Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

Pancreatic juice cytology for diagnosing invasive pancreatic carcinoma/high-grade pancreatic intraepithelial neoplasia without visible tumors on endoscopic ultrasound.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most cases present only indirect imaging findings without visible tumors on endoscopic ultrasound (EUS). Therefore, EUS-guided fine-needle aspiration/biopsy is not applicable. An alternative diagnostic method is pancreatic juice cytology (PJC) via endoscopic naso-pancreatic drainage (ENPD-PJC), which is not the standard practice. This study aimed to investigate ENPD-PJC for diagnosing suspected PDAC/HG-PanIN cases without visible tumors on EUS. METHODS: Data of patients with suspected PDAC/HG-PanIN without visible tumors who underwent PJC were retrospectively evaluated. One PJC sample was collected during endoscopic retrograde pancreatography (ERP-PJC), and 12 samples were collected during ENPD-PJC, 3-hourly for cytological analysis. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC positivity indicated cytologically positive samples. Patients with positive/negative PJC with follow-up for <4-years were excluded as undiagnosed cases. A non-malignant diagnosis was based on histopathological absence/stable imaging findings for ≥4-years. The primary endpoint was to demonstrate that ERP/ENPD-PJC has a higher diagnostic ability than ERP-PJC. RESULTS: Twenty-two patients with histopathologically diagnosed PDAC/HG-PanIN and 31 with a non-malignant diagnosis were enrolled. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC showed sensitivities of 36.4 %, 86.4 %, and 77.3 %, specificities of 93.5 %, 87.1 %, and 93.5 %, and accuracies of 69.8 %, 86.7 %, and 86.7 %, respectively. ERP/ENPD-PJC and ENPD-PJC demonstrated superior sensitivity and accuracy compared to ERP-PJC. A greater occurrence of positive outcomes markedly distinguished true positives from false positives. CONCLUSIONS: ERP/ENPD-PJC and ENPD-PJC had higher diagnostic accuracies for PDAC/HG-PanIN without visible tumors on EUS. ENPD-PJC is recommended for the diagnosis of these lesions.

Evaluation of two-stage hepatectomy using portal vein embolization for colorectal liver metastasis: a retrospective nationwide cohort survey in Japan.

INTRODUCTION: Two-stage hepatectomy (TSH) enables patients to undergo surgery for colorectal liver metastasis (CRLM) which one-stage hepatectomy cannot remove. Although the outcome of TSH has been reported, there is no original report from Japan. The aim of this retrospective study was to evaluate the outcome of TSH in Japanese patients with CRLM. METHODS: We conducted a retrospective cohort study using the nationwide database that included clinical information of 12,519 patients treated with CRLM between 2005 and 2017 in Japan. The primary outcome measure was overall survival. The second outcome measure was progression-free survival. Fisher's exact test, chi-squared test and Mann-Whitney U test were conducted to examine an intergroup difference. Univariate and multivariate analyses were performed using Cox regression model. Survival analysis was performed by Kaplan-Meier method and log-rank test. RESULTS: Of the database, 53 patients undergoing TSH using portal vein embolization (PVE) were identified and analyzed. Their morbidity and in-hospital mortality rate at the second hepatectomy were 26.4% and 0.0%. The mean observation period was 21.8 months. The estimated 1-, 3- and 5-year overall survival rate were 92.5%, 70.8% and 34.7%. Multivariate analyses showed that more than 10 liver nodules significantly increased the mortality risk by 4.2-fold (95%CI 1.224-14.99, P= 0.023). Survival analysis revealed that repeat hepatectomy for disease progression after TSH was superior to chemotherapy in overall survival (mean: 49.6 vs. 18.7, months, P= 0.004). CONCLUSION: In the Japanese cohort, TSH was confirmed to be a safety procedure with acceptable survival outcome. More than 10 liver nodules may be a predictor for unfavorable outcome of patients with CRLM undergoing TSH. Furthermore, repeat hepatectomy can be a salvage treatment for resectable intrahepatic recurrence after TSH.

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Gene Rearrangement and Expression of PRKACA and PRKACB Govern Morphobiology of Pancreatobiliary Oncocytic Neoplasms.

