilian M

2018-06-05

A 59-year-old man with non-ischemic cardiomyopathy underwent orthotopic heart transplantation. The donor, a 31-year-old male declared brain dead after a gunshot wound to the head, was considered high risk due to history of incarceration, illicit drug use and sex with a HIV positive partner. At organ procurement, the heart, kidneys, pancreas and liver looked grossly normal. A small right lower lobe nodule was noticed, and lung biopsy was performed. Bronchoscopy showed purulent secretions in the right lower lobe. Images from pathology are presented. Lung biopsy confirmed the presence of hyalinized cyst wall containing organism- like structures. A combination of culture, microscopic morphology, and gene sequencing was used to identify the causative organism. The patient and all other organ recipients received appropriate antifungal prophylaxis and remain asymptomatic six months post- transplant. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease.

PubMed

Go, Kristina L; Delitto, Daniel; Judge, Sarah M; Gerber, Michael H; George, Thomas J; Behrns, Kevin E; Hughes, Steven J; Judge, Andrew R; Trevino, Jose G

2017-07-01

Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model. The purpose of this study was to evaluate the degree to which an orthotopic PDX model of PC recapitulates these aspects of the human disease. Human PDX-derived PC tumors were implanted directly into the pancreas of NOD.Cg-Prkdc Il2rg/SzJ mice. Tumor growth, metastasis, and muscle wasting were then evaluated. Orthotopically implanted PDX-derived tumors consistently incorporated into the murine pancreatic parenchyma, metastasized to both the liver and lungs and induced muscle wasting directly proportional to the size of the tumor, consistent of the cancer cachexia syndrome. Through the orthotopic implantation technique described, we demonstrate a highly reproducible model that recapitulates both local and systemic aspects of human PC.

The customization of APACHE II for patients receiving orthotopic liver transplants

PubMed Central

Moreno, Rui

2002-01-01

General outcome prediction models developed for use with large, multicenter databases of critically ill patients may not correctly estimate mortality if applied to a particular group of patients that was under-represented in the original database. The development of new diagnostic weights has been proposed as a method of adapting the general model – the Acute Physiology and Chronic Health Evaluation (APACHE) II in this case – to a new group of patients. Such customization must be empirically tested, because the original model cannot contain an appropriate set of predictive variables for the particular group. In this issue of Critical Care, Arabi and co-workers present the results of the validation of a modified model of the APACHE II system for patients receiving orthotopic liver transplants. The use of a highly heterogeneous database for which not all important variables were taken into account and of a sample too small to use the Hosmer–Lemeshow goodness-of-fit test appropriately makes their conclusions uncertain. PMID:12133174

Endoscopic treatment of bile duct complications after orthotopic liver transplantation.

PubMed

Polese, L; Cillo, U; Brolese, A; Boccagni, P; Neri, D; Bassi, D; Erroi, F; Zanus, G; D'Amico, D F; Norberto, L

2007-01-01

To assess the indications and results of endoscopic retrograde cholangio-pancreatography (ERCP) in patients who have undergone ortotopic liver transplantation (OLT). We reviewed data from 42 consecutive patients who underwent ERCP for biliary complications after OLT over an 8-year period, in particular recording indications and success of the treatment after a mean of 17 months follow-up. Cholangiograms performed in 33/42 patients (79%) displayed anastomotic strictures in 17 patients (52%), bile duct stones in 8 (24%), both bile duct stones and an anastomotic stricture in 2 (6%), papillary stenosis in 1 (3%), and anastomotic biliary leakage in 1 (3%). In contrast, the contrastogram was normal in four patients (12%). Stone extraction was completed in 9/10 patients (90%) with a mean of 1.2 sessions, while stricture dilation was achieved in 12/19 patients (63%) after a mean of 1.7 sessions, by stent positioning (n = 7), balloon dilation (n = 4), or Soehendra dilator (n = 1). Both biliary leakage and papillary stenosis were cured by ERCP. Only one procedure-related complication -- severe pancreatitis (2.4%) -- was observed and no mortality. ERCP is a safe and effective mode of management of bile duct complications after OLT. It should be attempted before a surgical approach. Better results are obtained for treatment of biliary stones than of anastomotic strictures.

Alkaline phosphatase: the next independent predictor of the poor 90-day outcome in alcoholic hepatitis.

PubMed

Kasztelan-Szczerbinska, Beata; Slomka, Maria; Celinski, Krzysztof; Szczerbinski, Mariusz

2013-01-01

Determination of risk factors relevant to 90-day prognosis in AH. Comparison of the conventional prognostic models such as Maddrey's modified discriminant function (mDF) and Child-Pugh-Turcotte (CPT) score with newer ones: the Glasgow Alcoholic Hepatitis Score (GAHS); Age, Bilirubin, INR, Creatinine (ABIC) score, Model for End-Stage Liver Disease (MELD), and MELD-Na in the death prediction. The clinical and laboratory variables obtained at admission were assessed. The mDF, CPT, GAHS, ABIC, MELD, and MELD-Na scores' different areas under the curve (AUCs) and the best threshold values were compared. Logistic regression was used to assess predictors of the 90-day outcome. One hundred sixteen pts fulfilled the inclusion criteria. Twenty (17.4%) pts died and one underwent orthotopic liver transplantation (OLT) within 90 days of follow-up. No statistically significant differences in the models' performances were found. Multivariate logistic regression identified CPT score, alkaline phosphatase (AP) level higher than 1.5 times the upper limit of normal (ULN), and corticosteroids (CS) nonresponse as independent predictors of mortality. The CPT score, AP > 1.5 ULN, and the CS nonresponse had an independent impact on the 90-day survival in AH. Accuracy of all studied scoring systems was comparable.

A true orthotopic gastric cancer murine model using electrocoagulation.

PubMed

Bhullar, Jasneet Singh; Makarawo, Tafadzwa; Subhas, Gokulakkrishna; Alomari, Ahmed; Silberberg, Boris; Tilak, Jacqueline; Decker, Milessa; Mittal, Vijay K

2013-07-01

Orthotopic mouse models of human gastric cancer represent an important in vivo tool for testing chemotherapeutic agents and for studying intraluminal factors. Currently, orthotopic mouse models of gastric cancer require an operative procedure involving either injection or implantation of tumor cells in stomach layers. The resultant tumor does not grow from the stomach's mucosal surface, so it does not mimic the human disease process. A low-dose gastric mucosal coagulation was done transorally in the body of stomach using a specially designed polyethylene catheter in 16 female severe combined immunodeficient mice. This was followed by the instillation of SNU-16 human gastric cancer tumor cells (1 × 10(6) cells). Five mice each were euthanized at 1 and 2 months, and 6 mice were euthanized at 3 months. Three control mice underwent electrocoagulation alone and 3 mice underwent cell line instillation alone. Tumors were detected in 11 of 16 experimental mice, but not in the control mice. Tumors were noted in mice at 1 month. Over time, there was an increase in tumor growth and metastasis to lymph nodes and surrounding organs. Histopathologic evaluation showed that the tumors grew from the gastric mucosa. Our model is easy to create and overcomes the limitations of the existing models, as the tumor arises from the stomach's mucosal layer and mimics the human disease in terms of morphology and biologic behavior. This is the first report of a true orthotopic gastric cancer murine model. This model opens new doors for additional studies that were not possible earlier. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Radical cystectomy with W-shaped orthotopic ileal neobladder constructed with non-absorbable titanium staples-long term follow-up.

PubMed

Kravchick, Sergey; Lobik, Leonid; Paz, Adrian; Stepnov, Eugeny; Ben-Dor, David; Cytron, Shmuel

2013-01-01

We retrospectively assessed our experience with the W-shaped orthotopic ileal pouch, which was constructed with non-absorbable titanium staples. For these purpose, we discuss the results of bladder capacity, urinary continence and early and long-term postoperative complications. We included in the study 17 patients who underwent radical cystoprostatectomy followed by construction of an orthotopic W-shaped ileal pouch between October 2000 and November 2009. A 65-70 cm segment of ileum was isolated and prearranged into a W-configuration, leaving two 10 cm intact segments on both sides of the ileal fragment. In our technique we entirely anatomized all adjacent limbs in order to create a sphere-shaped pouch. The ureters were directly anastomized to both intact segments of the ileal division. All our patients underwent pouchscopy 6 months after operation and annually. Mean operative time for neobladder reconstruction and ureteral anastomoses was 87 ± 7.67 minutes. In one patient a leak from the ileo-ileal anastomosis was confirmed on the 3rd day after operation. In 2 cases unilateral stricture of the ureteral-neobladder anastomosis was documented. Staple lines were mostly covered with ileal mucosa after 6 months. The mean functional bladder capacity was 340 ± 27.6 mL and 375 ± 43.4 mL at 6 and 12 months, respectively. First-year daytime and nighttime continence was good and acceptable in 90% and 78% of patients, while it increased to 95% during the 2nd year. The long term follow-up shows that non-absorbable titanium staples can be safely used for creation of an orthotopic ileal neobladder. However, these data should be further validated in a larger series of patients.

Incidence, risk factors and ERCP outcome for biliary complications after cadaveric OLT.

PubMed

Martins, Fernanda Prata; De Paulo, Gustavo Andrade; Conceição, Raquel Dilgerian; Zurstrassen, Maria Paula; Thomé, Tadeu; Ferraz-Neto, Ben-Hur; Ferrari, Angelo Paulo

2011-01-01

Biliary complications (BC) occur in up to 39.5% of patients after orthotopic liver transplantation (OLT), being an important source of post-transplant morbidity. The aim is to evaluate the incidence of BC after OLT, associated risk factors and outcome after endoscopic treatment. A retrospective case series between June 2005 and December 2008, including 195 patients that underwent 216 OLT from deceased donors. Thirty-one patients (14.3%) presented at least 1 BC, anastomotic stricture being the most frequent (83.8%). Non-anastomotic stricture was present in 1 (3.2%) and anastomotic fistula in 1. One patient presented anastomotic disconnection at ERCP. BC occurred 94.6 (7-487) days after OLT. Twenty-seven patients underwent endoscopic treatment, on average 2.6 ERCPs were performed per patient. Global endoscopic treatment success rate was 77.3%; being 73.7% for stenosis and 100% (3/3) for anastomotic fistula with stenosis. Recurrence of biliary stricture was observed in 3 patients, all referred to endoscopic re-treatment. ERCP complications: 2 (2.8%) stent migrations, 1 (1.4%) early stent occlusion, 1 (1.4%) respiratory distress and 1(1.4%) severe acute pancreatitis and death. There was no correlation between studied risk factors and BC's occurrence. ERCP was effective for the treatment of BC after OLT. Studied risk factors had no correlation with BC.

Orthotopic heart transplant versus left ventricular assist device: A national comparison of cost and survival

PubMed Central

Mulloy, Daniel P.; Bhamidipati, Castigliano M.; Stone, Matthew L.; Ailawadi, Gorav; Kron, Irving L.; Kern, John A.

2012-01-01

Objectives Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. Methods All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. Results The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%–6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). Conclusions Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been significantly greater than those for orthotopic heart transplantation. Because of the evolving healthcare economics climate, with increasing emphasis on the costs and comparative effectiveness, a concerted effort at LVAD cost containment and judicious usage is essential to preserve the viability of this invaluable treatment. PMID:23246055

Predictive Value of Serum Creatinine, Blood Urea Nitrogen, Uric Acid, and β2-Microglobulin in the Evaluation of Acute Kidney Injury after Orthotopic Liver Transplantation.

PubMed

Lu, Hai-Yang; Ning, Xin-Yu; Chen, Ying-Qi; Han, Shu-Jun; Chi, Ping; Zhu, Sai-Nan; Yue, Yun

2018-05-05

As a major complication after orthotopic liver transplantation (OLT), the occurrence of acute kidney injury (AKI) is frequently defined by serum creatinine (Cr); however, the accuracy of commonly used blood urea nitrogen (BUN), uric acid (UA), and β 2 -microglobulin (β 2 -MG) remains to be explored. This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation. Patients who underwent OLT in three centers between July 2003 and December 2013 were enrolled. The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and classified by stage. Measurement data were analyzed using the t-test or Wilcoxon rank-sum test; enumerated data were analyzed using the Chi-square test or Fisher's exact test. Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic (ROC) curve analysis. This study excluded 976 cases and analyzed 697 patients (578 men and 119 women); the post-OLT AKI incidence was 0.409. Compared with the no-AKI group, the AKI group showed very significant differences in Model for End-stage Liver Disease score (14.74 ± 9.91 vs. 11.07 ± 9.54, Z = 5.404; P < 0.001), hepatic encephalopathy (45 [15.8%] vs. 30 [7.3%], χ 2 = 12.699; P < 0.001), hemofiltration (28 [9.8%] vs. 0 [0.0%], χ 2 = 42.171; P < 0.001), and 28-day mortality (23 [8.1%] vs. 9 [2.2%], χ 2 = 13.323; P <0.001). Moreover, mean values of Cr, BUN, UA, and β 2 -MG in the AKI group differed significantly at postoperative days 1, 3, and 7 (all P < 0.001). ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 (sensitivity 80.1%, specificity 75.7%, cutoff value 88.23 μmol/L), 0.916 for Stage 2 (sensitivity 87.6%, specificity 82.6%, cutoff value 99.9 μmol/L), and 0.972 for Stage 3 (sensitivity 94.1%, specificity 88.2%, cutoff value 122.90 μmol/L). The sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.

Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil.

PubMed

Ishida, Kaoru; Ito, Chie; Ohmori, Yukimi; Kume, Kohei; Sato, Kei A; Koizumi, Yuka; Konta, Akari; Iwaya, Takeshi; Nukatsuka, Mamoru; Kobunai, Takashi; Takechi, Teiji; Nishizuka, Satoshi S

2017-05-23

Drug-tolerant cancer cell subpopulations are responsible for relapse after chemotherapy. By continuously exposing the gastric cancer cell line MKN45 to 5-FU for >100 passages, we established a 5-fluorouracil (5-FU)-tolerant line, MKN45/5FU. Orthotopic xenografts of MKN45/5FU cells in the stomach of nude mice revealed that these cells had a high potential to metastasize to sites such as the liver. Levels of phosphorylated phosphatidylinositide 3-kinase (PI3K) increased both in 5-FU-tolerant subpopulations according to the 5-FU dose, and in gastric submucosal orthotopic xenografts of MKN45/5FU cells. Sequential administration of 5-FU and a PI3K inhibitor, GDC-0941, targeted the downstream ribosomal S6 kinase phosphorylation to significantly suppress 5-FU-tolerant subpopulations and tumor propagation of orthotopic MKN45/5FU xenografts. These results suggest that administration of 5-FU followed by GDC-0941 may suppress disease relapse after 5-FU-based gastric cancer chemotherapy.

Invasive Saccharomyces cerevisiae in a liver transplant patient: case report and review of infection in transplant recipients.

PubMed

Popiel, K Y; Wong, P; Lee, M J; Langelier, M; Sheppard, D C; Vinh, D C

2015-06-01

Saccharomyces cerevisiae, an ascosporogenous yeast commonly used in the production of food, is an emerging infection in immunocompromised patients. We report the case of a 60-year-old man whose orthotopic liver transplant was complicated by S. cerevisiae fungemia and peritoneal abscess, successfully treated with caspofungin and drainage. We also review the literature of invasive saccharomycoses in recipients of hematologic and solid organ transplants. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intracardiac tromboembolism during liver transplantation.

PubMed

Longo, S; Palacios, M; Tinti, M E; Siri, J; de Brahi, J I; Cabrera Shulmeyer, M C

2018-03-20

We describe a case of intraoperative cardiac trombosis during orthotopic liver transplant surgery that resulted in intraoperative death. By using transesophageal echocardiography, the cause of the descompensation of the patient could be determined and the mechanism of trombus migration from thrombi from the venous circulation to the left heart was accurately observed. Copyright © 2018 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Long-Term Follow-Up After Successful Transjugular Intrahepatic Portosystemic Shunt Placement in a Pediatric Patient with Budd-Chiari Syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carnevale, Francisco Cesar, E-mail: fcarnevale@uol.com.br; Szejnfeld, Denis, E-mail: denis@cura.com.br; Moreira, Airton Mota

Orthotopic liver transplantation is the standard of care in patients with Budd-Chiari syndrome (BCS), and transjugular intrahepatic portosystemic shunt (TIPS) has become an important adjunct procedure while the patient is waiting for a liver. No long-term follow up of TIPS in BCS patients has been published in children. We report successful 10-year follow-up of a child with BCS and iatrogenic TIPS dysfunction caused by oral contraceptive use.

[Establishment of a nude mouse model of highly metastatic gastric lymphoma constructed with orthotopic transplantation of surgical specimen].

PubMed

Yang, Bo; Tuo, Shuai; Tuo, Chao-wei; Zhang, Ning; Liu, Qiu-zhen

2010-06-01

To construct a mouse model of highly metastatic gastric lymphoma with orthotopic transplantation of human primary gastric lymphoma specimen. A fresh surgical specimen of primary gastric lymphoma was obtained intraoperatively and implanted into the submucosa of stomach in nude mice. Tumor formation, invasion, metastasis, morphological characteristics under light microscopy and electron microscopy, immunohistochemistry,and the karyotype of orthotopically transplanted tumor cells were studied. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice(HGBL-0305) was successfully established. Histopathology of transplanted tumors showed primary gastric diffuse large B cell lymphoma. CD19, CD20, CD22 and CD79alpha were positive, while CD3 and CD7 were negative. The number of chromosome ranged from 56 to 69. DNA index(DI) was 1.47+/-0.12(i.e. heteroploid). Until now, HGBL-0305 model has been maintained for 45 generations by orthotopic passage for almost 4 years in nude mice. A total of 156 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumor cells were both 100%. The autonomic growth of the transplanted tumor cells invaded and destructed all the layers of the nude mice stomach. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 69.5%, 55.6%, 45.7%, and 30.5%, respectively. An orthotopic highly metastatic model of human primary gastric lymphoma in nude mice is successfully established. HGBL-0305 model may simulate the natural course of primary gastric lymphoma in human and provides an ideal animal model for studies on pathogenesis, metastasis biology and anti-metastatic therapies of primary gastric lymphoma.

Algorithm for prioritization of patients on the waiting list for liver transplantation.

PubMed

Gambato, M; Senzolo, M; Canova, D; Germani, G; Tomat, S; Masier, A; Russo, F P; Perissinotto, E; Zanus, G; Cillo, U; Burra, P

2007-01-01

Prioritization of patients on the waiting list (WL) for OLT is still a critical issue. Numerous models have been developed to predict mortality before and after OLT. The aim of the study was to prospectively evaluate cirrhotics with and without hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT) severity of liver disease on the WL and at transplant, mortality on the WL and after OLT, and their correlations. An algorithm based on seven patient variables (MELD, CTP, UNOS, HCC, BMI, waiting time, age) was created by software dedicated to prioritize patients on the waiting list. We evaluated 118 patients including 75 men and 43 women of age range 19 to 66 years, who underwent OLT from July 2004 to June 2006. Mean CTP and MELD at listing were 8.44 (range 6-12) and 13 (range 2-24), respectively. Overall mortality on the WL at 24 months was 13%, which was significantly higher among patients with MELD > 25 compared to patients with MELD 0 to 15 (P < .0001) or MELD 16 to 25 (P = .0007) at listing. Mean MELD at OLT was 15 (range 7-36), which was significantly lower in patients with than without HCC (MELD 12 vs 16; P = .0003). Six hundred-day patient survival was significantly lower among patients with MELD > 25 compared to patients with MELD < 25 at OLT (P = .017), whereas no difference in survival was observed between patients with and without HCC. The sickest patients are characterized by high mortality both on the waiting list and after liver transplantation. Patients with HCC are transplanted in better condition compared to patients without HCC with the same survival.

Livers from fasted rats acquire resistance to warm and cold ischemia injury.

PubMed

Sumimoto, R; Southard, J H; Belzer, F O

1993-04-01

Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold ischemia. In fact, the livers appeared to be better able to tolerate ischemia when obtained from fasted rats. Thus donor nutritional status may be an important factor for outcome of liver transplantation. Livers from fasted donors may be capable of tolerating long-term preservation better than livers from fed donors.

Neonatal liver cell donation: a case report.

PubMed

Godfrey, Kathleen; Kish, Mary Z

2014-01-01

Traditional organ transplant options for newborns have been rare. There continues to be an increasing need for organs for transplant and a limited number of available organs, especially for small children. Liver cell transplantation is a promising alternative to orthotopic liver transplantation to treat liver-based inborn errors of metabolism.1 The procedure is minimally invasive and can be performed repeatedly. The safety of the procedure has been well established, and the clinical results are encouraging.1 The liver cell donation process is an option for families who experience the loss of a newborn and offers them a legacy for their child by providing life for others. The purpose of this article is to discuss the neonatal liver cell donation process and present a case report of an anencephalic infant whose parents chose to participate in this unique program.

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice

PubMed Central

2014-01-01

Background Advanced hepatocellular carcinoma (HCC) patients undergo significant tumor growth and metastasis. Here, we investigated bufalin for treating HCC, which exhibits anti-tumor activities in many tumor cell lines. Method In our experiment, HCCLM3-R cells were injected into nude mice to form subcutaneous human HCC tumors that were implanted into the liver to establish orthotopic transplantation tumor models. Bufalin was injected intraperitoneally at 1 or 1.5 mg/kg. LY294002 (100 mg/kg), a potent inhibitor of Akt which reduced the levels of pAkt in HCCLM3 cell lines, was injected intraperitoneally into one group thrice weekly. The control was injected with an equal volume of saline. Morphological alterations were evaluated in the liver and lung by stereomicroscopy, the apoptotic rate was measured by TUNEL staining, and expression of AKT/GSK3β/β-catenin/E-cadherin signaling pathway-related proteins was detected by immunohistochemistry (IHC) and western blot analysis. Results These results suggested that the sizes and qualities of orthotopic transplanted tumors as well as pulmonary metastasis decreased markedly at the highest bufalin dose compared with that in the control. Orthotopic transplanted tumor tissues were necrotic in bufalin-treated groups and the apoptotic cell number was markedly higher at the highest bufalin dose compared with that in the control. Certain changes of expression of AKT/GSK3β/β-catenin/E-cadherin signaling pathway-related proteins were in tumor tissues, which were related to the bufalin dose. Similar results were observed in the LY294002-treated group. Conclusion Based on the above, one can draw conclusions that bufalin has significant anti-tumor activities and reduces the metastatic potential in an orthotopic transplantation tumor model of human HCC. Inhibition of AKT/GSK3β/β-catenin/E-cadherin signaling pathways by bufalin may show therapeutic effects in advanced HCC patients. PMID:24581171

MicroRNA-Regulated Non-Viral Vectors with Improved Tumor Specificity in an Orthotopic Rat Model of Hepatocellular Carcinoma

PubMed Central

Ronald, John A.; Katzenberg, Regina; Nielsen, Carsten H.; Jae, Hwan Jun; Hofmann, Lawrence V.; Gambhir, Sanjiv S.

2013-01-01

In hepatocellular carcinoma, tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs are powerful negative regulators of gene expression and many are down-regulated in human HCC. We identified seven miRNAs that are also down-regulated in tumors in a rat hepatoma model (p<0.05) and attempted to improve tumor specificity by constructing a panel of luciferase-expressing vectors containing binding sites for these microRNAs. Attenuation of luciferase expression by the corresponding microRNAs was confirmed across various cell lines and in mouse liver. We then tested our vectors in tumor-bearing rats and identified two microRNAs, miR-26a and miR-122, that significantly decreased expression in liver compared to control vector (6.40% and 0.26%, respectively; p<0.05). In tumor, miR-122 had a non-significant trend towards decreased (~50%) expression , while miR-26 had no significant effect on tumor expression. To our knowledge this is the first work using differentially expressed microRNAs to de-target transgene expression in an orthotopic hepatoma model and identification of miR-26a in addition to miR-122 for de-targeting liver. Considering the heterogeneity of microRNA expression in human HCC, this information will be important in guiding development of more personalized vectors for the treatment of this devastating disease. PMID:23719066

Split liver transplantation: a reliable approach to expand donor pool.

PubMed

Yan, Ji-Qi; Becker, Thomas; Peng, Cheng-Hong; Li, Hong-Wei; Klempnauer, Juergen

2005-08-01

Orthotopic liver transplantation as a successful treatment of end-stage liver disease is hampered by a persistent lack of cadaveric organs. Split liver transplantation, which was first successfully performed by Medical School of Hannover in 1988, has become a mature surgical technique to expand the donor pool. Between 1993 and 1999, split liver transplantation activities have increased in Europe from 1.2% to 10.4% in all performed liver transplantations. Current data have strongly supported that the survival rate of patients after split liver transplantation is not significantly different from that of patients after whole-size orthotopic liver transplantation. The most important step of donor graft selection is surgeon's observation judged by the experience of individual transplant center. The paper aims to provide the guideline of donor selection, hepatic graft splitting, and recipient management as well. Medical School of Hannover has accumulated plentiful experience of split liver transplantation for more than 10 cases ever since 1998. Besides that, we also reviewed a variety of literatures from other famous European and American centers specialized in this field for many years. According to our experience combined with the view points of others, the donor should meet the following criteria as well: (1) age less than 50 years; (2) hemodynamics stable; (3) ICU less than 5 days; (4) Na less than 170 mmol/L or better if less than 150 mmol/L. In 1996 and 1997, the Hamburg group and the UCLA group separately introduced a breakthrough technique performing split liver transplantation in situ. Evidently, the in situ technique has been limited by prolonged time of donor organ procurement, coordination with other organ procurement teams, and even extra burden on donor hospital. Some groups, therefore, have restored the ex situ or bench splitting technique, and fortunately the transplant outcomes of the ex situ technique are equivalent to those of the in situ one. Recently some new techniques have been introduced to split the liver for two adult patients, including the split-cava technique. It is clear that the most important factor for determining the prognosis of the patient is the time of receiving liver transplantation, not the type of liver transplantation. We still need to pay close attention to the graft to recipient weight ratio (GRWR) and the UNOS classification or MELD score before the patient is subjected to split liver transplantation.

Serious gaming for orthotopic liver transplant anesthesiology: A randomized control trial.

PubMed

Katz, Daniel; Zerillo, Jeron; Kim, Sang; Hill, Bryan; Wang, Ryan; Goldberg, Andrew; DeMaria, Samuel

2017-04-01

Anesthetic management of orthotopic liver transplantation (OLT) is complex. Given the unequal distributions of liver transplant surgeries performed at different centers, anesthesiology providers receive relatively uneven OLT training and exposure. One well-suited modality for OLT training is the "serious game," an interactive application created for the purpose of imparting knowledge or skills, while leveraging the self-motivating elements of video games. We therefore developed a serious game designed to teach best practices for the anesthetic management of a standard OLT and determined if the game would improve resident performance in a simulated OLT. Forty-four residents on the liver transplant rotation were randomized to either the gaming group (GG) or the control group (CG) prior to their introductory simulation. Both groups were given access to the same educational materials and literature during their rotation, but the GG also had access to the OLT Trainer. Performance on the simulations were recorded on a standardized grading rubric. Both groups experienced an increase in score relative to baseline that was statistically significant at every stage. The improvements in scores were greater for the GG participants than the CG participants. Overall score improvement between the GG and CG (mean [standard deviation]) was statistically significant (GG, 7.95 [3.65]; CG, 4.8 [4.48]; P = 0.02), as were scores for preoperative assessment (GG, 2.67 [2.09]; CG, 1.17 [1.43]; P = 0.01) and anhepatic phase (GG, 1.62 [1.01]; CG, 0.75 [1.28]; P = 0.02). Of the residents with game access, 81% were "very satisfied" or "satisfied" with the game overall. In conclusion, adding a serious game to an existing educational curriculum for liver transplant anesthesia resulted in significant learning gains for rotating anesthesia residents. The intervention was straightforward to implement and cost-effective. Liver Transplantation 23 430-439 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

[Surgical techniques in liver transplantation].

PubMed

Chan, Carlos; Plata-Muñoz, Juan José; Franssen, Bernardo

2005-01-01

Liver transplantation (LT) is probably the biggest surgical aggression that a patient can endure. It was considered only as a last option in the era of experimental LT, yet it evolved into the definitive treatment for some types of acute and chronic end stage liver disease. In terms of technique LT is the most complex of all types of transplantations. The surgical procedure in itself is well established and has changed little through time. Liver transplantation owes its improvement to better and more systematic anesthetic procedures and to perioperative care more than being due to improvement of the surgical technique. The first surgical procedure was described by Thomas Starzl in 1969. His initial work has been strengthened with the development of venous bypass, the refinement in vascular and biliary reconstruction technique and the development of the split liver. Up to date technical aspects of orthotopic liver transplantation are described in the present article.

Combined en bloc liver/pancreas transplantation in two different patients

PubMed Central

Chen, Zhi-Shui; Meng, Fan-Ying; Chen, Xiao-Ping; Liu, Dun-Gui; Wei, Lai; Jiang, Ji-Pin; Du, Dun-Feng; Zhang, Wei-Jie; Ming, Chang-Sheng; Gong, Nian-Qiao

2009-01-01

Combined en bloc liver/pancreas transplantation (CLPT) was used primarily in the treatment of otherwise non-resectable upper abdominal malignancy. In fact, a more appropriate indication is in patients with liver disease and insulin-dependent diabetes mellitus (IDDM). Here, we report on two successful cases of CLPT at our hospital. One was a patient with non-resectable advanced liver cancer. The recipient survived for 23 mo and finally died of recurrent tumor. The other was a patient with severe biliary complication after orthotopic liver transplantation and preoperative IDDM. We performed CLPT with a modified surgical technique of preserving the native pancreas. He is currently liver-disease- and insulin-free more than 27 mo post-transplant. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of CLPT and a modification of the surgical procedure. PMID:19469010

Anesthetic and Perioperative Management of Nontransplant Surgery in Patients After Liver Transplant.

PubMed

Ersoy, Zeynep; Ayhan, Asude; Ozdemirkan, Aycan; Polat, Gulsi Gulsah; Zeyneloglu, Pinar; Arslan, Gulnaz; Haberal, Mehmet

2017-02-01

We aimed to document the anesthetic management and metabolic, hemodynamic, and clinical outcomes of liver-graft recipients who subsequently undergo nontransplant surgical procedures. We retrospectively analyzed the data of 96 liver-graft recipients who underwent 144 nontransplant surgeries between October 1998 and April 2016 at Başkent University Hospital. The median patient age at the time of nontransplant surgery was 32 years, and 35% were female (n = 33). The median time between transplant and nontransplant surgery was 1231 days. The most frequent types of nontransplant surgery were abdominal (22%), orthopedic (16%), and urologic (13%). Seventy patients had an American Society of Anesthesiologists status of 2 (49%); the status was 3 in 71 patients (49%) and 4 in 3 patients (2%). Of the 144 procedures, 23 were emergent (16%) and 48% were abdominal. General anesthesia was used in 69%, regional anesthesia in 19%, and sedoanalgesia in 11%. Twenty-five patients required intraoperative blood-product transfusion (17%). Intraoperative hemodynamic instability developed in 17% of patients, and hypoxemia developed in 2%. Eleven patients remained intubated at the end of surgery (8%). Of the 144 procedures, 19 (13%) required transfer to the intensive care unit, 108 (75%) transferred to the ward, and the remaining 17 (12%) were discharged on the same day. Eight patients developed respiratory failure (6%), 7 had renal dysfunction (5%), 4 had coagulation abnormalities (3%), and 10 had infectious complications (7%) in the early postoperative period. The median hospital stay was 4 days, and 5 patients (4%) developed rejection during hospitalization. Five patients died of respiratory or infectious complications (4%). Most liver-graft recipients who undergo nontransplant surgery are given general anesthesia, transferred to the ward after the procedure, and discharged without major complications. We suggest that orthotopic liver transplant recipients may undergo nontransplant surgery without any postoperative graft dysfunction.

FXR controls the tumor suppressor NDRG2 and FXR agonists reduce liver tumor growth and metastasis in an orthotopic mouse xenograft model.

PubMed

Deuschle, Ulrich; Schüler, Julia; Schulz, Andreas; Schlüter, Thomas; Kinzel, Olaf; Abel, Ulrich; Kremoser, Claus

2012-01-01

The farnesoid X receptor (FXR) is expressed predominantly in tissues exposed to high levels of bile acids and controls bile acid and lipid homeostasis. FXR(-/-) mice develop hepatocellular carcinoma (HCC) and show an increased prevalence for intestinal malignancies, suggesting a role of FXR as a tumor suppressor in enterohepatic tissues. The N-myc downstream-regulated gene 2 (NDRG2) has been recognized as a tumor suppressor gene, which is downregulated in human hepatocellular carcinoma, colorectal carcinoma and many other malignancies.We show reduced NDRG2 mRNA in livers of FXR(-/-) mice compared to wild type mice and both, FXR and NDRG2 mRNAs, are reduced in human HCC compared to normal liver. Gene reporter assays and Chromatin Immunoprecipitation data support that FXR directly controls NDRG2 transcription via IR1-type element(s) identified in the first introns of the human, mouse and rat NDRG2 genes. NDRG2 mRNA was induced by non-steroidal FXR agonists in livers of mice and the magnitude of induction of NDRG2 mRNA in three different human hepatoma cell lines was increased when ectopically expressing human FXR. Growth and metastasis of SK-Hep-1 cells was strongly reduced by non-steroidal FXR agonists in an orthotopic liver xenograft tumor model. Ectopic expression of FXR in SK-Hep1 cells reduced tumor growth and metastasis potential of corresponding cells and increased the anti-tumor efficacy of FXR agonists, which may be partly mediated via increased NDRG2 expression. FXR agonists may show a potential in the prevention and/or treatment of human hepatocellular carcinoma, a devastating malignancy with increasing prevalence and limited therapeutic options.

Impact of N-acetylcysteine on the hepatic microcirculation after orthotopic liver transplantation.

PubMed

Koeppel, T A; Lehmann, T G; Thies, J C; Gehrcke, R; Gebhard, M M; Herfarth, C; Otto, G; Post, S

1996-05-15

Recent observations showed an improvement of hepatic macro- and microhemodynamics as well as survival rates after warm ischemia of the liver following treatment with N-acetylcysteine (NAC). In this study we assessed the influence of NAC on the hepatic microcirculation after orthotopic liver transplantation (OLT) using intravital fluorescence microscopy. OLT with simultaneous arterialization was performed in 16 male Lewis rats following cold storage in University of Wisconsin solution for 24 hr. Within the experimental group (n = 8) donors received NAC (400 mg/kg) 25 min before hepatectomy. In addition, high-dose treatment of recipients with NAC (400 mg/kg) was started with reperfusion. Control animals (n = 8) received an equivalent amount of Ringer's solution. Intravital fluorescence microscopy was performed 30-90 min after reperfusion assessing acinar and sinusoidal perfusion, leukocyte-endothelium interaction, and phagocytic activity. Treatment with NAC reduced the number of nonperfused sinusoid from 52.4 +/- 0.8% to 15.7 +/- 0.5% (p = 0.0001) (mean +/- SEM). Furthermore, we achieved a significant reduction of leukocytes adhering to sinusoidal endothelium (per mm2 liver surface) from 351.9 +/- 13.0 in controls to 83.6 +/- 4.2 in the experimental group (P = 0.0001). In postsinusoidal venules, treatment with NAC decreased the number of sticking leukocytes (per mm2 endothelium) from 1098.5 +/- 59.6 to 425.9 +/- 37.7 (P = 0.0001). Moreover, bile flow was significantly increased after therapy with NAC (4.3 +/- 1.2 vs. 2.2 +/- 0.7 ml/90 min x 100g liver) (P < 0.05). Phagocytic activity was not influenced by application of NAC. We conclude that high-dose therapy with NAC in OLT attenuates manifestations of microvascular perfusion failure early after reperfusion and should be considered as a means to reduce reperfusion injury.

Chloroquine inhibits hepatocellular carcinoma cell growth in vitro and in vivo

PubMed Central

HU, TAO; LI, PEI; LUO, ZHONGGUANG; CHEN, XIAOYU; ZHANG, JINGYANG; WANG, CHUNYAO; CHEN, PING; DONG, ZIMING

2016-01-01

Recently, chloroquine (CQ) has been widely used to improve the efficacy of different chemotherapy drugs to treat tumors. However, the effects of single treatment of CQ on liver cancer have not been investigated. In the present study, we examined the effects of CQ on the growth and viability of liver cancer cells in vitro and in vivo, and revealed that CQ treatment triggered G0/G1 cell cycle arrest, induced DNA damage and apoptosis in a dose- and time-dependent manner in liver cancer cells. Moreover, administration of CQ to tumor-bearing mice suppressed the tumor growth in an orthotopic xenograft model of liver cancer. These findings extend our understanding and suggest that CQ could be repositioned as a treatment option for liver cancer as a single treatment or in combination. PMID:26530158

Impact of MLH1 expression on tumor evolution after curative surgical tumor resection in a murine orthotopic xenograft model for human MSI colon cancer.

PubMed

Meunier, Katy; Ferron, Marianne; Calmel, Claire; Fléjou, Jean-François; Pocard, Marc; Praz, Françoise

2017-09-01

Colorectal cancers (CRCs) displaying microsatellite instability (MSI) most often result from MLH1 deficiency. The aim of this study was to assess the impact of MLH1 expression per se on tumor evolution after curative surgical resection using a xenograft tumor model. Transplantable tumors established with the human MLH1-deficient HCT116 cell line and its MLH1-complemented isogenic clone, mlh1-3, were implanted onto the caecum of NOD/SCID mice. Curative surgical resection was performed at day 10 in half of the animals. The HCT116-derived tumors were more voluminous compared to the mlh1-3 ones (P = .001). Lymph node metastases and peritoneal carcinomatosis occurred significantly more often in the group of mice grafted with HCT116 (P = .007 and P = .035, respectively). Mlh1-3-grafted mice did not develop peritoneal carcinomatosis or liver metastasis. After surgical resection, lymph node metastases only arose in the group of mice implanted with HCT116 and the rate of cure was significantly lower than in the mlh1-3 group (P = .047). The murine orthotopic xenograft model based on isogenic human CRC cell lines allowed us to reveal the impact of MLH1 expression on tumor evolution in mice who underwent curative surgical resection and in mice whose tumor was left in situ. Our data indicate that the behavior of MLH1-deficient CRC is not only governed by mutations arising in genes harboring microsatellite repeated sequences but also from their defect in MLH1 as such. © 2017 Wiley Periodicals, Inc.

NIRF Optical/PET Dual-Modal Imaging of Hepatocellular Carcinoma Using Heptamethine Carbocyanine Dye

PubMed Central

Zhang, Caiqin; Zhao, Yong; Zhao, Ningning; Tan, Dengxu; Zhang, He; Chen, Xue; Zhang, Hai; An, Jiaze

2018-01-01

Combining near-infrared fluorescence (NIRF) and nuclear imaging techniques provides a novel approach for hepatocellular carcinoma (HCC) diagnosis. Here, we report the synthesis and characteristics of a dual-modality NIRF optical/positron emission tomography (PET) imaging probe using heptamethine carbocyanine dye and verify its feasibility in both nude mice and rabbits with orthotopic xenograft liver cancer. This dye, MHI-148, is an effective cancer-specific NIRF imaging agent and shows preferential uptake and retention in liver cancer. The corresponding NIRF imaging intensity reaches 109/cm2 tumor area at 24 h after injection in mice with HCC subcutaneous tumors. The dye can be further conjugated with radionuclide 68Ga (68Ga-MHI-148) for PET tracing. We applied the dual-modality methodology toward the detection of HCC in both patient-derived orthotopic xenograft (PDX) models and rabbit orthotopic transplantation models. NIRF/PET images showed clear tumor delineation after probe injection (MHI-148 and 68Ga-MHI-148). The tumor-to-muscle (T/M) standardized uptake value (SUV) ratios were obtained from PET at 1 h after injection of 68Ga-MHI-148, which was helpful for effectively capturing small tumors in mice (0.5 cm × 0.3 cm) and rabbits (1.2 cm × 1.8 cm). This cancer-targeting NIRF/PET dual-modality imaging probe provides a proof of principle for noninvasive detection of deep-tissue tumors in mouse and rabbit and is a promising technique for more accurate and early detection of HCC. PMID:29706843

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Isoflurane: An Ideal Anesthetic for Rodent Orthotopic Liver Transplantation Surgery?

PubMed

Cao, D; Liu, Y; Li, J; Gong, J

2016-10-01

Because the choice of anesthetic affects the rodent orthotopic liver transplantation (OLT) model, we compared the effects of isoflurane, ketamine, chloral hydrate, and pentobarbital on the OLT model. OLT was performed using the two-cuff technique. Two hundred male rats were randomly divided into five groups: control, isoflurane, ketamine, chloral hydrate, and pentobarbital groups. Rectal temperatures, respiratory rates, arterial blood values (pH, PaCO 2 , PaO 2 , and SatO 2 ), liver function tests and histopathology, recovery times, and anhepatic stage mortality rates were assessed. Compared with controls, respiratory rates decreased by 20% in the isoflurane group, and decreased by 40%-50% in the ketamine, chloral hydrate, and pentobarbital groups. The PaO 2 , SatO 2 , and pH levels in the ketamine, chloral hydrate, and pentobarbital groups were significantly lower than those in the isoflurane and control groups (P < .05). Only the pentobarbital group displayed significant liver histopathologic changes along with significantly higher levels of serum alanine aminotransferase and total bilirubin, but a significantly lower level of serum albumin, compared with the control group (P < .05). The isoflurane group had a 0% anhepatic stage mortality rate compared with rates of 30%-40% in the other anesthetic groups. Isoflurane should be the preferred anesthetic for rodent OLT surgery due to its minimal respiratory and hepatic physiological effects as well as its low anhepatic phase mortality rate. Secondary to isoflurane, ketamine and chloral hydrate may be administered as donor anesthetics. Pentobarbital use should be avoided entirely in rodent OLT surgery due to its significant hepatotoxic effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of pretransplant renal function on survival after liver transplantation.

PubMed

Gonwa, T A; Klintmalm, G B; Levy, M; Jennings, L S; Goldstein, R M; Husberg, B S

1995-02-15

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Seventh-day syndrome: a catastrophic event after liver transplantation: case report.

PubMed

Pereira, M; Ferreira, I; Gandara, J; Ferreira, S; Lopes, V; Coelho, A; Vizcaino, R; Marinho, A; Daniel, J; Miranda, H P

2015-05-01

Seventh-day syndrome (7DS) is an early serious complication of liver transplantation, characterized by sudden failure of a previously normally functioning liver graft ∼1 week after the surgery. Although it is an uncommon event, it has major associated mortality. As its etiology is yet to be recognized, the only currently available treatment is retransplantation. We present 3 cases of orthotopic liver transplantation recipients who had an initial uneventful recovery after surgery followed by a dramatic rise of serum liver enzyme levels ∼7 days later and hepatic failure with subsequent graft loss and death despite high-dose immunosuppressive therapy. Histologic findings showed massive centrolobular hemorrhage and hepatocellular necrosis with reduced inflammation. It is essential to review and accumulate more clinical and laboratory information to better understand this syndrome and to better prevent and treat it. Copyright © 2015 Elsevier Inc. All rights reserved.

Liver heterotopia in the head of a patient with osteosarcoma of the maxilla. A paracrine tumor-induced hepatogenesis?

PubMed

Corsi, Alessandro; Riminucci, Mara

2017-02-01

Heterotopia of liver tissue is uncommon. It has been reported at various sites, more frequently near the orthotopic liver, including gallbladder, hepatic ligaments, omentum, and retroperitoneum, rarely within the diaphragm and the thoracic cavity, and never within the head. We report here a 22-year-old patient surgically treated for a maxillary osteosarcoma in which microscopic liver tissue islands were incidentally detected in the respiratory mucosa of the surgical margin. The islands comprised well-differentiated HepPar-1-positive hepatocytes and were surrounded by cytokeratin-7- and cytokeratin-19-positive bile duct-like structures. This case, which is unique in the medical literature, may suggest an inductive paracrine effect of the osteosarcoma cells by secretion of factors promoting hepatocyte specification of primitive endodermal progenitors and subsequent liver morphogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of oral vancomycin in recurrent primary sclerosing cholangitis following liver transplantation

PubMed Central

Hey, Penelope; Lokan, Julie; Johnson, Paul; Gow, Paul

2017-01-01

Primary sclerosing cholangitis (PSC) is a liver disease that leads to progressive destruction and stricturing of the biliary tree. Unfortunately, apart from orthotopic liver transplantation (OLT), there are no universally accepted therapies to treat this disease. Even following transplantation, recurrence of PSC is seen in approximately one quarter of patients and leads to high rates of graft failure. Oral vancomycin, through possible immunomodulatory and anti-inflammatory mechanisms, has been shown in small-scale studies to be successful in improving liver function tests in patients with pretransplant PSC. We report the first case of an adult patient diagnosed with recurrent PSC 4 years after OLT who was treated with oral vancomycin leading to complete normalisation of his liver biochemistry. This case adds to the growing literature of a potential therapeutic role for this antibiotic in PSC and highlights interesting questions regarding mechanisms of disease. PMID:28951512

[Astigmatism after keratoplasty: influence of orthotopic transplantation].

PubMed

Feuerstacke, J; Hellwinkel, O; Naydis, I; Linke, S; Klemm, M

2014-09-01

Patients undergoing corneal transplantation often suffer from postoperative reduced vision due to high astigmatism. This retrospective study analyzed the influence of heterotopic or orthotopic transplantation on astigmatism and visual outcome. In this study 373 eyes of 334 patients were analyzed. Group 1 (OT) contained 186 eyes, which underwent orthotopic transplantation (side of recipient and donor corresponded), whereas group 2 (HT) included 187 heterotopic keratoplasties (donor cornea placed in the recipient's contralateral side). After 1, 3, 6, 12 and 24 months the median of keratometric astigmatism, objective astigmatism, topographic astigmatism and best corrected visual acuity (BCVA) were assessed and compared between groups. The long-term results showed no statistically significant differences regarding keratometric and objective astigmatism, whereas topographic astigmatism differed significantly (p = 0.04) after 3 months. We observed a lower astigmatism of 5.7 dpt (range 3.08-7.78 dpt) in group OT than in the group HT with 7.1 dpt (range 3.9-10.7 dpt). No differences were found at the other time points. The BCVA showed a significantly better effect after 1 month (p = 0.01) in the OT group of 0.2 (0.1-0.3) than in HT group of 0.1 (0.05/0.25). In the postoperative course no additional significant dissimilarities were documented. Heterotopic and orthotopic keratoplasty show no significant long-term differences in astigmatism and visual outcom.

Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model

PubMed Central

Choi, Goeun; Piao, Huiyan; Alothman, Zeid A; Vinu, Ajayan; Yun, Chae-Ok; Choy, Jin-Ho

2016-01-01

Methotrexate (MTX), an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug-clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco’s Modified Eagle’s Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection. PMID:26855572

Targeted expression of BikDD combined with metronomic doxorubicin induces synergistic antitumor effect through Bax activation in hepatocellular carcinoma

PubMed Central

Dai, Huei-Yue; Chen, Hui-Yu; Lai, Wei-Chen; Hung, Mien-Chie; Li, Long-Yuan

2015-01-01

Conventional chemotherapy is commonly used to treat advanced non-resectable hepatocellular carcinoma (HCC) but this treatment modality has not demonstrated convincing survival benefit in HCC patients. Our previous studies indicated that targeted expression of therapeutic BikDD driven by a liver cancer-specific α-fetoprotein promoter/enhancer (eAFP) in the VISA backbone (eAFP-VISA-BikDD) significantly and specifically kills HCC cells in multiple orthotopic animal models. To enhance its therapeutic efficacy, we combined eAFP-VISA-BikDD with chemotherapeutic agents and found that eAFP-VISA-BikDD plus doxorubicin (Dox) or 5-fluorouracil (5-FU) demonstrated synergistic cytotoxicity in HCC cells. Specifically, the combination of eAFP-VISA-BikDD plus Dox markedly induced apoptosis via increased Bax mitochondrial translocation and cytoplasmic cytochrome c release. Compared with either agent alone, a low dose of Dox combined with eAFP-VISA-BikDD induced better antitumor effect and prolonged longer survival of mice in two orthotopic liver cancer xenograft models. Our findings provide strong preclinical support for evaluating the combined therapy of eAFP-VISA-BikDD and Dox in a clinical setting as a treatment option for HCC. PMID:26247632

Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model.

PubMed

Choi, Goeun; Piao, Huiyan; Alothman, Zeid A; Vinu, Ajayan; Yun, Chae-Ok; Choy, Jin-Ho

2016-01-01

Methotrexate (MTX), an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug-clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco's Modified Eagle's Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection.

Mucocele of the cystic duct remnant after orthotopic liver transplant: a problem revisited.

PubMed

Chatterjee, Suvadip; Das, Debasish; Hudson, Mark; Bassendine, Margaret Fiona; Scott, John; Oppong, Kofi Ernest; Sen, Gourab; French, Jeremy J

2011-06-01

Mucocele of the cystic duct remnant is an uncommon hepatobiliary complication of a liver transplant. Current practice usually involves either excising the cystic duct, or incorporating the distal end of the transected cystic duct into the suture line of the biliary anastomosis to ensure drainage. We report a patient who developed cystic duct remnant mucocele after the latter approach was adopted. We believe that this is likely related to delayed anastomotic stricturing, which prevented draining from the remnant cystic duct. We also discuss the incidence, pathology, investigations, and treatment of this condition.

Multifocal avascular necrosis after liver transplantation: an unusual presentation of the antiphospholipid syndrome.

PubMed

Mundo, J; Peris, P; Monegal, A; Navasa, M; Cervera, R; Guañiabens, N

2006-01-01

We describe the case of a 31-year-old man who presented with an antiphospholipid syndrome (APS), which manifested as multifocal avascular necrosis (AVN) one year after orthotopic liver transplantation. The patient developed multiple AVN affecting hips, left knee, humerus and tarsal bones just after withdrawal of corticosteroid therapy. Three years later when lupus anticoagulant was detected, he began anticoagulant treatment and no further AVN episodes were observed. It is important to be aware of this clinical manifestation of APS, especially in these cases where it can be easily overlooked because of corticosteroid therapy.

Extreme hepatic resections for the treatment of advanced hepatoblastoma: Are planned close margins an acceptable approach?

PubMed

Fonseca, Adriana; Gupta, Abha; Shaikh, Furqan; Ramphal, Raveena; Ng, Vicky; McGilvray, Ian; Gerstle, J Ted

2018-02-01

Orthotopic liver transplantation (OLT) is considered the standard for children with hepatoblastoma (HB) in whom complete surgical resection is not possible. However, OLT is not always available or feasible. To describe the outcome of children with HB who were initially deemed unresectable and underwent complex hepatectomy with planned close margins, and ultimately avoided OLT. Demographic data, surgical and pathologic details, and survival information were collected from children treated for HB between January 2010 to December 2015. Among six children (median age 12 months (3-41 months)), PRETEXT classification was III (n = 2), III/IV (n = 1), and IV (n = 3). Patients received a median of six cycles (range 4-7) of platinum-based induction chemotherapy; five received doxorubicin. Experienced pediatric surgeons performed extended right and left hepatectomy in five and one patients, respectively, with assistance of an experienced liver transplant surgeon (n = 4). Microscopic margins were positive (n = 2) and negative but close (n = 4; 2-5 mm). Two patients required vascular reconstruction of the vena cava. At median follow-up of 3.3 years (1.7-4.6 years), there was no evidence of local recurrence. One patient had recurrence of pulmonary disease 3 months after surgery. Patients with advanced HB treated with complex surgical resections with positive or close negative margins had good outcomes without OLT. We suggest that planned positive or close microscopic margins in highly selected HB patients may spare the morbidity of OLT and offer an alternative for those ineligible for OLT. Our experience illustrates the importance of a multidisciplinary team specialized in the management of liver tumors. © 2017 Wiley Periodicals, Inc.

Ultrastructural basis for the efficiency of an ileal orthotopic neobladder 27 years after surgery.

PubMed

Orlandini, G; Guizzardi, S; Ferretti, S; Simonazzi, M; Bucci, G; Gatti, R

2002-01-01

The morphological and functional basis of the excellent clinical outcome of ileal orthotopic neobladders are largely unknown. Only long-term follow-up studies will provide an adequate answer to this unsettled question. We have studied a patient who underwent this type of surgery over 27 years ago. Besides an important secretive adaptation we have found, at the ultrastructural level, that the monolayered epithelium does not show signs of true metaplasia and that changes had occurred in the intercellular junctions, namely that desmosomes are significantly increased. Although limited to a single case, these features, if confirmed by further observations, suggest a working hypothesis for the understanding of the definitive phenotypic adaptation of the ileal epithelium to the new aggressive environment. Copyright 2002 S. Karger AG, Basel

Left Lateral Sectionectomy of the Native Liver and Combined Living-Related Liver–Kidney Transplantation for Primary Hyperoxaluria Type 1

PubMed Central

Chen, Guo-Yong; Wei, Si-Dong; Zou, Zhong-Wu; Tang, Gao-Feng; Sun, Jian-Jun; Zhou, Shao-Tang

2015-01-01

Abstract Primary hyperoxaluria type I (PH1), the most severe form of primary hyperoxalurias, is a liver disease of the metabolic defect in glyoxylate detoxification that can be corrected by liver transplantation. A 21-year-old man presented to our center after 4 months of regular hemodialysis for kidney failure caused by nephrolithiasis. A diagnosis of PH1 was confirmed by mutations of the AGXT gene. Left lateral sectionectomy of the native liver was performed; and auxiliary partial orthotopic liver transplantation (APOLT) and kidney transplantation were carried out synchronously using a living donor. After transplantation, the patient's plasma oxalate and creatinine levels substantially decreased and the patient recovered well with good dual grafts function. APOLT and kidney transplantation can compensate the liver deficient in liver enzyme production and aid the renal elimination of oxalate, thus serving as an effective treatment option for patients with PH1. In conclusion, left lateral sectionectomy of the native liver and combined living-related liver–kidney transplantation can be a surgical option for PH1. PMID:26252291

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer.

PubMed

Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

2017-06-07

To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI ( P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites ( P = 0.009), liver metastasis ( P = 0.035), and decreased survival time ( P = 0.022). N-syndecan expression was significantly associated with tumor size ( P = 0.025), but not with survival time ( P = 0.539). High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer.

Successful cardiac transplantation outcomes in patients with adult congenital heart disease.

PubMed

Menachem, Jonathan N; Golbus, Jessica R; Molina, Maria; Mazurek, Jeremy A; Hornsby, Nicole; Atluri, Pavan; Fuller, Stephanie; Birati, Edo Y; Kim, Yuli Y; Goldberg, Lee R; Wald, Joyce W

2017-09-01

The purpose of our study is (1) to characterise patients with congenital heart disease undergoing heart transplantation by adult cardiac surgeons in a large academic medical centre and (2) to describe successful outcomes associated with our multidisciplinary approach to the evaluation and treatment of adults with congenital heart disease (ACHD) undergoing orthotopic heart transplantation (OHT). Heart failure is the leading cause of death in patients with ACHD leading to increasing referrals for OHT. The Penn Congenital Transplant Database comprises a cohort of patients with ACHD who underwent OHT between March 2010 and April 2016. We performed a retrospective cohort study of the 20 consecutive patients. Original cardiac diagnoses include single ventricle palliated with Fontan (n=8), dextro-transposition of the great arteries after atrial switch (n=4), tetralogy of Fallot (n=4), pulmonary atresia (n=1), Ebstein anomaly (n=1), unrepaired ventricular septal defect (n=1) and Noonan syndrome with coarctation of the aorta (n=1). Eight patients required pretransplant inotropes and two required pretransplant mechanical support. Nine patients underwent heart-liver transplant and three underwent heart-lung transplant. Three patients required postoperative mechanical circulatory support. Patients were followed for an average of 38 months as of April 2016, with 100% survival at 30 days and 1 year and 94% overall survival (19/20 patients). ACHD-OHT patients require highly specialised, complex and multidisciplinary healthcare. The success of our programme is attributed to using team-based, patient-centred care including our multidisciplinary staff and specialists across programmes and departments. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Equivalent survival following liver transplantation in patients with non-alcoholic steatohepatitis compared with patients with other liver diseases.

PubMed

Kennedy, Christopher; Redden, David; Gray, Stephen; Eckhoff, Devin; Massoud, Omar; McGuire, Brendan; Alkurdi, Basem; Bloomer, Joseph; DuBay, Derek A

2012-09-01

Orthotopic liver transplantation (LT) in non-alcoholic steatohepatitis (NASH) is increasing in parallel with the obesity epidemic. This study retrospectively reviewed the clinical outcomes of LTs in NASH (n = 129) and non-NASH (n = 775) aetiologies carried out at a single centre between 1999 and 2009. Rates of 1-, 3- and 5-year overall survival in NASH (90%, 88% and 85%, respectively) were comparable with those in non-NASH (92%, 86% and 80%, respectively) patients. Mortality within 4 months of LT was twice as high in NASH as in non-NASH patients (8.5% vs. 4.2%; P = 0.04). Compared with non-NASH patients, post-LT mortality in NASH patients was more commonly caused by infectious (38% vs. 26%; P < 0.05) or cardiac (19% vs. 7%; P < 0.05) aetiologies. Five-year survival was lower in NASH patients with a high-risk phenotype (age >60 years, body mass index >30 kg/m(2), with hypertension and diabetes) than in NASH patients without these characteristics (72% vs. 87%; P = 0.02). Subgroup analyses revealed that 5-year overall survival in NASH was equivalent to that in Laennec's cirrhosis (85% vs. 80%; P 0.87), but lower than that in cirrhosis of cryptogenic aetiology (85% vs. 96%; P = 0.04). Orthotopic LT in NASH was associated with increased early postoperative mortality, but 1-, 3- and 5-year overall survival rates were equivalent to those in non-NASH patients. © 2012 International Hepato-Pancreato-Biliary Association.

Clinical outcomes of liver transplantation for HBV-related hepatocellular carcinoma: data from the NIH HBV OLT study.

PubMed

Han, Steven-Huy; Reddy, K Rajender; Keeffe, Emmet B; Soldevila-Pico, Consuelo; Gish, Robert; Chung, Raymond T; Degertekin, Bulent; Lok, Anna

2011-01-01

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is an indication for orthotopic liver transplantation (OLT) in patients with tumor stage within the United Network for Organ Sharing criteria. The number of patients listed for HBV-related HCC is increasing, while the number of patients listed for HBV-related cirrhosis is declining presumptively because of the availability of more effective oral nucleos(t)ide analogues. This study presents the final, long-term outcome of patients transplanted for HBV-related HCC in the National Institutes of Health (NIH) HBV OLT Study Group. Ninety-eight patients (52.4%) in the NIH HBV OLT cohort underwent OLT for HBV-related HCC. With a mean follow-up of 36.5 months post-OLT, 12 (12.2%) patients developed recurrence of HCC. Multivariate analysis did not find a statistically significant role of gender, tumor stage at OLT, pre-OLT HCC treatment, recurrence of HBV, or duration of HCC diagnosis pre-OLT in predicting HCC recurrence. Serum alpha-fetoprotein (AFP) level >200 ng/mL at transplant was found to be statistically significant in predicting HCC recurrence (p=0.003). HCC recurrence was significantly associated with decreased post-OLT survival. HCC is the most common indication for OLT in patients with chronic hepatitis B in the era of more effective oral antivirals. Serum AFP at the time of OLT is significantly associated with HCC recurrence. © 2010 John Wiley & Sons A/S.

Cost/efficacy clinical trial about the use of T-tube in cadaveric donor liver transplant: preliminary results.

PubMed

Amador, A; Charco, R; Marti, J; Alvarez, G; Ferrer, J; Mans, E; Fuster, J; Fondevila, C; Garcia-Valdecasas, J C

2005-03-01

Biliary reconstruction is the most common cause of morbidity associated with orthotopic liver transplantation. Our objective was to assess the complications and hospital resources related to the use of a T-tube. Among 95 liver transplants performed from October 2002 to November 2003, 84 patients were randomized to receive a T-tube or no T-tube. We analyzed all patients with a follow-up of at least of 3 months. Fifty-five transplants were analyzed with 8 months mean follow-up, including twenty eight with T-tube and twenty seven without a T-tube. No patient died during the follow-up. The overall rate of biliary complications was 45.4% (25/55) including 21/28 (75%) in the T-tube group and 4/27(14.8%) in the non-T-tube group (P < .0001). Complications related to T-tube extraction occurred in 48.2% (13/27), including 3 cholangitis and 10 leaks. The costs of hospital resources due to radiological studies were 5329 capital JE, Ukrainian for the T-tube group vs 5785 capital JE, Ukrainian for the non-T-tube group. The costs of hospital resources due to treatment were 28,280 capital JE, Ukrainian for the T-tube group vs 10,088 capital JE, Ukrainian for the non-T-tube group. Use of a T-tube during orthotopic liver transplantation does not seem justified. Biliary anastomosis stenting is followed by an increased incidence of complications, most of which are related to its use. Hospital stay, radiological studies, and cost of hospital resources are higher among the T-tube patients. Therefore its systematic use is not advisable.

Analysis of 83 consecutive liver transplants performed at a tertiary care reference hospital in the interior of the state of Sao Paulo.

