Therapeutic Implications of Ceritinib in Cholangiocarcinoma beyond ALK Expression and Mutation.

Cholangiocarcinoma (CCA) is a difficult-to-treat cancer, with limited therapeutic options and surgery being the only curative treatment. Standard chemotherapy involves gemcitabine-based therapies combined with cisplatin, oxaliplatin, capecitabine, or 5-FU with a dismal prognosis for most patients. Receptor tyrosine kinases (RTKs) are aberrantly expressed in CCAs encompassing potential therapeutic opportunity. Hence, 112 RTK inhibitors were screened in KKU-M213 cells, and ceritinib, an approved targeted therapy for ALK-fusion gene driven cancers, was the most potent candidate. Ceritinib's cytotoxicity in CCA was assessed using MTT and clonogenic assays, along with immunofluorescence, western blot, and qRT-PCR techniques to analyze gene expression and signaling changes. Furthermore, the drug interaction relationship between ceritinib and cisplatin was determined using a ZIP synergy score. Additionally, spheroid and xenograft models were employed to investigate the efficacy of ceritinib in vivo. Our study revealed that ceritinib effectively killed CCA cells at clinically relevant plasma concentrations, irrespective of ALK expression or mutation status. Ceritinib modulated multiple signaling pathways leading to the inhibition of the PI3K/Akt/mTOR pathway and activated both apoptosis and autophagy. Additionally, ceritinib and cisplatin synergistically reduced CCA cell viability. Our data show ceritinib as an effective treatment of CCA, which could be potentially explored in the other cancer types without ALK mutations.

Comparative outcomes of extended distal pancreatectomy and distal pancreatectomy.

PURPOSE: Patients with locally advanced pancreatic body/tail tumors, gastric cancer, or colon cancer often have contiguous organ involvement requiring extensive pancreatic resection. This study was performed to compare surgical complications and the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between distal pancreatectomy (DP) with extended organ resection and standard DP. METHODS: In total, 128 patients who underwent DP from January 2012 to January 2021 were retrospectively reviewed. Extended DP was defined according to the International Study Group of Pancreatic Surgery definition. RESULTS: Of the 128 patients, 62 (48.4%) underwent extended DP and 66 (51.6%) underwent DP. Blood loss was greater (p < 0.001), the incidence of major complications was higher (p = 0.032), and the hospital stay was longer (p = 0.002) in the extended DP group than in the DP group. There were no differences in the incidence of CR-POPF, the readmission rate, or the need for postoperative intervention drainage. Univariate and multivariate analyses showed that extended DP was not a risk factor for CR-POPF or major complications. CONCLUSION: Extended DP can be performed with comparable CR-POPF occurrence and mortality but increased morbidity when compared with standard DP.

Timing of laparoscopic cholecystectomy after endoscopic retrograde cholangiopancreatography in cholelithiasis patients: A systematic review and meta-analysis.

There are many variations and unclear definitions of the appropriate timing of laparoscopic cholecystectomy (LC) after endoscopic retrograde cholangiopancreatography (ERCP), and there is still a lack of consistency about the appropriate timing. Inappropriate timing can be associated with serious comorbidity and can affect the patients. This meta-analysis was conducted to assess the operative outcomes and morbidity to provide a benefit to the patients based on the best timing of LC after ERCP. Randomized controlled trials (RCTs) and retrospective studies were identified from the PubMed and Scopus databases from inception to July 2021. A meta-analysis was performed to estimate the treatment effects on operative outcomes and morbidity. Four RCTs and four retrospective studies met our inclusion criteria. A meta-analysis indicated that patients who received LC after ERCP on the same day or within 72 hours had about 0.354 days shorter length of hospital stay with a shorter operative time of about 0.111-1.835 minutes and a lower risk of complications around 37%-73%. Our evidence suggests that the appropriate timing of LC after ERCP is either the same day or within 72 hours for treating cholelithiasis patients based on the severity of disease.

