Renal Artery Repair with Kidney Autotransplantation for Renal Artery Aneurysms.

OBJECTIVE: Kidney autotransplantation (ATx) is a treatment option for distal renal artery aneurysm (RAA). This systematic review evaluated the indications, treatment strategy, and outcome of kidney ATx to verify the value of this procedure in treating RAA. DATA SOURCES: PubMed, Embase, and Web of Science. REVIEW METHODS: All study types were included, except study protocols and animal studies, without time or language restrictions. Data sources were reviewed until April 2021 to identify relevant articles evaluating operating time, cold and warm ischaemia time, total complications, length of hospital stay, and mortality rate in patients with RAA receiving kidney ATx. RESULTS: The literature search retrieved 644 articles. Of these, 55 clinical studies (including 37 case reports and 18 case series) investigating 199 patients were eligible for inclusion. Endovascular treatment had failed in 17% of 70 patients with RAA. Heterotopic kidney ATx was performed in 81% of patients, and 19% received orthotopic kidney ATx. Unplanned nephrectomy was reported in only one patient (0.1%). Post-operative complications were reported in 6.9% of patients, including urinary tract infection (2.0%), wound infection (1.3%), acute renal insufficiency (0.6%), graft thrombosis (0.6%), kidney hypoperfusion (0.6%), haematoma (0.6%), lymphocoele (0.6%), pseudoaneurysm (0.6%), and arterial occlusion (0.6%). None of the patients died peri-operatively, and organ loss was reported in only one patient (0.05%). No further organ loss or death was reported during follow up (median follow up duration 12 months). CONCLUSION: In patients with distal perihilar RAA, surgical repair with kidney ATx appears to be a suitable alternative when endovascular approaches are not appropriate. In these cases, kidney ATx saves the kidney and provides good clinical outcomes. However, these findings should be interpreted with caution, considering the lack of data regarding the adverse events, potential for favourable publication bias among included studies, and the absence of consecutive series and prospective trials.

Portocaval shunt can optimize transhepatic flow following extended hepatectomy: a short-term study in a porcine model.

The aim of this study was to evaluate whether the portocaval shunt (PCS) corrects these unwanted changes in transhepatic flow after extended hepatectomy (EH). Forty female Landrace pigs were divided into two main groups: (A) EH (75%) and (B) no EH. Group A was divided into 3 subgroups: (A1) EH without PCS; (A2) EH with side-to-side PCS; and (A3) EH with end-to-side PCS. Group B was divided into 2 subgroups: (B1) side-to-side PCS and (B2) end-to-side PCS. HAF, PVF, and PVP were measured in each animal before and after the surgical procedure. EH increased the PVF/100 g (173%, p < 0.001) and PVP (68%, p < 0.001) but reduced the HAF/100 g (22%, p = 0.819). Following EH, side-to-side PCS reduced the increased PVF (78%, p < 0.001) and PVP (38%, p = 0.001). Without EH, side-to-side PCS reduced the PVF/100 g (68%, p < 0.001) and PVP (12%, p = 0.237). PVP was reduced by end-to-side PCS following EH by 48% (p < 0.001) and without EH by 21% (p = 0.075). PCS can decrease and correct the elevated PVP and PVF/100 g after EH to close to the normal values prior to resection. The decreased HAF/100 g in the remnant liver following EH is increased and corrected through PCS.

ARFI shear-wave elastography with simulation of acute urinary tract obstruction in an ex vivo porcine kidney model.

METHODS: A total of 20 heparinized pig kidneys were investigated at 10 intrapelvic hydrostatic pressure steps (0-90 mmHg). SWE (ARFI; Virtual TouchTM IQ, Siemens) measurements were taken at three different measuring regions and in two measuring sequences using a linear ultrasonography probe (9L4, Siemens). Median values of 10 shear-wave speed (SWS) measurements were calculated for each pressure step. Logarithmic transformed median SWS values were analyzed in a linear mixed model. RESULTS: SWS increased significantly with increasing intrapelvic pressure. Median SWS for all kidneys in both measuring sequences and all measuring regions was 1.47 m/s (interquartile range [IQR], 0.38 m/s) at 0 mmHg, 1.94 m/s (IQR, 0.42 m/s) at 30 mmHg, 2.07 m/s (IQR, 0.43 m/s) at 60 mmHg, 2.24 m/s (IQR, 0.49 m/s) at 90 mmHg. The correlation between pelvic pressure increase and median SWS values for the central parenchyma was significantly higher compared with the peripheral parenchyma. CONCLUSION: Acutely increased renal pelvic pressure correlates with increasing SWS values in ARFI elastography in an ex vivo porcine kidney model.