PubMed

Lombardi, Ana Carolina; Mente, Enio David; Sankarankutty, Ajith Kumar; Souza, Fernanda Fernandes; Teixeira, Andreza Corrêa; Cagnolati, Daniel; Souza, Maria Eliza Jordani de; Silva, Orlando de Castro e

2011-12-01

To analyze pre-, intra- and immediate postoperative parameters of patients submitted to liver transplantation. Eighty-three consecutive orthotopic liver transplants performed from January 2009 to July 2011 were analyzed. The patients were divided into 2 groups: A, survivors (MELD between 9 and 60) and B, non-survivors (MELD between 14 and 40), with 30.6% of group A patients being CHILD C, 51℅ CHILD B and 18,4℅ CHILD A. In group B, 32.1℅ of the patients were CHILD C, 42,9℅ CHILD B, and 25℅ CHILD A. All orthotopic liver transplantations were performed using the piggyback technique without a portacaval shunt. Systemic arterial pressure and serum ALT and AST levels were determined preoperatively and 5, 60 and 1440 minutes after arterial graft revascularization. Serum ALT and AST profiles were evaluated for seven days after surgery. Systemic arterial blood pressure levels, time of hot and hypothermic ischemia and time of graft implant were statistically similar for the two groups (p>0.05). Serum levels (U/L) of ALT and AST at the 5, 60 and 1440 minute time points after arterial revascularization of the graft were also similar for the two groups studied, as also were the serum ALT and AST profiles. No statistically significant difference in any of the parameters studied was detected between the two groups. Under the conditions of the present study and on the basis of the parameters evaluated, no direct relation was detected between the intraoperative period and the type of patient outcome in the two groups studied.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD).

PubMed

Czigany, Zoltan; Schöning, Wenzel; Ulmer, Tom Florian; Bednarsch, Jan; Amygdalos, Iakovos; Cramer, Thorsten; Rogiers, Xavier; Popescu, Irinel; Botea, Florin; Froněk, Jiří; Kroy, Daniela; Koch, Alexander; Tacke, Frank; Trautwein, Christian; Tolba, Rene H; Hein, Marc; Koek, Ger H; Dejong, Cornelis H C; Neumann, Ulf Peter; Lurje, Georg

2017-10-10

Orthotopic liver transplantation (OLT) has emerged as the mainstay of treatment for end-stage liver disease. In an attempt to improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with a higher incidence of primary graft non-function and/or delayed graft function. As such, several strategies have been developed aiming at reconditioning poor quality ECD liver allografts. Hypothermic oxygenated machine perfusion (HOPE) has been successfully tested in preclinical experiments and in few clinical series of donation after cardiac death OLT. HOPE ECD-DBD is an investigator-initiated, open-label, phase-II, prospective multicentre randomised controlled trial on the effects of HOPE on ECD allografts in donation after brain death (DBD) OLT. Human whole organ liver grafts will be submitted to 1-2 hours of HOPE (n=23) via the portal vein before implantation and are going to be compared with a control group (n=23) of patients transplanted after conventional cold storage. Primary (peak and Δ peak alanine aminotransferase within 7 days) and secondary (aspartate aminotransferase, bilirubin and international normalised ratio, postoperative complications, early allograft dysfunction, duration of hospital and intensive care unit stay, 1-year patient and graft survival) endpoints will be analysed within a 12-month follow-up. Extent of ischaemia-reperfusion (I/R) injury will be assessed using liver tissue, perfusate, bile and serum samples taken during the perioperative phase of OLT. The study was approved by the institutional review board of the RWTH Aachen University, Aachen, Germany (EK 049/17). The current paper represent the pre-results phase. First results are expected in 2018. NCT03124641. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Implantability, Complications, and Follow-Up After Transjugular Intrahepatic Portosystemic Stent-Shunt Creation With the 6F Self-Expanding Sinus-SuperFlex-Visual Stent.

PubMed

Spira, Daniel; Wiskirchen, Jakub; Lauer, Ulrich; Ketelsen, Dominik; Nikolaou, Konstantin; Wiesinger, Benjamin

2016-07-01

The transjugular intrahepatic portosystemic stent-shunt (TIPSS) builds a shortcut between the portal vein and a liver vein, and represents a sophisticated alternative to open surgery in the management of portal hypertension or its complications. To describe clinical experiences with a low-profile nitinol stent system in TIPSS creation, and to assess primary and long-term success. Twenty-six patients (5 females, 21 males; mean age 54.6 years) were treated using a low-profile 6F self-expanding sinus-SuperFlex-Visual stent system. The indication for TIPSS creation was refractory bleeding in 9 of the 26 patients, refractory ascites in 18 patients, and acute thrombosis of the portal vein confluence in one patient. Portosystemic pressure gradients before and after TIPSS, periprocedural and long-term complications, and the time to orthotopic liver transplantation (OLT) or death were recorded. The portosystemic pressure gradient was significantly reduced, from 20.9 ± 6.3 mmHg before to 8.2 ± 2.3 mmHg after TIPSS creation (P < 0.001). Procedure-related complications included acute tract occlusion (n = 2), liver hematoma (n = 1), hepatic encephalopathy (n = 1), and cardiac failure (n = 1). Three of the 26 patients had late-onset TIPSS occlusion (at 12, 12, and 39 months after TIPSS creation). Three patients died within one week after the procedure due to their poor general condition (multiorgan failure, acute respiratory distress syndrome, necrotizing pancreatitis, and aspiration pneumonia). Another four patients succumbed to their underlying advanced liver disease within one year after TIPSS insertion. Seven patients underwent OLT at a mean time of 9.4 months after TIPSS creation. The sinus-SuperFlex-Visual stent system can be safely deployed as a TIPSS device. The pressure gradient reduction was clinically sufficient to treat the patients' symptoms, and periprocedural complications were due to the TIPSS procedure per se rather than to the particular stent system employed in this study.

Using old liver grafts for liver transplantation: where are the limits?

PubMed

Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

2014-08-21

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

Using old liver grafts for liver transplantation: Where are the limits?

PubMed Central

Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

2014-01-01

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573

[Cardiac transplantation and neoplasms: experiences at Escola Paulista de Medicina of the Federal University of São Paulo].

PubMed

Mello Junior, Walter Teixeira de; Branco, João Nelson R; Catani, Roberto; Aguiar, Luciano de Figueiredo; Paez, Rodrigo Pereira; Buffolo, Enio

2006-02-01

To study the occurrence and types of neoplasms developed by patients who underwent an orthotopic cardiac transplantation under the Program of Cardiac Transplantation of Escola Paulista de Medicina, Federal University of São Paulo. This is an observational study of 106 patients who underwent orthotopic cardiac transplantation from November 1986 to September 2002 and survived at least thirty days following the procedure. The triple immunosuppressive regimen given included cyclosporin A, azathioprine and a corticosteroid agent. Only two patients received OKT3 in addition to the regimen established. Mean follow-up was 61.4 months (ranging from two months to 192 months). Twenty-three patients (21.3%) developed neoplasms--56.5% of these were skin neoplasm, 30.1%, solid tumors, and 13.4% of post-transplant lymphoproliferative disease (PTLD). Mean interval between transplantation and diagnosis of neoplasm was: 54.9 months for skin neoplasm; 24.8 months for solid tumors and 70.3 months for PTLD. Malignant neoplasms are relatively common in the population studied. Skin cancer was the most common type compared to the other types of neoplasms. Solid tumors were more frequently diagnosed than the lymphoproliferative diseases in the population examined.

Liver transplantation in infants younger than 1 year of age.

PubMed Central

Colombani, P M; Cigarroa, F G; Schwarz, K; Wise, B; Maley, W E; Klein, A S

1996-01-01

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults. PMID:8645039

Intraoperative Portal Flow of Less Than 1 Liter per Minute After Orthotopic Liver Transplantation Is Not Associated Per Se With an Increased Rate of Early Graft Dysfunction.

PubMed

Gastaca, M; Prieto, M; Valdivieso, A; Ruiz, P; Ventoso, A; Palomares, I; Matarranz, A; Martinez-Indart, L; Ortiz de Urbina, J

2016-09-01

The aim of this study was to determine whether a portal flow of <1,000 mL/min in orthotopic liver transplantation (OLT) is associated with a higher incidence of early graft dysfunction (EGD) and graft loss. A retrospective study was performed of 540 OLTs carried out consecutively from December 2004 to December 2013. Patients were divided into 2 groups: group A, portal flow <1,000 mL/min; and group B, portal flow >1,000 mL/min. We studied the incidence of EGD and graft survival. A subanalysis was performed to define the minimum acceptable portal flow/100 g of liver weight to reduce the development EGD and graft loss. Group A included 29 patients and group B, 511 patients. Group A had significantly lower-weight donors and recipients, female recipients with cholestatic disease, lower MELD scores, and lower hepatic artery flow. EGD occurred in 7 patients in group A (24.1%) versus 101 patients in group B (19.8%; P = .43). No significant differences were found in 1- and 5-year graft survival. A portal flow of <80 mL/min/100 g of liver weight was related to a significantly higher risk of developing EGD (odds ratio, 4.35; 95% confidence interval [CI], 1.46-12.91; P = .008) and graft loss (hazard ratio, 4.05; 95% CI, 1.32-12.42; P = .014). Intraoperative portal flow of <1,000 mL/min in OLT was not related per se with a higher incidence of EGD or graft loss. Significantly higher risk of developing EGD and graft loss was associated with a portal flow of <80 mL/min/100 g of liver weight. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluorescence spectroscopy for assessment of liver transplantation grafts concerning graft viability and patient survival

NASA Astrophysics Data System (ADS)

Vollet Filho, José D.; da Silveira, Marina R.; Castro-e-Silva, Orlando; Bagnato, Vanderlei S.; Kurachi, Cristina

2015-06-01

Evaluating transplantation grafts at harvest is essential for its success. Laser-induced fluorescence spectroscopy (LIFS) can help monitoring changes in metabolic/structural conditions of tissue during transplantation. The aim of the present study is to correlate LIFSobtained spectra of human hepatic grafts during liver transplantation with post-operative patients' mortality rate and biochemical parameters, establishing a method to exclude nonviable grafts before implantation. Orthotopic liver transplantation, piggyback technique was performed in 15 patients. LIFS was performed under 408nm excitation. Collection was performed immediately after opening donor's abdominal cavity, after cold perfusion, end of back-table period, and 5 min and 1 h after warm perfusion at recipient. Fluorescence information was compared to lactate, creatinine, bilirubin and INR levels and to survival status. LIFS was sensitive to liver changes during transplantation stages. Study-in-progress; initial results indicate correlation between fluorescence and life/death status of patients.

Side-to-side cavocavostomy with an endovascular stapler: Rescue technique for severe hepatic vein and/or inferior vena cava outflow obstruction after liver transplantation using the piggyback technique.

PubMed

Quintini, Cristiano; Miller, Charles M; Hashimoto, Koji; Philip, Ding; Uso, Teresa Diago; Aucejo, Federico; Kelly, Dympna; Winans, Charles; Eghtesad, Bijan; Vogt, David; Fung, John

2009-01-01

Venous outflow obstruction is a rare but potentially lethal complication after orthotopic liver transplantation (OLT) with the "piggyback" technique. Therapeutic options include angioplasty with or without stent placement, surgical reconstruction of the venous anastomosis, and retransplantation. Surgical options are technically very challenging and the outcomes discouraging. We describe here two cases of venous outflow obstruction in recipients of piggyback liver grafts, one involving both the vena cava and hepatic veins and the other affecting only hepatic vein outflow. Both patients were treated successfully with side-to-side cavo-cavostomy using an endovascular (endo-GIA) stapler. This novel technique is fast and effective in resolving the outflow obstruction. Copyright 2008 AASLD.

[Affective syndromes in liver transplant recipients: ¿mediated neurotoxicity immunosuppressive?].

PubMed

Restrepo, Diana Patricia; Tamayo, Alejandra

2015-01-01

The onset of affective and psychotic in liver transplant patients symptoms, raises the need to explore the possible etiologies of mental symptoms. Case report and literature review. Four clinical cases of patients undergoing orthotopic liver transplantation, who in the early post transplant showed affective symptoms, delusions and psychomotor agitation for which they needed psychiatric hospitalization and treatment with psychotropic drugs are presented. Three of the patients had clinical improvement and one patient died by suicide. The development of mental symptoms in the post-transplant period opens the possibility of considering the secondary organic mental disorder a basic condition. The adverse drug reaction may explain affective mental disorders in these four cases were reported. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

PubMed

Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao

2017-12-07

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Efficacy of oral vancomycin in recurrent primary sclerosing cholangitis following liver transplantation.

PubMed

Hey, Penelope; Lokan, Julie; Johnson, Paul; Gow, Paul

2017-09-25

Primary sclerosing cholangitis (PSC) is a liver disease that leads to progressive destruction and stricturing of the biliary tree. Unfortunately, apart from orthotopic liver transplantation (OLT), there are no universally accepted therapies to treat this disease. Even following transplantation, recurrence of PSC is seen in approximately one quarter of patients and leads to high rates of graft failure. Oral vancomycin, through possible immunomodulatory and anti-inflammatory mechanisms, has been shown in small-scale studies to be successful in improving liver function tests in patients with pretransplant PSC. We report the first case of an adult patient diagnosed with recurrent PSC 4 years after OLT who was treated with oral vancomycin leading to complete normalisation of his liver biochemistry. This case adds to the growing literature of a potential therapeutic role for this antibiotic in PSC and highlights interesting questions regarding mechanisms of disease. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Impact of Ischemic Preconditioning on Outcome in Clinical Liver Surgery: A Systematic Review

PubMed Central

Chu, Michael J. J.; Vather, Ryash; Hickey, Anthony J. R.; Phillips, Anthony R. J.; Bartlett, Adam S. J. R.

2015-01-01

Background. Ischemia-reperfusion injury is a major cause of post-liver-surgery complications. Ischemic preconditioning (IPC) has been demonstrated to protect against ischemia-reperfusion injury. Clinical studies have examined IPC in liver surgery but with conflicting results. This systematic review aimed to evaluate the effects of IPC on outcome in clinical liver surgery. Methods. An electronic search of OVID Medline and Embase databases was performed to identify studies that reported outcomes in patients undergoing liver surgery subjected to IPC. Basic descriptive statistics were used to summarise data from individual clinical studies. Results. 1093 articles were identified, of which 24 met the inclusion criteria. Seven topics were selected and analysed by subgroup. There were 10 studies in cadaveric liver transplantation, 2 in living-related liver transplantation, and 12 in liver resection. IPC decreases hepatocellular damage in liver surgery as determined by transaminases but does not translate to any significant clinical benefit in orthotopic liver transplant or liver resection. Conclusions. Available clinical evidence does not support routine use of IPC in liver surgery as it does not offer any apparent benefit in perioperative outcome. Further clinical studies will need to be carried out to determine the subset of patients that will benefit from IPC. PMID:25756045

Societal reintegration following cadaveric orthotopic liver transplantation.

PubMed

Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah; Molinari, Michele

2016-06-01

Studies on patients' societal reintegration following orthotopic liver transplantation (OLT) are scarce. Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re-integration following OLT and potential barriers they might have encountered. Among 157 eligible patients 110 (70%) participated. Mean participants' age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. Although patients' satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients' economical status and societal ability to recoup resources committed for OLT.

A 20-year period of orthotopic liver transplantation activity in a single center: a time series analysis performed using the R Statistical Software.

PubMed

Santori, G; Andorno, E; Morelli, N; Casaccia, M; Bottino, G; Di Domenico, S; Valente, U

2009-05-01

In many Western countries a "minimum volume rule" policy has been adopted as a quality measure for complex surgical procedures. In Italy, the National Transplant Centre set the minimum number of orthotopic liver transplantation (OLT) procedures/y at 25/center. OLT procedures performed in a single center for a reasonably large period may be treated as a time series to evaluate trend, seasonal cycles, and nonsystematic fluctuations. Between January 1, 1987 and December 31, 2006, we performed 563 cadaveric donor OLTs to adult recipients. During 2007, there were another 28 procedures. The greatest numbers of OLTs/y were performed in 2001 (n = 51), 2005 (n = 50), and 2004 (n = 49). A time series analysis performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria), a free software environment for statistical computing and graphics, showed an incremental trend after exponential smoothing as well as after seasonal decomposition. The predicted OLT/mo for 2007 calculated with the Holt-Winters exponential smoothing applied to the previous period 1987-2006 helped to identify the months where there was a major difference between predicted and performed procedures. The time series approach may be helpful to establish a minimum volume/y at a single-center level.

Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

PubMed Central

Chapiro, Julius; Wood, Laura D.; Lin, MingDe; Duran, Rafael; Cornish, Toby; Lesage, David; Charu, Vivek; Schernthaner, Rüdiger; Wang, Zhijun; Tacher, Vania; Savic, Lynn Jeanette; Kamel, Ihab R.

2014-01-01

Purpose To evaluate the diagnostic performance of three-dimensional (3Dthree-dimensional) quantitative enhancement-based and diffusion-weighted volumetric magnetic resonance (MR) imaging assessment of hepatocellular carcinoma (HCChepatocellular carcinoma) lesions in determining the extent of pathologic tumor necrosis after transarterial chemoembolization (TACEtransarterial chemoembolization). Materials and Methods This institutional review board–approved retrospective study included 17 patients with HCChepatocellular carcinoma who underwent TACEtransarterial chemoembolization before surgery. Semiautomatic 3Dthree-dimensional volumetric segmentation of target lesions was performed at the last MR examination before orthotopic liver transplantation or surgical resection. The amount of necrotic tumor tissue on contrast material–enhanced arterial phase MR images and the amount of diffusion-restricted tumor tissue on apparent diffusion coefficient (ADCapparent diffusion coefficient) maps were expressed as a percentage of the total tumor volume. Visual assessment of the extent of tumor necrosis and tumor response according to European Association for the Study of the Liver (EASLEuropean Association for the Study of the Liver) criteria was performed. Pathologic tumor necrosis was quantified by using slide-by-slide segmentation. Correlation analysis was performed to evaluate the predictive values of the radiologic techniques. Results At histopathologic examination, the mean percentage of tumor necrosis was 70% (range, 10%–100%). Both 3Dthree-dimensional quantitative techniques demonstrated a strong correlation with tumor necrosis at pathologic examination (R2 = 0.9657 and R2 = 0.9662 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively) and a strong intermethod agreement (R2 = 0.9585). Both methods showed a significantly lower discrepancy with pathologically measured necrosis (residual standard error [RSEresidual standard error] = 6.38 and 6.33 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively), when compared with non-3Dthree-dimensional techniques (RSEresidual standard error = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3Dthree-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCChepatocellular carcinoma lesions treated with TACEtransarterial chemoembolization. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028783

Laparoscopic Sleeve Gastrectomy for Morbid Obesity in Patients After Orthotopic Liver Transplant: a Matched Case-Control Study.

PubMed

Tsamalaidze, Levan; Stauffer, John A; Arasi, Lisa C; Villacreses, Diego E; Franco, Jose Salvador Serrano; Bowers, Steven; Elli, Enrique F

2018-02-01

Obesity is frequently encountered in patients with orthotopic liver transplant (OLT). The role of bariatric surgery is still unclear for this specific population. The aim of this study was to review our experience with laparoscopic sleeve gastrectomy (LSG) after OLT. We performed a retrospective case-control study of patients undergoing LSG after OLT from 2010 to 2016. OLT-LSG patients were matched by age, sex, body mass index (BMI), and year to non-OLT patients undergoing LSG. Demographics, operative variables, postoperative events, and long-term weight loss with comorbidity resolution were collected and compared between cases and controls. Of 303 patients undergoing LSG, 12 (4%) had previous OLT. They were matched to 36 non-OLT patients. No difference was found between groups in the American Society of Anesthesiologists class, mean operative time, or postoperative morbidity. The non-OLT group, however, had a significantly shorter mean hospital stay than the OLT group (1.7 vs 3.1 days; P < .001). There were no conversions to open procedures. For patients with long-term follow-up, change in BMI after LSG was similar between the groups, but the non-OLT patients had significantly more excess body weight loss at 2 years (53.7 vs 45.2%; P < .001). Similar resolution of comorbid conditions was noted in both groups. LSG caused no changes in dosage of immunosuppressive medications, and no liver complications occurred. LSG after OLT in appropriately selected patients appears to have similar outcomes to LSG in non-OLT patients.

Accurate Prediction of Drug-Induced Liver Injury Using Stem Cell-Derived Populations

PubMed Central

Szkolnicka, Dagmara; Farnworth, Sarah L.; Lucendo-Villarin, Baltasar; Storck, Christopher; Zhou, Wenli; Iredale, John P.; Flint, Oliver

2014-01-01

Despite major progress in the knowledge and management of human liver injury, there are millions of people suffering from chronic liver disease. Currently, the only cure for end-stage liver disease is orthotopic liver transplantation; however, this approach is severely limited by organ donation. Alternative approaches to restoring liver function have therefore been pursued, including the use of somatic and stem cell populations. Although such approaches are essential in developing scalable treatments, there is also an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. We used a renewable human stem cell resource, from defined genetic backgrounds, and drove them through developmental intermediates to yield highly active, drug-inducible, and predictive human hepatocyte populations. Most importantly, stem cell-derived hepatocytes displayed equivalence to primary adult hepatocytes, following incubation with known hepatotoxins. In summary, we have developed a serum-free, scalable, and shippable cell-based model that faithfully predicts the potential for human liver injury. Such a resource has direct application in human modeling and, in the future, could play an important role in developing renewable cell-based therapies. PMID:24375539

Long-term management of cirrhosis. Appropriate supportive care is both critical and difficult.

PubMed

Habib, A; Bond, W M; Heuman, D M

2001-03-01

Orthotopic liver transplantation has emerged as an important treatment option for patients with advanced liver disease. However, each year the number of new cases of cirrhosis exceeds the number of livers available for transplantation by a factor of 5 to 10. This translates into long waiting lists and restrictive criteria for selecting transplant recipients. Until advances in surgical technique or biotechnology increase the availability of organs for transplantation, the majority of patients with advanced liver disease will have to be managed medically for years--perhaps indefinitely. Early consultation with a liver transplant center can be helpful. The transplant hepatologist and surgeon can help with triage decisions, guide workup, provide advice about patient care, optimize the timing of transplantation, offer specialized diagnostic and therapeutic options, and help the treating physician stay abreast of the continuous changes in this complex field. In the final analysis, however, it is often the skill and diligence of the primary care physician in diagnosing liver disease, identifying and treating correctable causes, optimizing the patient's health and nutrition, and anticipating and preventing catastrophic complications that determine whether the patient lives or dies.

[Hepatic cell transplantation. Technical and methodological aspects].

PubMed

Pareja, Eugenia; Martínez, Amparo; Cortés, Miriam; Bonora, Ana; Moya, Angel; Sanjuán, Fernando; Gómez-Lechón, M José; Mir, José

2010-03-01

Hepatic cell transplantation consists of grafting already differentiated cells such as hepatocytes. Human hepatocytes are viable and functionally active. Liver cell transplantation is carried out by means of a 3-step method: isolation of hepatocytes from donor liver rejected for orthotopic transplantation, preparing a cell suspension for infusion and, finally, hepatocytes are implanted into the recipient. There are established protocols for the isolation of human hepatocytes from unused segments of donor livers, based on collagenase digestion of cannulated liver tissue at 37 degrees C. The hepatocytes can be used fresh or cryopreserved. Cryopreservation of isolated human hepatocytes would then be available for planned use. In cell transplant, the important aspects are: infusion route, number of cells, number of infusions and viability of the cells. The cells are infused into the patient through a catheter inserted via portal vein or splenic artery. Liver cell transplantation allows liver tissue to be used that would, otherwise, be discarded, enabling multiple patients to be treated with hepatocytes from a single tissue donor. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

Pleiotrophin and N-syndecan promote perineural invasion and tumor progression in an orthotopic mouse model of pancreatic cancer

PubMed Central

Yao, Jun; Zhang, Lu-Lin; Huang, Xu-Mei; Li, Wen-Yao; Gao, She-Gan

2017-01-01

AIM To detect the expression of pleiotrophin (PTN) and N-syndecan in pancreatic cancer and analyze their association with tumor progression and perineural invasion (PNI). METHODS An orthotopic mouse model of pancreatic cancer was created by injecting tumor cells subcapsularly in a root region of the pancreas beneath the spleen. Pancreatic cancer tissues were taken from 36 mice that survived for more than 90 d. PTN and N-syndecan proteins were detected by immunohistochemistry and analyzed for their correlation with pathological features, PNI, and prognosis. RESULTS The expression rates of PTN and N-syndecan proteins were 66.7% and 61.1%, respectively, in cancer tissue. PTN and N-syndecan expression was associated with PNI (P = 0.019 and P = 0.032, respectively). High PTN expression was closely associated with large bloody ascites (P = 0.009), liver metastasis (P = 0.035), and decreased survival time (P = 0.022). N-syndecan expression was significantly associated with tumor size (P = 0.025), but not with survival time (P = 0.539). CONCLUSION High PTN and N-syndecan expression was closely associated with metastasis and poor prognosis, suggesting that they may promote tumor progression and PNI in the orthotopic mouse model of pancreatic cancer. PMID:28638231

Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post-transplant liver injury and promotes regeneration in a 20% rat partial liver transplant model.

PubMed

Huda, Kamrul A S M; Guo, Lei; Haga, Sanae; Murata, Hiroshi; Ogino, Tetsuya; Fukai, Moto; Yagi, Takahito; Iwagaki, Hiromi; Tanaka, Noriaki; Ozaki, Michitaka

2006-05-01

Signal transducer and activator of transcription-3 (STAT3) is one of the most important transcription factors for liver regeneration. This study was designed to examine the effects of constitutively activated STAT3 (STAT3-C) on post-transplant liver injury and regeneration in a rat 20% partial liver transplant (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C gene was introduced intraportally into liver grafts and clamped for 30 min during cold preservation. After orthotopic PLTx, liver graft/body weights and serum biochemistry were monitored, and both a histological study and DNA binding assay were performed. STAT3-C protein expression and its binding to DNA in the liver graft were confirmed by Western blotting and electrophoretic mobility shift assay (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration effectively and rapidly. The serum levels of alanine aminotransferase/aspartate aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However, albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the activation of STAT3 in the liver graft may be a potentially effective clinical strategy for improving the outcome of small-for-size liver transplantation.

Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats

NASA Astrophysics Data System (ADS)

Thorling, Camilla A.; Liu, Xin; Burczynski, Frank J.; Fletcher, Linda M.; Gobe, Glenda C.; Roberts, Michael S.

2011-11-01

Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery. In orthotopic transplantation, the donor liver is exposed to periods of ischemia and when oxygenated blood is reintroduced to the liver, oxidative stress may develop and lead to graft failure. The aim of this project was to investigate whether noninvasive multiphoton and fluorescence lifetime imaging microscopy, without external markers, were useful in detecting early liver damage caused by I/R injury. Localized hepatic ischemia was induced in rats for 1 h followed by 4 h reperfusion. Multiphoton and fluorescence lifetime imaging microscopy was conducted prior to ischemia and up to 4 h of reperfusion and compared to morphological and biochemical assessment of liver damage. Liver function was significantly impaired at 2 and 4 h of reperfusion. Multiphoton microscopy detected liver damage at 1 h of reperfusion, manifested by vacuolated cells and heterogeneous spread of damage over the liver. The damage was mainly localized in the midzonal region of the liver acinus. In addition, fluorescence lifetime imaging showed a decrease in cellular metabolic activity. Multiphoton and fluorescence lifetime imaging microscopy detected evidence of early I/R injury both structurally and functionally. This provides a simple noninvasive technique useful for following progressive liver injury without external markers.

The Chinese Herb Jianpijiedu Contributes to the Regulation of OATP1B2 and ABCC2 in a Rat Model of Orthotopic Transplantation Liver Cancer Pretreated with Food Restriction and Diarrhea

PubMed Central

Sun, Baoguo; Chen, Yan; Xiang, Ting; Zhang, Lei; Chen, Zexiong; Zhang, Shijun; Zhou, Houming; Chen, Shuqing

2015-01-01

Traditional Chinese Medicine Jianpijiedu decoction (JPJD) could improve the general status of liver cancer patients in clinics, especially the symptoms of decreased food intake and diarrhea. In this study, our results showed that the survival rate of the liver cancer with food restriction and diarrhea (FRD-LC) rats was lower than the liver cancer (LC) rats, and the tumor volume of the FRD-LC rats was higher than the LC rats. It was also shown that the high dose of JPJD significantly improved the survival rate, weight, and organ weight when compared with FRD-LC-induced rats. Moreover, JPJD administration upregulated the mRNA and protein levels of ABCC2 and downregulated the mRNA and protein levels of OATP1B2 in liver tissues. However, opposite results were observed in the cancer tissues. In conclusion, the study indicated that the Chinese Medicine JPJD could contribute to the rats with liver cancer which were pretreated with food restriction and diarrhea by regulating the expression of ABCC2 and OATP1B2 in liver tissues and cancer tissues. PMID:26665149

Color-Coded Imaging of Syngeneic Orthotopic Malignant Lymphoma Interacting with Host Stromal Cells During Metastasis.

PubMed

Matsumoto, Takuro; Suetsugu, Atsushi; Hasegawa, Kosuke; Nakamura, Miki; Aoki, Hitomi; Kunisada, Takahiro; Tsurumi, Hisashi; Shimizu, Masahito; Hoffman, Robert M

2016-04-01

The EL4 cell line was previously derived from a lymphoma induced in a C57/BL6 mouse by 9,10-dimethyl-1,2-benzanthracene. In a previous study, EL4 lymphoma cells expressing red fluorescent protein (EL4-RFP) were established and injected into the tail vein of C57/BL6 green fluorescent protein (GFP) transgenic mice. Metastasis was observed at multiple sites which were also enriched with host GFP-expressing stromal cells. In the present study, our aim was to establish an orthotopic model of EL4-RFP. In the present study, EL4-RFP lymphoma cells were injected in the spleen of C57/BL6 GFP transgenic mice as an orthotopic model of lymphoma. Resultant primary tumor and metastases were imaged with the Olympus FV1000 scanning laser confocal microscope. EL4-RFP metastasis was observed 21 days later. EL4-RFP tumors in the spleen (primary injection site), liver, supra-mediastinum lymph nodes, abdominal lymph nodes, bone marrow, and lung were visualized by color-coded imaging. EL4-RFP metastases in the liver, lymph nodes, and bone marrow in C57/BL6 GFP mice were rich in GFP stromal cells such as macrophages, fibroblasts, dendritic cells, and normal lymphocytes derived from the host animal. Small tumors were observed in the spleen, which were rich in host stromal cells. In the lung, no mass formation of lymphoma cells occurred, but lymphoma cells circulated in lung peripheral blood vessels. Phagocytosis of EL4-RFP lymphoma cells by macrophages, as well as dendritic cells and fibroblasts, were observed in culture. Color-coded imaging of the lymphoma microenvironment suggests an important role of stromal cells in lymphoma progression and metastasis. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Portopulmonary hypertension: Updated review].

PubMed

Rodríguez-Almendros, Nielzer; Toapanta-Yanchapaxi, Liz N; Aguirre Valadez, Jonathan; Espinola Zavaleta, Nilda; Muñoz-Martínez, Sergio G; García-Juárez, Ignacio

Portopulmonary hypertension (PPH) is a rare condition worldwide, although epidemiological data are unknown in Mexico. However, chronic liver diseases are very prevalent in Mexico. PPH is the 4th subtype in frequency in the group of pulmonary arterial hypertension. Its diagnosis is made within 2 scenarios: patients with suspected pulmonary hypertension and candidates for orthotopic liver transplantation (OLT). Both echocardiogram and a right cardiac catheterisation are crucial for diagnosis in both cases. PPH is a challenge for OLT, since it can significantly increase perioperative mortality. The use of specific therapy is the cornerstone of this disease, as a measure to improve the outcome of those who become candidates for OLT with moderate to severe PPH. It is important to recognise that PPH can be a contraindication to OLT. The role of lung-liver transplantation or heart-lung-liver transplantation as a measure to heal pulmonary vascular disease in patients with PPH is still uncertain. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Differences in health-related quality of life scores after orthotopic liver transplantation with respect to selected socioeconomic factors.

PubMed

Saab, Sammy; Bownik, Hillary; Ayoub, Noel; Younossi, Zobair; Durazo, Francisco; Han, Steven; Hong, Johnny C; Farmer, Douglas; Busuttil, Ronald W

2011-05-01

One of the current ultimate goals of orthotopic liver transplantation (OLT) is the improvement of patients' health-related quality of life (HRQOL). The purpose of this study was to look at the effects of socioeconomic and demographic differences on the short-term and long-term HRQOL outcomes of OLT recipients. Three hundred three adult OLT recipients who were seen at the University of California Los Angeles were administered the Medical Outcomes Study Short Form 36 (SF-36), the Chronic Liver Disease Questionnaire (CLDQ), and a demographic survey. A parsimonious model of 12 socioeconomic and demographic predictors was identified. Their simultaneous influence on each SF-36 and CLDQ HRQOL domain score was evaluated with multivariate linear regression and backward selection. Hepatitis C virus impaired HRQOL; this was shown in the SF-36 Vitality and Bodily Pain domains and in most CLDQ domains. Females experienced more HRQOL impairment only within the CLDQ Abdominal Symptoms domain. OLT recipients who were married had better SF-36 Role-Emotion domain scores. OLT recipients with more than 12 years of education had better SF-36 Physical Functioning scores. Employed OLT recipients had less HRQOL impairment; this was evidenced by better scores in multiple domains of the SF-36 and the CLDQ. OLT patients with health maintenance organization or preferred provider organization insurance had higher HRQOL scores within almost all SF-36 and CLDQ domains. Patients with a mix of public and private insurance had significantly higher HRQOL scores in comparison with those with only public insurance. Identifying patients at higher risk for worse HRQOL scores, less satisfaction with OLT results, and greater problems with fatigue or mental health stressors will assist transplant centers in using their medical teams to develop early interventions and multidisciplinary approaches to improve HRQOL outcomes after OLT. Copyright © 2011 American Association for the Study of Liver Diseases.

Feasibility of using marginal liver grafts in living donor liver transplantation

PubMed Central

Lan, Xiang; Zhang, Hua; Li, Hong-Yu; Chen, Ke-Fei; Liu, Fei; Wei, Yong-Gang; Li, Bo

2018-01-01

Liver transplantation (LT) is one of the most effective treatments for end-stage liver disease caused by related risk factors when liver resection is contraindicated. Additionally, despite the decrease in the prevalence of hepatitis B virus (HBV) over the past two decades, the absolute number of HBsAg-positive people has increased, leading to an increase in HBV-related liver cirrhosis and hepatocellular carcinoma. Consequently, a large demand exists for LT. While the wait time for patients on the donor list is, to some degree, shorter due to the development of living donor liver transplantation (LDLT), there is still a shortage of liver grafts. Furthermore, recipients often suffer from emergent conditions, such as liver dysfunction or even hepatic encephalopathy, which can lead to a limited choice in grafts. To expand the pool of available liver grafts, one option is the use of organs that were previously considered “unusable” by many, which are often labeled “marginal” organs. Many previous studies have reported on the possibilities of using marginal grafts in orthotopic LT; however, there is still a lack of discussion on this topic, especially regarding the feasibility of using marginal grafts in LDLT. Therefore, the present review aimed to summarize the feasibility of using marginal liver grafts for LDLT and discuss the possibility of expanding the application of these grafts. PMID:29930466

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma

PubMed Central

Zhang, Caiqin; Zhao, Yong; Zhang, He; Chen, Xue; Zhao, Ningning; Tan, Dengxu; Zhang, Hai; Shi, Changhong

2017-01-01

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC. PMID:28635650

The Application of Heptamethine Cyanine Dye DZ-1 and Indocyanine Green for Imaging and Targeting in Xenograft Models of Hepatocellular Carcinoma.

PubMed

Zhang, Caiqin; Zhao, Yong; Zhang, He; Chen, Xue; Zhao, Ningning; Tan, Dengxu; Zhang, Hai; Shi, Changhong

2017-06-21

Near infrared fluorescence (NIRF) imaging has strong potential for widespread use in noninvasive tumor imaging. Indocyanine green (ICG) is the only Food and Drug Administration (FDA) -approved NIRF dye for clinical diagnosis; however, it is unstable and poorly targets tumors. DZ-1 is a novel heptamethine cyanine NIRF dye, suitable for imaging and tumor targeting. Here, we compared the fluorescence intensity and metabolism of DZ-1 and ICG. Additionally, we assayed their specificities and abilities to target tumor cells, using cultured hepatocellular carcinoma (HCC) cell lines, a nude mouse subcutaneous xenograft model of liver cancer, and a rabbit orthotopic transplantation model. We found that DZ-1 accumulates in tumor tissue and specifically recognizes HCC in subcutaneous and orthotopic models. The NIRF intensity of DZ-1 was one order of magnitude stronger than that of ICG, and DZ-1 showed excellent intraoperative tumor targeting in the rabbit model. Importantly, ICG accumulated at tumor sites, as well as in the liver and kidney. Furthermore, DZ-1 analog-gemcitabine conjugate (NIRG) exhibited similar tumor-specific targeting and imaging properties, including inhibition of tumor growth, in HCC patient-derived xenograft (PDX) mice. DZ-1 and NIRG demonstrated superior tumor-targeting specificity, compared to ICG. We show that DZ-1 is an effective molecular probe for specific imaging, targeting, and therapy in HCC.

From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world

PubMed Central

Dimitroulis, Dimitrios; Damaskos, Christos; Valsami, Serena; Davakis, Spyridon; Garmpis, Nikolaos; Spartalis, Eleftherios; Athanasiou, Antonios; Moris, Demetrios; Sakellariou, Stratigoula; Kykalos, Stylianos; Tsourouflis, Gerasimos; Garmpi, Anna; Delladetsima, Ioanna; Kontzoglou, Konstantinos; Kouraklis, Gregory

2017-01-01

Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries. The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus, nonalcoholic fatty liver disease, consumption of aflatoxins and tobacco smocking. Clinical presentation varies widely; patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy. Imaging is the first key and one of the most important aspects at all stages of diagnosis, therapy and follow-up of patients with HCC. The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines. Up until now, HCC remains a challenge to early diagnose, and treat effectively; treating management is focused on hepatic resection, orthotopic liver transplantation, ablative therapies, chemoembolization and systemic therapies with cytotocix drugs, and targeted agents. This review article describes the current evidence on epidemiology, symptomatology, diagnosis and treatment of hepatocellular carcinoma. PMID:28839428

From diagnosis to treatment of hepatocellular carcinoma: An epidemic problem for both developed and developing world.

PubMed

Dimitroulis, Dimitrios; Damaskos, Christos; Valsami, Serena; Davakis, Spyridon; Garmpis, Nikolaos; Spartalis, Eleftherios; Athanasiou, Antonios; Moris, Demetrios; Sakellariou, Stratigoula; Kykalos, Stylianos; Tsourouflis, Gerasimos; Garmpi, Anna; Delladetsima, Ioanna; Kontzoglou, Konstantinos; Kouraklis, Gregory

2017-08-07

Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy and the third cause of cancer-related death in the Western Countries. The well-established causes of HCC are chronic liver infections such as hepatitis B virus or chronic hepatitis C virus, nonalcoholic fatty liver disease, consumption of aflatoxins and tobacco smocking. Clinical presentation varies widely; patients can be asymptomatic while symptomatology extends from right upper abdominal quadrant paint and weight loss to obstructive jaundice and lethargy. Imaging is the first key and one of the most important aspects at all stages of diagnosis, therapy and follow-up of patients with HCC. The Barcelona Clinic Liver Cancer Staging System remains the most widely classification system used for HCC management guidelines. Up until now, HCC remains a challenge to early diagnose, and treat effectively; treating management is focused on hepatic resection, orthotopic liver transplantation, ablative therapies, chemoembolization and systemic therapies with cytotocix drugs, and targeted agents. This review article describes the current evidence on epidemiology, symptomatology, diagnosis and treatment of hepatocellular carcinoma.

[Application of hepatic segment resection combined with rigid choledochoscope in the treatment of complex hepatolithiasis guided by three-dimensional visualization technology].

PubMed

Xiang, Nan; Fang, Chihua

2015-05-01

To study the value of hepatic segment resection combined with rigid choledochoscope by the three-dimensional (3D) visualization technology in the diagnosis and treatment of complex hepatolithiasis. Enhance computed tomography (CT) data of 46 patients with complex hepatolithiasis who were admitted to the Zhujiang Hospital of the Southern Medical University from July 2010 to June 2014 were collected.All of the CT data were imported into the medical image three-dimensional visualization system (MI-3DVS) for 3D reconstruction and individual 3D types. The optimal scope of liver resection and the remnant liver volume were determined according to the individualized liver segments which were made via the distribution and variation of hepatic vein and portal vein, the distribution of bile duct stones and stricture of the bile duct, which provided guidance for intraoperative hepatic lobectomy and rigid choledochoscope for the remnant calculus lithotripsy. Outcomes of individual 3D types: 10 cases of type I, 11 cases of IIa, 23 cases of IIb, 2 cases of IIc, 19 cases coexisted with history of biliary surgery. The variation of hepatic artery was appeared 6 cases. The variation of portal vein was appeared 8 cases. The remaining liver volume for virtual hepatic lobectomy controlled more than 50%. Eighteen cases underwent left lateral hepatectomy, 8 cases underwent left liver resection, 8 cases underwent right posterior lobe of liver resection, 4 cases underwent the right hepatic resection, 4 cases underwent IV segment liver resection, 2 cases underwent right anterior lobe of liver resection, 2 cases underwent left lateral hepatectomy combined with right posterior lobe of liver resection, 26 cases underwent targeting treatment of rapid choledochoscope and preumatic lithotripsy. The actual surgical procedure was consistent with the preoperative surgical planning. There was no postoperative residual liver ischemia,congestion, liver failure occurred in this study. The intraoperative calculus clearance rate was 91.3% (42/46) because 4 cases of postoperatively residual calculi were not suitable for one stage management due to suppurative cholangitis but removed calculus successfully with rigid choledochoscope through T tube fistula. Hepatic segment resection combined with rigid choledochoscope under the guidance of three-dimensional visualization technology achieves accurate preoperative diagnosis and higher complete stone clearance rate of complicated hepatolithiasis.

Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis.

PubMed

Ben-Ari, Z; Broida, E; Monselise, Y; Kazatsker, A; Baruch, J; Pappo, O; Skappa, E; Tur-Kaspa, R

2000-03-01

Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.

How do we manage post-OLT redundant bile duct?

PubMed

Torres, Victor; Martinez, Nicholas; Lee, Gabriel; Almeda, Jose; Gross, Glenn; Patel, Sandeep; Rosenkranz, Laura

2013-04-28

To address endoscopic outcomes of post-Orthotopic liver transplantation (OLT) patients diagnosed with a "redundant bile duct" (RBD). Medical records of patients who underwent OLT at the Liver Transplant Center, University Texas Health Science Center at San Antonio Texas were retrospectively analyzed. Patients with suspected biliary tract complications (BTC) underwent endoscopic retrograde cholangiopancreatography (ERCP). All ERCP were performed by experienced biliary endoscopist. RBD was defined as a looped, sigmoid-shaped bile duct on cholangiogram with associated cholestatic liver biomarkers. Patients with biliary T-tube placement, biliary anastomotic strictures, bile leaks, bile-duct stones-sludge and suspected sphincter of oddi dysfunction were excluded. Therapy included single or multiple biliary stents with or without sphincterotomy. The incidence of RBD, the number of ERCP corrective sessions, and the type of endoscopic interventions were recorded. Successful response to endoscopic therapy was defined as resolution of RBD with normalization of associated cholestasis. Laboratory data and pertinent radiographic imaging noted included the pre-ERCP period and a follow up period of 6-12 mo after the last ERCP intervention. One thousand two hundred and eighty-two patient records who received OLT from 1992 through 2011 were reviewed. Two hundred and twenty-four patients underwent ERCP for suspected BTC. RBD was reported in each of the initial cholangiograms. Twenty-one out of 1282 (1.6%) were identified as having RBD. There were 12 men and 9 women, average age of 59.6 years. Primary indication for ERCP was cholestatic pattern of liver associated biomarkers. Nineteen out of 21 patients underwent endoscopic therapy and 2/21 required immediate surgical intervention. In the endoscopically managed group: 65 ERCP procedures were performed with an average of 3.4 per patient and 1.1 stent per session. Fifteen out of 19 (78.9%) patients were successfully managed with biliary stenting. All stents were plastic. Selection of stent size and length were based upon endoscopist preference. Stent size ranged from 7 to 11.5 Fr (average stent size 10 Fr); Stent length ranged from 6 to 15 cm (average length 9 cm). Concurrent biliary sphincterotomy was performed in 10/19 patients. Single ERCP session was sufficient in 6/15 (40.0%) patients, whereas 4/15 (26.7%) patients needed two ERCP sessions and 5/15 (33.3%) patients required more than two (average of 5.4 ERCP procedures). Single biliary stent was sufficient in 5 patients; the remaining patients required an average of 4.9 stents. Four out of 19 (21.1%) patients failed endotherapy (lack of resolution of RBD and recurrent cholestasis in the absence of biliary stent) and required either choledocojejunostomy (2/4) or percutaneous biliary drainage (2/4). Endoscopic complications included: 2/65 (3%) post-ERCP pancreatitis and 2/10 (20%) non-complicated post-sphincterotomy bleeding. No endoscopic related mortality was found. The medical records of the 15 successful endoscopically managed patients were reviewed for a period of one year after removal of all biliary stents. Eleven patients had continued resolution of cholestatic biomarkers (73%). One patient had recurrent hepatitis C, 2 patients suffered septic shock which was not associated with ERCP and 1 patient was transferred care to an outside provider and records were not available for our review. Although surgical biliary reconstruction techniques have improved, RBD represents a post-OLT complication. This entity is rare however, endoscopic management of RBD represents a reasonable initial approach.

Comparison of hepatic MDCT, MRI, and DSA to explant pathology for the detection and treatment planning of hepatocellular carcinoma.

PubMed

Ladd, Lauren M; Tirkes, Temel; Tann, Mark; Agarwal, David M; Johnson, Matthew S; Tahir, Bilal; Sandrasegaran, Kumaresan

2016-12-01

The diagnosis and treatment plan for hepatocellular carcinoma (HCC) can be made from radiologic imaging. However, lesion detection may vary depending on the imaging modality. This study aims to evaluate the sensitivities of hepatic multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) in the detection of HCC and the consequent management impact on potential liver transplant patients. One hundred and sixteen HCC lesions were analyzed in 41 patients who received an orthotopic liver transplant (OLT). All of the patients underwent pretransplantation hepatic DSA, MDCT, and/or MRI. The imaging results were independently reviewed retrospectively in a blinded fashion by two interventional and two abdominal radiologists. The liver explant pathology was used as the gold standard for assessing each imaging modality. The sensitivity for overall HCC detection was higher for cross-sectional imaging using MRI (51.5%, 95% confidence interval [CI]=36.2-58.4%) and MDCT (49.8%, 95% CI=43.7-55.9%) than for DSA (41.7%, 95% CI=36.2-47.3%) ( P =0.05). The difference in false-positive rate was not statistically significant between MRI (22%), MDCT (29%), and DSA (29%) ( P =0.67). The sensitivity was significantly higher for detecting right lobe lesions than left lobe lesions for all modalities (MRI: 56.1% vs. 43.1%, MDCT: 55.0% vs. 42.0%, and DSA: 46.9% vs. 33.9%; all P <0.01). The sensitivities of the three imaging modalities were also higher for lesions ≥2 cm vs. <2 cm (MRI: 73.4% vs. 32.7%, MDCT: 66.9% vs. 33.8%, and DSA: 62.2% vs. 24.1%; all P <0.01). The interobserver correlation was rated as very good to excellent. The sensitivity for detecting HCC is higher for MRI and MDCT than for DSA, and so cross-sectional imaging modalities should be used to evaluate OLT candidacy.

Postoperative Pleural Effusions After Orthotopic Heart Transplant: Cause, Clinical Manifestations, and Course.

PubMed

Ulubay, Gaye; Küpeli, Elif; Er Dedekargınoğlu, Balam; Savaş Bozbaş, Şerife; Alekberov, Mahal; Salman Sever, Özlem; Sezgin, Atilla

2016-11-01

Postoperative pleural effusions are common in patients who undergo cardiac surgery and orthotopic heart transplant. Postoperative pleural effusions may also occur as postcardiac injury syndrome. Most of these effusions are nonspecific and develop as a harmless complication of the surgical procedure itself and generally have a benign course. Here, we investigated the cause and clinical and laboratory features of postoperative early and late pleural effusions in orthotopic heart transplant patients. We retrospectively reviewed the medical records of 50 patients who underwent orthotopic heart transplant between 2004 and 2015 at Baskent University. Patient demographics and clinical and laboratory data, including cause of heart failure, presence of pleural effusions at chest radiography in the first year after transplant, timing of onset, microbiologic and biochemical analyses of pleural effusions, and treatment strategies were noted. Mean age of patients was 39.22 ± 13.83 years (39 men, 11 women). Reason for heart failure was dilated cardiomyopathy in most patients (76%). Nineteen patients (38%) had postoperative pleural effusions, with 15 patients (78.9%) with pleural effusion during the first week after transplant. Of these, 4 patients had recurrent pleural effusion. A diagnostic thoracentesis was performed in 10 patients, with 4 showing transudative effusion and 6 showing exudative effusion secondary to infection (2 patients), postcardiac injury syndrome (1 patient), and hemothorax (3 patients). Aspergillus fumigatus was detected by quantitative culture from pleural effusion in 1 patient. Tube thoracoscopy drainage was performed in 10 patients (25%), and 2 patients received antibiotic therapy. Pleural effusions are frequent after cardiac transplant. Complications may occur in a small portion of patients, with most effusions being nonspecific and having a benign course with spontaneous resolution. Early diagnostic thoracentesis could improve postoperative outcomes in these patients.

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor.

PubMed

Liu, Xiang-Feng; Long, Hai-Jiao; Miao, Xiong-Ying; Liu, Guo-Li; Yao, Hong-Liang

2017-07-01

Fisetin (3,3',4',7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein‑coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF‑β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression.

Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor

PubMed Central

Liu, Xiang-Feng; Long, Hai-Jiao; Miao, Xiong-Ying; Liu, Guo-Li; Yao, Hong-Liang

2017-01-01

Fisetin (3,3′,4′,7-tetrahydroxyflavone), a natural abundant flavonoid, is produced in different vegetables and fruits. Fisetin has been reported to relate to various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Dopamine receptors (DRs) belonging to G protein-coupled receptor family, are known as the target of ~50% of all modern medicinal drugs. DRs consist of various proteins, functioning as transduction of intracellular signals for extracellular stimuli. We found that fisetin performed as DR2 agonist to suppress liver cancer cells proliferation, migration and invasion. Caspase-3 signaling was activated to induce apoptosis for fisetin administration. Furthermore, TGF-β1 was also inhibited in fisetin-treated liver cancer cells, reducing epithelial-mesenchymal transition (EMT). Additionally, fisetin downregulated VEGFR1, p-ERK1/2, p38 and pJNK, ameliorating liver cancer progression. In vivo, the orthotopically implanted tumors from mice were inhibited by fisetin adminisatration accompanied by prolonged survival rate and higher levels of dopamine. Together, the results indicated a novel therapeutic strategy to suppress liver cancer progression associated with DR2 regulation, indicating that dopamine might be of importance in liver cancer progression. PMID:28560391

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

[State of hepatocyte transplantation: a risk or a chance?].

PubMed

Leckel, K; Blaheta, R A; Markus, B H

2003-04-01

Over the past few years, hepatocyte transplantation has been considered as an alternative method for orthotopic liver transplantation for the treatment of various liver diseases. Beside curative approach for genetic metabolic deficiencies (familial hypercholesterolemia, hemophilia, etc.), it could be a useful tool for bridging the waiting period until an appropriate donor organ is obtained. In preclinical animal studies, hepatocytes injected intraperitoneally, intraportally or into the spleen settle down in the diseased liver. This enables genetic modification to correct inborn metabolic deficiencies and improves survival in acute liver failure. In 1992, the first clinical transplantation of isolated hepatocytes in 10 patients was performed. In 1998, Fox and coworkers described the successful transplantation of allogeneic liver cells in a child with Crigler-Najjar syndrome. Accomplished studies of Strom et al. resp. Bilir et al. of the same year proved the effectiveness of liver cell transplantation for transient treatment of acute liver failure. Prerequisite of this cell-based therapeutic strategy is a sufficient amount of highly differentiated hepatocytes, hence, a well established in-vitro cell-culture technique is necessary to yield a reproducible number of proliferating hepatocytes and to preserve the physiological cell function. This review discusses the different experimental approaches regarding the cultivation of human hepatocytes and also the use of alternative cell sources (like animal hepatocytes, immortalized cells of human origin, progenitor cells from fetal human liver/liver stem cells) for hepatocyte transplantation.

Porcine alanine transaminase after liver allo-and xenotransplantation

PubMed Central

Ekser, Burcin; Gridelli, Bruno; Cooper, David K.C.

2013-01-01

Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3 Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3 Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording. PMID:22360753

Hepatocyte transplantation for liver-based metabolic disorders.

PubMed

Dhawan, Anil; Mitry, Ragai R; Hughes, Robin D

2006-01-01

Hepatocyte transplantation is being investigated as an alternative to orthotopic liver transplantation in patients with liver-based metabolic disorders. The progress made in this field to date is reviewed. Protocols have been developed using collagenase perfusion to isolate human hepatocytes from unused donor liver tissue. Hepatocytes with a high viability can often be obtained and can be cryopreserved for later use, though with loss of function on thawing. For clinical use, hepatocytes must be prepared in clean GMP conditions with cells meeting criteria of function and lack of microbial contamination before patient use. Hepatocytes are infused intraportally into the patient's liver, where a proportion of cells will engraft and replace the deficient metabolic function without the need for major surgery. Twenty patients have now received hepatocyte transplantation, including eight children at King's College Hospital. There was a range of aetiologies of liver disease: familial hypercholesterolaemia, Crigler-Najjar syndrome type 1, urea cycle defects, infantile Refsum disease, glycogen storage disease type Ia, inherited factor VII deficiency and progressive familial intrahepatic cholestasis type 2. Clinical improvement and partial correction of the metabolic abnormality was observed in most cases. Considerable progress has been made in developing the technique, but hepatocyte transplantation is limited by the available supply of liver tissue. Hepatocytes derived from stem cells could provide alternative sources of cells in the future.

Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2014-04-01

The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

Risk factors for alcohol relapse following orthotopic liver transplantation: a systematic review.

PubMed

Rustad, James K; Stern, Theodore A; Prabhakar, Maithri; Musselman, Dominique

2015-01-01

Each year, 5000-6000 individuals undergo orthotopic liver transplantation (OLT) in the United States, and of these, nearly 18% have alcoholic liver disease. Relapse to alcohol occurs in more than 40% of patients with OLT for alcoholic liver disease. We sought to identify factors that predict relapse to alcohol or medication nonadherence following OLT in patients with alcoholic liver disease and to review what randomized clinical interventions have addressed these factors following OLT. Our hypothesis was that there would be factors before and after OLT that predict relapse to alcohol following OLT, and that these, if targeted, might improve sobriety and associated outcomes of adherence with medications and appointments. We performed a review (focusing on articles published since 2004) with PubMed and MEDLINE searches using the following search terms: liver transplantation, recidivism, alcohol relapse, and predictors of alcohol relapse. We supplemented the online searches with manual reviews of article reference lists and selected relevant articles for further review by author consensus. In largely white populations, prospective studies document that shorter length of pretransplantation sobriety is a significant predictor of time to first drink and time to binge use. Presence of psychiatric comorbidity, high score on standardized High-risk Alcoholism Relapse Scale, and diagnosis of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) alcohol dependence are predictive of posttransplantation alcohol relapse. Pretransplantation alcohol use history variables (e.g., family history of alcoholism) reliably discriminate between complete abstainers and those who drink, while medical and psychosocial characteristics at early post-liver transplantation period (e.g., more bodily pain) maximally discriminate patterns of alcohol use. Alcoholic individuals with early-onset, rapidly accelerating moderate use and early-onset, continuously increasing heavy use have more than double the prevalence of steatohepatitis or rejection on biopsy and graft failure and more frequent mortality resulting from recurrent alcoholic liver disease than late-onset (i.e., peak of heaviest drinking at 6y posttransplantation) alcohol users do. Fortunately, pretransplantation screening combined with a structured pretransplantation management program and a 12-step program attendance reduced recidivism. No randomized clinical trials have been performed that target pretransplantation risk factors in individuals with alcoholic liver disease before or after OLT to improve post-OLT outcomes. Recent research findings suggest that screening can reveal individuals who are vulnerable to alcohol relapse and targeted intervention can prevent their relapse to alcohol. Based on existing addiction treatments (e.g., relapse prevention plan construction), randomized clinical trials tailored to post-OLT patients should be conducted to improve their survival and quality of life. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xing, Minzhi; Sakaria, Sonali; Dhanasekaran, Renumathy

Background and AimsTo evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria.MethodsOur transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan–Meier estimation and log-rank test.ResultsOf 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B).more » Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03).ConclusionsBridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.« less

Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction.

PubMed

Cortes, Miriam; Pareja, Eugenia; García-Cañaveras, Juan C; Donato, M Teresa; Montero, Sandra; Mir, Jose; Castell, José V; Lahoz, Agustín

2014-09-01

Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD. A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients. A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary non-function (n=4). A metabolomic biosignature that accurately differentiates donor livers, which later showed EAD or IGF, has been deciphered. The remarkable metabolomic differences between donor livers before transplant can relate to their different quality. The proposed metabolomic approach may become a clinical tool for donor liver quality assessment and for anticipating graft function before transplant. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Perioperative management in orthotopic liver transplantation: results of an Italian national survey.

PubMed

Biancofiore, G; Della Rocca, G

2012-06-01

No data are available on the perioperative approach during orthotopic liver transplantation (OLT) in Italy, apart from sporadically single center studies. The Department of Anesthesia cooperating with each Italian licensed OLT center received a questionnaire regarding preoperative evaluation, intraoperative anesthesia management, anesthetic drugs, blood components therapy, perioperative monitoring, supportive therapies, postoperative care, staff and organization. Twenty-two centers were surveyed and 17 returned the questionnaire. Center specific protocols for OLT anesthesia exist in 12 centers. Balanced anesthesia (volatile anesthetic agents and continuous infusion of opioids) is the standard anesthetic method. In 14 cases a thromboelastogram is available; one center reported not to have a rapid infusion device available. Pulmonary artery catheterization with a continuous cardiac output device is the most used hemodynamic monitoring system; in case of hemodynamic instability, the combination of dopamine/noradrenaline resulted the first choice before vascular clamping whereas noradrenaline alone after graft's reperfusion. No difference about which intraoperative phase is mostly characterized by the use of blood components was reported. Postoperative care is provided on anesthesiological-guided Intensive Care Units (ICU) in all the surveyed centers and in three centers the ICU is dedicated only to transplant patients. The results of this survey show that in Italy the perioperative management of patients undergoing OLT is not homogeneous. This database allows to debate on the best practices and pathways for perioperative management of these patients, and to stimulate future clinical trials aimed to assess the different component and steps forwards of the whole process.

Epsilon-aminocaproic acid improves postrecirculation hemodynamics by reducing intraliver activated protein C consumption in orthotopic liver transplantation.

PubMed

Kong, H Y; Wen, X H; Huang, S Q; Zhu, S M

2014-01-01

Activated protein C (APC) is related to regulating the inflammatory response and hemodynamic stability upon reperfusion in cardiac operations and orthotopic liver transplantation (OLT). Epsilon-aminocaproic acid (EACA) is frequently used to treat fibrinolysis during OLT. It also has inhibitory effects related to the inflammatory response. However, it remains to be determined whether EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion during OLT. Fifty-nine recipients were randomized to receive either EACA (150 mg kg(-1) given intravenously prior to incision, followed by 15 mg kg(-1) h(-1) infusion until 2 h after the graft reperfusion) or the same volume of saline. Blood samples to assess plasma APC and protein C were obtained immediately before and after reperfusion from the inferior caval effluent or the portal veins for calculation of transliver differences (Δ). Hemodynamics and vasoactive medication use during the reperfusion period were observed in both groups. No transhepatic changes in protein C were found in either group. Immediately after reperfusion, a marked intraliver consumption of APC was noted in all recipients (P < 0.001), and intraliver consumption of APC in the control group was greater than that in the EACA-treated group (P < 0.05). Fewer requirements for vasoactive medication use after reperfusion and better initial graft function were noted in the EACA-treated group (P < 0.05). EACA can attenuate intraliver APC consumption and improve hemodynamic stability after reperfusion and initial graft function during OLT.

Protein C activity and postoperative metabolic liver function after liver transplantation.

PubMed

Wagener, G; Diaz, G; Guarrera, J V; Minhaz, M; Renz, J F; Sladen, R N

2012-06-01

Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT). We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5. The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score. Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Liver Transplantation for Urea Cycle Disorders: Analysis of the United Network for Organ Sharing Database.

PubMed

Yu, L; Rayhill, S C; Hsu, E K; Landis, C S

2015-10-01

Urea cycle disorders (UCD) are caused by rare inherited defects in the urea cycle enzymes leading to diminished ability to convert ammonia to urea in the liver. The resulting excess of circulating ammonia can lead to central nervous system toxicity and irreversible neurologic damage. Most cases are identified in children. However, UCDs can also be diagnosed in adulthood, and liver transplant is occasionally required. We examined the UNOS database to evaluate outcomes in adult and pediatric patients who underwent liver transplant as treatment for a UCD. We identified 265 pediatric and 13 adult patients who underwent liver transplant for a UCD between 1987 and 2010. The majority (68%) of these patients were transplanted before age 5 years. Ornithine transcarbamylase (OTC) deficiency was the most common UCD in both adults and children who underwent transplant. UCD patients who underwent liver transplant were younger, more likely to be male (67%), had lower pediatric end-stage liver disease/model for end-stage liver disease scores, and were more likely to be Caucasian or Asian compared with all other patients transplanted during the same time period. UCD patients did not have an increased utilization of living donor transplantation in this US cohort. Univariate and multivariate risk factor analyses were performed and did not reveal any significant factors that were predictive of post-transplant death or graft loss. Excellent outcomes were seen in both children and adults with UCDs who underwent transplant with overall 1-, 5-, and 10-year survivals of 93%, 89%, and 87%, respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

Post-operative imaging in liver transplantation: State-of-the-art and future perspectives

PubMed Central

Girometti, Rossano; Como, Giuseppe; Bazzocchi, Massimo; Zuiani, Chiara

2014-01-01

Orthotopic liver transplantation (OLT) represents a major treatment for end-stage chronic liver disease, as well as selected cases of hepatocellular carcinoma and acute liver failure. The ever-increasing development of imaging modalities significantly contributed, over the last decades, to the management of recipients both in the pre-operative and post-operative period, thus impacting on graft and patients survival. When properly used, imaging modalities such as ultrasound, multidetector computed tomography, magnetic resonance imaging (MRI) and procedures of direct cholangiography are capable to provide rapid and reliable recognition and treatment of vascular and biliary complications occurring after OLT. Less defined is the role for imaging in assessing primary graft dysfunction (including rejection) or chronic allograft disease after OLT, e.g., hepatitis C virus (HCV) recurrence. This paper: (1) describes specific characteristic of the above imaging modalities and the rationale for their use in clinical practice; (2) illustrates main imaging findings related to post-OLT complications in adult patients; and (3) reviews future perspectives emerging in the surveillance of recipients with HCV recurrence, with special emphasis on MRI. PMID:24876739

HCV-RNA quantification in liver bioptic samples and extrahepatic compartments, using the abbott RealTime HCV assay.