CP-673451, a Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces Apoptosis in Opisthorchis viverrini-Associated Cholangiocarcinoma via Nrf2 Suppression and Enhanced ROS.

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) play essential roles in promoting cholangiocarcinoma (CCA) cell survival by mediating paracrine crosstalk between tumor and cancer-associated fibroblasts (CAFs), indicating the potential of PDGFR as a target for CCA treatment. Clinical trials evaluating PDGFR inhibitors for CCA treatment have shown limited efficacy. Furthermore, little is known about the role of PDGF/PDGFR expression and the mechanism underlying PDGFR inhibitors in CCA related to Opisthorchis viverrini (OV). Therefore, we examined the effect of PDGFR inhibitors in OV-related CCA cells and investigated the molecular mechanism involved. We found that the PDGF and PDGFR mRNAs were overexpressed in CCA tissues compared to resection margins. Notably, PDGFR-α showed high expression in CCA cells, while PDGFR-ß was predominantly expressed in CAFs. The selective inhibitor CP-673451 induced CCA cell death by suppressing the PI3K/Akt/Nrf2 pathway, leading to a decreased expression of Nrf2-targeted antioxidant genes. Consequently, this led to an increase in ROS levels and the promotion of CCA apoptosis. CP-673451 is a promising PDGFR-targeted drug for CCA and supports the further clinical investigation of CP-673451 for CCA treatment, particularly in the context of OV-related cases.

Early postoperative serum aspartate aminotransferase for prediction of post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication of hepatectomy. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data on or after postoperative day (POD) 5, which may delay treatment for patients at risk. The present study aimed to determine the associations between early postoperative (POD1) serum aminotransferase levels and PHLF. METHODS: The medical records of patients who underwent hepatectomy at Ramathibodi Hospital from January 2008 to December 2019 were retrospectively examined. Patients were classified into PHLF and non-PHLF groups. Preoperative characteristics, intraoperative findings, and early postoperative laboratory data (serum AST, ALT, bilirubin, and international normalized ratio (INR) on POD0 to POD5) were analyzed. RESULTS: A total of 890 patients were included, of whom 31 (3.4%) had PHLF. Cut-off points for AST of 260 U/L and ALT of 270 U/L on POD1 were predictive of PHLF. In multivariate analysis, AST > 260 U/L on POD1, ICG-R15, major hepatectomy, blood loss, and INR were independently associated with PHLF. CONCLUSIONS: Early warning from elevated serum AST on POD1, before a definitive diagnosis of PHLF is made on POD5, can help alert physicians that a patient is at risk, meaning that active management and vigilant monitoring can be initiated as soon as possible.

Effect of local anaesthetic infiltration on postoperative pain after laparoscopic cholecystectomy: randomized clinical trial.

BACKGROUND: Local anaesthetic infiltration is widely used to reduce pain after laparoscopic cholecystectomy (LC). This trial evaluated the effect of depth of local anaesthetic infiltration on postoperative pain reduction after LC. METHODS: Patients undergoing elective LC between March 2018 and February 2019 were randomized into no infiltration, subcutaneous infiltration, and rectus sheath infiltration using bupivacaine. The primary outcome was 24-h postoperative cumulative morphine use, and the secondary outcomes were mean 24-h Numerical Rating Scale (NRS) for pain, and nausea, and vomiting. Subgroups were compared and multivariable analyses were performed. RESULTS: Out of 170 eligible patients, 162 were selected and 150 patients were analysed: 48 in the no-infiltration group, 50 in the subcutaneous infiltration group, and 52 in the rectus sheath infiltration group. The groups had similar clinical features, although mean BMI was higher in the subcutaneous infiltration group (P = 0.001). The 24-h cumulative morphine use in the rectus sheath infiltration group was significantly lower than in the no-infiltration group (P = 0.043), but no difference was observed between the subcutaneous infiltration and no-infiltration groups (P = 0.999). One hour after surgery, the rectus sheath infiltration group had a significantly lower NRS score than the no-infiltration and subcutaneous infiltration groups respectively (P = 0.006 and P = 0.031); however, the score did not differ among the three groups at any of the time points from 2 h after the surgery. The incidence of nausea or vomiting was comparable among the three groups. Multivariable analysis documented that a lower dose of morphine use was associated with rectus sheath infiltration (P = 0.004) and diabetes (P = 0.001); whereas, increased morphine use was associate with age (P = 0.040) and a longer duration of surgery (P = 0.007). CONCLUSIONS: Local anaesthetic infiltration into the rectus sheath reduced postoperative cumulative morphine use and the immediate NRS score in patients undergoing LC; however, the pain scores were comparable 2 h after surgery. REGISTRATION NUMBER: TCTR20201103002 (http://www.thaiclinicaltrials.org).