A systematic review and quantitative analysis of different therapies for pancreas divisum.

BACKGROUND: Pancreas divisum is the most common anatomical variation of pancreatic ductal system affecting 5-10% of population. Therapy includes different endoscopic and surgical procedures. The aim of this article was to summarize actual evidence of different treatment. METHODS: A Medline search was performed to identify all studies, investigating endoscopic or surgical therapy of Pancreas divisum. An individual data simulation model was applied to compare endoscopic and surgical studies. RESULT: 56 observational studies (31 endoscopic and 25 surgical studies) were included in analyses. Surgery was significantly superior to endoscopic treatment in terms of success rate (72% vs. 62.3), complication rate (23.8% vs. 31.3%) and re-intervention rate (14.4% vs. 28.3%). CONCLUSION: Surgery may be superior to endoscopy in terms of treatment success and complications. There is no study comparing these two therapies. Consequently, a randomized trial is needed to clarify if endoscopy or surgery is superior in the therapy of pancreas divisum.

Indocyanine green fluorescence imaging in hepatobiliary surgery.

Indocyanine green (ICG) is a fluorescent dye that has been widely used for fluorescence imaging during hepatobiliary surgery. ICG is injected intravenously, selectively taken up by the liver, and then secreted into the bile. The catabolism and fluorescence properties of ICG permit a wide range of visualization methods in hepatobiliary surgery. We have characterized the applications of ICG during hepatobiliary surgery into: 1) liver mapping, 2) cholangiography, 3) tumor visualization, and 4) partial liver graft evaluation. In this literature review, we summarize the current understanding of ICG use during hepatobiliary surgery. Intra-operative ICG fluorescence imaging is a safe, simple, and feasible method that improves the visualization of hepatobiliary anatomy and liver tumors. Intravenous administration of ICG is not toxic and avoids the drawbacks of conventional imaging. In addition, it reduces post-operative complications without any known side effects. ICG fluorescence imaging provides a safe and reliable contrast for extra-hepatic cholangiography when detecting intra-hepatic bile leakage following liver resection. In addition, liver tumors can be visualized and well-differentiated hepatocellular carcinoma tumors can be accurately identified. Moreover, vascular reconstruction and outflow can be evaluated following partial liver transplantation. However, since tissue penetration is limited to 5-10mm, deeper tissue cannot be visualized using this method. Many instances of false positive or negative results have been reported, therefore further characterization is required.

Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma.

Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival of CC patients. Global genomic analyses identified a few recurrently mutated genes, some of them in genes involved in epigenetic patterning. In a previous study, we demonstrated global DNA methylation changes in CC, indicating major contribution of epigenetic alterations to cholangiocarcinogenesis. Here, we aimed at the identification and characterization of CC-related, differentially methylated regions (DMRs) in potential microRNA promoters and of genes targeted by identified microRNAs. Twenty-seven hypermethylated and 13 hypomethylated potential promoter regions of microRNAs, known to be associated with cancer-related pathways like Wnt, ErbB, and PI3K-Akt signaling, were identified. Selected DMRs were confirmed in 2 independent patient cohorts. Inverse correlation between promoter methylation and expression suggested miR-129-2 and members of the miR-200 family (miR-200a, miR-200b, and miR-429) as novel tumor suppressors and oncomiRs, respectively, in CC. Tumor suppressor genes deleted in liver cancer 1 (DLC1), F-box/WD-repeat-containing protein 7 (FBXW7), and cadherin-6 (CDH6) were identified as presumed targets in CC. Tissue microarrays of a representative and well-characterized cohort of biliary tract cancers (n=212) displayed stepwise downregulation of CDH6 and association with poor patient outcome. Ectopic expression of CDH6 on the other hand, delayed growth in the CC cell lines EGI-1 and TFK-1, together suggesting a tumor suppressive function of CDH6. Our work represents a valuable repository for the study of epigenetically altered miRNAs in cholangiocarcinogenesis and novel putative, CC-related tumor suppressive miRNAs and oncomiRs.

Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs.

Pancreatic ductal adenocarcinoma (PDAC) clinically has a very poor prognosis. No small molecule is available to reliably achieve cures. Meisoindigo is chemically related to the natural product indirubin and showed substantial efficiency in clinical chemotherapy for CML in China. However, its effect on PDAC is still unknown. Our results showed strong anti-proliferation effect of meisoindigo on gemcitabine-resistant PDACs. Using a recently established primary PDAC cell line, called Jopaca-1 with a larger CSCs population as model, we observed a reduction of CD133+ and ESA+/CD44+/CD24+ populations upon treatment and concomitantly a decreased expression of CSC-associated genes, and reduced cellular mobility and sphere formation. Investigating basic cellular metabolic responses, we detected lower oxygen consumption and glucose uptake, while intracellular ROS levels increased. This was effectively neutralized by the addition of antioxidants, indicating an essential role of the cellular redox balance. Further analysis on energy metabolism related signaling revealed that meisoindigo inhibited LKB1, but activated AMPK. Both of them were involved in cellular apoptosis. Additional in situ hybridization in tissue sections of PDAC patients reproducibly demonstrated co-expression and -localization of LKB1 and CD133 in malignant areas. Finally, we detected that CD133+/CD44+ were more vulnerable to meisoindigo, which could be mimicked by LKB1 siRNAs. Our results provide the first evidence, to our knowledge, that LKB1 sustains the CSC population in PDACs and demonstrate a clear benefit of meisoindigo in treatment of gemcitabine-resistant cells. This novel mechanism may provide a promising new treatment option for PDAC.

Hepatic Hemodynamic Changes Following Stepwise Liver Resection.

AIM: Extended liver resection has increased during the last decades. However, hepatic hemodynamic changes after resection and the consequent complications like post hepatectomy liver failure are still a challenging issue. The aim of this study was to systematically evaluate the role of stepwise liver resection on hepatic hemodynamic changes. METHODS: To evaluate this effect we performed 25, 50, and 75 % sequential liver resections in 10 pigs. Before and after each resection, the hepatic artery flow and portal vein flow in relation to the remnant liver volume (RLV) as well as hepatic vascular pressures were measured and compared between the groups. RESULTS: Following sequential liver resection, the hepatic artery flow /100 g decreases and the portal vein flow increases up to 17 and 167 % following extended liver resection (75 %), respectively. Also, during stepwise liver resection, the portal vein pressure increases gradually up to 33 % following extended hepatectomy (75 %). CONCLUSION: Sequential decrease in the RLV decreases the hepatic artery flow /100 g and increases the portal vein flow /100 g and portal vein pressure. As the consequence, the liver goes under more poor-oxygenated blood supply and higher pressure. This may be one of the most important mechanisms of the post hepatectomy liver failure in case of extended liver resection.

Towards markerless navigation for percutaneous needle insertions.

PURPOSE: Percutaneous needle insertions are increasingly used for diagnosis and treatment of abdominal lesions. The challenging part of computed tomography (CT)-guided punctures is the transfer of the insertion trajectory planned in the CT image to the patient. Conventionally, this often results in several needle repositionings and control CT scans. To address this issue, several navigation systems for percutaneous needle insertions have been presented; however, none of them has thus far become widely accepted in clinical routine. Their benefit for the patient could not exceed the additional higher costs and the increased complexity in terms of bulky tracking systems and specialized markers for registration and tracking. METHODS: We present the first markerless and trackerless navigation concept for real-time patient localization and instrument guidance. It has specifically been designed to be integrated smoothly into the clinical workflow and does not require markers or an external tracking system. The main idea is the utilization of a range imaging device that allows for contactless and radiation-free acquisition of both range and color information used for patient localization and instrument guidance. RESULTS: A first feasibility study in phantom and porcine models yielded a median targeting accuracy of 6.9 and 19.4 mm, respectively. CONCLUSIONS: Although system performance remains to be improved for clinical use, expected advances in camera technology as well as consideration of respiratory motion and automation of the individual steps will make this approach an interesting alternative for guiding percutaneous needle insertions.

