Comparison of Survival Outcomes between Radical Antegrade Modular Pancreatosplenectomy and Conventional Distal Pancreatosplenectomy for Pancreatic Body and Tail Cancer: Korean Multicenter Propensity Score Match Analysis.

(1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure.

Association between hypotension during pancreatectomy and development of postoperative diabetes.

CONTEXT: With advancements in long-term survival after pancreatectomy, post-pancreatectomy diabetes has become a concern, and the risk factors are not established yet. Pancreatic islets are susceptible to ischemic damage, though there is a lack of clinical evidence regarding glycemic deterioration. OBJECTIVE: To investigate association between hypotension during pancreatectomy and development of post-pancreatectomy diabetes. DESIGN: In this retrospective, longitudinal cohort study, we enrolled patients without diabetes who underwent distal pancreatectomy or pancreaticoduodenectomy between January 2005 and December 2018, from two referral hospitals in Korea. MAIN OUTCOME MEASURES: Intraoperative hypotension [IOH] was defined as a 20% or greater reduction in systolic blood-pressure. The primary and secondary outcomes were incident diabetes and postoperative Homeostatic Model Assessment [HOMA] indices. RESULTS: We enrolled 1,129 patients (average age, 59 years; 49% men; 35% distal pancreatectomy). IOH occurred in 83% (median duration, 25 minutes; interquartile range [IQR], 5-65). During a median follow-up of 3.9 years, diabetes developed in 284 patients (25%). The cumulative incidence of diabetes was proportional to increases in the duration and depth of IOH (P < 0.001). For the median duration in an IOH when compared to a reference time of 0 minute, the hazard ratio [HR] was 1.48 (95% CI, 1.14-1.92). The effect was pronounced with distal pancreatectomy compared to pancreaticoduodenectomy. Furthermore, the duration of IOH was inversely correlated with 1-year HOMA beta-cell function (P < 0.002), but not with HOMA insulin resistance. CONCLUSIONS: These results support the hypothesis that IOH during pancreatectomy may elevate risk of diabetes by inducing beta cell insufficiency.

Evolution of laparoscopic liver resection in the last two decades: lessons from 2000 cases at a referral Korean center.

BACKGROUND AND AIMS: Laparoscopic liver resection (LLR) has evolved to become the standard surgical approach in many referral centers worldwide. The aim of this study was to analyze how LLR evolved at a single high-volume referral center since its introduction, more than two decades ago. METHODS: Data from all consecutive LLR between January 2003 and September 2022 at the Seoul National University Bundang Hospital were analyzed. Perioperative outcomes were compared between three time periods, with major technological innovations considered as landmarks: before introduction of laparoscopic-US and CUSA (2003-2006), before (2006-2015) and after (2015-2022) introduction of high-definition scope. RESULTS: During the analyzed time periods the number of technically challenging procedures increased from 39.2 to 61.1% (p < 0.001). The most recent period showed shorter median operation time (from 267.5' to 175', p < 0.001), lower median estimated blood loss (EBL) (from 500 to 300 ml, p < 0.001), lower intraoperative transfusions (from 33.8 to 9.3%, p < 0.001), shorter median postoperative hospital stay (from 12 to 6 days, p < 0.001). The time period, a technical major resection and an underlying liver cirrhosis were found to be the associated with longer operation time (p < 0.001) in the multivariable linear regression analysis, while tumor size, technically major surgeries and liver cirrhosis were associated with higher EBL (p < 0.001). CONCLUSION: During the last two decades, the indications for patients undergoing LLR have expanded significantly, including more and more challenging procedures and frail patients. Despite such challenges, perioperative outcomes improved, although technically major procedures, cirrhotic patients and huge tumors have still to be considered challenging situations.

Intra-arterial lipo-prostaglandin E1 infusion for arterial spasm in liver transplantation: A case report.