PubMed

Antonucci, FrancescoPaolo; Cento, Valeria; Sorbo, Maria Chiara; Manuelli, Matteo Ciancio; Lenci, Ilaria; Sforza, Daniele; Di Carlo, Domenico; Milana, Martina; Manzia, Tommaso Maria; Angelico, Mario; Tisone, Giuseppe; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

2017-08-01

We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment. Total RNA and DNA quantification from tissue-biopsies allowed normalization of HCV-RNA concentrations in IU/μg of total RNA and IU/10 6 liver-cells, respectively. HCV-RNA was successfully quantified with high reliability in liver biopsies, lymph nodes and ascitic fluid samples. Among the 17 untreated patients, a positive and significant HCV-RNA correlation between serum and NT liver-samples was observed (Pearson: rho=0.544, p=0.024). Three DAA-treated patients were HCV-RNA "undetectable" in serum, but still "detectable" in all tested liver-tissues. Differently, only one DAA-treated patient, tested after sustained-virological-response, showed HCV-RNA "undetectability" in liver-tissue. HCV-RNA was successfully quantified with high reliability in liver bioptic samples and extrahepatic compartments, even when HCV-RNA was "undetectable" in serum. Abbott RealTime HCV-assay is a good diagnostic tool for HCV quantification in intra- and extra-hepatic compartments, whenever a bioptic sample is available. Copyright © 2017 Elsevier B.V. All rights reserved.

Perioperative Characteristics of Siblings Undergoing Liver or Kidney Transplant.

PubMed

Ersoy, Zeynep; Ozdemirkan, Aycan; Pirat, Arash; Torgay, Adnan; Arslan, Gulnaz; Haberal, Mehmet

2015-11-01

Reasons for chronic liver and kidney failure may vary; sometimes more than 1 family member may be affected, and may require a transplant. The aim of this study was to examine the similarities or differences between the perioperative characteristics of siblings undergoing liver or kidney transplant. The medical records of 6 pairs of siblings who underwent liver transplant and 4 pairs of siblings who underwent kidney transplant at Baskent University Hospital between 1989 and 2014 were retrospectively analyzed. Collected data included demographic features; comorbidities; reasons for liver and kidney failure; perioperative laboratory values; intraoperative hemodynamic parameters; use and volume of crystalloids, colloids, blood products, cell saver system, and albumin; duration of anesthesia; urine output; and postoperative follow-up data. The mean age of the 6 sibling pairs who underwent liver transplant was 16.3 ± 12.2 years. All 12 patients had Child-Pugh grade B cirrhosis, with mean disease duration of 7.8 ± 3.9 years. There were no significant differences between siblings with respect to intraoperative blood product transfusion, crystalloid and colloid fluid replacements, hypotension frequency, blood gas analyses, urinary output, duration of anhepatic phase, inotropic agent administration, postoperative laboratory values, need for mechanical ventilation and vasopressors, occurrence of acute renal failure and infections, and duration intensive care unit stay (P > .05). The mean age of the 4 sibling pairs who underwent kidney transplant was 21.3 ± 6.4 years, with mean duration of renal insufficiency of 2.2 ± 1.6 years. There were no significant differences between siblings with respect to intraoperative crystalloid and colloid fluid administration, duration of anesthesia, intraoperative mannitol and furosemide administration, and postoperative laboratory values (P > .05). In conclusion, the 6 sibling pairs who underwent liver transplant and 4 sibling pairs who underwent kidney transplant in our cohort had similar perioperative characteristics.

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model

PubMed Central

Higuchi, Tamami; Yokobori, Takehiko; Naito, Tomoharu; Kakinuma, Chihaya; Hagiwara, Shinji; Nishiyama, Masahiko; Asao, Takayuki

2018-01-01

Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer. PMID:29435042

The potential of induced pluripotent stem cell derived hepatocytes.

PubMed

Hannoun, Zara; Steichen, Clara; Dianat, Noushin; Weber, Anne; Dubart-Kupperschmitt, Anne

2016-07-01

Orthotopic liver transplantation remains the only curative treatment for liver disease. However, the number of patients who die while on the waiting list (15%) has increased in recent years as a result of severe organ shortages; furthermore the incidence of liver disease is increasing worldwide. Clinical trials involving hepatocyte transplantation have provided encouraging results. However, transplanted cell function appears to often decline after several months, necessitating liver transplantation. The precise aetiology of the loss of cell function is not clear, but poor engraftment and immune-mediated loss appear to be important factors. Also, primary human hepatocytes (PHH) are not readily available, de-differentiate, and die rapidly in culture. Hepatocytes are available from other sources, such as tumour-derived human hepatocyte cell lines and immortalised human hepatocyte cell lines or porcine hepatocytes. However, all these cells suffer from various limitations such as reduced or differences in functions or risk of zoonotic infections. Due to their significant potential, one possible inexhaustible source of hepatocytes is through the directed differentiation of human induced pluripotent stem cells (hiPSCs). This review will discuss the potential applications and existing limitations of hiPSC-derived hepatocytes in regenerative medicine, drug screening, in vitro disease modelling and bioartificial livers. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Outcomes after liver transplantation of patients with Indo-Asian ethnicity.

PubMed

Rocha, Chiara; Perera, M Thamara; Roberts, Keith; Bonney, Glenn; Gunson, Bridget; Nightingale, Peter; Bramhall, Simon R; Isaac, John; Muiesan, Paolo; Mirza, Darius F

2015-04-01

The impact of ethnicity on outcomes after orthotopic liver transplantation (OLT) is unclear. The British Indo-Asian population has a high incidence of liver disease but its contribution to the national deceased donor pool is small. We evaluated access to and outcomes of OLT in Indo-Asians. We compared 182 Indo-Asians with white patients undergoing OLT. Matching criteria were transplantation year, liver disease, age, sex. Donor and recipient characteristics, postoperative outcomes, including patient and graft survival, OLT era (early, 1987-2001; late, 2002-2011) were compared. Survival was also analyzed by underlying disease-acute liver failure (ALF) and chronic liver failure. Indo-Asians had higher diabetes incidence. There were no differences in waiting time for transplantation, despite smaller body size and more uncommon blood groups (B, AB) among Indo-Asians. In the early era, patient survival for Indo-Asians with ALF was worse when compared to whites. In the late era, graft and patient survival at 1, 2, and 5 years were similar between groups. This study demonstrates that Indo-Asian patients have equal access to OLT and comparable outcomes to whites in the United Kingdom. Survival has improved among Indo-Asian patients; this may be attributable to careful patient selection in case of ALF, though improvement of patient management may have contributed.

Domino liver transplantation in maple syrup urine disease: a case report and review of the literature.

PubMed

Badell, I R; Hanish, S I; Hughes, C B; Hewitt, W R; Chung, R T; Spivey, J R; Knechtle, S J

2013-03-01

Improved outcomes have expanded the indications for liver transplantation, thus aggravating the already limited supply of donor organs. Domino liver transplantation (DLT) has been one strategy to augment the supply of donor organs in cases of inborn errors of metabolism. One such disease is maple syrup urine disease (MSUD), an inherited disorder of branched-chain amino acid (BCAA) metabolism. We report on the transplantation of a deceased donor liver into a patient with MSUD, and the sequential transplantation of the explanted liver into a patient with hemophilia A, HIV, hepatitis C, and a low priority on the transplant waiting list. At 30 months, the MSUD recipient has had significant correction of BCAA metabolism on a protein-unrestricted diet and no progression of neuropsychiatric symptoms. The DLT recipient has been cured of hemophilia and has normal BCAA homeostasis. This case provides further evidence that elective orthotopic liver transplantation for MSUD attenuates the disease with restoration of BCAA metabolism, and that DLT in this setting can achieve excellent results in ESLD patients. It is possible that domino grafts from patients with MSUD could be used in more conventional recipients, but additional studies and longer-term outcomes are needed to determine the validity of DLT in MSUD. Copyright © 2013 Elsevier Inc. All rights reserved.

An experience of liver transplantation in Latin America: a medical center in Colombia

PubMed Central

Londoño, Mauricio; Marín, Juan; Muñoz, Octavio; Mena, Álvaro; Guzmán, Carlos; Hoyos, Sergio; Restrepo, Juan; Arbeláez, María; Correa, Gonzalo

2015-01-01

Objectives: Liver transplantation is the treatment of choice for acute and chronic liver failure, for selected cases of tumors, and for conditions resulting from errors in metabolism. This paper reports the experience of a medical center in Latin America. Methods: Were conducted 305 orthotopic liver transplantations on 284 patients between 2004 and 2010. Of these patients, 241 were adults undergoing their first transplantation. Results: The average age of patients was 52 years old, and 62% of the individuals were male. The most common indication was alcoholic cirrhosis. The rate of patient survival after 1 and 5 years was 82 and 72% respectively. The rate of liver graft survival after 1 and 5 years was 78 and 68% respectively. The main cause of death was sepsis. Complications in the hepatic artery were documented for 5% of the patients. Additionally, 14.5% of the patients had complications in the biliary tract. Infections were found in 41% of the individuals. Acute rejection was observed in 30% of the subjects, and chronic rejection in 3%. Conclusion: In conclusion, liver transplantation at our medical center in Colombia offers good mid-term results, with a complication rate similar to that reported by other centers around the world. PMID:26019379

Development of a Preclinical Orthotopic Xenograft Model of Ewing Sarcoma and Other Human Malignant Bone Disease Using Advanced In Vivo Imaging

PubMed Central

Batey, Michael A.; Almeida, Gilberto S.; Wilson, Ian; Dildey, Petra; Sharma, Abhishek; Blair, Helen; Hide, I. Geoff; Heidenreich, Olaf; Vormoor, Josef; Maxwell, Ross J.; Bacon, Chris M.

2014-01-01

Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG) and Rag2−/−/γc−/− mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000–5000) injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised “malignant” bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which resemble the human disease. We have shown the utility of small animal bioimaging for tracking disease progression, making this model a useful assay for preclinical drug testing. PMID:24409320

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

PubMed

Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

2017-04-01

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

[Portal perfusion with right gastroepiploic vein flow in liver transplant].

PubMed

Mendoza-Sánchez, Federico; Javier-Haro, Francisco; Mendoza-Medina, Diego Federico; González-Ojeda, Alejandro; Cortés-Lares, José Antonio; Fuentes-Orozco, Clotilde

Liver transplantation in patients with liver cirrhosis, portal vein thrombosis, and cavernous transformation of the portal vein, is a complex procedure with high possibility of liver graft dysfunction. It is performed in 2-19% of all liver transplants, and has a significantly high mortality rate in the post-operative period. Other procedures to maintain portal perfusion have been described, however there are no reports of liver graft perfusion using right gastroepiploic vein. A 20 year-old female diagnosed with cryptogenic cirrhosis, with a Child-Pugh score of 7 points (class "B"), and MELD score of 14 points, with thrombosis and cavernous transformation of the portal vein, severe portal hypertension, splenomegaly, a history of upper gastrointestinal bleeding due to oesophageal varices, and left renal agenesis. The preoperative evaluation for liver transplantation was completed, and the right gastroepiploic vein of 1-cm diameter was observed draining to the infrahepatic inferior vena cava and right suprarenal vein. An orthotopic liver transplantation was performed from a non-living donor (deceased on January 30, 2005) using the Piggy-Back technique. Portal vein perfusion was maintained using the right gastroepiploic vein, and the outcome was satisfactory. The patient was discharged 13 days after surgery. Liver transplantation was performed satisfactorily, obtaining an acceptable outcome. In this case, the portal perfusion had adequate blood flow through the right gastroepiploic vein. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging

PubMed Central

England, Christopher G.; Huang, Justin S.; James, Kurtis T.; Zhang, Guandong; Gobin, André M.; Frieboes, Hermann B.

2015-01-01

Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5±8.2 and 23.3±4.1 particles/100μm2 within 10μm from the nearest source and few nanoparticles beyond 50μm, respectively. The spleen had 35.5±9.3 particles/100μm2 within 10μm with penetration also limited to 50μm. For SGN, the liver showed 31.1±4.1 particles/100μm2 within 10μm of the nearest source with penetration hindered beyond 30μm. The spleen and tumor showed uptake of 22.1±6.2 and 15.8±6.1 particles/100μm2 within 10μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09±0.14 in the liver, 0.74±0.12 in the spleen, and 0.43±0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43±0.07 in the liver, 0.30±0.06 in the spleen, and 0.20±0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in pancreatic tumors with the goal to improve nanotherapeutic efficacy. PMID:26046360

Porcine alanine transaminase after liver allo-and xenotransplantation.

PubMed

Ekser, Burcin; Gridelli, Bruno; Cooper, David K C

2012-01-01

Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording. © 2012 John Wiley & Sons A/S.

Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

PubMed

Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

2016-01-01

Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of monitoring tumour development surpassing manual tumour inspection.

Liver resection for metastases of tracheal adenoid cystic carcinoma: Report of two cases.

PubMed

Hashimoto, Shintaro; Sumida, Yorihisa; Tobinaga, Shuichi; Wada, Hideo; Wakata, Kouki; Nonaka, Takashi; Kunizaki, Masaki; Hidaka, Shigekazu; Kinoshita, Naoe; Sawai, Terumitsu; Nagayasu, Takeshi

2018-05-16

Tracheal adenoid cystic carcinoma (ACC) is rare and accounts for <1% of all lung cancers. Although ACC is classified as a low-grade tumor, metastases are frequently identified in the late period. Extrapulmonary metastases are rare, and their resection has rarely been reported. Case 1: A 77-year-old man underwent tracheal resection for ACC with postoperative radiation (60 Gy) 14 years before　(at the age of 63). He underwent two subsequent pulmonary resections for metastases. Fourteen years after the first operation, he underwent extended right posterior segmentectomy with resection of segment IV and radiofrequency ablation for metastases of ACC to the liver. He was diagnosed with metastases to the kidney with peritoneal dissemination 4 years after the liver resection and died of pneumonia 2 years later. Case 2: A 53-year-old woman underwent a two-stage operation involving tracheal resection for ACC and partial resection of liver segments II and V for metastases of ACC to the liver. The tracheal margin was histopathologically positive. Postoperative radiation was performed, and she was tumor-free for 10 months after the liver resection. Complete resection of tracheal ACC provides better survival. Radiotherapy is also recommended. However, the optimal treatment for metastases of ACC is unclear, especially because liver resection for metastases of tracheal ACC is rarely reported. Our two cases of metastases of tracheal ACC were surgically managed with good outcomes. Liver resection for metastases of tracheal ACC may contribute to long survival. Copyright © 2018. Published by Elsevier Ltd.

Umbilical hernia management during liver transplantation.

PubMed

de Goede, B; van Kempen, B J H; Polak, W G; de Knegt, R J; Schouten, J N L; Lange, J F; Tilanus, H W; Metselaar, H J; Kazemier, G

2013-08-01

Patients with liver cirrhosis scheduled for liver transplantation often present with a concurrent umbilical hernia. Optimal management of these patients is not clear. The objective of this study was to compare the outcomes of patients who underwent umbilical hernia correction during liver transplantation through a separate infra-umbilical incision with those who underwent correction through the same incision used to perform the liver transplantation. In the period between 1990 and 2011, all 27 patients with umbilical hernia and liver cirrhosis who underwent hernia correction during liver transplantation were identified in our hospital database. In 17 cases, umbilical hernia repair was performed through a separate infra-umbilical incision (separate incision group) and 10 were corrected from within the abdominal cavity without a separate incision (same incision group). Six patients died during follow-up; no deaths were attributable to intraoperative umbilical hernia repair. All 21 patients who were alive visited the outpatient clinic to detect recurrent umbilical hernia. One recurrent umbilical hernia was diagnosed in the separate incision group (6 %) and four (40 %) in the same incision group (p = 0.047). Two patients in the same incision group required repair of the recurrent umbilical hernia; one of whom underwent emergency surgery for bowel incarceration. The one recurrent hernia in the separate incision group was corrected electively. In the event of liver transplantation, umbilical hernia repair through a separate infra-umbilical incision is preferred over correction through the same incision used to perform the transplantation.

Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

NASA Astrophysics Data System (ADS)

O'Hara, Julia A.; Samkoe, Kimberley S.; Chen, Alina; Isabelle, Martin; Hoopes, P. J.; Hasan, Tayyaba; Pogue, Brian W.

2012-02-01

Photodynamic therapy (PDT) that uses the second generation photosensitizer, verteporfin (VP), is a developing therapy for pancreatic cancer. The optimal timing of light delivery related to VP uptake and distribution in pancreatic tumors will be important information to obtain to improve treatment for this intractable disease. In this work we examined uptake and distribution of VP in two orthotopic pancreatic tumors with different histological structure. ASPC-1 (fast-growing) and Panc-1 (slower growing) tumors were implanted in SCID mice and studied when tumors were approximately 100mm3. In a pilot study, these tumors had been shown to differ in uptake of VP using lightinduced fluorescence spectroscopy (LIFS) in vivo and fluorescence imaging ex vivo and that work is extended here. In vivo fluorescence mean readings of tumor and liver increased rapidly up to 15 minutes after photosensitizer injection for both tumor types, and then continued to increase up to 60 minutes post injection to a higher level in ASPC-1 than in Panc-1. There was variability among animals with the same tumor type, in both liver and tumor uptake and no selectivity of tumor over liver. In this work we further examined VP uptake at multiple time points in relation to microvascular density and perfusion, using DiOC7 (to mark blood vessels) and VP fluorescence in the same tissue slices. Analysis of DiOC7 fluorescence indicates that AsPC-1 and Panc-1 have different vascular densities but AsPC-1 vasculature is more perfusive. Analysis of colocalized DiOC7 and VP fluorescence showed ASPC-1 with higher accumulation of VP 3 hrs after injection and more VP at a distance from blood vessels compared to Panc-1. This work shows the need for techniques to analyze photosensitizer distribution in order to optimize photodynamic therapy as an effective treatment for pancreatic tumors.

Success and complications of an intra-ductal fully covered self-expanding metal stent (ID-FCSEMS) to treat anastomotic biliary strictures (AS) after orthotopic liver transplantation (OLT).

PubMed

Aepli, Patrick; St John, Andrew; Gupta, Saurabh; Hourigan, Luke F; Vaughan, Rhys; Efthymiou, Marios; Kaffes, Arthur

2017-04-01

Anastomotic biliary strictures (AS) after orthotopic liver transplantation (OLT) belong to the most common biliary complications and cause the biggest morbidity burden after OLT. Metal stents for benign biliary strictures are gaining acceptance with many published series. Traditional metal stent designs seem to have poor durability in AS after OLT. Novel intra-ductal stents are showing promise in these strictures. As a result, we designed a special stent with an antimigration waist and a short stent length with a long removal string that rests in the duodenum for easy removal. This is a retrospective multi-centre Australian study of AS after OLT treated with a novel intra-ductal fully covered self-expanding metal stent. From August 2008 to October 2014, records from three liver transplant centres were reviewed. Totally 36 ID-FCSEMS were inserted in 31 cases to treat an AS after OLT. The mean age of the patients was 56 years, and 61 % were male. The mean time of AS presentation after OLT was 20.3 months. Eight out of our 31 patients were previously treated using multiple plastic stenting over time without any success. Treatment with the ID-FCSEMS was performed with an average treatment time of 3.8 months. Stricture resolution was achieved in 100 %. All attempted stents removals were successful without any difficulty. Complications were reported in 6.5 %. It was pleasing that only one case of stent migration (2.8 %) was seen. Follow-up showed seven cases of AS recurrence (24.1 %), and all were treated successfully with repeat ERCP and stenting (some metal, some plastic). This novel ID-FCSEMS has a high clinical success and low complication rate, and in particular, there was only one case of stent migration. As a result, this stent type is preferred to traditional metal stents for treating AS after OLT.

CLINICAL FACTORS ASSOCIATED WITH BIOCHEMICAL ADRENAL-CORTISOL INSUFFICIENCY IN HOSPITALIZED PATIENTS

PubMed Central

Ben-Shlomo, Anat; Mirocha, James; Liu, Ning-Ai; Sheinin, Renee C.; Melmed, Shlomo

2014-01-01

Background Diagnosis of adrenal-cortisol insufficiency is often misleading in hospitalized patients as clinical and biochemical features overlap with co-morbidities. We analyzed clinical determinants associated with a biochemical diagnosis of adrenal-cortisol insufficiency in non-ICU hospitalized patients. Methods In a retrospective cohort study we reviewed 4668 inpatients with random morning cortisol levels ≤15 μg/dL hospitalized in our center between 2003 and 2010. Using serum cortisol threshold level of 18 μg/dL 30 and/or 60 minutes after cortrosyn (250 μg) injection to define biochemical adrenal-cortisol status, we characterized and compared insufficient (n=108, serum cortisol ≤18 μg/dL) and sufficient ( n=394; serum cortisol >18 μg/dL) non-ICU hospitalized patients. Results Commonly reported clinical and routine biochemical adrenal-cortisol insufficiency features were similar between insufficient and sufficient inpatients. Biochemical adrenal-cortisol insufficiency was associated with increased frequency of liver disease, specifically hepatitis C (p=0.01) and prior orthotopic liver transplantation (p<0.001), HIV (p=0.005) and reported preexisting male hypogonadism (p<0.001) as compared to biochemical adrenal-cortisol sufficiency group. Forty percent of insufficient inpatients were not treated with glucocorticoids after diagnosis. Multivariable logistic analysis demonstrated that inpatients with higher cortisol levels (p=0.0001), higher diastolic blood pressure (p=0.05) and females (p=0.009) were more likely not to be treated, while those with previous short-term glucocorticoid treatment (p=0.002), had other co-existing endocrine diseases (p=0.005) or received an inhospital endocrinology consultation (p<0.0001) were more likely to be replaced with glucocorticoids. Conclusions Commonly reported adrenal-cortisol insufficiency features do not reliably identify hospitalized patients biochemically confirmed to have this disorder. Co-morbidities including hepatitis C, prior orthotopic liver transplantation, HIV, and reported pre-existing male hypogonadism may help identify hospitalized non-ICU patients for more rigorous adrenal insufficiency assessment. PMID:24632056

Prevention of hypothermia in patients undergoing orthotopic liver transplantation using the humigard® open surgery humidification system: a prospective randomized pilot and feasibility clinical trial.

PubMed

Weinberg, Laurence; Huang, Andrew; Alban, Daniel; Jones, Robert; Story, David; McNicol, Larry; Pearce, Brett

2017-01-23

Perioperative thermal disturbances during orthotopic liver transplantation (OLT) are common. We hypothesized that in patients undergoing OLT the use of a humidified high flow CO 2 warming system maintains higher intraoperative temperatures when compared to standardized multimodal strategies to maintain thermoregulatory homeostasis. We performed a randomized pilot study in adult patients undergoing primary OLT. Participants were randomized to receive either open wound humidification with a high flow CO 2 warming system in addition to standard care (Humidification group) or to standard care alone (Control group). The primary end point was nasopharyngeal core temperature measured 5 min immediately prior to reperfusion of the donor liver (Stage 3 - 5 min). Secondary endpoints included intraoperative PaCO 2 , minute ventilation and the use of vasoconstrictors. Eleven patients were randomized to each group. Both groups were similar for age, body mass index, MELD, SOFA and APACHE II scores, baseline temperature, and duration of surgery. Immediately prior to reperfusion (Stage 3 - 5 min) the mean (SD) core temperature was higher in the Humidification Group compared to the Control Group: 36.0 °C (0.13) vs. 35.4 °C (0.22), p = 0.028. Repeated measured ANOVA showed that core temperatures over time during the stages of the transplant were higher in the Humidification Group compared to the Control Group (p < 0.0001). There were no significant differences in the ETCO 2 , PaCO 2 , minute ventilation, or inotropic support. The humidified high flow CO 2 warming system was superior to standardized multimodal strategies in maintaining normothermia in patients undergoing OLT. Use of the device was feasible and did not interfere with any aspects of surgery. A larger study is needed to investigate if the improved thermoregulation observed is associated with improved patient outcomes. ACTRN12616001631493 . Retrospectively registered 25 November 2016.

Recipient’s Genetic R702W NOD2 Variant Is Associated with an Increased Risk of Bacterial Infections after Orthotopic Liver Transplantation

PubMed Central

van Hoek, Bart; van den Berg, Arie P.; Porte, Robert J.; Blokzijl, Hans; Coenraad, Minneke J.; Hepkema, Bouke G.; Schaapherder, Alexander F.; Ringers, Jan; Weersma, Rinse K.; Verspaget, Hein W.

2013-01-01

Introduction Orthotopic liver transplantation (OLT) is accompanied by a significant postoperative infection risk. Immunosuppression to prevent rejection increases the susceptibility to infections, mainly by impairing the adaptive immune system. Genetic polymorphisms in the lectin complement pathway of the donor have recently been identified as important risk determinants of clinically significant bacterial infection (CSI) after OLT. Another genetic factor involved in innate immunity is NOD2, which was reported to be associated with increased risk of spontaneous bacterial peritonitis in cirrhotic patients. Methods We assessed association of three genetic NOD2 variants (R702W, G908R and 3020insC) with increased risk of CSI after OLT. 288 OLT recipient-donor pairs from two tertiary referral centers were genotyped for the three NOD2 variants. The probability of CSI in relation to NOD2 gene variants was determined with cumulative incidence curves and log-rank analysis. Results The R702W NOD2 variant in the recipient was associated with CSI after OLT. Eight out of 15 (53.3%) individuals with a mutated genotype compared to 80/273 (29.3%) with wild type genotype developed CSI (p=0.027, univariate cox regression), illustrated by a higher frequency of CSI after OLT over time (p=0.0003, log rank analysis). Multivariate analysis (including the donor lectin complement pathway profile) showed independence of this R702W NOD2 association from other risk factors (HR 2.0; p=0.04). The other NOD2 variants, G908R and 3020insC, in the recipient were not associated with CSI. There was no association with CSI after OLT for any of the NOD2 variants in the donor. Conclusion The mutated NOD2 R702W genotype in the recipient is independently associated with an increased risk of bacterial infections after liver transplantation, indicating a predisposing role for this genetic factor impairing the recipient’s innate immune system. PMID:23977330

Surgical treatment of liver metastasis of gastric cancer: a retrospective multicenter cohort study (KSCC1302).

PubMed

Oki, Eiji; Tokunaga, Shoji; Emi, Yasunori; Kusumoto, Tetsuya; Yamamoto, Manabu; Fukuzawa, Kengo; Takahashi, Ikuo; Ishigami, Sumiya; Tsuji, Akihito; Higashi, Hidefumi; Nakamura, Toshihiko; Saeki, Hiroshi; Shirabe, Ken; Kakeji, Yoshihiro; Sakai, Kenji; Baba, Hideo; Nishimaki, Tadashi; Natsugoe, Shoji; Maehara, Yoshihiko

2016-07-01

The necessity of surgical treatment of liver metastases of gastric cancer is still controversial. We conducted a multicenter retrospective cohort study of liver-limited metastasis of gastric cancer treated surgically between 2000 and 2010. In this study, 103 patients were registered, with nine patients excluded from the analysis as they did not meet the eligibility criteria. Of the 94 patients, 69 underwent surgical resection, 11 underwent surgical resection combined with radiofrequency ablation or microwave coagulation therapy for small or deep tumors, and 14 underwent radiofrequency ablation or microwave coagulation therapy only. Synchronous and metachronous metastases were found in 37 and 57 patients, respectively. The 3- and 5-year overall survival rates of all the patients were 51.4 and 42.3 %, respectively. The 3- and 5-year relapse-free survival rates were 29.2 and 27.7 %, respectively. No significant difference in prognosis was observed between the patients who underwent surgical resection and those who underwent ablation therapy. The patients with hepatic solitary lesions and low-grade lymph node metastases of primary gastric cancer had significantly better overall survival and relapse-free survival. To our knowledge, this study is the largest series and first multicenter cohort study of liver-limited metastasis of gastric cancer. The study indicated that patients with a single liver metastasis with a grade lower than N2 lymph node metastasis of the primary lesion are the best candidates for liver resection.

Pure laparoscopic hepatectomy in semiprone position for right hepatic major resection.

PubMed

Ikeda, Tetsuo; Mano, Yohei; Morita, Kazutoyo; Hashimoto, Naotaka; Kayashima, Hirohito; Masuda, Atsuro; Ikegami, Toru; Yoshizumi, Tomoharu; Shirabe, Ken; Maehara, Yoshihiko

2013-02-01

Pure laparoscopic liver resection is technically difficult for tumors located in the dorsal anterior and posterior sectors. We have developed a maneuver to perform pure laparoscopic hepatectomy in the semiprone position which was developed for resecting tumors located in these areas. The medical records have been reviewed retrospectively in 30 patients who underwent laparoscopic liver resection in the semiprone position for carcinoma in the dorsal anterior or posterior sectors of the right liver between 2008 and 2011. Seventeen liver tumors were primary liver tumors and 13 were colorectal metastases. Of the 30 patients, 11 (36.6 %) underwent major hepatectomy [right hemihepatectomy in 7 (23.3 %) and posterior sectionectomy in 4 (13.3 %)]. Anatomical minor resection, such as S6 or S7 segmentectomy, was performed in five patients (16.6 %). Five patients with liver metastasis underwent a simultaneous laparoscopic resection. There was no mortality, reoperation, or conversion to open procedures. There were no hepatectomy-related complications such as postoperative bleeding, bile leakage, or liver failure. Pure laparoscopic hepatectomy in the semiprone position for tumors present in the dorsal anterior and posterior sectors is feasible and safe. This method expands the indications for laparoscopic liver resection for tumors.

Living donor liver transplantation in maple syrup urine disease - Case series and world's youngest domino liver donor and recipient.

PubMed

Mohan, N; Karkra, S; Rastogi, A; Vohra, V; Soin, A S

2016-05-01

MSUD occurs due to deficiency of enzyme BCKAD required for metabolism of leucine, isoleucine, and valine leading to the accumulation of these and their ketoacids causing acute metabolic decompensation manifesting as encephalopathy or sudden death. The patient requires special protein-restricted diet to survive. As this enzyme is expressed in liver, liver transplantation has been successfully performed as a cure. We report two patients of MSUD who underwent LDLT while their livers were used as a domino graft for other biliary cirrhotic patients. A 22-month-old male child diagnosed as a case of classic MSUD underwent LDLT from an altruistic aunt as donor following which his serum leucine levels normalized on an unrestricted protein diet. His liver was used as a domino graft. A 38-month-old female child with diagnosed MSUD underwent LDLT from a swap donor, and her liver was used as a domino graft. Her DQ improved post-transplant. LDLT from non-heterozygous donors is a cure for classical MSUD. Their livers can be used as domino grafts for non-MSUD cases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation

PubMed Central

Xiang, D; Liu, C-C; Wang, M-J; Li, J-X; Chen, F; Yao, H; Yu, B; Lu, L; Borjigin, U; Chen, Y-X; Zhong, L; Wangensteen, K J; He, Z-Y; Wang, X; Hu, Y-P

2014-01-01

Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)–/– mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation. PMID:24853430

Safe and successful endoscopic initial treatment and long-term eradication of gastric varices by endoscopic ultrasound-guided Histoacryl (N-butyl-2-cyanoacrylate) injection.

PubMed

Gubler, Christoph; Bauerfeind, Peter

2014-09-01

Optimal endoscopic treatment of gastric varices is still not standardized nowadays. Actively bleeding varices may prohibit a successful endoscopic injection therapy of Histoacryl® (N-butyl-2-cyanoacrylate). Since 2006, we have treated gastric varices by standardized endoscopic ultrasound (EUS) guided Histoacryl injection therapy without severe adverse events. We present a large single-center cohort over 7 years with a standardized EUS-guided sclerotherapy of all patients with gastric varices. Application was controlled by fluoroscopy to immediately detect any glue embolization. Only perforating veins located within the gastric wall were treated. In the follow up, we repeated this treatment until varices were eradicated. Utmost patients (36 of 40) were treated during or within 24 h of active bleeding. About 32.5% of patients were treated while visible bleeding. Histoacryl injection was always technically successful and only two patients suffered a minor complication. Acute bleeding was stopped in all patients. About 15% (6 of 40) of patients needed an alternative rescue treatment in the longer course. Three patients got a transjugular portosystemic shunt and another three underwent an orthotopic liver transplantation. Mean long-term survival of 60 months was excellent. Active bleeding of gastric varices can be treated successfully without the necessity of gastric rinsing with EUS-guided injection of Histoacryl.

Non-operative management of isolated liver trauma.

PubMed

Li, Min; Yu, Wen-Kui; Wang, Xin-Bo; Ji, Wu; Li, Jie-Shou; Li, Ning

2014-10-01

Liver trauma is the most common abdominal emergency with high morbidity and mortality. Now, non-operative management (NOM) is a selective method for liver trauma. The aim of this study was to determine the success rate, mortality and morbidity of NOM for isolated liver trauma. Medical records of 81 patients with isolated liver trauma in our unit were analyzed retrospectively. The success rate, mortality and morbidity of NOM were evaluated. In this series, 9 patients with grade IV-V liver injuries underwent emergent operation due to hemodynamic instability; 72 patients, 6 with grade V, 18 grade IV, 29 grade III, 15 grade II and 4 grade I, with hemodynamic stability received NOM. The overall success rate of NOM was 97.2% (70/72). The success rates of NOM in the patients with grade I-III, IV and V liver trauma were 100%, 94.4% and 83.3%. The complication rates were 10.0% and 45.5% in the patients who underwent NOM and surgical treatment, respectively. No patient with grade I-II liver trauma had complications. All patients who underwent NOM survived. NOM is the first option for the treatment of liver trauma if the patient is hemodynamically stable. The grade of liver injury and the volume of hemoperitoneum are not suitable criteria for selecting NOM. Hepatic angioembolization associated with the correction of hypothermia, coagulopathy and acidosis is important in the conservative treatment for liver trauma.

Cardiovascular risk after orthotopic liver transplantation, a review of the literature and preliminary results of a prospective study.

PubMed

Pisano, Giuseppina; Fracanzani, Anna L; Caccamo, Lucio; Donato, Maria F; Fargion, Silvia

2016-10-28

Improved surgical techniques and greater efficacy of new anti-rejection drugs have significantly improved the survival of patients undergoing orthotopic liver transplantation (OLT). This has led to an increased incidence of metabolic disorders as well as cardiovascular and cerebrovascular diseases as causes of morbidity and mortality in OLT patients. In the last decade, several studies have examined which predisposing factors lead to increased cardiovascular risk ( i.e ., age, ethnicity, diabetes, NASH, atrial fibrillation, and some echocardiographic parameters) as well as which factors after OLT ( i.e ., weight gain, metabolic syndrome, immunosuppressive therapy, and renal failure) are linked to increased cardiovascular mortality. However, currently, there are no available data that evaluate the development of atherosclerotic damage after OLT. The awareness of high cardiovascular risk after OLT has not only lead to the definition of new but generally not accepted screening of high risk patients before transplantation, but also to the need for careful patient follow up and treatment to control metabolic and cardiovascular pathologies after transplant. Prospective studies are needed to better define the predisposing factors for recurrence and de novo occurrence of metabolic alterations responsible for cardiovascular damage after OLT. Moreover, such studies will help to identify the timing of disease progression and damage, which in turn may help to prevent morbidity and mortality for cardiovascular diseases. Our preliminary results show early occurrence of atherosclerotic damage, which is already present a few weeks following OLT, suggesting that specific, patient-tailored therapies should be started immediately post OLT.

BreastDefend™ prevents breast-to-lung cancer metastases in an orthotopic animal model of triple-negative human breast cancer

PubMed Central

JIANG, JIAHUA; THYAGARAJAN-SAHU, ANITA; LOGANATHAN, JAGADISH; ELIAZ, ISAAC; TERRY, COLIN; SANDUSKY, GEORGE E.; SLIVA, DANIEL

2012-01-01

We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. Oral application of BD (100 mg/kg of body weight for 4 weeks) by intragastric gavage did not affect body weight or activity of liver enzymes and did not show any sign of toxicity in liver, spleen, kidney, lung and heart tissues in mice. Moreover, BD significantly decreased the change in tumor volume over time compared to the control group (p=0.002). BD treatment also markedly decreased the incidence of breast-to-lung cancer metastasis from 67% (control) to 20% (BD) (p<0.05) and the number of metastases from 2.8 (0.0, 48.0) in the control group to 0.0 (0.0, 14.2) in the BD treatment group (p<0.05). Finally, anti-metastatic activity of BD in vivo was further confirmed by the downregulation of expression of PLAU (urokinase plasminogen activator, uPA) and CXCR4 (C-X-C chemokine receptor-4) genes in breast tumors. In conclusion, BD may be considered as a biological therapeutic agent against invasive breast cancers. PMID:22842551

Characteristics and Outcomes of Neutropenia after Orthotopic Liver Transplantation

PubMed Central

Alraddadi, B; Nierenberg, NE; Price, LL; Chow, JKL; Poutsiaka, DD; Rohrer, RJ; Cooper, JT; Freeman, RB; Snydman, DR

2015-01-01

Neutropenia after orthotopic liver transplantation (LT) is relatively common but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] less than or equal to 1000/mm3) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, blood stream infection (BSI), invasive fungal infection (IFI), Cytomegalovirus (CMV) disease and graft rejection within the first year of LT. Of the 304 LT recipients, 73 (24%) developed neutropenia, 5 (7%) of whom had grade 4 neutropenia (ANC less than 500/mm3). The following were independent predictors for neutropenia: Child-Turcotte-Pugh score (HR 1.15; 95% CI 1.02, 1.28; p=0.02), BSI (HR 2.89; 95% CI 1.64, 5.11; p=<0.001), CMV disease (HR 4.28; 95% CI 1.55, 11.8; p=0.005), baseline tacrolimus trough level (HR 1.02; 95% CI 1.01, 1.03; p=0.007) and later era LT (2004–2009 versus 1999–2003) (HR 2.28; 95% CI 1.43, 3.65; p=<0.001). Moreover, neutropenia was found to be an independent predictor for mortality within the first year of LT (HR 3.76; 95% CI 1.84, 7.68; p= <0.001). Conclusion Our data suggest that neutropenia within a year after LT is not unusual and is an important predictor of mortality. PMID:26336061

Recurrent Primary Biliary Cirrhosis: Peritransplant Factors and Ursodeoxycholic Acid Treatment Post-Liver Transplant

PubMed Central

Guy, Jennifer E.; Qian, Peiqing; Lowell, Jeffrey A.; Peters, Marion G.

2014-01-01

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known. PMID:16184542

Successful Treatment of Corticosteroid with Antiviral Therapy for a Neonatal Liver Failure with Disseminated Herpes Simplex Virus Infection

PubMed Central

Maeba, Shinji; Hasegawa, Shunji; Shimomura, Maiko; Ichimura, Takuya; Takahashi, Kazumasa; Motoyama, Masashi; Fukunaga, Shinnosuke; Ito, Yoshinori; Ichiyama, Takashi; Ohga, Shouichi

2015-01-01

Background Herpes simplex virus (HSV) infection carries one of the poorest outcomes of neonatal liver failure (NLF). Neonates with disseminated HSV infection can develop hemophagocytic lymphohistiocytosis (HLH), and occasionally need orthotopic liver transplantation. Early interventions may be critical for the cure of NLF. Case Report We describe herewith a 6-day-old neonate with fulminant hepatic failure due to disseminated HSV-1 infection, who successfully responded to high-dose corticosteroid therapy 72 hours after the onset of disease. Preceding acyclovir, gamma globulin, and exchange blood transfusion therapies failed to control the disease. Methylprednisolone pulse therapy led to a drastic improvement of liver function and cytokine storms, and prevented the disease progression to HLH. Sustained levels of plasma and cerebrospinal fluid HSV DNA declined after prolonged acyclovir therapy. Bilateral lesions of the periventricular white matter areas, assessed by magnetic resonance imaging, disappeared at 3 months of age. The infant showed normal growth and development at 4 years of age. Conclusion Early anti-hypercytokinemia therapy using corticosteroid, and prolonged antiviral therapy might only provide the transplantation-free cure of NLF with HSV dissemination. PMID:26495160

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

PubMed

Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

Environmental peer pressure: CD4+ T cell help in tolerance and transplantation.

PubMed

Tedesco, Dana; Grakoui, Arash

2018-01-01

The liver participates in a multitude of metabolic functions that are critical for sustaining human life. Despite constant encounters with antigenic-rich intestinal blood, oxidative stress, and metabolic intermediates, there is no appreciable immune response. Interestingly, patients undergoing orthotopic liver transplantation benefit from a high rate of graft acceptance in comparison to other solid organ transplant recipients. In fact, cotransplantation of a donor liver in tandem with a rejection-prone graft increases the likelihood of graft acceptance. A variety of players may account for this phenomenon including the interaction of intrahepatic antigen-presenting cells with CD4 + T cells and the preferential induction of forkhead box P3 (Foxp3) expression on CD4 + T cells following injurious stimuli. Ineffective insult management can cause chronic liver disease, which manifests systemically as the following: antibody-mediated disorders, ineffective antiviral and antibacterial immunity, and gastrointestinal disorders. These sequelae sharing the requirement of CD4 + T cell help to coordinate aberrant immune responses. In this review, we will focus on CD4 + T cell help due to the shared requirements in hepatic tolerance and coordination of extrahepatic immune responses. Overall, intrahepatic deviations from steady state can have deleterious systemic immune outcomes and highlight the liver's remarkable capacity to maintain a balance between tolerance and inflammatory response while simultaneously being inundated with a panoply of antigenic stimuli. Liver Transplantation 24 89-97 2018 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Perioperative and oncologic outcomes of minimally invasive liver resection for colorectal metastases: A case-control study of 130 patients.

PubMed

Karagkounis, Georgios; Akyuz, Muhammet; Guerron, Alfredo Daniel; Yazici, Pinar; Aucejo, Federico N; Quintini, Cristiano; Miller, Charles M; Vogt, David P; Fung, John J; Berber, Eren

2016-10-01

Our aim was to compare the perioperative and oncologic outcomes of open liver resection and minimally invasive liver resection in the management of colorectal liver metastases. Patients who underwent minimally invasive liver resection for colorectal liver metastases between January 2006 and June 2015 at a single center were identified and matched by extent of resection to consecutive open liver resection patients from the same period. Clinicopathologic characteristics, perioperative data, recurrence, and survival outcomes were collected and analyzed based on intention-to-treat. Sixty-five patients underwent minimally invasive liver resection during this period and were matched to 65 consecutive open liver resection patients, with similar baseline demographic, tumor, and chemotherapy parameters. Conversion to open occurred in 5 (7.7%) minimally invasive liver resection patients. R0 resection rates and operative times were comparable, but the estimated blood loss was less in the minimally invasive liver resection group (median 200 mL vs 400 mL, P < .001), as were perioperative transfusion rates (4.6% vs 15.4%, P = .04). The duration of stay was shorter after minimally invasive liver resection (median 4 days vs 6 days, P < .001), while major and minor complication rates were similar and no perioperative mortality was recorded. At a median follow-up of 28 months, there was no difference regarding disease-free (P = .90) or overall survival (P = .37). In selected patients with colorectal liver metastases, minimally invasive liver resection resulted in similar oncologic outcomes, with decreased blood loss and shorter duration of stay compared to patients who underwent open liver resection. Copyright © 2016 Elsevier Inc. All rights reserved.

Orthotopic model of canine osteosarcoma in athymic rats for evaluation of stereotactic radiotherapy.

PubMed

Schwartz, Anthony L; Custis, James T; Harmon, Joseph F; Powers, Barbara E; Chubb, Laura S; LaRue, Susan M; Ehrhart, Nicole P; Ryan, Stewart D

2013-03-01

To develop an orthotopic model of canine osteosarcoma in athymic rats as a model for evaluating the effects of stereotactic radiotherapy (SRT) on osteosarcoma cells. 26 athymic nude rats. 3 experiments were performed. In the first 2 experiments, rats were injected with 1 × 10(6) Abrams canine osteosarcoma cells into the proximal aspect of the tibia (n = 12) or distal aspect of the femur (6). Tumor engraftment and progression were monitored weekly via radiography, luciferase imaging, and measurement of urine pyridinoline concentration for 5 weeks and histologic evaluation after euthanasia. In the third experiment, 8 rats underwent canine osteosarcoma cell injection into the distal aspect of the femur and SRT was administered to the affected area in three 12-Gy fractions delivered on consecutive days (total radiation dose, 36 Gy). Percentage tumor necrosis and urinary pyridinoline concentrations were used to assess local tumor control. The short-term effect of SRT on skin was also evaluated. Tumors developed in 10 of 12 tibial sites and all 14 femoral sites. Administration of SRT to rats with femoral osteosarcoma was feasible and successful. Mean tumor necrosis of 95% was achieved histologically, and minimal adverse skin effects were observed. The orthotopic model of canine osteosarcoma in rats developed in this study was suitable for evaluating the effects of local tumor control and can be used in future studies to evaluate optimization of SRT duration, dose, and fractionation schemes. The model could also allow evaluation of other treatments in combination with SRT, such as chemotherapy or bisphosphonate, radioprotectant, or parathyroid hormone treatment.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.

PubMed

Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

2014-10-14

To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

PubMed

Xie, Yirui; Chen, Huazhong; Zhu, Biao; Qin, Nan; Chen, Yunbo; Li, Zhengfeng; Deng, Min; Jiang, Haiyin; Xu, Xiangfei; Yang, Jiezuan; Ruan, Bing; Li, Lanjuan

2014-11-01

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-β were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-β and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.

Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) liver imaging: Potential application in liver transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodle, E.S.; Vera, D.R.; Ward, R.E.

1984-01-01

Tc-NGA is a hepatocyte receptor-specific imaging agent whose uptake by the liver has been shown to be dependent upon blood flow and receptor concentration. The combination of anatomic and physiologic information obtained with Tc-NGA may provide a new tool for studying hepatic function in liver transplant recipients. To evaluate the potential role of Tc-NGA in liver transplant recipients, studies were performed in four groups of pigs: controls (n=18); common bile duct (CBD) ligation (n=8); orthotopic liver transplant (n=9); and acute hepatic artery ligation (n=1). Serial studies performed in two animals with CBD ligation demonstrated normal imaging anatomy with minor changesmore » in the hepatic time-activity curves when compared to control studies. Studies in liver-transplanted animals showed significant changes in the hepatic time-activity curves during acute rejection and in preservation-related ischemic injury. Tc-NGA also demonstrated focal areas of hepatic infarction in a hepatic allograft within 24 hours of transplantation. The hepatic artery ligation study showed massive changes in the hepatic time-activity curve within two hours after ligation, with a diffuse decrease in hepatic activity. These results indicate that: (1) extrahepatic biliary tract obstruction causes only minor changes in Tc-NGA uptake; (2) Tc-NGA uptake by the liver is very sensitive to acute hepatic ischemia; (3) Tc-NGA may indicate the presence of preservation damage in the early postoperative period; and (4) Tc-NGA hepatic time-activity curves demonstrate significant changes during acute rejection.« less

Economic burden of cancer among patients with surgical resections of the lung, rectum, liver and uterus: results from a US hospital database claims analysis.

PubMed

Kalsekar, Iftekhar; Hsiao, Chia-Wen; Cheng, Hang; Yadalam, Sashi; Chen, Brian Po-Han; Goldstein, Laura; Yoo, Andrew

2017-12-01

To determine hospital resource utilization, associated costs and the risk of complications during hospitalization for four types of surgical resections and to estimate the incremental burden among patients with cancer compared to those without cancer. Patients (≥18 years old) were identified from the Premier Research Database of US hospitals if they had any of the following types of elective surgical resections between 1/2008 and 12/2014: lung lobectomy, lower anterior resection of the rectum (LAR), liver wedge resection, or total hysterectomy. Cancer status was determined based on ICD-9-CM diagnosis codes. Operating room time (ORT), length of stay (LOS), and total hospital costs, as well as frequency of bleeding and infections during hospitalization were evaluated. The impact of cancer status on outcomes (from a hospital perspective) was evaluated using multivariable generalized estimating equation models; analyses were conducted separately for each resection type. Among the identified patients who underwent surgical resection, 23 858 (87.9% with cancer) underwent lung lobectomy, 13 522 (63.8% with cancer) underwent LAR, 2916 (30.0% with cancer) underwent liver wedge resection and 225 075 (11.3% with cancer) underwent total hysterectomy. After adjusting for patient, procedural, and hospital characteristics, mean ORT, LOS, and hospital cost were statistically higher by 3.2%, 8.2%, and 9.2%, respectively for patients with cancer vs. no cancer who underwent lung lobectomy; statistically higher by 6.9%, 9.4%, and 9.6%, respectively for patients with cancer vs. no cancer who underwent LAR; statistically higher by 4.9%, 14.8%, and 15.7%, respectively for patients with cancer vs. no cancer who underwent liver wedge resection; and statistically higher by 16.0%, 27.4%, and 31.3%, respectively for patients with cancer vs. no cancer who underwent total hysterectomy. Among patients who underwent each type of resection, risks for bleeding and infection were generally higher among patients with cancer as compared to those without cancer. In this analysis, we found that patients who underwent lung lobectomy, lower anterior resection of the rectum (LAR), liver wedge resection or total hysterectomy for a cancer indication have significantly increased hospital resource utilization compared to these same surgeries for benign indications.

[A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

PubMed

Komiyama, Sosuke; Izumiya, Yasuhito; Kimura, Yu; Nakashima, Shingo; Kin, Syuichi; Kawakami, Sadao

2018-03-01

A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

Biodistribution and Pharmacokinetic Analysis of Combination Lonidamine and Paclitaxel Delivery in an Orthotopic Animal Model of Multi-drug Resistant Breast Cancer Using EGFR-Targeted Polymeric Nanoparticles

PubMed Central

Milane, Lara; Duan, Zhen-feng; Amiji, Mansoor

2011-01-01

The aim of this study was to assess the biodistribution and pharmacokinetics of epidermal growth factor receptor (EGFR)-targeted polymer blend nanoparticles loaded with the anticancer drugs lonidamine and paclitaxel. Plasma, tumor, and tissue distribution profiles were quantified in an orthotopic animal model of multi-drug resistant (MDR) breast cancer and were compared to treatment with non-targeted nanoparticles and to treatment with drug solution. Poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/EGFR targeting peptide (PLGA/PEG/EFGR peptide) construct was synthesized for incorporation in poly(ε-caprolactone) (PCL) particles to achieve active EGFR targeting. An isocratic HPLC method was developed to quantify lonidamine and paclitaxel in mice plasma, tumors, and vital organs. The targeted nanoparticles demonstrated superior pharmacokinetic profile relative to drug solution and non-targeted nanoparticles, particularly for lonidamine delivery. The first target site of accumulation is the liver, followed by the kidneys, and then the tumor mass; maximal tumor accumulation occurs at 3 hours post-administration. Lonidamine/paclitaxel combination therapy administered via EGFR-targeted polymer blend nanocarriers may become a viable platform for the future treatment of MDR cancer. PMID:21220050

The safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in the treatment of orthotopic liver transplant recipients with recurrent hepatitis C: real-world data.

PubMed

Pyrsopoulos, Nikolaos; Trilianos, Panagiotis; Lingiah, Vivek A; Fung, Phoenix; Punnoose, Merlin

2018-07-01

Recurrent hepatitis C (RHC) in orthotopic liver transplantation (OLT) population is associated with accelerated rates of fibrosis, low efficacy and decreased tolerability with traditional therapies. The aim of this study was to evaluate the safety and efficacy of ledipasvir/sofosbuvir (LED/SOF) with or without ribavirin (RBV) in OLT patients with RHC. Patients at least 3 months post-OLT and with documented RHC were treated with LED/SOF with or without RBV for either 12 or 24 weeks. End-of-treatment and sustained virological response 12 weeks after the completion of treatment were documented. Patients were closely monitored for treatment-related adverse effects and the potential need for adjustment in their immunosuppression. Seventy-one patients were included in the study. Median age was 62 years. Median time from OLT was 55 months. Twenty-six (36.6%) patients were treatment-naive and 45 (63.4%) had previously failed interferon-based therapies. The majority of patients (57.7%) had stage F0-F2 fibrosis. Sixty-seven (94.3%) patients completed 12 weeks of LED/SOF with RBV, three patients completed 12 or 24 weeks of LED/SOF without RBV, and one patient completed only 8 weeks of LED/SOF without RBV owing to severe allograft dysfunction. Sustained virological response was near universal in our cohort (98.5%) regardless of genotype, fibrosis stage, and regimen or treatment duration. Most commonly reported side effects were malaise and gastrointestinal upset. No patient required adjustment in immunosuppression and no episodes of rejection were documented during treatment. The combination of LED/SOF with RBV for 12 weeks or LED/SOF for 24 weeks is very effective and safe in treating OLT recipients with RHC.

Total donor ischemic time: relationship to early hemodynamics and intensive care morbidity in pediatric cardiac transplant recipients.

PubMed

Rodrigues, Warren; Carr, Michelle; Ridout, Deborah; Carter, Katherine; Hulme, Sara Louise; Simmonds, Jacob; Elliott, Martin; Hoskote, Aparna; Burch, Michael; Brown, Kate L

2011-11-01

Single-center studies have failed to link modest increases in total donor ischemic time to mortality after pediatric orthotopic heart transplant. We aimed to investigate whether prolonged total donor ischemic time is linked to pediatric intensive care morbidity after orthotopic heart transplant. Retrospective cohort review. Tertiary pediatric transplant center in the United Kingdom. Ninety-three pediatric orthotopic heart transplants between 2002 and 2006. Total donor ischemic time was investigated for association with early post-orthotopic heart transplant hemodynamics and intensive care unit morbidities. Of 43 males and 50 females with median age 7.2 (interquartile range 2.2, 13.0) yrs, 62 (68%) had dilated cardiomyopathy, 20 (22%) had congenital heart disease, and nine (10%) had restrictive cardiomyopathy. The mean total donor ischemic time was 225.9 (sd 65.6) mins. In the first 24 hrs after orthotopic heart transplant, age-adjusted mean arterial blood pressure increased (p < .001), mean pulmonary arterial pressure fell (p = .012), but central venous pressure (p = .58) and left atrial pressure (p = .20) were unchanged. After adjustment for age, primary diagnosis, pre-orthotopic heart transplant mechanical support, and marginal donor factors, longer total donor ischemic time was significantly associated with lower mean arterial blood pressure (p < .001) in the first 24 hrs after orthotopic heart transplant, longer post-orthotopic heart transplant mechanical ventilation (p = .03), longer post-orthotopic heart transplant stay in the intensive care unit (p = .004), and longer post-orthotopic heart transplant stay in hospital (p = .02). Total donor ischemic time was not related to levels of mean pulmonary arterial pressure (p = .62), left atrial pressure (p = .38), or central venous pressure (p = .76) early after orthotopic heart transplant. Prolonged total donor ischemic time has an adverse effect on the donor organ, contributing to lower mean arterial blood pressure, as well as more prolonged ventilation and intensive care unit and hospital stays post-orthotopic heart transplant, reflecting increased morbidity.

Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

PubMed

Hara, Y; Ogata, Y; Shirouzu, K

2000-12-01

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

Intestinal microbiota and innate immunity-related gene alteration in cirrhotic rats with liver transplantation.

PubMed

Xie, Y R; Liu, S L; Liu, X; Luo, Z B; Zhu, B; Li, Z F; Li, L J; He, Y; Jiang, L; Li, H; Ruan, B

2011-12-01

The present study investigated the alteration of intestinal microbiota, innate immunity-related genes, and bacterial translocation in rats with cirrhosis and liver transplantation. Specific pathogen-free Sprague-Dawley rats were randomized into 4 groups: (1) normal controls (N); (2) liver cirrhosis (LC); (3) normal control groups with liver transplantation (LTN); and (4) liver cirrhosis with liver transplantation (LTC). We examined plasma endotoxin, bacterial tacslocation, denaturing gradient gel electrophoresis (DGGE) profile of intestinal mucosa-associated bacteria, abundance of key bacterial populations, and expression of innate immunity-related gene. The LTC and LC group, showed higher endotoxin levels (1.08±0.73 EU/mL and 0.74±0.70 EU/mL, respectively) than the N group (0.27±0.13 EU/mL; P<.05). the incidence of bacterial translocation (BT) to liver and mesenteric lymph nodes (MLN), and the number of total bacteria were increased significantly in the LTC and LC groups compared with the N group (P<.05). The counts of Lactobacilli and Bacteroides were lower, whereas Enterobacteria were higher in the LC than the N group (P<.05). Mucins (MUC2, MUC3) and Toll-like receptors (TLR2, TLR4) messenger RNA (mRNA) expression were significantly higher in the LC and LTC groups than the N group (P<.05). The marked difference between the groups in the overall structure of the bacterial community was also generated by DGGE profiles. Liver cirrhosis disturbs intestinal microbiota and innate immunity-related genes, which contributes to endotoxemia and bacterial translocation. These had not completely recovered in cirrhotic rats until 1 month after orthotopic liver transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.

Hepcidin expression does not rescue the iron-poor phenotype of Kupffer cells in Hfe-null mice after liver transplantation.

PubMed

Garuti, Cinzia; Tian, Yinghua; Montosi, Giuliana; Sabelli, Manuela; Corradini, Elena; Graf, Rolf; Ventura, Paolo; Vegetti, Alberto; Clavien, Pierre-Alain; Pietrangelo, Antonello

2010-07-01

Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver-the source of the iron regulatory hormone hepcidin-in pathogenesis in mice. We exchanged livers between Hfe wild-type (+/+) and Hfe null (-/-) mice by orthotopic liver transplantation (OLT) and assessed histopathology, serum and tissue iron parameters, and hepatic hepcidin messenger RNA expression. At 6-8 months after OLT, Hfe(-/-) mice that received Hfe(-/-) livers maintained the hemochromatosis phenotype: iron accumulation in hepatocytes but not Kupffer cells (KC), increased transferrin levels, and low levels of iron in the spleen. Hfe(+/+) mice that received Hfe(-/-) livers had increased levels of iron in serum and liver and low levels of iron in spleen. However, they did not develop the iron-poor KCs that characterize hemochromatosis: KCs appeared iron rich, although hepatic hepcidin expression was low. Transplantation of Hfe(+/+) livers into Hfe(-/-) mice prevented hepatic iron accumulation but did not return spleen and plasma levels of iron to normal; KCs still appeared to be iron poor, despite normal hepcidin expression. In Hfe(-/-) mice, transplantation of livers from Hfe(+/+) mice reversed the iron-loading phenotype associated with hemochromatosis (regardless of Hfe expression in intestine). However, KCs still had low levels of iron that were not affected by hepatic hepcidin expression. These findings indicate an independent, iron-modifying effect of HFE in KCs. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ultrasound-guided direct delivery of 3-bromopyruvate blocks tumor progression in an orthotopic mouse model of human pancreatic cancer.

PubMed

Ota, Shinichi; Geschwind, Jean-Francois H; Buijs, Manon; Wijlemans, Joost W; Kwak, Byung Kook; Ganapathy-Kanniappan, Shanmugasundaram

2013-06-01

Studies in animal models of cancer have demonstrated that targeting tumor metabolism can be an effective anticancer strategy. Previously, we showed that inhibition of glucose metabolism by the pyruvate analog, 3-bromopyruvate (3-BrPA), induces anticancer effects both in vitro and in vivo. We have also documented that intratumoral delivery of 3-BrPA affects tumor growth in a subcutaneous tumor model of human liver cancer. However, the efficacy of such an approach in a clinically relevant orthotopic tumor model has not been reported. Here, we investigated the feasibility of ultrasound (US) image-guided delivery of 3-BrPA in an orthotopic mouse model of human pancreatic cancer and evaluated its therapeutic efficacy. In vitro, treatment of Panc-1 cells with 3-BrPA resulted in a dose-dependent decrease in cell viability. The loss of viability correlated with a dose-dependent decrease in the intracellular ATP level and lactate production confirming that disruption of energy metabolism underlies these 3-BrPA-mediated effects. In vivo, US-guided delivery of 3-BrPA was feasible and effective as demonstrated by a marked decrease in tumor size on imaging. Further, the antitumor effect was confirmed by (1) a decrease in the proliferative potential by Ki-67 immunohistochemical staining and (2) the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphospate nick end labeling staining. We therefore demonstrate the technical feasibility of US-guided intratumoral injection of 3-BrPA in a mouse model of human pancreatic cancer as well as its therapeutic efficacy. Our data suggest that this new therapeutic approach consisting of a direct intratumoral injection of antiglycolytic agents may represent an exciting opportunity to treat patients with pancreas cancer.