Major histocompatibility complex class I expression impacts on patient survival and type and density of immune cells in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTC) are rare malignant tumours with a poor prognosis. Previously, we have presented a detailed characterisation of the inflammatory infiltrate in BTC. Here, we analysed the impact of the expression of major histocompatibility complex class I (MHC I) on patient survival and the quantity, as well as the quality of tumour-infiltrating immune cell types in BTC. METHODS: MHC I expression was assessed semi-quantitatively in 334 BTC, including extrahepatic (n=129) and intrahepatic cholangiocarcinomas (n=146), as well as adenocarcinomas of the gallbladder (n=59). In addition, 71 high-grade biliary intraepithelial lesions (BilIN 3) were included. Results were correlated with data on antitumour inflammation and investigated with respect to their association with clinicopathological variables and patient survival. RESULTS: BTC showed a wide spectrum of different MHC I expression patterns ranging from complete negativity in some tumours to strong homogenous expression in others. In BilIN 3, significantly higher MHC I expression levels were seen compared to invasive tumours (P=0.004). Patients with strong tumoural MHC I expression had a significantly higher overall survival probability (median survival benefit: 8 months; P=0.006). MHC I expression strongly correlated with the number of tumour-infiltrating T-lymphocytes (CD4(+) and CD8(+)) and macrophages. CONCLUSIONS: Differences of MHC I expression predict patient outcome and show correlations with specific components of the inflammatory infiltrate in BTC. These findings contribute to a better understanding of immune response and immune escape phenomena in cholangiocarcinogenesis.

Long-Term Follow-Up of Kidney Transplant Recipients With Polycystic Kidney Disease.

OBJECTIVES: Patients with polycystic kidney disease are candidates for kidney transplant. We report the results of our single center study of 250 first transplant recipients with polycystic kidney disease (autosomal dominant [64%], medullary cystic [16%], autosomal recessive [6%], and nonspecified [14%]). MATERIALS AND METHODS: Patient groups were divided and analyzed according to the origin of the graft (deceased donor or living donor). We also analyzed demographic data of donors and recipients, waiting time, duration of dialysis, transfusion, nephrectomy, hospitalization, morbidities, and graft and patient survival. The study was approved by the Ethical Review Committee of the Institute. All of the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. RESULTS: The deceased-donor group comprised 79% and the living-donor group comprised 21% of the cases. Nephrectomy was performed on 21% of the recipients. The deceased-donor group showed significantly higher values than the living-donor group regarding rate of hemodialysis (82% vs 68%), duration of dialysis (1571 vs 1002 days), waiting time (1129 vs 33 days), and blood transfusions (45% vs 27%). In deceased-donor versus living-donor transplant recipients, surgical complications included arterial stenosis (1% vs 0%), venous thrombosis (1% vs 0%), urine leakage (0.5% vs 1.9%), ureteral stenosis (0.5% vs 0%), reflux (0% vs 1.9%), lymphocele (11.7% vs 8.1%), and hernia (5.2% vs 8.1%), with no statistically significant differences shown between the groups. The living-donor group had graft and patient survival rates as high as the deceased-donor group. CONCLUSIONS: The low rate of morbidity and excellent survival rates make kidney transplant an excellent option for patients with polycystic kidney disease. Although fear of future appearance of polycystic kidney disease may reduce the rate of related living donors, our study showed that graft and patient survival rates in the living-donor group were as high as in the deceased-donor group.

Is microdialysis useful for early detection of acute rejection after kidney transplantation?