BACKGROUND: Hepatic artery obstruction is a critical consideration in graft outcomes after living donor liver transplantation. We report a case of diffuse arterial vasospasm that developed immediately after anastomosis and was managed with an intra-arterial infusion of lipo-prostaglandin E1 (PGE1). CASE SUMMARY: A 57-year-old male with hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma underwent ABO-incompatible living donor liver transplant. The grafted hepatic artery was first anastomosed to the recipient's right hepatic artery stump. However, the arterial pulse immediately weakened. Although a new anastomosis was performed using the right gastroepiploic artery, the patient's arterial pulse rate remained poor. We attempted angiographic intervention immediately after the operation; it showed diffuse arterial vasospasms like 'beads on a string'. We attempted continuous infusion of lipo-PGE1 overnight via an intra-arterial catheter. The next day, arterial flow improved without any spasms or strictures. The patient had no additional arterial complications or related sequelae at the time of writing, 1-year post-liver transplantation. CONCLUSION: Angiographic evaluation is helpful in cases of repetitive arterial obstruction, and intra-arterial infusion of lipo-PGE1 may be effective in treating diffuse arterial spasms.

Laparoscopic anatomical versus non-anatomical liver resection for hepatocellular carcinoma in the posterosuperior segments: a propensity score matched analysis.

Background: Since laparoscopic anatomical resection (LAR) for tumors, especially located in the posterosuperior (PS) segments of the liver remains difficult, laparoscopic non-anatomical resection (LNAR) are generally preferred. To compare the clinical outcomes between LAR and LNAR for hepatocellular carcinoma (HCC) located in the PS segments. Methods: We retrospectively reviewed the data for 1,029 patients who underwent hepatectomy for HCC between 2004 and 2019. Of 167 patients who underwent laparoscopic hepatectomy for HCC in PS segments, 64 underwent LNAR and 103 underwent LAR. Patients were matched one-to-one using propensity score matching (46:46). Results: LNAR was associated with significantly shorter operation time (P=0.001), lower estimated blood loss (P=0.001), lower transfusion rate (P=0.006) and shorter hospital stay (P=0.012) than LAR. The respective 1- ,3-, and 5-year overall survival rates (LAR: 95.3%, 87.1%, and 77.8%; LNAR: 96.7%, 91.6%, and 85.0%; P=0.262) and recurrence-free survival rates (LAR: 75.7%, 70.3%, and 68.9%; LNAR: 81.8%, 58.3%, and 55.3%; P=0.879) were similar. The intrahepatic recurrence rate was significantly higher in LNAR group than in LAR group (78.6% vs. 57.1%, P=0.023), but the post-recurrence treatments differed significantly between the two groups (P=0.016); the re-resection rate was much greater in the LNAR group (45.0% vs. 0%) group. The respective 1-, 3-, and 5-year post-recurrence survival rates were similar in the LAR and LNAR groups (P=0.212). After recurrence, survival in re-resection group was significantly greater than not (P=0.026). Conclusions: LNAR is safe and feasible for HCC located in PS segments, and provided acceptable oncologic outcomes that are comparable to those of LAR. LNAR can be considered for patient with tumor located in PS segment when LAR is not feasible.

Analysis of Recent Improvement of Survival Outcomes in Patients with Pancreatic Cancer Who Underwent Upfront Surgery.

Background/Aims: : Recently, patients with pancreatic cancer (PC) who underwent resection have exhibited improved survival outcomes, but comprehensive analysis is limited. We analyzed the trends of contributing factors. Methods: : Data of patients with resected PC were retrospectively collected from the Korean Health Insurance Review and Assessment Service (HIRA) database and separately at our institution. Cox regression analysis was conducted with the data from our institution a survival prediction score was calculated using the ß coefficients. Results: : Comparison between the periods 2013-2015 (n=3,255) and 2016-2018 (n=3,698) revealed a difference in the median overall survival (25.9 months vs not reached, p<0.001) when analyzed with the HIRA database which was similar to our single-center data (2013-2015 [n=119] vs 2016-2018 [n=148], 20.9 months vs 32.2 months, p=0.003). Multivariable analyses revealed six factors significantly associated with better OS, and the scores were as follows: age >70 years, 1; elevated carbohydrate antigen 19-9 at diagnosis, 1; R1 resection, 1; stage N1 and N2, 1 and 3, respectively; no adjuvant treatment, 2; FOLFIRINOX or gemcitabine plus nab-paclitaxel after recurrence, 4; and other chemotherapy or supportive care only after recurrence, 5. The rate of R0 resection (69.7% vs 80.4%), use of adjuvant treatment (63.0% vs 74.3%), and utilization of FOLFIRINOX or gemcitabine plus nab-paclitaxel (25.2% vs 47.3%) as palliative chemotherapeutic regimen, all increased between the two time periods, resulting in decreased total survival prediction score (mean: 7.32 vs 6.18, p=0.004). Conclusions: : Strict selection of surgical candidates, more use of adjuvant treatment, and adoption of the latest combination regimens for palliative chemotherapy after recurrence were identified as factors of recent improvement.