Association of the rate of bilirubin decrease with major morbidity in patients undergoing preoperative biliary drainage before pancreaticoduodenectomy.

OBJECTIVE: The objective of this study was to examine the relationship between the rate of bilirubin decrease following preoperative biliary drainage before pancreaticoduodenectomy and postoperative morbidity. METHODS: Records of patients who underwent pancreaticoduodenectomy at the Department of Surgery in Ramathibodi Hospital between January 2008 and December 2019 were retrospectively reviewed. The patients were classified into either an adequate or inadequate drainage rate groups according to the bilirubin decrease rate. Major morbidity was defined as higher than grade II in the Clavien-Dindo classification. Risk factors for major morbidity were analyzed by logistic regression analysis. RESULTS: In total, 166 patients were included in the study. Major morbidity was observed in 36 patients (21.6%). Adequate biliary drainage rate was observed in 39 patients (23.4%). Patients who had major morbidity were less likely to have come from the adequate biliary drainage rate group than the inadequate group (38.9% vs. 61.1%). However, through multivariate logistic analysis, only body mass index, operative time, and pancreatic duct diameter were independent factors associated with major morbidity, whereas the bilirubin decrease rate was not. CONCLUSIONS: Bilirubin decrease rate following preoperative biliary drainage has no significant association with major postoperative morbidity after pancreaticoduodenectomy.

Prospective randomized controlled trial of omental roll-up technique on pancreatojejunostomy anastomosis for reducing perioperative complication in patients undergoing pancreatoduodenectomy.

BACKGROUND: Wrapping pancreatojejunal anastomosis with omentum to prevent postoperative pancreatic fistula (POPF) has only been reported in non-randomized, controlled trials. Therefore, this study aimed to conduct a randomized, controlled trial to compare outcomes between omental roll-up and non-omental roll-up in pancreatojejunal anastomosis. METHODS: This single-center, randomized, two-arm trail (Clinical Trials Register: NCT03083938) was conducted between February 2017 and February 2019. We studied 34 patients in the omental roll-up group and 34 patients in the non-omental roll-up group. The primary endpoint was the incidence of clinically relevant POPF. Thirty-day mortality and morbidity were recorded. RESULTS: Patients' demographic data were not significantly different between the two groups, except for histological diagnosis, with a significantly higher incidence of pancreatic cancer in the omental roll-up group (n = 15, 44.1%) than in the non-omental roll-up group (n = 9, 26.4%) (P = 0.042). There was one death in the non-omental roll-up group due to myocardial infarction. The incidence of POPF was not different between the omental roll-up group (n = 5, 14.7%) and non-omental roll-up group (n = 7, 20.6%) (P = 0.525). No differences were found in postoperative hemorrhage after pancreatectomy, delayed gastric emptying, and chyle leakage between the groups. CONCLUSION: This study shows that omental roll-up does not decrease the incidence of POPF after pancreatoduodenectomy.

Predictors of surgical site infection after pancreaticoduodenectomy.

