Comparison of pure laparoscopic donor right posterior sectionectomy versus right hemihepatectomy for living donor liver transplantation.

The right posterior section (RPS) graft for living donor liver transplantation is an alternative graft in a live liver donor with insufficient remnant left lobe volume and portal vein anomaly. Although there have been some reports regarding pure laparoscopic donor right posterior sectionectomy (PLDRPS), no study has compared PLDRPS versus pure laparoscopic donor right hemihepatectomy (PLDRH). The aim of our study was to compare the surgical outcomes of PLDRPS versus PLDRH at centers achieving a complete transition from open to laparoscopic approach in liver donor surgery. From March 2019 to March 2022, a total of 351 living donor liver transplantations, including 16 and 335 donors who underwent PLDRPS and PLDRH, respectively, were included in the study. In the donor cohort, there were no significant differences in major complication (≥grade III) rate and comprehensive complication index between the PLDRPS versus PLDRH group (6.3% vs. 4.8%; p = 0.556 and 2.7 ± 8.6 vs.1.7 ± 6.4; p = 0.553). In the recipient cohort, there was a significant difference in major complication (≥grade III) rate (62.5% vs. 35.2%; p = 0.034) but no significant difference in comprehensive complication index (18.3 ± 14.9 vs. 15.2 ± 24.9; p = 0.623) between the PLDRPS and PLDRH groups. PLDRPS in live liver donors with portal vein anomaly and insufficient left lobe was technically feasible and safe with experienced surgeons. The PLDRPS group might be comparable with the PLDRH group based on the surgical outcomes of donors and recipients. However, in terms of recipient outcomes, more careful selection of donors of the RPS graft and further research in a large number of cases are necessary to evaluate the usefulness of PLDRPS.

Role and limitation of neoadjuvant hepatic arterial infusion chemotherapy in advanced hepatocelluar carcinoma patients with Child-Pugh class A.

BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) have a poor oncologic outcome. In this study, we evaluated the role and limitation of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients with Child-Pugh class A and the efficacy of liver resection subsequent to downstaging after neoadjuvant HAIC. METHODS: In the present retrospective study, 103 patients with advanced HCC, who underwent neoadjuvant HAIC from April 2003 to March 2015 were analyzed. Response to HAIC was evaluated by dividing time period into after 3 cycles and after 6 cycles, each defined as early and late period. Liver resection after neoadjuvant HAIC was offered in patients who were considered as possible candidates for curative resection with tumor-free margin as well as sufficient future liver remnant volume. RESULTS: The median survival time (MST) in all patients was 14 ± 1.7 months. Response rate and disease control rate were 36.3% (37) and 81.4% (83) in early period, respectively, and 26.4% (14) and 47.2% (25), in late period, respectively (P = 0.028). Twelve patients (11.7%) underwent liver resection after neoadjuvant HAIC and the MST was 37 ± 6.6 months. One-, 3-, and 5-year recurrence-free survival after liver resection were 58.3%, 36.5%, and 24.3% respectively. Liver resection was identified as the only independent prognostic factor that associated with overall survival in multivariate analysis (P = 0.002) CONCLUSION: HAIC could be further alternative for the treatment of advanced HCC in patients with good liver function. If liver resection is possible after neoadjuvant HAIC, liver resection would provide better outcomes than HAIC alone.

Surgical strategy for T1 gallbladder cancer: a nationwide multicenter survey in South Korea.