Percutaneous Transhepatic Portography for the Treatment of Early Portal Vein Thrombosis After Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adani, Gian Luigi, E-mail: adanigl@hotmail.com; Baccarani, Umberto; Risaliti, Andrea

2007-11-15

We treated three cases of early portal vein thrombosis (PVT) by minimally invasive percutaneous transhepatic portography. All patients developed PVT within 30 days of major hepatic surgery (one case each of orthotopic liver transplantation, splenectomy in a previous liver transplant recipient, and right extended hepatectomy with resection and reconstruction of the left branch of the portal vein for tumor infiltration). In all cases minimally invasive percutaneous transhepatic portography was adopted to treat this complication by mechanical fragmentation and pharmacological lysis of the thrombus. A vascular stent was also positioned in the two cases in which the thrombosis was related tomore » a surgical technical problem. Mechanical fragmentation of the thrombus with contemporaneous local urokinase administration resulted in complete removal of the clot and allowed restoration of normal blood flow to the liver after a median follow-up of 37 months. PVT is an uncommon but severe complication after major surgery or liver transplantation. Surgical thrombectomy, with or without reconstruction of the portal vein, and retransplantation are characterized by important surgical morbidity and mortality. Based on our experience, minimally invasive percutaneous transhepatic portography should be considered an option toward successful recanalization of early PVT after major liver surgery including transplantation. Balloon dilatation and placement of a vascular stent could help to decrease the risk of recurrent thrombosis when a defective surgical technique is the reason for the thrombosis.« less

Bioartificial liver assist devices in support of patients with liver failure.

PubMed

Patzer II, John F; Lopez, Roberto C; Zhu, Yue; Wang, Zi-Fa; Mazariegos, George V; Fung, John J

2002-02-01

Bioartificial liver assist devices (BALs) offer an opportunity for critical care physicians and transplant surgeons to stabilize patients prior to orthotopic liver transplantation. Such devices may also act as a bridge to transplant, providing liver support to patients awaiting transplant, or as support for patients post living-related donor transplant. Four BAL devices that rely on hepatocytes cultured in hollow fiber membrane cartridges (Circe Biomedical HepatAssist(r), Vitagen ELADTM, Gerlach BELS, and Excorp Medical BLSS) are currently in various stages of clinical evaluation. Comparison of the four devices shows that several unique approaches based upon the same overall system architecture are possible. Preliminary results of the Excorp Medical BLSS Phase I safety evaluation at the University of Pittsburgh, after treating four patients (F, 41, acetominophen-induced, two support periods; M, 50, Wilson's disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy-induced, one support period, are presented. All patients presented with hypoglycemia and transient hypotension at the start of extracorporeal perfusion. Hypoglycemia was treated by IV dextrose and the transient hypotension responded positively to IV fluid bolus. Heparin anticoagulation was used only in the second patient. No serious or adverse events were noted in the four patients. Moderate Biochemical response to support was noted in all patients. More complete characterization of the safety of the BLSS requires completion of the Phase I safety evaluation.

Lack of Clinical Relevance of ANA and ASMA Positivity in Patients with Liver Transplantation without a History of Autoimmune Diseases.

PubMed

Pellegrini, Lucienne; Parrilli, Gianpaolo; Santonicola, Antonella; Cinquanta, Luigi; Caputo, Cesare; Ciacci, Carolina; Zingone, Fabiana

2017-01-01

The relevance of isolated autoimmunity elevation in orthotopic liver transplantation (OLT) patients is unknown. Our aim was to analyse how serum autoantibodies change in time and to evaluate their clinical relevance in OLT patients. Patients were invited to provide samples to evaluate ANA, AMA, ASMA, and LKM at the time of enrolment ( T 0), after 6 months ( T 6), and after 12 months ( T 12). We included 114 patients in the study (76% males, median age 62.5 years), finding isolated elevation of at least one serum antibody in up to 80% of them. We described fluctuating positive autoantibodies in the one year of observation, with only 45.6% of patients positive for ANA and less than 2% positive for ASMA, at all three times. Isolated elevation of tissue antibodies was not related to gender, age, HCC at transplant, early rejection, cause of transplantation, immunotherapy taken, and age at the time of the study. We did not detect a higher prevalence of positive autoimmunity in patients with signs of liver injury. ANA and ASMA evaluation in patients with liver transplantation and no history of autoimmune disease has no clinical relevance, since it varies in time and is not related to any risk factors or liver injury. Routine autoimmunity evaluation should be avoided.

Lack of Clinical Relevance of ANA and ASMA Positivity in Patients with Liver Transplantation without a History of Autoimmune Diseases

PubMed Central

Pellegrini, Lucienne; Parrilli, Gianpaolo; Santonicola, Antonella; Cinquanta, Luigi; Caputo, Cesare

2017-01-01

The relevance of isolated autoimmunity elevation in orthotopic liver transplantation (OLT) patients is unknown. Our aim was to analyse how serum autoantibodies change in time and to evaluate their clinical relevance in OLT patients. Patients were invited to provide samples to evaluate ANA, AMA, ASMA, and LKM at the time of enrolment (T0), after 6 months (T6), and after 12 months (T12). We included 114 patients in the study (76% males, median age 62.5 years), finding isolated elevation of at least one serum antibody in up to 80% of them. We described fluctuating positive autoantibodies in the one year of observation, with only 45.6% of patients positive for ANA and less than 2% positive for ASMA, at all three times. Isolated elevation of tissue antibodies was not related to gender, age, HCC at transplant, early rejection, cause of transplantation, immunotherapy taken, and age at the time of the study. We did not detect a higher prevalence of positive autoimmunity in patients with signs of liver injury. ANA and ASMA evaluation in patients with liver transplantation and no history of autoimmune disease has no clinical relevance, since it varies in time and is not related to any risk factors or liver injury. Routine autoimmunity evaluation should be avoided. PMID:28337446

The Development of Stem Cell-Based Treatment for Liver Failure.

PubMed

Zhu, Tiantian; Li, Yuwen; Guo, Yusheng; Zhu, Chuanlong

2017-01-01

Liver failure is a devastating clinical syndrome with a persistently mortality rate despite advanced care. Orthotopic liver transplantation protected patients from hepatic failure. Yet, limitations including postoperative complications, high costs, and shortages of donor organs defect its application. The development of stem cell therapy complements the deficiencies of liver transplantation, due to the inherent ability of stem cells to proliferate and differentiate. Understand the source of stem cells, as well as the advantages and disadvantages of stem cell therapy. Based on published papers, we discussed the cell sources and therapeutic effect of stem cells. We also summarized the pros and cons, as well as optimization of stem cell-based treatment. Finally outlook future prospects of stem cell therapy. Stem cells may be harvested from a variety of human tissues, and then used to promote the convalescence of hepatocellular function. The emergence of the co-cultured system, tissueengineered technology and genetic modfication has further enhanced the functionality of stem cells. However, the tumorigenicity, the low survival rate and the scarcity of long-term treatment effect are obstacles for the further development of stem cell therapy. In this review, we highlight current research findings and present the future prospects in the area of stem cell-based treatment for liver failure. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

PubMed

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to combat liver disease in the human clinic.

Hepatic Tissue Environment in NEMO-Deficient Mice Critically Regulates Positive Selection of Donor Cells after Hepatocyte Transplantation

PubMed Central

Kaldenbach, Michaela; Cubero, Francisco Javier; Erschfeld, Stephanie; Liedtke, Christian; Trautwein, Christian; Streetz, Konrad

2014-01-01

Background Hepatocyte transplantation (HT) is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF)-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. Methods Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT) and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa). Results Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. Conclusion This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and opens a new door for the applicability of this technique to combat liver disease in the human clinic. PMID:24979756

Presence of intrahepatic (total and ccc) HBV DNA is not predictive of HBV recurrence after liver transplantation.

PubMed

Hussain, Munira; Soldevila-Pico, Consuelo; Emre, Sukru; Luketic, Velimir; Lok, Anna S F

2007-08-01

Previous studies reported that hepatitis B virus (HBV) deoxyribonucleic acid (DNA) can be detected in livers of patients who received transplants for hepatitis B despite the absence of serological markers of HBV recurrence. Quantification of HBV DNA was not performed and presence of covalently closed circular (ccc) DNA was not analyzed in most studies. We aimed to quantify total and ccc HBV DNA in explant liver and post-orthotopic liver transplantation (OLT) biopsies and to correlate the values with HBV recurrence post-OLT. Frozen liver tissue from 34 patients (9 with explant liver only, 9 with explant liver and post-OLT liver biopsies, and 16 with post-OLT biopsies only) in the National Institutes of Health HBV-OLT study was examined using real-time polymerase chain reaction (PCR). Among the 18 patients with explant liver, 7 were hepatitis B e antigen (HBeAg)-positive, 8 had detectable serum HBV DNA, and 10 received antiviral therapy prior to OLT. Total and ccc HBV DNA was detected in explant livers of 17 and 16 patients, respectively. Of the 10 patients who received antiviral therapy pre-OLT, serum HBV DNA was undetectable in 8 at transplantation but 7 had detectable total and ccc HBV DNA in their explant liver. Of the 25 patients with post-OLT biopsies, total HBV DNA was detected in 83% and ccc DNA in 17% of 47 biopsies, although only 2 patients had HBV recurrence. In conclusion, total and ccc HBV DNA could be detected in explant livers of most patients despite antiviral therapy pre-OLT. Total but not ccc HBV DNA could be detected in post-OLT liver biopsies of most patients despite undetectable serum HBV DNA and hepatitis B surface antigen (HBsAg). Our findings suggest that occult HBV reinfection occurs in most HBV patients after OLT and continued administration of appropriate prophylactic therapy is important in preventing overt HBV recurrence. Copyright (c) 2007 AASLD.

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative.

PubMed

Sun, Baoguo; Meng, Jun; Xiang, Ting; Zhang, Lei; Deng, Liuxiang; Chen, Yan; Luo, Haoxuan; Yang, Zhangbin; Chen, Zexiong; Zhang, Shijun

2016-03-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire.

Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative

PubMed Central

SUN, BAOGUO; MENG, JUN; XIANG, TING; ZHANG, LEI; DENG, LIUXIANG; CHEN, YAN; LUO, HAOXUAN; YANG, ZHANGBIN; CHEN, ZEXIONG; ZHANG, SHIJUN

2016-01-01

The aim of this study was to investigate the effects of the Chinese herbal formulation Jianpijiedu (JPJD) in a rat model of orthotopic hepatocellular carcinoma (OHC). The tumor-bearing rats underwent food restriction combined with laxative (FRL) treatment in order to model the nutritional and digestive symptoms of patients with hepatocellular carcinoma. In addition, the study aimed to elucidate the effect of JPJD on the T cell receptor Vβ-chain complementarity-determining region 3 (TCRVβCDR3) repertoire and the underlying mechanism. The FRL rat model was established by alternate-day food restriction and the oral administration of Glauber's salt (sodium sulfate), based on which the OHC model was then established. Subsequently, the FRL-OHC induced animals received JPJD or thymopentin-5 (TP5) for 17 days. Differences in the TCRVβCDR3 repertoire in the rat thymus, liver and hepatocellular carcinoma tissues were analyzed by polymerase chain reaction. Compared with the FRL-OHC model animals without any treatment, those treated with JPJD exhibited significantly inhibited hepatocellular carcinoma growth (P<0.05), reduced weight loss (P<0.01) and stable visceral indices (P<0.05). Furthermore, the JPJD treatment appeared to improve Simpsons diversity index (Ds) values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in the thymus, liver and hepatocellular carcinoma tissues. However, no anti-hepatoma effects were evident in the rats treated with TP5. In addition, TP5 increased the Ds values and the quasi-Gaussian distribution rate of the TCRVβCDR3 repertoire in hepatocellular carcinoma tissues compared with those in the JPJD-treated group. The anti-hepatoma effects of JPJD in FRL-OHC-induced animals may be due to the promotion of the Ds values of the TCRVβCDR3 repertoire. PMID:26997998

Clinical values of AFP, GPC3 mRNA in peripheral blood for prediction of hepatocellular carcinoma recurrence following OLT: AFP, GPC3 mRNA for prediction of HCC.

PubMed

Wang, Yuliang; Shen, Zhongyang; Zhu, Zhijun; Han, Ruifa; Huai, Mingsheng

2011-03-01

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Annually, about 200,000 patients died of HCC in China. Liver transplantation (LT) holds great theoretical appeal in treating HCC. However, the high recurrence rate after transplantation is the most important limiting factor for long-term survival. To assess the value of alpha-fetoprotein (AFP) messenger RNA (mRNA), Glypican-3 (GPC3) mRNA-expressing cells in the peripheral blood (PB) for prediction of HCC recurrence following orthotopic liver transplantation (OLT). 29 patients with HCC who underwent OLT with a minimum clinical follow-up of 12 months were included in this retrospective study. We detected AFP mRNA, GPC3 mRNA-expressing cells in the PB by TaqMan real-time reverse transcriptase-polymerase chain reaction (RT-PCR), pre-, intra- and post-operatively. The early recurrence of patients was evaluated. 8 (28%), 15 (52%), and 9 (31%) patients had AFP mRNA detected pre-, intra-, and post-operatively, respectively. With 12 months of follow-up, HCC recurred in 7 (24%) patients. Univariate analysis revealed that positive pre- and post-operative AFP mRNA, TNM stage as well as vascular invasion were significant predictors for the HCC recurrence. Multivariate analysis revealed that being positive for AFP mRNA pre-operatively remained a significant risk factor for HCC recurrence after OLT. GPC3 mRNA was expressed in all PB samples. There was no significant difference in the expression levels of GPC3 mRNA between the HCC and control groups. There were no significant differences in GPC3 mRNA expression values between those patients with and without tumor recurrence. The pre-operative detection of circulating AFP mRNA-expressing cells could be a useful predictor for HCC recurrence following OLT. GPC3 mRNA-expressing cells in PB seem to have no diagnostic value.

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis

PubMed Central

Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L.; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J.; Rafii, Shahin; Ding, Bi-Sen

2017-01-01

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. Here, we show that targeting both the vascular niche and perivascular fibroblasts establishes “hospitable soil” to foster incorporation of “seed”, in this case the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NADPH Oxidase 4 (NOX4) synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs (HgfiΔEC/iΔEC) aberrantly upregulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially-inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in HgfiΔEC/iΔEC mice recapitulated the phenotype of human and mouse fibrotic livers and lungs. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. PMID:28855398

Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis

PubMed Central

Zhang, Zhiqiang; Li, Zhennan; Zou, Chen; Zhang, Jingjing; Zhu, Yi; Miao, Yi

2015-01-01

Background/aims: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis. Methodology: To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis). Results: The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). Conclusions: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies. PMID:26550120

Identification Of Inequalities In The Selection Of Liver Surgery For Colorectal Liver Metastases In Sweden.

PubMed

Norén, A; Sandström, P; Gunnarsdottir, K; Ardnor, B; Isaksson, B; Lindell, G; Rizell, M

2018-04-01

Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p < 0.0001). Patients with liver metastases from rectal cancer (p < 0.0001) and men more often underwent liver resection (p = 0.006). A difference was found between health-care regions for the frequency of liver surgery (p < 0.0001). Patients >70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the low referral rate. The proximity to a hepatobiliary unit seems important to enhance the patient's chances of being offered liver surgery.

Clinical experience with the N-shaped ileal neobladder: assessment of complications, voiding patterns, and quality of life in our series of 58 patients.

PubMed

Joniau, S; Benijts, J; Van Kampen, M; De Waele, M; Ooms, J; Van Cleynenbreugel, B; Van Poppel, H

2005-05-01

The purpose of this retrospective study was to assess complications, voiding patterns, and quality of life in patients with an orthotopic bladder substitution, using an N-shaped ileal neobladder. Between May 1996 and December 2002, 58 patients (52 men and 6 women) underwent an orthotopic ileal neobladder reconstruction after radical cystectomy. The mean age was 47 for the female and 60 for the male patients. In all patients an N-shaped ileal pouch was constructed. This pouch has not yet been described in the literature before. All procedures were performed by the same surgeon (HVP) and the mean follow-up was 38 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), and as pouch-related and non-pouch-related. The patients took part in a pelvic floor re-education programme for as long as they were incontinent. All patients completed a retrospective Quality of Life questionnaire, based on the QLQ-C30 questionnaire, which was validated by the EORTC's Study Group on Quality of Life. In 38% of the patients, early complications occurred, whereas 48% had late complications. The most frequent early complications were diarrhea (24%) and pyelonephritis (9%). Diarrhea was again the most frequently mentioned non-pouch-related complication (19%). The most frequently observed pouch-related late complication was ileo-urethral stenosis. This occurred in five patients. All of these 5 patients were re-operated using a minimally invasive approach. Daytime continence was achieved in 95% of patients and nighttime continence in 66%. Hyper-continence with subsequent need for CISC was observed in 5 out of 6 women (83%) and 0 out of 52 men (0%). The retrospective QoL questionnaire learned that the impact of bladder removal and orthotopic bladder substitution has acceptable impact on patient's everyday life. Diarrhea was mentioned as being the most discomforting complication by most of the patients. We describe a modified orthotopic ileal neobladder: the ileal N-pouch. The functional results with this pouch are good. Complication rates and QoL are comparable with the larger series published by other authors, using different ileal neobladder reconstructions.

Correlations between A/H1N1 influenza and acute cellular rejection in liver transplantation patients.

PubMed

Stucchi, R S B; Boin, I F S F; Angerami, R Nogueira; Sinckoc, V; Sa, F Cesar; Seva-Pereira, T; Escanhoela, C A Fazzio

2010-12-01

Influenza is a common cause of respiratory infection in transplant recipients. It is expected that A/H1N1 influenza virus causes more severe disease in solid-organ recipients. Our goal was to describe two A/H1N1 infections that occurred after Orthotopic liver transplantation followed by acute allograft rejection episodes. From March 2009 to March 2010 we observe two liver transplant patients with symptoms suggestive of A/H1N1 infection. The diagnosis was out based on a temperature of 37.8°C (100°F) or higher and the presence of a cough or using materials from anasopharyngeal and oropharyngeal swabs a sore throat. The diagnosis was confirmed by viral RNA detection by real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR) using materials from nasopharyngeal and oropharyngeal swabs. We performed the RT-PCR assay for A/H1N1 detection in a liver biopsy from one patient. Both patients were treated with usual doses of oseltamivir (75 mg twice daily for 5 days). One patient developed acute bacterial sinusitis requiring antibiotic therapy. Thereafter the liver enzymes increased and transplant biopsies showed moderate-to-severe acute cellular rejection. They were treated with corticosteroids. The liver enzymes normalized after 3 months. A/H1N1 influenza can lead to a severe acute cellular rejection episode with corticosteroid resistant treatment in liver transplant patients. Transplant centers should be aware of a possible relationship between A/H1N1 infections and acute allograft rejection episodes. Copyright © 2010 Elsevier Inc. All rights reserved.

Aging promotes neoplastic disease through effects on the tissue microenvironment.

PubMed

Marongiu, Fabio; Serra, Maria Paola; Doratiotto, Silvia; Sini, Marcella; Fanti, Maura; Cadoni, Erika; Serra, Monica; Laconi, Ezio

2016-12-06

A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells. At 3 months post-Tx, the mean size of donor-derived clusters was 11±3 cells in young vs. 42±8 in old recipients. At 8 months post-Tx, no visible lesion were detected in any of 21 young recipients, while 17/18 animals transplanted at old age displayed hepatic nodules, including 7 large tumors. All tumors expressed the DPPIV marker enzyme, indicating that they originated from transplanted cells. Expression of senescence-associated β-galactosidase was common in liver of 18-month old animals, while it was a rare finding in young controls. Finally, both mRNA and IL6 protein were found to be increased in the liver of aged rats compared to young controls. These results are interpreted to indicate that the microenvironment of the aged liver promotes the growth of pre-neoplastic hepatocytes.

De-novo cholangiocarcinoma in native common bile duct remnant following OLT for primary sclerosing cholangitis.

PubMed

Landaverde, Carmen; Ng, Vivian; Sato, Alisa; Tabibian, James; Durazo, Francisco; Busuttil, Ronald

2009-01-01

Primary sclerosing cholangitis (PSC) is a chronic, progressive, inflammatory and obstructive disease of the intra- and extra-hepatic bile ducts of unknown etiology. Currently, orthotopic liver transplantation (OLT) is the only definitive treatment for PSC-related end-stage liver disease. However, PSC has been known to recur in the grafted liver. Roux-en-Y hepaticojejunostomy is more commonly performed than choledochocholedochostomy for PSC, although choledochocholedochostomy has been found to be safe and efficacious for PSC if the distal common bile duct is uninvolved at the time of OLT. Our case is unique in that it describes a patient who developed de-novo cholangiocarcinoma in the remnant portion of the native common bile duct six years after OLT with choledochocholedochostomy for PSC-associated end-stage liver disease without having PSC recurrence. In conclusion, our case report indicates that choledochocholedochostomy may not be desirable in PSC due to an increased risk of developing cholangiocarcinoma in the native common bile duct. This risk exists as well with a Roux-en-Y hepaticojejunostomy in the remaining intra-duodenal and intra-pancreatic biliary epithelium, although in theory to a lesser extent. Therefore, the risk of developing cholangiocarcinoma in the recipient common bile duct can only be completely eliminated by performing a Whipple procedure at the time of OLT.

Bariatric Surgery Is Gaining Ground as Treatment of Obesity After Heart Transplantation: Report of Two Cases.

PubMed

Tsamalaidze, Levan; Elli, Enrique F

2017-11-01

Experience with bariatric surgery in patients after orthotopic heart transplantation (OHT) is still limited. We performed a retrospective review of patients who underwent bariatric surgery after OHT from January 1, 2010 to December 31, 2016. Two post-OHT patients with BMI of 37.5 and 36.2 kg/m² underwent laparoscopic robotic-assisted Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy, respectively. Quality of life substantially improved for both patients. Bariatric surgery is safe and feasible in OHT patients, despite numerous risk factors. Careful selection of patients is required with proper preoperative management and overall care. Due to the complexity of treatment and perioperative care in this specific population, these operations should be done in high-volume centers with multidisciplinary teams composed of bariatric, cardiac transplant surgeons and critical care physicians. Bariatric surgery can be highly effective for treatment of obesity after OHT.

Risk of in-hospital complications after radical cystectomy for urinary bladder carcinoma: population-based follow-up study of 7608 patients

PubMed Central

Hemelrijck, Mieke; Thorstenson, Andreas; Smith, Philip; Adolfsson, Jan; Akre, Olof

2013-01-01

Objective To evaluate the risk of different in-hospital complications for patients undergoing a radical cystectomy (RC), as limited nationwide population data on short- and long-term complications after RC is available, despite it being the standard treatment for localised muscle-invasive urinary bladder cancer (UBC). Patients and Methods In all, 7608 persons underwent a RC after UBC diagnosis, as registered in the Swedish National Patient Register between 1964 and 2008. We estimated the frequency and incidences and calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards models. Results Urinary tract infection/septicaemia was the most common complication following radical cystectomy, with an incidence of 90.4 per 1,000 person years. There was a higher risk of urinary tract infection among patients who had a continent cutaneous reservoir (HR: 1.11 (0.94–1.30) or orthotopic neobladder 1.21 (1.05–1.39) than among those with ileal conduit. Similarly, continent cutaneous reservoir and orthotopic neobladder were associated with increased risks for wound and abdominal wall hernias, stones in the urinary tract, hydronephrosis and nephrostomy tube treatment, and kidney failure. In contrast, risk of bowel obstruction was lower among those with orthotopic neobladder than those with ileal conduit (HR: 0.64 (0.50–0.81)) and those with continent cutaneous reservoir (HR: 0.92 (0.73–1.16). Conclusions In-hospital complications after RC are numerous and continue to accumulate for many years after surgery, indicating the need for life-long follow-up of these patients. Comparison between different types of diversion should, however, be made with care because of potential confounding by indication. PMID:23906011

Orthotopic bladder substitution in men revisited: identification of continence predictors.

PubMed

Koraitim, M M; Atta, M A; Foda, M K

2006-11-01

We determined the impact of the functional characteristics of the neobladder and urethral sphincter on continence results, and determined the most significant predictors of continence. A total of 88 male patients 29 to 70 years old underwent orthotopic bladder substitution with tubularized ileocecal segment (40) and detubularized sigmoid (25) or ileum (23). Uroflowmetry, cystometry and urethral pressure profilometry were performed at 13 to 36 months (mean 19) postoperatively. The correlation between urinary continence and 28 urodynamic variables was assessed. Parameters that correlated significantly with continence were entered into a multivariate analysis using a logistic regression model to determine the most significant predictors of continence. Maximum urethral closure pressure was the only parameter that showed a statistically significant correlation with diurnal continence. Nocturnal continence had not only a statistically significant positive correlation with maximum urethral closure pressure, but also statistically significant negative correlations with maximum contraction amplitude, and baseline pressure at mid and maximum capacity. Three of these 4 parameters, including maximum urethral closure pressure, maximum contraction amplitude and baseline pressure at mid capacity, proved to be significant predictors of continence on multivariate analysis. While daytime continence is determined by maximum urethral closure pressure, during the night it is the net result of 2 forces that have about equal influence but in opposite directions, that is maximum urethral closure pressure vs maximum contraction amplitude plus baseline pressure at mid capacity. Two equations were derived from the logistic regression model to predict the probability of continence after orthotopic bladder substitution, including Z1 (diurnal) = 0.605 + 0.0085 maximum urethral closure pressure and Z2 (nocturnal) = 0.841 + 0.01 [maximum urethral closure pressure - (maximum contraction amplitude + baseline pressure at mid capacity)].

Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation.

PubMed

Nemes, Balázs; Gámán, György; Polak, Wojciech G; Gelley, Fanni; Hara, Takanobu; Ono, Shinichiro; Baimakhanov, Zhassulan; Piros, Laszlo; Eguchi, Susumu

2016-07-01

Extended-criteria donors (ECDs) have an impact on early allograft dysfunction (EAD), biliary complications, relapse of hepatitis C virus (HCV), and survivals. Early allograft dysfunction was frequently seen in grafts with moderate and severe steatosis. Donors after cardiac death (DCD) have been associated with higher rates of graft failure and biliary complications compared to donors after brain death. Extended warm ischemia, reperfusion injury and endothelial activation trigger a cascade, leading to microvascular thrombosis, resulting in biliary necrosis, cholangitis, and graft failure. The risk of HCV recurrence increased by donor age, and associated with using moderately and severely steatotic grafts. With the administration of protease inhibitors sustained virological response was achieved in majority of the patients. Donor risk index and EC donor scores (DS) are reported to be useful, to assess the outcome. The 1-year survival rates were 87% and 40% respectively, for donors with a DS of 0 and 3. Graft survival was excellent up to a DS of 2, however a DS >2 should be avoided in higher-risk recipients. The 1, 3 and 5-year survival of DCD recipients was comparable to optimal donors. However ECDs had minor survival means of 85%, 78.6%, and 72.3%. The graft survival of split liver transplantation (SLT) was comparable to that of whole liver orthotopic liver transplantation. SLT was not regarded as an ECD factor in the MELD era any more. Full-right-full-left split liver transplantation has a significant advantage to extend the high quality donor pool. Hypothermic oxygenated machine perfusion can be applied clinically in DCD liver grafts. Feasibility and safety were confirmed. Reperfusion injury was also rare in machine perfused DCD livers.

Multidisciplinary management of hepatoblastoma in children: Experience from a developing country.

PubMed

Shanmugam, Naresh; Scott, Julius Xavier; Kumar, Vimal; Vij, Mukul; Ramachandran, Priya; Narasimhan, Gomathy; Reddy, Mettu Srinivas; Kota, Venugopal; Munirathnam, Deenadayalan; Kelgeri, Chayarani; Sundaram, Karthick; Rela, Mohamed

2017-03-01

Advances in chemotherapy, liver resection techniques, and pediatric liver transplantation have vastly improved survival in children with hepatoblastoma (HB). These are best managed by a multidisciplinary team (MDT) in a setting where all treatment options are available. Until recently, this was difficult to achieve in India. All children (<16 years) with HB treated in a pediatric liver surgery and transplantation unit between January 2011 and July 2016 were reviewed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, and outcomes were extracted from a prospectively managed database. Thirty children were treated for HB during the study period. Nine children were PRETEXT 4, 7 were PRETEXT 3, 13 were PRETEXT 2, and 1 was PRETEXT 1 (where PRETEXT is pretreatment extension). All children received a neoadjuvant chemotherapy before surgery followed by an adjuvant chemotherapy. Nineteen children had complete resection, while six underwent primary living donor liver transplantation. There were six mortalities including five children who poorly responded to chemotherapy with progressive tumor extension. At a median follow-up of 30 months, two children who underwent resection and one child who underwent liver transplant had disease recurrence. Improved outcomes can be achieved in children with HB even in countries with limited resources when they are managed by MDTs with expertise in pediatric oncology, liver resection, and liver transplantation. © 2016 Wiley Periodicals, Inc.

Laparoscopic kidney orthotopic transplant: preclinical study in the pig model.

PubMed

He, B; Musk, G C; Mou, L; Waneck, G L; Delriviere, L

2013-06-01

Laparoscopic surgery has rapidly expanded in clinical practice replacing conventional open surgery over the last three decades. Laparoscopic donor nephrectomy has been favored due to its multiple benefits. The aim of this study was to explore the safety and feasibility of kidney transplantation by a laparoscopic technique in a pig model. The study was approved by the university animal ethics committee. Eight female pigs (Sus Scrofra, weighing 45-50 kg) were divided into 2 groups: group I included 4 animals that underwent laparoscopic kidney orthotopic transplantation on the left side. The right kidney was remained functional in situ. The pigs recovered and were observed for 1 week. In the 4 hosts group II pigs underwent a laparoscopic kidney transplantation on the left side. With simultaneous clipping of the right ureter. After recovery, the pigs were observed for 4 weeks. A laparotomy for examination was performed prior to euthanasia. All 4 group I pigs survived for 1 week. The laparotomy showed normal graft perfusion with wall patent renal artery and vein as well as satisfactory urine output upon transection of ureter in 3 hosts. Renal artery stenosis occurred in one pig. In The Immediate kidney graft function was achieved in 3 group II pigs. The fourth died following extubation due to laryngospasm despite a functional graft. The average creatinine levels were 195.5 μmol/L on day 3; 224.5 μmol/L at week 1; 127 μmol/L at week 2; 182.7 umol/L at week 3; and 154.7 umol/L at week 4. Laparoscopic kidney transplantation was feasible and safe in a pig model with immediate graft function. This study will provide further evidence to support application of laparoscopic technique to human kidney transplant. Copyright © 2013 Elsevier Inc. All rights reserved.

Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria.

PubMed

Meirow, Dror; Ra'anani, Hila; Shapira, Moran; Brenghausen, Masha; Derech Chaim, Sanaz; Aviel-Ronen, Sarit; Amariglio, Ninette; Schiff, Eyal; Orvieto, Raoul; Dor, Jehoshua

2016-08-01

To report the single-center results of orthotopic retransplantations of cryopreserved ovarian tissue in cancer survivors and evaluate the validity of commonly accepted procedure limitations. Prospective cohort study. Tertiary university-affiliated assisted reproduction technology (ART) and oncology centers. Twenty cancer survivors who underwent ovarian transplantation of frozen-thawed ovarian tissue with the aim to conceive. Ovarian tissue cryopreservation (OTCP) and transplantation, endocrine monitoring, in vitro fertilization (IVF). Endocrine profile, IVF, pregnancies, live births. The patient ages at tissue harvesting ranged from 14 to 39 years. Fifteen women had hematologic malignancies, and two had leukemia (chronic myelogenous leukemia and acute myelogenous leukemia). Ten patients were exposed to nonsterilizing chemotherapy before OTCP. After transplantation, the endocrine recovery rate was 93%. Fourteen patients underwent IVF treatments with a fertilization rate of 58%. Sixteen pregnancies were achieved (10 after IVF, 6 spontaneous), resulting in 10 live births, two (twins) after harvesting from the mother at the age of 37. Two pregnancies are currently ongoing. After transplantation, 53% of patients conceived, and 32% delivered at least once. One patient conceived four times. Preharversting chemotherapy exposure was not associated with inferior outcomes. All patients, including two leukemia survivors, remained cancer free. Orthotopic transplantation of thawed ovarian tissue is a highly effective measure to restore fertility in sterilized cancer patients. Chemotherapy exposure before harvesting and age >35 is a realistic option in selected patients. Retransplantation in leukemic patients is possible after application of maximal safety measures. These results have led the national ethical and professional authorities to decide for the first time not to consider OTCP as an experimental modality for fertility preservation. NCT02659592. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction

PubMed Central

Chu, Michael JJ; Premkumar, Rakesh; Hickey, Anthony JR; Jiang, Yannan; Delahunt, Brett; Phillips, Anthony RJ; Bartlett, Adam SJR

2016-01-01

AIM: To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). METHODS: Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. RESULTS: Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria. PMID:27217699

EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

PubMed

Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

2011-03-01

Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

Incidence and Risk Factors for Liver Abscess After Thermal Ablation of Liver Neoplasm

PubMed Central

Su, Xiu-Feng; Li, Na; Chen, Xu-Fang; Zhang, Lei; Yan, Ming

2016-01-01

Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most frequently used thermal ablation methods for the treatment of liver cancer. Liver abscess is a common and severe complication of thermal ablation treatment. Objectives The objective of this study was to determine the incidence and risk factors of liver abscess formation after thermal ablation of liver cancer. Materials and Methods The clinical data of 423 patients who underwent 691 thermal ablation procedures for liver cancer were collected in order to retrospectively analyze the basic characteristics, incidence, and risk factors associated with liver abscess formation. Patients with multiple risk factors for liver abscess formation were enrolled in a risk factor group, and patients with no risk factors were enrolled in a control group. The chi-square test and multiple logistic regression analysis were used to analyze the relationship between the occurrence of liver abscesses and potential risk factors. Results Two hundred and eight patients underwent 385 RFA procedures, and 185 patients underwent 306 MWA procedures. The total incidence of liver abscesses was 1.7%, while the rates in the RFA group (1.8%) and MWA groups (1.6%) were similar (P > 0.05). The rates of liver abscesses in patients who had child-pugh class B and class C cirrhosis (P = 0.0486), biliary tract disease (P = 0.0305), diabetes mellitus (P = 0.0344), and porta hepatis tumors (P = 0.0123) were 4.0%, 6.7%, 6.5%, and 13.0%, respectively. There was a statistically significant difference between these four groups and the control group (all P < 0.05). The incidence of liver abscesses in the combined ablation and percutaneous ethanol injection (PEI) group (P = 0.0026) was significantly lower than that of the ablation group (P < 0.05). Conclusions The incidence of liver abscesses after liver cancer thermal ablation is low. Child-Pugh Class B and Class C cirrhosis, biliary tract disease, diabetes mellitus, and porta hepatis tumors are four significant risk factors. Combined ablation and PEI reduces the rate of liver abscesses. PMID:27642345

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

PubMed Central

Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

2014-01-01

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT. PMID:25320538

Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.

PubMed

Daige, Christopher L; Wiggins, Jason F; Priddy, Leslie; Nelligan-Davis, Terri; Zhao, Jane; Brown, David

2014-10-01

miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers. ©2014 American Association for Cancer Research.

Adherence to immunosuppressive therapy following liver transplantation: an integrative review.

PubMed

Oliveira, Ramon Antônio; Turrini, Ruth Natália Teresa; Poveda, Vanessa de Brito

2016-08-29

to investigate the evidence available in the literature on non-adherence to immunosuppressive therapy among patients undergoing liver transplantation. integrative literature review, including research whose sample consisted of patients aged over 18 years undergoing liver transplantation. It excluded those containing patients undergoing multiple organ transplants. For the selection of articles, Medline / Pubmed, CINAHL, LILACS, Scopus and Embase were searched. The search period corresponded to the initial date of indexation of different bases, up to the deadline of February 10, 2015, using controlled and uncontrolled descriptors: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance and patient compliance. were located 191 investigations, 10 of which met the objectives of the study and were grouped into four categories, namely: educational process and non-adherence; non-adherence related to the number of daily doses of immunosuppressive medications; detection methods for non-adherence and side effects of therapy. there were risk factors related to the health service, such as control and reduction of the number of doses; related to the individual, such as being male, divorced, alcohol or other substances user, exposed to low social support and being mentally ill. investigar as evidências disponíveis na literatura sobre a não adesão à terapêutica imunossupressora entre pacientes submetidos ao transplante de fígado. revisão integrativa da literatura, que incluiu investigações cuja amostra era composta por pacientes com idade igual ou superior a 18 anos, submetidos a transplante de fígado. Excluíram-se as que continham pacientes submetidos a transplantes de múltiplos órgãos. Para a seleção dos artigos foram consultadas as bases Medline/Pubmed, CINAHL, LILACS, Scopus e Embase. O período de busca determinado correspondeu à data inicial de indexação das diferentes bases, até a data limite de 10 de fevereiro de 2015, empregando-se os descritores controlados e não controlados: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance e patient compliance. foram localizadas 191 investigações, das quais 10 atenderam aos objetivos do estudo e foram agrupadas em quatro categorias, a saber: processo educativo e ocorrência de não adesão; não adesão relacionada ao número de doses diárias dos medicamentos imunossupressores; métodos de detecção da não adesão e efeitos colaterais da terapêutica. verificou-se a existência de fatores de risco relacionados ao serviço de saúde, como controle e redução do número de doses; relacionados ao indivíduo, como ser do sexo masculino, divorciado, usuário de álcool ou outras substâncias, expostos a menor suporte social e portadores de transtorno mental. investigar la evidencia disponible en la literatura sobre la falta de adherencia a la terapia inmunosupresora en los pacientes sometidos a trasplante hepático. revisión integradora de la literatura, que incluye investigaciones cuya muestra estaba constituida por pacientes mayores de 18 años sometidos a trasplante hepático. Se excluyeron aquellos que tenían pacientes sometidos a trasplantes de varios órganos. Para la selección de los artículos fueron consultadas las bases Medline / Pubmed, CINAHL, LILACS, Scopus y Embase. El período de búsqueda determinado correspondió a la fecha inicial de indexación de las diferentes bases, con fecha límite de 10 de febrero de 2015, usándose descriptores controlados y no controlados: liver transplantation, hepatic transplantation, liver orthotopic transplantation, medication adherence, medication non-adherence, medication compliance e patient compliance. se localizaron 191 investigaciones, de los cuales 10 cumplieron con los objetivos del estudio y se agruparon en cuatro categorías, a saber: proceso educativo y ocurrencia de no adhesión; falta de adhesión relacionada con el número de dosis diarias de medicamentos inmunosupresores; métodos de detección de la falta de adhesión y los efectos secundarios de la terapia. se verificaron factores de riesgo relacionados con el servicio de salud, tales como el control y la reducción del número de dosis; inherentes a la persona, como ser hombre, divorciado, usuario de alcohol u otras sustancias, expuestos a un menor apoyo social y portadores de enfermedades mentales.

Circulating FoxP3+ Regulatory T and Interleukin17-Producing Th17 Cells Actively Influence HBV Clearance in De Novo Hepatitis B Virus Infected Patients after Orthotopic Liver Transplantation

PubMed Central

Li, Jin; Yang, Mei; Liu, Yuan; Guo, Xiaodong; Li, Hanwei; Liu, Zhenwen; Zhao, Jingmin

2015-01-01

Objective To longitudinally investigate the role of FoxP3+ Regulatory T cells (Treg) and interleukin17-producing T helper 17 cells (Th17) in De Novo Hepatitis B Virus infection after orthotopic Liver Transplantation (DNHB-OLT), and analyze the possible correlation between these cells and HBV clearance of the disease. Methods We enrolled 12 control cases after orthotopic Liver Transplantation (OLT) and 24 patients, including 12 diagnosed with DNHB-OLT and 12 diagnosed with Acute Hepatitis B Virus infection (AHB), into the study from the liver transplantation and research center at Beijing 302 Hospital. Flow cytometry was used to detect the frequencies of Treg and Th17, and ELISA was applied to detect the concentration of IL6, IL22, TGF-β and IL2 in peripheral blood. We also measured the gene expression level by real time-quantitative PCR and protein expression using immunohistochemistry and western-blot. Furthermore, we divided DNHB-OLT patients into the clearance and non-clearance groups and examined longitudinally Th17, Treg cells at different times. Results The percentage of Treg cells, expression of FoxP3 mRNA and related anti-inflammatory cytokines such as IL2 and TGF-β1 in the DNHB-OLT group were significantly higher than that in the AHB and OLT groups. The percentage of Th17 cells, expression of RORγt mRNA and related pro-inflammatory cytokines such as IL17 and IL22 in the DNHB-OLT group were significantly lower than that in the AHB group, but the levels of these cytokines are very similar to the OLT group. The ratios of Treg to Th17 in the DNHB-OLT group were significantly higher than that in the OLT and AHB groups. Treg frequencies significantly correlated with HBV DNA, whereas IL17 frequencies didn’t significantly correlate with ALT. In DNHB-OLT patients, the clearance group was accompanied by a rapid increase in the Th17 cells during the first 4th week and afterwards continuously decrease to the control group, together with a continuously decrease in Treg cells from the onset time point, which lead to a significant reduction in the ratios of Treg to Th17. The non-clearance group was accompanied by an increase in the Treg cells during the first 4th week and afterwards sharply decrease, together with a relatively stable and unchanged Th17 cells, which lead to a significant change in the ratios. In addition, compared to clearance group, the ratios of Treg to Th17 in non-clearance group were significantly higher at the onset point, 4th and 12th week, but no difference at 24th week. Conclusion DNHB-OLT patients possessed a favorable Treg differentiation environment, accompanied by a sustained higher preferentially Treg frequencies and up-regulation of related anti-inflammatory cytokines. The immune imbalance of the ratios between Treg and Th17 existed in DNHB-OLT patients. The changes of the ratios during the DNHB-OLT events were associated with HBV clearance, which suppressed immune inflammation reaction as well as inhibited ability of specific HBV clearance and led to immune escape and chronicity. PMID:26367459

Total Pelvic Supralevator Exenteration with Ileo-Colic Orthotopic Neobladder for Locoregional Recurrence after Cervical Cancer - A Case Report.

PubMed

Bacalbaşa, Nicolae; Bălescu, Irina; Braşoveanu, Vladislav

2016-01-01

Pelvic exenteration is one of the most aggressive surgical interventions in gynaecologic surgical oncology, but, in the same time, is the only potentially curative treatment of locoregional recurrence after cervical cancer. Due to improvements in surgical technique and postoperative management, the overall survival increased signifficantly in the last decades. Trying to improve the quality of life, multiple models of reconstruction of urinary and digestive tract have been developed. In this report we present the case of a 51 years old female who underwent a total supralevator exenteration with ileo colic neobladder reconstruction with good oncologic and functional outcomes. Celsius.

Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

NASA Astrophysics Data System (ADS)

Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

2014-03-01

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

Inorganic nanovehicle targets tumor in an orthotopic breast cancer model.

PubMed

Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

2014-03-21

The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

Liver xenotransplantation.

PubMed

Marino, I R; Tzakis, A G; Fung, J J; Todo, S; Doyle, H R; Manez, R; Starzl, T E

1993-10-01

During the past 30 years orthotopic liver transplantation has become a highly successful form of surgical treatments. The significant advances achieved in this field have led to an increased demand for organs and created a wide gap between organ availability and organ supply. A wider availability of organs for transplantation would allow an expansions rather than a contraction of the indications for transplantation, and, at the same time a relaxation of the patient selection criteria. All these facts clearly justify the renewed interest observed in the last decade in xenotransplantation. The original concept of xenografting, meaning the transplantation of cells, tissues, or organs between different species, is so ancient that it is easily recognizable in Greek and Roman mythology. The centaur Chiron, the teacher of Esculapius, and the Chimera are legendary examples of discordant xenogeneic creatures. However, it is only during this century that scientists have been able to bring this idea into the clinical arena. The early efforts were prompted by the shortage of humans organs at a time when there were few alternatives for treating end-stage organ failure.

Oncogenic Role of SND1 in Development and Progression of Hepatocellular Carcinoma

PubMed Central

Jariwala, Nidhi; Rajasekaran, Devaraja; Mendoza, Rachel G.; Shen, Xue-Ning; Siddiq, Ayesha; Akiel, Maaged A.; Robertson, Chadia L.; Subler, Mark A.; Windle, Jolene J.; Fisher, Paul B.; Sanyal, Arun J.; Sarkar, Devanand

2017-01-01

SND1, a subunit of the miRNA regulatory complex RISC, has been implicated as an oncogene in hepatocellular carcinoma (HCC). In this study, we show that hepatocyte-specific SND1 transgenic mice (Alb/SND1 mice) develop spontaneous HCC with partial penetrance and exhibit more highly aggressive HCC induced by chemical carcinogenesis. Livers from Alb/SND1 mice exhibited a relative increase in inflammatory markers and spheroid-generating tumor initiating cells (TIC). Mechanistic investigations defined roles for Akt and NF-κB signaling pathways in promoting TIC formation in Alb/SND1 mice. In human xenograft models of subcutaneous or orthotopic HCC, administration of the selective SND1 inhibitor 3′, 5′-deoxythymidine bisphosphate (pdTp) inhibited tumor formation without effects on body weight or liver function. Our work establishes an oncogenic role for SND1 in promoting TIC formation, and highlights pdTp as a highly selective SND1 inhibitor as a candidate therapeutic lead to treat advanced HCC. PMID:28428278

Human Hepatocyte Growth Factor (hHGF)-Modified Hepatic Oval Cells Improve Liver Transplant Survival

PubMed Central

Li, Li; Ran, Jiang-Hua; Li, Xue-Hua; Liu, Zhi-Heng; Liu, Gui-Jie; Gao, Yan-Chao; Zhang, Xue-Li; Sun, Hiu-Dong

2012-01-01

Despite progress in the field of immunosuppression, acute rejection is still a common postoperative complication following liver transplantation. This study aims to investigate the capacity of the human hepatocyte growth factor (hHGF) in modifying hepatic oval cells (HOCs) administered simultaneously with orthotopic liver transplantation as a means of improving graft survival. HOCs were activated and isolated using a modified 2-acetylaminofluorene/partial hepatectomy (2-AAF/PH) model in male Lewis rats. A HOC line stably expressing the HGF gene was established following stable transfection of the pBLAST2-hHGF plasmid. Our results demonstrated that hHGF-modified HOCs could efficiently differentiate into hepatocytes and bile duct epithelial cells in vitro. Administration of HOCs at the time of liver transplantation induced a wider distribution of SRY-positive donor cells in liver tissues. Administration of hHGF-HOC at the time of transplantation remarkably prolonged the median survival time and improved liver function for recipients compared to these parameters in the other treatment groups (P<0.05). Moreover, hHGF-HOC administration at the time of liver transplantation significantly suppressed elevation of interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) levels while increasing the production of IL-10 and TGF-β1 (P<0.05). HOC or hHGF-HOC administration promoted cell proliferation, reduced cell apoptosis, and decreased liver allograft rejection rates. Furthermore, hHGF-modified HOCs more efficiently reduced acute allograft rejection (P<0.05 versus HOC transplantation only). Our results indicate that the combination of hHGF-modified HOCs with liver transplantation decreased host anti-graft immune responses resulting in a reduction of allograft rejection rates and prolonging graft survival in recipient rats. This suggests that HOC-based cell transplantation therapies can be developed as a means of treating severe liver injuries. PMID:23028627

Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation.

PubMed

Hrydziuszko, Olga; Perera, M Thamara P R; Laing, Richard; Kirwan, Jennifer; Silva, Michael A; Richards, Douglas A; Murphy, Nick; Mirza, Darius F; Viant, Mark R

2016-01-01

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations.

Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation

PubMed Central

Laing, Richard; Kirwan, Jennifer; Silva, Michael A.; Richards, Douglas A.; Murphy, Nick; Mirza, Darius F.; Viant, Mark R.

2016-01-01

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations. PMID:27835640

Rewarming preservation by organ perfusion system for donation after cardiac death liver grafts in pigs.

PubMed

Matsuno, N; Obara, H; Watanabe, R; Iwata, S; Kono, S; Fujiyama, M; Hirano, T; Kanazawa, H; Enosawa, S

2014-05-01

Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. RMP is expected to facilitate the recovery of the DCD liver grafts. Copyright © 2014 Elsevier Inc. All rights reserved.

Liver transplantation for hepatocellular carcinoma: the Hong Kong experience.

PubMed

Ng, Kelvin K; Lo, Chung Mau; Chan, See Ching; Chok, Kenneth S; Cheung, Tan-To; Fan, Sheung Tat

2010-09-01

Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors' experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. "Fast-track" LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.

Preclinical evaluation of severely defective manganese-based nanocrystal as a liver-specific contrast media for MR imaging: comparison with Gd-EOB-DTPA and MnDPDP.

PubMed

Zhang, Yu; Xiao, Xiao-Ping; Shu, Ting; Cai, Jing; Xiao, Xin-Lan; Li, Yan-Shu; Zhang, Zhong-Wei; Tang, Qun

2018-06-01

Manganese-based (chemically formulated of KMnF 3 ) nanocrystal was evaluated as a liver-specific contrast agent for MR imaging and its imaging performance was also compared with those of two commercial hepatobiliary contrast media (Gd-EOB-DTPA and MnDPDP). KMnF 3 nanocrystal was post-treated using a plasma technique to cause severe defects, leading to appropriate water dispersibility and high relaxivity. Severely defective KMnF 3 nanocrystal (SD-KMnF 3 ) has characteristic high tolerance, as evidenced by cytotoxicity on the macrophage cell, and acute and subchronic toxicity on the healthy mouse. SD-KMnF 3 showed better hepatic MR imaging as the T 1 relaxation time of the liver decreased to only 17% of the control group, compared to 22% of the control group for Gd-EOB-DTPA (P < 0.01) and 42% of the control group for MnDPDP (P < 0.001). As applied to MR imaging of the allograft orthotopic model of liver cancer, statistical studies demonstrated that SD-KMnF 3 significantly improved the tumor's contrast-to-noise ratio, compared with Gd-EOB-DTPA (P < 0.01) and MnDPDP (P < 0.01) by spin-echo pulse sequence, and even better performance (P < 0.001) by gradient-echo sequence. Our findings indicate that SD-KMnF 3 could serve as a hepatic contrast agent for imaging liver cancer such as hepatocarcinoma or metastatic lesions.

[The influence with block the endotoxin signal transduction for ischemia/reperfusion injury of graft liver in rats].

PubMed

Liu, Zuo-jin; Li, Sheng-wei; Li, Xu-hong; Peng, Yong; You, Hai-bo; Li, Shou-bai; Gong, Jian-ping

2006-09-01

To explore the feasibility of interleukin 1 receptor associated kinase-4 (IRAK-4) as gene therapy target for liver ischemia/reperfusion injury (I/RI) and effective approach in vivo for short hairpin RNA (shRNA) interference used to gene therapy in liver graft hqappened. Sprague-Dawley rats were randomly divided into three groups: the control group, the in vivo transfection group (IVT) and the cold ischemia transfection group (CIT). Experiments of orthotopic liver transplantation were performed by two-cuff method. CIT were perfused with IRAK-4-shRNA plasmid (pSIIRAK-4) during cold ischemia phase, IVT received the equivalent volumes (2 mL) of pSIIRAK-4 after portal vein inosculated, and the control group leaved without any treatment. At 0 min, 60 min and 180 min after reperfusion, the expression of IRAK-4 gene and protein level were determined by RT-PCR and Western blot. The serum TNF-alpha level was detected by ELISA. Liver histopathological changes and cell apoptosis were observed by electron microscope and TUNEL. After reperfusion, the expression of IRAK-4 were largely depressed in CIT than that of IVT and the control group (P < 0.01), and furthermore, the serum TNF-alpha level, proportion of hepatocyte apoptosis and severity of hepatocyte injury were also lower than the latter. These results indicate that depression IRAK-4 expression with IRAK-4-shRNA through portal vein perfusion during cold ischemia phase could effectively blunt graft hepatic I/RI.

Preclinical evaluation of severely defective manganese-based nanocrystal as a liver-specific contrast media for MR imaging: comparison with Gd-EOB-DTPA and MnDPDP

NASA Astrophysics Data System (ADS)

Zhang, Yu; Xiao, Xiao-ping; Shu, Ting; Cai, Jing; Xiao, Xin-lan; Li, Yan-shu; Zhang, Zhong-wei; Tang, Qun

2018-06-01

Manganese-based (chemically formulated of KMnF3) nanocrystal was evaluated as a liver-specific contrast agent for MR imaging and its imaging performance was also compared with those of two commercial hepatobiliary contrast media (Gd-EOB-DTPA and MnDPDP). KMnF3 nanocrystal was post-treated using a plasma technique to cause severe defects, leading to appropriate water dispersibility and high relaxivity. Severely defective KMnF3 nanocrystal (SD-KMnF3) has characteristic high tolerance, as evidenced by cytotoxicity on the macrophage cell, and acute and subchronic toxicity on the healthy mouse. SD-KMnF3 showed better hepatic MR imaging as the T 1 relaxation time of the liver decreased to only 17% of the control group, compared to 22% of the control group for Gd-EOB-DTPA (P < 0.01) and 42% of the control group for MnDPDP (P < 0.001). As applied to MR imaging of the allograft orthotopic model of liver cancer, statistical studies demonstrated that SD-KMnF3 significantly improved the tumor’s contrast-to-noise ratio, compared with Gd-EOB-DTPA (P < 0.01) and MnDPDP (P < 0.01) by spin-echo pulse sequence, and even better performance (P < 0.001) by gradient-echo sequence. Our findings indicate that SD-KMnF3 could serve as a hepatic contrast agent for imaging liver cancer such as hepatocarcinoma or metastatic lesions.

Evaluation of the anti-neoplastic effect of sorafenib on liver cancer through bioluminescence tomography

NASA Astrophysics Data System (ADS)

Liang, Qian; Ye, Jinzuo; Du, Yang; Chi, Chongwei; Tian, Jie

2017-03-01

Hepatocellular carcinoma (HCC) is one of the most important leading causes of cancer-related deaths worldwide. In this study, we evaluated the efficacy of sorafenib on hepatocellular carcinoma through bioluminescence tomography (BLT) based on Micro-CT/BLT multi-modal system. Initially, the human hepatocellular carcinoma cell line HepG2-Red-FLuc, which was transfected with luciferase gene, was cultured. And then, the orthotopic liver tumor mouse model was established on 4 5 weeks old athymic male Balb/c nude mice by inoculating the HepG2-Red-FLuc cell suspension into the liver lobe under isoflurane anesthesia. 15 20 days after tumor cells implantation, the mice were divided into two groups including the sorafenib treatment group and the control group. The mice in the treatment group were treated with sorafenib with dosage of 62 mg/kg/day by oral gavage for continuous 14 days, and the mice in the control group were treated with sterile water at equal volume. The tumor growth and drug treatment efficacy were dynamically monitored through BLT. The results in this study showed that the growth of liver cancer can be dynamically monitored from very early stage, and also the sorafenib treatment efficacy can be reliably and objectively assessed using BLT imaging method. Our experimental result demonstrated sorafenib can inhibit the tumor growth effectively. BLT enabled the non-invasive and reliable assessment of anti-neoplastic drug efficacy on liver cancer.

Surgical procedures in liver transplant patients: A monocentric retrospective cohort study.

PubMed

Sommacale, Daniele; Nagarajan, Ganesh; Lhuaire, Martin; Dondero, Federica; Pessaux, Patrick; Piardi, Tullio; Sauvanet, Alain; Kianmanesh, Reza; Belghiti, Jacques

2017-05-01

Pre-existing chronic liver diseases and the complexity of the transplant surgery procedures lead to a greater risk of further surgery in transplanted patients compared to the general population. The aim of this monocentric retrospective cohort study was to assess the epidemiology of surgical complications in liver transplanted patients who require further surgical procedures and to characterize their post-operative risk of complications to enhance their medical care. From January 1997 to December 2011, 1211 patients underwent orthotropic liver transplantation in our center. A retrospective analysis of prospectively collected data was performed considering patients who underwent surgical procedures more than three months after transplantation. We recorded liver transplantation technique, type of surgery, post-operative complications, time since the liver transplant and immunosuppressive regimens. Among these, 161 patients (15%) underwent a further 183 surgical procedures for conditions both related and unrelated to the transplant. The most common surgical procedure was for an incisional hernia repair (n = 101), followed by bilioenteric anastomosis (n = 44), intestinal surgery (n = 23), liver surgery (n = 8) and other surgical procedures (n = 7). Emergency surgery was required in 19 procedures (10%), while 162 procedures (90%) were performed electively. Post-operative mortality and morbidity were 1% and 30%, respectively. According to the Dindo-Clavien classification, the most common grade of morbidity was grade III (46%), followed by grade II (40%). Surgical procedures on liver transplanted patients are associated with a significantly high risk of complications, irrespective of the time elapsed since transplantation. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Assessment of liver size by ultrasonography.

PubMed

Patzak, Monika; Porzner, Marc; Oeztuerk, Suemeyra; Mason, Richard Andrew; Wilhelm, Manfred; Graeter, Tilmann; Kratzer, Wolfgang; Haenle, Mark Martin; Akinli, Atilla Serif

2014-09-01

To determine liver span sonographically in a randomly selected population sample and identify factors that affect liver size. A total of 1,789 subjects (963 females, 826 males; mean age 41.8 ± 12.8 years) underwent sonographic examination of the liver in the midclavicular line to determine liver span. Subjects underwent physical examination and blood tests and completed a standardized interview questionnaire. The average liver span in the midclavicular line for the overall collective was 15.0 ± 1.5 cm; the average for females was 14.9 ± 1.6 cm and 15.1 ± 1.5 cm for males. Liver span exceeded 16 cm in 24.3% of subjects. Results of the multivariate analysis showed that, of the factors potentially influencing liver span, gender, age, body mass index, body height, fatty liver (p < 0.0001), waist-to-hip ratio (p = 0.015), and metabolic syndrome (p = 0.032) are significant. By contrast, diabetes mellitus, alcohol consumption, tobacco consumption, physical activity, and laboratory findings showed no influence. Sonographic measurement of liver span in the midclavicular line is a simple method for routine clinical use. Gender, age, body mass index, waist-to-hip ratio, body height, hepatic steatosis, and metabolic syndrome are factors associated with liver span. © 2014 Wiley Periodicals, Inc.

High mortality after ALPPS for perihilar cholangiocarcinoma: case-control analysis including the first series from the international ALPPS registry

PubMed Central

Olthof, Pim B.; Coelen, Robert J.S.; Wiggers, Jimme K.; Koerkamp, Bas Groot; Malago, Massimo; Hernandez-Alejandro, Roberto; Topp, Stefan A.; Vivarelli, Marco; Aldrighetti, Luca A.; Campos, Ricardo Robles; Oldhafer, Karl J.; Jarnagin, William R.; van Gulik, Thomas M.

2017-01-01

Introduction Resection of perihilar cholangiocarcinoma (PHC) entails high-risk surgery with substantial postoperative mortality reported up to 18%, even in specialized centers. The aim of this study was to compare outcomes of PHC patients who underwent associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) to patients with a small functional liver remnant who underwent resection without ALPSS. Methods All patients who underwent ALPPS for PHC were identified from the international ALPPS registry and matched controls were selected from a standard resection cohort from two centers based on future remnant liver size. Outcomes included morbidity, mortality, and overall survival. Results Of the 37 patients who had undergone ALPPS for PHC in the registry, 29 had sufficient data for analyses. ALPPS for PHC was associated with a 48% (14/29) 90-day mortality and median OS of 6 months. A total of 257 patients underwent major liver resection for PHC without ALPPS. The 90-day mortality was 13% and median OS 46 months. The 29 ALPPS patients were matched to 29 patients resected without ALPPS, with similar future liver remnant volume (P=0.480). Mortality in the matched control group was 24% (P=0.100) and median OS was 27 months (P = 0.064). Discussion Outcomes of ALPPS for PHC appear inferior when compared to standard extended resections in high-risk patients. Considering these outcomes, portal vein embolization should remain the preferred method to increase future remnant liver volume in PHC patients. ALPPS is not recommended for PHC due to the 48% 90-day mortality in expert centers. PMID:28279621

S-Adenosylmethionine attenuates bile duct early warm ischemia reperfusion injury after rat liver transplantation.

PubMed

Tang, Yong; Chu, Hongpeng; Cao, Guojun; Du, Xiaolong; Min, Xiaobo; Wan, Chidan

2018-03-01

Warm ischemia reperfusion injury (IRI) plays a key role in biliary complication, which is a substantial vulnerability of liver transplantation. The early pathophysiological changes of IRI are characterized by an excessive inflammatory response. S-Adenosylmethionine (SAM) is an important metabolic intermediate that modulates inflammatory reactions; however, its role in bile duct warm IRI is not known. In this study, male rats were treated with or without SAM (170 μmol/kg body weight) after orthotopic autologous liver transplantation. The histopathological observations showed that bile duct injury in the IRI group was more serious than in the SAM group. The alanine aminotransferase (ALT), alkaline phosphatase (ALP) and direct bilirubin (DBIL) levels in the serum of the IRI group were significantly increased compared to the SAM group (P < .05). Simultaneously, SAM effectively improved the survival of the transplant recipients. Furthermore, the H 2 O 2 and malondialdehyde (MDA) of the IRI group were much higher compared to the SAM group (P < .05). The GSH/GSSG ratio in the SAM group was significantly increased by SAM treatment compared to the IRI group (P < .05). SAM administration significantly inhibited macrophage infiltration in liver and bile duct tissues, down-regulated TNF-α levels and up-regulated IL-10 expression in bile duct tissues compared to the IRI group (P < .05). The number of apoptotic biliary epithelial cells and caspase-3-positive cells in IRI rat livers were much higher compared to those in SAM-treated rats at 24 h after liver transplantation (P < .05). These data suggested that SAM protected bile ducts against warm IRI by suppressing oxidative stress, inflammatory reactions and apoptosis of biliary epithelial cells after liver transplantation.α. Copyright © 2018 Elsevier Ltd. All rights reserved.

Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells*

PubMed Central

Mou, Xiao-zhou; Lin, Jian; Chen, Jin-yang; Li, Yi-fei; Wu, Xiao-xing; Xiang, Bing-yu; Li, Cai-yun; Ma, Ju-ming; Xiang, Charlie

2013-01-01

Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues. PMID:24190442

Primary non-function is frequently associated with fatty liver allografts and high mortality after re-transplantation.