BACKGROUND: Surgical site infection (SSI) is one of the most common complications after pancreaticoduodenectomy (PD). Thus, it is beneficial to preoperatively identify patients at high risk of developing SSI. The primary aim of the present study was to identify the factors associated with SSI after PD, and the secondary aim was to identify the adverse outcomes associated with the occurrence of SSI. METHODS: A single-centre retrospective study was conducted. All 280 patients who underwent PD at our institution from January 2008 to December 2018 were enrolled. Demographic and perioperative data were reviewed, and the potential risk factors for developing SSI and the adverse outcomes related to SSI were analysed. RESULTS: A total of 90 patients (32%) developed SSI. Fifty-one patients developed incisional SSI, and 39 developed organ/space SSI. Multivariate logistic analysis revealed that the significant risk factors for developing incisional SSI were preoperative biliary drainage (odds ratio, 3.04; 95% confidence interval, 1.36-6.79; p < 0.05) and postoperative pancreatic fistula (odds ratio, 2.78; 95% confidence interval, 1.43-5.38; p < 0.05), and the risk factors for developing organ/space SSI were preoperative cholangitis (odds ratio, 10.07; 95% confidence interval, 2.31-49.75; p < 0.05) and pancreatic fistula (odds ratio, 6.531; 95% confidence interval, 2.30-18.51; p < 0.05). Enterococcus spp., Escherichia coli and Klebsiella pneumoniae were the common bacterial pathogens that caused preoperative cholangitis as well as SSI after PD. The patients in the SSI group had a longer hospital stay and a higher rate of delayed gastric emptying than patients in the non-SSI group. CONCLUSIONS: The presence of postoperative pancreatic fistula was a significant risk factor for both incisional and organ/space SSI. Any efforts to reduce postoperative pancreatic fistula would decrease the incidence of incisional SSI as well as organ/space SSI after pancreaticoduodenectomy. Preoperative biliary drainage should be performed in selected patients to reduce the incidence of incisional SSI. Minimizing the occurrence of preoperative cholangitis would decrease the incidence of developing organ/space SSI.

Fluorescence cholangiography enhances surgical residents' biliary delineation skill for laparoscopic cholecystectomies.

BACKGROUND: Laparoscopic cholecystectomy (LC) is a minimally invasive procedure, often performed by surgical residents (SRs). Fluorescence cholangiography (FC) enables real-time identification of biliary anatomy. AIM: To investigate the benefit of FC for enhancing SRs' identification skills. METHODS: Prospective data was collected from January 2018 to June 2018 at our hospital. The study cohorts were the SRs (study group, n = 15) and the surgical staff (SS; control group, n = 9). Participants were assigned to watch videos of LCs with FC from five different patients who had gallbladder disease, and identify structures in the video clips (including cystic duct, common bile duct, common hepatic duct, and cystic artery), first without FC, and then with FC. RESULTS: In the without-FC phase, the overall misidentification rate by SRs (21.7%) was greater than that of the SS (11.8%; P = 0.018), However, in the FC phase, the two groups did not significantly differ in misidentification rates (23.3% vs 23.3%, P = 0.99). Paired-structure analysis of the without-FC and with-FC phases for the SR group found a significantly higher misidentification rate in the without-FC phase than the with-FC phase (21.9% vs 10.9%; P < 0.01). However, misidentification rates in the with-FC phase did not significantly differ between SRs and SS. CONCLUSION: FC enhanced identification skills of inexperienced surgeons during LC compared with conventional training. Combined with simulation-based video training, FC is a promising tool for enhancing technical and decision skills of trainees and inexperienced surgeons.

Outcomes of delayed endoscopic retrograde cholangiopancreatography in patients with acute biliary pancreatitis with cholangitis.