Intraductal oncocytic papillary neoplasms (IOPNs) are distinct from intraductal papillary mucinous neoplasms based on characteristic morphologic and genetic features represented by fusion genes involving PRKACA or PRKACB (PRKACA/B). However, pancreatic and biliary tumors with partial oncocytic features are often encountered clinically, and their molecular features are yet to be clarified. This study included 80 intraductal papillary neoplasms: 32 tumors with mature IOPN morphology (typical), 28 with partial or subclonal oncocytic features (atypical), and 20 without oncocytic features (control). We analyzed PRKACA/B fusion genes, including ATP1B1::PRKACA, DNAJB1::PRKACA, and ATP1B1::PRKACB, by reverse-transcription PCR; mRNA expression of fusion genes and nonrearranged PRKACA/B genes by quantitative reverse-transcription PCR; mutations in KRAS, BRAF, and GNAS by targeted sequencing or droplet digital PCR; and the expression of cyclic adenosine monophosphate (cAMP)-dependent protein kinase catalytic subunits α (PRKACA) and ß (PRKACB), phosphorylated cAMP response element-binding protein, and aberrations of p16, p53, SMAD4, STK11, and ß-catenin by immunohistochemistry. PRKACA/B fusion genes were detected in 100% (32/32) of typical, 46% (13/28) of atypical, and 0% (0/20) of control (P < .05). Expression of PRKACA, PRKACB, and phosphorylated cAMP response element-binding protein was upregulated in neoplasms with PRKACA/B fusion genes (P < .05). mRNA expression of the PRKACA/B fusion genes and protein expression of PRKACA or PRKACB tended to be higher in typical than in atypical cases (mRNA, P = .002; protein expression, P = .054). In some atypical neoplasms with mixed subtypes, PRKACA/B fusion genes were superimposed exclusively on oncocytic components. Typical IOPNs harbored fewer KRAS and GNAS mutations than control samples and fewer alterations in p53 and STK11 than atypical samples (P < .05). In conclusion, PRKACA/B fusion genes not only are the characteristic drivers of IOPNs but also play a crucial role in the development of subclonal oncocytic neoplasms. Moreover, oncocytic morphology is strongly associated with upregulation of PRKACA/B, which may provide clues for potential therapeutic options.

Patlak Reconstruction Using Dynamic 18 F-FDG PET Imaging for Evaluation of Malignant Liver Tumors : A Comparison of HCC, ICC, and Metastatic Liver Tumors.

PURPOSE OF THE REPORT: The aim of this study was to explore the different patterns of dynamic whole-body (D-WB) FDG PET/CT parameters among liver malignancy types as potential diagnostic clues and investigate the association between static and dynamic PET/CT parameters for each tumor histology. PATIENTS AND METHODS: Seventy-one patients with intrahepatic cholangiocarcinoma (ICC), metastatic liver tumor (MLT), or hepatocellular carcinoma (HCC) who underwent D-WB and static dual-time-point FDG PET/CT were enrolled. We obtained Pearson correlation coefficients between the metabolic rate of FDG (MR FDG ; mg/min/ 100ml) or distribution volume of free FDG (DV FDG , %) and static PET/CT parameters. We compared MR FDG and DV FDG values by tumor type and performed receiver operating characteristic analyses for MR FDG and static images. RESULTS: A total of 12 ICC, 116 MLT, and 36 HCC lesions were analyzed. MR FDG and DV FDG showed excellent correlation with early (SUV e ) and delayed SUV max (SUV d ) ( r = 0.71~0.97), but DV FDG in the HCC lesions did not ( r = 0.62 and 0.69 for SUV e and SUV d , respectively) ( P < 0.001 for all). HCC lesions showed significantly lower MR FDG (2.43 ± 1.98) and DV FDG (139.95 ± 62.58) than ICC (5.02 ± 3.56, 207.06 ± 97.13) and MLT lesions (4.51 ± 2.47, 180.13 ± 75.58) ( P < 0.01 for all). The optimal MR FDG could differentiate HCC from ICC and MLT with areas under the curve of 0.84 and 0.80, respectively. Metastatic liver tumor lesions showed the widest distribution of MR FDG and DV FDG values but with no significant difference among most primary sites. CONCLUSIONS: MR FDG was strongly correlated with SUV max in the 3 malignancies and showed utility for differentiating HCC from ICC and MLT. Each tumor type has a different glucose metabolism, and D-WB FDG PET/CT imaging has the potential to visualize those differences.

Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

The Outcome of Salvage Liver Transplantation and Liver Resection for Recurrent Hepatocellular Carcinoma Using the 5-5-500 Rule, Japanese Extended Liver Transplantation Criteria for Hepatocellular Carcinoma.

BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) is limited to Child-Pugh class C patients according to the Japanese HCC treatment algorithm. However, extended criteria of LT for HCC, known as the 5-5-500 rule, were published in 2019. Hepatocellular carcinoma reportedly has a high recurrence rate after primary treatment. We hypothesized that the outcome of recurrent HCC would be improved if the 5-5-500 rule were adopted for patients with recurrent HCC. We, therefore, analyzed the outcomes of surgical treatment (liver resection [LR] and LT) for recurrent HCC using the 5-5-500 rule in our institute. METHODS: Fifty-two patients younger than 70 years of age received surgical treatment for recurrent HCC using our institute's 5-5-500 rule from 2010 to 2019. We divided these patients into the LR and LT groups in the first study. The 10-year overall survival and re-recurrence-free survival were analyzed. The second study analyzed the risk factors of re-recurrence after surgical treatment for recurrent HCC. RESULTS: In the first study, the background characteristics of the 2 groups (LR and LT) showed no significant difference, except for age and Child-Pugh classification. There was no significant difference in the overall survival between groups (P = .35), but the re-recurrence-free survival in the LR group was significantly shorter than that in the LT group (P < .01). In the second study, the male sex and LR were risk factors of re-recurrence after surgical treatment for recurrent HCC. Child-Pugh's class did not contribute to re-recurrence. CONCLUSIONS: To improve the outcomes of recurrent HCC, LT is the better choice, regardless of the Child-Pugh class.

Pancreatic duct epithelial malignancy suggested by large focal pancreatic parenchymal atrophy in cystic diseases of the pancreas.

BACKGROUND: /Objectives: A cystic lesion is common in the pancreas. Focal pancreatic parenchymal atrophy (FPPA) has been reported as a sign of high-grade pancreatic intraepithelial neoplasia/carcinoma in situ (HGP/CIS). Some cystic lesions accompany FPPA. However, the relationship between a cystic lesion, FPPA, and the histopathological background of the pancreatic duct is unknown. METHODS: We retrospectively evaluated the data of 98 patients with a cystic lesion who underwent serial pancreatic juice aspiration cytologic examination (SPACE) because of accompanying FPPA, increased size of the cystic lesion, and pancreatic duct stricture at the base. RESULTS: The clinical diagnosis of a cystic lesion was intraductal papillary mucinous neoplasia (IPMN) and cysts in 72 (73.5%) and 26 (26.5%) patients, respectively. Ninety of the 98 patients (91.8%) had FPPA. Positive results (adenocarcinoma and suspicion) on SPACE were observed in 56 of all cases (57.1%), 48 of IPMN (66.7%), 8 of cysts (30.8%), and 54 of FPPA (59.3%), and were significantly associated with IPMN (p = 0.002) and the large FPPA (>269.79 mm2,p = 0.0001); moreover, these disorders are considerably related (p = 0.0003). Fifty patients (51.0%) with positive results on SPACE underwent surgery, with the histopathological diagnosis of epithelial malignancy in 42 patients (42.9%, 42/50, 84%). Many cystic lesions clinically diagnosed as IPMN were dilated branches covered by pancreatic intraepithelial neoplasia. CONCLUSIONS: Positive results on SPACE were significantly associated with the clinical diagnosis of IPMN and the large FPPA. Moreover, these disorders are significantly related. Surgery owing to positive results could lead to the histopathological diagnosis of HGP/CIS.

Role of EUS combined with a newly modified scoring system to detect pancreatic high-grade precancerous lesions.

Backgrounds and Objectives: Although pancreatic cancer (PC) has an extremely poor prognosis, the 5-year survival rate of patients with pancreatic high-grade precancerous lesion without invasive carcinoma (PHP) is favorable. PHP diagnosis and identification of patients requiring intervention are needed. We aimed to validate a modified PC detection scoring system regarding its detection ability for PHP and PC in the general population. Subjects and Methods: We modified an existing PC detection scoring system that incorporates low-grade risk (LGR) factors (family history, presence of diabetes mellitus [DM] or worsening DM, heavy drinking, smoking, stomach symptoms, weight loss, and pancreatic enzyme) and high-grade risk (HGR) factors (new-onset DM, familial PC, jaundice, tumor biomarkers, chronic pancreatitis, intraductal papillary mucinous neoplasm, cysts, hereditary PC syndrome, and hereditary pancreatitis). Each factor was scored as one point; LGR score ≥3 points and/or HGR score ≥1 point (positive scores) were indicative of PC. The newly modified scoring system incorporated main pancreatic duct dilation as an HGR factor. The PHP diagnosis rate using this scoring system combined with EUS was prospectively analyzed. Results: Among 544 patients with positive scores, 10 had PHP. The diagnosis rates were 1.8% for PHP and 4.2% for invasive PC. Although the number of LGR and HGR factors tended to increase with PC progression, none of the individual factors were significantly different between patients with PHP and those without lesions. Conclusion: The newly modified scoring system evaluating multiple factors associated with PC could potentially identify patients with higher risk of PHP or PC.