INTRODUCTION: Acute rejection following kidney transplantation (KTx) is still one of the challenging complications leading to chronic allograft failure. The aim of this study was to investigate the role of microdialysis (MD) in the early detection of acute graft rejection factor following KTx in porcine model. METHODS: Sixteen pigs were randomized after KTx into case (n = 8, without immunosuppressant) and control groups (n = 8, with immunosuppressant). The rejection diagnosis in our groups was confirmed by histopathological evidences as "acute borderline rejection". Using MD, we monitored the interstitial concentrations of glucose, lactate, pyruvate, glutamate and glycerol in the transplanted grafts after reperfusion. RESULTS: In the early post-reperfusion phase the lactate level in our case group was significantly higher comparing to the control group and remained in higher levels until the end of monitoring. The lactate to pyruvate ratio showed a considerable increase in the case group during the post-reperfusion phase. The other metabolites (glucose, glycerol, glutamate) were nearly at the same levels at the end of our monitoring in both study groups. CONCLUSION: The increase in lactate and lactate to pyruvate ratios seems to be an indicator for early detection of acute rejection after KTx. Therefore, MD as a minimally invasive measurement tool may help to identify the need to immunosuppression adjustment in the early KTx phase before the clinical manifestation of the rejection.

A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: it's time to randomize.

BACKGROUND: Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The aim of the present systematic review was to provide recommendations for clinical practice and research on the basis of surgical morbidity, such as pancreas fistula, delayed gastric empting, safety, and clinical significance of laparoscopic versus open distal pancreatectomy for malignant and nonmalignant diseases of the pancreas. METHODS: A systematic literature search (MEDLINE) was performed to identify all types of studies comparing laparoscopic distal pancreatectomy and open distal pancreatectomy. Random effects meta-analyses were calculated after critical appraisal of the included studies and presented as odds ratios or mean differences each with corresponding 95% confidence intervals. RESULTS: A total of 4,148 citations were retrieved initially; available data of 29 observational studies (3,701 patients overall) were included in the meta-analyses. Five systematic reviews on the same topic were found and critically appraised. Meta-analyses showed superiority of laparoscopic distal pancreatectomy in terms of blood loss, time to first oral intake, and hospital stay. All other parameters of operative morbidity and safety showed no difference. Data on oncologic radicality and effectiveness are limited. CONCLUSION: Laparoscopic distal pancreatectomy seems to be a safe and effective alternative to open distal pancreatectomy. No more nonrandomized trials are needed within this context. A large, randomized trial is warranted and should focus on oncologic effectiveness, defined end points, and cost-effectiveness.

Expanding the indications of pancreas transplantation alone.

OBJECTIVES: Total pancreatectomy (TP) is associated with postoperative endocrine and exocrine insufficiency. Especially, insulin therapy reduces quality of life and may lead to long-term complications. We review the literature with regard to the potential option of pancreas transplantation alone (PTA) after TP in patients with chronic pancreatitis or benign tumors. METHODS: A MEDLINE search (1958-2013) using the terminologies pancreas transplantation, pancreas transplantation alone, total pancreatectomy, morbidity, mortality, insulin therapy, and quality of life was performed. In addition, the current book and congress publications were reviewed. RESULTS: Total pancreatectomy after benign and borderline tumors as well as chronic pancreatitis is continuously increasing. Despite improvement of exogenous insulin therapy, more than 50% of these patients experience severe glucose control problems, which cause up to 50% long-term mortality. Pancreas transplantation alone can cure both endocrine and exocrine insufficiency and reduce the associated risks. The 3-year graft and patient survival rates after PTA are up to 73% and 100%, respectively. CONCLUSIONS: Pancreas transplantation alone after TP in patients with pancreatitis or benign tumors improves the recipient's quality of life and reduces long-term mortality. Considering the amount of available organs and potential candidates, PTA can be a treatment option for patients after TP with chronic pancreatitis or benign tumors.

A systematic review of localization, surgical treatment options, and outcome of insulinoma.