OBJECTIVE: The recommended treatment for acute biliary pancreatitis(ABP) with cholangitis is urgent endoscopic retrograde cholangiopancreatography(ERCP). However, tight schedules in the endoscopy room mean that urgent ERCP may not always be performed. This study aimed to compare the outcomes of early (≤72 h) and delayed(>72 h) ERCP in patients with ABP with cholangitis. METHODS: Ninety-five patients diagnosed with ABP with cholangitis who underwent ERCP between May 2012 and April 2018 were retrospectively reviewed. RESULTS: Sixty-seven patients(70.5%) were classified in the early ERCP and 28(29.5%) in the delayed ERCP groups. There was no significant difference in pancreatitis severity between the groups. Total bilirubin was higher in the early compared with the late ERCP group (5.7 ± 5.2 versus 3.5 ± 2.3 mg/dL, p = 0.03). Fewer patients in the early group had end-stage renal disease (0 versus 3, p = 0.006) and relatively fewer patients in the early group took aspirin (15(22.4%) versus 12(42.9%), p = 0.04). There were no significant differences between the early and delayed ERCP groups in terms of mortality (2(3.0%) versus 0), disease-related complications(11 (16.4%) versus 5(17.9%), p = 0.86), or ERCP-related complications(5(7.5%) versus 3(10.7%), p = 0.60). The total length of stay(LoS) was shorter in the early group(6.3 ± 4.4 versus 9.8 ± 6.1 days, p = 0.002). The rate of complete stone removal was lower in the early compared with the delayed ERCP group(32/42(76.2%) versus 18/18(100%), p = 0.02). CONCLUSION: Delayed ERCP can be performed in selected patients with ABP with cholangitis, with similar complication rates but longer LoS compared with early ERCP.

Preoperative serum albumin is associated with intra-abdominal infection following major hepatectomy.

BACKGROUND: Major hepatectomy is a complex surgical procedure with high morbidity. Intra-abdominal infection (IAI) is common following hepatectomy and affects treatment outcomes. This study was performed to investigate perioperative factors and determine whether the preoperative serum albumin level is associated with IAI following major hepatectomy. METHODS: From January 2008 to December 2018, 268 patients underwent major hepatectomy. We retrospectively analyzed demographic data and preoperative and perioperative variables. IAI was defined as organ/space surgical site infection. Risk factors for IAI were analyzed by logistic regression analysis. RESULTS: In total, 268 patients were evaluated. IAI was observed in 38 patients (14.6%). The mortality rate in the IAI group was 15.7%. Multivariate logistic analysis confirmed that the serum albumin level (odds ratio 0.91; 95% confidence interval 0.84-0.97; P = 0.03) and operative duration (odds ratio 1.50; 95% confidence interval 1.18-1.91; P < 0.01) were independent factors associated with IAI. A logistic model using the serum albumin level and operative duration to estimate the probability of IAI was analyzed. The area under the receiver operating characteristic curve for predicting IAI was 0.78. CONCLUSION: The serum albumin level and operative duration were independent factors predicting IAI following major hepatectomy.

Correlation of serum albumin and prognostic nutritional index with outcomes following pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex surgical procedure with a high morbidity rate. The serious complications are major risk factors for poor long-term surgical outcome. Studies have reported an association between early postoperative prognostic nutritional index (PNI) and prediction of severe complications after abdominal surgery. However, there have been no studies on the use of early postoperative PNI for predicting serious complications following PD. AIM: To analyze the risk factors and early postoperative PNI for predicting severe complications following PD. METHODS: We retrospectively analyzed 238 patients who underwent PD at our hospital between January 2007 and December 2017. The postoperative complications were classified according to the Dindo-Clavien classification. Grade III-V postoperative complications were classified as serious. The risk factors for serious complications were analyzed by univariate analysis and multivariate logistic regression analysis. RESULTS: Overall complications were detected in 157 of 238 patients (65.9%) who underwent PD. The grade III-V complication rate was 26.47% (63/238 patients). The mortality rate was 3.7% (9/238 patients). Multivariate logistic regression analysis revealed that preoperative serum albumin [odds ratio (OR): 0.883, 95% confidence interval (CI): 0.80-0.96; P < 0.01] and PNI on postoperative day 3 < 40.5 (OR: 2.77, 95%CI: 1.21-6.38, P < 0.05) were independent factors associated with grade III-V postoperative complications. CONCLUSION: Perioperative albumin is an important factor associated with serious complications following PD. Low early postoperative PNI (< 40.5) is a predictor for serious complications.