Development and Validation of a Prognostic Classification Model Predicting Postoperative Adverse Outcomes in Older Surgical Patients Using a Machine Learning Algorithm: Retrospective Observational Network Study.

BACKGROUND: Older adults are at an increased risk of postoperative morbidity. Numerous risk stratification tools exist, but effort and manpower are required. OBJECTIVE: This study aimed to develop a predictive model of postoperative adverse outcomes in older patients following general surgery with an open-source, patient-level prediction from the Observational Health Data Sciences and Informatics for internal and external validation. METHODS: We used the Observational Medical Outcomes Partnership common data model and machine learning algorithms. The primary outcome was a composite of 90-day postoperative all-cause mortality and emergency department visits. Secondary outcomes were postoperative delirium, prolonged postoperative stay (≥75th percentile), and prolonged hospital stay (≥21 days). An 80% versus 20% split of the data from the Seoul National University Bundang Hospital (SNUBH) and Seoul National University Hospital (SNUH) common data model was used for model training and testing versus external validation. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) with a 95% CI. RESULTS: Data from 27,197 (SNUBH) and 32,857 (SNUH) patients were analyzed. Compared to the random forest, Adaboost, and decision tree models, the least absolute shrinkage and selection operator logistic regression model showed good internal discriminative accuracy (internal AUC 0.723, 95% CI 0.701-0.744) and transportability (external AUC 0.703, 95% CI 0.692-0.714) for the primary outcome. The model also possessed good internal and external AUCs for postoperative delirium (internal AUC 0.754, 95% CI 0.713-0.794; external AUC 0.750, 95% CI 0.727-0.772), prolonged postoperative stay (internal AUC 0.813, 95% CI 0.800-0.825; external AUC 0.747, 95% CI 0.741-0.753), and prolonged hospital stay (internal AUC 0.770, 95% CI 0.749-0.792; external AUC 0.707, 95% CI 0.696-0.718). Compared with age or the Charlson comorbidity index, the model showed better prediction performance. CONCLUSIONS: The derived model shall assist clinicians and patients in understanding the individualized risks and benefits of surgery.

Hepatic artery protection using a polyglycolic acid sheet during pancreaticoduodenectomy: A multicenter study.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is the most feared complication after pancreaticoduodenectomy (PD). The most common cause is erosion of the gastroduodenal artery stump. Preventive measures have been previously reported, but a consensus is lacking. The aim of this study was to analyze the preventive effect of reinforcing the hepatic artery using a polyglycolic acid (PGA) sheet during PD. METHODS: A multicenter retrospective study was performed, collecting data from three tertiary hospitals in Korea. Patients receiving PD from January 2016 to December 2021 were included. The primary endpoint was rate of PPH from the hepatic artery. Arterial reinforcement (AR) was performed by wrapping the artery with Neoveil (Gunze Ltd) and applying fibrin glue. The perioperative data of patients who did not receive AR were compared with data of those who received AR. RESULTS: A total of 904 patients were analyzed. The rate of PPH from the hepatic artery was significantly lower in the AR group. (3.5% vs 0.7%, p = .002) In patients with CR-POPF, the 90 day mortality rate of the AR group was less than half that of the non-AR group (7.2% vs 3.5%, p = .455) Risk factor analysis showed CR-POPF to be an independent risk factor for PPH. Arterial reinforcement was shown to be a strong protective factor for PPH (OR 0.20, 95% CI: 0.05-0.72, p = .014). CONCLUSIONS: AR of the hepatic artery using Neoveil and fibrin glue is a simple method that greatly reduces the rate of PPH after PD.

Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives.

Pancreatic adenocarcinoma (PDAC) is one of the most common and lethal human cancers worldwide. Surgery followed by adjuvant chemotherapy offers the best chance of a long-term survival for patients with PDAC, although only approximately 20% of the patients have resectable tumors when diagnosed. Neoadjuvant chemotherapy (NACT) is recommended for borderline resectable pancreatic cancer. Several studies have investigated the role of NACT in treating resectable tumors based on the recent advances in PDAC biology, as NACT provides the potential benefit of selecting patients with favorable tumor biology and controls potential micro-metastases in high-risk patients with resectable PDAC. In such challenging cases, new potential tools, such as ct-DNA and molecular targeted therapy, are emerging as novel therapeutic options that may improve old paradigms. This review aims to summarize the current evidence regarding the role of NACT in treating non-metastatic pancreatic cancer while focusing on future perspectives in light of recent evidence.

Glucose Regulation after Partial Pancreatectomy: A Comparison of Pancreaticoduodenectomy and Distal Pancreatectomy in the Short and Long Term.

BACKGRUOUND: Long term quality of life is becoming increasingly crucial as survival following partial pancreatectomy rises. The purpose of this study was to investigate the difference in glucose dysregulation after pancreaticoduodenectomy (PD) or distal pancreatectomy (DP). METHODS: In this prospective observational study from 2015 to 2018, 224 patients who underwent partial pancreatectomy were selected: 152 (67.9%) received PD and 72 (32.1%) received DP. Comprehensive assessment for glucose regulation, including a 75 g oral glucose tolerance test was conducted preoperatively, and 1, 12, and 52 weeks after surgery. Patients were further monitored up to 3 years to investigate development of new-onset diabetes mellitus (NODM) in patients without diabetes mellitus (DM) at baseline or worsening of glucose regulation (≥1% increase in glycosylated hemoglobin [HbA1c]) in those with preexisting DM. RESULTS: The disposition index, an integrated measure of ß-cell function, decreased 1 week after surgery in both groups, but it increased more than baseline level in the PD group while its decreased level was maintained in the DP group, resulting in a between-group difference at the 1-year examination (P<0.001). During follow-up, the DP group showed higher incidence of NODM and worsening of glucose regulation than the PD group with hazard ratio (HR) 4.29 (95% confidence interval [CI], 1.49 to 12.3) and HR 2.15 (95% CI, 1.09 to 4.24), respectively, in the multivariate analysis including dynamic glycemic excursion profile. In the DP procedure, distal DP and spleen preservation were associated with better glucose regulation. DP had a stronger association with glucose dysregulation than PD. CONCLUSION: Proactive surveillance of glucose dysregulation is advised, particularly for patients who receive DP.

Prognostic Effect of Liver Resection in Extended Cholecystectomy for T2 Gallbladder Cancer Revisited: A Retrospective Cohort Study With Propensity Score-matched Analysis.

OBJECTIVE: This study aimed to evaluate the effect of liver resection on the prognosis of T2 gallbladder cancer (GBC). BACKGROUND: Although extended cholecystectomy [lymph node dissection (LND) + liver resection] is recommended for T2 GBC, recent studies have shown that liver resection does not improve survival outcomes relative to LND alone. METHODS: Patients with pT2 GBC who underwent extended cholecystectomy as an initial procedure and did not reoperation after cholecystectomy at 3 tertiary referral hospitals between January 2010 and December 2020 were analyzed. Extended cholecystectomy was defined as either LND with liver resection (LND+L group) or LND only (LND group). We conducted 2:1 propensity score matching to compare the survival outcomes of the groups. RESULTS: Of the 197 patients enrolled, 100 patients from the LND+L group and 50 from the LND group were successfully matched. The LND+L group experienced greater estimated blood loss ( P <0.001) and a longer postoperative hospital stay ( P =0.047). There was no significant difference in the 5-year disease-free survival (DFS) of the 2 groups (82.7% vs 77.9%, respectively, P =0.376). A subgroup analysis showed that the 5-year DFS was similar in the 2 groups in both T substages (T2a: 77.8% vs 81.8%, respectively, P =0.988; T2b: 88.1% vs 71.5%, respectively, P =0.196). In a multivariable analysis, lymph node metastasis [hazard ratio (HR) 4.80, P =0.006] and perineural invasion (HR 2.61, P =0.047) were independent risk factors for DFS; liver resection was not a prognostic factor (HR 0.68, P =0.381). CONCLUSIONS: Extended cholecystectomy including LND without liver resection may be a reasonable treatment option for selected T2 GBC patients.

