Comparison study for surgical outcomes of right versus left side hemihepatectomy to treat hilar cholangiocellular carcinoma

Purpose: Major liver resection and radical lymph node dissection has been accepted as a definite treatment of choice for hilar cholangiocarcinoma (HC). However, the perioperative and survival outcomes of right hemihepatectomy (RH) and left hemihepatectomy (LH) still remain controversial. Thus, this study aimed to compare the surgical and oncological outcomes of RH and LH in HC patients. Methods: From January 2000 to January 2018, a total of 326 patients underwent surgical resection for HC at Yonsei University College of Medicine in Seoul, Korea. Among the 326 patients, we excluded 130 patients and selected 196 patients, who underwent hemihepatectomy with caudate lobectomy. Among these 196 patients, 114 patients underwent RH, and 82 patients underwent LH. We compared the clinicopathological features as well as the surgical and oncologic outcomes of the RH and LH groups. Results: There were no significant differences in disease-free survival (P = 0.473) or overall survival (P = 0.946) in the RH and LH groups. The LH group had fewer complications compared with the RH group, including postoperative ascites (RH: 15 [13.2%] vs. LH: 3 [3.7%], P = 0.023); however, the LH group had more bile leakage complications (RH: 5 [4.4%] vs. LH: 12 [14.6%], P = 0.012). The average time lag from portal vein embolization to operation was 25.80 ± 12.06 days (n = 45). There was no difference in postoperative liver failure (P = 0.402), although there were significantly more frequent ascites after RH (P = 0.023). Conclusion: LH might be a good alternative option for the surgical treatment of HC given appropriate tumor location and biliary anatomy indications.ope

Current status of robotic surgery for liver transplantation

Successfully performing laparoscopic procedures in donor hepatectomy provides better quality of life and minimizes surgical complications for the donor. However, only a few experienced institutions can perform laparoscopic donor hepatectomy, which has a long learning curve and unergonomic surgical conditions. Meanwhile, robotic surgical systems have advanced to the point that they can compensate for the limitations of laparoscopic surgical systems. A robotic system provides a steady and magnified three-dimensional visualization with a wide range of motion and tremor-free instrumentation. Due to the benefits of robotic systems, robotic donor hepatectomy has been successfully performed in recent years. Therefore, the aim of this review is to present the current circumstances regarding the use of robotic systems in liver transplantation.ope

Single Center Experience of Biliary Reconstruction in Living Donor Liver Transplantation: Duct-to-Duct Anastomosis

Background: Duct-to-duct anastomosis is the most common biliary reconstruction method in living donor liver transplantation. However, biliary complications can frequently occur. The objective of this study was to examine biliary complications and related risk factors of patients with living donor liver transplantation during the last 12 years in our institution. Methods: Surgical outcomes of 252 consecutive patients with duct-to-duct anastomosis for biliary reconstruction in living donor liver transplantation between December 2000 and July 2012 were analyzed retrospectively. Results: Among the 252 patients, there were 65 cases (25.8%) of biliary complications. Before 2010, the incidence of biliary complications was 30.4% (56 of 184 cases). After 2011, the incidence was significantly (P<0.05) decreased to 13.2% (nine out of 68 cases). The complication rate of anastomosis of two separated bile ducts of graft to recipient two separated bile ducts using cystic duct and common bile duct of recipient was 50% (10 out of 20), which was relatively higher compared to that of single to single duct anastomosis (47 out of 191, 24.6%) or multiple duct to single duct anastomosis (eight out of 41, 19.5%). Conclusions: Duct to duct anastomosis between two separated bile ducts of a graft to two separated bile ducts of a recipient, the most common biliary reconstruction method, was associated with higher rate of biliary complications. Complications related to biliary reconstruction of living donor liver transplantation was gradually decreased. Standardization of bile duct anastomosis might lead to sequential reduction of biliary complications in living donor liver transplantations.ope

Unplanned conversion during minimally invasive liver resection for hepatocellular carcinoma: risk factors and surgical outcomes

Purpose: Unplanned conversion is sometimes necessary during minimally invasive liver resection (MILR) of hepatocellular carcinoma (HCC). The aims of this study were to compare surgical outcomes of planned MILR and unplanned conversion and to investigate the risk factors after unplanned conversion. Methods: We retrospectively analyzed 286 patients who underwent MILR with HCC from January 2006 to December 2017. All patients were divided into a MILR group and an unplanned conversion group. The clinicopathologic characteristics and outcomes were compared between the 2 groups. In addition, surgical outcomes in the conversion group were compared with the planned open surgery group (n = 505). Risk factors for unplanned conversion were analyzed. Results: Of the 286 patients who underwent MILR, 18 patients (6.7%) had unplanned conversion during surgery. The unplanned conversion group showed statistically more blood loss, higher transfusion rate and postoperative complication rate, and longer hospital stay compared to the MILR group, whereas no such difference was observed in comparison with the planned open surgery group. There were no significant differences in overall and disease-free survival among 3 groups. The right-sided sectionectomy (right anterior and posterior sectionectomy), central bisectionectomy and tumor size were risk factors of unplanned conversion. Conclusion: Unplanned conversion during MILR for HCC was associated with poor perioperative outcomes, but it did not affect long-term oncologic outcomes in our study. In addition, when planning right-sided sectionectomy or central bisectionectomy for a large tumor (more than 5 cm), we should recommend open surgery or MILR with an informed consent for unplanned open conversions.ope