BACKGROUND: The aim of this study was to investigate the clinical features and clinical outcomes of T1 gallbladder (GB) cancer and to determine an appropriate surgical strategy for T1 GB cancer. METHODS: A nationwide multicenter study, in which 16 University Hospitals in Korea participated, was performed from 1995 to 2004. A total of 258 patients, 117 patients with T1a and 141 patients with T1b disease were enrolled. Clinicopathologic findings and long-term follow-up results were analyzed after a consensus meeting of the Korean Pancreas Surgery Club was held. RESULTS: Simple cholecystectomy was performed in 95 patients (81.2 %) with T1a tumor and in 89 patients (63.1 %) with T1b tumor (p < 0.01). Lymph node metastasis was observed in 2.9 % of T1a patients and in 9.9 % of T1b patients (p = 0.391). A significant difference in 5-year disease-specific survival (DSS) rates was observed between T1a and T1b patients (96.4 vs 84.8 %, respectively, p = 0.03). However, no significant 5-year DSS rate difference was observed between those who underwent simple cholecystectomy or extended cholecystectomy, regardless of whether lymph node dissection was performed or whether lymph node metastasis was present. There was no significant difference in recurrence-free survival between simple cholecystectomy and extended cholecystectomy. CONCLUSIONS: There was no superiority of extended cholecystectomy over simple cholecystectomy in the aspect of survival and recurrence especially in T1b gallbladder cancer. Furthermore, the effectiveness of regional lymphadenectomy for treatment purpose remains questionable. Therefore, simple cholecystectomy could be recommended as a surgical strategy of T1 gallbladder cancer.

Surgical outcomes of hepatocellular carcinoma with bile duct tumor thrombus: a Korean multicenter study.

BACKGROUND: The long-term outcomes after resection for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) are unclear. This multicenter study was conducted to determine the prognosis of HCC patients with macroscopic BDTT who underwent resection with curative intent. METHODS: Of 4,308 patients with HCC from four Korean institutions, this single-arm retrospective study included 73 patients (1.7 %) who underwent resection for HCC with BDTT. RESULTS: Jaundice was also present in 34 patients (46.6 %). According to Ueda classification, BDTT was type 2 in 34 cases (46.6 %) and type 3 in 39 cases (53.4 %). Biliary decompression was performed in 33 patients (45.2 %), decreasing the median lowest bilirubin level to 1.4 mg/dL before surgery. Systematic hepatectomy was performed in 69 patients (94.5 %), and concurrent bile duct resection was performed in 31 patients (42.5 %). Surgical curability types were R0 (n = 57; 78.1 %), R1 (n = 11; 15.1 %), and R2 (n = 5; 6.8 %). Patient survival rates were 76.5 % at 1 year, 41.4 % at 3 years, 32.0 % at 5 years, and 17.0 % at 10 years. Recurrence rates were 42.9 % at 1 year, 70.6 % at 3 years, 77.3 % at 5 years, and 81.1 % at 10 years. Results of univariate survival analysis showed that maximal tumor size, bile duct resection, and surgical curability were significant risk factors for survival, and surgical curability was a significant risk factor for recurrence. Multivariate analysis did not reveal any independent risk factors. CONCLUSIONS: Hepatocellular carcinoma patients with BDTT achieved relatively favorable long-term results after resection; therefore extensive surgery should be recommended when complete resection is anticipated.

Validation of quantitative prognostic prediction using ADV score for resection of hepatocellular carcinoma: A Korea-Japan collaborative study with 9200 patients.

BACKGROUND: A score derived from the concentrations of α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) and tumor volume (TV), called ADV score, has been shown to be prognostic of hepatocellular carcinoma (HCC) recurrence following hepatic resection (HR) or liver transplantation. METHODS: This multicenter, multinational validation study included 9200 patients who underwent HR from 2010 to 2017 at 10 Korean and 73 Japanese centers, and were followed up until 2020. RESULTS: AFP, DCP, and TV showed weak correlations (ρ ≤ .463, r ≤ .189, p < .001). Disease-free survival (DFS), overall survival (OS), and post-recurrence survival rates were dependent on 1.0 log and 2.0 log intervals of ADV scores (p < .001). Receiver operating characteristic (ROC) curve analysis showed that ADV score cutoffs of 5.0 log for DFS and OS yielded the areas under the curve ≥ .577, with both being significantly prognostic of tumor recurrence and patient mortality at 3 years. ADV score cutoffs of ADV 4.0 log and 8.0 log, derived through K-adaptive partitioning method, showed higher prognostic contrasts in DFS and OS. ROC curve analysis showed that an ADV score cutoff of 4.2 log was suggestive of microvascular invasion, with both microvascular invasion and an ADV score cutoff of 4.2 log showing similar DFS rates. CONCLUSIONS: This international validation study demonstrated that ADV score is an integrated surrogate biomarker for post-resection prognosis of HCC. Prognostic prediction using ADV score can provide reliable information that can assist in planning treatment of patients with different stages of HCC and guide individualized post-resection follow-up based on the relative risk of HCC recurrence.