PubMed

Kulik, Ulf; Lehner, Frank; Klempnauer, Jürgen; Borlak, Jürgen

2017-08-01

The shortage of liver donations demands the use of suboptimal grafts with steatosis being a frequent finding. Although ≤30% macrovesicular steatosis is considered to be safe the risk for primary non-function (PNF) and outcome after re-transplantation (re-OLT) is unknown. Among 1205 orthotopic liver transplantations performed at our institution the frequency, survival and reason of re-OLT were evaluated. PNF (group A) cases and those with initial transplant function but subsequent need for re-OLT (group B) were analysed. Histopathology and clinical judgement determined the cause of PNF and included an assessment of hepatic steatosis. Additionally, survival of fatty liver allografts (group C) not requiring re-OLT was considered in Kaplan-Meier and multivariate regression analysis. A total of 77 high urgency re-OLTs were identified and included 39 PNF cases. Nearly 70% of PNF cases were due to primary fatty liver allografts. The 3-month in-hospital mortality for PNF cases after re-OLT was 46% and the mean survival after re-OLT was 0.5 years as compared to 5.2 and 5.1 years for group B, C, respectively, (P<.008). In multivariate Cox regression analysis only hepatic steatosis was associated with an inferior survival (HR 4.272, P=.002). The MELD score, donor BMI, age, cold ischaemic time, ICU stay, serum sodium and transaminases did not influence overall survival. Our study highlights fatty liver allografts to be a major cause for PNF with excessive mortality after re-transplantation. The findings demand the development of new methods to predict risk for PNF of fatty liver allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Knockdown of microRNA-155 in Kupffer cells results in immunosuppressive effects and prolongs survival of mouse liver allografts.

PubMed

Li, Jinzheng; Gong, Junhua; Li, Peizhi; Li, Min; Liu, Yiming; Liang, Shaoyong; Gong, Jianping

2014-03-27

Our previous studies have shown that Kupffer cells (KCs) play a crucial role in postoperative pathologic changes. Recent reports have demonstrated that microRNA-155 (miR-155) is associated with inflammation and upregulation of proinflammatory mediators in the peripheral blood and allografts of transplant patients. However, the precise mechanism for this remains unknown. KCs isolated from BALB/c mice were transfected with miR-155 mimic or inhibitor. Levels of suppressor of cytokine signaling 1/Janus kinase/signal transducer and activator of transcription (SOCS1/JAK/STAT) proteins and surface molecules (MHC-II, CD40, and CD86) were then measured. T-cell proliferation and apoptosis were evaluated in mixed lymphocyte reactions. Orthotopic liver transplantation was performed in mice after miR-155 short hairpin RNA lentivirus treatment, and postoperative survival, liver function and histology, and mRNA and protein expression were analyzed. miR-155 knockdown in KCs decreased MHC-II, CD40, and CD86 expression, suppressed antigen-presenting function, and affected SOCS1/JAK/STAT inflammatory pathways. In addition, KCs transfected with miR-155 inhibitor and cocultured with T lymphocytes showed reduced T-cell responses but a greater number of apoptotic T cells. Finally, miR-155 suppression in graft liver prolonged liver allograft survival and improved liver function. The changes were closely associated with the levels of T helper 1 and 2 (Th1/Th2) cytokines and T-cell apoptosis, but a direct mechanistic link in vivo was not established. These data suggest miR-155 regulates the balance of Th1/Th2 cytokines and the maturation and function of KCs in mice. miR-155 repression in KCs positively regulates KC function toward immunosuppression and prolongs liver allograft survival.

Pre-liver transplant psychosocial evaluation predicts post-transplantation outcomes.

PubMed

Benson, Ariel A; Rowe, Mina; Eid, Ahmad; Bluth, Keren; Merhav, Hadar; Khalaileh, Abed; Safadi, Rifaat

2018-08-01

Psychosocial factors greatly impact the course of patients throughout the liver transplantation process. A retrospective chart review was performed of patients who underwent liver transplantation at Hadassah-Hebrew University Medical Center between 2002 and 2012. A composite psychosocial score was computed based on the patient's pre-transplant evaluation. Patients were divided into two groups based on compliance, support and insight: Optimal psychosocial score and Non-optimal psychosocial score. Post-liver transplantation survival and complication rates were evaluated. Out of 100 patients who underwent liver transplantation at the Hadassah-Hebrew University Medical Center between 2002 and 2012, 93% had a complete pre-liver transplant psychosocial evaluation in the medical record performed by professional psychologists and social workers. Post-liver transplantation survival was significantly higher in the Optimal group (85%) as compared to the Non-optimal group (56%, p = .002). Post-liver transplantation rate of renal failure was significantly lower in the Optimal group. No significant differences were observed between the groups in other post-transplant complications. A patient's psychosocial status may impact outcomes following transplantation as inferior psychosocial grades were associated with lower overall survival and increased rates of complications. Pre-liver transplant psychosocial evaluations are an important tool to help predict survival following transplantation.

Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation

PubMed Central

Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

2015-01-01

AIM: To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. METHODS: Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD+, a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. RESULTS: The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD+ (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced levels of both caspase 12 and caspase 3. Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. However, no changes were observed in protein or mRNA expression of SIRT3. Finally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration. CONCLUSION: The present study reports that losartan induces SIRT1 expression and activity, and that it reduces hepatic injury in a ROLT model. PMID:26185373

Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation.

PubMed

Pantazi, Eirini; Bejaoui, Mohamed; Zaouali, Mohamed Amine; Folch-Puy, Emma; Pinto Rolo, Anabela; Panisello, Arnau; Palmeira, Carlos Marques; Roselló-Catafau, Joan

2015-07-14

To investigate a possible association between losartan and sirtuin 1 (SIRT1) in reduced-size orthotopic liver transplantation (ROLT) in rats. Livers of male Sprague-Dawley rats (200-250 g) were preserved in University of Wisconsin preservation solution for 1 h at 4 °C prior to ROLT. In an additional group, an antagonist of angiotensin II type 1 receptor (AT1R), losartan, was orally administered (5 mg/kg) 24 h and 1 h before the surgical procedure to both the donors and the recipients. Transaminase (as an indicator of liver injury), SIRT1 activity, and nicotinamide adenine dinucleotide (NAD(+), a co-factor necessary for SIRT1 activity) levels were determined by biochemical methods. Protein expression of SIRT1, acetylated FoxO1 (ac-FoxO1), NAMPT (the precursor of NAD+), heat shock proteins (HSP70, HO-1) expression, endoplasmic reticulum stress (GRP78, IRE1α, p-eIF2) and apoptosis (caspase 12 and caspase 3) parameters were determined by Western blot. Possible alterations in protein expression of mitogen activated protein kinases (MAPK), such as p-p38 and p-ERK, were also evaluated. Furthermore, the SIRT3 protein expression and mRNA levels were examined. The present study demonstrated that losartan administration led to diminished liver injury when compared to ROLT group, as evidenced by the significant decreases in alanine aminotransferase (358.3 ± 133.44 vs 206 ± 33.61, P < 0.05) and aspartate aminotransferase levels (893.57 ± 397.69 vs 500.85 ± 118.07, P < 0.05). The lessened hepatic injury in case of losartan was associated with enhanced SIRT1 protein expression and activity (5.27 ± 0.32 vs 6.08 ± 0.30, P < 0.05). This was concomitant with increased levels of NAD(+) (0.87 ± 0.22 vs 1.195 ± 0.144, P < 0.05) the co-factor necessary for SIRT1 activity, as well as with decreases in ac-FoxO1 expression. Losartan treatment also provoked significant attenuation of endoplasmic reticulum stress parameters (GRP78, IRE1α, p-eIF2) which was consistent with reduced levels of both caspase 12 and caspase 3. Furthermore, losartan administration stimulated HSP70 protein expression and attenuated HO-1 expression. However, no changes were observed in protein or mRNA expression of SIRT3. Finally, the protein expression pattern of p-ERK and p-p38 were not altered upon losartan administration. The present study reports that losartan induces SIRT1 expression and activity, and that it reduces hepatic injury in a ROLT model.

Bile duct ligation in developing rats: temporal progression of liver, kidney, and brain damage.

PubMed

Sheen, Jiunn-Ming; Huang, Li-Tung; Hsieh, Chih-Sung; Chen, Chih-Cheng; Wang, Jia-Yi; Tain, You-Lin

2010-08-01

Cholestatic liver disease may result in progressive end-stage liver disease and other extrahepatic complications. We explored the temporal progression of bile duct ligation (BDL)-induced cholestasis in developing rats, focusing on brain cognition and liver and kidney pathology, to elucidate whether these findings were associated with asymmetric dimethylarginine and oxidative stress alterations. Three groups of young male Sprague-Dawley rats were studied: one group underwent laparotomy (sham), another group underwent laparotomy and BDL for 2 weeks (BDL2), and a third group underwent laparotomy and BDL for 4 weeks (BDL4). The effect of BDL on liver was represented by transforming growth factor beta1 levels and histology activity index scores, which were worse in the BDL4 rats than in the BDL2 rats. BDL4 rats also exhibited more severe spatial memory deficits than BDL2 rats. In addition, renal injury was more progressive in BDL4 rats than in BDL2 rats because BDL4 rats displayed higher Cr levels, elevated tubulointerstitial injury scores, neutrophil gelatinase-associated lipocalin, and symmetric dimethylarginine levels. Our findings highlight the fact that young BDL rats exhibit similar trends of progression of liver, kidney, and brain damage. Further studies are needed to better delineate the nature of progression of organ damage in young cholestatic rats. Copyright 2010 Elsevier Inc. All rights reserved.

Predictors of the use of orthotopic bladder reconstruction after radical cystectomy for bladder cancer: data from a pilot study of 1756 cases 2004-2011.

PubMed

Hounsome, Luke S; Abel, Gary A; Verne, Julia; Neal, David E; Lyratzopoulos, Georgios

2013-06-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: How often orthotopic reconstruction should be used after radical cystectomy is uncertain. Male sex, younger age, affluence, white ethnicity and treatment in specialist hospitals may be associated with more frequent use. More evidence about the level and likely variation in the use of orthotopic surgery is needed to establish whether there are inequalities and unmet need. In England during the study period orthotopic bladder reconstruction was likely to be used in about one in 15 patients treated by radical cystectomy. This is lower than previously reported in US series or European studies. Men and younger patients were more likely to be treated by orthotopic reconstruction, as were more affluent patients and those with less advanced disease. Whether clinical reasons or patient choice can explain some of this variation is unclear. There was no evidence for variation between different English cancer networks. A specific procedure code to allow routine analysis of population-based nationwide data would be invaluable for ongoing monitoring of potential inequalities and unmet need. To examine variation in the use of orthotopic bladder reconstruction. Variability in the use of orthotopic reconstruction may indicate potential for quality improvement. We analysed data from the British Association of Urological Surgeons Cancer Registry Complex Operations data set and Hospital Episode Statistics, covering the period 2004-2011. Three-level (patient, consultant and cancer network) mixed effect logistic regression models were used to examine sociodemographic and organizational variation in use of orthotopic reconstruction. The primary outcome was the odds ratio for use of orthotopic reconstruction for different patient groups. The final analysis sample included 1756 patients with bladder cancer who were treated by cystectomy by 121 consultants in 17 cancer networks. Of these, 120 (6.8%) were treated by orthotopic bladder reconstruction by 49 consultants in 14 cancer networks. In multivariable analysis, use of orthotopic surgery was higher in younger patients (odds ratio [OR] = 0.37 per increasing 10-year age group from 30-39 to ≥70, P ≤ 0.001) and men (OR = 2.31, P = 0.005). There was also some evidence of less frequent use among more deprived patients (OR per decreasing deprivation quintile 1.17, P = 0.037) and those with advanced disease (OR per increase in stage category 0.8, P = 0.037). After accounting for patient- and consultant-level variation, there was very limited variation in the use of orthotopic reconstruction between different cancer networks. Within the study context, use of orthotopic surgery was relatively rare and variable between patients with different characteristics but not between different cancer networks. The extent by which this variation reflects variation in quality of care or patient choice is uncertain. Examining the dissemination of orthotopic surgery use using nationwide data is advisable. © 2013 BJU International.

Postoperative liver volume was accurately predicted by a medical image three dimensional visualization system in hepatectomy for liver cancer.

PubMed

Cai, Wei; Fan, Yingfang; Hu, Haoyu; Xiang, Nan; Fang, Chihua; Jia, Fucang

2017-06-01

Liver cancer is the second most common cause of cancer death worldwide. The hepatectomy is the most effective and the only potentially curative treatment for patients with resectable neoplasm. Precisely preoperative assessment of remnant liver volume is essential in preventing postoperative liver failure. The aim of our study is to report our experience of using a medical image three dimensional (3D) visualization system (MI-3DVS), which was developed by our team, in assisting hepatectomy for patients with liver cancer. Between January 2010 and June 2016, 69 patients with liver cancer underwent hepatic resection based on the MI-3DVS were enrolled in this study. All patients underwent CT scan 5 days before the surgery and within 5 days after resection. CT images were reconstructed with the MI-3DVS to assist to perform hepatectomy. Simple linear regression, intra-class correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate the relationship and agreement between actual excisional liver volume (AELV) and predicted excisional liver volume (PELV). Among 69 patients in this study, 62(89.85%) of them were diagnosed with hepatocellular carcinoma by histopathologic examination, and 41(59.42%) underwent major hepatectomy. The average AELV was 330.13 cm 3 and the average PELV was 287.67 cm 3 . The simple regression equation is AELV = 1.016 × PELV+30.39(r = 0.966; p < 0.0003). PELV (ICC = 0.964) achieved an excellent agreement with AELV with statistical significance (p < 0.001). 65 of 69 dots are in the range of 95% confidence interval in Bland-Altman analyses. The MI-3DVS has advantages of simple usage and convenient hold. It is accurate in assessment of postoperative liver volume and improve safety in liver resection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hybrid procedure in living donor liver transplantation.

PubMed

Soyama, A; Takatsuki, M; Hidaka, M; Adachi, T; Kitasato, A; Kinoshita, A; Natsuda, K; Baimakhanov, Z; Kuroki, T; Eguchi, S

2015-04-01

We have previously reported a hybrid procedure that uses a combination of laparoscopic mobilization of the liver and subsequent hepatectomy under direct vision in living donor liver transplantation (LDLT). We present the details of this hybrid procedure and the outcomes of the procedure. Between January 1997 and August 2014, 204 LDLTs were performed at Nagasaki University Hospital. Among them, 67 recent donors underwent hybrid donor hepatectomy. Forty-one donors underwent left hemihepatectomy, 25 underwent right hemihepatectomy, and 1 underwent posterior sectionectomy. First, an 8-cm subxiphoid midline incision was made; laparoscopic mobilization of the liver was then achieved with a hand-assist through the midline incision under the pneumoperitoneum. Thereafter, the incision was extended up to 12 cm for the right lobe and posterior sector graft and 10 cm left lobe graft procurement. Under direct vision, parenchymal transection was performed by means of the liver-hanging maneuver. The hybrid procedure for LDLT recipients was indicated only for selected cases with atrophic liver cirrhosis without a history of upper abdominal surgery, significant retroperitoneal collateral vessels, or hypertrophic change of the liver (n = 29). For total hepatectomy and splenectomy, the midline incision was sufficiently extended. All of the hybrid donor hepatectomies were completed without an extra subcostal incision. No significant differences were observed in the blood loss or length of the operation compared with conventional open procedures. All of the donors have returned to their preoperative activity level, with fewer wound-related complaints compared with those treated with the use of the conventional open procedure. In recipients treated with the hybrid procedure, no clinically relevant drawbacks were observed compared with the recipients treated with a regular Mercedes-Benz-type incision. Our hybrid procedure was safely conducted with the same quality as the conventional open procedure in both LDLT donors and recipients. Copyright © 2015 Elsevier Inc. All rights reserved.

Infrahepatic vena cavocavostomy, a modification of the piggyback technique for liver transplantation.

PubMed

Khanmoradi, Kamran; Defaria, Werviston; Nishida, Seigo; Levi, David; Kato, Tomoaki; Moon, Jang; Selvaggi, Gennaro; Tzakis, Andreas

2009-05-01

We describe our experience with a modification of the piggyback (PB) technique for orthotopic liver transplantation in which the donor infrahepatic vena cava is used as the venous outflow tract. From May 1997 to January 2006, a total of 109 cases using this technique were performed in 101 patients. Collected data included recipient demographics and diagnosis, warm ischemia time, use of venovenous bypass or temporary portacaval shunt and complications related to the venous outflow and graft, and patient survival. Data were compared with the patients undergoing standard PB technique during the same period. The reasons for using the technique were grouped according to whether there was a problem with the recipient hepatic veins or a concern about the length or diameter of the donor suprahepatic vena cava. These included the presence of a transjugular intrahepatic portosystemic shunt (eight cases), retransplantation (22 cases), thin-walled, friable hepatic veins (32 cases), Budd-Chiari syndrome (two cases), domino liver procurement (six cases), reduced or split liver grafts (five cases), and graft inferior vena cava to recipient hepatic veins size discrepancy (34 cases). There was no graft loss. The warm ischemia time was 39.65 minutes compared with 37 minutes in the standard PB group. The long-term graft and patient survival rates were similar in the two groups. Infrahepatic vena cavocavostomy is a useful variation of the standard PB technique.

Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome.

PubMed

Kreuzer, Martin; Gähler, Dagmar; Rakenius, Annette C; Prüfe, Jenny; Jack, Thomas; Pfister, Eva-Doreen; Pape, Lars

2015-12-01

Acute kidney injury (AKI) is a major complication in children with hepatic failure which leads to increased morbidity and mortality. The aim of this study was to provide paediatric data on the prevalence of dialysis-dependent AKI (dAKI), the feasibility and efficacy of dialysis methods and outcome. We conducted a retrospective analysis of 367 children listed for orthotopic liver transplantation (OLT) in our centre during the past decade. Data on 30 children (15 boys, 15 girls) were compiled for retrospective analysis, and data on dialysis feasibility and efficacy were available for 26 of these. Median age was 3.5 (range 0.4-17.7) years. Median MELD (Model For End-Stage Liver Disease) score was 33. dAKI was caused by hepato-renal syndrome in 16 of the 30 children. Twenty-one patients were treated with continuous veno-venous haemofiltration (CVVH), and nine patients received peritoneal dialysis (PD). Overall mortality was 77%. Mortality within the PD-group was 100 % versus 67% in the CVVH-group (p = 0.039). Urea reduction rate within the first 24 h of treatment was 12.9% in the PD group and 23.5% in the CVVH group (p = 0.019). Children with end-stage liver disease have a high risk for dAKI associated with high mortality. CVVH is associated with better efficacy and less mortality than PD.

Etiology and microbial patterns of pulmonary infiltrates in patients with orthotopic liver transplantation.

PubMed

Torres, A; Ewig, S; Insausti, J; Guergué, J M; Xaubet, A; Mas, A; Salmeron, J M

2000-02-01

To evaluate the etiology and microbial patterns of pulmonary infiltrates in liver transplant patients using a bronchoscopic diagnostic approach and the impact of diagnostic results on antimicrobial treatment decisions. A prospective cohort study. A 1,000-bed tertiary-care university hospital. Fifty consecutive liver transplant patients with 60 episodes of pulmonary infiltrates (33 episodes during mechanical ventilation) were studied using flexible bronchoscopy with protected specimen brush (PSB) and BAL. A definite infectious etiology was confirmed in 29 episodes (48%). Eighteen episodes corresponded to probable pneumonia (30%), 10 episodes had noninfectious etiologies (17%), and 3 remained undetermined (5%). Opportunistic infections were the most frequent etiology (16/29, 55%, including 1 mixed etiology). Bacterial infections (mainly Gram-negative) accounted for 14 of 29 episodes (48%), including 1 of mixed etiology. The majority of bacterial pneumonia episodes (n = 10, 71%) occurred in period 1 (1 to 28 days posttransplant) during mechanical ventilation, whereas opportunistic episodes were predominant in periods 2 and 3 (29 to 180 days and > 180 days posttransplant, respectively; n = 14, 82%). Microbial treatment was changed according to diagnostic results in 21 episodes (35%). Microbial patterns in liver transplant patients with pulmonary infiltrates corresponded to nosocomial, mainly Gram-negative bacterial pneumonia in period 1, and to opportunistic infections in period 2 and, to a lesser extent, period 3. A comprehensive diagnostic evaluation including PSB and BAL fluid examination frequently guided specific antimicrobial therapy.

Fully Covered Self-Expandable Metal Stents for Treatment of Both Benign and Malignant Biliary Disorders

PubMed Central

Abdel Samie, Ahmed; Theilmann, Lorenz

2012-01-01

Transpapillary stents are increasingly being used for biliary strictures, whether benign or malignant. However, there are different stent types and available data is controversial. Recently, completely covered self-expandable metal stents (CSEMSs) have been proposed as an alternative therapeutic option in different biliary indications, including strictures of the distal bile duct, anastomotic stenosis after orthotopic liver transplantation, bile duct leaks, periampullary perforation following endoscopic sphincterotomy (ES), and postsphincterotomy bleeding. Despite the higher costs of these devices, fully covered self-expanding metal stents seem to be a suitable therapeutic option to relief biliary obstruction due to bile duct stenosis, regardless of the underlying cause. PMID:22761543

Quality of life after radical cystectomy for bladder cancer in men with an ileal conduit or continent urinary diversion: A comparative study

PubMed Central

Asgari, M. A.; Safarinejad, M. R.; Shakhssalim, N.; Soleimani, M.; Shahabi, A.; Amini, E.

2013-01-01

Aim: To investigate quality of life (QoL) domains with three forms of urinary diversions, including ileal conduit, MAINZ pouch, and orthotopic ileal neobladder after radical cystectomy in men with muscle-invasive bladder cancer. Materials and Methods: In a prospective study, 149 men underwent radical cystectomy and urinary diversion (70 ileal conduit, 16 MAINZ pouch, and 63 orthotopic ileal neobladder). Different domains of QoL, including general and physical conditions, psychological status, social status, sexual life, diversion-related symptoms, and satisfaction with the treatment were assessed using an author constructed questionnaire. Assessment was performed at three months postoperatively. Results: In questions addressing psychological status, social status, and sexual life, patients with continent diversion had a more favorable outcome (P = 0.002, P = 0.01, and P = 0.002, respectively). The rate of erectile dysfunction did not differ significantly between the three groups (P = 0.21). The rate and global satisfaction was higher with the MAINZ pouch (68.7%) and ileal neobladder (76.2%) as compared with the ileal conduit group (52.8%) (P = 0.002). Conclusion: Continent urinary diversion after radical cystectomy provides better results in terms of QoL as compared with ileal conduit diversion. PMID:24049384

Low estimated glomerular filtration rate and chronic kidney failure following liver transplant: a retrospective cohort study.

PubMed

Narciso, Roberto C; Ferraz, Leonardo R; Rodrigues, Cassio J O; Monte, Júlio C M; Mie, Sérgio; Dos Santos, Oscar F P; Paes, Ângela T; Cendoroglo, Miguel; Jaber, Bertrand L; Durão, Marcelino S; Batista, Marcelo C

2013-07-01

Patients undergoing orthotropic liver transplant (LTx) often present with chronic kidney disease (CKD). Identification of patients who will progress to end-stage renal disease (ESRD) might allow not only the implementation of kidney protective measures but also simultaneous kidney transplant. Retrospective cohort study in adults who underwent LTx at a single center. ESRD, death, and composite of ESRD or death were studied outcomes. 331 patients, who underwent LTx, were followed up for 2.6 ± 1.4 years; 31 (10%) developed ESRD, 6 (2%) underwent kidney transplant after LTx and 25 (8%) remained on chronic hemodialysis. Patients with preoperative eGFR lesser than 60 ml/min per 1.73 m2 had a 4-fold increased risk of developing ESRD after adjustment for sex, diabetes mellitus, APACHE II score, use of nephrotoxic drugs, and severe liver graft failure (HR = 3.95, 95% CI 1.73, 9.01; p = 0.001). Other independent risk factors for ESRD were preoperative diabetes mellitus and post-operative severe liver graft dysfunction. These findings emphasize low eGFR prior to LTx as a predictor for ESRD or death. The consideration for kidney after liver transplant as a treatment modality should be taken into account for those who develop chronic kidney failure after LTx.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

PubMed

Okumura, Shinya; Uemura, Tadahiro; Zhao, Xiangdong; Masano, Yuki; Tsuruyama, Tatsuaki; Fujimoto, Yasuhiro; Iida, Taku; Yagi, Shintaro; Bezinover, Dmitri; Spiess, Bruce; Kaido, Toshimi; Uemoto, Shinji

2017-09-01

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Expanded Criteria for Hepatocellular Carcinoma in Liver Transplant.

PubMed

Haberal, Mehmet; Akdur, Aydıncan; Moray, Gökhan; Arslan, Gülnaz; Özçay, Figen; Selçuk, Haldun; Özdemir, Handan

2017-03-01

Hepatocellular carcinoma is the sixth most common cancer worldwide and is the third highest cause of malignancy-related death. Because of its typically late diagnosis, median survival is approximately 6 to 20 months, with 5-year survival of < 12%. Hepatocellular carcinoma typically arises in the background of cirrhosis, with liver transplant regarded as the optimal therapy for selected patients. Initially, orthotopic liver transplant was limited to patients with extensive unresectable tumors, resulting in uniformly dismal outcomes due to high tumor recurrence rates. Here, we evaluated our long-term results with expanded-criteria liver transplant. From December 1988 to January 2017, we performed 552 liver transplants at Baskent University. In candidates with hepatocellular carcinoma, our expanded criteria for liver transplant is applied regardless of tumor size and number, includes those without major vascular invasion and without distant metastasis, and those with negative cytology (if the patient has ascites). Since 1994, of 61 liver transplants for hepatocellular carcinoma, 36 patients received transplants according to our expanded criteria. Of 36 expanded-criteria patients, 11 were children and 25 were adults. Sixteen patients (4 pediatric, 12 adult) were within our expanded criteria both radiologically and pathologically before transplant. The other 20 patients (7 pediatric, 13 adult) were within Milan criteria radiologically before transplant; however, after liver transplant, when pathologic specimens were evaluated, patients were found to be within our center's expanded criteria. During follow-up, 9/36 patients (25%) had hepatocellular carcinoma recurrence. In pediatric patients, 5-year and 10-year survival rates were 90%; in adults, 5-year survival was 58.7% and 10-year survival was 49.7%. Overall 5-year and 10-year survival rates were 71.7% and 62.7%. Liver transplant is safe and effective in patients with hepatocellular carcinoma in combination with interventional radiology procedures, regardless of tumor size and number, without major vascular invasion and distant metastasis.

Lower incidence of bronchiolitis obliterans in pediatric liver-lung transplant recipients with cystic fibrosis.

PubMed

Faro, Albert; Shepherd, Ross; Huddleston, Charles B; Lowell, Jeffrey; Gandhi, Sanjiv; Nadler, Michelle; Sweet, Stuart C

2007-06-15

Simultaneous liver-lung transplantation is an infrequent but technically feasible procedure in patients with end-stage lung disease and advanced liver disease. We characterize the outcomes of pediatric patients who underwent this procedure at our institution. We performed a retrospective, case-control study and reviewed the medical records of all patients referred to our transplant program from its inception. Seven patients were listed for simultaneous liver-lung transplant. The five patients who survived to transplant were matched to 13 controls who underwent isolated bilateral sequential lung transplant for underlying diagnosis, age at time of transplant, gender, and era of transplant. Outcome measures included patient and graft survival, occurrence of bronchiolitis obliterans (BO), and episodes of rejection. Of the five study patients who underwent liver-lung transplant, one died of multiorgan failure 11 days after transplant compared with 9 of 13 controls who died. The median survival for the study patients was 89 months (range, 0-112 months) compared with the controls, who had a median survival of 34 months (range, 0-118 months). The remaining four patients had bronchiolitis obliterans syndrome scores of 0 compared with 5 of 13 control patients (P=0.02). The rate of acute rejection per 100 patient days was 0.012 for the study patients compared with 0.11 for the controls (P=0.025). Simultaneous liver-lung transplantation is a technically feasible procedure with excellent long-term outcomes. The surviving study subjects remain free from bronchiolitis obliterans syndrome. These results suggest that the transplanted liver may bestow immunologic privilege to the lung allograft.

Epstein-Barr DNA serology and positron-emission tomography imaging of the head and neck in pediatric transplant recipients.

PubMed

Sidell, Douglas; Venick, Robert S; Shapiro, Nina L

2014-05-01

Epstein-Barr virus (EBV) infection is a potential precursor of post-transplantation lymphoproliferative disorder (PTLD) in the pediatric transplant patient. Positron-emission tomography (PET) imaging is increasingly utilized in this population to monitor for neoplasia and PTLD. We assess the association between EBV serum titers and Waldeyer's ring and cervical lymph node PET positivity in the pediatric transplant recipient. Retrospective analysis of EBV serology and PET imaging results in pediatric orthotopic liver transplantation (OLT) recipients. Imaging results and laboratory data were reviewed for all pediatric OLT recipients from January 2005 to July 2011 at a single institution. Charts were evaluated for PET positivity at Waldeyer's ring or cervical lymphatics, and for EBV serology results. Demographic data extracted include patient sex and age at transplantation. A total of 122 pediatric OLT recipients were reviewed. Twelve patients (10%) underwent PET imaging. Overall, four patients (33%) had evidence of PET positivity at Waldeyer's ring or cervical lymphatics. Five patients (42%) had positive EBV serology. There was a significant association between PET imaging results and EBV DNA serology results (P = .01). PTLD surveillance in the pediatric transplant recipient is an important component of long-term care in this population. Although PET imaging is a new modality in monitoring pediatric transplant recipients for early signs of PTLD, an association between EBV serology and PET imaging results appears to exist. With increased implementation, PET imaging will likely prove valuable in its ability to monitor the transplant recipient at risk for PTLD. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Using PEGylated iron oxide nanoparticles with ultrahigh relaxivity for MR imaging of an orthotopic model of human hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Wang, Ruizhi; Hu, Yong; Yang, Yuchan; Xu, Wei; Yao, Mingrong; Gao, Dongmei; Zhao, Yan; Zhan, Songhua; Shi, Xiangyang; Wang, Xiaolin

2017-02-01

Hepatocellular carcinoma (HCC) is the most common type of liver malignant tumor, which is often diagnosed in advanced stages, resulting in low survival rate. The sensitive diagnosis of early HCC presents a great interest. Herein, a novel superparamagnetic contrast agent composed of iron oxide nanoparticles is reported. Firstly, polyethyleneimine-coated iron oxide (Fe3O4@PEI) nanoparticles (NPs) were synthesized via a mild reduction route, followed by their modification of polyethylene glycol monomethyl ether ( mPEG-COOH) via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride coupling chemistry. After acetylation of the remaining PEI amines, the PEGylated Fe3O4 (Fe3O4@PEI.Ac- mPEG-COOH) NPs were successively characterized via different techniques. The Fe3O4@PEI.Ac- mPEG-COOH probes with an Fe3O4 NP size of 9 nm are water dispersible and cytocompatible within the given concentration range. The percentages of PEI and m-PEG-COOH on the particles surface are calculated to be 15.5 and 7.2%, respectively. Prior to the administration of Fe3O4@PEI.Ac- mPEG-COOH NPs of ultrahigh r 2 relaxivity (461.29 mM-1 s-1) via tail intravenous injection for MR imaging of HCC, the orthotopic model of HCC was established in the nude mice by surgical transplantation with HCCLM3 cells. The analysis of MR signal intensity (SI) in the orthotopic tumor model demonstrated that the developed Fe3O4@PEI.Ac- mPEG-COOH NPs were able to infiltrate into the tumor area through the enhanced permeability and retention (EPR) effect reaching the bottom at 2 h postinjection. The developed Fe3O4@PEI.Ac- mPEG-COOH NPs may be further applied for theranostics of different diseases through combing various therapeutic agents.

Comparison of the WarmCloud and Bair Hugger Warming Devices for the Prevention of Intraoperative Hypothermia in Patients Undergoing Orthotopic Liver Transplantation: A Randomized Clinical Trial

PubMed Central

Pearce, Brett; Mattheyse, Linda; Ellard, Louise; Desmond, Fiona; Pillai, Param; Weinberg, Laurence

2018-01-01

Background The avoidance of hypothermia is vital during prolonged and open surgery to improve patient outcomes. Hypothermia is particularly common during orthotopic liver transplantation (OLT) and associated with undesirable physiological effects that can adversely impact on perioperative morbidity. The KanMed WarmCloud (Bromma, Sweden) is a revolutionary, closed-loop, warm-air heating mattress developed to maintain normothermia and prevent pressure sores during major surgery. The clinical effectiveness of the WarmCloud device during OLT is unknown. Therefore, we conducted a randomized controlled trial to determine whether the WarmCloud device reduces hypothermia and prevents pressure injuries compared with the Bair Hugger underbody warming device. Methods Patients were randomly allocated to receive either the WarmCloud or Bair Hugger warming device. Both groups also received other routine standardized multimodal thermoregulatory strategies. Temperatures were recorded by nasopharyngeal temperature probe at set time points during surgery. The primary endpoint was nasopharyngeal temperature recorded 5 minutes before reperfusion. Secondary endpoints included changes in temperature over the predefined intraoperative time points, number of patients whose nadir temperature was below 35.5°C and the development of pressure injuries during surgery. Results Twenty-six patients were recruited with 13 patients randomized to each group. One patient from the WarmCloud group was excluded because of a protocol violation. Baseline characteristics were similar. The mean (standard deviation) temperature before reperfusion was 36.0°C (0.7) in the WarmCloud group versus 36.3°C (0.6) in the Bairhugger group (P = 0.25). There were no statistical differences between the groups for any of the secondary endpoints. Conclusions When combined with standardized multimodal thermoregulatory strategies, the WarmCloud device does not reduce hypothermia compared with the Bair Hugger device in patients undergoing OLT. PMID:29707629

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

PubMed

Mekahli, Djalila; van Stralen, Karlijn J; Bonthuis, Marjolein; Jager, Kitty J; Balat, Ayşe; Benetti, Elisa; Godefroid, Nathalie; Edvardsson, Vidar O; Heaf, James G; Jankauskiene, Augustina; Kerecuk, Larissa; Marinova, Svetlana; Puteo, Flora; Seeman, Tomas; Zurowska, Aleksandra; Pirenne, Jacques; Schaefer, Franz; Groothoff, Jaap W

2016-11-01

The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults. Cohort study. We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries. Liver transplantation. Transplantation and patient survival. 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4). No data for liver disease of kidney therapy recipients. Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus.

PubMed

He, Xiao-Shun; Fu, Shun-Jun; Zhao, Qiang; Zhu, Xiao-Feng; Wang, Dong-Ping; Han, Ming; Ju, Wei-Qiang; Ma, Yi; Jiao, Xing-Yuan; Yuan, Xiao-Peng; Hu, An-Bin; Guo, Zhi-Yong

2017-09-01

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis.

PubMed

Zhang, Yu; Davis, Celestia; Shah, Sapana; Hughes, Daniel; Ryan, James C; Altomare, Diego; Peña, Maria Marjorette O

2017-01-01

Liver metastasis is the major cause of death from colorectal cancer (CRC). Understanding its mechanisms is necessary for timely diagnosis and development of effective therapies. Interleukin-33 (IL-33) is an IL-1 cytokine family member that uniquely functions as a cytokine and nuclear factor. It is released by necrotic epithelial cells and activated innate immune cells, functioning as an alarmin or an early danger signal. Its role in invoking type 2 immune response has been established; however, it has contrasting roles in tumor development and metastasis. We identified IL-33 as a potently upregulated cytokine in a highly metastatic murine CRC cell line and examined its role in tumor growth and metastasis to the liver. IL-33 was transgenically expressed in murine and human adenocarcinoma and carcinoma cell lines and their growth and spontaneous metastasis to the liver were assessed in orthotopic models of CRC in wild-type C57Bl/6 and Il33 knockout mice. The results showed that increased expression of IL-33 in CRC cells enhanced their tumor take, growth, and liver metastasis. Tumor- rather than host-derived IL-33 induced the enhanced recruitment of CD11b + GR1 + and CD11b + F4/80 + myeloid cells to remodel the tumor microenvironment by increased expression of mobilizing cytokines, and tumor angiogenesis by activating endothelial cells. IL-33 expression was elevated in patient tumor tissues, induced early in adenoma development, and activated by pro-inflammatory cytokines derived from the tumor microenvironment. The data suggest that tumor-derived IL-33 modulates the tumor microenvironment to potently promote colon carcinogenesis and liver metastasis, underscoring its potential as a therapeutic target. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Targeting the vascular and perivascular niches as a regenerative therapy for lung and liver fibrosis.

PubMed

Cao, Zhongwei; Ye, Tinghong; Sun, Yue; Ji, Gaili; Shido, Koji; Chen, Yutian; Luo, Lin; Na, Feifei; Li, Xiaoyan; Huang, Zhen; Ko, Jane L; Mittal, Vivek; Qiao, Lina; Chen, Chong; Martinez, Fernando J; Rafii, Shahin; Ding, Bi-Sen

2017-08-30

The regenerative capacity of lung and liver is sometimes impaired by chronic or overwhelming injury. Orthotopic transplantation of parenchymal stem cells to damaged organs might reinstate their self-repair ability. However, parenchymal cell engraftment is frequently hampered by the microenvironment in diseased recipient organs. We show that targeting both the vascular niche and perivascular fibroblasts establishes "hospitable soil" to foster the incorporation of "seed," in this case, the engraftment of parenchymal cells in injured organs. Specifically, ectopic induction of endothelial cell (EC)-expressed paracrine/angiocrine hepatocyte growth factor (HGF) and inhibition of perivascular NOX4 [NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 4] synergistically enabled reconstitution of mouse and human parenchymal cells in damaged organs. Reciprocally, genetic knockout of Hgf in mouse ECs ( Hgf iΔEC/iΔEC ) aberrantly up-regulated perivascular NOX4 during liver and lung regeneration. Dysregulated HGF and NOX4 pathways subverted the function of vascular and perivascular cells from an epithelially inductive niche to a microenvironment that inhibited parenchymal reconstitution. Perivascular NOX4 induction in Hgf iΔEC/iΔEC mice recapitulated the phenotype of human and mouse liver and lung fibrosis. Consequently, EC-directed HGF and NOX4 inhibitor GKT137831 stimulated regenerative integration of mouse and human parenchymal cells in chronically injured lung and liver. Our data suggest that targeting dysfunctional perivascular and vascular cells in diseased organs can bypass fibrosis and enable reparative cell engraftment to reinstate lung and liver regeneration. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Gene Therapy for Liver Transplantation Using Adenoviral Vectors: CD40–CD154 Blockade by Gene Transfer of CD40Ig Protects Rat Livers from Cold Ischemia and Reperfusion Injury

PubMed Central

Ke, Bibo; Shen, Xiu-Da; Gao, Feng; Busuttil, Ronald W.; Löwenstein, Pedro R.; Castro, Maria G.; Kupiec-Weglinski, Jerzy W.

2010-01-01

Liver injury induced by ischemia/reperfusion (I/R) is the prime factor in delayed or loss graft function following transplantation. CD4+ T lymphocytes are key cellular mediators of antigen-independent inflammatory response triggered by I/R. We attempted to modulate rat liver I/R injury by targeted gene therapy with CD40Ig, which blocks the CD40–CD154 costimulation pathway. One hundred percent of Ad-CD40Ig-pretreated orthotopic liver transplants (OLTs) subjected to 24 h of cold (4°C) ischemia survived >14 days (vs 50% in untreated/Ad-β-gal groups). Ad-CD40Ig treatment decreased sGOT levels and depressed neutrophil infiltration, compared with controls. These functional data correlated with histological Suzuki’s grading of hepatic injury, which in untreated/Ad-β-gal groups showed severe necrosis (>60%) and moderate to severe sinusoidal congestion; the Ad-CD40Ig-pretreated group revealed minimal sinusoidal congestion/necrosis. Unlike in controls, OLT expression of mRNA coding for IL-2/IFN-γ remained depressed, whereas that of IL-4/IL-13 reciprocally increased in the Ad-CD40Ig group. Ad-CD40Ig reduced frequency of TUNEL+ cells and proapoptotic Caspase-3, but enhanced antioxidant HO-1 and antiapoptotic Bcl-2/Bcl-xl expression. Thus, prolonged blockade of CD40–CD154 by CD40Ig exerts potent cytoprotection against hepatic I/R injury. These results provide the rationale for a novel gene therapy approach to maximize the organ donor pool through the safer use of liver transplants exposed to prolonged cold ischemia. PMID:14741776

Factors influencing long-term quality of life and depression in German liver transplant recipients: a single-centre cross-sectional study.

PubMed

Zahn, Alexandra; Seubert, Lisa; Jünger, Jana; Schellberg, Dieter; Weiss, Karl Heinz; Schemmer, Peter; Stremmel, Wolfgang; Sauer, Peter; Gotthardt, Daniel Nils

2013-06-26

Health-related quality of life (HRQOL) following orthotopic liver transplantation (OLT) has become increasingly important. Therefore, we aimed to identify factors affecting HRQOL after OLT. This cross-sectional, single-centre study surveyed 281 OLT patients. Survey tools included the Short Form (SF-36) Health Survey, the Patient Health Questionnaire 9 (PHQ9), and a self-designed employment questionnaire. Patient medical records were reviewed. Participants included 187 men (mean age at OLT: 50 [± 11; 13-69] years). Primary indications for OLT were viral hepatitis (28%), alcoholic liver disease (35%), cholestatic liver disease (11%), and others (26%). Follow-up ranged from 2 to 136 months. Clinical factors associated with improved HRQOL were age ≤ 45 years at OLT and current MELD score <=≤ 13. Time after OLT and indication for transplantation affected SF-36 HRQOL. SF-36 physical component summary scales plateaued at 3-years post-OLT and then stabilized. For the SF-36 HRQOL, scores were the lowest in all domains for OLT recipients transplanted for chronic viral hepatitis and for unemployed patients, whereas sex and number of transplantations showed no significant differences. The PHQ9 results showed that depression was significantly more frequent among patients with current MELD score ≥ 13 or impaired liver function and those transplanted for chronic viral hepatitis or unemployed patients. Age and sex did not influence PHQ9 results. Medical and psychosocial support is crucial for long-term HRQOL after OLT. Developing multidisciplinary interventions to address issues such as employment, age, MELD score, and liver function may improve long-term HRQOL in these patients.

Histological long-term outcomes from acute antibody-mediated rejection following ABO-compatible liver transplantation.

PubMed

Del Bello, Arnaud; Danjoux, Marie; Congy-Jolivet, Nicolas; Lavayssière, Laurence; Esposito, Laure; Muscari, Fabrice; Kamar, Nassim

2017-04-01

Acute antibody-mediated rejection (aAMR) is an unusual complication after orthotopic ABO-compatible liver transplantation. To date, the clinical and histological long-term outcomes after aAMR are not well known. Herein, we describe nine cases of aAMR that occurred in our liver-transplant center between 2008 and 2016, with an initial and reevaluation liver biopsy available for reexamination. Two patients presented with aAMR at 10.5 (10, 11) days post-transplantation, caused by preformed donor-specific antibodies. Seven other recipients developed de novo donor-specific antibodies and aAMR at 11.2 (3-24) months post-transplantation. Eight of the nine patients received a B-cell targeting agent (rituximab, with or without plasma exchange), associated with polyclonal antibodies (three patients) or intravenous immunoglobulins (three patients). At the last follow up (i.e. 21 [4-90] months post-aAMR), seven patients were alive, including two patients with normal liver tests. Grafts' survival was 66%. A liver biopsy performed at 11.5 (5-48.5) months after the first biopsy showed no significant improvement in aAMR score (from 2 ± 1.3 to 1.6 ± 1.5, P = 0.6), a significant improvement in chronic AMR score (from 37 ± 9 to 25 ± 8, P = 0.003) and an increase in the Metavir score (1.2 ± 0.6 to 2.1 ± 0.9, P = 0.03). In this study, a B-cell-depleting agent seemed to improve the prognosis of aAMR in selected cases, but several patients kept active lesions antibody-mediated rejection. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Endoscopic management of biliary complications following liver transplantation after donation from cardiac death donors.

PubMed

Croome, Kris P; McAlister, Vivian; Adams, Paul; Marotta, Paul; Wall, William; Hernandez-Alejandro, Roberto

2012-09-01

Previous studies have shown a higher incidence of biliary complications following donation after cardiac death (DCD) liver transplantation compared with donation after brain death (DBD) liver transplantation. The endoscopic management of ischemic type biliary strictures in patients who have undergone DCD liver transplants needs to be characterized further. A retrospective institutional review of all patients who underwent DCD liver transplant from January 2006 to September 2011 was performed. These patients were compared with all patients who underwent DBD liver transplantation in the same time period. A descriptive analysis of all DCD patients who developed biliary complications and their subsequent endoscopic management was also performed. Of the 36 patients who received DCD liver transplants, 25% developed biliary complications compared with 13% of patients who received DBD liver transplants (P=0.062). All DCD allograft recipients who developed biliary complications became symptomatic within three months of transplantation. Ischemic type biliary strictures in DCD allograft recipients included disseminated biliary strictures in two patients, biliary strictures of the hepatic duct bifurcation in three patients and biliary strictures of the donor common hepatic duct in three patients. There was a trend toward increasing incidence of total biliary complications in recipients of DCD liver allografts compared with those receiving DBD livers, and the rate of diffuse ischemic cholangiopathy was significantly higher. Focal ischemic type biliary strictures can be treated effectively in DCD liver transplant recipients with favourable results. Diffuse ischemic type biliary strictures in DCD liver transplant recipients ultimately requires retransplantation.

Comparison of Causes of Death After Heart Transplantation in Patients With Left Ventricular Ejection Fractions ≤35% Versus >35.

PubMed

Birati, Edo Y; Mathelier, Hansie; Molina, Maria; Hanff, Thomas C; Mazurek, Jeremy A; Atluri, Pavan; Acker, Michael A; Rame, J Eduardo; Margulies, Kenneth B; Goldberg, Lee R; Jessup, Mariell

2016-04-15

Sudden cardiac death (SCD) is a common cause of death in the general population, occurring in 300,000 to 350,000 people in the United States alone. Currently, there are no data supporting implantable cardioverter-defibrillator therapy in patients who underwent orthotopic heart transplant (OHT) with low left ventricular ejection fraction (LVEF). In this retrospective study, we included all patients who underwent primary OHT at our institution from 2007 to 2013. We compared the cause of death in patients who underwent OHT and evaluated the correlation of the cause of death and the patients' LVEF. Our objectives were to determine whether patients who underwent OHT with LVEF <35% are at increased risk for SCD compared with those who underwent OHT with normal LVEF. To summarize our results, a total of 345 patients were included in our study (mean age 50 ± 14 years, 68% men). The mean follow-up was 1,260 ± 698 days. Forty patients (11.5%) died >6 months after OHT. Surviving patients had higher LVEF compared with deceased patients (64 ± 7% and 50 ± 24%, respectively, p ≤0.001). In all, 10 (25%) of the deceased patients died suddenly, 9 (23%) from sepsis, and 8 (20%) from malignancy. Of the 11 deceased patients with LVEF ≤35%, 2 patients (18%) died suddenly compared with 9 SCDs among the 29 deceased patients (31%) with LVEF >35% (p = 0.54). In conclusion, patients who underwent OHT who died were more likely to have LVEF <35%, and a quarter of the deceased patients who underwent OHT died suddenly. A reduced LVEF was not associated with an increased risk of SCD. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of marginal grafts in deceased donor liver transplant: assessment of early outcomes.

PubMed

Godara, Rajesh; Naidu, C Sudeep; Rao, Pankaj P; Sharma, Sanjay; Banerjee, Jayant K; Saha, Anupam; Vijay, Kapileshwer

2014-03-01

Orthotopic liver transplantation has become a routinely applied therapy for an expanding group of patients with end-stage liver disease. Shortage of organs has led centers to expand their criteria for the acceptance of marginal donors. There is current debate about the regulation and results of liver transplantation using marginal grafts. The study included data of all patients who received deceased donor liver grafts between March 2007 to December 2011. Patients with acute liver failure, living donor transplantation, split liver transplantation, and retransplantation were excluded. Early allograft dysfunction, primary nonfunction, patient survival, and incidence of surgical complications were measured. A total of 33 patients were enrolled in this study. There were 20 marginal and 13 nonmarginal grafts. The two groups were well matched regarding age, sex and indication of liver transplantation, model for end-stage liver disease score, technique of transplant, requirement of vascular reconstruction, warm ischemia time, blood loss, mean operative time, etc. In our study, posttransplant peak level of liver enzymes, international normalization ratio, and bilirubin were not statistically significant in the marginal and nonmarginal group. Wound infection occurred in 10 % of marginal compared with 7.7 % of nonmarginal graft recipients (p > 0.05). In the marginal group, the incidences of vascular complications, hepatic artery thrombosis (four), and portal vein thrombosis (one) were not statistically significant compared to the nonmarginal group. Acute rejection was observed in a total of seven patients (21.2 %)-five (25 %) in the marginal group and two (15.4 %) in the nonmarginal graft recipients. Primary nonfunction occurred in three (9.1 %) patients-two (10 %) in the marginal and one (7.7 %) in the nonmarginal group. Average patient survival for the whole group was 91 % at 1 week, 87.8 % at 3 months, and 84.8 % at 6 months. Because organ scarcity persists, additional pressure will build to use a greater proportion of the existing donor pool. The study, although small, clearly indicates that marginal livers can assure a normal early functional recovery after transplantation.

Detection of mouse liver cancer via a parallel iterative shrinkage method in hybrid optical/microcomputed tomography imaging

NASA Astrophysics Data System (ADS)

Wu, Ping; Liu, Kai; Zhang, Qian; Xue, Zhenwen; Li, Yongbao; Ning, Nannan; Yang, Xin; Li, Xingde; Tian, Jie

2012-12-01

Liver cancer is one of the most common malignant tumors worldwide. In order to enable the noninvasive detection of small liver tumors in mice, we present a parallel iterative shrinkage (PIS) algorithm for dual-modality tomography. It takes advantage of microcomputed tomography and multiview bioluminescence imaging, providing anatomical structure and bioluminescence intensity information to reconstruct the size and location of tumors. By incorporating prior knowledge of signal sparsity, we associate some mathematical strategies including specific smooth convex approximation, an iterative shrinkage operator, and affine subspace with the PIS method, which guarantees the accuracy, efficiency, and reliability for three-dimensional reconstruction. Then an in vivo experiment on the bead-implanted mouse has been performed to validate the feasibility of this method. The findings indicate that a tiny lesion less than 3 mm in diameter can be localized with a position bias no more than 1 mm the computational efficiency is one to three orders of magnitude faster than the existing algorithms; this approach is robust to the different regularization parameters and the lp norms. Finally, we have applied this algorithm to another in vivo experiment on an HCCLM3 orthotopic xenograft mouse model, which suggests the PIS method holds the promise for practical applications of whole-body cancer detection.

Comparison of survival outcomes after anatomical resection and non-anatomical resection in patients with hepatocellular carcinoma

PubMed Central

Kim, Seheon; Kim, Seokwhan; Song, Insang

2015-01-01

Backgrounds/Aims Liver resection is a curative procedure performed worldwide for hepatocellular carcinoma (HCC). Deciding on the appropriate resection range for postoperative hepatic function preservation is an important surgical consideration. This study compares survival outcomes of HCC patients who underwent anatomical or non-anatomical resection, to determine which offers the best clinical survival benefit. Methods One hundred and thirty-one patients underwent liver resection with HCC, between January 2007 and February 2015, and were divided into two groups: those who underwent anatomical liver resection (n=88) and those who underwent non-anatomical liver resection (n=43). Kaplan-Meier survival analysis and Cox regressions were used to compare the disease-free survival (DFS) and overall survival (OS) rates between the groups. Results The mean follow-up periods were 27 and 40 months in the anatomical and non-anatomical groups, respectively (p=0.229). The 3- and 5-year DFS rates were 70% and 60% in the anatomical group and 62% and 48% in the non-anatomical group, respectively. The 3 and 5-year OS rates were 94% and 78% in the anatomical group, and 86% and 80% in the non-anatomical group, respectively. The anatomical group tended to show better outcomes, but the findings were not significant. However, a relative risk of OS between the anatomical and non-anatomical group was 0.234 (95% CI, 0.061-0.896; p=0.034), which is statistically significant. Conclusions Although statistical significance was not detected in survival curves, anatomical resection showed better results. In this respect, anatomical resection is more likely to perform in HCC patients with preserve liver function than non-anatomical resection. PMID:26693235

The Impact of Laparoscopic Approaches on Short-term Outcomes in Patients Undergoing Liver Surgery for Metastatic Tumors.

PubMed

Karagkounis, Georgios; Seicean, Andreea; Berber, Eren

2015-06-01

To compare the perioperative outcomes associated with open and laparoscopic (LAP) surgical approaches for liver metastases. The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all adult patients who underwent surgical therapy for metastatic liver tumors between 2006 and 2012 (N=7684). Patients who underwent >1 procedure were excluded. Logistic regression after matching on propensity scores was used to assess the association between surgical approaches and perioperative outcomes. A total of 4555 patients underwent open resection, 387 LAP resection, 297 open radiofrequency ablation (RFA), and 265 LAP RFA. In propensity-matched samples (over 95% of patients successfully matched), there was no significant difference between LAP resection and LAP RFA in perioperative complications and length of stay and both compared favorably with their open counterparts. Minimally invasive approaches for secondary hepatic malignancies were associated with improved postoperative morbidity and length of stay and should be preferred in appropriate patients.

Methods for Tumor Targeting with Salmonella typhimurium A1-R.

PubMed

Hoffman, Robert M; Zhao, Ming

2016-01-01

Salmonella typhimurium A1-R (S. typhimurium A1-R) has shown great preclinical promise as a broad-based anti-cancer therapeutic (please see Chapter 1 ). The present chapter describes materials and methods for the preclinical study of S. typhimurium A1-R in clinically-relevant mouse models. Establishment of orthotopic metastatic mouse models of the major cancer types is described, as well as other useful models, for efficacy studies of S. typhimurium A1-R or other tumor-targeting bacteria, as well. Imaging methods are described to visualize GFP-labeled S. typhimurium A1-R, as well as GFP- and/or RFP-labeled cancer cells in vitro and in vivo, which S. typhimurium A1-R targets. The mouse models include metastasis to major organs that are life-threatening to cancer patients including the liver, lung, bone, and brain and how to target these metastases with S. typhimurium A1-R. Various routes of administration of S. typhimurium A1-R are described with the advantages and disadvantages of each. Basic experiments to determine toxic effects of S. typhimurium A1-R are also described. Also described are methodologies for combining S. typhimurium A1-R and chemotherapy. The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies.

Cluster analysis identifies three urodynamic patterns in patients with orthotopic neobladder reconstruction.

PubMed

Kim, Kwang Hyun; Yoon, Hyun Suk; Song, Wan; Choo, Hee Jung; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Lee, Dong Hyeon

2017-01-01

To classify patients with orthotopic neobladder based on urodynamic parameters using cluster analysis and to characterize the voiding function of each group. From January 2012 to November 2015, 142 patients with bladder cancer underwent radical cystectomy and Studer neobladder reconstruction at our institute. Of the 142 patients, 103 with complete urodynamic data and information on urinary functional outcomes were included in this study. K-means clustering was performed with urodynamic parameters which included maximal cystometric capacity, residual volume, maximal flow rate, compliance, and detrusor pressure at maximum flow rate. Three groups emerged by cluster analysis. Urodynamic parameters and urinary function outcomes were compared between three groups. Group 1 (n = 44) had ideal urodynamic parameters with a mean maximal bladder capacity of 513.3 ml and mean residual urine volume of 33.1 ml. Group 2 (n = 42) was characterized by small bladder capacity with low compliance. Patients in group 2 had higher rates of daytime incontinence and nighttime incontinence than patients in group 1. Group 3 (n = 17) was characterized by large residual urine volume with high compliance. When we examined gender differences in urodynamics and functional outcomes, residual urine volume and the rate of daytime incontinence were only marginally significant. However, females were significantly more likely to belong to group 2 or 3 (P = 0.003). In multivariate analysis to identify factors associated with group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017) and male gender (OR 7.57, P = 0.003) were identified as significant factors. While patients with ileal neobladder present with various voiding symptoms, three urodynamic patterns were identified by cluster analysis. Approximately half of patients had ideal urodynamic parameters. The other two groups were characterized by large residual urine and small capacity bladder with low compliance. Young age and male gender appear to have a favorable impact on urodynamic and voiding outcomes in patients undergoing orthotopic neobladder reconstruction.

Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?

PubMed

Kodiatte, Thomas Alex; George, Sam Varghese; Chacko, Raju Titus; Ramakrishna, Banumathi

2017-01-01

Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.

Clinical and molecular characterisation of a prospectively collected cohort of children and adolescents with polycythemia vera.

PubMed

Cario, Holger; Schwarz, Klaus; Herter, Jan M; Komrska, Vladimir; McMullin, Mary F; Minkov, Milen; Niemeyer, Charlotte; Pospisilova, Dagmar; Reinhard, Harald; Debatin, Klaus-Michael; Pahl, Heike L

2008-08-01

The clinical, haematological, molecular and treatment data of eight paediatric patients with polycythemia vera (PV) were collected prospectively. One patient developed PV after treatment for large-cell anaplastic lymphoma. Budd-Chiari syndrome was diagnosed in two patients, necessitating orthotopic liver transplantation in one and transjugular portosystemic shunting in the other. The remaining patients presented with non-specific symptoms. Endogenous erythroid colonies were detected in all cases examined. The JAK2(V617F) mutation was found in six patients; two patients displayed JAK2 exon 12 mutations, including one novel mutation (JAK2(H538-K539delinsI)). CD177 (PRV-1) mRNA expression was increased in three of five patients tested.

Clinical and molecular characterisation of a prospectively collected cohort of children and adolescents with polycythemia vera

PubMed Central

Cario, Holger; Schwarz, Klaus; Herter, Jan M.; Komrska, Vladimir; McMullin, Mary F.; Minkov, Milen; Niemeyer, Charlotte; Pospisilova, Dagmar; Reinhard, Harald; Debatin, Klaus-Michael; Pahl, Heike L.

2014-01-01

Summary The clinical, haematological, molecular and treatment data of eight paediatric patients with polycythemia vera (PV) were collected prospectively. One patient developed PV after treatment for large-cell anaplastic lymphoma. Budd-Chiari syndrome was diagnosed in two patients, necessitating orthotopic liver transplantation in one and transjugular portosystemic shunting in the other. The remaining patients presented with non-specific symptoms. Endogenous erythroid colonies were detected in all cases examined. The JAK2V617F mutation was found in six patients; two patients displayed JAK2 exon 12 mutations, including one novel mutation (JAK2H538-K539delinsI). CD177 (PRV-1) mRNA expression was increased in three of five patients tested. PMID:18557746

Childhood Abuse, Nonadherence, and Medical Outcome in Pediatric Liver Transplant Recipients

ERIC Educational Resources Information Center

Shemesh, Eyal; Annunziato, Rachel A.; Yehuda, Rachel; Shneider, Benjamin L.; Newcorn, Jeffrey H.; Hutson, Carolyn; Cohen, Judith A.; Briere, John; Gorman, Jack M.; Emre, Sukru

2007-01-01

Objective: The study assessed the relationship between a history of child abuse, nonadherence to medications, and medical outcome in children who had a liver transplant. Method: Abuse history for children and adolescents ages 8 to 21 who underwent a liver transplantation at Mount Sinai Medical Center in New York was obtained in interviews in 2002.…

An initial report on the intraoperative use of indocyanine green fluorescence imaging in the surgical management of liver tumorss.

PubMed

Takahashi, Hideo; Zaidi, Nisar; Berber, Eren

2016-10-01

There has been a recent interest in the use of Indocyanine green (ICG) imaging. The aim of this study is to review our initial experience in liver surgery. ICG fluorescent imaging was used in 15 patients undergoing surgical treatment of their liver tumors between 2015 and 2016. ICG imaging was initially performed, followed by intraoperative ultrasound (IOUS). Findings on fluorescence were compared with preoperative cross-sectional imaging and IOUS. Sixty-two lesions were identified, with 34 located superficially and 28 deeply in the liver. While 13 patients underwent surgery for malignant liver metastases, two patients had operations for benign liver diseases. Seven patients underwent open or robotic liver resections, five laparoscopic microwave liver ablation, and three diagnostic laparoscopy. ICG identified all of the superficial lesions. IOUS identified 98% of all lesions. The most benefit of ICG was in showing the margins of the superficial lesions in real-time and guiding surgical treatment, which was limited by IOUS. This is the first North American study to evaluate the potential utility of ICG during liver surgery. Its major benefit seems to be in providing real-time feedback to the surgeon about the margins of superficial tumors for resection or ablation. J. Surg. Oncol. 2016;114:625-629. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Nonalcoholic steatohepatitis (NASH) after pancreaticoduodenectomy: association of pancreatic exocrine deficiency and infection.

