Po-Da Chen

Combined treatment with Denbinobin and Fas ligand has a synergistic cytotoxic effect in human pancreatic adenocarcinoma BxPC-3 cells.

Background and purpose:  Human pancreatic carcinoma is a highly malignant cancer. Previous studies have shown that the decoy receptor 3 (DcR3) for Fas ligand (FasL) plays significant roles in tumour progression and immune suppression. In the present study, we evaluated the anti‐cancer activity of a natural compound, denbinobin (5‐hydroxy‐3,7‐dimethoxy‐1,4‐phenanthraquinone), through decreasing DcR3 levels in human pancreatic adenocarcinoma cell lines.

Robotic liver donor right hepatectomy: A pure, minimally invasive approach.

Right hepatectomy for a living liver donor via a pure minimally invasive approach is a challenging procedure and only a few cases have been reported. Between May 2013 and August 2015, 13 patients underwent robotic living donor right hepatectomy in our institute, and 54 patients received open surgery. In this series, no conversion was conducted for robotic donor right hepatectomy. The 2 groups shared similar blood loss (169 versus 146 mL), complication rates (7.7% versus 9.3%), and recovery of donor liver function (peak alanine aminotransferase, 269 versus 252 IU/mL). The robotic group needed longer operation time (596 versus 383 minutes) but less postoperative patient‐controlled analgesia (0.58 versus 0.84 ng/kg) and a shorter period before returning to work/school (52.9 versus 100.0 days) and sex (100.0 versus 156.0 days). For recipient outcomes regarding the donor procedure, the robotic group shared similar experiences in early allograft dysfunction, complications, and 1‐year recipient liver function with the open group. With respect to documented benefits of minimally invasive left‐sided liver donor procedure, the development of right donor hepatectomy is slow. In conclusion, with substantial improvements in patient recovery after the minimally invasive approach, the robotic platform would be a big step toward completing pure minimally invasive liver donor surgery. Liver Transplantation 22 1509–1518 2016 AASLD.

Robotic major hepatectomy: Is there a learning curve?

Background. Robotic hepatectomy has been suggested as a safe and effective management of liver disease. However, no large case series have documented the learning curve for robotic major hepatectomy. Method. We conducted a retrospective study for robotic major hepatectomy performed by the same operative team between January 2012 and October 2015 and evaluated the learning curve for operation time using the cumulative sum method, presented as cumulative sumoperation time. Results. Overall, there were 183 robotic hepatectomies, 92 of which were performed in patients who underwent robotic major hepatectomy: left hemihepatectomy was performed in 32 (34.8%) patients, right hemihepatectomy in 41 (44.6%), left trisectionectomy in 3 (3.3%), right trisectionectomy in 6 (6.5%), and 8‐5‐4 trisegmentectomy in 10 (10.8%). The median duration of surgery was 434 minutes (142–805 minutes) and the median blood loss was 195 mL (50–2,000 mL). Fifty‐nine percent of patients had malignancies, and those with advanced stages of cancer had more blood loss during an operation. The cumulative sumoperation time model of robotic major hepatectomy suggested that the learning curve comprised 3 characteristic phases: initial (phase 1, 15 patients), intermediate (phase 2, 25 patients), and mature (phase 3, 52 patients). The learning effects were underlined by shorter operation time and hospital stay after phase 1 and less blood loss after phase 2. Conclusion. This is the largest series regarding robotic major hepatectomy. Our findings suggest that a solid training program based on the learning curve should be considered for beginners of robotic hepatectomy. Participants should evaluate the evolution of our minimally invasive hepatectomy before considering our robotic experience.

Gender differences in renal transplant graft survival

BACKGROUND/PURPOSE A long-term retrospective study was conducted to assess the risk factors of renal transplant graft failure focusing on the effects of gender of both the donor and the recipient. METHODS Medical records of primary renal transplantation performed in a single transplant hospital were reviewed. Cases of ABO incompatibility, positive cross-matches, or multiple organ transplants were excluded. A total of 766 patient records were reviewed, and variables were analyzed with Kaplan-Meier survival curves and Cox regression to determine the independent factors associated with graft survival. RESULTS The overall 5-year graft and patient survival rates were 84.7% and 92.2%, respectively. Univariate analysis showed significantly poorer prognosis in male patients and in those with acute rejection, delayed function, or more mismatches in human lymphocyte antigens. Multivariate analysis with step-wise regression identified three independent prognostic factors for poor graft survival (male gender, acute rejection, and delayed function). The 5-year graft survival rates for female and male patients were 87.9% and 81.3%, respectively. The risk ratio of graft failure for male renal transplant recipients was 1.3732, when compared with that for female patients. The risk ratios for those with acute rejection and delayed function were 1.8330 and 1.5422, respectively. CONCLUSION Male gender, in addition to acute rejection and delayed function, was found to be an independent prognostic factor for poor renal transplant survival in this long-term retrospective study.