The value of analyzing textbook outcomes after laparoscopic hepatectomy-a narrative review.

Background and Objective: Guidelines are required because of the wide variability in care provided to patients with similar characteristics and similar medical conditions. Quality indicators were developed many years ago to assess the quality of care provided by hospitals. Since then, it has become evident that a composite set of factors can better characterize the patient's quality of care. The objectives of this review were to analyze the textbook outcomes (TO) applied in surgery, focusing on laparoscopic hepatectomy. Methods: Data pertaining to quality indicators used in hospitals and their surgical applications were retrieved from medical literature by searching PubMed and Google Scholar for articles published between 1912 and 2022. Search terms included quality indicators, outcome indicators, TOs, TOs after surgery, TOs after hepatectomy, and clinical indicators. Key Content and Findings: Since their inception, TO have been applied to various procedures and their impacts on patients have been assessed. TO and their implications have been studied for a variety of surgical procedures and were recently extended to laparoscopic hepatectomy. TO of laparoscopic left lateral sectionectomy and right hemihepatectomy were recently assessed, and benchmark values have been defined. TO are useful tools for assessing hospital performance and for optimizing the outcomes of patients undergoing laparoscopic hepatectomy. Conclusions: At present, TO only consider surgeon-related factors. However, it is important to include the patient's perspective when defining TO. Although TO were recently applied to laparoscopic hepatectomy, there is still a need to further evaluate their application in this setting. Achieving TO was shown to have a positive impact on long-term outcomes and this needs to be studied for different liver resection procedures.

Impact of Drain Position on Drain Fluid Amylase, Fluid Collection and Postoperative Pancreatic Fistula after Distal Pancreatectomy.

BACKGROUND: The current definition for postoperative pancreatic fistula (POPF) is based on the drain fluid amylase (DFA), and drains must be positioned adequately. We investigated the impact of DFA level, drain position and fluid collection after distal pancreatectomy (DP). METHODS: We performed a retrospective study of 516 patients who underwent DP between June 2004 and December 2018. Patients were excluded if DP was not main procedure, DFA was not measured, postoperative computed tomography (CT) was not performed, or drains were removed before CT. Demographic and perioperative data were analyzed in 422 eligible patients. RESULTS: Of 422 patients, 49(11.6%) had clinically relevant (CR)-POPF and 102(24.2%) had a malpositioned drain. There was no difference in CR-POPF rate between the high and low DFA groups (12.6% vs 10.7%, P = 0.649). Drain malposition was more frequently associated with symptomatic fluid collection and CR-POPF than well-positioned drains. Male sex, high body mass index, transfusion, and drain malposition were CR-POPF risk factors. In subgroup analysis, drain malposition was also an independent risk factor for CR-POPF in the low DFA group. CONCLUSIONS: After DP, the incidence of CR-POPF in the high and low DFA groups was similar and drain malposition increased the risk of CR-POPF. Thus, the ISGPS definition of POPF based on DFA levels is limited in DP, and DFA levels should be interpreted together with the drain position.

Validation of the Anatomical and Biological Definitions of Borderline Resectable Pancreatic Cancer According to the 2017 International Consensus for Survival and Recurrence in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Upfront Surgery.