PubMed

Murata, Yasuhiro; Mizuno, Shugo; Kato, Hiroyuki; Kishiwada, Masashi; Ohsawa, Ichiro; Hamada, Takashi; Usui, Masanobu; Sakurai, Hiroyuki; Tabata, Masami; Nishimura, Keisuke; Fukutome, Kazuo; Isaji, Shuji

2011-08-01

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

Antibody-Mediated Rejection of Human Orthotopic Liver Allografts

PubMed Central

Demetris, A. Jake; Jaffe, Ron; Tzakis, A.; Ramsey, Glenn; Todo, S.; Belle, Steven; Esquivel, Carlos; Shapiro, Ron; Markus, Bernd; Mroczek, Elizabeth; Van Thiel, D. H.; Sysyn, Greg; Gordon, Robert; Makowka, Leonard; Starzl, Tom

1988-01-01

A clinicopathologic analysis of liver transplantation across major ABO blood group barriers was carried out 1) to determine if antibody-mediated (humoral) rejection was a cause of graft failure and if humoral rejection can be identified, 2) to propose criteria for establishing the diagnosis, and 3) to describe the clinical and pathologic features of humoral rejection. A total of 51 (24 primary) ABO-incompatible (ABO-I) liver grafts were transplanted into 49 recipients. There was a 46% graft failure rate during the first 30 days for primary ABO-I grafts compared with an 11% graft failure rate for primary ABO compatible (ABO-C), crossmatch negative, age, sex and priority-matched control patients (P < 0.02). A similarly high early graft failure rate (60%) was seen for nonprimary ABO-I grafts during the first 30 days. Clinically, the patients experienced a relentless rise in serum transaminases, hepatic failure, and coagulopathy during the first weeks after transplant. Pathologic examination of ABO-I grafts that failed early demonstrated widespread areas of geographic hemorrhagic necrosis with diffuse intraorgan coagulation. Prominent arterial deposition of antibody and complement components was demonstrated by immunoflourescent staining. Elution studies confirmed the presence of tissue-bound, donor-specific isoagglutinins within the grafts. No such deposition was seen in control cases. These studies confirm that antibody mediated rejection of the liver occurs and allows for the development of criteria for establishing the diagnosis. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:3046369

Defibrotide for the treatment of veno-occlusive disease after liver transplantation.

PubMed

Mor, E; Pappo, O; Bar-Nathan, N; Shaharabani, E; Shapira, Z; Tur-Kaspa, R; Ben-Ari, Z

2001-10-15

Veno-occlusive disease (VOD) after liver transplantation is associated with acute rejection and poor outcome. The use of antithrombotic and thrombolytic agents is limited by their toxicity. Defibrotide is a polydeoxyribonucleotide with thrombolytic and antithrombotic properties and no systemic anticoagulant effect. Defibrotide, 35-40 mg/kg/day, was administered intravenously for 21 days on a compassionate-use basis to two patients aged 66 and 49 years. VOD had developed 6 weeks and 4 months after orthotopic liver transplantation for hepatitis C and hepatitis B infection, respectively. VOD was diagnosed clinically by findings of weight gain (8.5% and 16%), ascites, jaundice (serum bilirubin 5.4 mg/dl and 21.7 mg/dl), and severe coagulopathy (in one patient), and histologically by the presence of hemorrhagic centrilobular necrosis and fibrous stenosis of the hepatic venules. One of the patients had received azathioprine as part of the immunosuppressive regimen. There was no evidence of acute cellular rejection histologically. After 3 weeks of defibrotide administration, the first patient showed complete clinical resolution of the VOD, and serum bilirubin level normalized. He is alive 6 months after transplantation. The second patient, treated at a later stage of disease, showed marked improvement in the coagulopathic state, but there was no resolution of the VOD. He died 2 months later of multiorgan failure due to Escherichia coli sepsis. Neither patient had side effects from the drug. Defibrotide is a promising drug for the treatment of VOD after liver transplantation and needs to be evaluated in large, prospective studies.

Reduction of rewarming injury of the hepatic graft by a heat insulator.

PubMed

Wakiyama, S; Yanaga, K; Soejima, Y; Nishizaki, T; Sugimachi, K

1997-04-01

The deleterious effect of rewarming in orthotopic liver transplantation is recognized. This study examined the significance of rewarming the hepatic allograft, and the possibility of using a heat insulator to reduce rewarming injury. After total hepatectomy in rats with in situ perfusion by chilled (4 degrees C) lactated Ringer's solution, the livers were divided into four groups of ten each: group 1, 4-h preservation in chilled Ringer's solution and 15 min of rewarming; group 2, 6-h preservation in chilled Ringer's solution; group 3, 6-h preservation in chilled Ringer's solution and 15 min of rewarming; group 4, 6-h preservation in chilled Ringer's solution and 15 min of rewarming with a heat insulator. Glutamic-pyruvic transaminase (GPT) and N-acetyl-beta-glucosaminidase (NAG) concentrations in the final graft effluent, and the amount of adenosine 5'-triphosphate (ATP) in liver tissue after preservation, were measured. GPT and NAG concentrations in the final graft effluent of group 3 were higher than those of group 2 (P < 0.01), whereas values in group 4 were lower than those of group 3 (P < 0.05). The final ATP concentration in group 3 was significantly lower than that in group 2 (P < 0.01), whereas the value in group 4 was significantly higher than that of group 3 (P < 0.01). Rewarming diminishes the viability of a liver graft with degradation of ATP, and a heat insulator reduces rewarming injury.

Serial volumetric assessment of large for size liver grafts after whole cadaveric liver transplant in adults: do large liver grafts shrink in size?

PubMed

Bekheit, Mohamed; Rajakannu, Muthukumarassamy; Bucur, Petru; Adam, Rene; SaCunha, Antonio; Castaing, Denis; Cherqui, Daniel; Vibert, Eric

2016-02-01

After whole graft orthotopic liver transplantation (OLT), adaptation of the large grafts' volume to recipient weight is widely accepted despite the paucity of evidence on this subject. Thirty nine patients with GRWR > 2.5% were included in this study and subsequently divided into two groups with 3 ≥ GRWR > 3%. Patients had CT scans at three predetermined time points after OLT used for measuring the liver volume. The objective of this study is to evaluate the volumetric changes of whole large liver grafts after adult OLT. At LT, the mean graft recipient body weight ratio (GRWR) was 3.1 ± 0.4%. The mean liver weight was 1881 ± 68 g at LT, 2014 ± 99 ml at one week, 1725 ± 126 ml at 3 months, and 1632 ± 117 (ml) at >6 months. There is an initial increase at 1 week after LT and a subsequent decrease of liver volume on later measurements. None of the late volume measurements were significantly different from the initial graft volume at liver transplant in pair wise comparisons ANOVA repeated measures (p > 0.05). Similarly, the mean GRWR did not change significantly between the initial calculation at transplantation date and the subsequent measurements during the different study time points (F = 0.04, p = 0.96) with a mean of 3.1% (95% CI = 2.2-4.2). AUC ROC discriminated a cutoff of 3% for the initial GRWR above which grafts tend to decrease in size over time (c statistics = 0.74, p = 0.036). In a Clustered ANOVA repeated measures, there was no significant difference in the changes of liver volume between both groups. However, patients with GRWR > 3 showed a trend towards a latent reduction in volume over the tracing period. There was a tendency, but none significant; towards a higher bilirubin, AST, ALT levels over the first postoperative days in recipients with GRWR > 3. Large grafts do not significantly decrease in size. Nonetheless, grafts weighing >3% of the GRWR show a different trend towards decrease in size over time. Copyright © 2015. Published by Elsevier Ltd.

Can tricuspid annuloplasty of the donor heart reduce valve insufficiency following cardiac transplantation with bicaval anastomosis?

PubMed

Fiorelli, Alfredo I; Oliveira, José L; Santos, Ronaldo H B; Coelho, Guilherme B; Oliveira, Adriana S; Lourenço-Filho, Domingos D; Lapenna, Gisele; Dias, Ricardo R; Bacal, Fernando; Bocchi, Edimar A; Stolf, Noedir A G

2010-06-01

The aim of this study was to evaluate the degree of tricuspid valve insufficiency after orthotopic cardiac transplantation with bicaval anastomosis and prophylactic donor heart annuloplasty. At present, our cardiac transplantation experience includes 478 cases. After January 2002, we included 30 consecutive patients in this study who had undergone orthotopic cardiac transplantation and survived >6 months. The patients were divided into 2 groups: group I, 15 patients who underwent transplantation with prophylactic tricuspid annuloplasty on the donor heart with the De Vega technique; and group II, 15 patients who underwent transplantation without this procedure. Their preoperative clinical characteristics were the same. During the late postoperative follow-up, the degree of tricuspid insufficiency was evaluated by transthoracic Doppler echocardiography and assessed according to the Simpson scale: 0, absent; 1, mild; 2, moderate; and 3, severe. Hemodynamic parameters were evaluated invasively by means of a Swan-Ganz catheter during routine endomyocardial biopsies. The mean follow-up time was 26.9 +/- 5.4 months (range, 12-36 months). In group I, 1 patient (6.6%) died from infection in the 18th month after the operation; the death was not related to the annuloplasty. In group II, 1 death (6.6%) occurred after 10 months because of rejection (P > .05). After the 24-month follow-up, the mean degree of tricuspid insufficiency was 0.4 +/- 0.5 in group I and 1.7 +/- 0.9 in group II (P < .05). Similarly, the 2 groups were significantly different with respect to the right atrium pressure, which was higher in group II. Prophylactic tricuspid annuloplasty on the donor heart was able to reduce significantly the degree of valvular insufficiency, even in cardiac transplantation with bicaval anastomosis; however, it did not modify significantly the hemodynamic performance of the allograft during the investigation period. It is very important to extend the observation period and casuistics to verify other benefits that this technique may offer.

Does adjuvant radiotherapy suppress liver regeneration after partial hepatectomy?

PubMed

Choi, Jin-Hwa; Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young; Kim, Sun Whe; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Ha, Sung W

2009-05-01

To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 +/- 38.3cm(3) and 81.5 +/- 75.6cm(3), respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.

Post-traumatic hepatic artery pseudo-aneurysm combined with subphrenic liver abscess treated with embolization

PubMed Central

Sun, Long; Guan, Yong-Song; Wu, Hua; Pan, Wei-Min; Li, Xiao; He, Qing; Liu, Yuan

2006-01-01

A 23-year-old man with post-traumatic hepatic artery pseudo-aneurysm and subphrenic liver abscess was admitted. He underwent coil embolization of hepatic artery pseudo-aneurysm. The pseudo-aneurysm was successfully obstructed and subphrenic liver abscess was controlled. Super-selective trans-catheter coil embolization may represent an effective treatment for hepatic artery pseudo-aneurysm combined with subphrenic liver abscess in the absence of other therapeutic alternatives. PMID:16718774

Post-traumatic hepatic artery pseudo-aneurysm combined with subphrenic liver abscess treated with embolization.

PubMed

Sun, Long; Guan, Yong-Song; Wu, Hua; Pan, Wei-Min; Li, Xiao; He, Qing; Liu, Yuan

2006-05-07

A 23-year-old man with post-traumatic hepatic artery pseudo-aneurysm and subphrenic liver abscess was admitted. He underwent coil embolization of hepatic artery pseudo-aneurysm. The pseudo-aneurysm was successfully obstructed and subphrenic liver abscess was controlled. Super-selective trans-catheter coil embolization may represent an effective treatment for hepatic artery pseudo-aneurysm combined with subphrenic liver abscess in the absence of other therapeutic alternatives.

Twenty-Year Outcome After Right Ventricular Outflow Tract Repair Using Heterotopic Pulmonary Conduits in Infants and Children.

PubMed

Hoxha, Stiljan; Torre, Salvatore; Rungatscher, Alessio; Sandrini, Camilla; Rossetti, Lucia; Barozzi, Luca; Faggian, Giuseppe; Luciani, Giovanni Battista

2016-01-01

Durability of pulmonary conduits (PCs) used for reconstruction of the right ventricular outflow tract (RVOT) may be affected by a variety of factors. Among these, the technique used for PC implantation, whether in orthotopic or heterotopic position, strictly dependent upon the underlying anatomy, has been suggested to influence long-term outcome after RVOT repair. To determine the outcome of heterotopic implantation in infants and children treated at our institution, late results of heterotopic PC in non-Ross patients were analyzed and compared with data of orthotopic PC in age-matched pediatric Ross patients operated during the same time period. Between November 1991 and January 2015, 58 infants and children, 32 male and 26 female, with a median age of 9.4 years (range 1 day-18 years) underwent implantation of heterotopic PC (31 homografts [HG] and 27 xenografts [XG]) for reconstruction of RVOT. Median age in the XG group was significantly lower than in the HG group (0.9 vs. 13.4 years, P = 0.01), while male/female ratio was similar. Fifty (86%) patients had undergone one or more prior cardiac operations, while 32 (55%) required associated procedures during PC implantation. Comparison with data in 305 children and with a median age of 9.4 years, receiving orthotopic PC between 1990 and 2012 (Italian Pediatric Ross Registry), was undertaken. Descriptive, univariate, and Kaplan-Meier analysis defined outcome. There were three (5.2%) early and five (9.0%) late deaths, during a median follow-up of 7.6 years (range 2 months-23 years). Patients having XG had trend toward higher hospital mortality (2/27 vs. 1/31, P = 0.2), but similar late mortality (2/24 vs. 3/30, P = 0.3). Overall survival was 88 and 62%, while freedom from PC replacement was 49 and 21%, at 10 and 20 years, respectively. The latter proved significantly worse than freedom from orthotopic PC replacement, which was 94 ± 2 and 70 ± 9% at 10 and 20 years (P = 0.02). When stratified for type of heterotopic PC, late survival proved comparable (81 and 81% for XG vs. 92 and 60% for HG, at 10 and 20 years, respectively, P = 0.7). However, freedom from PC replacement was significantly higher in patients with heterotopic HG (21 and 5% for XG vs. 63 and 48% for HG, at 10 and 20 years, respectively, P = 0.001). RVOT repair using either XG or HG in heterotopic position is a safe procedure associated with low hospital mortality and satisfactory late survival. Freedom from reoperation is significantly lower than that observed in age-matched children having orthotopic HG. Freedom from reoperation in heterotopic XG is poorer than in HG, although different baseline demography may have influenced this finding. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Response of the oxygen uptake efficiency slope to orthotopic heart transplantation: lack of correlation with changes in central hemodynamic parameters and resting lung function.

PubMed

Van Laethem, Christophe; Goethals, Marc; Verstreken, Sofie; Walravens, Maarten; Wellens, Francis; De Proft, Margot; Bartunek, Jozef; Vanderheyden, Marc

2007-09-01

Recently, a new linear measure of ventilatory response to exercise, the oxygen uptake efficiency slope (OUES), was proposed in the evaluation of heart failure patients. No data are available on the response of the OUES after orthotopic heart transplantation (HTx). Thirty patients who underwent HTx between 1999 and 2003 were included in the study. Data from maximal cardiopulmonary exercise test, resting pulmonary function and hemodynamic assessment were collected before the transplant at time of screening and 1 year after HTx. During the first year after HTx, OUES and normalized OUES for body weight (OUES/kg) increased significantly from 15.6 +/- 4.9 to 19.7 +/- 4.8 (p < 0.05). Changes in OUES/kg were significantly correlated with changes in peak VO2, VAT and peak VE, and inversely to changes in peak VD/VT, but not to changes in VE/VCO2 slope (all p < 0.05). Changes in OUES or OUES/kg did not correlate with any changes in measures of resting lung volumes or capacities and measures of central hemodynamic function after HTx. OUES improved significantly after HTx, but, similar to other exercise parameters, remained considerably impaired. The changes in OUES were highly correlated with the improvements in other exercise variables, but did not correlate with marked improvements in central hemodynamics or resting lung function.

Liver transplant center performance profiling: 2005-2011 reports of the Scientific Registry for Transplant Recipients.

PubMed

Kettelhut, Valeriya V; Nayar, Preethy

2013-06-01

CONTEXT-Transplant center performance profiling provides important information for various concerned parties. Comparing a transplant center's performance against the performance of the best-in-class centers may help in understanding the performance thresholds for the underperforming centers. OBJECTIVES-(1) To identify and describe "Centers for Medicare and Medicaid Services (CMS)-red-flag" performers and the "best-in-class" performers and (2) to examine the relationships between a center's performance profile and outcomes such as 1-year observed mortality, 1-month observed mortality, 1-year risk-adjusted mortality, and volume. METHODS-The data for analysis was obtained from the published reports on the Scientific Registry for Transplant Recipients (SRTR) website for adult liver transplant programs compiled for the rolling 2 1/2-year cohorts of patients and included 7 cohorts of liver transplant recipients in the study from January through July 1, 2002, through December 31, 2010. We defined 4 performance profiles: CMS-red-flag, lower-than-expected, higher-than-expected, and best-in-class performers. RESULTS-The current SRTR methods classify approximately 7% of the adult liver centers as CMS-red-flag performers and 6% of the centers as best-in-class performers in every reported period. Neither of the low-volume centers (<30 liver transplants per 2 1/2-year cohort) was profiled as CMS-red-flag until the 2010 reporting period. The transplant center's profile was significantly associated with the 1-year and 1-month observed mortality rates in every reported cohort (P< .001). CONCLUSION-The CMS-red-flag profile can be characterized with the following: (1) the highest observed 1-year mortality, (2) the highest observed 1-month mortality, (3) a very large difference between the observed and adjusted mortality rates, and (4) the center volume greater than 30 liver transplants per 2 1/2-year cohort. The SRTR methods are not sensitive for performance profiling in the centers that perform fewer than 30 orthotopic liver transplants per 2 1/2-year cohort.

[Extracorporeal reconstruction of arteries of a transplant of the liver for its subsequent implantation and surgical aspects of arterial anatomy the hepatoduodenal area].

PubMed

Khubutiia, M Sh; Guliaev, V A; Novruzbekov, M S; Lemenev, V L; Driaev, V T

2014-01-01

Orthotopic liver transplantation (OLT) remains the only and radical method of treating patients with terminal stages of chronic diffuse hepatic diseases (cirrhoses), of patients with various congenital metabolic lesions of the liver, autoimmune diseases characterized by lesions of bile ducts, as well as series of both primary and secondary tumorous hepatic lesions. Liver transplantation is one of the most complicated operative interventions. Difficulty of OLT is determined by multifactorial and well-coordinated work of various medical services at the pre-, intra- and postoperative stage of management. One of the important components of success in transplantation consists in providing adequate arterial blood flow of the transplanted organ, which is achieved by extracorporeal reconstruction of the transplant. Variants of arterial blood supply of the liver are observed in each third donor. These anatomical peculiarities increase probability of a surgical error, which is considerably higher if not taking into consideration the complicated anatomy of the donor organ and its misalignment with the anatomical peculiarities of the recipient. Surgeon's responsibility is especially great during taking out the liver from the donor, as well as during its preparation for implantation. Procurement of the liver and pancreas from the same donor for transplantation to two different recipients may be accompanied and followed by the so-called conflict of interests which the surgeon has to decide in favour of the both during procurement of the organ for its extracorporeal processing. The sequence of the presented surgical manipulations on hepatic and pancreatic vessels, as well as anatomical reference points make it possible to preserve the vessels of the maximum length for the both organs. A wide variety of the structure of hepatic vessels may be divided into three types, depending upon the number of the sources of arterial blood supply.

Heat stroke leading to acute liver injury & failure: A case series from the Acute Liver Failure Study Group.

PubMed

Davis, Brian C; Tillman, Holly; Chung, Raymond T; Stravitz, Richard T; Reddy, Rajender; Fontana, Robert J; McGuire, Brendan; Davern, Timothy; Lee, William M

2017-04-01

In the United States, nearly 1000 annual cases of heat stroke are reported but the frequency and outcome of severe liver injury in such patients is not well described. The aim of this study was to describe cases of acute liver injury (ALI) or failure (ALF) caused by heat stroke in a large ALF registry. Amongst 2675 consecutive subjects enrolled in a prospective observational cohort of patients with ALI or ALF between January 1998 and April 2015, there were eight subjects with heat stroke. Five patients had ALF and three had ALI. Seven patients developed acute kidney injury, all eight had lactic acidosis and rhabdomyolysis. Six patients underwent cooling treatments, three received N-acetyl cysteine (NAC), three required mechanical ventilation, three required renal replacement therapy, two received vasopressors, one underwent liver transplantation, and two patients died-both within 48 hours of presentation. All cases occurred between May and August, mainly in healthy young men because of excessive exertion. Management of ALI and ALF secondary to heat stroke should focus on cooling protocols and supportive care, with consideration of liver transplantation in refractory patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single-Institution Results of Image-Guided Nonplugged Percutaneous Versus Transjugular Liver Biopsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hardman, Rulon L., E-mail: hardmanr@uthscsa.edu; Perrich, Kiley D.; Silas, Anne M.

2011-04-15

Purpose: To retrospectively review patients who underwent transjugular and image-guided percutaneous biopsy and compare the relative risk of ascites, thrombocytopenia, and coagulopathy. Materials and Methods: From August 2001 through February 2006, a total of 238 liver biopsies were performed. The radiologist reviewed all patient referrals for transjugular biopsy. These patients either underwent transjugular biopsy or were reassigned to percutaneous biopsy (crossover group). Patients referred to percutaneous image-guided liver biopsy underwent this same procedure. Biopsies were considered successful if a tissue diagnosis could be made from the samples obtained. Results: A total of 36 transjugular biopsies were performed with 3 totalmore » (8.3%) and 1 major (2.8%) complications. A total of 171 percutaneous biopsies were performed with 10 (5.8%) total and 3 (1.8%) major complications. The crossover group showed a total of 4 (12.9%) complications with 1 (3.2%) major complication. Sample adequacy was 91.9% for transjugular and 99.5% for percutaneous biopsy. Conclusion: Both transjugular and percutaneous liver biopsy techniques are efficacious and safe. Contraindications such as thrombocytopenia, coagulopathy, and ascites are indicators of greater complications but are not necessarily prevented by transjugular biopsy. Percutaneous biopsy more frequently yields a diagnostic specimen than transjugular biopsy.« less

Real-time Non-invasive Spectral Imaging of Orthotopic Red Fluorescent Protein-expressing Lung Tumor Growth in Nude Mice.

PubMed

Zhang, Yong; Zhang, Nan; Zhao, Ming; Hoffman, Robert M

2015-07-01

Orthotopic implantation of cancer allows metastasis to occur. The most patient-like metastatic orthotopic models are developed with surgical orthotopic implantation using intact tissue in order to preserve the natural tissue structure of the tumor which contains both cancer cells and stroma. In the present study, we performed a simple thoracotomy by making an intercostal incision between the fourth and fifth ribs on the left side of the chest of nude mice. Lung tumor fragments expressing red fluorescent protein were then implanted on the left lung. It was possible to monitor tumor formation in the lung non-invasively by spectral imaging using the Maestro system with a liquid tunable filter. The model described here has high tumorigenicity in the lung (100%) and a low mortality rate (5%). This imageable nude mouse model using surgical orthotopic implantation of lung cancer will be useful for all types of longitudinal studies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Laparoscopic splenectomy for patients with liver cirrhosis: Improvement of liver function in patients with Child-Pugh class B.

PubMed

Yamamoto, Naoki; Okano, Keiichi; Oshima, Minoru; Akamoto, Shitaro; Fujiwara, Masao; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Masaki, Tsutomu; Suzuki, Yasuyuki

2015-12-01

We aimed to assess the short-term outcomes of laparoscopic splenectomy (LS) and liver function at 1 year after splenectomy in the patients with liver cirrhosis. Forty-five patients with liver cirrhosis and hypersplenism underwent LS. We reviewed electronic medical records regarding the liver functional reserve, the etiology of liver cirrhosis, and the presence of hepatocellular carcinoma and esophago-gastric varices. Prospectively collected data of perioperative variables, postoperative complications, and long-term liver function were analyzed. Forty-five patients had a chronic liver disease classified into Child-Pugh classes (A/B/C: 23/20/2). The etiologies of disease were hepatitis C virus infection in 34 patients, hepatitis B virus infection in 4, and others in 7. Fourteen patients underwent procedures in addition to LS, including hepatectomy (n = 7) and devascularization for esophagogastric varices (n = 8). Postoperative complications occurred in 11 patients (24%). Neither postoperative liver failure nor in-hospital mortality occurred. White blood cell and platelet counts determined 7 days, 1 month, and 1 year after LS doubled or increased more than twice compared with the preoperative values (P < .001). One year after LS, patients who had been classified preoperatively into Child-Pugh class B had decreased total serum bilirubin levels (P = .03), and increased prothrombin activity (P = 003) and decreased Child-Pugh scores (P = .001). The Child-Pugh classifications improved in 14 of 18 patients (78%) who had Child-Pugh class B preoperatively. LS is a safe and feasible procedure for hypersplenism in patients with liver cirrhosis. In addition, LS most likely ameliorates liver function at 1 year after LS in patients with Child-Pugh class B liver cirrhosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

PubMed

Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

2016-07-01

Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. © 2016 Royal Australasian College of Physicians.

Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

PubMed Central

2013-01-01

Background Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. Methods We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. Results TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. Conclusions We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies. PMID:23937707

[Urethroplasty in hypoplastic-dysplastic corpus spongiosum and short urethra].

PubMed

Vitarelli, Antonio; Divenuto, Lucia; Altomare, Mauro; Masiello, Giuseppe; Pagliarulo, Arcangelo

2013-01-01

Congenital penile curvature and chordee are a rare malformative condition most frequently associated with hypospadias, but varying degrees of penile curvature are observed with an orthotopic meatus. Disease becomes evident after puberty, when curvature becomes more apparent with erection. We present a case of a young man (16 years old), with ventral congenital penile curvature without hypospadias and with hypoplastic-dysplastic corpus spongiosum and short urethra, who could not have normal sexual intercourses. The patient underwent first-stage urethroplasty with urethral opening and graft of buccal mucosa and creation of a temporary hypospadic meatus. No post-operative complications were observed. There were no residual penile curvatures. Results are promising and satisfactory after the first surgical stage and provide a solid ground for the final reconstruction.

4D-CT scans reveal reduced magnitude of respiratory liver motion achieved by different abdominal compression plate positions in patients with intrahepatic tumors undergoing helical tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Yong, E-mail: hu.yong@zs-hospital.sh.cn; Zhou,

Purpose: While abdominal compression (AC) can be used to reduce respiratory liver motion in patients receiving helical tomotherapy for hepatocellular carcinoma, the nature and extent of this effect is not well described. The purpose of this study was to evaluate the changes in magnitude of three-dimensional liver motion with abdominal compression using four-dimensional (4D) computed tomography (CT) images of several plate positions. Methods: From January 2012 to October 2015, 72 patients with intrahepatic carcinoma and divided into four groups underwent 4D-CT scans to assess respiratory liver motion. Of the 72 patients, 19 underwent abdominal compression of the cephalic area betweenmore » the subxiphoid and umbilicus (group A), 16 underwent abdominal compression of the caudal region between the subxiphoid area and the umbilicus (group B), 11 patients underwent abdominal compression of the caudal umbilicus (group C), and 26 patients remained free breathing (group D). 4D-CT images were sorted into ten-image series, according to the respiratory phase from the end inspiration to the end expiration, and then transferred to treatment planning software. All liver contours were drawn by a single physician and confirmed by a second physician. Liver relative coordinates were automatically generated to calculate the liver respiratory motion in different axial directions to compile the 10 ten contours into a single composite image. Differences in respiratory liver motion were assessed with a one-way analysis of variance test of significance. Results: The average respiratory liver motion in the Y axial direction was 4.53 ± 1.16, 7.56 ± 1.30, 9.95 ± 2.32, and 9.53 ± 2.62 mm in groups A, B, C, and D, respectively, with a significant change among the four groups (p < 0.001). Abdominal compression was most effective in group A (compression plate on the subxiphoid area), with liver displacement being 2.53 ± 0.93, 4.53 ± 1.16, and 2.14 ± 0.92 mm on the X-, Y-, and Z-axes, respectively. There was no significant difference in respiratory liver motion between group C (displacement: 3.23 ± 1.47, 9.95 ± 2.32, and 2.92 ± 1.10 mm on the X-, Y-, and Z-axes, respectively) and group D (displacement: 3.35 ± 1.55, 9.53 ± 2.62, and 3.35 ± 1.73 mm on the X-, Y-, and Z-axes, respectively). Abdominal compression was least effective in group C (compression on caudal umbilicus), with liver motion in this group similar to that of free-breathing patients (group D). Conclusions: 4D-CT scans revealed significant liver motion control via abdominal compression of the subxiphoid area; however, this control of liver motion was not observed with compression of the caudal umbilicus. The authors, therefore, recommend compression of the subxiphoid area in patients undergoing external radiotherapy for intrahepatic carcinoma.« less

Pathological Roles of Interleukin-22 in the Development of Recurrent Hepatitis C after Liver Transplantation

PubMed Central

Li, Jin; Cheung, Eddie; Li, Hanwei; Zhao, Jingmin; Liu, Hongling; Liu, Zhenwen; Zhang, Min

2016-01-01

Objective The aim of this study was to longitudinally evaluate and analyze the role of interleukin-22-producing CD4 positive cells (IL-22) in the pathogenesis of Hepatitis C Virus recurrence after Orthotopic Liver Transplantation (HCV-OLT). Methods 15 HCV-OLT, 15 age- and gender- matched non-HCV post-OLT (OLT) and 15 hepatitis C virus infected (HCV) patients were enrolled into our study from the liver transplantation and research center at Beijing 302 Hospital. We determined the frequencies of IL-22 using flow cytometry and expression of IL-22 mRNA using PCR in peripheral blood and liver tissue. We also divided HCV-OLT patients into rapid fibrosis progression (RFP) and slow fibrosis progression (SFP), examined IL-22 cells and analyzed the correlations between IL-22 frequencies and liver injury, fibrosis and clinical parameters. Moreover, we investigated the role of IL-22 in Human Hepatic Stellate Cells (HSCs). Results The levels of serum IL-22, frequencies of IL-22 producing cells in peripheral blood mononuclear cells, and expression of IL-22 mRNA and protein in the liver in the HCV-OLT group were significantly higher than that in the HCV and OLT groups. Furthermore, eight (53.3%) patients developed RFP after two years; another three patients were diagnosed liver cirrhosis. The frequencies of IL-22 were much higher in RFP compared with SFP, while no significant difference existed between OLT and SFP. Intrahepatic IL-22 positive cells were located in fibrotic areas and significantly correlated with α-smooth muscle actin (α-SMA) and fibrosis staging scores, not with grading scores and HCRVNA. In vitro, IL-22 administration prevented HSCs apoptosis, promoted HSCs proliferation and activation, up-regulated the expression of HSC-sourced growth factors including α-SMA, TGF-β and TIMP-1, and increased the production of liver fibrosis markers including laminin, hyaluronic acid and collagen type IV. Conclusion Peripheral and intrahepatic IL-22 is up-regulated and plays a pathological role in exacerbating liver fibrosis by activating HSCs in HCV-OLT patients, which may predict RFP and serve as an attractive target for anti-fibrotic therapy. PMID:27123854

Tanshinone IIA promotes the proliferation of WB-F344 hepatic oval cells via Wnt/β-catenin signaling

PubMed Central

ZE, XINGYU; JIA, JIDONG; LI, XINMIN; YOU, HONG; ZHAO, XINYAN; ZHANG, DONG; WANG, BAOEN

2016-01-01

Tanshinone IIA (TSA) is a widely used traditional Chinese medicine, which has been demonstrated to protect damaged liver cells and is currently administered in the treatment of liver fibrosis. Liver precursor cells, also termed oval cells, are key in the repair of liver tissues following injury. However, whether TSA improves the function of liver cells and protects the liver from injury by enhancing the growth and proliferation of hepatic oval cells remains to be elucidated. In the present study, low to moderate concentrations of TSA were observed to stimulate proliferation, did not induce apoptosis in WB-F344 rat hepatic oval cells and the increased expression levels of β-catenin. WB-F344 cells were treated with various concentrations of TSA (0–80 µg/ml) for 24, 48, 72 and 96 h. Cell proliferation was measured using a Cell Counting kit-8 (CCK-8) assay, a 5-ethynyl-2′-deoxyuridine assay and a carboxyfluorescein diacetate succinimidyl ester (CFSE) assay. The CCK-8 assay demonstrated that treatment of WB-F344 cells with 20–40 µg/ml TSA for up to 72 h significantly increased proliferation. Similar results were observed in the subsequent EdU and CFSE assays. Furthermore, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay demonstrated that 20–40 µg/ml TSA treatment for up to 96 h did not induce apoptosis of the WB-F344 cells. Notably, the results of western blot, immunofluorescence and reverse transcription-quantitative polymerase chain reaction analyses demonstrated that treatment of the WB-F344 cells with 20–40 µg/ml TSA for up to 72 h significantly increased the expression levels of β-catenin. These data indicated that TSA at concentrations between 20 and 40 µg/ml may induce WB-F344 cell proliferation by activating the canonical Wnt signaling pathway. The results of the present study suggest that TSA may be a useful natural agent to enhance repair and regeneration of the injured liver, and improve liver regeneration following orthotopic liver transplantation. PMID:26709094

CXCR3+CD4+ T cells mediate innate immune function in the pathophysiology of liver ischemia/reperfusion injury.

PubMed

Zhai, Yuan; Shen, Xiu-da; Hancock, Wayne W; Gao, Feng; Qiao, Bo; Lassman, Charles; Belperio, John A; Strieter, Robert M; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W

2006-05-15

Ischemia-reperfusion injury (IRI), an innate immune-dominated inflammatory response, develops in the absence of exogenous Ags. The recently highlighted role of T cells in IRI raises a question as to how T lymphocytes interact with the innate immune system and function with no Ag stimulation. This study dissected the mechanism of innate immune-induced T cell recruitment and activation in rat syngeneic orthotopic liver transplantation (OLT) model. Liver IRI was induced after cold storage (24-36 h) at 4 degrees C in University of Wisconsin solution. Gene products contributing to IRI were identified by cDNA microarray at 4-h posttransplant. IRI triggered increased intrahepatic expression of CXCL10, along with CXCL9 and 11. The significance of CXCR3 ligand induction was documented by the ability of neutralizing anti-CXCR3 Ab treatment to ameliorate hepatocellular damage and improve 14-day survival of 30-h cold-stored OLTs (95 vs 40% in controls; p < 0.01). Immunohistology analysis confirmed reduced CXCR3+ and CD4+ T cell infiltration in OLTs after treatment. Interestingly, anti-CXCR3 Ab did not suppress innate immune activation in the liver, as evidenced by increased levels of IL-1beta, IL-6, inducible NO synthase, and multiple neutrophil/monokine-targeted chemokine programs. In conclusion, this study demonstrates a novel mechanism of T cell recruitment and function in the absence of exogenous Ag stimulation. By documenting that the execution of innate immune function requires CXCR3+CD4+ T cells, it highlights the critical role of CXCR3 chemokine biology for the continuum of innate to adaptive immunity in the pathophysiology of liver IRI.

[Cause of death after liver transplantation: an analysis of 41 cases in 382 patients].

PubMed

Rayes, N; Bechstein, W O; Keck, H; Blumhardt, G; Lohmann, R; Neuhaus, P

1995-01-01

The aim of this study was to analyse the causes of death after liver transplantation in order to find and to avoid preventable fatal complications if possible. Between September 1988 and September 1993 415 orthotopic liver transplantations in 382 patients were performed at the Rudolf Virchow University Hospital in Berlin. During the same interval 41 (10.7%) of these patients died. Their clinical records were reviewed. The main cause of death was infection (29.3%), followed by recurrent malignancy (21.9%). Less patients died because of hepatitis B-reinfection (14.6%), chronic rejection (7.3%), hemorrhage (7.3%), cardiac failure (7.3%), trauma (4.8%), hypoxia (4.8%) and recurrence of alcoholic liver disease (4.8%). There was a wide spectrum of opportunistic infectious agents with CMV and Pneumocystis carinii being the most important pathogenic organisms. Only one isolated bacterial infection as principle cause of death was found. In all fatal infections the lung was the primary site of infection, 7 patients additionally developed sepsis. Altogether 75 patients (19.6%) with hepatitis B-cirrhosis were transplanted. Six of them (8%) developed a fatal hepatitis B-reinfection. Malignancy was the indication for OLT in 41 patients (10.7%). Six of these patients (14.6%) died because of recurrent tumor. Regarding the whole series, most deaths occurred four to twelve months (58.5%) and only five (12.2%) during the first month after OLT. Recurrence of primary disease is an important factor regarding total mortality. Therefore it is necessary to practise a careful selection of liver transplant recipients. In the future more attention needs to be drawn towards prevention, identification and management of opportunistic infections.

Elective living donor liver transplantation by hybrid hand-assisted laparoscopic surgery and short upper midline laparotomy.

PubMed

Eguchi, Susumu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Hidaka, Masaaki; Tomonaga, Tetsuo; Muraoka, Izumi; Kanematsu, Takashi

2011-11-01

Although the technique of liver transplantation is well developed, the invasiveness of the operation can be decreased with laparoscopic procedures. We performed elective living donor liver transplantation (LDLT) through a short midline incision combined with hand-assisted laparoscopic surgery (HALS). Nine selected patients with end stage liver disease underwent the procedure between July, 2010 and February, 2011 (median age 60, median Child-Pugh 9, median MELD score 14). Splenectomy was performed simultaneously in 7 cases. The liver (and spleen) were mobilized by a sealing device under a HALS procedure with an 8-cm upper midline incision, followed by explantation of the diseased liver (and spleen) through the upper midline incision which was extended to 12 to 15 cm. Partial liver grafts were implanted through the upper midline incision. The median duration of the operation was 741 minutes, the median time needed for anastomosis was 48 minutes, the median blood loss was 3,940 g, and the median liver weight was 866 g. Eight recipients are alive and have good graft function. A difficult implantation for one patient required an additional right transverse incision. When compared with 13 recent liver recipients who underwent LDLT with a regular Mercedes-Benz-type incision, no clinically relevant drawbacks of the HALS hybrid procedure were observed. We have shown the feasibility and safety of LDLT performed through a short midline incision without abdominal muscle disruption with the aid of HALS. Copyright © 2011 Mosby, Inc. All rights reserved.

Laparoscopic management of liver metastases from uveal melanoma.

PubMed

Akyuz, Muhammet; Yazici, Pınar; Dural, Cem; Yigitbas, Hakan; Okoh, Alexis; Bucak, Emre; McNamara, Michael; Singh, Arun; Berber, Eren

2016-06-01

Although uveal melanoma is a rare disease, its metastasis to the liver is associated with a poor survival. The aim of this study is to analyze the survival after surgical treatment of uveal melanoma metastases to the liver. Within 15 years, 44 patients with uveal melanoma metastases to the liver were managed at a single center. Medical records were reviewed to identify patients who underwent surgical treatment of their liver disease. Clinical and oncologic results were compared to those patients who were managed otherwise. T test, Chi-square test, and Kaplan-Meier survival analyses were performed. There were 16 patients who underwent surgical treatment (laparoscopic liver resection, n = 2 and laparoscopic radiofrequency ablation, n = 14), compared to 28 patients who received systemic therapy. The groups were similar regarding demographics and size of primary tumor. The interval between diagnoses of primary tumor and liver metastases was longer for the surgical group (58 vs 22 months, respectively, p = 0.010). Although the dominant liver tumor size was similar, the average number of liver tumors was 4 in the surgical group and 10 in the systemic therapy group (p < 0.0001). The median survival after diagnosis of liver metastases was 35 months in the surgical group and 15 months in the systemic therapy group (p ≤ 0.0001). Five-year survival was zero in the systemic therapy group and 22 % in the surgical group. This study shows that surgical treatment of liver metastases in selected patients with uveal melanoma, who have limited liver tumor burden and a long interval to metastases development, may result in long-term survival.

Diagnostic Usefulness of APRI and FIB-4 for the Prediction of Liver Fibrosis After Liver Transplantation in Patients Infected with Hepatitis C Virus.

PubMed

Imai, H; Kamei, H; Onishi, Y; Ishizu, Y; Ishigami, M; Goto, H; Ogura, Y

2018-06-01

Aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) are well known as representative indirect serum biomarkers related to liver fibrosis. The usefulness of these markers for the diagnosis of liver fibrosis after liver transplantation (LT) in hepatitis C virus (HCV)-infected patients and the influence of splenectomy were investigated. From June 2003 to May 2014, 31 HCV-infected patients who underwent LT and postoperative follow-up liver biopsies were included in this study. The association between liver fibrosis and serum biomarkers and the influence of splenectomy on APRI and FIB-4 were also investigated. A total of 195 biopsy specimens were collected, and liver fibrosis was identified as: F0, 59.7%; F1, 34.1%; and F2, 6.3%. Both APRI and FIB-4 were significantly higher in patients who showed F1 and F2 in liver biopsy specimen than F0 (P values, .009 and .022, respectively); sensitivity and specificity of APRI were, respectively, 63.4% and 66.7%, and those of FIB-4 were 57.7% and 69.6%. In 11 patients (35.5%) who underwent splenectomy at the time of LT, the cutoff values for APRI and FIB-4 were 0.61 and 1.41, which were significantly lower than the corresponding values (1.00 and 3.64) of patients without splenectomy. APRI and FIB-4 could effectively estimate liver fibrosis after LT for HCV-related liver disease. For LT patients with splenectomy, APRI and FIB-4 were also useful to estimate liver fibrosis, but the standard values should be adjusted lower than those for patients without splenectomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Portal vein embolization improves rate of resection of extensive colorectal liver metastases without worsening survival outcomes

PubMed Central

Shindoh, Junichi; Tzeng, Ching-Wei D.; Aloia, Thomas A.; Curley, Steven A.; Zimmitti, Giuseppe; Wei, Steven H.; Huang, Steven Y.; Gupta, Sanjay; Wallace, Michael J.; Vauthey, Jean-Nicolas

2017-01-01

Background Most patients requiring an extended right hepatectomy (ERH) have an inadequate standardized future liver remnant (sFLR) and need preoperative portal vein embolization (PVE). However, the clinical and oncologic impact of PVE in such patients remains unclear. Methods All consecutive patients from MD Anderson Cancer Center with colorectal liver metastases (CLM) requiring ERH at presentation from 1995 through 2012. The surgical and oncologic outcomes were compared between patients with adequate and inadequate sFLRs at presentation. Results Of the 265 patients requiring ERH, 126 (47.5%) had an adequate sFLR at presentation, and 123 of them underwent curative resection. Of the 139 patients (52.5%) who had an inadequate sFLR and underwent PVE, 87 (62.6% PVE) underwent curative resection. Thus, PVE increased the curative resection rate from 123/265 (46.4%) at baseline to 210/265 (79.2%). Among patients who underwent ERH, rates of major complications and 90-day mortality were similar in the non-PVE and PVE groups (22.0% and 4.1% vs. 31% and 7%, respectively); overall survival (OS) and disease-free survival (DFS) were also similar in these 2 groups. Among patients with an inadequate sFLR at presentation, patients who underwent ERH had significantly better median OS (50.2 months) than patients who underwent noncurative surgery (21.3 months) or did not undergo surgery (24.7 months) (p=0.002). Conclusions PVE enables curative resection in two-thirds of patients with CLM who have an inadequate sFLR to tolerate ERH at presentation. Patients who undergo curative resection after PVE have OS and DFS equivalent to that of patients who never needed PVE. PMID:24227364

Intrahepatic bilioenteric anastomosis after biliary complications of liver transplantation: operative rescue of surgical failures.

PubMed

Mercado, Miguel Angel; Vilatobá, Mario; Chan, Carlos; Domínguez, Ismael; Leal, Rafael Paulino; Olivera, Marco Antonio

2009-03-01

Biliary complications after orthotopic liver transplantation (OLT) are multifactorial in origin. In most series, the frequency of such complications ranges from 5-20%. Most can be treated by endoscopy and/or interventional radiology. For cases in which this option is not successful, surgical approach is indicated. We report the results of reoperation using an intrahepatic bilioenteric anastomosis. The medical charts of patients with biliary complications after OLT during a 10-year period (1997-2007), who failed to respond to nonsurgical treatment and were surgically treated, were reviewed. Roux-en-Y hepatojejunostomy was performed. Segments IV and V were partially removed after cutting the hilar plate, thus obtaining healthy ducts without ischemic or inflammatory reaction and allowing a wide hepatojejunostomy. Five cases (8.4%) with biliary complications after duct-to-duct anastomosis not amenable to further endoscopic management or interventional radiology were identified. Hepaticojejunostomy was achieved in all cases (wide, tension-free, nonischemic, fine hydrolyzable sutures), and segments IV and V were partially removed. No cholangitis, jaundice, and liver function test abnormalities were present in the postoperative. Mean follow-up was 24 months. Only one patient died of causes not related to bile duct reconstruction during follow-up. Intrahepatic hepatojejunostomy with partial resection of segments IV and V offers an excellent therapeutic alternative for biliary complications that require a surgical approach after OLT.

Increased Hepatic Iron Content Predicts Poor Survival in Patients With Iron Overload Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Sivgin, Serdar; Baldane, Suleyman; Deniz, Kemal; Zararsiz, Gokmen; Kaynar, Leylagul; Cetin, Mustafa; Unal, Ali; Eser, Bulent

2016-08-01

Iron overload results in increased infection, venous-oclusive disease and hepatic dysfunction in allogeneic hematopoietic stem cell transplant (alloHSCT) recipients. Liver is one of the most common sites of iron overload. A total of 50 alloHSCT recipients that underwent liver biopsy in Erciyes Stem Cell Transplantation Hospital, Erciyes University, between 2004 and 2011 were enrolled in the study. The liver biopsy specimens have been obtained from the archives of Erciyes University, Department of Pathology and stainned for iron content. The mean age was found 34 ± 11 years. For median overall survival (OS); 53 months (min-max: 41-65) in patients with grade 0, 55 months (min-max: 47-64) in patients with grade 1, in patients with grade 2 patients 25.4 months (11.5-39.4 ), grade 3 patients 29.3 months (min-max: 12.3-46.3) and grade 4 patients 2.6 months (min-max: 2.0-3.3). Overall survival was correlated with the degree of liver iron content and it was statistically significant in Kaplan-Meier analysis (P < .001). Disease-free survival was found (DFS); grade 0 patients 47.1 months (min-max: 32.0-62.0), grade 1 patients 36.9 months (min-max: 21.0-65.0), grade 2 patients 23.5 months (min-max: 12.0-59.0), grade 3 patients 27.4 months (min-max: 5.3-59.3) and grade 4 patients 2.6 months (min-max: 2.0-3.0). For DFS; it was negatively correlated with the degree of liver iron content nevertheless; it was not was statistically significant in Kaplan-Meier analysis (P = .093).Hepatic iron overload might be associated with poor survival in patients with transfusional iron overload that underwent alloHSCT. Hepatic iron content might be associated with poorer prognosis in patients with iron overload that underwent alloHSCT. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcomes in children who underwent transplantation for autoimmune hepatitis.

PubMed

Martin, Steven R; Alvarez, Fernando; Anand, Ravinder; Song, Changhong; Yin, Wanrong

2011-04-01

The outcomes of 113 children with autoimmune hepatitis (AIH), registered with Studies of Pediatric Liver Transplantation and who underwent transplantation between 1995 and 2006, were compared with those who underwent transplantation for other diagnoses (non-AIH). A total of 4.9% of liver transplants were for AIH; 81% of these patients had AIH type 1 and most underwent transplantation for complications of chronic disease (60%), the majority in females (72%). Transplantation for fulminant AIH was more common in males (52.5% versus 47.5% chronic; P = 0.042). Patients with AIH differed from non-AIH patients by: age (13.0 ± 0.4 versus 4.6 ± 0.1 years; P < 0.0001), sex (64.6% female versus 52.9%; P = 0.016), ethnicity (48.7% white versus 58.2%; P < 0.0001), initial immunosuppression (tacrolimus-based: 72.6% versus 62.6%; P = 0.045; mycophenolate mofetil use: 31.0% versus 21.6%; P = 0.02), and immunosuppression at 2 years after transplant (monotherapy: 51.9% versus 17.3%; P < 0.0001). Late (>3 months), but not steroid-resistant or chronic, rejection was more common in AIH (log-rank P = 0.0015). The 5-year posttransplant survival for AIH was 86% (95% confidence interval: 73-93). Patient and graft survival, infectious and metabolic complications, and retransplantation rates did not differ between AIH and non-AIH groups. In conclusion, the higher risk for late acute rejection and greater degree of immunosuppression does not compromise outcomes of liver transplantation for AIH. Children who undergo transplantation for AIH in North America are typically female adolescents with complications of chronic AIH type 1 and include more children of African American or Latino American origin compared to the overall liver transplant population. These observations may inform detection, treatment, and surveillance strategies designed to reduce the progression of autoimmune hepatitis and subsequently, the need for transplantation. Copyright © 2010 American Association for the Study of Liver Diseases.

Transient elastography for diagnosis of advanced fibrosis and portal hypertension in patients with hepatitis C recurrence after liver transplantation.

PubMed

Carrión, Jose A; Navasa, Miquel; Bosch, Jaume; Bruguera, Miquel; Gilabert, Rosa; Forns, Xavier

2006-12-01

Recurrence of hepatitis C after liver transplantation (LT) is the main cause of graft loss and retransplantation. Frequent liver biopsies are essential to follow-up hepatitis C virus (HCV)-induced liver damage. However, liver biopsy is an invasive and expensive procedure. We evaluated prospectively the diagnostic accuracy of noninvasive measurement of liver stiffness (by transient elastography) to assess the severity of hepatitis C recurrence after LT. For this purpose, we included 124 HCV-infected liver transplant recipients who underwent 169 liver biopsies and 129 hepatic hemodynamic studies with determination of hepatic venous pressure gradient (HVPG). Simultaneously, patients underwent measurement of liver stiffness. Liver fibrosis was mild (F0-F1) in 96 cases (57%) and significant (F2-F4) in 73 (43%). HVPG was normal (<6 mm Hg) in 69 cases (54%) and elevated (>or=6 mm Hg) in 60 (46%). Using a liver stiffness cutoff value of 8.5 kilopascals, the sensitivity, specificity, negative predictive value, and positive predictive value for diagnosis of fibrosis >or=F2 were 90%, 81%, 79%, and 92%, respectively. The area under the curve (AUC) for diagnosis of fibrosis >or=F2, >or=F3 and F4 were 0.90, 0.93, and 0.98, respectively. There was a close direct correlation between liver stiffness and HVPG (Pearson coefficient, 0.84; P < 0.001) and the AUC for diagnosis of portal hypertension (HVPG >or=6 mm Hg) was 0.93. Importantly, none of the individuals with liver stiffness below the cutoff value had either bridging fibrosis (F3) or cirrhosis (F4) or significant portal hypertension (HVPG >or=10 mm Hg). In conclusion, determination of liver stiffness is an extremely valuable tool to assess the severity of HCV recurrence after LT and in reducing the need of follow-up liver biopsies.

CDDO-Me inhibits tumor growth and prevents recurrence of pancreatic ductal adenocarcinoma.

PubMed

Gao, Xiaohua; Deeb, Dorrah; Liu, Yongbo; Liu, Patricia; Zhang, Yiguan; Shaw, Jiajiu; Gautam, Subhash C

2015-12-01

Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) has shown potent antitumorigenic activity against a wide range of cancer cell lines in vitro and inhibited the growth of liver, lung and prostate cancer in vivo. In the present study, we examined the antitumor activity of CDDO-Me for pancreatic ductal adenocarcinoma (PDAC) cells with and without activating K-ras mutations. Treatment of K-ras mutant MiaPaCa-2 and K-ras normal BxPC-3 cells with CDDO-Me elicited strong antiproliferative and proapoptopic responses in both cell lines in culture. The inhibition of cell proliferation and induction of apoptosis was accompanied by the inhibition of antiapoptotic/prosurvival p-Akt, NF-кB and p-mTOR signaling proteins. For testing efficacy of CDDO-Me in vivo heterotopic and orthotopic xenografts were generated by implanting BxPC-3 and MiaPaCa-2 cells subcutaneously and in the pancreatic tail, respectively. Treatment with CDDO-Me significantly inhibited the growth of BxPC-3 xenografts and reduced the levels of p-Akt and p-mTOR in tumor tissue. In mice with orthotopic MiaPaCa-2 xenografts, treatment with CDDO-Me prolonged the survival of mice when administered following the surgical resection of tumors. The latter was attributed to the eradication of residual PDAC remaining after resection of tumors. These preclinical data demonstrate the potential of CDDO-Me for treating primary PDAC tumors and for preventing relapse/recurrence through the destruction of residual disease.

Toxoplasmosis in the non-orthotopic heart transplant recipient population, how common is it? Any indication for prophylaxis?

PubMed

Dhakal, Reshika; Gajurel, Kiran; Montoya, Jose G

2018-06-06

Unlike in orthotopic heart transplant (OHT) setting where toxoplasma prophylaxis is a standard practice in pretransplant toxoplasma seronegative recipients who have received donor hearts from seropositive donors (D+/R-), there is no consensus regarding prophylaxis in non-OHT recipients. The incidence of toxoplasma disease in non-OHT recipients is less than 1% but its true burden is underestimated. Among 31 cases of toxoplasma disease reported from 2004 through 2017, renal and liver transplant recipients comprised of 90% of cases. A total of 94% of 18 recipients with known pretransplant serology were seronegative recipients (mostly D+/R-). Out of 16 recipients with adequate information, 10 (63%) and five (31%) were deemed to be donor derived and nondonor-derived primary toxoplasmosis respectively. Tissue invasive reactivation was uncommon. Almost all cases were described in patients not on prophylaxis at the time of presentation. Universal screening of donor/recipient toxoplasma serology for risk stratification is beneficial as illustrated by reports of fatal cases of toxoplasmosis due to unavailability of positive donor serology results. Toxoplasma disease in non-OHT predominantly occurs in pretransplant seronegative recipients- mostly in D+/R- group and is rare in seropositive recipients. Posttransplant prophylaxis should be targeted against the high-risk D+/R- group and should be considered in seropositive recipients in whom unusually high immunosuppression is implemented. Toxoplasma serologies and PCR should be used in combination for the diagnosis of toxoplasmosis in non-OHT patients.

Lymph Nodes and Survival in Pancreatic Neuroendocrine Tumors (pNET)

PubMed Central

Krampitz, Geoffrey W.; Norton, Jeffrey A.; Poultsides, George A.; Visser, Brendan C.; Sun, Lixian; Jensen, Robert T.

2012-01-01

Background The significance of lymph node metastases on survival of patients with pNET is controversial. Hypothesis Lymph node metastases decrease survival in patients with pNET. Design Prospective databases of the National Institutes of Health (NIH) and Stanford University Hospital (SUH) were queried. Main Outcome Measures Overall survival, disease-related survival, and time to development of liver metastases Results 326 underwent surgical exploration for pNET at the NIH (n=216) and SUH (n=110). 40 (13%) and 305 (94%) underwent enucleation and resection, respectively. Of the patients who underwent resection, 117 (42%) had partial pancreatectomy and 30 (11%) had a Whipple procedure. 41 also had liver resections, 21 wedge resections and 20 lobectomies. Average follow-up was 8 years (range 0.3–28.6 years). The 10-year overall survival for patients with no metastases or lymph node metastases only was similar at 80%. As expected, patients with liver metastases had a significantly decreased 10-year survival of 30% (p<0.001). The time to development of liver metastases was significantly reduced for patients with lymph node metastases alone compared to those with none (p<0.001). For the NIH cohort with longer follow-up, disease-related survival was significantly different for those patients with no metastases, lymph node metastases alone, and liver metastases (p<0.0001). Extent of lymph node involvement in this subgroup showed that disease-related survival decreased as a function of number of lymph nodes involved (p=0.004). Conclusion As expected, liver metastases decrease survival of patients with pNET. Patients with lymph node metastases alone have a shorter time to development of liver metastases that is dependent on the number of lymph nodes involved. With sufficient long-term follow-up, lymph node metastases decrease disease-related survival. Careful evaluation of number and extent of lymph node involvement is warranted in all surgical procedures for pNET. PMID:22987171

Increased Risk of Death for Patients on the Waitlist for Liver Transplant Residing at Greater Distance From Specialized Liver Transplant Centers in the United States.

PubMed

Cicalese, Luca; Shirafkan, Ali; Jennings, Kristofer; Zorzi, Daria; Rastellini, Cristiana

2016-10-01

We have previously shown that patients listed for orthotopic liver transplantation (OLT) in United Network for Organ Sharing Region 4 (Texas and Oklahoma) have higher waitlist mortality rates when residing more than 30 miles from specialized liver transplant centers (LTC). Considering that findings might only be exclusive for this region with its peculiarities in terms of having the highest land surface extensions, lowest population densities, and largest rural populations. We investigated the entire OLT patient population in the United States to assess if our previous regional findings are nationally validated and if a rural, micropolitan, or metropolitan residence location affects outcome of waitlisted OLT patients in the nation. Patients waiting for OLT in the United States from 2002 to 2012 were stratified by distance from the patients' residence to LTC and by Rural Urban Commuting Area (RUCA) codes classification. Statistical analyses were performed to evaluate risk of mortality on the waitlist and the likelihood to receive an OLT using a Cox proportional hazards model and a generalized additive model with a logistic link. Survival time and probability of death while on the waitlist for OLT using distance to LTC showed significant increased risk with the distance (P = 0.001 and P < 0.0001, respectively). At the same time, using RUCA classification as the variable did not show significance (P = 0.14 and P = 0.73, respectively). Distance from an LTC is a risk factor of mortality on the waitlist for OLT, whereas RUCA classification is not a significant factor.

Improved amino acid, bioenergetic metabolite and neurotransmitter profiles following human amnion epithelial cell transplant in intermediate maple syrup urine disease mice.

PubMed

Skvorak, Kristen J; Dorko, Kenneth; Marongiu, Fabio; Tahan, Veysel; Hansel, Marc C; Gramignoli, Roberto; Arning, Erland; Bottiglieri, Teodoro; Gibson, K Michael; Strom, Stephen C

2013-06-01

Orthotopic liver transplant (OLT) significantly improves patient outcomes in maple syrup urine disease (MSUD; OMIM: 248600), yet organ shortages point to the need for alternative therapies. Hepatocyte transplantation has shown both clinical and preclinical efficacy as an intervention for metabolic liver diseases, yet the availability of suitable livers for hepatocyte isolation is also limited. Conversely, human amnion epithelial cells (hAEC) may have utility as a hepatocyte substitute, and they share many of the characteristics of pluripotent embryonic stem cells while lacking their safety and ethical concerns. We reported that like hepatocytes, transplantation of hAEC significantly improved survival and lifespan, normalized body weight, and significantly improved branched-chain amino acid (BCAA) levels in sera and brain in a transgenic murine model of intermediate maple syrup urine disease (imsud). In the current report, we detail the neural and peripheral metabolic improvements associated with hAEC transplant in imsud mice, including amino acids associated with bioenergetics, the urea cycle, as well as the neurotransmitter systems for serotonin, dopamine, and gamma-aminobutyric acid (GABA). This stem cell therapy results in significant global correction of the metabolic profile that characterizes the disease, both in the periphery and the central nervous system, the target organ for toxicity in iMSUD. The significant correction of the disease phenotype, coupled with the theoretical benefits of hAEC, particularly their lack of immunogenicity and tumorigenicity, suggests that human amnion epithelial cells deserve serious consideration for clinical application to treat metabolic liver diseases. Copyright © 2013. Published by Elsevier Inc.

Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.

PubMed

Chen, Kaiyun; Zhu, Shuguang; Xiang, Guoan; Duan, Xiaopeng; He, Jiwen; Chen, Guihua

2016-05-01

To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.

Diffusion-weighted MRI in intrahepatic bile duct adenoma arising from the cirrhotic liver.

PubMed

An, Chansik; Park, Sumi; Choi, Yoon Jung

2013-01-01

A 64-year-old male patient with liver cirrhosis underwent a CT study for hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed brisk arterial enhancement and persistent hyperenhancement in the portal phase, but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the tumor showed an apparent diffusion coefficient twofold greater than that of the background liver parenchyma, which suggested that the lesion was benign. The histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver cirrhosis.

Elevated C-reactive protein and hypoalbuminemia measured before resection of colorectal liver metastases predict postoperative survival.

PubMed

Kobayashi, Takashi; Teruya, Masanori; Kishiki, Tomokazu; Endo, Daisuke; Takenaka, Yoshiharu; Miki, Kenji; Kobayashi, Kaoru; Morita, Koji

2010-01-01

Few studies have investigated whether the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score measured before resection of colorectal liver metastasis (CRLM), can predict postoperative survival. Sixty-three consecutive patients who underwent curative resection for CRLM were investigated. GPS was calculated on the basis of admission data as follows: patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminemia (<35 g/l) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. Significant factors concerning survival were the number of liver metastases (p = 0.0044), carcinoembryonic antigen level (p = 0.0191), GPS (p = 0.0029), grade of liver metastasis (p = 0.0033), and the number of lymph node metastases around the primary cancer (p = 0.0087). Multivariate analysis showed the two independent prognostic variables: liver metastases > or =3 (relative risk 2.83) and GPS1/2 (relative risk 3.07). GPS measured before operation and the number of liver metastases may be used as novel predictors of postoperative outcomes in patients who underwent curative resection for CRLM. Copyright 2010 S. Karger AG, Basel.

Liver parenchyma transection-first approach in hemihepatectomy with en bloc caudate lobectomy for hilar cholangiocarcinoma: A safe technique to secure favorable surgical outcomes.

PubMed

Kawabata, Yasunari; Hayashi, Hikota; Yano, Seiji; Tajima, Yoshitsugu

2017-06-01

Although hemihepatectomy with total caudate lobectomy (hemiHx-tc) is essential for the surgical treatment of hilar cholangiocarcinoma, the advantage of an anterior approach for hemiHx-tc has not been fully discussed technically; the significance of an anterior approach without liver mobilization for preventing infectious complications also remains unknown. The liver parenchyma transection-first approach (Hp-first) technique is an early transection of the hepatic parenchyma without mobilization of the liver that utilizes a modified liver-hanging maneuver to avoid damaging the future remnant liver. Between May 2010 and August 2016, a total of 40 consecutive patients underwent surgery for hilar cholangiocarcinoma. Of these, 19 patients underwent a conventional hemihepatectomy with total caudate lobectomy (cHx), while 21 patients received a Hp-first. The patients in the Hp-first group had significantly less intraoperative blood loss (P < 0.001) and blood transfusion (P < 0.001), a lower incidence of postoperative hyperbilirubinemia (p = 0.023), a lower incidence of liver failure (p = 0.038), a lower hospital death rate (p = 0.042), and a better 2-year disease-free survival rate (p = 0.010) than those in the cHx group. The liver parenchyma transection-first approach is the preferred technique for hemiHx-tc in hilar cholangiocarcinoma because it resulted in improved surgical outcomes as compared with the conventional approach. © 2017 Wiley Periodicals, Inc.

