Metabolic tumor burden as a prognostic indicator after neoadjuvant chemotherapy in pancreatic cancer.

BACKGROUND: There is no standardized assessment for evaluating response although neoadjuvant chemotherapy (NAT) is widely accepted for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). This study was aimed to evaluate NAT response using positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG-PET/CT) parameters alongside carbohydrate antigen (CA) 19-9 levels. METHODS: Patients who underwent surgery after NAT for BRPC and LAPC between 2017 and 2021 were identified. The study assessed the prognostic value of PET-derived parameters after NAT, determining cutoff values using the K-adaptive partitioning method. It created four groups based on the elevation or normalization of PET parameters and CA19-9 levels, comparing survival between these groups. RESULTS: Of 200 eligible patients, FOLFIRINOX and gemcitabine-based NAT were administered in 167 and 34 patients, respectively (mean NAT cycles, 8.3). In a multivariate analysis, metabolic tumor volume (MTV) demonstrated the most robust performance in assessing response (HR 3.11, 95% CI 1.73-5.58, P <0.001) based on cut-off value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels <37 IU/L (median survival; 35.5 vs. 20.9 mo, P <0.001) and CA19-9 levels ≥37 IU/L (median survival; 34.3 vs. 17.8 mo, P =0.03). In patients suspected to be Lewis antigen negative, predictive performance of MTV was found to be limited ( P =0.84). CONCLUSION: Elevated MTV is an influential prognostic factor for worse survival, regardless of post-NAT CA19-9 levels. These results could be helpful in identifying patients with a poor prognosis despite normalization of CA19-9 levels after NAT.

Clinical outcomes of second-line therapy following disease progression on first-line modified FOLFIRINOX for borderline resectable and locally advanced pancreatic adenocarcinoma.

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.

Clinical implication of the geometric location (fundal end versus cystic ductal end) of gallbladder cancer.

BACKGROUND: Management of early-stage gallbladder cancer is becoming more important as the rate of early detection is increasing. Although there have been many studies about the clinical implication of the invasion depth or peritoneal/hepatic location of gallbladder cancers, there is no study on the clinical implication of the geometric location of cancer along the longitudinal length of the gallbladder. METHODS: The location of gallbladder cancer was defined as the geometric center of the primary site of a tumour, which lies on the longitudinal diameter of the surgical specimens. We compared the oncologic outcomes following surgery between gallbladder cancers located on the fundal end and those located on the cystic ductal end. We also analysed patients with stage 1 gallbladder cancer who recurred after surgery. RESULTS: A total of 575 patients with gallbladder cancer were included in this study. Patients with gallbladder cancer on the cystic ductal end had significantly lower rates of recurrence-free survival (P = 0.016) and overall survival (P = 0.023) compared to those with gallbladder cancer on the fundal end. Among 90 patients with stage 1 gallbladder cancer, three patients had a recurrence, all of whom had cystic ductal end gallbladder cancer and showed cystic duct invasion or concomitant xanthogranulomatous cholecystitis in permanent pathology. CONCLUSIONS: Gallbladder cancers on the cystic ductal end had worse postoperative oncologic outcomes compared with those on the fundal end.

Comparison of Surgical Outcomes of Laparoscopic and Robotic Surgery in Adult Choledochal Cysts.

Background: Minimally invasive surgery (MIS) for cyst excision and Roux-en-Y hepaticojejunostomy (HJ) is widely performed for adult choledochal cysts. Few articles compared the robotic and laparoscopic approaches for choledochal cysts. Methods: Between 2014 and 2022, 157 patients who underwent MIS for choledochal cysts were retrospectively analyzed. Perioperative outcomes of patients who underwent totally robotic surgery, robot-assisted surgery, and laparoscopic surgery were compared, respectively. Also, postoperative outcomes of patients with robotic reconstruction and laparoscopic reconstruction during HJ were compared. Results: Perioperative outcomes were comparable between robotic and laparoscopic groups. The suturing technique for the anterior and posterior walls of the HJ differed significantly between the robotic and laparoscopic reconstruction groups (P = .001). However, there were no significant differences in postoperative outcomes, including total complications (P = .304), major complications (P = .411), and postoperative interventions (P = .411), between the two groups. Conclusions: The robotic and laparoscopic approaches for adult choledochal cysts have comparable surgical outcomes. In the MIS era, robotic surgery could be an alternative surgical option for adult choledochal cysts.

Evaluation of postoperative outcomes of minimally invasive distal pancreatectomy for left-sided pancreatic tumors based on the modified frailty index: a retrospective cohort study.