BACKGROUND: The International Consensus Criteria (ICC) (2017) redefined patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) according to anatomical, biological, and conditional aspects. However, these new criteria have not been validated comprehensively. The aim of this retrospective cohort study was to validate the anatomical and biological definitions of BR-PDAC for oncological outcomes in patients with resectable (R) and BR-PDAC undergoing upfront surgery. METHODS: A total of 404 patients who underwent upfront surgery for R- and BR-PDAC from 2004 to 2020 were included. The patients were classified according to the ICC as follows: resectable (R) (n = 259), anatomical borderline (BR-A) (n = 43), biological borderline (BR-B) (n = 81), and anatomical and biologic borderline (BR-AB) (n = 21). RESULTS: Compared with the R and BR-B groups, the BR-A and BR-AB groups had higher postoperative complication rates (16.5% and 27.2% vs 32.5% and 33.4%; P < 0.001) and significantly lower R0 resection rates (85.7% and 80.2% vs 65.1% and 61.9%; P = 0.003). In contrast, compared with the R and BR-A groups, the BR-B (32.1%) and BR-AB (57.1%) groups had higher early recurrence rates (within postoperative 6 months) (16.5% and 25.6% vs 32.1% and 57.1%; P < 0.001) and significantly lower 3-year recurrence-free survival rates (36.1% and 20.7% vs 12.1% and 7.8%; P < 0.001). CONCLUSION: Anatomically defined BR-PDAC was associated with a higher risk of margin-positive resection and postoperative complication rates, while biologically defined BR-PDAC was associated with higher early recurrence rates and lower survival rates. Thus, the anatomical and biological definitions are useful in predicting the prognosis and determining the usefulness of neoadjuvant therapy.

Validation of original, alternative, and updated alternative fistula risk scores after open and minimally invasive pancreatoduodenectomy in an Asian patient cohort.

BACKGROUND: This study aimed to validate and compare the performance of the original fistula risk scores (o-FRS), alternative (a-FRS), and updated alternative FRS (ua-FRS) after open pancreatoduodenectomy (OPD) and laparoscopic pancreatoduodenectomy (LPD) in an Asian patient cohort. METHODS: Data of 597 consecutive patients who underwent PD (305 OPD, 274 LPD) were collected from two tertiary centers. Model performance was assessed using the area under the receiver operating curve (AUC). RESULTS: The overall AUC values of o-FRS, a-FRS, and ua-FRS were 0.67, 0.69, and 0.68, respectively, which were lower than those of the Western validation. Three FRS systems had similar AUC values in the overall and OPD groups, whereas ua-FRS had a higher AUC than o-FRS in the LPD group. The accuracy of ua-FRS (47.2%) was higher than that of o-FRS (39.0%) and a-FRS (19.5%) overall, but low specificity and low positive predictive value were observed regardless of the operative type across the three FRS systems. In the multivariate analysis, pathology, estimated blood loss, and body mass index were not independent risk factors for CR-POPF in the OPD and LPD groups. CONCLUSIONS: Current FRS systems have some limitations, including a relatively lower performance in an Asian cohort, low positive predictive values, and inclusion of insignificant risk factors.

Arterial reinforcement following pancreatoduodenectomy: The solution to prevent delayed hemorrhage caused by postoperative pancreatic fistula.

PURPOSE: Delayed hemorrhage (DH) is a rare and yet well-known fatal complication associated with postoperative pancreatic fistula (POPF) in pancreatoduodenectomy (PD). The study aimed to investigate whether arterial reinforcement (AR) using polyglycolic acid sheets (PAS) followed by fibrin sealant (FS) to the hepatic artery could prevent DH in the setting of POPF after PD. METHODS: A total of 345 patients underwent PD for periampullary tumors from March 2011 to March 2022. From March 2011 to March 2018, 225 patients underwent PD, and AR was not performed (non-AR group). From April 2018 to March 2022, 120 patients underwent PD, and AR was performed (AR group). AR was achieved by wrapping the proper hepatic artery all the way down to the celiac artery with PAS followed by coating with FS. Demographic profile and various outcomes including DH of these two groups were compared and analyzed retrospectively. RESULTS: In non-AR group, 48 (21.3%) and 12 (5.3%) patients had grade B and C POPF, respectively. In AR group, 26 (21.7%) and four (3.3%) patients had grade B and C POPF, respectively. The incidence of POPF was not statistically significant (p = .702) between the groups. Among the patients with grade B or C POPF, DH occurred in 14 (23.3%) patients in non-AR group and only one patient in AR group (p = .016). Of the 15 patients with DH, four (26.7%) patients died. CONCLUSION: AR using PAS and FS is effective in preventing DH in the setting of POPF.