Inhibition of CXXC5 function reverses obesity-related metabolic diseases

Background: Metabolic diseases, including type 2 diabetes, have long been considered incurable, chronic conditions resulting from a variety of pathological conditions in obese patients. Growing evidence suggests the Wnt/β-catenin pathway is a major pathway in adipose tissue remodelling, pancreatic β-cell regeneration and energy expenditure through regulation of key metabolic target genes in various tissues. CXXC5-type zinc finger protein 5 (CXXC5) is identified negative feedback regulator of the Wnt/β-catenin pathway that functions via Dishevelled (Dvl) binding. Methods: Expression level of CXXC5 was characterised in clinical samples and diabetes-induced mice model. Diabetes-induced mice model was established by using high-fat diet (HFD). HFD-fed mice treated with KY19334, a small molecule inhibiting CXXC5-Dvl protein-protein interaction (PPI), was used to assess the role of CXXC5 in metabolic diseases. Results: Here, we show that CXXC5 is overexpressed with suppression of Wnt/β-catenin signalling in visceral adipose tissues of patients with obesity-related diabetes. Meanwhile, Cxxc5-/- mice fed an HFD exhibited resistance to metabolic dysregulation. KY19334 restores the lowered Wnt/β-catenin signalling and reverses metabolic abnormalities as observed in HFD-fed Cxxc5-/- mice. Administration of KY19334 on HFD-fed mice had a long-lasting glucose-controlling effect through remodelling of adipocytes and regeneration of pancreatic β-cells. Conclusion: Overall, the inhibition of CXXC5 function by small molecule-mediated interference of Dvl binding is a potential therapeutic strategy for the treatment of obesity-related diabetes.ope

Can the presence of KRAS mutations guide the type of liver resection during simultaneous resection of colorectal liver metastasis?

Backgrounds/aims: It is generally accepted that non-anatomical resection (NAR) in colorectal liver metastasis (CRLM) has comparable safety and efficacy compared to anatomical resection (AR); however, there are reports that AR may have better outcomes in KRAS mutated CRLM. This study aimed to determine the effects of KRAS mutations and surgical techniques on survival outcomes in CRLM patients. Methods: Two hundred fifty patients who underwent hepatic resection of CRLM with known KRAS mutational status between 2007 and 2018 were analyzed. A total of 94 KRAS mutated CRLM and 156 KRAS wild-type CRLM were subdivided by surgical approach and compared for short- and long-term outcomes. Results: In both KRAS wild-type and mutated type, there was no difference in estimated blood loss, postoperative complications, and 30-day mortality. There was no difference in disease-free survival (DFS) between AR and NAR in both groups (p = 0.326, p = 0.954, respectively). Finally, there was no difference in intrahepatic DFS between AR and NAR groups in both the KRAS groups (p = 0.165, p = 0.516, respectively). Conclusions: The presence of KRAS mutation may not be a significant factor when deciding the approach in simultaneous resection of CRLM.ope

Effect of sarcopenia on postoperative ICU admission and length of stay after hepatic resection for Klatskin tumor

Background: Hepatic resection of Klatskin tumors usually requires postoperative intensive care unit (ICU) admission because of its high morbidity and mortality. Identifying surgical patients who will benefit most from ICU admission is important because of scarce resources but remains difficult. Sarcopenia is characterised by the loss of skeletal muscle mass and is associated with poor surgical outcomes. Methods: We retrospectively analysed th.e relationship between preoperative sarcopenia and postoperative ICU admission and length of ICU stay (LOS-I) in patients who underwent hepatic resection for Klatskin tumors. Using preoperative computed tomography scans, the cross-sectional area of the psoas muscle at the level of the third lumbar vertebra was measured and normalised to the patient’s height. Using these values, the optimal cut-off for diagnosing sarcopenia was determined using receiver operating characteristic curve analysis for each sex. Results: Of 330 patients, 150 (45.5%) were diagnosed with sarcopenia. Patients with preoperative sarcopenia presented significantly more frequently to the ICU (77.3% vs. 47.9%, p < 0.001) and had longer total LOS-I (2.45 vs 0.89 days, p < 0.001). Moreover, patients with sarcopenia showed a significantly higher postoperative length of hospital stay, severe complication rate, and in-hospital mortality. Conclusions: Sarcopenia correlated with poor postoperative outcomes, especially with the increased requirement of postoperative ICU admission and prolonged LOS-I after hepatic resection in patients with Klatskin tumors.ope