OBJECTIVE: Insulinoma with an incidence of 0.4% is a rare pancreatic tumor. Preserving surgery is the treatment of choice. Exact localization is necessary to plan the appropriate approach. This article gives an overview on localization and surgical strategies for treatment of insulinoma. METHODS: In this systematic review, 114 articles with 6222 cases of insulinoma were reviewed with emphasis on localization techniques and surgical treatment. RESULTS: Insulinoma happens mostly in the fifth decade of life, with a higher incidence in men. They occur mostly sporadic (94%), benign (87%), and single (90%). Insulinomas are mostly smaller than 20 mm (84%). The tumors are distributed almost equally in the pancreas. CONCLUSIONS: Computed tomography is routinely used as first choice preoperatively. Intraoperative inspection, palpation, and sonography were applied with high success rate. Intraoperative sonography is considered as the most reliable technique. Enucleation is the most administered type of surgery (56%). Different types of resection include distal pancreatectomy (32%), Whipple procedure (3%), and subtotal pancreatectomy (<3%). Despite the development of laparoscopy, open approach is the favorite method (90%). The most common surgical complication is fistula. The mortality rate of open approach was higher (4 vs 0%). Despite high cure rate, recurrence of insulinoma occurs in 7% after surgery.

Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway.

UNLABELLED: The molecular mechanisms underlying the genesis of cholangiocarcinomas (CCs) are poorly understood. Epigenetic changes such as aberrant hypermethylation and subsequent atypical gene expression are characteristic features of most human cancers. In CC, data regarding global methylation changes are lacking so far. We performed a genome-wide analysis for aberrant promoter methylation in human CCs. We profiled 10 intrahepatic and 8 extrahepatic CCs in comparison to non-neoplastic biliary tissue specimens, using methyl-CpG immunoprecipitation (MCIp) combined with whole-genome CpG island arrays. DNA methylation was confirmed by quantitative mass spectrometric analysis and functional relevance of promoter hypermethylation was shown in demethylation experiments of two CC cell lines using 5-aza-2'deoxycytidine (DAC) treatment. Immunohistochemical staining of tissue microarrays (TMAs) from 223 biliary tract cancers (BTCs) was used to analyze candidate gene expression at the protein level. Differentially methylated, promoter-associated regions were nonrandomly distributed and enriched for genes involved in cancer-related pathways including Wnt, transforming growth factor beta (TGF-ß), and PI3K signaling pathways. In CC cell lines, silencing of genes involved in Wnt signaling, such as SOX17, WNT3A, DKK2, SFRP1, SFRP2, and SFRP4 was reversed after DAC administration. Candidate protein SFRP2 was substantially down-regulated in neoplastic tissues of all BTC subtypes as compared to normal tissues. A significant inverse correlation of SFRP2 protein expression and pT status was found in BTC patients. CONCLUSION: We provide a comprehensive analysis to define the genome-wide methylation landscape of human CC. Several candidate genes of cancer-relevant signaling pathways were identified, and closer analysis of selected Wnt pathway genes confirmed the relevance of this pathway in CC. The presented global methylation data are the basis for future studies on epigenetic changes in cholangiocarcinogenesis.

BRAF V600E-specific immunohistochemistry reveals low mutation rates in biliary tract cancer and restriction to intrahepatic cholangiocarcinoma.

BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. Other types of cancer may also benefit from BRAF mutation-targeted therapies. In biliary tract cancer, reported BRAF mutation rates are highly controversial, ranging from 0 to 33% in adenocarcinoma of the gallbladder and 0 to 22% in cholangiocarcinoma. We here analyzed tissue microarrays of a large cohort of biliary tract cancer (n=377) including 159 intrahepatic cholangiocarcinomas, 149 extrahepatic cholangiocarcinomas, and 69 adenocarcinomas of the gallbladder for BRAF V600E mutation using a highly sensitive immunohistochemical screening approach implementing the BRAF V600E protein-specific antibody VE1. All VE1-positive cases as well as 42 VE1-negative cases were additionally analyzed by Sanger sequencing. In total, only 5 VE1-positive cases were detected (5/377; 1%). BRAF V600E mutation was confirmed by direct sequencing in all cases. All 5 mutated cases were intrahepatic cholangiocarcinomas (5/159; 3%). None of the extrahepatic cholangiocarcinomas and adenocarcinomas of the gallbladder were VE1 positive. Apart from the subtype restriction of BRAF V600E mutation to intrahepatic cholangiocarcinoma and a female predominance (4 female, 1 male), no significant correlation with clinicopathological data and patient outcome was detected. In conclusion, we demonstrate that BRAF V600E mutation is a rare event in biliary tract cancer, accounting for only 1% of all subtypes, and is restricted to intrahepatic cholangiocarcinoma. In addition, we demonstrate that VE1 immunohistochemistry is a feasible approach to routinely screen for BRAF V600E mutation in biliary tract cancer patients, thereby facilitating the detection of rare patients who may benefit from BRAF mutation-targeted therapies.