Factors influencing patterns of recurrence following pancreaticoduodenectomy for patients with distal bile duct cancer and ampulla of Vater cancer.

Backgrounds/Aims: Pancreaticoduodenectomy (PD) is a standard surgical procedure for patients with periampullary cancer. During the follow-up period after PD, recurrence can be observed in various places with different prognosis. The aim of this study was to clarify the pattern of recurrence and factors affecting the survival of patients with periampullary cancer. Methods: Overall, 88 patients who received PD for distal common bile duct cancer or ampulla of Vater cancer were finally included and their clinical characteristics were analyzed. Patients were divided into three groups: recurrence-free (RF) group, an isolated locoregional recurrence (LR) group, and a distant metastasis (DM) group. Prognostic factors affecting recurrence in each group were analyzed and a survival analysis was performed. Results: Perineural invasion (PNI), T stage, and lymphovascular invasion (LVI) were significant risk factors for LR and PNI, lymph node metastasis, LVI, and T stage were associated with DM group compared to RF group in univariate analysis, respectively. N stage and PNI were significant risk factors (p = 0.046, p = 0.041) in overall survival of the LR and the DM groups. There was no significant difference in 5-year overall survival between the LR and DM groups. Conclusions: T stage was a significant risk factor of LR, while PNI was a significant risk factor of DM. There was no significant difference in overall survival depending on the site of recurrence.

Determination of malignant and invasive predictors in branch duct type intraductal papillary mucinous neoplasms of the pancreas: a suggested scoring formula.

Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.

Laparoscopic hepatobiliary and pancreatic surgery: my trials and current status in Korea.

There has been a dramatic change in surgical care over the past 30 years with the introduction of laparoscopic surgery. It was my great fortune that I could experience laparoscopic surgery during my resident training period. After beginning to work for my hospital in 1995, I tried laparoscopic surgery in many surgical fields, including hepatobiliary and pancreatic (HBP), colon, stomach, and vascular surgery (endoscopic saphenous vein harvesting, endoscopic subfascial perforating vein interruption to treat skin complications in patients with deep vein insufficiency in the lower leg). In Sabiston, Textbook of Surgery, published in 1997, laparoscopic Whipple and major liver resection were not accepted at the time but now are. There are three possible reasons that may explain this shift. The first one is the 30 years of experience using advanced techniques; all of us know that "Seeing is believing," and "A thousand hearings are not worth one seeing." Next is the availability of three-dimensional imaging with magnification which enables us to perform difficult surgeries. The last one is the use of good instruments and an advanced surgical platform. In this paper, I would like to share my past and recent trials with advanced HBP laparoscopic surgery, as well as its current status in Korea and future directions.

Expression of p16 protein in gallbladder carcinoma and its precancerous conditions.