The outcome of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 for resectable pancreatic ductal adenocarcinoma.

Aim: This study was performed to evaluate the efficacy of a multidisciplinary approach incorporating neoadjuvant chemoradiotherapy with S1 (S1-NACRT) for resectable pancreatic ductal adenocarcinoma. Methods: The medical records of 132 patients who received S1-NACRT for resectable pancreatic ductal adenocarcinoma from 2010 to 2019 were reviewed. The S1-NACRT regimen consisted of S1 at a dose of 80-120 mg/body/day together with 1.8 Gy of radiation in 28 fractions. The patients were re-evaluated 4 weeks after S1-NACRT completion, and a pancreatectomy was then considered. Results: Adverse events of S1-NACRT ≥grade 3 occurred in 22.7% of the patients, and 1.5% discontinued therapy. Of the 112 patients who underwent a pancreatectomy, 109 underwent R0 resection. Adjuvant chemotherapy with relative dose intensity ≥50% was administered to 74.1% of the patients who underwent resection. The median overall survival of all patients was 47 months, and the median overall survival and recurrence-free survival of patients who underwent resection was 71 and 32 months, respectively. According to the multivariate analyses of prognostic factors for overall survival in patients who underwent resection, negative margin status (hazard ratio: 0.182; P = 0.006) and relative dose intensity of adjuvant chemotherapy ≥50% (hazard ratio 0.294; P < 0.001) were independent prognostic factors of overall survival. Conclusions: A multidisciplinary approach incorporating S1-NACRT for resectable pancreatic ductal adenocarcinoma demonstrated acceptable tolerability and good local control and resulted in comparable survival benefits.

Laparoscopic left hepatectomy in a goat as a training model for laparoscopic anatomic liver resection: results of training courses with a total of 70 goats.

BACKGROUND: To create a suitable animal model for the training of laparoscopic anatomic liver resection, we performed left hepatectomy using a goat and found its suitability. We have since started using goats for wet-lab training and have gradually standardized the relevant procedures. Herein, we report our standardized training procedures using a goat and discuss its feasibility as a novel training model. METHODS: The standardized wet-lab training courses of laparoscopic liver resection conducted on 62 tables with a total of 70 goats were reviewed. The training course began by encircling the hepatoduodenal ligament for the Pringle maneuver, which was repeated during the parenchymal dissection. Following partial liver resection of the left lateral section, left hepatectomy was performed by a standardized procedure for humans in which the liver was split, exposing the entire length of the middle hepatic vein trunk from the dorsal side after extrahepatic transection of the left Glissonean pedicle. If a goat deceased before initiating left hepatectomy, the training was restarted with a new goat. The surgical procedures were performed by surgeons of varying skill levels. RESULTS: A total of 184 surgeons including 10 surgical residents participated in the training. Partial liver resection was initiated in 62 tables, with 8 (13%) dying during or after the procedure of partial liver resection. Subsequently, left hepatectomy was initiated in 61 and completed in 59 tables (98%), regardless of whether the goat survived or deceased, and was not completed in 2 tables (3%) due to time limitation. In 14 tables (23%), the goats deceased during the procedure, however, the procedure was completed. The causes of death were multifactorial, including massive bleeding, reperfusion injury after the Pringle maneuver, and carbon dioxide gas embolism. CONCLUSIONS: Left hepatectomy in a goat is useful as a training model for laparoscopic anatomic liver resection.

Validation study of the JSHBPS nomogram for patients with colorectal liver metastases who underwent hepatic resection in the recent era - a nationwide survey in Japan.

BACKGROUND: The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs. METHODS: Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index). RESULTS: In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group. CONCLUSIONS: The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients.

Comprehensive data of 4502 patients newly diagnosed with colorectal liver metastasis between 2015 and 2017, and prognostic data of 2427 patients newly diagnosed with colorectal liver metastasis in 2013 and 2014: Third report of a nationwide survey in Japan.

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously.

An International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery (TOLS).