Platelet-to-Lymphocyte Ratio and Large Tumor Size Predict Microvascular Invasion after Resection for Hepatocellular Carcinoma

Background: Recurrence after curative resection of hepatocellular carcinoma (HCC) is associated with early death and poor prognosis. Microvascular invasion (mVI) is strongly associated with disease recurrence. Although many studies have examined the relationship between various serum inflammatory indices and post-treatment prognosis, little is known about preoperative predictors of microvascular invasion in HCC. Methods: Patients who underwent curative hepatic resection for HCC at our institute from January 2006 to December 2016 were retrospectively reviewed. The associations between mVI and various potential risk factors, including tumor size, hepatitis B and C virus infection, Child­Pugh scores, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio, were analyzed. Optimal cut-off values were determined using receiver operating characteristic curves. Results: A total of 330 HCC patients were enrolled in this study, of whom 74 (22.4%) had tumors with mVI. After univariate analysis, two parameters were significantly associated with mVI after hepatic resection: platelet-to-lymphocyte ratio ≥102 (odds ratio [OR] 2.385, p = 0.001) and tumor size ≥5 cm (OR 4.29, p < 0.001). Both variables remained significant risk factors for mVI after multivariate analysis: platelet-to-lymphocyte ratio ≥102 (OR 1.831, p = 0.034) and tumor size ≥5 cm (OR 3.791, p < 0.001). Conclusions: Large tumor size (≥5 cm) and high platelet-to-lymphocyte ratio (≥102) are independent predictive factors for mVI in HCC.

Prognostic role of alpha-fetoprotein response after hepatocellular carcinoma resection.

AIM: To investigate whether the change in pre-/post-operation serum alpha-fetoprotein (AFP) levels is a predictive factor for hepatocellular carcinoma (HCC) outcomes. METHODS: We retrospectively analyzed 334 HCC patients who underwent hepatic resection at our hospital between January 2006 and December 2016. The patients were classified into three groups according to their change in serum AFP levels: (1) the normal group, pre-AFP ≤ 20 ng/mL and post-AFP ≤ 20 ng/mL; (2) the response group, pre-AFP > 20 ng/mL and post-AFP decrease of ≥ 50% of pre-AFP; and (3) the non-response group, pre-AFP level > 20 ng/mL and post-AFP decrease of < 50% or higher than pre-AFP level, or any pre-AFP level < 20 ng/mL but post-AFP >20 ng/mL. RESULTS: Univariate and multivariate analyses revealed that multiple tumors [hazard ratio (HR): 1.646, 95%CI: 1.15-2.35, P < 0.05], microvascular invasion (mVI) (HR: 1.573, 95%CI: 1.05-2.35, P < 0.05), and the non-response group (HR: 2.425, 95% CI: 1.42-4.13, P < 0.05) were significant independent risk factors for recurrence-free survival. Similarly, multiple tumors (HR: 1.99, 95%CI: 1.12-3.52, P < 0.05), mVI (HR: 3.24, 95%CI: 1.77-5.90, P < 0.05), and the non-response group (HR: 3.62, 95%CI: 1.59-8.21, P < 0.05) were also significant independent risk factors for overall survival. The non-response group had significantly lower overall survival rates and recurrence-free survival rates than both the normal group and the response group (P < 0.05). Thus, patients with no response regarding post-surgery AFP levels were associated with poor outcomes. CONCLUSION: Serum AFP responses are significant prognostic factors for the surgical outcomes of HCC patients, suggesting post-resection AFP levels can direct the management of HCC patients.

Prognostic factors in patients with HBV-related hepatocellular carcinoma following hepatic resection.