BACKGROUND/AIMS: Adenocarcinoma of the gallbladder is a highly malignant neoplasm. p16 is a tumor suppressor gene protein, which is a cyclin-dependent kinase inhibitor that regulates the G1-S phase of the cell cycle. The purpose of the present study was to investigate the expression of p16 in gallbladder carcinoma and its precancerous conditions and to examine the relationship between p16 expression and clinicopathological parameters. METHODOLOGY: Formalin-fixed, paraffin-embedded tissue sections from 20 cases of normal gallbladder, 20 cases of chronic cholecystitis, 20 cases of gallbladder adenoma, 20 cases of dysplasia, and 58 cases of adenocarcinoma were examined. The expression of p16 was evaluated by immunohistochemical analysis. RESULTS: In normal gallbladder, no expression of p16 was found. In chronic cholecystitis, expression of p16 was not found. In gallbladder adenomas, expression of p16 was found in 20% (4/20). In low grade dyspalsias, expression of p16 was not found. In high grade dysplasias, p16 expression was present in 45.0% (9/20). In gallbladder adenocarcinomas, p16 expression was found in 27.6% (16/58). Expression of p16 correlated significantly with histologic grade (p < 0.05). No correlation was found between p16 expression and age, gender, tumor size, gross type, location, vascular invasion, lymph node metastasis, and TNM stage, respectively. CONCLUSIONS: P16 protein overexpression is an early and relatively common event in carcinogenesis of gallbladder carcinoma. Expression of p16 protein is absent in normal or chronic cholecystitis. Expression of p16 may be an ancillary diagnostic marker of gallbladder carcinoma and its precancerous conditions.

Bioelectrical impedance may predict cell viability during ischemia and reperfusion in rat liver.

Ischemia and reperfusion (I/R) injury is a major cause of hepatic failure after liver surgery, but no method could monitor or predict it real-time during surgery. We measured bioelectrical impedance (BEI) and cell viability to assess the usefulness of BEI during I/R in rat liver. A 70% partial liver ischemia model was used. BEI was measured at various frequencies. Adenosine triphosphate (ATP) content, and palmitic acid oxidation rate were measured, and histological changes were observed in order to quantify liver cell viability. BEI changed significantly during ischemia at low frequency. In the ischemia group, BEI increased gradually during 60 min of ischemia and had a tendency to plateau thereafter. The ATP content decreased below 20% of the baseline level. In the I/R group, BEI recovered to near baseline level. After 24 hr of reperfusion, the ATP contents decreased to below 50% in 30, 60 and 120 min of ischemia and the palmitic acid metabolic rates decreased to 91%, 78%, and 74%, respectively, compared with normal liver. BEI may be a good tool for monitoring I/R during liver surgery. The liver is relatively tolerant to ischemia, however after reperfusion, liver cells may be damaged depending upon the duration of ischemia.

A Comparison of Short-Term Outcomes between Laparoscopic and Open Liver Resection in Elderly Patients.

Purpose: The aim of this study was to compare the short-term outcomes between laparoscopic liver resection (LLR) and open liver resection (OLR) in elderly patients with hepatic tumors. Methods: From January 2013 to December 2019, a retrospective study was conducted for a total of 143 patients with over 70 years of age, who underwent liver resection for hepatic tumors. Forty-five patients who received biliary reconstruction at the same time were excluded. According to surgical approaches, 98 patients were classified into LLR and OLR groups. All postoperative complications were classified according to the Clavien-Dindo grading system and the Comprehensive Complication Index (CCI). Results: Incidence of the postoperative complications was not statistically different between LLR and OLR groups. The CCI was significantly lower in the LLR group, with a median of 8.556, and a median of 19.698 in the OLR group (p=0.042). The length of hospital stay in the LLR group was significantly shorter than in the OLR group (p=0.008). Conclusion: LLR is safe and feasible as a treatment for hepatic tumor in elderly patients with potentially less postoperative complications compared to OLR.

Clinical impact of anatomical resection on long-term outcomes after hepatectomy for primary solitary hepatocellular carcinoma with or without preoperative positron emission tomography positivity.