OBJECTIVE: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. BACKGROUND: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. METHODS: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. RESULTS: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. CONCLUSIONS: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study.

BACKGROUND: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. METHODS: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. RESULTS: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255). CONCLUSIONS: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Left hepatectomy with suprahepatic inferior vena cava resection and reconstruction under veno-arterial extracorporeal membrane oxygenation for intrahepatic cholangiocarcinoma: a case report.

BACKGROUND: Curative surgery is the most effective treatment for intrahepatic cholangiocarcinoma (ICC). When an ICC involves the suprahepatic inferior vena cava (IVC), hepatectomy with suprahepatic IVC resection and reconstruction is challenging. For reconstruction of the suprahepatic IVC, total hepatic vascular exclusion (THVE), veno-venous bypass, and/or in situ hypothermic portal perfusion are required, but mortality and morbidity remain high. CASE PRESENTATION: We present a 73-year-old woman with mass-forming ICC which invaded the suprahepatic IVC and middle hepatic vein. Left hepatectomy, suprahepatic IVC resection, and reconstruction with an artificial graft were successfully performed during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) to maintain blood pressure. While clamping the IVC diagonally, the right hepatic vein confluence could be preserved. No congestion in the right liver was seen; therefore, there was no requirement for the Pringle maneuver or THVE during reconstruction. No morbidity or mortality was seen after surgery. CONCLUSIONS: Hepatectomy with suprahepatic IVC resection and reconstruction under V-A ECMO can be performed safely. When an ICC invades the suprahepatic IVC, V-A ECMO during resection and reconstruction of the suprahepatic IVC with an artificial graft is recommended as one of the options.

Intrahepatic Cholangiocarcinoma With Neither Intrahepatic Metastasis Nor Lymph Node Metastasis Is the Optimal Indication for Hepatectomy With Adjuvant Therapy.

Background/Aim: The optimal indication of hepatectomy with adjuvant therapy for intrahepatic cholangiocarcinoma (ICC) has not been evaluated in detail. Patients and Methods: We retrospectively studied 224 patients with ICC who underwent hepatectomy between 2000 and 2019. Prognostic factors for overall survival (OS) were evaluated by univariate and multivariate analysis. A total of 127 patients were treated with adjuvant therapy (62 patients with chemotherapy and 65 patients with immunotherapy) after hepatectomy, and 97 patients were treated with hepatectomy alone. Results: Intrahepatic metastasis (IM), lymph node metastasis (LNM) of ICC, adjuvant chemotherapy, and adjuvant immunotherapy were significant prognostic factors for OS on multivariate analysis. In 127 patients with neither IM nor LNM, the 5-year OS rate was significantly higher in 36 patients with adjuvant chemotherapy (81%) and in 34 patients with adjuvant immunotherapy (68%) than in 57 patients with hepatectomy alone (45%). Conclusion: The absence of IM or LNM is the optimal indication for hepatectomy with adjuvant therapy in patients with ICC.

Randomized phase III trial of intravenous and intraperitoneal paclitaxel with S-1 versus gemcitabine plus nab-paclitaxel for pancreatic ductal adenocarcinoma with peritoneal metastasis (SP study).

The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ).

Application of a novel surgical difficulty grading system during laparoscopic cholecystectomy.

BACKGROUND: Prevention of bile duct injury and vasculo-biliary injury while performing laparoscopic cholecystectomy (LC) is an unsolved problem. Clarifying the surgical difficulty using intraoperative findings can greatly contribute to the pursuit of best practices for acute cholecystitis. In this study, multiple evaluators assessed surgical difficulty items in unedited videos and then constructed a proposed surgical difficulty grading. METHODS: We previously assembled a library of typical video clips of the intraoperative findings for all LC surgical difficulty items in acute cholecystitis. Fifty-one experts on LC assessed unedited surgical videos. Inter-rater agreement was assessed by Fleiss's κ and Gwet's agreement coefficient (AC). RESULTS: Except for one item ("edematous change"), κ or AC exceeded 0.5, so the typical videos were judged to be applicable. The conceivable surgical difficulty gradings were analyzed. According to the assessment of difficulty factors, we created a surgical difficulty grading system (agreement probability = 0.923, κ = 0.712, 90% CI: 0.587-0.837; AC2  = 0.870, 90% CI: 0.768-0.972). CONCLUSION: The previously published video clip library and our novel surgical difficulty grading system should serve as a universal objective tool to assess surgical difficulty in LC.