BACKGROUND: To analyze prognostic factors following hepatic resection in patients with HBV-related hepatocellular carcinoma. METHODS: We retrospectively analyzed 217 patients with HBV-related hepatocellular carcinoma who underwent hepatic resection at our hospital between January 2006 and December 2015. Disease-free survival and overall survival rates were analyzed using the Kaplan-Meier method and the log-rank test. The association between recurrence and survival and various clinicopathological factors, including serum alpha-fetoprotein (AFP) level, platelet count, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, antiplatelet therapy, antiviral therapy, hepatitis C virus infection, and tumor-related characteristics, were assessed using univariate and multivariate logistic regression analysis. RESULTS: The 1-, 3-, and 5-year overall survival rates were 91, 84, and 79%, respectively, and the recurrence-free survival rates were 72, 51, and 44%, respectively. High post-operative AFP level (hazard ratio [HR] 1.112, 95% confidence interval [CI]: 1.02-1.21, P = 0.007), multiple tumors (HR 1.991, 95% CI: 1.11-3.56, P = 0.021), and no antiviral treatment (HR 1.823, 95% CI: 1.07-3.09, P = 0.026) were independent risk factors for recurrence. High post-operative AFP level (HR 1.222, 95% CI: 1.09-1.36, P < 0.001), multiple tumors (HR 2.715, 95% CI: 1.05-7.02, P = 0.039), and recurrence (HR 12.824, 95% CI: 1.68-97.86, P = 0.014) were independent risk factors for mortality. No other factors analyzed were associated with outcomes in this patient cohort. CONCLUSIONS: High post-operative serum alpha-fetoprotein level and multiple tumors, but not inflammatory factors, were risk factors for poor prognosis in HBV-related hepatocellular carcinoma patients after resection.

Risk factors for pancreatic fistula following pancreaticoduodenectomy: A retrospective study in a Thai tertiary center.

AIM: To analyze the risk factors of postoperative pancreatic fistula following pancreaticoduodenectomy in a Thai tertiary care center. METHODS: We retrospectively analyzed 179 patients who underwent pancreaticoduodenectomy at our hospital from January 2001 to December 2016. Pancreatic fistula were classified into three categories according to a definition made by an International Study Group on Pancreatic Fistula. The risk factors for pancreatic fistula were analyzed by univariate analysis and multivariate logistic regression analysis. RESULTS: Pancreatic fistula were detected in 88/179 patients (49%) who underwent pancreaticoduodenectomy. Fifty-eight pancreatic fistula (65.9%) were grade A, 22 cases (25.0%) were grade B and eight cases (9.1%) were grade C. Clinically relevant pancreatic fistula were detected in 30/179 patients (16.7%). The 30-d mortality rate was 1.67% (3/179 patients). Multivariate logistic regression analysis revealed that soft pancreatic texture (odds ratio = 3.598, 95%CI: 1.77-7.32) was the most significant risk factor for pancreatic fistula. A preoperative serum bilirubin level of > 3 mg/dL was the most significant risk factor for clinically relevant pancreatic fistula according to univariate and multivariate analysis. CONCLUSION: Soft pancreatic tissue is the most significant risk factor for postoperative pancreatic fistula. A high preoperative serum bilirubin level (> 3 mg/dL) is the most significant risk factor for clinically relevant pancreatic fistula.

Robotic Technique for Accessing Left Hepatic Vein Through Ligamentum Venosum in Left Hepatectomy: How I Do It?