Hepatocyte-Like Cells Derived From Mouse Induced Pluripotent Stem Cells Produce Functional Coagulation Factor IX in a Hemophilia B Mouse Model.

Hemophilia B (HB) is an inherited deficiency in coagulation factor IX (FIX) that leads to prolonged bleeding after injury. Although hepatocyte transplantation has been demonstrated to be an effective therapeutic strategy for HB, the quality and sources of hepatocytes still limit their application. Recently, stem cells were proposed as an alternative source of donor cells for cell-based therapy. Much research has been devoted to the properties of stem cells that can be differentiated into functional hepatocytes, thereby providing a new cell source for cell-based therapy. Induced pluripotent stem cells (iPSCs) represent a renewable source of hepatocytes for cell-based therapy; these cells exhibit pluripotency and differentiation ability and can be derived from somatic cells. These iPSCs are highly similar to embryonic stem cells (ESCs). We hypothesized that hepatocyte-like cells derived from iPSCs would have therapeutic efficiency in a mouse model of HB. To test this hypothesis, we differentiated iPSCs toward hepatocytes by stepwise protocol and then transplanted these cells into HB mice. We found that these cells shared many characteristics with hepatocytes, such as albumin synthesis, metabolic capacity, glycogen storage, and ureagenesis. Moreover, iPSC-derived hepatocyte transplantation led to increased coagulation factor IX activity, improved thrombus generation, and better hemostasis parameters, and the transferred cells were localized in the liver in recipient HB mice. In conclusion, our results clearly demonstrate that hepatocyte-like cells derived from iPSCs represent a potential cell source for cell-based therapy in the treatment of HB.

Protection against acetaminophen-induced acute liver failure by omentum adipose tissue derived stem cells through the mediation of Nrf2 and cytochrome P450 expression

BackgroundAcetaminophen (APAP) overdose causes acute liver failure (ALF) in animals and humans via the rapid depletion of intracellular glutathione (GSH) and the generation of excess reactive oxygen species (ROS) that damage hepatocytes. Stem cell therapy is a potential treatment strategy for ALF.MethodsWe isolated mesenchymal stem cells (MSCs) from mice omentum adipose tissue-derived stem cells (ASCs) and transplanted them into a mouse model of APAP-induced ALF to explore their therapeutic potential. In addition, we performed in vitro co-culture studies with omentum-derived ASCs and primary isolated hepatocytes to demonstrate the hepatoprotective effect of omentum-derived ASCs on hepatocytes that were subjected to APAP-induced damage.ResultASC transplantation significantly improved the survival rate of mice with ALF and attenuated the severity of APAP-induced liver damage by suppressing cytochrome P450 activity to reduce the accumulation of toxic nitrotyrosine and the upregulation of NF-E2-related factor 2 (Nrf2) expression, resulting in an increase in the subsequent antioxidant activity. These effects protected the hepatocytes from APAP-induced damage through the suppression of downstream MAPK signal activation and inflammatory cytokine production.Conclusionsour results demonstrate that omentum-derived ASCs are an alternative source of ASCs that regulate the antioxidant response and may represent a beneficial therapeutic strategy for ALF.

Use of robotics in liver donor right hepatectomy

Liver transplantation is the best solution for end stage liver disease, and has been widely accepted and rapidly developed in the past decades. Along with the improved outcomes of liver transplantation, living-related donor transplantation has been conducted to overcome the shortage of the deceased donor. The most important aspects of the living-related liver transplantation are donor safety and fast recovery after graft procurement. Meanwhile, the rapid progress of minimally invasive surgery (MIS) in general surgery has generated heated debate regarding the appropriateness of MIS in living-related donor graft hepatectomy. Technical innovations and instrument enhancements have been allowing recruitment of more potential candidates through smaller wounds and better surgical experience. Although MIS has been documented with safety and feasibility in complex liver surgery, the progress is slow in regard to the application of MIS in donor graft hepatectomy. Pioneer surgeons have devoted themselves to develop the pure MIS approach for the liver donor surgery, but the steep learning curve for pure MIS major hepatectomy remains a major barrier for wide adoption. The introduction of robotic system may lower the barrier for entry for practice into MIS donor hepatectomy.

Successful rescue of transplant ureteral obstruction by Boari flap.

2013, C4d+, and in February 2013, C4d+. Coronary angiogram was performed on August 2012 which revealed normal coronary arteries. Because of the concerns for noncompliance, belatacept was initiated in March 2013 for maintenance therapy in addition to her current immunosuppressive regimen of tacrolimus, sirolimus, mycophenolate mofetil, and prednisone. Belatacept was dosed at 750 mg (10 mg/kg) intravenously on days 0, 7, 14, 28, and for the subsequent 2 months, then 500 mg monthly thereafter. The patient received a total of eight doses of belatacept. Tacrolimus and sirolimus levels still fluctuated while on belatacept and at some points were below the lower limit of detection. Biopsies after starting belatacept remained grade 0, negative for cellular rejection and histologic features of antibody mediated rejection (macrophages, endothelial swelling), but C4d staining was not performed. Coronary angiogram performed on July 2013 revealed normal coronary arteries. Echocardiography report from October 2013 revealed left ventricular ejection fraction of 61%. The patient expired because of cardiac arrest in October 2013. Autopsy was not performed. Figure 1 depicts the timeline of the rejection episodes from transplant to patient death.

