Background Preservation of the spleen in distal pancreatectomy has recently attracted considerable attention. Our current study aimed in the first instance to define the safety of lap-WT in relation to the capacity of this technique to achieve preservation of the spleen and secondly to investigate the effectiveness of a planned lap-WT procedure or early conversion to lap-WT in selected patients with a large tumor attached to the splenic vessels.MethodsAmong 1056 patients who underwent a laparoscopic distal pancreatectomy between January 2005 and December 2014 at our hospital, 122 (24.6 %) underwent lap-WT which were analyzed. The 122 patients were categorized into two groups chronologically (early group: 2005–2012, late group: 2013–2014).ResultsThe median follow-up was 35 months, and the median operation time was 181 min. The median postoperative hospital stay was 7 days, and the median estimated blood loss was 316 ml. Postoperative complications occurred in 9 patients (7.3 %), including 4 patients (3.2 %) with major pancreatic fistula (ISGPF grade B, C). A reoperation to address postoperative bleeding was needed in one patient. During a median follow-up of 35 months, there were no clinical significant splenic infarctions or gastric varices in any case. All patients were observed conservatively. In patients in the late group who underwent the lap-WT, the mean operating time (171 vs. 205 min, p = 0.001) and mean estimated blood loss (232.1 vs. 370.0 ml, p = 0.017) were significantly less than the early group cases who received lap-WT.ConclusionsA lap-WT is a safe treatment strategy in select cases when used as a way of preserving the spleen. When splenic vessel preservation is technically challenging, for example when the tumor is enlarged or is attached to the splenic vessels, planned lap-WT or early conversion to lap-WT may be a feasible option.
Hepatic artery thrombosis (HAT) can result in biliary tree necrosis and graft loss, necessitating retransplantation. The most effective treatment approach is still controversial. This study was performed to review the outcomes of HAT after living donor liver transplantation (LDLT) and to clarify the feasibility of different strategies. From May 1996 to August 2017, LDLT using the right lobe was performed in 827 adult patients in our center. Our technique of hepatic artery (HA) reconstruction is end-to-end anastomosis under a microscope (10×). Diagnosis of HAT was performed using Doppler sonography and computed tomography (CT) angiography. HAT was initially treated with surgical or endovascular procedure, and retransplantation was considered according to the graft condition. Among the 827 cases of LDLT using the right lobe, HAT occurred in 16 (1.9%) cases within 1 month after transplantation. Within the first week, 7 of these HAT cases (43.8%) occurred (early HAT), while the remaining 9 cases (56.2%) occurred between the first week and 1 month (late HAT). The incidence of graft failure was high in early HAT (42.9%), and the frequency of biliary complications was high in late HAT (77.8%). The success rate of HA recanalization was 62.5% (10/16): 100% (5/5) after reoperation and 45.5% (5/11) after the endovascular procedure. Of the patients in whom treatment failed in late HAT (n = 5), 4 underwent neovascularization during observation. A total of 5 patients underwent graft failure, and 3 of these patients underwent repeat liver transplantation (LT). Mortality occurred in 3 patients, including 1 in the surgical group and 2 in the endovascular group. In conclusion, early diagnosis and aggressive treatment of HAT are necessary to avoid graft failure, and the choice of treatment depends on various factors. Although further studies are required, early HAT requires preparation for graft failure, while late HAT requires treatment for biliary complications.
Liver cancer exhibits the fourth most common cause of cancer-associated mortality worldwide. Due to the rapid growth, solid tumors undergo severe hypoxia and produce high levels of extracellular adenosine to maintain homeostasis. A previous study indicated that the hypoxic condition in liver cancer increased hepatic adenosine, which is known to facilitate cancer survival and proliferation. Extracellular adenosine has been revealed to regulate pathological and physiological processes in cells and tissues. However, its pathophysiological role in liver cancer remains undetermined. Emerging evidence has indicated that the adenosine A2B receptor promotes the progression of liver cancer. Therefore, it was hypothesized that HIF-1α is a transcriptional regulator of A2B in human liver cancer. The current study determined A2B expression of a number of liver cancer cell lines and performed functional studies of HIF-1α as a master transcriptional regulator of hepatic A2B signaling during hypoxic conditions. The current study aimed to identify the promoter region of A2B, which has a hypoxia response element, by performing luciferase assays. The present study demonstrated that reduced HIF-1α expression is associated with low expression of A2B, and HIF-1α overexpression is associated with A2B induction. Furthermore, the siRNA-mediated downregulation of A2B inhibited the growth and proliferation of HepG2, which is a liver cancer cell line. The relationship between HIF-1α and A2B expression was also identified in human liver cancer specimens. In conclusion, the current study indicated that A2B is induced by the HIF-1α transcriptional regulator during hypoxia, and it may be a potential pharmacologic and therapeutic target for the treatment of patients with liver cancer.