BACKGROUND: There is little evidence indicating that anatomical resection (AR) is associated with improved survival in patients with solitary hepatocellular carcinoma (HCC) who were preoperatively evaluated by positron emission tomography (PET). The aim of our study was to compare the oncologic outcomes of AR in PET-positive versus PET-negative patients with HCC. METHODS: From January 2007 to September 2015, 259 patients with preoperative PET underwent hepatectomy as the primary treatment for solitary HCC. Patients were divided into four groups according to PET uptake and hepatectomy type [AR or non-anatomical resection (NAR)]: Group 1 (PET-negative and AR, n=62); Group 2 (PET-negative and NAR, n= 46); Group 3 (PET-positive and AR, n=100); Group 4 (PET-positive and NAR, n=51). RESULTS: PET positivity was associated with higher protein induced by vitamin K antagonist-II (P=0.025), lager tumor size (P=0.05), microvascular invasion (MVI) (P=0.012), and portal vein invasion (P=0.031). In Kaplan-Meier analysis for RFS, Group 1 showed remarkable difference from Group 3 and Group 4 (P=0.045, P=0.023, respectively). In the PET-positive subgroup with HCC under 3 cm, AR was associated with better RFS than NAR (P=0.016). CONCLUSIONS: A combination of AR and PET negativity showed good prognosis in long-term outcomes. Finally, AR can decrease the risk of tumor recurrence in patients with a solitary PET-positive HCC less than 3 cm.

Cellular mechanisms of hepatocyte growth factor-mediated urokinase plasminogen activator secretion by MAPK signaling in hepatocellular carcinoma.

AIMS AND BACKGROUND: The hepatocyte growth factor, its receptor c-Met, and urokinase-type plasminogen mediate various cellular responses on activation, including proliferation, survival, invasion, and metastasis. The regulatory mechanisms for the proliferation and the particular invasive phenotypes of hepatocellular carcinoma are not yet fully understood. In order to clarify the intracellular downstream signal for hepatocyte growth factor/c-Met signaling in tumor progression and metastasis in hepatoma, we determined the effects of a specific MEK1 inhibitor (PD 098059) and a p38 kinase inhibitor (SB 203580) on hepatocyte growth factor-mediated cell proliferation and urokinase-type plasminogen expression in hepatoma cell lines (HepG2 and Hep3B). RESULTS: Hepatocyte growth factor treatment induced the phosphorylation of ERK and p38 kinase in a dose-dependent manner, resulting in an early peak of phosphorylation at 3 to 10 min, which then rapidly decreased to a near basal level. Pretreatment with PD 098059 reduced hepatocyte growth factor-mediated cell proliferation and urokinase-type plasminogen secretion. In contrast, SB 203580 pretreatment enhanced cell proliferation and urokinase-type plasminogen secretion due to induction of ERK phosphorylation. Treatment with PD 098059 and SB 203580 resulted in a decrease in phospho-ERK activity. Stable expression of dominant negative-MEK1 in HepG2 cells showed a decrease in hepatocyte growth factor-mediated urokinase-type plasminogen secretion. CONCLUSIONS: Such results suggest that interaction of an MEK/ERK and a p38 kinase might be critical in intrahepatic invasion and metastasis of human hepatoma cells.

Preliminary Findings on the Effectiveness of Meaning-Centered Psychotherapy in Patients with Pancreatobiliary Cancer.

PURPOSE: This study investigated the effectiveness of meaning-centered psychotherapy (MCP), which is known to be a helpful psychotherapeutic intervention in distressing conditions, for patients with pancreatobiliary cancer. MATERIALS AND METHODS: We recruited 37 patients with pancreatobiliary cancer from three university general hospitals and assessed their psychological characteristics. Patients who reported clinically significant emotional distress were recommended to undergo MCP. Patients who consented to MCP were provided four sessions of the therapy. Patient psychological characteristics were assessed again 2 months after MCP. For statistical comparison, outcome variables included anxiety, depression, mental adjustment to cancer, and quality of life (QoL), as well as the degree of stress and physical symptoms. RESULTS: Sixteen patients completed the MCP and the final assessment 2 months later. In the initial assessment, the patients receiving MCP showed higher levels of anxiety and depression than those not receiving MCP, and QoL was also lower in terms of role function, emotional function, social function, and global QoL. At the 2-month follow-up, the MCP group showed a significant improvement in anxiety (p=0.007), depression (p=0.010), and anxious preoccupation (p<0.001). In addition, QoL significantly improved in the MCP group, while there was no significant change in the non-MCP group. CONCLUSION: In this study, MCP showed potential therapeutic benefits against emotional distress in patients with pancreatobiliary cancer, improving their QoL.