Do we need animal hands-on courses for transplantation surgery?

BACKGROUND: Transplantation surgery requires many years of training. This study evaluates and presents the results of our recent four-yr animal hands-on courses of transplantation surgery on participants' training. METHODS: Since 2008, five two-d hands-on courses of transplantation surgery were performed on swine models at our department. Sixty-one participants were asked to answer three questionnaires (pre-course, immediate post-course, subsequent post-course). The questions pertained to their past education, expectations, and evaluation of our courses, as well as our course's effectiveness in advancing their surgical abilities. The results were analyzed, compared and are presented herein. RESULTS: On average, 1.8 multiorgan procurements, 2.3 kidney, 1.5 liver, and 0.7 pancreas transplantations were performed by each participant. 41.7% of participants considered their previous practical training only satisfactory; 85% hoped for more opportunities to practice surgery; 73.3% evaluated our courses as very good; and 95.8% believed that our courses had fulfilled their expectations. 66% found the effectiveness of our course in advancing their surgical abilities very good; 30% good, and 4% satisfactory. CONCLUSION: Animal hands-on courses of transplantation surgery are one of the best options to learn and practice different operations and techniques in a near to clinical simulated model. Regular participation in such courses with a focus on practical issues can provide optimal opportunities for trainees with the advantage of direct mentoring and feedback.

Evaluating the effects of extended cold ischemia on interstitial metabolite in grafts in kidney transplantation using microdialysis.

PURPOSE: During kidney transplantation (KTx), the length of cold ischemia time (CIT) and the subsequent changes in energy metabolism may lead to variations in interstitial metabolites. Using microdialysis (MD), we evaluated the effects of a short and long CIT on changes of these metabolites. METHODS: Sixteen pigs were randomized in two identical groups, one with a short CIT and the other one with a long CIT. Using MD in the transplanted grafts, we evaluated the parenchyma concentrations of glucose, lactate, pyruvate, glutamate and glycerol in different stages. RESULTS: We noted that during the warm ischemia time (WIT) and in the early post-reperfusion phase glucose levels increased more significantly in the long CIT group and remained high until the end of monitoring. At the end of CIT and during WIT, the long CIT group had a significantly higher glycerol level, but the level dropped gradually in the late post-reperfusion phase and reached a steady state in both groups. CONCLUSIONS: The extended CIT clearly results in considerably impaired graft metabolism. The high interstitial glucose levels within hours after KTx could be considered as a marker of primary delayed function of the graft. Furthermore, the glycerol value could reflect the extent of graft injury during the ischemia time or in case of acute impairment of graft perfusion.

Technical guidelines for porcine liver allo-transplantation: a review of literature.

Experimental animal research has been pivotal in the development of clinical liver transplantation (LTx). Results obtained in these experiments have been applied in clinic and clinical challenges have been scrutinized in animal laboratories. Porcine model is an optimal model in the field of experimental LTx research. Here, we present the various techniques of experimental LTx in the porcine model in detail. Different methods and modifications have been described. The following major steps have been discussed in detail: donor liver preparation, recipient operation including recipient hepatectomy, and reconstruction phase, including the reconstruction of suprahepatic inferior vena cava (SHIVC), portal vein (PV), infrahepatic inferior vena cava (IHIVC), hepatic artery (HA) and bile duct (BD). IHIVC and SHIVC are anastomosed end to end directly or with the use of prosthesis anastomosed side to side. The PV anastomosis is performed end to end between donor and recipient PV, Cuff method or Stump method. Arterialization has been accomplished via carrel patch or donor HA end to end with recipient HA. There are three major methods for reconstruction of BD: end to end or end to side choledochocholedochostomy or choledojejunostomy with Roux-en-Y jejunal loop. Each method has advantages and disadvantages regarding the objectives of the study; the most physiological techniques may be preferred for long-term survival studies, while the faster techniques may be selected for experimentations aiming the direct postoperative phase.