Modified Liver Hanging Maneuver for En-bloc Right-sided Hepatectomy Combined with Total Caudate Lobectomy for Colon-Cancer Liver Metastasis and Hepatocellular Carcinoma.

PubMed

Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Kikuchi, Yutaro; Endo, Itaru; Koda, Keiji; Togo, Shinji; Hoffman, Robert M; Tanaka, Kuniya

2016-04-01

A right-sided hepatectomy with total caudate lobectomy is indicated for colorectal-cancer liver metastases (CLM) and hepatocellular carcinomas (HCC) located in the caudate lobe with extension to the right lobe of the liver. Caudate-lobe resection (i.e. segmentectomy 1 according to the Brisbane terminology) is one of the most difficult types of hepatectomy to carry out radically and safely. The deep portion of hepatic transection around the caudate lobe, hepatic veins and inferior vena cava is a critical source of massive bleeding. Prolonged transection can increase blood loss. We analyzed the outcome of 10 patients who underwent right-sided hepatectomy with caudate lobectomy using a modified liver hanging maneuver (mLHM) in comparison with 16 patients who underwent the operation without mLHM. Blood loss during liver transection and blood loss per unit area of cut surface were significantly less in the mLHM group (p=0.014 and 0.015, respectively). In patients diagnosed pathologically with liver impairment, transection time was significantly shorter in the mLHM group (p=0.038), as were red blood cell transfusion volume (p=0.042) and blood loss (p=0.049) during transection. Use of mLHM can potentially improve surgical outcomes by reducing blood loss and transection time, which are especially important for patients with liver impairment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

AST-to-platelet ratio index in non-invasive assessment of long-term graft fibrosis following pediatric liver transplantation.

PubMed

D'Souza, Rashmi S; Neves Souza, Lara; Isted, Alexander; Fitzpatrick, Emer; Vimalesvaran, Sunitha; Cotoi, Corina; Amin, Saista; Heaton, Nigel; Quaglia, Alberto; Dhawan, Anil

2016-03-01

Long-term graft fibrosis occurs in the majority of pediatric liver transplant recipients. Serial biopsies to monitor graft health are impractical and invasive. The APRI has been evaluated in pediatric liver disease, but not in the context of post-transplantation fibrosis. We aimed to investigate the validity of APRI as a predictor of long-term graft fibrosis in pediatric liver transplant recipients. This was a retrospective, observational study of a cohort of children who underwent liver transplantation at King's College Hospital between 1989 and 2003, with a relevant dataset available. Protocol liver biopsies were performed at 10-yr follow-up and fibrosis was graded using the Ishak scoring system, with S3-6 denoting "significant fibrosis." APRI was calculated concurrently with biopsy. A total of 39 asymptomatic patients (20 males; median age at transplant, 1.43 yr) underwent protocol liver biopsies at a median of 10.39 yr post-transplantation. APRI was associated with significant fibrosis (p = 0.012). AUROC for APRI as a predictor of significant fibrosis was 0.74 (p = 0.013). The optimal cutoff APRI value for significant fibrosis was 0.45 (sensitivity = 0.67; specificity = 0.79; PPV = 0.67; NPV = 0.79). APRI appears to be a useful non-invasive adjunct in the assessment of significant graft fibrosis in the long-term follow-up of pediatric liver transplant survivors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A subclinical high tricuspid regurgitation pressure gradient independent of the mean pulmonary artery pressure is a risk factor for the survival after living donor liver transplantation.

PubMed

Saragai, Yosuke; Takaki, Akinobu; Umeda, Yuzo; Matsusaki, Takashi; Yasunaka, Tetsuya; Oyama, Atsushi; Kaku, Ryuji; Nakamura, Kazufumi; Yoshida, Ryuichi; Nobuoka, Daisuke; Kuise, Takashi; Takagi, Kosei; Adachi, Takuya; Wada, Nozomu; Takeuchi, Yasuto; Koike, Kazuko; Ikeda, Fusao; Onishi, Hideki; Shiraha, Hidenori; Nakamura, Shinichiro; Morimatsu, Hiroshi; Ito, Hiroshi; Fujiwara, Toshiyoshi; Yagi, Takahito; Okada, Hiroyuki

2018-05-15

Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT). We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion (subclinical high TRPG; n = 34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO 2 0.6 (mPAP-FIO 2 0.6) was also assessed. Patients exhibiting pO 2  < 80 mmHg and an alveolar-arterial oxygen gradient (AaDO 2 ) ≥ 15 mmHg were categorized as potentially having HPS (subclinical HPS; n = 29). The clinical course after LDLT was investigated according to subclinical high TRPG. A subclinical high TRPG (p = 0.012) and older donor age (p = 0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO 2 0.6 was expected to correlate with a worse survival, a high mPAP-FIO 2 0.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt. In cirrhosis patients, mPAP-FIO 2 0.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.

Targeting Cancer Protein Profiles with Split-Enzyme Reporter Fragments to Achieve Chemical Resolution for Molecular Imaging

DTIC Science & Technology

2013-08-01

We next tested the utility of the construct to accumulate in tumors expressing EGFR using an orthotopic mouse model for brain tumors. Glioma cells...filament tumor marker, identified implanted cells within the orthotopic mouse model which were of human origin, i.e. Gli36Δ5 cells, and demonstrated that...forward into in vivo animal tumor model studies. • In vivo imaging of EGFR targeted-complex in orthotopic mouse model of brain tumor. • Ex vivo validation

Donor Age-Based Analysis of Liver Transplantation Outcomes: Short- and Long-Term Outcomes Are Similar Regardless of Donor Age.

PubMed

Chapman, William C; Vachharajani, Neeta; Collins, Kelly M; Garonzik-Wang, Jackie; Park, Yikyung; Wellen, Jason R; Lin, Yiing; Shenoy, Surendra; Lowell, Jeffrey A; Doyle, M B Majella

2015-07-01

The shortage of donor organs has led to increasing use of extended criteria donors, including older donors. The upper limit of donor age that produces acceptable outcomes continues to be explored. In liver transplantation, with appropriate selection, graft survival and patient outcomes would be comparable regardless of age. We performed a retrospective analysis of 1,036 adult orthotopic liver transplantations (OLT) from a prospectively maintained database performed between January 1, 2000 and December 31, 2013. The study focus group was liver transplantations performed using grafts from older (older than 60 years) deceased donors. Deceased donor liver transplantations done during the same time period using grafts from younger donors (younger than 60 years) were analyzed for comparison. Both groups were further divided based on recipient age (less than 60 years and 60 years or older). Donor age was the primary variable. Recipient variables included were demographics, indication for transplantation, Model for End-Stage Liver Disease (MELD), graft survival, and patient survival. Operative details and postoperative complications were analyzed. Patient demographics and perioperative details were similar between groups. Patient and graft survival rates were similar in the 4 groups. Rates of rejection (p = 0.07), bile leak (p = 0.17), and hepatic artery thrombosis were comparable across all groups (p = 0.84). Hepatitis C virus recurrence was similar across all groups (p = 0.10). Thirty-one young recipients (less than 60 years) received grafts from donors aged 70 or older. Their survival and other complication rates were comparable to those in the young donor to young recipient group. Comparable outcomes in graft and patient survivals were achieved using older donors (60 years or more), regardless of recipient age, without increased rate of complications. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

KEAP1-NRF2 COMPLEX IN ISCHEMIA-INDUCED HEPATOCELLULAR DAMAGE OF MOUSE LIVER TRANSPLANTS

PubMed Central

Ke, Bibo; Shen, Xiu-Da; Zhang, Yu; Ji, Haofeng; Gao, Feng; Yue, Shi; Kamo, Naoko; Zhai, Yuan; Yamamoto, Masayuki; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy W.

2015-01-01

Background The Keap1-Nrf2 signaling pathway regulates host cell defense responses against oxidative stress and maintains the cellular redox balance. Aims&Methods: We investigated the function/molecular mechanisms by which Keap1-Nrf2 complex may influence liver ischemia/reperfusion injury (IRI) in a mouse model of hepatic cold storage (20h at 4 C) followed by orthotopic liver transplantation (OLT). Results The Keap1 hepatocyte-specific knock-out (HKO) in the donor liver ameliorated post-transplant IRI, evidenced by improved hepatocellular function and OLT outcomes (Keap1HKO Keap1HKO; 100% survival), as compared with controls (WT WT; 50% survival; p<0.01). In contrast, donor liver Nrf2 deficiency exacerbated IRI in transplant recipients (Nrf2KO Nrf2KO; 40% survival). Ablation of Keap1 signaling reduced macrophage/neutrophil trafficking, pro-inflammatory cytokine programs, and hepatocellular necrosis/apoptosis, while simultaneously promoting anti-apoptotic functions in OLTs. At the molecular level, Keap1HKO increased Nrf2 levels, stimulated Akt phosphorylation, and enhanced expression of anti-oxidant Trx1, HIF-1 , and HO-1. Pretreatment of liver donors with PI3K inhibitor (LY294002) disrupted Akt/HIF-1 signaling and recreated hepatocellular damage in otherwise IR-resistant Keap1HKO transplants. In parallel in vitro studies, hydrogen peroxide-stressed Keap1-deficient hepatocytes were characterized by enhanced expression of Nrf2, Trx1, and Akt phosphorylation, in association with decreased release of lactate dehydrogenase (LDH) in cell culture supernatants. Conclusions Keap1-Nrf2 complex prevents oxidative injury in IR-stressed OLTs through Keap1 signaling, which negatively regulates Nrf2 pathway. Activation of Nrf2 induces Trx1 and promotes PI3K/Akt, crucial for HIF-1 activity. HIF-1 -mediated overexpression of HO-1/CyclinD1 facilitates cytoprotection by limiting hepatic inflammatory responses, and hepatocellular necrosis/apoptosis in PI3K-dependent manner. PMID:23867319

Liver transplantation for Wilson's disease in pediatric patients: decision making and timing.

PubMed

Narumi, S; Umehara, M; Toyoki, Y; Ishido, K; Kudo, D; Kimura, N; Kobayashi, T; Sugai, M; Hakamada, K

2012-03-01

Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilson's disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilson's disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention. Copyright © 2012 Elsevier Inc. All rights reserved.

Condyle-Specific Matching Does Not Improve Midterm Clinical Outcomes of Osteochondral Allograft Transplantation in the Knee.

PubMed

Wang, Dean; Jones, Kristofer J; Eliasberg, Claire D; Pais, Mollyann D; Rodeo, Scott A; Williams, Riley J

2017-10-04

Condyle-specific matching for osteochondral allograft transplantation (OCA) pairs donor and recipient condyles in an attempt to minimize articular incongruity. While the majority of cartilage defects are located on the medial femoral condyle, lateral femoral condyles are more commonly available as a graft source. The purpose of this study was to compare the clinical outcomes of patients treated with non-orthotopic (lateral-to-medial condyle or medial-to-lateral condyle) OCA with those treated with traditional orthotopic (medial-to-medial condyle or lateral-to-lateral condyle) OCA. We hypothesized that clinical outcomes would be similar between groups at midterm follow-up. A retrospective review of prospectively collected data on patients treated with OCA from 2000 to 2014 was conducted. Seventy-seven patients with a full-thickness cartilage defect of a femoral condyle were treated with either orthotopic (n = 50) or non-orthotopic (n = 27) OCA. A minimum follow-up of 2 years was required for analysis. Patients in each group were matched according to sex, age, and total chondral defect size. Reoperations and patient responses to validated outcome measures were reviewed. Failure was defined as any revision cartilage procedure or conversion to knee arthroplasty. The mean duration of follow-up was 4.0 years (range, 2 to 16 years). The orthotopic and non-orthotopic OCA groups were comparable in terms of demographics, the mean number of prior ipsilateral knee operations, and the percentage of concomitant procedures at baseline. Reoperation (p = 0.427) and failure (p = 0.917) rates did not differ significantly between groups. Both groups demonstrated significant increases in the Short Form-36 (SF-36) physical functioning and pain, International Knee Documentation Committee (IKDC), and Knee Outcome Survey-Activities of Daily Living (KOS-ADL) scores compared with baseline (p < 0.004). Outcome scores (baseline and postoperative) and change scores did not differ significantly between groups. Clinical outcomes do not differ between patients treated with orthotopic OCA and those treated with non-orthotopic OCA, suggesting that condyle-specific matching may not be necessary. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A hypoxia- and {alpha}-fetoprotein-dependent oncolytic adenovirus exhibits specific killing of hepatocellular carcinomas.

PubMed

Kwon, Oh-Joon; Kim, Pyung-Hwan; Huyn, Steven; Wu, Lily; Kim, Minjung; Yun, Chae-Ok

2010-12-15

Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE). We constructed Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE(6)/hAFPΔ19 and Ad-HRE(12)/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging. Ad-HRE(12)/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE(12)/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE(12)/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection. The results presented here show the advantages of incorporating HREs into a hAFP promoter-driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment-selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE(12)/hAFPΔ19 make it a promising therapeutic agent in the treatment of liver cancers. ©2010 AACR.

Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies.

PubMed

Sun, Xu; Ma, Xueman; Li, Qiwei; Yang, Yong; Xu, Xiaolong; Sun, Jiaqi; Yu, Mingwei; Cao, Kexin; Yang, Lin; Yang, Guowang; Zhang, Ganlin; Wang, Xiaomin

2018-08-01

Fisetin, a natural flavonoid found in a variety of edible and medical plants, has been suggested to inhibit the proliferation of various tumor cells and to induce apoptosis. However, the effects of fisetin on breast cancer have rarely been reported and the underlying mechanism is still undefined. The present study explored the anti‑cancer effects of fisetin on mammary carcinoma cells and the underlying mechanisms. Following treatment with fisetin, viability of 4T1, MCF‑7 and MDA‑MB‑231 cells were measured by MTT assay. The inhibitory effects of fisetin on proliferation, migration and invasion were evaluated in 4T1 cells using proliferation array, wound‑healing assay, and HUV‑EC‑C‑cell barrier based on electrical cell‑substrate impedance sensing platform. Cell apoptosis was analyzed by flow cytometry, and western blotting analysis was performed to identify target molecules. A 4T1 orthotopic mammary tumor model was used to assess the fisetin‑inhibition on tumor growth in vivo. Test kits were used to examine the liver and kidney function of tumor‑bearing mice. The results suggest that fisetin suppressed the proliferation of breast cancer cells, suppressed the metastasis and invasiveness of 4T1 cells, and induced the apoptosis of 4T1 cells in vitro. The potent anti‑cancer effect of fisetin was associated with the regulation of the phosphatidylinositol‑3‑kinase/protein kinase B/mammalian target of rapamycin pathway. In vivo experiments demonstrated that fisetin suppressed the growth of 4T1 cell‑derived orthotopic breast tumors and enhanced tumor cell apoptosis, and the evaluated alanine amino transferase and aspartate amino transferase levels in serum of tumor‑bearing mice suggested that fisetin may lead to side effects on liver biochemical function. The present study confirms that fisetin exerted an anti‑mammary carcinoma effect. However, in vivo experiments also revealed that fisetin had low solubility and low bioavailability. Further investigation is required to determine the clinical value of fisetin.

Surgically-Induced Weight Loss Significantly Improves Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome

PubMed Central

Mattar, Samer G.; Velcu, Laura M.; Rabinovitz, Mordechai; Demetris, A J.; Krasinskas, A M.; Barinas-Mitchell, Emma; Eid, George M.; Ramanathan, Ramesh; Taylor, Debra S.; Schauer, Philip R.

2005-01-01

Objective: To evaluate the effects of surgical weight loss on fatty liver disease in severely obese patients. Summary Background Data: Nonalcoholic fatty liver disease (NAFLD), a spectrum that extends to liver fibrosis and cirrhosis, is rising at an alarming rate. This increase is occurring in conjunction with the rise of severe obesity and is probably mediated in part by metabolic syndrome (MS). Surgical weight loss operations, probably by reversing MS, have been shown to result in improvement in liver histology. Methods: Patients who underwent laparoscopic surgical weight loss operations from March 1999 through August 2004, and who agreed to have an intraoperative liver biopsy followed by at least one postoperative liver biopsy, were included. Results: There were 70 patients who were eligible. All patients underwent laparoscopic operations, the majority being laparoscopic Roux-en-Y gastric bypass. The mean excess body weight loss at time of second biopsy was 59% ± 22% and the time interval between biopsies was 15 ± 9 months. There was a reduction in prevalence of metabolic syndrome, from 70% to 14% (P < 0.001), and a marked improvement in liver steatosis (from 88% to 8%), inflammation (from 23% to 2%), and fibrosis (from 31% to 13%; all P < 0.001). Inflammation and fibrosis resolved in 37% and 20% of patients, respectively, corresponding to improvement of 82% (P < 0.001) in grade and 39% (P < 0.001) in stage of liver disease. Conclusion: Surgical weight loss results in significant improvement of liver morphology in severely obese patients. These beneficial changes may be associated with a significant reduction in the prevalence of the metabolic syndrome. PMID:16192822

The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma.

PubMed

Pierie, Jean-Pierre E N; Muzikansky, Alona; Tanabe, Kenneth K; Ott, Mark J

2005-07-01

Optimal management of patients with hepatocellular carcinoma (HCC) is controversial. This study was conducted to evaluate the outcome of tumor resection versus assignment to a liver transplant waiting list (WL) in patients with HCC. Prospectively collected patient data from 1970 to 1997 on 313 patients with HCC were retrospectively analyzed by multivariate analysis to determine the effect of liver disease, method of treatment, and tumor-related factors on survival. A total of 199 patients underwent nonsurgical palliative care (PC), 81 underwent partial liver resection (LR), and 33 were assigned to a liver transplant WL, of which 22 received a donor liver. A total of 91%, 53%, and 91% of the patients had cirrhotic livers in the PC, LR, and WL groups, respectively (P < .001). In the LR group, the absence of a tumor capsule (P < .0001) and a poorly differentiated tumor (P = .027) were both adverse prognostic factors. In the WL group, hepatitis B (P = .02) and American Joint Committee on Cancer tumor stage III (P = .019) were adverse prognostic factors. The 3-year survival rates were 4%, 33%, and 38% for the PC, LR, and WL patients, respectively (P < .0001). The 3-year survival rate in the LR patients was 51% in patients without cirrhosis and 15% in patients with cirrhosis (P < .0001). Patients with locally unresectable tumors, distant disease, or both will continue to receive PC. Patients assigned to liver transplant WLs run the risk of not receiving a donor liver, in which case their survival is predicted to be poor. Survival after resection in a group of patients with advanced tumors is worse than that after transplantation; however, shortages of donor livers presently preclude transplantation in this population of patients.

Incidence of late atrial fibrillation in bilateral lung versus heart transplants.

PubMed

Magruder, J Trent; Plum, William; Crawford, Todd C; Grimm, Joshua C; Borja, Marvin C; Berger, Ronald D; Tandri, Harikrishna; Calkins, Hugh; Cameron, Duke E; Mandal, Kaushik

2016-10-01

We compared the incidence of late-onset atrial fibrillation in orthotopic heart transplant recipients and bilateral orthotopic lung transplant recipients. We reviewed the records of all heart and lung transplant operations carried out in our institution between 1995 and 2015. We performed 1:1 propensity-matching based on patient age, sex, body mass index, and hypertension. Our primary outcome, late-onset atrial fibrillation, was defined as atrial fibrillation occurring after discharge following hospitalization for transplantation. Over the study period, 397 orthotopic heart transplants and 240 bilateral orthotopic lung transplants were performed. Propensity matching resulted in 173 pairs who were matched with respect to age, sex, body mass index, and preoperative hypertension. The median follow-up was 5.3 years for heart transplant patients and 3.1 years for lung transplant patients. Late-onset atrial fibrillation occurred in 11 heart transplant patients (5 of whom had biopsy-proven evidence of rejection) and 19 lung transplant patients (2 of whom had biopsy-proven evidence of rejection). On Kaplan-Meier analysis, the probability of late-onset atrial fibrillation at 5 years was 4.3% for heart transplant patients vs. 13.9% for lung transplant patients (log-rank p = 0.01). We documented an increased probability of late-onset atrial fibrillation among bilateral orthotopic lung transplant patients compared to orthotopic heart transplant patients. This was a hypothesis-generating study that suggests a potential role for cardiac autonomic innervation in the genesis of atrial fibrillation. © The Author(s) 2016.

Early and Long-Term Outcomes of Patients Undergoing Liver Resection and Diaphragm Excision for Advanced Colorectal Liver Metastases

PubMed Central

Lordan, Jeffrey T; Riga, Angela; Worthington, Tim R; Karanjia, Nariman D

2009-01-01

INTRODUCTION At present, liver resection offers the best long-term outcome and only chance for cure in patients with colorectal liver metastases. However, there are no large series that report the early and long-term outcomes of patients who require simultaneous diaphragm excision. This study was designed to investigate these patients. PATIENTS AND METHODS A total of 285 consecutive liver resections were performed over a 10-year period. Of these, 258 had liver resections alone and 27 underwent liver resection and simultaneous diaphragm excision. Data were collected prospectively and analysed retrospectively. Pre-operative assessment was standardised. The outcomes between the two groups were compared. RESULT There was no difference in age, hospital stay or intra-operative blood loss. The diaphragm was histologically involved in four out of 27 resections. As a result, the cancer involved resection margin incidence was greater in the liver resection and diaphragm excision group (14.8% versus 3.9%; P = 0.12). The median tumour size was also different between the two groups (60 mm versus 30 mm; P = 0.001). The liver and diaphragm resection group had a greater peri-operative complication rate (44.4% versus 21.3%; P = 0.02) and mortality (7.4% versus 1.6%; P = 0.25). Overall and disease-free survival was significantly worse in the group who underwent simultaneous diaphragm excision and liver resection (P = 0.04 and P = 0.005, respectively). Diaphragm invasion was found to be an independent predictor of poor overall outcome (P = 0.02). CONCLUSION Liver resection and simultaneous diaphragm excision have a greater incidence of peri-operative morbidity and mortality and a significantly worse long-term outcome compared with liver resection alone. However, these data suggest that liver resection in the presence of diaphragm invasion may still offer a favourable outcome compared with chemotherapy treatment alone. Therefore, we believe that diaphragm involvement by tumour should not be a contra-indication to hepatectomy. PMID:19558763

Evaluation of neovascularization patterns in an orthotopic rat glioma model with dynamic contrast-enhanced MRI.

PubMed

Xuesong, Du; Wei, Xue; Heng, Liu; Xiao, Chen; Shunan, Wang; Yu, Guo; Weiguo, Zhang

2017-09-01

Background Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been proved useful in evaluating glioma angiogenesis, but the utility in evaluating neovascularization patterns has not been reported. Purpose To evaluate in vivo real-time glioma neovascularization patterns by measuring glioma perfusion quantitatively using DCE-MRI. Material and Methods Thirty Sprague-Dawley rats were used to establish C6 orthotopic glioma model and underwent MRI and pathology detections. As MRI and pathology were performed at six time points (i.e. 4, 8, 12, 16, 20, and 24 days) post transplantation, neovascularization patterns were evaluated via DCE-MRI. Results Four neovascularization patterns were observed in glioma tissues. Sprout angiogenesis and intussusceptive microvascular growth located inside tumor, while vascular co-option and vascular mimicry were found in the tumor margin and necrotic area, respectively. Sprout angiogenesis and intussusceptive microvascular growth increased with K trans , K ep , and V p inside tumor tissue. In addition, K ep and V p were positively correlated with sprout angiogenesis and intussusceptive microvascular growth. Vascular co-option was decreased at 12 and 16 days post transplantation and correlated negatively with K trans and K ep detected in the glioma margin, respectively. Changes of vascular mimicry showed no significant statistical difference at the six time points. Conclusion Our results indicate that DCE-MRI can evaluate neovascularization patterns in a glioma model. Furthermore, DCE-MRI could be an imaging biomarker for guidance of antiangiogenic treatments in humans in the future.

Recurrent protein-losing enteropathy and tricuspid valve insufficiency in a transplanted heart: a causal relationship?

PubMed

Aggarwal, Sanjeev; Delius, Ralph E; Walters, Henry L; L'Ecuyer, Thomas J

2012-01-01

This case report describes a toddler who developed a protein-losing enteropathy (PLE) 4 years after orthotopic heart transplantation (OHT). He was born with a hypoplastic left heart syndrome for which he underwent a successful Norwood procedure, a Hemi-Fontan palliation, and a Fontan palliation at 18 months of age. Fifteen months following the Fontan operation, he developed a PLE and Fontan failure requiring OHT. Four years after OHT, he developed a severe tricuspid regurgitation and a PLE. His PLE improved after tricuspid valve replacement. It is now 2 years since his tricuspid valve replacement and he remains clinically free of ascites and peripheral edema with a normal serum albumin level. His prosthetic tricuspid valve is functioning normally. © 2011 Wiley Periodicals, Inc.

Urea cycle disorders: a case report of a successful treatment with liver transplant and a literature review.

PubMed

Foschi, Francesco Giuseppe; Morelli, Maria Cristina; Savini, Sara; Dall'Aglio, Anna Chiara; Lanzi, Arianna; Cescon, Matteo; Ercolani, Giorgio; Cucchetti, Alessandro; Pinna, Antonio Daniele; Stefanini, Giuseppe Francesco

2015-04-07

The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders (UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant (OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.

OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

PubMed Central

Shi, Jun; Wei, Pin-Kang; Zhang, Shen; Qin, Zhi-Feng; Li, Jun; Sun, Da-Zhi; Xiao, Yan; Yu, Zhi-Hong; Lin, Hui-Ming; Zheng, Guo-Jing; Su, Xiao-Mei; Chen, Ya-Lin; Liu, Yan-Fang; Xu, Ling

2008-01-01

AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthotopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplan-tation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors. PMID:18720543

Calcified telangiectatic hyperplastic nodule associated with vascular malformation in a child: a case report.

PubMed

Marti, Josep; Trivedi, Anshu; D'Alessandro, Valentina; Roayaie, Sasan; Rosen, Ally; Arnon, Ronen; Thung, Swan

2015-04-01

This is a case report of an asymptomatic 4-year-old girl who was found to have a nodule at the lateral left lobe of the liver. She underwent transabdominal liver ultrasound and abdominal MRI that showed calcification and intense arterial enhancement but they failed to clearly exclude malignancy. The patient underwent an unremarkable laparoscopic wedge liver resection of the lesion because of its location and size. Pathological examination showed features compatible with a benign telangiectatic hyperplastic nodule with vascular malformation and calcification. CD34 immunostained the proliferative vascular lining cells while CK7 and CK19 highlighted the normal bile ducts present within the lesion. The diagnosis of a telangiectatic hyperplastic nodule associated with vascular malformation has been scarcely reported in children and our case shows for the first time that it can also present with calcifications.

[A Case of Chemotherapy with FOLFOXIRI plus Cetuximab for Liver Metastasis of Sigmoid ColonCan cer].

PubMed

Saito, Akina; Konishi, Ken; Fukunaga, Mutsumi; Takiguchi, Nobuo; Nakai, Shigeto; Honda, Shoko; Yukimoto, Ryohei; Okamoto, Aoi; Takeoka, Tomohira; Matsuno, Hiroshi; Okada, Kazuyuki; Ota, Hideo; Yokoyama, Shigekazu; Konishi, Muneharu; Kobayashi, Kenji

2018-03-01

We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2 tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under laparotomy, and after the operation, received 7 courses of chemotherapy with FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and laparotomy and liver right lobectomy were performed. Histopathology revealed a modified, Grade 2 tumor regression. He has been followed for 1 year 4months after the operation.

Orthotopic Patient-Derived Glioblastoma Xenografts in Mice.

PubMed

Xu, Zhongye; Kader, Michael; Sen, Rajeev; Placantonakis, Dimitris G

2018-01-01

Patient-derived xenografts (PDX) provide in vivo glioblastoma (GBM) models that recapitulate actual tumors. Orthotopic tumor xenografts within the mouse brain are obtained by injection of GBM stem-like cells derived from fresh surgical specimens. These xenografts reproduce GBM's histologic complexity and hallmark biological behaviors, such as brain invasion, angiogenesis, and resistance to therapy. This method has become essential for analyzing mechanisms of tumorigenesis and testing the therapeutic effect of candidate agents in the preclinical setting. Here, we describe a protocol for establishing orthotopic tumor xenografts in the mouse brain with human GBM cells.

[Anorectal Malignant Melanoma Is a Very Rare Disease and Has a Poor Prognosis].

PubMed

Yoshida, Yuta; Noura, Shingo; Matsumura, Tae; Hirota, Masaki; Shuto, Takashi; Muratsu, Arisa; Yasuyama, Harunobu; Takata, Akihiro; Koga, Chikato; Kameda, Chizu; Murakami, Masahiro; Kawabata, Ryohei; Shimizu, Junzo; Miwa, Hideaki; Hasegawa, Junichi

2017-11-01

We performed abdomino-perineal-resection(APR)on 2 cases of anorectal malignant melanoma. The first case was a 70- year-old woman suffering from bloody stool. Colonoscopy showed a black tumor in the rectum. Biopsy revealed a malignant melanoma. A CT scan showed multiple lung metastases and liver metastasis. She underwent surgery for the purpose of bleeding control, but died shortly thereafter because her liver and lung metastases had worsened. The second case was a 43- years-old man suffering from bloody stool. He had a black type 3 tumor in the rectum. A biopsy revealed malignant melanoma. A CT scan showed lateral lymph node swelling. He underwent APR with right side-lateral dissection. An established treatment for anorectal malignant melanoma has not been agreed upon and it is controversial. We experienced 2 cases that underwent surgery and we report them along with relevant information from the literature.

Randomized Trial of Studer Pouch versus T-Pouch Orthotopic Ileal Neobladder in Patients with Bladder Cancer.

PubMed

Skinner, Eila C; Fairey, Adrian S; Groshen, Susan; Daneshmand, Siamak; Cai, Jie; Miranda, Gus; Skinner, Donald G

2015-08-01

The need to prevent reflux in the construction of an orthotopic ileal neobladder is controversial. We designed the USC-STAR trial to determine whether the T-pouch neobladder that included an antireflux mechanism was superior to the Studer pouch in patients with bladder cancer undergoing radical cystectomy. This single center, randomized, controlled trial recruited patients with clinically nonmetastatic bladder cancer scheduled to undergo radical cystectomy with neobladder. Eligible patients were randomly assigned to undergo T-pouch or Studer ileal orthotopic neobladder. Treatment assignment was not masked. The primary end point was change in renal function from baseline to 3 years. The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation was used to calculate the estimated glomerular filtration rate. Between February 2002 and November 2009, 237 patients were randomly assigned to T-pouch ileal orthotopic neobladder and 247 to Studer ileal orthotopic neobladder. Baseline characteristics did not differ between the groups. Between baseline and 3 years the estimated glomerular filtration rate decreased by 6.4 ml/minute/1.73 m(2) in the Studer group and 6.6 ml/minute/1.73 m(2) in the T-pouch group (p=0.35). Multivariable analysis showed that type of ileal orthotopic neobladder was not independently associated with 3-year renal function (p=0.63). However, baseline estimated glomerular filtration rate, age and urinary tract obstruction were independently associated with 3-year decline in renal function. Cumulative risk of urinary tract infection and overall late complications were not different between the groups, but the T-pouch was associated with an increased risk of secondary diversion related surgeries. T-pouch ileal orthotopic neobladder with an antireflux mechanism did not prevent a moderate reduction in renal function observed at 3 years compared to the Studer pouch, but did result in an increase in diversion related secondary surgical procedures. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease.

PubMed

Al-Busafi, Said A; Ghali, Peter; Wong, Philip; Novales-Diaz, Javier A; Deschênes, Marc

2012-03-01

Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy. To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD. From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists. NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively. Xe-133 liver scan proved to be a safe, reliable, noninvasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.

Under Utilization of Pancreas Transplants in Cystic Fibrosis Recipients in the United Network Organ Sharing (UNOS) Data 1987-2014.

PubMed

Usatin, D J; Perito, E R; Posselt, A M; Rosenthal, P

2016-05-01

Despite a high prevalence of pancreatic endocrine and exocrine insufficiency in cystic fibrosis (CF), pancreas transplantation is rarely reported. United Network for Organ Sharing (UNOS) data were used to examine utilization of pancreas transplant and posttransplant outcomes in CF patients. Between 1987-2014, CF patients (N = 4600) underwent 17 liver-pancreas, three lung-pancreas, one liver-lung pancreas, four kidney-pancreas, and three pancreas-only transplants. Of the 303 CF patients who received liver transplantation, 20% had CF-related diabetes (CFRD) before transplantation, and nine of those received a liver-pancreas transplant. Of 4241 CF patients who underwent lung transplantation, 33% had CFRD before transplantation, and three of those received a pancreas transplant. Of 49 CF patients who received a liver-lung transplant, 57% had CFRD before transplantation and one received a pancreas transplant. Posttransplantation diabetes developed in 7% of CF pancreas transplant recipients versus 24% of CF liver and 29% of CF lung recipients. UNOS has no data on pancreas exocrine insufficiency. Two-year posttransplantation survival was 88% after liver-pancreas transplant, 33% after lung-pancreas transplant, and 100% after pancreas-kidney and pancreas-only transplants. Diabetes is common pretransplantation and posttransplantation in CF solid organ transplant recipients, but pancreas transplantation remains rare. Further consideration of pancreas transplant in CF patients undergoing other solid organ transplant may be warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection.

PubMed

Cieslak, Kasia P; Bennink, Roelof J; de Graaf, Wilmar; van Lienden, Krijn P; Besselink, Marc G; Busch, Olivier R C; Gouma, Dirk J; van Gulik, Thomas M

2016-09-01

(99m)Tc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated. 163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m(2) were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods. 29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods. Implementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Intraperitoneal administration of apigenin in liver ischemia/reperfusion injury protective effects.

PubMed

Tsaroucha, Alexandra K; Tsiaousidou, Anastasia; Ouzounidis, Nikolaos; Tsalkidou, Evanthia; Lambropoulou, Maria; Giakoustidis, Dimitrios; Chatzaki, Ekaterini; Simopoulos, Constantinos

2016-11-01

Hepatic injury caused by ischemia/reperfusion (I/R) is a clinical problem associated with major liver surgery. Among other flavonoids, apigenin has shown a promising effect on I/R cases. In this study, we have investigated the effects of apigenin after liver I/R injury in rats. Forty eight rats were randomized into the following eight groups: (1) Control-sham group: rats subjected to the surgical procedure, except for liver I/R; (2) DMSO group: rats subjected to surgery, except for liver I/R given the apigenin solvent dimethyl-sulfoxide intraperitoneally; (3) C60 group; (4) C120 group; (5) C240 group: rats underwent liver ischemia for 45 min followed by reperfusion for 60 min, 120 min, and 240 min; (6) AP60 group; (7) AP120 group; (8) AP240 group: rats underwent liver ischemia for 45 min, and then given apigenin (5 mg) intraperitoneally followed by reperfusion for 60 min, 120 min, and 240 min. Reverse transcription polymerase chain reaction was performed on liver tissues to measure BCL-2/BAX expression, enzyme-linked immunosorbent assay to measure M30/M65 and ICAM-1. Immunohistochemistry was used to identify M30 biomarker in liver tissues. Quantitative variables were tested by Kolmogorov-Smirnov test, repeated measures analysis of variance/Friedman test. Gene levels were assessed by Student's t-test/Mann-Whitney U-test. BCL-2 levels were significantly higher in I/R apigenin groups than in I/R control groups. BAX levels were lower in the AP240 group than in C240 group. Prolongation of reperfusion resulted in increased activation of M30. ICAM-1 levels were lower in the AP240 group than in C240 group. Apigenin seems to inhibit the process of apoptosis and ameliorate the hepatic I/R injury.

Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases.

PubMed

Matsuki, Ryota; Mise, Yoshihiro; Saiura, Akio; Inoue, Yosuke; Ishizawa, Takeaki; Takahashi, Yu

2016-11-01

The feasibility of parenchymal-sparing hepatectomy has yet to be assessed based on the tumor location, which affects the choice of treatment in patients with colorectal liver metastases. Sixty-three patients underwent first curative hepatectomy for deep-placed colorectal liver metastases whose center was located >30 mm from the liver surface. Operative outcomes were compared among patients who underwent parenchymal-sparing hepatectomy or major hepatectomy (≥3 segments). Parenchymal-sparing hepatectomy and major hepatectomy were performed for deep-placed colorectal liver metastases in 40 (63%) and 23 (37%) patients, respectively. Resection time was longer in the parenchymal-sparing hepatectomy than in the major hepatectomy group (57 vs 39 minutes) (P = .02) and cut-surface area was wider (120 vs 86 cm 2 ) (P < .01). Resected volume was smaller in the parenchymal-sparing hepatectomy than in the major hepatectomy group (251 vs 560 g) (P < .01). No differences were found between the 2 groups for total operation time (306 vs 328 minutes), amount of blood loss (516 vs 400 mL), rate of major complications (10% vs 13%), and positive operative margins (5% vs 4%). Overall, recurrence-free, and liver recurrence-free survivals did not differ between the 2 groups. Direct major hepatectomy without portal venous embolization could not have been performed in 40% of the parenchymal-sparing hepatectomy group (16/40) because of the small liver remnant volume. Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases was performed safely without compromising oncologic radicality. Parenchymal-sparing hepatectomy can increase the number of patients eligible for an operation by halving the resection volume and by increasing the chance of direct operative treatment in patients with ill-located colorectal liver metastases. Copyright © 2016 Elsevier Inc. All rights reserved.

Phase 1-2 pilot clinical trial in patients with decompensated liver cirrhosis treated with bone marrow-derived endothelial progenitor cells.

PubMed

D'Avola, Delia; Fernández-Ruiz, Verónica; Carmona-Torre, Francisco; Méndez, Miriam; Pérez-Calvo, Javier; Prósper, Felipe; Andreu, Enrique; Herrero, José Ignacio; Iñarrairaegui, Mercedes; Fuertes, Carmen; Bilbao, José Ignacio; Sangro, Bruno; Prieto, Jesús; Quiroga, Jorge

2017-10-01

The aim of this nonrandomized, open label, phase 1 clinical trial was to evaluate the safety and the feasibility of the treatment with autologous bone marrow-derived endothelial progenitor cells (EPC) in decompensated liver cirrhosis. In addition, the changes in liver function and hepatic venous pressure gradient (HVPG) and their relation with the characteristics of the cellular product were analyzed. Twelve patients with Child-Pugh ≥8 liver cirrhosis underwent bone marrow harvest for ex vivo differentiation of EPC. The final product was administered through the hepatic artery in a single administration. Patients underwent clinical and radiologic follow-up for 12 months. The phenotype and the ability to produce cytokines and growth factors of the final cellular suspension were analyzed. Eleven patients were treated (feasibility 91%). No treatment-related severe adverse events were observed as consequence of any study procedure or treatment. Model for end-stage liver disease score improved significantly (P 0.042) in the first 90 days after cells administration and 5 of the 9 patients alive at 90 days showed a decreased of HVPG. There was a direct correlation between the expression of acetylated-low density lipoprotein and von Willebrand factor in the cellular product and the improvement in liver function and HVPG. The treatment with EPCs in patients with decompensated liver cirrhosis is safe and feasible and might have therapeutic potential. Patients receiving a higher amount of functionally active EPC showed an improvement of liver function and portal hypertension suggesting that the potential usefulness of these cells for the treatment of liver cirrhosis deserves further evaluation. Copyright © 2016 Elsevier Inc. All rights reserved.

Acceleration of hepatobiliary dynamics in liver transplant donors.

PubMed

Aktaş, A; Koyuncu, A; Yalçin, H

2004-01-01

This study compared hepatobiliary scintigraphy findings in livers before and after liver graft donation to examine whether there is a change in hepatobiliary dynamics. Nine donors underwent hepatobiliary scintigraphy with intravenous injection of Tc-99m mebrofenin 1 day before and during the first week after left liver lobectomy. Five donors also underwent additional scintigraphy more than 1 year postsurgery. Images were acquired every second for the first minute, and then every minute for the next 40 minutes. Hepatic arterial perfusion index and portal perfusion index(PPI) were calculated from the images acquired during the first minute. For the function phase the computed parameters included: hepatic extraction efficiency, (HEE), time to appearance of activity in the intrahepatic biliary channels, and in the intestine, time to half maximal activity, and activity retained in the liver parenchyma at 40 minutes. Time to appearance of intrahepatic biliary channels and of intestinal activity was shorter among scintigraphies obtained within 1 week postsurgery compared to the preoperative values. Early after the operation HEE increased and PPI decreased significantly. Visual inspection of the scintigraphy scan obtained in all donors, within the first week postsurgery revealed hypertrophy of the right liver lobe. None of the patients showed progression of right lobe activity to the left side, even among scans obtained more than 1 year after donation. Reduced time to activity in the biliary channels and intestine and increased HEE suggest acceleration of hepatobiliary dynamics.

Combined microwave ablation and systemic chemotherapy for liver metastases from oesophageal cancer: Preliminary results and literature review.

PubMed

Zhou, Fubo; Yu, Xiaoling; Liang, Ping; Cheng, Zhigang; Han, Zhiyu; Yu, Jie; Liu, Fangyi; Tan, Shuilian; Dai, Guanghai; Bai, Li

2016-08-01

Oesophageal cancer is a highly aggressive disease with about 50% of patients presenting with advanced or metastatic disease at initial diagnosis. In this study we assessed combined microwave ablation (MWA) and systemic chemotherapy in the treatment of liver metastases arising from oesophageal squamous cell carcinoma (OSCC). Between February 2009 and June 2014, OSCC patients who underwent percutaneous MWA + concurrent systemic chemotherapy and systemic chemotherapy alone for liver metastases were enrolled in this study. Overall survival (OS) and progression-free survival (PFS) were recorded and compared between groups. In total 15 patients with 25 liver metastases who underwent ultrasound-guided percutaneous MWA and chemotherapy were enrolled in this study. Technical success was achieved in 96% (24/25) of metastatic liver tumours. No major or minor complications associated with MWA procedures were observed. The median OS and PFS from initial MWA were 13 months and 4 months. The 1-, 2-, 3-, 4-year OS rates after MWA were 53.3%, 26.7%, 13.3%, and 13.3%, respectively. The 1- and 2-year PFS rates after MWA were 26.7% and 13.3%. The OS and PFS of the MWA + systemic chemotherapy group were superior than those of patients who received systemic chemotherapy alone (P = 0.011 and 0.030, respectively). Combined MWA with systemic chemotherapy is a feasible, safe and effective treatment for liver metastases from OSCC.

The Safety and Feasibility of Three-Dimensional Visualization Technology Assisted Right Posterior Lobe Allied with Part of V and VIII Sectionectomy for Right Hepatic Malignancy Therapy.

PubMed

Hu, Min; Hu, Haoyu; Cai, Wei; Mo, Zhikang; Xiang, Nan; Yang, Jian; Fang, Chihua

2018-05-01

Hepatectomy is the optimal method for liver cancer; the virtual liver resection based on three-dimensional visualization technology (3-DVT) could provide better preoperative strategy for surgeon. We aim to introduce right posterior lobe allied with part of V and VIII sectionectomy assisted by 3-DVT as a promising treatment for massive or multiple right hepatic malignancies to retain maximum residual liver volume on the basis of R0 resection. Among 126 consecutive patients who underwent hepatectomy, 9 (7%) underwent right posterior lobe allied with part of V and VIII sectionectomy. 21 (17%) underwent right hemihepatectomy (RH). The virtual RH was performed with 3-DVT, which provided better observation of spatial position relationship between tumor and vessels, and the more accurate estimation of the remnant liver volume. If remnant liver volume was <40%, right posterior lobe allied with part of V and VIII sectionectomy should be undergone. Then, the precut line ought to be planned on the basis of protecting the portal branch of subsegment 5 and 8. The postoperative outcome of patients was compared before and after propensity score matching. Nine patients meeting the eligibility criteria received right posterior lobe allied with part of V and VIII sectionectomy. The variables, including the overall mean operation time, blood transfusion, operation length, liver function, and postoperative complications, were similar between two groups before and after propensity matching. The postoperative first, third, fifth, and seventh days mean value of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin had no significant difference compared with preoperative value. One patient in each group had recurrence six months after surgery. Right posterior lobe allied with part of V and VIII sectionectomy based on 3-DVT is safe and feasible surgery way, and can be a very promising method in massive or multiple right hepatic malignancy therapy.

Orthotopic Liver Transplantation in High-Risk Patients

PubMed Central

Gayowski, Timothy; Marino, Ignazio R.; Singh, Nina; Doyle, Howard; Wagener, Marilyn; Fung, John J.; Starzl, Thomas E.

2010-01-01

Background One of the most controversial areas in patient selection and donor allocation is the high-risk patient. Risk factors for mortality and major infectious morbidity were prospectively analyzed in consecutive United States veterans undergoing liver transplantation under primary tacrolimus-based immunosuppression. Methods Twenty-eight pre-liver transplant, operative, and posttransplant risk factors were examined univariately and multivariately in 140 consecutive liver transplants in 130 veterans (98% male; mean age, 47.3 years). Results Eighty-two percent of the patients had post-necrotic cirrhosis due to viral hepatitis or ethanol (20% ethanol alone), and only 12% had cholestatic liver disease. Ninety-eight percent of the patients were hospitalized at the time of transplantation (66% United Network for Organ Sharing [UNOS] 2, 32% UNOS 1). Major bacterial infection, posttransplant dialysis, additional immunosuppression, readmission to intensive care unit (P=0.0001 for all), major fungal infection, posttransplant abdominal surgery, posttransplant intensive care unit stay length of stay (P<0.005 for all), donor age, pretransplant dialysis, and creatinine (P<0.05 for all) were significantly associated with mortality by univariate analysis. Underlying liver disease, cytomegalovirus infection and disease, portal vein thrombosis, UNOS status, Childs-Pugh score, patient age, pretransplant bilirubin, ischemia time, and operative blood loss were not significant predictors of mortality. Patients with hepatitis C (HCV) and recurrent HCV had a trend towards higher mortality (P=0.18). By multivariate analysis, donor age, any major infection, additional immunosuppression, post-transplant dialysis, and subsequent transplantation were significant independent predictors of mortality (P<0.05). Major infectious morbidity was associated with HCV recurrence (P=0.003), posttransplant dialysis (P=0.001), pretransplant creatinine, donor age, median blood loss, intensive care unit length of stay, additional immunosuppression, and biopsy-proven rejection (P<0.05 for all). By multivariate analysis, intensive care unit length of stay and additional immunosuppression were significant independent predictors of infectious morbidity (P<0.03). HCV recurrence was of borderline significance (P=0.07). Conclusions Biologic and physiologic parameters appear to be more powerful predictors of mortality and morbidity after liver transplantation. Both donor and recipient variables need to be considered for early and late outcome analysis and risk assessment modeling. PMID:9500623

[Surgical treatment of pulmonary metastases from colon and rectal cancer].

PubMed

Togashi, Ken-ichi; Aoki, K; Hirahara, H; Sugawara, M; Oguma, F

2004-09-01

We retrospectively studied the surgical treatment for pulmonary metastases from colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age 61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22 patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies for metastatic rectal cancer. The median interval between the primary procedure and lung resection for metastases was 26 months in the patients with colon carcinoma and 32 months in the patients with rectal cancer. In the patients with colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video-assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1 video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1 underwent exploratory thoracotomy. All procedures except exploratory thoracotomy were curative operations. There was no mortality. Overall 5-year survival was 56% (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and 45% for patients with rectal metastases (n=22), and there was no significant difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus, and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer. Pulmonary resection for metastases from colon carcinoma may have better prognosis than that from rectal cancer. However, further investigation may be required to obtain convincing conclusions.

Bridging locoregional therapy for hepatocellular carcinoma prior to liver transplantation.

PubMed

Heckman, Jason T; Devera, Michael B; Marsh, J Wallis; Fontes, Paulo; Amesur, Nikhil B; Holloway, Shane E; Nalesnik, Michael; Geller, David A; Steel, Jennifer L; Gamblin, T Clark

2008-11-01

The impact of locoregional therapy prior to liver transplantation for hepatocellular carcinoma utilizing either transcatheter arterial chemoembolization (TACE), yttrium-90 ((90)Y), radiofrequency ablation (RFA), or resection prior to orthotopic liver transplantation (OLT) is largely unknown. We sought to examine locoregional therapies and their effect on survival compared with transplantation alone. A retrospective review of a prospectively collected database. 123 patients were included. Patients were analyzed in two groups. Group I consisted of 50 patients that received therapy (20 TACE; 16 (90)Y; 13 RFA, 3 resections). Group II consisted of 73 patients transplanted without therapy. Median list time was 28 days (range 2-260 days ) in group I, and 24 days (range 1-380 days) in group II. Median time from therapy to OLT was 3.8 months (range 9 days to 68 months). Twelve patients (24%) were successfully downstaged (8 TACE, 2 (90)Y, 2 RFA/resection). Overall 1-, 3-, and 5-year survival were 81%, 74%, and 74%, respectively. Survival was not statistically significantly different between the two groups (P = 0.53). The 12 patients downstaged did not have a significant difference in survival as compared with the patients who received therapy but did not respond or the patients who were transplanted without therapy (P = 0.76). Our report addresses locoregional therapy for hepatocellular carcinoma as a bridge to transplant. There was no statistical difference in overall survival between patients treated and those not treated prior to transplant. We provide further evidence that locoregional therapy is a safe tool for patients on the transplant list, does not impact survival, and can downstage selected patients to allow life-saving liver transplantation.

The role of FDG-PET in detecting rejection after liver transplantation.

PubMed

Watson, Ashley M; Bhutiani, Neal; Philips, Prejesh; Davis, Eric G; Eng, Mary; Cannon, Robert M; Jones, Christopher M

2018-05-15

The activation and increased metabolic activity of T cells in acute cellular rejection could allow fluoro-2-deoxyglucose positron emission tomography to be utilized for detection of acute cellular rejection. The objective of this study was to evaluate the effectiveness of fluoro-2-deoxyglucose positron emission tomography in detecting acute cellular rejection in the clinical setting. Fluoro-2-deoxyglucose positron emission tomography studies were performed on 88 orthotopic liver transplant patients at 7 and 17 days postoperatively (first positron emission tomography and second positron emission tomography, respectively). Additional studies were performed if patients had suspicion of rejection and at resolution of rejection (third positron emission tomography and fourth positron emission tomography, respectively). A circular region of interest was placed over the liver for semiquantitative evaluation of fluoro-2-deoxyglucose positron emission tomography images by means of standard uptake values. Eighteen of 88 patients in our study (20.5%) had histologically proven acute cellular rejection during a 16 ± 11 day follow-up. There was no significant difference between the standard uptake values of first positron emission tomography among non-rejecters versus rejecters (2.05 ±0.46 non-rejecters versus 1.82 ± 0.40 rejecters, P = .127). Within the rejection cohort, the standard uptake values from the third positron emission tomography (rejection) were higher compared to the first positron emission tomography (baseline) (2.41 ± 0.48 third positron emission tomography versus 1.82 ± 0.41 first positron emission tomography, P < .001). Increased signal on fluoro-2-deoxyglucose positron emission tomography over baseline is associated with acute cellular rejection in liver transplant recipients. Additional prospective validation studies are essential to define the role of fluoro-2-deoxyglucose positron emission tomography scan as an early marker for acute cellular rejection. Copyright © 2018 Elsevier Inc. All rights reserved.

Ventral incisional hernia (VIH) repair after liver transplantation (OLT) with a biological mesh: experience in 3 cases.

PubMed

Schaffellner, S; Sereinigg, M; Wagner, D; Jakoby, E; Kniepeiss, D; Stiegler, P; Haybäck, J; Müller, H

2016-05-01

Hernias after orthotopic liver transplant (OLT) occur in about 30 % of cases. Predisposing factors in liver cirrhotic patients of cases are ascites, low abdominal muscle mass and cachexia before and immunosuppression after OLT. Standard operative transplant-technique even in small hernias is to implant a mesh. For patients after liver transplantation a porcine non-cross linked biological patch being less immunogenic than synthetic and cross-linked meshes is chosen for ventral incisional hernia repair. 3 patients (1 female, 2 male), OLT indications Hepatitis C, exogenous- toxic cirrhosis, median-age 53 (51 - 56) and median time to hernia occurrence after OLT were 10 month (6 - 18 m) are documented. 2 patients suffered from diabetes, 2 from chronic-obstructive lung disease. Maintenance immunosuppressions were Everolimus in 1 patient, Everolimus + MMF in the second and Everolimus +Tacrolimus in the third patient. The biological was chosen for hernia repair due to the preexisting risk- factors. Meshes, 10 × 16 cm were placed, in IPOM (Intra-Peritonel-Onlay-Mesh) -position by relaparatomy. Insolvable, monofile, interrupted sutures were used. All patients recovered primarily, and were dismissed within 10 d post OP. No wound healing disorders or signs of postoperative infections occurred. All are free of hernia recurrence in a mean observation time of 22 month (10 - 36). The usage of porcine non-cross-linked biological patches seems feasible for incisional hernia repair after OLT. Wound infections in these patients have been observed with other meshes. Further investigation is needed to prove potential superiority of this biological to the other meshes. © Georg Thieme Verlag KG Stuttgart · New York.

Distinct enzyme profiles in patients with cryptogenic cirrhosis reflect heterogeneous causes with different outcomes after liver transplantation (OLT): a long-term documentation before and after OLT.

PubMed

Berg, Thomas; Neuhaus, Ruth; Klein, Reinhild; Leder, Korinna; Lobeck, Hartmut; Bechstein, Wolf-Otto; Müller, Andrea R; Wiedenmann, Bertram; Hopf, Uwe; Berg, Peter A; Neuhaus, Peter

2002-09-27

Sound information is lacking about the clinical presentation of cryptogenic cirrhosis and its outcome after orthotopic liver transplantation (OLT). Among 856 patients who have been transplanted at our center, 40 patients had no evidence of any known etiologies and were therefore defined as suffering from cryptogenic cirrhosis. Their median follow-up period before OLT was 78 months (range, 1-264), and after OLT 97 months (range, 1-132). Laboratory and histological data were evaluated according to features being compatible either with a toxic, hepatitic, or cholestatic condition. The clinical and histological findings differed specifically between these three groups. The toxic-like group (GGT 4-18 x upper limit of normal [ULN]) expressed significantly higher IgA levels, had histologically more often fatty liver changes, and risk factors for non-alcoholic steatohepatitis predominated (56% compared with 3% in the other groups, P=0.01). The hepatitic-like group (ALT 2-18 x ULN) showed histologically features of chronic hepatitis or hepatitic cirrhosis, and only among these patients a median International Autoimmune Hepatitis (IAH) score of 13 was found suggesting autoimmune hepatitis (AiH). In the cholestatic group (AP 2-8 x ULN) histology was compatible with a non-toxic inflammatory process but IAH score excluded AiH in all. After OLT, actuarial graft and patients survival was 90% at 5 years. Mild or moderate graft hepatitis occurred in 9 patients (23%) and was significantly associated with a pre-OLT IAH score >or= 10 (P =0.008). This study provides arguments that cryptogenic cirrhosis is a heterogeneous disease in which autoimmune mechanisms might be predominately involved and being responsible for recurrence of chronic liver disease observed in some instances after OLT.

Large-for-size liver transplant: a single-center experience.

PubMed

Akdur, Aydincan; Kirnap, Mahir; Ozcay, Figen; Sezgin, Atilla; Ayvazoglu Soy, Hatice Ebru; Karakayali Yarbug, Feza; Yildirim, Sedat; Moray, Gokhan; Arslan, Gulnaz; Haberal, Mehmet

2015-04-01

The ideal ratio between liver transplant graft mass and recipient body weight is unknown, but the graft probably must weigh 0.8% to 2.0% recipient weight. When this ratio > 4%, there may be problems due to large-for-size transplant, especially in recipients < 10 kg. This condition is caused by discrepancy between the small abdominal cavity and large graft and is characterized by decreased blood supply to the liver graft and graft dysfunction. We evaluated our experience with large-for-size grafts. We retrospectively evaluated 377 orthotopic liver transplants that were performed from 2001-2014 in our center. We included 188 pediatric transplants in our study. There were 58 patients < 10 kg who had living-donor living transplant with graft-to-bodyweight ratio > 4%. In 2 patients, the abdomen was closed with a Bogota bag. In 5 patients, reoperation was performed due to vascular problems and abdominal hypertension, and the abdomen was closed with a Bogota bag. All Bogota bags were closed in 2 weeks. After closing the fascia, 10 patients had vascular problems that were diagnosed in the operating room by Doppler ultrasonography, and only the skin was closed without fascia closure. No graft loss occurred due to large-for-size transplant. There were 8 patients who died early after transplant (sepsis, 6 patients; brain death, 2 patients). There was no major donor morbidity or donor mortality. Large-for-size graft may cause abdominal compartment syndrome due to the small size of the recipient abdominal cavity, size discrepancies in vascular caliber, insufficient portal circulation, and disturbance of tissue oxygenation. Abdominal closure with a Bogota bag in these patients is safe and effective to avoid abdominal compartment syndrome. Early diagnosis by ultrasonography in the operating room after fascia closure and repeated ultrasonography at the clinic may help avoid graft loss.

Graft reconditioning with nitric oxide gas in rat liver transplantation from cardiac death donors.

PubMed

Kageyama, Shoichi; Yagi, Shintaro; Tanaka, Hirokazu; Saito, Shunichi; Nagai, Kazuyuki; Hata, Koichiro; Fujimoto, Yasuhiro; Ogura, Yasuhiro; Tolba, Rene; Shinji, Uemoto

2014-03-27

Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor. We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group). Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (P<0.001), hyaluronic acid (P<0.05), and malondialdehyde (MDA) (P<0.001), hepatic interleukin-6 expression (IL-6) (P<0.05), and hepatic tumor necrosis factor-alpha (TNF-α) expression (P<0.001). Hepatic eNOS expression (P<0.001) was upregulated, whereas hepatic iNOS (P<0.01) and ET-1 (P<0.001) expressions were downregulated. The damage of hepatocyte and sinusoidal endothelial cells (SECs) were lower in group-VSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (P<0.01). These results suggest that VSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.

The potential of 5-fluorocytosine/cytosine deaminase enzyme prodrug gene therapy in an intrahepatic colon cancer model.

PubMed

Nyati, M K; Symon, Z; Kievit, E; Dornfeld, K J; Rynkiewicz, S D; Ross, B D; Rehemtulla, A; Lawrence, T S

2002-07-01

Colorectal cancer can metastasize to the liver, but remain liver confined for years. A critical step in developing treatments for intrahepatic cancer involves assessment in an orthotopic intrahepatic model. The purpose of this study was to develop a noninvasive intrahepatic tumor model to study the efficacy of 5-flucytosine/yeast cytosine deaminase (5FC/yCD)-based gene therapy for liver tumors. Luciferase expressing human colorectal carcinoma (HT-29luc) cells were generated by retroviral infection and implanted in the left liver lobe of nude mice. The bioluminescence was measured every week for a period of 1 month, then animals were killed and tumors were measured by calipers. After we found a correlation between photon counts and tumor size, animals were implanted with tumors composed of either 0%, 10%, or 100% yCD/HT-29luc cells, and treated with 5FC. Tumor bioluminescence was measured during treatment and tumor histology examined at the time of death. We found that 5FC caused significant regression of yCD expressing tumors. Furthermore, visible tumors at the time of death, which emitted little bioluminescence, contained little or no viable tumor. We then developed an adenoviral vector for yCD. Intraperitoneal administration of adenovirus containing yCD led to the production of yCD enzyme within intrahepatic tumors. These results suggest that (1) intrahepatic cancer responds to 5FC when cells express yCD; (2) the luciferin-luciferase system permits non-invasive real time imaging of viable intrahepatic cancer; and (3) this system can be used to carry out gene therapy experiments using yCD adenovirus.

Increased Renal Clearance of Rocuronium Compensates for Chronic Loss of Bile Excretion, via upregulation of Oatp2.

PubMed

Wang, Long; Zhou, Mai-Tao; Chen, Cai-Yang; Yin, Wen; Wen, Da-Xiang; Cheung, Chi-Wai; Yang, Li-Qun; Yu, Wei-Feng

2017-01-13

Requirement for rocuronium upon surgery changes only minimally in patients with end-stage liver diseases. Our study consisted of both human and rat studies to explore the reason. The reduction rate of rocuronium infusion required to maintain neuromuscular blockade during the anhepatic phase (relative to paleohepatic phase) was examined in 16 children with congenital biliary atresia receiving orthotopic liver transplantation. Pharmacodynamics and pharmacokinetics of rocuronium were studied based on BDL rats. The role of increased Oatp2 and decrease Oatp1 expressions in renal compensation were explored. The reduction of rocuronium requirements significantly decreased in obstructively jaundiced children (24 ± 9 vs. 39 ± 11%). TOF50 in BDL rats was increased by functional removal of the kidneys but not the liver, and the percentage of rocuronium excretion through urine increased (20.3 ± 6.9 vs. 8.6 ± 1.8%), while that decreased through bile in 28d-BDL compared with control group. However, this enhanced renal secretion for rocuronium was eliminated by Oatp2 knock-down, rather than Oatp1 overexpression (28-d BDL vs. Oatp1-ShRNA or Oatp2-ShRNA, 20.3 ± 6.9 vs. 17.0 ± 6.6 or 9.3 ± 3.2%). Upon chronic/sub-chronic loss of bile excretion, rocuronium clearance via the kidneys is enhanced, by Oatp2 up-regulation.

Fluorescence labeled microbubbles for multimodal imaging.