BACKGROUNDRecently, the exclusive use of mesenchymal stem cell (MSC)-secreted molecules, called secretome, rather than cells, has been evaluated for overcoming the limitations of cell-based therapy, while maintaining its advantages. However, the use of naïve secretome may not fully satisfy the specificity of each disease. Therefore, it appears to be more advantageous to use the functionally reinforced secretome through a series of processes involving physico-chemical adjustments or genetic manipulation rather than to the use naïve secretome.AIMTo determine the therapeutic potential of the secretome released from miR-122-transfected adipose-derived stromal cells (ASCs).METHODSWe collected secretory materials released from ASCs that had been transfected with antifibrotic miR-122 (MCM) and compared their antifibrotic effects with those of the naïve secretome (CM). MCM and CM were intravenously administered to the mouse model of thioacetamide-induced liver fibrosis, and their therapeutic potentials were compared.RESULTSMCM infusion provided higher therapeutic potential in terms of: (A) Reducing collagen content in the liver; (B) Inhibiting proinflammatory cytokines; and (C) Reducing abnormally elevated liver enzymes than the infusion of the naïve secretome. The proteomic analysis of MCM also indicated that the contents of antifibrotic proteins were significantly elevated compared to those in the naïve secretome.CONCLUSIONWe could, thus, conclude that the secretome released from miR-122-transfected ASCs has higher antifibrotic and anti-inflammatory properties than the naïve secretome. Because miR-122 transfection into ASCs provides a specific way of potentiating the antifibrotic properties of ASC secretome, it could be considered as an enhanced method for reinforcing secretome effectiveness.
PurposeThe aim of this study was to analyze survival outcomes in 1,000 consecutive liver transplantations (LTs) performed at a single institution from 1993 to April 2017.MethodsThe study population was divided into 2 groups based on donor type: deceased donor LT (DDLT; n = 181, 18.1%) and living donor LT (LDLT; n = 819; 81.9%), and into 3 periods based on the number of cases (first 300 cases, middle 300 cases, last 400 cases).ResultsInfection was the most common cause of death, accounting for 34.8% (95 of 273). Mortality due to hepatocellular carcinoma recurrence occurred most frequently between 1 and 5 years after transplantation. Mortality rate by graft rejection was highest between 5 and 10 years after transplantation. And mortality by de novo malignancy occurred most frequently after 10 years after transplantation. The patient survival rates for the entire population at 5 and 10 years were 74.7%, and 68.6%, respectively. There was no difference in survival rate between the LDLT and DDLT groups (P = 0.188). Cause of disease, disease severity, case period, and retransplantation had a significant association with patient survival (P = 0.002, P = 0.031, P = 0.003, and P = 0.024, respectively).ConclusionSurgical techniques and perioperative management for transplant patients have improved and undergone standardization. Controlling perioperative infection and managing patients with HCC as LT candidates will result in better outcomes.
PurposeAlmost all liver diseases are known to be accompanied by increased levels of reactive oxygen species (ROS), regardless of the cause of the liver disorder. However, little is known about the role of hypoxic conditioned media (HCM) in the view of pro-oxidative/antioxidative balance.MethodsNormoxic conditioned media (NCM) and HCM were obtained after culturing adipose-derived stem cells in 20% O2 or 1% O2 for 24 hours, respectively. Their effects on the expression of various markers reflecting pro-oxidative/antioxidative balance were investigated in both in vitro (thioacetamide-treated AML12 cells) and in vivo (partially hepatectomized mice) models of liver injury, respectively.ResultsHCM treatment induced the higher expression of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase than did NCM in the in vitro model of liver injury. We also found that HCM increased the expression of nuclear factor erythroid 2-related factor (NRF2). The in vivo models of liver injury consistently validated the phenomenon of upregulated expression of antioxidant enzymes by HCM.ConclusionWe thus could conclude that HCM provides protection against ROS-related toxicity by increasing the expression of antioxidant enzymes, in part by releasing NRF2 in the injured liver.