Continued adjuvant FOLFIRINOX for BRPC or LAPC after neoadjuvant FOLFIRINOX.

PURPOSE: We aimed to assess the role of adjuvant FOLFIRINOX, in comparison with other adjuvant therapy, in patients who received neoadjuvant FOLFIRINOX and surgery for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). METHODS: Our target population was patients with BRPC or LAPC, who received adjuvant therapy following neoadjuvant FOLFIRINOX and surgery between June 2013 and October 2020. Multivariable Cox proportional-hazard model was used to identify factors associated with overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 244 patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX, 79 patients underwent subsequent surgery. Among them, 58 who received adjuvant therapy [median age, 63 years; 33 females (56.9%)] were included. Thirty patients received adjuvant modified FOLFIRINOX (mFOLFIRINOX), while 28 received adjuvant therapy other than FOLFIRINOX. In multivariable analysis, mFOLFIRINOX and post-treatment carbohydrate antigen 19-9 (CA 19-9) were significantly associated with OS and RFS. According to mFOLFIRINOX vs. other adjuvant therapy, median OS was not reached at 37.5 months of follow-up vs. 29.7 months (P = .012); and median RFS was 30.5 vs. 11.0 months (P = .028). According to post-treatment CA 19-9 (< 37 vs. ≥ 37 U/mL), median OS was 46.0 vs. 25.5 months (P = .022); and median RFS was 25.9 vs. 7.6 months (P = .012). CONCLUSION: Continued adjuvant mFOLFIRINOX and post-treatment CA 19-9 level were associated with survival in patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX and surgery. Continued adjuvant mFOLFIRINOX after neoadjuvant FOLFIRINOX could be considered for patients with good performance.

Development and Validation of a Difficulty Scoring System for Laparoscopic Liver Resection to Treat Hepatolithiasis.

Background and Objectives: A difficulty scoring system was previously developed to assess the difficulty of laparoscopic liver resection (LLR) for liver tumors; however, we need another system for hepatolithiasis. Therefore, we developed a novel difficulty scoring system (nDSS) and validated its use for predicting postoperative outcomes. Materials and Methods: This was a retrospective study. We used clinical data of 123 patients who underwent LLR for hepatolithiasis between 2003 and 2021. We analyzed the data to determine which indices were associated with operation time or estimated blood loss (EBL) to measure the surgical difficulty. We validated the nDSS in terms of its ability to predict postoperative outcomes, namely red blood cell (RBC) transfusion, postoperative hospital stay (POHS), and major complications defined as grade ≥IIIa according to the Clavien−Dindo classification (CDC). Results: The nDSS included five significant indices (range: 5−17; median: 8). The RBC transfusion rate (p < 0.001), POHS (p = 0.002), and major complication rate (p = 0.002) increased with increasing nDSS score. We compared the two groups of patients divided by the median nDSS (low: 5−7; high: 8−17). The operation time (210.7 vs. 240.7 min; p < 0.001), EBL (281.9 vs. 702.6 mL; p < 0.001), RBC transfusion rate (5.3% vs. 37.9%; p < 0.001), POHS (8.0 vs. 13.3 days; p = 0.001), and major complication rate (8.8% vs. 25.8%; p = 0.014) were greater in the high group. Conclusions: The nDSS can predict the surgical difficulty and outcomes of LLR for hepatolithiasis and may help select candidates for the procedure and surgical approach.

Gallbladder adenocarcinomas undergo subclonal diversification and selection from precancerous lesions to metastatic tumors.

We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was ERBB2 and TP53 (54.5%), followed by FBXW7 (27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia [BilIN]), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as SMAD4, ROBO1, and DICER1. In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.