Expanding the selection criteria of laparoscopic hepatectomy for hepatocellular carcinoma

The introduction of laparoscopic procedures is one of the milestones of surgical innovation over the past few decades. The advantages of minimally invasive approach have been gradually accepted owing to its less postoperative pain, reduced morbidity and faster recovery. Also, since the introduction of laparoscopic approach of liver surgery in 1955 (1), the benefit of the procedure had long been questioned but expected. The article by Piardi et al., entitled “Laparoscopic resection for hepatocellular carcinoma: comparison between Middle Eastern and Western experience” sought to compare the safety and feasibility of laparoscopic versus open liver resection for hepatocellular carcinoma between Middle Eastern and Western surgeons. To this end, 24 original studies with more than 15 patients were analyzed, while studies from both groups documented similar intraoperative and immediate postoperative outcomes. It is well documented that a positive histologic margin was associated with a higher incidence of postoperative HCC recurrence (2), and the long-term oncological result aroused debates for laparoscopic approach because of the difficult assessment and possible compromise of resection margin. Though some case series supported that the laparoscopic liver resection may be a safe and feasible approach (3,4), the risk of inadequate tumor resection of the procedure for malignancies still makes others hesitate. Among the discussions, good resection margins for laparoscopic hepatectomies were reported in the matched-pair comparative study conducted by Tranchart et al. (5), which suggested that with the appropriate preoperative choice of resection, the rate of the positive margin after laparoscopic resection could be similar or even lower than those after open hepatectomy. Furthermore, Piardi et al. documented that excellent outcomes could be obtained in the setting of underlying cirrhosis in both Middle Eastern and Western, and also confirmed that the laparoscopic liver resection for hepatocelluar carcinoma benefits to less blood loss, less transfusion requirement, and a shorter hospital stay. Besides, the fear of increasing the risk of trocar-site deposits may no longer be the consideration since no recurrence from trocar-sites was documented in the studied articles. Selection criteria for indications of laparoscopic liver resection in hepatocellular cancer may be varied among institutes. The surgical limit continued to expand (6,7), though once said the best candidate for laparoscopy were solitary lesions that were less than 5 cm, located in the anterior segments, and at a distance from transection, the hepatic hilum, and the vena cava (8). In fact, when planning a liver surgery for malignant disease, not only the safe margin but also the volume and functional reserve of the remnant liver are crucial. Apparently, compensated cirrhosis is a surgical contraindication since most hepatocellular carcinomas developed within chronic hepatitis or cirrhosis. Surgeons still face a big challenge dealing with these non-compensated cirrhotic patients. Interestingly, the article pointed out that studies from the Western tended to have uniform selection criteria in tumor size and location as well as the severity of the underlying disease. On the opposite, studies from Middle Eastern were reported with less clear criteria, which implied that Middle Eastern ones tended to use laparoscopic approach more aggressively. The indications for laparoscopic liver resection are expanding because of a wider acceptance of laparoscopic applications and improvement of the instrumentation and technology. In our experience of laparoscopic liver resection in hepatocellular carcinoma, the indications are expanding but require additional training, both in liver surgery and laparoscopic surgery. Furthermore, robotic assisted platforms are drawing focus and are gradually replacing some traditional laparoscopic applications.

Clinical experience of double primary gastric cancer and hepatocellular carcinoma

Background: With improvements in the prognosis of gastric cancer, the clinical importance of treating patients with both gastric cancer and hepatocellular carcinoma (HCC) is increasing because of the high prevalence of HCC in Taiwan. Patients and Methods: We reviewed the medical records of 5468 patients who received a diagnosis of primary gastric cancer at National Taiwan University Hospital between 1980 and 2010. Of these, we identified 18 patients with HCC. Results: Regarding the double cancer cases, six patients received a diagnosis of synchronous cancers, six patients received a diagnosis of HCC during follow-up for gastric cancer, and six patients had undergone HCC treatment before receiving a gastric cancer diagnosis. All the patients who received an HCC diagnosis after gastric cancer underwent curative therapy, except for one patient who had a large hepatic tumor. By contrast, of the patients who received an HCC diagnosis first, only one received an early gastric cancer diagnosis, and the remaining patients received an advanced gastric cancer diagnosis. Despite the presence of double cancers, surgical mortality did not occur in the patients who underwent curative-intended treatment. Conclusion: The study results suggest the necessity of closely following up patients with gastric cancer or HCC for the early diagnosis and treatment of the other malignancy. Aggressive treatments including surgery and radiofrequency ablation are safe and can prolong survival in some patients.