Impact of everolimus on survival after liver transplantation for hepatocellular carcinoma

Background/aims: This study aimed to investigate whether everolimus (EVR) affects long-term survival after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Methods: The data from 303 consecutive patients with HCC who had undergone LT from January 2012 to July 2018 were retrospectively reviewed. The patients were divided into two groups: 1) patients treated with EVR in combination with calcineurin inhibitors (CNIs) (EVR group; n=114) and 2) patients treated with CNI-based therapy without EVR (non-EVR group; n=189). Time to recurrence (TTR) and overall survival (OS) after propensity score (PS) matching were compared between the groups, and prognostic factors for TTR and OS were evaluated. Results: The EVR group exhibited more aggressive tumor biology than the non-EVR group, such as a higher number of tumors (P=0.003), a higher prevalence of microscopic vascular invasion (P=0.017) and exceeding Milan criteria (P=0.029). Compared with the PS-matched non-EVR group, the PS-matched EVR group had significantly better TTR (P<0.001) and OS (P<0.001). In multivariable analysis, EVR was identified as an independent prognostic factor for TTR (hazard ratio [HR], 0.248; P=0.001) and OS (HR, 0.145; P<0.001). Conclusion: Combined with CNIs, EVR has the potential to prolong long-term survival in patients undergoing LT for HCC. These findings warrant further investigation in a well-designed prospective study.ope

The Role of Bile Duct Probe for Bile Duct Division during Donor Right Hemihepatectomy

Background: To prevent bile duct related complications, exact division of donor bile duct is essential, not only for the recipient, but also for the donor during living donor liver transplantation. Cholangiography has been used for bile duct division during living donor right hemihepatectomy. This study was conducted to determine if bile duct probe could be used to replace cholangiography for bile duct division during living donor right hemihepatectomy. Methods: Surgical outcomes of 234 donors with right hemihepatectomy and duct to duct biliary anastomosis in living donor liver transplantation between January 2009 and December 2014 were retrospectively analyzed. A total of 85 donors used the bile duct probe for bile duct division during the right hemihepatectomy, whereas 149 donors used cholangiography. All donors underwent preoperative magnetic resonance cholangiopancreatography (MRCP). Results: The expected number of bile duct orifices based on MRCP did not differ significantly from the observed number of bile duct orifices after bile duct division (10 donors and five donors in each group were mismatched, P=0.238). The operation time was 384.7 minutes in the probe group, which was significantly shorter than that of the cholangiography group (400.4 minutes, P=0.041). Conclusions: Bile duct probing without intraoperative cholangiography might be a feasible procedure for bile duct division during living donor hemihepatectomy.ope

Clinical implication of tumor site in terms of node metastasis for intrahepatic cholangiocarcinoma

Background: The clinical implication of lymph node (LN) dissection of intrahepatic cholangiocarcinoma (ICCA) is still controversial, and LN metastasis (LNM) based on tumor site has not been confirmed yet. Methods: Patients who underwent curative-intent surgery at 10 tertiary referral centers were identified and divided into peripheral (PP) and near second confluence level tumor (NC) groups on the basis of the distance from the second confluence and ontological outcomes were compared. Results: Of 179 patients, 121 patients with LND were divided into the NC (n = 89) and PP groups (n = 32) on the basis of 4.5 cm from the second confluence. NC group showed higher LNM rate than PP group (46.1 vs 21.9%, p = 0.016) and NC was a risk factor for LNM (odds ratio: 4.367; 95% confidence interval: 1.234-15.453, p = 0.022). The 5-year overall survival (OS) rate (38.0% vs. 27.8%, p = 0.777) and recurrence-free survival (RFS) rates (22.8% vs. 25.8%, p = 0.742) showed no differences between the PP and NC groups. In the NC group, N1 patients showed worse 5-year OS (12.7% vs 39.0%, p = 0.004) and RFS (8.8% vs 28.6%, p = 0.004) than the NO patients. In the PP group, discordant results in 5-year OS (48.9% vs. 50.0%, p = 0.462) and RFS (41.3% vs. 0%, p = 0.056) were found between the NO and N1 patients. Conclusion: The NC group was an independent risk factor for LNM and LNM worsened prognosis in NC group for ICCA. In the PP group, LND should not be omitted because of high LNM rate and insufficient oncologic evidence.ope