Phosphatidic acid as a regulator of matrix metalloproteinase-9 expression via the TNF-alpha signaling pathway.

Phosphatidic acid (PA) is implicated in pathophysiological processes associated with cellular signaling events and inflammation, which include the expressional regulation of numerous genes. Here, we show that PA stimulation increases matrix metalloproteinase-9 (MMP-9) expression in macrophages through tumor necrosis factor (TNF)-alpha signaling. We performed antibody array analysis on proteins from macrophages stimulated with PA. PA was found to induce the production of TNF-alpha, but not of TNF receptor (TNFR)1 and TNFR2 in a time-dependent manner and stimulated significant, though delayed, MMP-9 expression. PA induced the phosphorylations of both ERK1/2 and p38, but not of c-jun amino-terminal kinase. Moreover, only ERK1/2 inhibition by U0126 suppressed PA-induced TNF-alpha production and MMP-9 expression. Neutralizing TNF-alpha, TNFR1 or TNFR2 antibodies significantly suppressed PA-induced MMP-9 expression, suggesting that the production of TNF-alpha in response to PA preceded the expression of MMP-9. Moreover, lipopolysaccharide-induced PA also led to TNF-alpha release and resulted in MMP-9 expression. Taken together, these observations suggest that PA may play a role in MMP-9 regulation through ERKs/TNF-alpha/TNFRs-dependent signaling pathway.

Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression.

Unmethylated CpG oligodeoxynucleotides (CpG ODNs) activate immune cells to produce immune mediators. This study demonstrates that in murine macrophage RAW 264.7 cells, CpG ODN-mediated matrix metalloproteinase-9 (MMP-9) expression is regulated at transcriptional level and requires de novo protein synthesis. Inhibition of ERK and p38 MAPK, but not JNK, results in significant decrease of CpG ODN-induced MMP-9 expression. We found that endosomal maturation inhibitors, chloroquine and bafilomycin A, block CpG ODN-induced ERK and p38 MAPK activation and the subsequent MMP-9 expression. We also observed that CpG ODN induces NF-kappaB activation and NF-kappaB is a downstream target of p38 MAPK. Taken together, our data demonstrate that CpG ODN triggers MMP-9 expression via TLR-9 dependent ERK and p38 MAPK activation followed by NF-kappaB activation.

Metformin restores the penile expression of nitric oxide synthase in high-fat-fed obese rats.

Obesity is a well-known risk factor for erectile dysfunction, which is associated with reduced penile nitric oxide synthase (NOS) expression. Recently it was reported that metformin activates AMP-activated protein kinase (AMPK), which increases the expression of neuronal (n) NOS and endothelial (e) NOS. Thus, to evaluate whether metformin restores NOS expression in penile tissue, we measured penile expression of nNOS and eNOS after 4 weeks of metformin treatment (300 mg/kg/d) in 5-month-old high-fat-fed obese (HFO) rats. HFO rats have increased fat accumulation in visceral areas and marked suppression of nNOS and eNOS expression in penile tissue. However, metformin treatment decreased visceral fat deposition and restored nNOS and eNOS expression in penile tissue. The levels of AMPK and phosphorylated AMPK were also decreased in HFO rats but were subsequently elevated by metformin treatment. These results suggest that expression of NOS was suppressed by the high-fat diet but restored by metformin treatment. The effect of metformin on the expression of NOS may be associated with its activation of AMPK.

Loss of heterozygosity on chromosome 10q23 and mutation of the phosphatase and tensin homolog deleted from chromosome 10 tumor suppressor gene in Korean hepatocellular carcinoma patients.