INTRODUCTION: Blood loss is associated with postoperative morbidity and mortality. Outflow control could be used concomitantly with inflow control for maximum reduction in blood loss during parenchymal transection. However, in left hepatectomy (LH) and left lateral sectionectomy (LLS), extrahepatic control of the left hepatic vein (LHV) is still less commonly used. Some authors reported extrahepatic LHV control technique using ligamentum venosum (LV) in open or laparoscopic surgery, but no reports of this technique in robotic surgery have been found. MATERIALS AND METHODS: The dissection of LV from the liver was performed, followed by clipping and transecting LV. The cephalad LV stump was retracted to the left inferior direction and then the dissection of the posterior part of LHV was performed until the opening space was connected to the anterior part of LHV. The LHV was encircled with the tape and vascular stapler was inserted to manage LHV stump. From 2013 to 2015, LHV was successfully encircled by using this technique in 7 out of 11 cases. The mean operative time was 244 minutes, the mean estimated blood loss was 300 mL, and the mean length of hospital stay was 4.8 days. Neither injury to LHV, nor complications related to the liver were found. DISCUSSION AND CONCLUSION: From our experiences, LHV was routinely controlled in robotic LH or LLS and the success rate was 60%. However, this technique is not recommended for the tumor that compresses or abuts LHV/LV, and in cirrhotic liver with associated hypertrophic left lateral segment.

Defining Surgical Difficulty According to the Perceived Complexity of Liver Resection: Validation of a Complexity Classification in Patients with Hepatocellular Carcinoma.

BACKGROUND: A classification system for defining the complexity of hepatectomy according to its technical difficulty was recently proposed as a consensus of a panel of experts. We validated this classification system for a prospective liver resection cohort in patients with hepatocellular carcinoma (HCC). METHOD: The complexity classification separated liver resections into three categories of complexity (low, medium, or high). We retrospectively reviewed 150 open hepatectomies between 1 March 2004 and 30 November 2013 in patients with HCC, and compared the perioperative outcomes according to the complexity classification. RESULTS: No differences in patient demographics or pathologic findings were observed among the three groups according to the complexity classification, which effectively differentiated the three groups in terms of intraoperative findings and short-term outcomes. The mean estimated blood loss (p = 0.001), rate of blood transfusion (p < 0.001), and mean operation time (p < 0.001) were significantly different among the three groups. The rates of overall and major complications (p = 0.026 and 0.005, respectively) were significantly greater in the high-complexity group. Multivariate analysis showed that the complexity classification was independently associated with major complications (odds ratio 4.73; p = 0.040); however, overall patient survival (p = 0.139) and disease-free survival (p = 0.076) were not significantly different among the three groups. CONCLUSION: The complexity classification effectively differentiated intraoperative and short-term outcomes, and was independently associated with major complications after hepatectomy in patients with HCC.

Outcomes of Simultaneous Major Liver Resection and Colorectal Surgery for Colorectal Liver Metastases.

BACKGROUND: The optimal surgical strategy for treating colorectal cancer liver metastases (CRLM) in patients requiring major liver resection (MLR) is controversial, especially in rectal cancer patients. METHOD: Between March 2004 and January 2015, 103 patients underwent MLR for CRLM and underwent MLR simultaneously with colorectal surgery (simultaneous group; n = 55) or MLR after colorectal surgery (liver-only group; n = 48). RESULTS: There were no significant differences in sex, age, ASA score, BMI, size and number of liver metastases, liver resection margin, surgical outcomes, and estimated blood loss. The rates of postoperative complications (simultaneous group vs. liver-only group; 76.4 % vs. 62.5 %; P = 0.126) and major complications (29.0 % vs. 25.0 %; P = 0.513) were also similar in both groups. The time to starting a soft diet was longer in the simultaneous group (6.0 days vs. 3.4 days; P < 0.001), but the length of hospital stay was similar (14.9 days vs. 13.3 days; P = 0.345). There were no perioperative deaths, anastomotic leakage, or septic complications. Among patients who underwent rectal surgery, the frequency of complications was greater in the simultaneous group (87.0 % vs. 56.2 %; P = 0.031), but there was no difference in major complications (34.7 % vs. 25.0 %; P = 0.822). The postoperative morbidity index was 0.204 and 0.180 in the simultaneous and liver-only groups, respectively, in all patients, and was 0.227 and 0.136, respectively, in the rectal surgery subgroup. CONCLUSION: Simultaneous MLR is feasible and safe in synchronous CRLM patients, including rectal cancer patients.