PubMed

Barrefelt, Åsa; Zhao, Ying; Larsson, Malin K; Egri, Gabriella; Kuiper, Raoul V; Hamm, Jörg; Saghafian, Maryam; Caidahl, Kenneth; Brismar, Torkel B; Aspelin, Peter; Heuchel, Rainer; Muhammed, Mamoun; Dähne, Lars; Hassan, Moustapha

2015-08-28

Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-μCT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

‘Extreme’ vasculobiliary injuries: association with fundus-down cholecystectomy in severely inflamed gallbladders

PubMed Central

Strasberg, Steven M; Gouma, Dirk J

2012-01-01

Objectives Extreme vasculobiliary injuries usually involve major hepatic arteries and portal veins. They are rare, but have severe consequences, including rapid infarction of the liver. The pathogenesis of these injuries is not well understood. The purpose of this study was to elucidate the mechanism of injury through an analysis of clinical records, particularly the operative notes of the index procedure. Methods Biliary injury databases in two institutions were searched for data on extreme vasculobiliary injuries. Operative notes for the index procedure (cholecystectomy) were requested from the primary institutions. These notes and the treatment records of the tertiary centres to which the patients had been referred were examined. Radiographs from the primary institutions, when available, as well as those from the tertiary centres, were studied. Results Eight patients with extreme vasculobiliary injuries were found. Most had the following features in common. The operation had been started laparoscopically and converted to an open procedure because of severe chronic or acute inflammation. Fundus-down cholecystectomy had been attempted. Severe bleeding had been encountered as a result of injury to a major portal vein and hepatic artery. Four patients have required right hepatectomy and one had required an orthotopic liver transplant. Four of the eight patients have died and one remains under treatment. Conclusions Extreme vasculobiliary injuries tend to occur when fundus-down cholecystectomy is performed in the presence of severe inflammation. Contractive inflammation thickens and shortens the cystic plate, making separation of the gallbladder from the liver hazardous. PMID:22151444

Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1–RAGE and AKT pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Ping; Dai, Weiqi; Wang, Fan

2014-01-24

Highlights: • Ethyl pyruvate inhibits liver cancer. • Promotes apoptosis. • Decreased the expression of HMGB1, p-Akt. - Abstract: Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)–receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethylmore » pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1–RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.« less

Living Donor Liver Transplantation for Wilson’s Disease Associated with Fulminant Hepatic Failure: A Case Report

PubMed Central

Huang, Yu; Takatsuki, Mitsuhisa; Soyama, Akihiko; Hidaka, Masaaki; Ono, Shinichiro; Adachi, Tomohiko; Hara, Takanobu; Okada, Satomi; Hamada, Takashi; Eguchi, Susumu

2018-01-01

Patient: Female, 17 Final Diagnosis: Fulminant Wilson’s disease Symptoms: General jaundice • malaise • abdominal pain Medication: — Clinical Procedure: ICU Specialty: Transplantology Objective: Rare disease Background: Liver transplantation is indicated for patients with Wilson’s disease (WD) who present either with acute liver failure or with end-stage liver disease and severe hepatic insufficiency as the first sign of disease. However, almost all reported cases have been treated with death donor liver transplantation. Here we report the case of a patient with WD associated with fulminant hepatic failure (WD-FHF) who underwent living donor liver transplantation (LDLT). Case Report: A 17-year-old female was diagnosed with WD-FHF based on high uric copper (10 603 μg/day, normal <100 μg/day), low serum ceruloplasmin (15 mg/dL, normal >20 mg/dL) and Kayser-Fleischer (K-F) corneal ring, and acute liver failure (ALF), acute renal failure (ARF) and grade 2 hepatic encephalopathy (HE). The model for end-stage liver disease (MELD) score was 35. Due to her critical condition, the patient underwent LDLT utilizing a right liver graft from her 44-year-old mother. The right hepatic vein (RHV) and inferior right hepatic vein (iRHV) were reconstructed. She developed severe liver dysfunction due to a crooked hepatic vein caused by compression from the large graft. To straighten the bend, a reoperation was performed. During the operation, we tried to relieve the compressed hepatic vein by adjusting the graft location, but the benefits were limited. We therefore performed stenting in both the RHV and iRHV on postoperative day 9. The patient gradually improved, exhibiting good liver and renal functions, and was finally discharged on postoperative day 114. Conclusions: When WD-FHF deteriorates too rapidly for conservative management, LDLT is an effective therapeutic strategy. PMID:29549236

Portal Vein Embolization with Contralateral Application of Stem Cells Facilitates Increase of Future Liver Remnant Volume in Patients with Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ludvík, Jaroslav, E-mail: ludvikj@fnplzen.cz; Duras, Petr; Třeška, Vladislav

ObjectivesThis study aimed to evaluate the progress of future liver remnant volume (FLRV) in patients with liver metastases after portal vein embolization (PVE) with the application of hematopoietic stem cells (HSCs) and compare it with a patients control group after PVE only.MethodsTwenty patients (group 1) underwent PVE with contralateral HSC application. Subsequently, CT volumetry with the determination of FLRV was performed at weekly intervals, in total three weeks. A sample of twenty patients (group 2) who underwent PVE without HSC application was used as a control group.ResultsThe mean of FLRV increased by 173.2 mL during three weeks after the PVE/HSC procedure,more » whereas by 98.9 mL after PVE only (p = 0.015). Furthermore, the mean daily growth of FLRV by 7.6 mL in group 1 was significantly higher in comparison with 4.1 mL in group 2 (p = 0.007).ConclusionsPVE with the application of HSC significantly facilitates growth of FLRV in comparison with PVE only. This method could be one of the new suitable approaches to increase the resectability of liver tumours.« less

PSC-derived Galectin-1 inducing epithelial-mesenchymal transition of pancreatic ductal adenocarcinoma cells by activating the NF-κB pathway

PubMed Central

Tang, Dong; Zhang, Jingqiu; Yuan, Zhongxu; Zhang, Hongpeng; Chong, Yang; Huang, Yuqin; Wang, Jie; Xiong, Qingquan; Wang, Sen; Wu, Qi; Tian, Ying; Lu, Yongdie; Ge, Xiao; Shen, Wenjing; Wang, Daorong

2017-01-01

Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues. In addition, our in vitro studies showed PSC-derived Galectin-1 promoted the proliferation, invasion, and survival (anti-apoptotic effects) of PANC-1 cells. We also showed PSC-derived Galectin-1 induced EMT of PANC-1 cells and activated the NF-кB pathway in vitro. Our mixed (PSCs and PANC-1 cells) mouse orthotopic xenograft model indicated that overexpression of Galectin-1 in PSCs significantly promoted the proliferation, growth, invasion, and liver metastasis of the transplanted tumor. Moreover, Galectin-1 overexpression in PSCs was strongly associated with increased expression of EMT markers in both the orthotopic xenograft tumor in the pancreas and in metastatic lesions of naked mice. We conclude that PSC-derived Galectin-1 promotes the malignant behavior of PDAC by inducing EMT via activation of the NF-κB pathway. Our results suggest that targeting Galectin-1 in PSCs could represent a promising therapeutic strategy for PDAC progression and metastasis. PMID:29156810

The JAK2/STAT3 inhibitor pacritinib effectively inhibits patient-derived GBM brain tumor initiating cells in vitro and when used in combination with temozolomide increases survival in an orthotopic xenograft model.

PubMed

Jensen, Katharine Victoria; Cseh, Orsolya; Aman, Ahmed; Weiss, Samuel; Luchman, Hema Artee

2017-01-01

The prognosis for patients diagnosed with glioblastoma multiforme (GBM) remains dismal, with current treatment prolonging survival only modestly. As such, there remains a strong need for novel therapeutic strategies. The janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 pathway regulates many cellular processes in GBM, including survival, proliferation, invasion, anti-apoptosis, and immune evasion. Here, we evaluated the preclinical efficacy of pacritinib, a novel compound targeting JAK2, using a collection of diverse patient-derived brain tumor initiating cells (BTICs). The effects of pacritinib on BTIC viability and sphere forming capacity were evaluated in vitro using the alamarBlue and neurosphere assays, respectively. On-target inhibition of JAK2/STAT3 signaling was investigated using western blotting. The efficacy of pacritinib was tested in vivo in pharmacokinetic analyses, liver microsome analyses, and Kaplan-Meier survival studies. In vitro, pacritinib decreased BTIC viability and sphere forming potential at low micromolar doses and demonstrated on-target inhibition of STAT3 signaling. Additionally, pacritinib was found to improve the response to temozolomide (TMZ) in TMZ-resistant BTICs. In vivo, systemic treatment with pacritinib demonstrated blood-brain barrier penetration and led to improved overall median survival in combination with TMZ, in mice orthotopically xenografted with an aggressive recurrent GBM BTIC culture. This preclinical study demonstrates the efficacy of pacritinib and supports the feasibility of testing pacritinib for the treatment of GBM, in combination with the standard of care TMZ.

Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR.

PubMed

Veiga, Sonia Rosa; Ge, Xuemei; Mercer, Carol A; Hernández-Alvarez, María Isabel; Thomas, Hala Elnakat; Hernández-Losa, Javier; Ramón Y Cajal, Santiago; Zorzano, Antonio; Thomas, George; Kozma, Sara C

2018-04-24

Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC. Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and Phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated pre-clinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. We found Phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with Phenformin, was highly efficacious in controlling tumor burden. However, more striking, pretreatment with Phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Treatment of HCC cells in vitro with the biguanide Phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Copyright ©2018, American Association for Cancer Research.

Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1-Stat3.

PubMed

Wu, Chuan Xing; Xu, Aimin; Zhang, Cathy C; Olson, Peter; Chen, Lin; Lee, Terence K; Cheung, Tan To; Lo, Chung Mau; Wang, Xiao Qi

2017-08-01

Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma, indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in hepatocellular carcinoma. Hepatocellular carcinoma spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells. PF-03084014 reduced the hepatocellular carcinoma sphere-derived orthotopic tumor and blocked the hepatocellular carcinoma tumor liver to lung metastasis. We further tested the PF-03084014 in PDX models and confirmed the inhibition tumor growth effect. In addition, a low dose of PF-03084014 induced hepatocellular carcinoma sphere differentiation, resulting in chemosensitization. Antitumor activity was associated with PF-03084014-induced suppression of Notch1 activity, decreased Stat3 activation and phosphorylation of the Akt signaling pathway, and reduced epithelial-mesenchymal transition. These are the key contributors to the maintenance of cancer stemness and the promotion of cancer metastasis. Moreover, the Notch-Stat3 association was implicated in the clinical hepatocellular carcinoma prognosis. Collectively, PF-03084014 revealed antitumor and antimetastatic effects in hepatocellular carcinoma, providing evidence for the potential use of gamma-secretase inhibitors as a therapeutic option for the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1531-43. ©2017 AACR . ©2017 American Association for Cancer Research.

The application of surgical navigation system using optical molecular imaging technology in orthotopic breast cancer and metastasis studies

NASA Astrophysics Data System (ADS)

Chi, Chongwei; Zhang, Qian; Kou, Deqiang; Ye, Jinzuo; Mao, Yamin; Qiu, Jingdan; Wang, Jiandong; Yang, Xin; Du, Yang; Tian, Jie

2014-02-01

Currently, it has been an international focus on intraoperative precise positioning and accurate resection of tumor and metastases. The methods such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role in preoperative accurate diagnosis. However, most of them are inapplicable for intraoperative surgery. We have proposed a surgical navigation system based on optical molecular imaging technology for intraoperative detection of tumors and metastasis. This system collects images from two CCD cameras for real-time fluorescent and color imaging. For image processing, the template matching algorithm is used for multispectral image fusion. For the application of tumor detection, the mouse breast cancer cell line 4T1-luc, which shows highly metastasis, was used for tumor model establishment and a model of matrix metalloproteinase (MMP) expressing breast cancer. The tumor-bearing nude mice were given tail vein injection of MMP 750FAST (PerkinElmer, Inc. USA) probe and imaged with both bioluminescence and fluorescence to assess in vivo binding of the probe to the tumor and metastases sites. Hematoxylin and eosin (H&E) staining was performed to confirm the presence of tumor and metastasis. As a result, one tumor can be observed visually in vivo. However liver metastasis has been detected under surgical navigation system and all were confirmed by histology. This approach helps surgeons to find orthotopic tumors and metastasis during intraoperative resection and visualize tumor borders for precise positioning. Further investigation is needed for future application in clinics.

Clinical impact and efficacy of lamivudine therapy in de novo hepatitis B infection after liver transplantation.

PubMed

Castells, Lluís; Vargas, Víctor; Rodríguez, Francisco; Allende, Helena; Buti, Maria; Sánchez-Avila, José F; Jardí, Rosendo; Margarit, Carlos; Pumarola, Tomás; Esteban, Rafael; Guardia, Jaime

2002-10-01

De novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT) in patients negative for hepatitis B surface antigen (HBsAg) is between 1.7% and 3.5% in areas with a low prevalence of HBV infection. The importance of this problem and the efficacy of lamivudine treatment has not been defined in areas with a high prevalence of positivity to antibody to hepatitis B core antigen (Anti-HBc). To define the characteristics and the clinical impact of de novo HBV infection in OLT recipients and to evaluate the efficacy of lamivudine treatment in this context, 229 HBsAg (-) donors (145 men, 84 women) were retrospectively evaluated between June 1994 and June 2000. Forty-eight recipients were excluded for various reasons. The final study population included 181 patients that were prospectively followed up for more than 6 months after OLT. When de novo HBV infection was detected, liver allograft biopsy was performed and treatment with lamivudine was indicated if patients were HBV-DNA-positive with elevated ALT levels. Survival time was defined as the interval between diagnosis of HBV infection and death or last follow-up visit. Thirty-one of 229 liver donors (13.5%) were anti-HBc(+). After a mean follow-up of 54.4+/-30 months, 9 of the 181 recipients (5%) developed de novo HBV infection; 8 of 27 recipients (29.6%) of livers from anti-HBc(+) donors as compared with only one of 154 recipients (0.6%) of livers from anti-HBc(-) donors P < 0.005). Liver biopsies performed in 8 of 9 cases showed chronic active hepatitis in 7 patients and acute hepatitis in one patient who cleared HBV spontaneously during the first 3 months. Seven patients were treated with lamivudine for a mean period of 24.5 months; HBV-DNA became negative in 5 of 7 (71.4%), and HBeAg became undetectable in 3 of 6 patients (50%). Patient actuarial survival rates at 1, 3, and 5 years were 100%, 94.7%, and 81.2% for recipients of anti-HBc (+) livers and 95.2%, 83%, and 77.3% for recipients of anti-HBc (-) livers P = ns). In our area, the appearance of de novo HBV infection after OLT is related to grafting livers from anti-HBc (+) donors is associated with a benign outcome, with no liver failure or graft loss, and treatment with lamivudine is highly effective in the control of HBV replication.

Anesthetic management during the first combined heart-liver transplant performed in Korea: a case report.

PubMed

Park, Hyejin; Park, Jungchan; Lee, Jonghwan; Kim, Gaabsoo

2017-10-01

Herein, we describe the anesthetic management during the first combined heart-liver transplant (CHLT) performed in Korea. Though CHLT is a rare procedure, accumulating evidence suggests that it is a feasible option for patients with coexisting heart and liver failure. A 45-year-old female patient presented with severe cardiac dysfunction requiring extracorporeal membrane oxygenation (ECMO) support and secondary congestive hepatopathy. The patient underwent consecutive heart and liver transplantation using extracorporeal circulatory devices-heart transplant with cardiopulmonary bypass, and liver transplant with peripheral ECMO. In this case report, we focus on the specific anesthetic considerations for CHLT pertaining to the challenges associated with dual pathophysiology.

Ovarian tissue cryopreservation in girls undergoing haematopoietic stem cell transplant: experience of a single centre.

PubMed

Biasin, E; Salvagno, F; Berger, M; Nesi, F; Quarello, P; Vassallo, E; Evangelista, F; Marchino, G L; Revelli, A; Benedetto, C; Fagioli, F

2015-09-01

Fertility after childhood haemopoietic stem cell transplant (HSCT) is a major concern. Conditioning regimens before HSCT present a high risk (>80%) of ovarian failure. Since 2000, we have proposed cryopreservation of ovarian tissue to female patients undergoing HSCT at our centre, to preserve future fertility. After clinical and haematological evaluation, the patients underwent ovarian tissue collection by laparoscopy. The tissue was analysed by histologic examination to detect any tumour contamination and then frozen following the slow freezing procedure and cryopreserved in liquid nitrogen. From August 2000 to September 2013, 47 patients planned to receive HSCT, underwent ovarian tissue cryopreservation. The median age at diagnosis was 11.1 years and at the time of procedure it was 13 years, respectively. Twenty-four patients were not pubertal at the time of storage, whereas 23 patients had already experienced menarche. The median time between laparoscopy and HSCT was 25 days. Twenty-six out of 28 evaluable patients (93%) developed hypergonadotropic hypogonadism at a median time of 23.3 months after HSCT. One patient required autologous orthotopic transplantation that resulted in one live birth. Results show a very high rate of iatrogenic hypergonadotropic hypogonadism, highlighting the need for fertility preservation in these patients.

Preoperative Transcatheter Selective Arterial Chemoembolization in Treatment of Unresectable Hepatoblastoma in Infants and Children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Jiaping; Chu Jianping, E-mail: truechu@hotmail.com; Yang Jianyong

2008-11-15

The purpose of this study was to evaluate the clinical feasibility and efficacy of transcatheter selective arterial chemoembolization (TACE) for unresectable hepatoblastoma in infants and children. The study was performed with the approval of our institutional review board. Sixteen patients (13 boys, 3 girls) with unresectable hepatoblastoma were treated one to three times with preoperative TACE in an effort to improve the surgical and clinical outcome. Their ages ranged from 50 days to 60 months, with a mean age of 20.4 months. All cases were pathologically proved hepatoblastoma by fine-needle biopsy. After an intra-arterial catheter was selectively inserted into themore » main feeding artery of the tumor, cycles of cisplatin (40 to 50 mg/m{sup 2}) and adriamycin (20 to 30 mg/m{sup 2}) mixed with lipiodol were given, followed by gelatin foam particles or stainless-steel coils. Tumor response was evaluated according to tumor shrinkage, {alpha}-fetoprotein (AFP) levels, and pathological findings. TACE procedure was performed one to three times, depending on the patient's response. Surgical resection was carried out when the tumor volume appeared sufficiently reduced to allow safe resection by either lobectomy or extended lobectomy. A marked reduction in tumor size associated with decreased AFP level occurred after treatment. According to paired-samples test, tumor shrinkage ranged from 19.0% to 82.0%, with a mean value of 59.2%. AFP levels decreased 99.0% to 29.0% from initial levels, with a mean decrease of 60.0%. TACE allowed subsequent complete surgical resection in 13 cases and the other 3 cases underwent partial resection. One patient underwent successful orthotopic liver transplantation after receiving TACE therapy. Pathological examination showed that the mean percentage of necrotic area in the surgical specimens was 87%. Overall survival rate at 1, 3, and 5 years was 87.5%, 68.7%, and 50%, respectively. Correspondingly, event-free survival rate was 75%, 62.5%, and 43.7%, respectively. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. We conclude that TACE is feasible, well tolerated, and effective in inducing surgical resectability of hepatoblastoma in pediatric patients, which has become an independent palliative or curative therapeutic option, especially for patients without distant metastasis.« less

Surgical treatment of childhood hepatoblastoma in the Netherlands (1990-2013).

PubMed

Busweiler, Linde A D; Wijnen, Marc H W A; Wilde, Jim C H; Sieders, Egbert; Terwisscha van Scheltinga, Sheila E J; van Heurn, L W Ernest; Ziros, Joseph; Bakx, Roel; Heij, Hugo A

2017-01-01

Achievement of complete surgical resection plays a key role in the successful treatment of children with hepatoblastoma. The aim of this study is to assess the surgical outcomes after partial liver resections for hepatoblastoma, focusing on postoperative complications, resection margins, 30-day mortality, and long-term survival. Chart reviews were carried out on all patients treated for hepatoblastoma in the Netherlands between 1990 and 2013. A total of 103 patients were included, of whom 94 underwent surgery. Partial hepatectomy was performed in 76 patients and 18 patients received a liver transplant as a primary procedure. In 42 of 73 (58 %) patients, one or more complications were reported. In 3 patients, information regarding complications was not available. Hemorrhage necessitating blood transfusion occurred in 33 (45 %) patients and 9 (12 %) patients developed biliary complications, of whom 8 needed one or more additional surgical interventions. Overall, 5-year disease-specific survival was 82, 92 % in the group of patients who underwent partial hepatectomy, and 77 % in the group of patients who underwent liver transplantation. Partial hepatectomy after chemotherapy in children with hepatoblastoma offers good chances of survival. This type of major surgery is associated with a high rate of surgical complications (58 %), which is not detrimental to survival.

Outcome of ABO-incompatible adult living-donor liver transplantation for patients with hepatocellular carcinoma.

PubMed

Yoon, Young-In; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin; Kim, Ki-Hun; Kim, Seok-Hwan; Kang, Woo-Hyoung; Cho, Hwui-Dong; Jwa, Eun-Kyoung; Kwon, Jae-Hyun; Tak, Eun-Young; Kirchner, Varvara A

2018-06-01

Living-donor liver transplantation (LDLT) can simultaneously cure hepatocellular carcinoma (HCC) and underlying liver cirrhosis, improving long-term results in patients with HCC. ABO-incompatible LDLT could expand the living-donor pool, reduce waiting times for deceased-donor liver transplantation, and improve long-term survival for some patients with HCC. We retrospectively reviewed the medical records of patients undergoing LDLT for HCC from November 2008 to December 2015 at a single institution in Korea. In total, 165 patients underwent ABO-incompatible and 753 patients underwent ABO-compatible LDLT for HCC. ABO-incompatible recipients underwent desensitization to overcome the ABO blood group barrier, including pretransplant plasma exchange and rituximab administration (300-375 mg/m 2 /body surface area). We performed 1:1 propensity score matching and included 165 patients in each group. 82.4% of ABO-incompatible and 83.0% of -compatible LDLT groups had HCC within conventional Milan criteria, respectively, and 92.1% and 92.7% of patients in each group had a Child-Pugh score of A or B. ABO-incompatible and -compatible LDLT groups were followed up for 48.0 and 48.7 months, respectively, with both groups showing comparable recurrence-free survival rates (hazard ratio [HR] 1.14; 95% CI 0.68-1.90; p = 0.630) and overall patient-survival outcomes (HR 1.10; 95% CI 0.60-2.00; p = 0.763). These findings suggested that ABO-incompatible liver transplantation is a feasible option for patients with HCC, especially for those with compensated cirrhosis with HCC within conventional Milan criteria. Despite hypothetical immunological concerns that the desensitization protocol for breaking through the ABO blood group barrier might have a negative impact on the recurrence of hepatocellular carcinoma, our experience demonstrated no significant differences in the long-term overall survival and recurrence-free survival rates between patients receiving ABO-compatible or ABO-incompatible liver transplantation. In conclusion, results from our institution indicated that ABO-incompatible living-donor liver transplantation constitutes a potentially feasible option for patients with hepatocellular carcinoma, especially those with compensated cirrhosis with hepatocellular carcinoma within conventional Milan criteria. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Silencing Intersectin 1 Slows Orthotopic Neuroblastoma Growth in Mice.

PubMed

Harris, Jamie; Herrero-Garcia, Erika; Russo, Angela; Kajdacsy-Balla, Andre; O'Bryan, John P; Chiu, Bill

2017-11-01

Neuroblastoma accounts for 15% of all pediatric cancer deaths. Intersectin 1 (ITSN1), a scaffold protein involved in phosphoinositide 3-kinase (PI3K) signaling, regulates neuroblastoma cells independent of MYCN status. We hypothesize that by silencing ITSN1 in neuroblastoma cells, tumor growth will be decreased in an orthotopic mouse tumor model. SK-N-AS neuroblastoma cells transfected with empty vector (pSR), vectors expressing scrambled shRNA (pSCR), or shRNAs targeting ITSN1 (sh#1 and sh#2) were used to create orthotopic neuroblastoma tumors in mice. Volume was monitored weekly with ultrasound. End-point was tumor volume >1000 mm. Tumor cell lysates were analyzed with anti-ITSN1 antibody by Western blot. Orthotopic tumors were created in all cell lines. Twenty-five days post injection, pSR tumor size was 917.6±247.7 mm, pSCR was 1180±159.9 mm, sh#1 was 526.3±212.8 mm, and sh#2 was 589.2±74.91 mm. sh#1-tumors and sh#2-tumors were smaller than pSCR (P=0.02), no difference between sh#1 and sh#2. Survival was superior in sh#2-tumors (P=0.02), trended towards improved survival in sh#1-tumors (P=0.09), compared with pSCR-tumors, no difference in pSR tumors. Western blot showed decreased ITSN1 expression in sh#1 and sh#2 compared with pSR and pSCR. Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis.

Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

PubMed

Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

2016-09-01

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

PubMed

Kuo, Elbert; Bharat, Ankit; Shih, Jennifer; Street, Tyler; Norris, Jenyi; Liu, Wei; Parks, William; Walter, Michael; Patterson, G Alexander; Mohanakumar, T

2006-10-01

Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

Local recurrence after microwave thermosphere ablation of malignant liver tumors: results of a surgical series.

PubMed

Takahashi, Hideo; Kahramangil, Bora; Berber, Eren

2018-04-01

Microwave thermosphere ablation is a new treatment modality that creates spherical ablation zones using a single antenna. This study aims to analyze local recurrence associated with this new treatment modality in patients with malignant liver tumors. This is a prospective clinical study of patients who underwent microwave thermosphere ablation of malignant liver tumors between September 2014 and March 2017. Clinical, operative, and oncologic parameters were analyzed using Kaplan-Meier survival and Cox proportional hazards model. One hundred patients underwent 301 ablations. Ablations were performed laparoscopically in 87 and open in 13 patients. Pathology included neuroendocrine liver metastasis (n = 115), colorectal liver metastasis (n = 100), hepatocellular cancer (n = 21), and other tumor types (n = 65). Ninety-day morbidity was 7% with one not procedure-related mortality. Median follow-up was 16 months with 65% of patients completing at least 12 months of follow-up. The rate of local tumor recurrence rate per lesion was 6.6% (20/301). Local tumor, new hepatic, and extrahepatic recurrences were detected in 15%, 40%, and 40% of patients, respectively. Local recurrence rate per pathology was 12% for both colorectal liver metastasis (12/100) and other metastatic tumors (8/65). No local recurrence was observed to date in the neuroendocrine liver metastasis and in the limited number of patients with hepatocellular cancers. Tumor size >3 cm and tumor type were independent predictors of local recurrence. This is the first study to analyze local recurrence after microwave thermosphere ablation of malignant liver tumors. Short-term local tumor control rate compares favorably with that reported for radiofrequency and other microwave technologies in the literature. Copyright © 2017 Elsevier Inc. All rights reserved.

The first Polish liver transplantation after Roux-en-Y gastric bypass surgery for morbid obesity: a case report and literature review.

PubMed

Marszałek, Rafał; Ziemiański, Paweł; Łągiewska, Beata; Pacholczyk, Marek; Domienik-Karłowicz, Justyna; Trzebicki, Janusz; Wierzbicki, Zbigniew; Jankowski, Krzysztof; Kosieradzki, Maciej; Wasiak, Dariusz; Jonas, Maurycy; Pruszczyk, Piotr; Durlik, Magdalena; Lisik, Wojciech; Chmura, Andrzej

2015-02-25

Morbid obesity is associated with liver pathology, most commonly non-alcoholic steatohepatitis (NASH) leading to cirrhosis. However, the morbid obesity impedes qualification for organ transplantation. We present a case report of a 56-year-old woman who underwent bariatric procedure followed by liver transplantation (LTx). Her initial weight was 130.2 kg (BMI 50.9 kg/m2). The patient had a history of arterial hypertension, diabetes, gonarthrosis, and obstructive sleep apnea syndrome and no history of alcohol abuse. She underwent Roux-en-Y gastric bypass (RYGB) procedure. The routine intraoperative liver biopsy revealed fibrosis (III°), steatosis (II°), and intra-acinar inflammation. The operation led to a substantial loss of weight. Two years after the surgery the patient was referred to the Transplantation Clinic of Department of General Surgery and Transplantology with suspicion of liver failure due to advanced cirrhosis, which could be a result of previously diagnosed NASH and, probably, excessive alcohol use after bariatric surgery. The patient was qualified for elective LTx, which was performed 3 years after the RYGB. Immediately before LTx, the patient's weight was 65 kg (BMI 25.4 kg/m²). The postoperative period was complicated by bleeding into the peritoneal cavity, which required reoperation. She also had renal failure, requiring renal replacement therapy. One year after LTx, she showed stable liver function with normal transaminases activity and bilirubin concentration, remission of diabetes, and good renal function. Steatohepatitis in morbidly obese patients may lead to cirrhosis. Bariatric procedure can be a bridge to liver transplantation for morbidly obese patients with advanced liver fibrosis.

Evaluation of Acoustic Radiation Force Impulse (ARFI) for Fibrosis Staging in Chronic Liver Diseases.

PubMed

Gani, Rino Alvani; Hasan, Irsan; Sanityoso, Andri; Lesmana, Cosmas Rinaldi A; Kurniawan, Juferdy; Jasirwan, Chyntia Olivia Maurine; Kalista, Kemal Fariz; Lutfie, Lutfie

2017-04-01

acoustic radiation force impulse (ARFI) is a new proposed noninvasive method for liver fibrosis staging. Integrated with B-mode ultrasonography, ARFI can be used to assess liver tissue condition. However its diagnostic accuracy is still being continuously evaluated. Also, there is lack of data regarding the utilization of ARFI in our population. This study aimed to evaluate the diagnostic value of ARFI as an alternative noninvasive modality for fibrosis staging in chronic hepatitis B and hepatitis C patients in our population. we conducted cross-sectional comparison of ARFI imaging and transient elastography on patients who underwent liver biopsy at Cipto Mangunkusumo Hospital. Fibrosis staging using METAVIR scoring system presented as standard reference. A total of 43 patients underwent liver biopsy was evaluated by ARFI imaging and transient elastography. Cut-off values were determined using receiver-operating characteristic (ROC). both liver stiffness determined by ARFI and transient elastography (TE) were moderately correlated with METAVIR score with value of 0.581 and 0.613, respectively (both P<0.01). Diagnostic accuracy of ARFI predicted significant fibrosis (F≥2) with area under receiver operating characteristic curve (AUROC) of 0.773 (95% CI 0.616-0.930) and even better for cirrhosis (F4 fibrosis), expressed as AUROC of 0.856 (95% CI 0.736-0.975). Transient elastography was better for significant fibrosis with AUROC of 0.761 (95% CI 0.601-0.920) and was best for prediction of cirrhosis, expressed as AUROC of 0.845 (95% CI 0.722-0.968). ARFI is provided with more convenient evaluation of liver tissue condition, and its diagnostic accuracy is not significantly different from TE for staging liver fibrosis.

Fractal Dimension of Tc-99m DTPA GSA Estimates Pathologic Liver Injury due to Chemotherapy in Liver Cancer Patients.

PubMed

Hiroshima, Yukihiko; Shuto, Kiyohiko; Yamazaki, Kazuto; Kawaguchi, Daisuke; Yamada, Masatoshi; Kikuchi, Yutaro; Kasahara, Kohei; Murakami, Takashi; Hirano, Atsushi; Mori, Mikito; Kosugi, Chihiro; Matsuo, Kenichi; Ishida, Yasuo; Koda, Keiji; Tanaka, Kuniya

2016-12-01

Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30 %, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P > .001 and P > .001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P = .357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P = .005; OR 36.5; 95 % CI 3.0-446.3) and steatohepatitis (P = .012; OR, 29.1; 95 % CI 2.1-400.1). FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.

Background of the FIB-4 index in Japanese non-alcoholic fatty liver disease.

PubMed

Wada, Takashi; Zeniya, Mikio

2015-01-01

We investigated the distribution and characteristics of the FIB-4 index of liver fibrosis in 1,441 Japanese men (age 50.7±10.2 years) and 304 women (age 53.9±10.3 years) who underwent comprehensive general health checkups and were identified as having non-alcoholic fatty liver disease. With respect to the FIB-4 index, differences according to sex, metabolic indices, and ultrasonic findings were investigated. Among 9,255 individuals who underwent comprehensive general health checkups, 2,750 (29.8%) were found to have mild fatty liver or fatty liver based on ultrasound findings. After excluding patients who consumed ≥150 g alcohol/week (818 individuals), those testing positive for hepatitis B surface antigens or hepatitis C virus antibody (184 individuals), and those for whom data were insufficient (three individuals), we investigated the FIB-4 indices in the remaining 1,745 subjects. There were no sex differences in the FIB-4 index. A total of 1,370 patients (78.5%) exhibited a low cut-off index (COI) (<1.30), 357 (20.5%), exhibited an indeterminate COI (1.30-2.67), and 18 (1.0%) exhibited a high COI (>2.67). There were no associations between the FIB-4 index and the constituent factors of metabolic syndrome. In contrast, there was a significant difference in the ln FIB-4 index between the patients with and without mild fatty liver or fatty liver on ultrasound among men (0.006±0.43 and -0.092±0.39, p<0.001), but not women. The FIB-4 index was is significantly lower in men, but not women, with fatty liver. The FIB-4 index must be calculated separately during medical checkups and evaluated in conjunction with ultrasound findings.

FIB-4 Index is a Predictor of Background Liver Fibrosis and Long-Term Outcomes After Curative Resection of Hepatocellular Carcinoma.

PubMed

Okamura, Yukiyasu; Ashida, Ryo; Yamamoto, Yusuke; Ito, Takaaki; Sugiura, Teiichi; Uesaka, Katsuhiko

2016-08-01

The FIB-4 index is a simple formula for predicting the degree of liver fibrosis. This study aimed to examine the relationship between the preoperative FIB-4 index and liver fibrosis in non-tumor regions of surgical specimens and to investigate whether the FIB-4 index is a useful predictor for long-term outcomes experienced by hepatocellular carcinoma (HCC) patients after curative resection. This study retrospectively analyzed 493 HCC patients treated with curative resection. The utility of the FIB-4 index as a predictor of advanced liver fibrosis (F3 or F4) was assessed. The cutoff value for the FIB-4 index was determined using a receiver operating characteristic curve analysis, and the impact of the FIB-4 index on overall and recurrence-free survival after surgery was evaluated. Advanced liver fibrosis was found in 236 patients (47.9 %). The FIB-4 index was significantly higher for the patients with advanced liver fibrosis than for those without this condition (P < 0.001). An FIB-4 index of 2.87 was the optimal cutoff point for predicting advanced liver fibrosis. The multivariate analysis showed the FIB-4 index to be an independent prognostic factor for recurrence-free and overall survival after curative resection only for patients who underwent hepatectomy as initial treatment (hazard ratio, 1.47 and 1.59; 95 % confidence interval, 1.12-1.93 and 1.09-2.32; P = 0.006 and 0.016, respectively). The study showed the FIB4-index to be a predictor of background liver fibrosis and long-term outcomes for HCC patients who underwent hepatectomy as their initial treatment.

Adverse cardiac events after orthotopic liver transplantation: a cross-sectional study in 389 consecutive patients.

PubMed

Nicolau-Raducu, Ramona; Gitman, Marina; Ganier, Donald; Loss, George E; Cohen, Ari J; Patel, Hamang; Girgrah, Nigel; Sekar, Krish; Nossaman, Bobby

2015-01-01

Current American College of Cardiology/American Heart Association guidelines caution that preoperative noninvasive cardiac tests may have poor predictive value for detecting coronary artery disease in liver transplant candidates. The purpose of our study was to evaluate the role of clinical predictor variables for early and late cardiac morbidity and mortality and the predictive values of noninvasive cardiac tests for perioperative cardiac events in a high-risk liver transplant population. In all, 389 adult recipients were retrospectively analyzed for a median follow-up time of 3.4 years (range = 2.3-4.4 years). Overall survival was 83%. During the first year after transplantation, cardiovascular morbidity and mortality rates were 15.2% and 2.8%. In patients who survived the first year, cardiovascular morbidity and mortality rates were 3.9% and 2%, with cardiovascular etiology as the third leading cause of death. Dobutamine stress echocardiography (DSE) and single-photon emission computed tomography had respective sensitivities of 9% and 57%, specificities of 98% and 75%, positive predictive values of 33% and 28%, and negative predictive values of 89% and 91% for predicting early cardiac events. A rate blood pressure product less than 12,000 with DSE was associated with an increased risk for postoperative atrial fibrillation. Correspondence analysis identified a statistical association between nonalcoholic steatohepatitis/cryptogenic cirrhosis and postoperative myocardial ischemia. Logistic regression identified 3 risk factors for postoperative acute coronary syndrome: age, history of coronary artery disease, and pretransplant requirement for vasopressors. Multivariable analysis showed statistical associations of the Model for End-Stage Liver Disease score and the development of acute kidney injury as risk factors for overall cardiac-related mortality. These findings may help in identifying high-risk patients and may lead to the development of better cardiac tests. © 2014 American Association for the Study of Liver Diseases.

Impact of Different Creatinine Measurement Methods on Liver Transplant Allocation

PubMed Central

Kaiser, Thorsten; Kinny-Köster, Benedict; Bartels, Michael; Parthaune, Tanja; Schmidt, Michael; Thiery, Joachim

2014-01-01

Introduction The model for end-stage liver disease (MELD) score is used in many countries to prioritize organ allocation for the majority of patients who require orthotopic liver transplantation. This score is calculated based on the following laboratory parameters: creatinine, bilirubin and the international normalized ratio (INR). Consequently, high measurement accuracy is essential for equitable and fair organ allocation. For serum creatinine measurements, the Jaffé method and enzymatic detection are well-established routine diagnostic tests. Methods A total of 1,013 samples from 445 patients on the waiting list or in evaluation for liver transplantation were measured using both creatinine methods from November 2012 to September 2013 at the university hospital Leipzig, Germany. The measurements were performed in parallel according to the manufacturer’s instructions after the samples arrived at the institute of laboratory medicine. Patients who had required renal replacement therapy twice in the previous week were excluded from analyses. Results Despite the good correlation between the results of both creatinine quantification methods, relevant differences were observed, which led to different MELD scores. The Jaffé measurement led to greater MELD score in 163/1,013 (16.1%) samples with differences of up to 4 points in one patient, whereas differences of up to 2 points were identified in 15/1,013 (1.5%) samples using the enzymatic assay. Overall, 50/152 (32.9%) patients with MELD scores >20 had higher scores when the Jaffé method was used. Discussion Using the Jaffé method to measure creatinine levels in samples from patients who require liver transplantation may lead to a systematic preference in organ allocation. In this study, the differences were particularly pronounced in samples with MELD scores >20, which has clinical relevance in the context of urgency of transplantation. These data suggest that official recommendations are needed to determine which laboratory diagnostic methods should be used when calculating MELD scores. PMID:24587188

Acute quadriplegic myopathy with myosin-deficient muscle fibres after liver transplantation: defining the clinical picture and delimiting the risk factors.

PubMed

Miró, O; Salmerón, J M; Masanés, F; Alonso, J R; Graus, F; Mas, A; Grau, J M

1999-04-27

In the last few years, rare cases of acute quadriplegic myopathy (AQM*) with myosin-deficient muscle fibres occurring after solid organ transplantation has been reported. The aim of the present study was to review all cases of AQM with myosin deficient fibres seen at our institution among a large series of patients after orthotopic liver transplants (OLT), with special attention to clinical aspects and associated risk factors. Additionally, an extensive review of all ultrastructurally demonstrated cases of AQM in transplant recipients is also included. Among patients involved in 281 consecutive liver transplant procedures performed in a 4-year period, 3 men and 1 woman developed an arreflexic, flaccid quadriplegia in the immediate postoperative period of OLT. After ruling out other causes of weakness, a muscle biopsy was performed and a loss of thick (myosin) filaments was confirmed by ultrastructural analysis in all cases. Accurate clinical, epidemiological, and evolutive data were recorded. Corticosteroids had been used at usual dosage given to liver transplant recipients; all four patients had several intra- and postoperative complications leading to receiving significantly higher amounts of hemoderivates, to develop renal failure in all cases, and to require a significantly higher number of reoperations within a few days after transplantation than our contemporaneous global series of liver transplant recipients. AQM patients required a significantly longer intensive care unit and hospital stay. Muscular recovery was the rule, but currently a mild myopathic gait remains in three patients. These and other reported cases of AQM do not histologically and clinically differ from AQM seen in other critically ill patients who have not had transplants. Patients with a complicated intra- and postoperative course of OLT who develop newly acquired acute muscle weakness should be suspected as having acute AQM with myosin-deficient muscle fibres. In this setting, differential diagnosis with other causes of weakness should be carried out, because the prognosis of this myopathy is good with early muscle rehabilitation therapy.

Impact factors and the optimal parameter of acoustic structure quantification in the assessment of liver fibrosis.

PubMed

Huang, Yang; Liu, Guang-Jian; Liao, Bing; Huang, Guang-Liang; Liang, Jin-Yu; Zhou, Lu-Yao; Wang, Fen; Li, Wei; Xie, Xiao-Yan; Wang, Wei; Lu, Ming-De

2015-09-01

The aims of the present study are to assess the impact factors on acoustic structure quantification (ASQ) ultrasound and find the optimal parameter for the assessment of liver fibrosis. Twenty healthy volunteers underwent ASQ examinations to evaluate impact factors in ASQ image acquisition and analysis. An additional 113 patients with liver diseases underwent standardized ASQ examinations, and the results were compared with histologic staging of liver fibrosis. We found that the right liver displayed lower values of ASQ parameters than the left (p = 0.000-0.021). Receive gain experienced no significant impact except gain 70 (p = 0.193-1.000). With regard to different diameter of involved vessels in regions of interest, the group ≤2.0 mm differed significantly with the group 2.1-5.0 mm (p = 0.000-0.033) and the group >5.0 mm (p = 0.000-0.062). However, the region of interest size (p = 0.438-1.000) and depth (p = 0.072-0.764) had no statistical impact. Good intra- and inter-operator reproducibilities were found in both image acquisitions and offline image analyses. In the liver fibrosis study, the focal disturbance ratio had the highest correlation with histologic fibrosis stage (r = 0.67, p < 0.001). In conclusion, the testing position, receive gain and involved vessels were the main factors in ASQ examinations and focal disturbance ratio was the optimal parameter in the assessment of liver fibrosis. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Acetaminophen (Paracetamol) induced acute liver failure - A social problem in an era of increasing tendency to self-treatment.

PubMed

Wróblewski, Tadeusz; Kobryń, Konrad; Kozieł, Sławomir; Ołdakowska-Jedynak, Urszula; Pinkas, Jarosław; Danielewicz, Roman; Ziarkiewicz-Wróblewska, Bogna; Krawczyk, Marek

2015-01-01

The widespread availability of medication without prescription, so-called over the counter (OTC), and the rapid development of health consciousness of Poles is associated with broad access to medical information in the mass media. This causes patients to recognize their own disease, cancel doctor's appointments, and begin self-treatment. This time and money-saving behavior, often signaled by pain, usually leads to the treatment of symptoms alone, without seeking the cause of the disease.The aim of the study was to present life-threatening paracetamol poisoning, and the treatment of acute liver failure. In 2002-2014, 35 patients were hospitalized due to acute paracetamol poisoning: 17 female and 18 male patients aged between 17-59 (mean 32.3 years). Patients were treated in the surgical intensive care unit, where their parameters of liver and renal function were continuously monitored. If there was no improvement in the liver function, patients underwent albumin dialysis with the Prometheus system and were qualified for liver transplantation (LTx). 26 patients were treated pharmacologically and 7 out of 9 patients who underwent LTx were dialyzed. Overall, 11 patients had 26 albumin dialysis in total; 4 patients died - 1 post-transplant and 3 pre-transplant. Paracetamol is the cause of many poisonings resulting from the lack of public awareness about toxic interactions with alcohol, and suicide attempts. Acetaminophen-induced acute liver failure concerns a small percentage of patients but can be successfully treated with albumin dialysis, and in extreme cases by liver transplantation.

Analysis of computed tomography density of liver before and after amiodarone administration.

PubMed

Matsuda, Masazumi; Otaka, Aoi; Tozawa, Tomoki; Asano, Tomoyuki; Ishiyama, Koichi; Hashimoto, Manabu

2018-05-01

To evaluate CT density of liver changes between before and after amiodarone administration. Twenty-five patients underwent non-enhanced CT including the liver before and after amiodarone administration. We set regions of interest (ROIs) at liver S8, spleen, paraspinal muscle, and calculated average CT density in these ROIs, then compared CT density between liver and other organs. Statistical differences between CT density of liver and various ratios before and after administration were determined, along with correlations between cumulative dose of amiodarone and liver density after administration, density change of liver, and various ratios after administration. Liver density, liver-to-spleen ratio, and liver-to-paraspinal muscle ratio differed significantly between before and after amiodarone administration. No significant correlations were found between cumulative doses of amiodarone and any of liver density after administration, density change of liver, or various ratios after administration. CT density of liver after amiodarone administration was significantly higher than that before administration. No correlations were identified between cumulative dose of amiodarone and either liver density after administration or density change of liver. Amiodarone usage should be checked when radiologists identify high density of the liver on CT.

Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ.

PubMed

Joo, Kyeung Min; Kim, Jinkuk; Jin, Juyoun; Kim, Misuk; Seol, Ho Jun; Muradov, Johongir; Yang, Heekyoung; Choi, Yoon-La; Park, Woong-Yang; Kong, Doo-Sik; Lee, Jung-Il; Ko, Young-Hyeh; Woo, Hyun Goo; Lee, Jeongwu; Kim, Sunghoon; Nam, Do-Hyun

2013-01-31

Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable "patient tumor's phenocopy" that represents molecular and functional heterogeneity of GBMs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Inhibiting platelet-derived growth factor beta reduces Ewing's sarcoma growth and metastasis in a novel orthotopic human xenograft model.

PubMed

Wang, Yong Xin; Mandal, Deendayal; Wang, Suizhau; Hughes, Dennis; Pollock, Raphael E; Lev, Dina; Kleinerman, Eugenie; Hayes-Jordan, Andrea

2009-01-01

Despite aggressive therapy, Ewing's sarcoma (ES) patients have a poor five-year overall survival of only 20-40%. Pulmonary metastasis is the most common form of demise in these patients. The pathogenesis of pulmonary metastasis is poorly understood and few orthotopic models exist that allow study of spontaneous pulmonary metastasis in ES. We have developed a novel orthotopic xenograft model in which spontaneous pulmonary metastases develop. While the underlying biology of ES is incompletely understood, in addition to the EWS-FLI-1 mutation, it is known that platelet-derived growth factor receptor beta (PDGFR-beta) is highly expressed in ES. Hypothesizing that PDGFR-beta expression is indicative of a specific role for this receptor protein in ES progression, the effect of PDGFR-beta inhibition on ES growth and metastasis was assessed in this novel orthotopic ES model. Silencing PDGFR-beta reduced spontaneous growth and metastasis in ES. Preclinical therapeutically relevant findings such as these may ultimately lead to new treatment initiatives in ES.

Resection of synchronous liver metastases between radiotherapy and definitive surgery for locally advanced rectal cancer: short-term surgical outcomes, overall survival and recurrence-free survival.

PubMed

Labori, K J; Guren, M G; Brudvik, K W; Røsok, B I; Waage, A; Nesbakken, A; Larsen, S; Dueland, S; Edwin, B; Bjørnbeth, B A

2017-08-01

There is debate as to the correct treatment algorithm sequence for patients with locally advanced rectal cancer with liver metastases. The aim of the study was to assess safety, resectability and survival after a modified 'liver-first' approach. This was a retrospective study of patients undergoing preoperative radiotherapy for the primary rectal tumour, followed by liver resection and, finally, resection of the primary tumour. Short-term surgical outcome, overall survival and recurrence-free survival are reported. Between 2009 and 2013, 45 patients underwent liver resection after preoperative radiotherapy. Thirty-four patients (76%) received neoadjuvant chemotherapy, 24 (53%) concomitant chemotherapy during radiotherapy and 17 (43%) adjuvant chemotherapy. The median time interval from the last fraction of radiotherapy to liver resection and rectal surgery was 21 (range 7-116) and 60 (range 31-156) days, respectively. Rectal resection was performed in 42 patients but was not performed in one patient with complete response and two with progressive metastatic disease. After rectal surgery three patients did not proceed to a planned second stage liver (n = 2) or lung (n = 1) resection due to progressive disease. Clavien-Dindo ≥Grade III complications developed in 6.7% after liver resection and 19% after rectal resection. The median overall survival and recurrence-free survival in the patients who completed the treatment sequence (n = 40) were 49.7 and 13.0 months, respectively. Twenty of the 30 patients who developed recurrence underwent further treatment with curative intent. The modified liver-first approach is safe and efficient in patients with locally advanced rectal cancer and allows initial control of both the primary tumour and the liver metastases. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Transjugular Intrahepatic Porto-Systemic Shunt in Patients with Liver Cirrhosis and Model for End-Stage Liver Disease ≥15.

PubMed

Ascha, Mona; Hanouneh, Mohamad; S Ascha, Mustafa; Zein, Nizar N; Sands, Mark; Lopez, Rocio; Hanouneh, Ibrahim A

2017-02-01

It is not known whether transjugular intrahepatic porto-systemic shunt (TIPS) is safe in patients with advanced liver cirrhosis. The aim of our study was to evaluate the impact of TIPS on transplant-free survival in patients with liver cirrhosis and MELD score ≥15. All adult patients who underwent TIPS at our institution between 2004 and 2011 were identified (N = 470). A total of 144 patients had MELD ≥15 at the time of TIPS. These patients were matched 1:1 to patients with liver cirrhosis who did not undergo TIPS based on age and MELD score using the greedy algorithm. Patients were followed up until time of death or liver transplantation. Kaplan-Meier curves and log-rank tests were used to test for differences in survival outcome between the two groups. A total of 288 patients with liver cirrhosis were included, of whom 144 underwent TIPS and 144 did not. The two groups were matched based on age and MELD score and were comparable with regard to gender and ethnicity. Mean MELD and Child-Pugh scores in the study population were 20.9 ± 6.5 and 10.5 ± 1.8, respectively. The most common indication for TIPS was varices (49 %), followed by refractory ascites (42 %). In the first 2 months post-TIPS, there was increased mortality or liver transplantation in patients who had TIPS compared to those who did not, but this did not reach statistical significance (p = 0.07). However, after 2 months, TIPS is associated with 56 % lower risk of dying or needing liver transplantation (p < 0.01) than cirrhotic patients who did not undergo TIPS. In patients with liver cirrhosis and MELD ≥15, TIPS might improve transplant-free survival for patients who live for at least 2 months after the procedure.

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

PubMed

Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. © 2016 Authors; published by Portland Press Limited.

Gastrointestinal tract and liver graft-versus-host disease in pediatric patients with hematopoietic progenitor cell transplantation at a tertiary care center in Mexico.

PubMed

Jaramillo-Esparza, C M; Consuelo-Sánchez, A; Acosta-Rodríguez-Bueno, C P; Ramón-García, G; Sadowinski-Pine, S W; Escobar-Sánchez, M A; Castorena-Villa, I; Gaytán-Morales, F; Vázquez-Frias, R

2018-02-24

Graft-versus-host disease (GVHD) is a common multisystemic complication of allogeneic hematopoietic cell transplantation. The most frequent presentations of graft-versus-host disease involve the skin, the gastrointestinal tract, and the liver. The aim of the present study was to know the frequency of gastrointestinal tract and liver GVHD and the characteristics of disease presentation in pediatric patients that underwent hematopoietic stem cell transplantation (HSCT) at a tertiary care hospital center in Mexico City. A retrospective study was carried out, utilizing the case records of patients that underwent HSCT in 2015, to determine the frequency of GVHD in pediatric patients at a Mexican tertiary care hospital center. In 2015, 16 HSCT were performed, 11 of which were carried out in males (68%). Only 3 patients developed graft-versus-host disease (18.7%). One patient presented with skin and liver GVHD and 2 patients presented with gastrointestinal tract and liver GVHD, which was the most frequent type. HSCT is still an uncommon procedure in Mexico and there is a lower frequency of gastrointestinal tract and liver GVHD than that reported in other studies. Most certainly, there will be an increase in this type of patient and risk factors in the Mexican population must still be determined to help predict the onset of GVHD. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

The value of liver magnetic resonance imaging in patients with findings of resectable pancreatic cancer on computed tomography.

PubMed

Chew, Cindy; O'Dwyer, Patrick J

2016-06-01

Accurate staging of patients with pancreatic cancer is important to avoid unnecessary operations. The aim of this study was to prospectively assess the impact of magnetic resonance (MR) imaging on preoperative staging of liver in patients with findings of resectable pancreatic cancer on computed tomography (CT). All patients who presented to a tertiary referral centre with pancreatic cancer between April 2012 and December 2013 were included in the study. Patients with findings of resectable disease on CT underwent further liver diffusion-weighted MR imaging, using a hepatocyte-specific contrast agent. A total of 583 patients with pancreatic cancer were referred. 69 (11.8%) had resectable disease on CT. Of these 69 patients, 16 (23.2%) had liver metastases on MR imaging, while 6 (8.7%) had indeterminate lesions. Of the 16 patients with positive MR imaging findings of liver metastases, 11 died of pancreatic cancer, with a mean survival time of nine months (95% confidence interval [CI] 5.22-14.05). The mean survival time of the 47 patients with negative MR imaging findings was 16 months (95% CI 14.33-18.10; p = 0.001). Subsequently, 22 of these patients underwent surgery, and only 1 (4.5%) patient was found to have liver metastasis at surgery. The results of the present study indicate that MR imaging improves the staging of disease in patients with resectable pancreatic cancer. Copyright: © Singapore Medical Association.

Hepatic encephalopathy before and neurological complications after liver transplantation have no impact on the employment status 1 year after transplantation

PubMed Central

Pflugrad, Henning; Tryc, Anita B; Goldbecker, Annemarie; Strassburg, Christian P; Barg-Hock, Hannelore; Klempnauer, Jürgen; Weissenborn, Karin

2017-01-01

AIM To investigate the impact of hepatic encephalopathy before orthotopic liver transplantation (OLT) and neurological complications after OLT on employment after OLT. METHODS One hundred and fourteen patients with chronic liver disease aged 18-60 years underwent neurological examination to identify neurological complications, neuropsychological tests comprising the PSE-Syndrome-Test yielding the psychometric hepatic encephalopathy score, the critical flicker frequency and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), completed a questionnaire concerning their occupation and filled in the short form 36 (SF-36) to assess health-related quality of life before OLT and 12 mo after OLT, if possible. Sixty-eight (59.6%) patients were recruited before OLT, while on the waiting list for OLT at Hannover Medical School [age: 48.7 ± 10.2 years, 45 (66.2%) male], and 46 (40.4%) patients were included directly after OLT. RESULTS Before OLT 43.0% of the patients were employed. The patients not employed before OLT were more often non-academics (employed: Academic/non-academic 16 (34.0%)/31 vs not employed 10 (17.6%)/52, P = 0.04), had more frequently a history of hepatic encephalopathy (HE) (yes/no; employed 15 (30.6%)/34 vs not employed 32 (49.2%)/33, P = 0.05) and achieved worse results in psychometric tests (RBANS sum score mean ± SD employed 472.1 ± 44.5 vs not employed 443.1 ± 56.7, P = 0.04) than those employed. Ten patients (18.2%), who were not employed before OLT, resumed work afterwards. The patients employed after OLT were younger [age median (range, min-max) employed 47 (42, 18-60) vs not employed 50 (31, 29-60), P = 0.01], achieved better results in the psychometric tests (RBANS sum score mean ± SD employed 490.7 ± 48.2 vs not employed 461.0 ± 54.5, P = 0.02) and had a higher health-related quality of life (SF 36 sum score mean ± SD employed 627.0 ± 138.1 vs not employed 433.7 ± 160.8; P < 0.001) compared to patients not employed after OLT. Employment before OLT (P < 0.001), age (P < 0.01) and SF-36 sum score 12 mo after OLT (P < 0.01) but not HE before OLT or neurological complications after OLT were independent predictors of the employment status after OLT. CONCLUSION HE before and neurological complications after OLT have no impact on the employment status 12 mo after OLT. Instead younger age and employment before OLT predict employment one year after OLT. PMID:28443157

Risk Factors for Bloodstream Infection After Living-donor Liver Transplantation in Children.

PubMed

Shoji, Kensuke; Funaki, Takanori; Kasahara, Mureo; Sakamoto, Seisuke; Fukuda, Akinari; Vaida, Florin; Ito, Kenta; Miyairi, Isao; Saitoh, Akihiko

2015-10-01

Postoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited. We retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI. Among the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P < 0.001) and cytomegalovirus (CMV) antigenemia positivity (P = 0.04) were independently associated with the development of BSI. The risk factors for BSI differed when we analyzed the subjects according to age (≤24 months and >24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia. The volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.

A multi-institutional analysis of 429 patients undergoing major hepatectomy for colorectal cancer liver metastases: The impact of concomitant bile duct resection on survival.

PubMed

Postlewait, Lauren M; Squires, Malcolm H; Kooby, David A; Weber, Sharon M; Scoggins, Charles R; Cardona, Kenneth; Cho, Clifford S; Martin, Robert C G; Winslow, Emily R; Maithel, Shishir K

2015-10-01

Data are lacking on long-term outcomes of patients undergoing major hepatectomy requiring bile duct resection (BDR) for the treatment of colorectal cancer liver metastases. Patients who underwent major hepatectomy (≥3 segments) for metastatic colorectal cancer from 2000-2010 at three US academic institutions were included. The primary outcome was disease-specific survival (DSS). Of 429 patients, nine (2.1%) underwent BDR, which was associated with pre-operative portal vein embolization (25.0% vs. 4.3%; P = 0.049). There were no significant differences in age, ASA class, margin status, number of lesions, tumor size, cirrhosis, perineural invasion, or lymphovascular invasion. BDR was independently associated with increased postoperative major complications (OR: 6.22; 95%CI:1.44-26.97; P = 0.015). There were no differences in length of stay, reoperation, readmission, or 30-day mortality. Patients who underwent BDR had markedly decreased DSS (9.3 vs. 39.9 mo; P = 0.002). When accounting for differences between the two groups, the need for BDR was independently associated with reduced DSS (HR: 3.06; 95%CI:1.12-8.34; P = 0.029). Major hepatectomy with concomitant bile duct resection is seldom performed in patients undergoing resection of colorectal cancer liver metastases and is associated with higher major morbidity and reduced disease-specific survival compared to major hepatectomy alone. Stringent selection criteria should be applied when patients may need bile duct resection during hepatectomy for colorectal cancer liver metastases. © 2015 Wiley Periodicals, Inc.

Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

PubMed

Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

2012-08-01

Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uller, Wibke, E-mail: wibke.uller@klinik.uni-regensburg.de; Knoppke, Birgit; Schreyer, Andreas G.

Purpose: Evaluation of the efficacy and safety of percutaneous treatment of vascular stenoses and occlusions in pediatric liver transplant recipients. Methods: Fifteen children (mean age 8.3 years) underwent interventional procedures for 18 vascular complications after liver transplantation. Patients had stenoses or occlusions of portal veins (n = 8), hepatic veins (n = 3), inferior vena cava (IVC; n = 2) or hepatic arteries (n = 5). Technical and clinical success rates were evaluated. Results: Stent angioplasty was performed in seven cases (portal vein, hepatic artery and IVC), and sole balloon angioplasty was performed in eight cases. One child underwent thrombolysismore » (hepatic artery). Clinical and technical success was achieved in 14 of 18 cases of vascular stenoses or occlusions (mean follow-up 710 days). Conclusion: Pediatric interventional radiology allows effective and safe treatment of vascular stenoses after pediatric liver transplantation (PLT). Individualized treatment with special concepts for each pediatric patient is necessary. The variety, the characteristics, and the individuality of interventional management of all kinds of possible vascular stenoses or occlusions after PLT are shown.« less

Cerebral Scedosporium apiospermum infection presenting with intestinal manifestations.

PubMed

Lin, D; Kamili, Q; Qurat-Ul-Ain, K; Lai, S; Musher, D M; Hamill, R

2013-06-01

We present a case of cerebral Scedosporium apiospermum infection presenting with intestinal manifestations in a 64-year-old male patient on immunosuppression for orthotopic liver transplantation. At admission, the patient's chief complaint was chronic watery diarrhea and he was found to have colonic ulcers on endoscopy. His hospital course was complicated by a tonic-clonic seizure caused by a left frontal brain abscess, with the causative agent being identified by culture. He was treated with lobectomy, high-dose intravenous voriconazole, and liposomal amphotericin with clinical, endoscopic, and histologic improvement. To our knowledge, S. apiospermum has not been previously described as a cause of colitis. The septate branching appearance of the Scedosporium species is similar to the more common Aspergillus species. This case of gastrointestinal Scedosporium brings into question previously reported cases of isolated gastrointestinal aspergillosis diagnosed by histopathology. Clinical suspicion for S. apiospermum must be maintained in immunosuppressed patients presenting with neurologic and gastrointestinal symptoms.

Magnetically-Responsive Nanoparticles for Vectored Delivery of Cancer Therapeutics

NASA Astrophysics Data System (ADS)

Klostergaard, Jim; Bankson, James; Woodward, Wendy; Gibson, Don; Seeney, Charles

2010-12-01

We propose that physical targeting of therapeutics to tumors using magnetically-responsive nanoparticles (MNPs) will enhance intratumoral drug levels compared to free drugs in an effort to overcome tumor resistance. We evaluated the feasibility of magnetic enhancement of tumor extravasation of systemically-administered MNPs in human xenografts implanted in the mammary fatpads of nude mice. Mice with orthotopic tumors were injected systemically with MNPs, with a focused magnetic field juxtaposed over the tumor. Magnetic resonance imaging and scanning electron microscopy both indicated successful tumor localization of MNPs. Next, MNPs were modified with poly-ethylene-glycol (PEG) and their clearance compared by estimating signal attenuation in liver due to iron accumulation. The results suggested that PEG substitution could retard the rate of MNP plasma clearance, which may allow greater magnetically-enhanced tumor localization. We propose that this technology is clinically scalable to many types of both superficial as well as some viscerable tumors with existing magnetic technology.