Background: The difference in volume change in a pancreatic remnant according to the type of pancreaticoenterostomy after pancreaticoduodenectomy (PD) for long-term follow-up is unknown. Also, there are few studies that evaluate the difference in general nutritional status and pancreatic endocrine function, including new-onset diabetes mellitus (NODM) depending on the type of pancreaticoenterostomy.This study aimed to compare serial pancreatic volume changes in pancreatic remnants between pancreatogastrostomy (PG) and pancreatojejunostomy (PJ) after PD and to evaluate the difference in general nutritional status and incidence of NODM between PG and PJ.Methods: This study enrolled 115 patients who had survived for more than 3 years after PD. They were divided into the PG group and the PJ group. Their clinicopathologic factors were collected and analyzed. We calculated serial pancreas volume and pancreatic duct size precisely from preoperative stage to 5 years after surgery by image-processing software specifically designed for navigation and visualization of multimodality and multidimensional images. Consecutive changes of albumin and body mass index (BMI) as related to general nutritional status were compared between the PG and PJ groups. To evaluate the incidence and risk factors of NODM following PD, subgroup analysis was performed in 88 patients who did not have diabetes preoperatively.Results: Most patient demographics were not significantly different between the PG group (n=45) and PJ group (n=70). There was no significant difference in volume reduction between the groups from postoperative 1 month to 5 years (PG group −18.21±14.66 mL versus PJ group −14.43±13.05 mL, P=0.209).But there was a significant difference in increased pancreatic duct size between the groups from postoperative 1 month to 5 years (PG group 1.66±2.20 mm versus PJ group 0.54±1.54 mm, P=0.007). There was no significant difference in the increase of total serum albumin between the groups for 5 years after surgery (PG group 0.51±0.47 g/dL, 14.3% versus PJ group 0.42±0.60 g/dL, 11.3%, P=0.437). There was also no significant difference in BMI decrease between the groups (PG group −1.13±3.12, −4.9% versus PJ group −1.97±2.01, −8.7%, P=0.206). On the whole, NODM was diagnosed in 19 patients out of the 88 patients (21.6%) who did not have DM preoperatively. The incidence of NODM was not significantly different between the groups (PG group 21.6% versus PJ group 21.5%, P=0.995). In addition, pancreaticoenterostomy was not an independent risk factor for NODM by logistic regression analysis (odds ratio, 0.997, 95% CI: 0.356-0.2.788, P=0.995). No other risk factors for NODM were found.Conclusions: PG and PJ following PD induced similar pancreatic volume reduction during long-term followup. There was no difference in general nutritional status or incidence of NODM between the groups after PD.
Backgrounds/AimsIdentifying pancreatic cancer patients at high risk of early mortality following surgical resection for pancreatic cancer is important to make optimal treatment decisions in multidisciplinary setting. The purpose of this study was to identify the factors related to early mortality in patients who underwent pancreatic resection for pancreatic adenocarcinoma.MethodsWe reviewed our institution's experience with all consecutive patients who underwent pancreatectomy for pancreatic adenocarcinoma from January 2000 to December 2010. One thousand patients were eligible for our study. Fifty-three patients who did not meet the study criteria were excluded. Based on 12 months after surgery, patients were divided into early mortality group or the remaining group. We performed logistic regression analysis to identify predictors of early mortality.ResultsAmong 947 patients who met our study criteria, 302 (31.9%) early mortality (defined as experiencing death within 12 months after surgery) occurred. Multivariate analysis revealed that patient age and surgery time period were statistically significant predictors of early mortality within six months after surgery. Poorly differentiated tumor and adjuvant chemotherapy were statistically significant predictors of early mortality within 12 months after surgery. Total pancreatectomy and lymphovascular invasion were significant (p<0.05) prognostic factors of early mortality within 6 or 12 months after surgery.ConclusionsWe suggest followings to avoid early mortality after pancreatic resection: patients with multiple risk factors related to early mortality after pancreatectomy should be considered for alternative treatment; patient's general condition and surgical technique improvement are important; and adjuvant therapy should be taken into consideration.
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