BACKGROUND: This study compared the postoperative outcomes of minimally invasive distal pancreatectomy (MIDP) for left-sided pancreatic tumors based on the modified frailty index (mFI). MATERIALS AND METHODS: This retrospective study included 2212 patients who underwent MIDP for left-sided pancreatic tumors between 2005 and 2019. Postoperative outcomes, including complications (morbidity and mortality), were analyzed using mFI, and the participants were divided into two groups: frail ( n =79) and nonfrail ( n =2133). A subanalysis of 495 MIDPs for pancreatic ductal adenocarcinoma was conducted to compare oncological outcomes. RESULTS: Clinically relevant postoperative pancreatic fistula was significantly higher in the frail group than in the nonfrail group. A significant between-group difference was observed in overall complications with Clavien-Dindo classification grade ≥III. Furthermore, the proportion of all complications before readmission was higher in the frail group than in the nonfrail group. Among all readmitted patients, the frail group had a higher number of grade ≥IV patients requiring ICU treatment. The frail group's 90-day mortality was 1.3%; the difference was statistically significant (nonfrail: 0.3%, P =0.021). In the univariate and multivariate logistic regression analyses, mFI ≥0.27 (odds ratio 3.231, 95% CI: 1.889-5.523, P <0.001), extended pancreatectomy, BMI ≥30 kg/m 2 , male sex, and malignancy were risk factors for Clavien-Dindo classification grade ≥III. CONCLUSION: mFI is a potential preoperative tool for predicting severe postoperative complications, including mortality, in patients who have undergone MIDP for left-sided tumors.

Outcomes of Distal Pancreatectomy With Celiac Axis Resection for Pancreatic Cancer.

OBJECTIVES: This study aimed to show the clinical and oncologic outcomes of distal pancreatectomy with celiac axis resection (DP-CAR) from a high-volume single center and analyze them from diverse perspectives. METHODS: Forty-eight patients with pancreatic body and tail cancer with celiac axis involvement who underwent DP-CAR were included in the study. The primary outcome was morbidity and 90-day mortality, and the secondary outcome was overall survival and disease-free survival. RESULTS: Morbidity (Clavien-Dindo classification grade ≥3) occurred in 12 patients (25.0%). Thirteen patients (27.1%) had pancreatic fistula grade B and 3 patients (6.3%) had delayed gastric emptying. The 90-day mortality was 2.1% (n = 1). The median overall survival was 25.5 months (interquartile range, 12.3-37.5 months) and median disease-free survival was 7.5 months (interquartile range, 4.0-17.0 months). During the follow-up period, 29.2% of participants survived for up to 3 years and 6.3% survived for up to 5 years. CONCLUSIONS: Despite its associated morbidity and mortality, DP-CAR should be considered as the only therapeutic option for pancreatic body and tail cancer with celiac axis involvement when carried out on carefully selected patients performed by a highly experienced group.

Robotic versus laparoscopic liver resections for hepatolithiasis: an international multicenter propensity score matched analysis.

INTRODUCTION: Minimally invasive liver resection (MILR) is widely recognized as a safe and beneficial procedure in the treatment of both malignant and benign liver diseases. Hepatolithiasis has traditionally been reported to be endemic only in East Asia, but has seen a worldwide uptrend in recent decades with increasingly frequent and invasive endoscopic instrumentation of the biliary tract for a myriad of conditions. To date, there has been a woeful lack of high-quality evidence comparing the laparoscopic (LLR) and robotic (RLR) approaches to treatment hepatolithiasis. METHODS: This is an international multicenter retrospective analysis of 273 patients who underwent RLR or LRR for hepatolithiasis at 33 centers in 2003-2020. The baseline clinicopathological characteristics and perioperative outcomes of these patients were assessed. To minimize selection bias, 1:1 (48 and 48 cases of RLR and LLR, respectively) and 1:2 (37 and 74 cases of RLR and LLR, respectively) propensity score matching (PSM) was performed. RESULTS: In the unmatched cohort, 63 (23.1%) patients underwent RLR, and 210 (76.9%) patients underwent LLR. Patient clinicopathological characteristics were comparable between the groups after PSM. After 1:1 and 1:2 PSM, RLR was associated with less blood loss (p = 0.003 in 1:2 PSM; p = 0.005 in 1:1 PSM), less patients with blood loss greater than 300 ml (p = 0.024 in 1:2 PSM; p = 0.027 in 1:1 PSM), and lower conversion rate to open surgery (p = 0.003 in 1:2 PSM; p < 0.001 in 1:1 PSM). There was no significant difference between RLR and LLR in use of the Pringle maneuver, median Pringle maneuver duration, 30-day readmission rate, postoperative morbidity, major morbidity, reoperation, and mortality. CONCLUSION: Both RLR and LLR were safe and feasible for hepatolithiasis. RLR was associated with significantly less blood loss and lower open conversion rate.

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX.

PURPOSE: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. RESULTS: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). CONCLUSION: Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Laparoscopic versus open pancreaticoduodenectomy with major vein resection for pancreatic head cancer.