Loss of heterozygosity (LOH) in the 10q23 chromosomal region was analyzed in 18 tissue samples from Korean hepatocellular carcinoma (HCC) patients. LOH at the phosphatase and tensin homolog deleted from chromosome 10 (PTEN) region (D10S215, AFMa086wg9 and D10S541) was found in 8 of the 18 (44.4%) HCCs. LOH (20%) and microsatellite instability (26.7%) were also frequently found at the D10S2177 locus, which is located on the telomere side of the PTEN region. LOH was found in other loci, such as AFM280we1 and D10S2281. The presence of LOH in regions other than the PTEN region on chromosome 10q23 suggested the presence of additional tumor suppressor gene(s). PTEN mutation was found in only a subset of HCCs: A single base insertion at the end of the 5'-end splice signal (AG-GUAAGUU) in intron 5 and a silent mutation in exon 6 (codon 188, CTG-Val to CTA). Our data collectively suggest that the genetic alterations of chromosome 10q23, including the PTEN gene, could be important in hepatocarcinogenesis in the Korean population.

An opportunity in difficulty: Japan-Korea-Taiwan expert Delphi consensus on surgical difficulty during laparoscopic cholecystectomy.

BACKGROUND: We previously identified 25 intraoperative findings during laparoscopic cholecystectomy (LC) as potential indicators of surgical difficulty per nominal group technique. This study aimed to build a consensus among expert LC surgeons on the impact of each item on surgical difficulty. METHODS: Surgeons from Japan, Korea, and Taiwan (n = 554) participated in a Delphi process and graded the 25 items on a seven-stage scale (range, 0-6). Consensus was defined as (1) the interquartile range (IQR) of overall responses ≤2 and (2) ≥66% of the responses concentrated within a median ± 1 after stratification by workplace and LC experience level. RESULTS: Response rates for the first and the second-round Delphi were 92.6% and 90.3%, respectively. Final consensus was reached for all the 25 items. 'Diffuse scarring in the Calot's triangle area' in the 'Factors related to inflammation of the gallbladder' category had the strongest impact on surgical difficulty (median, 5; IQR, 1). Surgeons agreed that the surgical difficulty increases as more fibrotic change and scarring develop. The median point for each item was set as the difficulty score. CONCLUSIONS: A Delphi consensus was reached among expert LC surgeons on the impact of intraoperative findings on surgical difficulty.

The "right" way is not always popular: comparison of surgeons' perceptions during laparoscopic cholecystectomy for acute cholecystitis among experts from Japan, Korea and Taiwan.

BACKGROUND: Generally, surgeons' perceptions of surgical safety are based on experience and institutional policy. Our recent pilot survey demonstrated that the acceptable duration of surgery and criteria for open conversion during laparoscopic cholecystectomy (LC) vary among workplaces. METHODS: A web-based survey was distributed to 554 expert LC surgeons in Japan, Korea, and Taiwan. The questionnaire covered LC experience, safety measures and recognition of landmarks, decision-making regarding conversion to open/partial cholecystectomy and the implications of this decision. Overall responses were compared among nations, and then stratified by LC experience level (lifetime cases 200-499, 500-999, and ≥1,000). RESULTS: The response rate was 92.6% (513/554); 67 surgeons with ≤199 LCs were excluded, and responses from 446 surgeons were analyzed. We observed significant differences among nations on almost all questions. Differences that remained after stratification by LC experience were on questions related to acceptable duration of surgery, adoption rates of intraoperative cholangiography, the "critical view of safety" technique, identification of Rouvière's sulcus, recognition of the SS-Inner layer theory, and intraoperative judgment to abandon conventional LC. CONCLUSIONS: Even among experts, surgeons' perceptions during LC are workplace-dependent. A novel grading system of surgical difficulty and standardized LC procedures are paramount to generate high-level evidence.