BACKGROUND/PURPOSE: Laparoscopic pancreaticoduodenectomy (PD) with major vein resection is a challenging procedure. Herein, we evaluated the feasibility and safety of laparoscopic vein resection in pancreatic head cancer with portal vein/superior mesenteric vein (PV/SMV) invasion, and compared the survival rate following laparoscopic surgery with that following open surgery. METHODS: We retrospectively reviewed the electronic medical records of all patients with pancreatic head cancer who underwent surgery performed by a single surgeon from January 2015 to December 2017. Kaplan-Meier curves were plotted to compare the disease-free survival, while Cox-proportional hazard models were used to analyze prognostic factors for survival. RESULTS: Among 76 patients, 63 underwent open PD and 13 underwent laparoscopic PD with PV/SMV resection. There was no significant difference in the rate of complications, including portal vein stenosis and portal vein thrombus, recurrence of tumors, or pathological outcomes after surgery between the groups. There was also no significant difference in disease-free survival (p = .803) between the two groups. Additionally, the surgical method was not an independent prognostic factor for disease-free survival. CONCLUSIONS: Laparoscopic PD with major vein resection can be feasibly performed in select patients with abutment and focal narrowing of the PV/SMV in pancreatic head cancer.

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.

Mixed adenoneuroendocrine carcinoma of the ampulla of Vater: Three case reports and a literature review.

Mixed adenoneuroendocrine carcinoma is defined as a tumor with a mixture of adenocarcinoma components and neuroendocrine neoplasm components. Each of these two components of mixed adenoneuroendocrine carcinoma accounts for at least 30% of all tumors. Mixed adenoneuroendocrine carcinoma might be located in the ampulla of Vater, a very rare location compared to other organs. Thus, its treatment and prognosis plans have not been established yet. We report three cases of mixed adenoneuroendocrine carcinoma occurring in the ampulla of Vater. Each patient had a different clinical course. In general, difficulty in preoperative diagnosis, risk of early recurrence, and poor disease course were main hallmarks of mixed adenoneuroendocrine carcinoma arising from the ampulla of Vater. However, one patient in this case report survived although she did not receive adjuvant chemotherapy due to her old age. Therefore, it is important to establish a careful treatment strategy for mixed adenoneuroendocrine carcinoma arising from the ampulla of Vater.

Minimally invasive versus open pancreaticoduodenectomy for distal bile duct cancer: an inverse probability of treatment weighting analysis of outcomes.

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) has been extended to periampullary cancers, but the oncologic outcome of MIPD for distal bile duct cancer (DBDC) has not been confirmed yet. METHODS: Patients who underwent pancreaticoduodenectomy (PD) for DBDC of stage I-IIb from 2015 to 2019 at a tertiary referral center were identified and divided into open PD (OPD) and MIPD groups, the latter including laparoscopic and robotic procedures. Survival was compared between the two groups after inverse probability of treatment weighting (IPTW) using predetermined factors, and exploratory mediation analysis was performed using surgery-derived outcomes. RESULTS: MIPD (n = 81) group had more female patients (46.9% vs 31.6%, p = 0.011) and longer operation time (366.2 min vs. 279.1 min, p < 0.001) than the OPD (n = 288) group before IPTW. Otherwise, intraoperative and immediate postoperative outcomes were comparable between the two groups. In oncologic outcomes, MIPD group showed comparable 3-year overall survival (78.2% vs 75.0%, p = 0.062) and recurrence-free survival (51.2% vs 53.4%, p = 0.871) rates with OPD group before IPTW, and MIPD was not related with survival (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.29-1.26, p = 0.18) and recurrence (HR 1.01, 95% CI 0.67-1.53, p = 0.949) after IPTW with consideration of potential mediators. Sensitivity analysis using propensity score matching also showed similar results for survival (HR 0.68, 95% CI 0.32-1.44, p = 0.312) and recurrence (HR 1.12, 95% CI 0.67-1.88, p = 0.653). CONCLUSION: MIPD and OPD groups showed similar postoperative and oncologic outcomes. MIPD could be a considerable treatment option without oncological compromise in high-volume centers.

Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma.

Background: Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCap versus Gem in an Asian population. Methods: This retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea. Results: Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66 versus 63 years, p = 0.001); otherwise, the groups had similar baseline characteristics. With median follow-up durations of 39.4 [95% confidence interval (CI), 36.9-45.0] and 39.4 (95% CI, 34.7-41.6) months in the Gem and GemCap groups, the median OS was 36.8 (95% CI, 29.7-43.5) and 46.1 (95% CI, 31.5-not reached) months in the Gem and GemCap groups, respectively [unadjusted hazard ratio (HR) = 0.7; 95% CI, 0.5-1.0; p = 0.07). The median recurrence-free survival was 14.3 (95% CI, 12.9-17.7) and 17.0 (95% CI, 13.3-28.2) months, respectively (p = 0.5). Hand-foot skin reactions (any grade, 15.3% versus 0.6%; p < 0.001), neutropenia (78.6% versus 67.7%, p = 0.04) and thrombocytopenia (30.5% versus 20.5%, p = 0.04) were more common in the GemCap group. Multivariate analysis revealed adjuvant GemCap - compared with Gem - to be significantly associated with better OS (adjusted HR = 0.6; 95% CI, 0.4-0.9; p = 0.01). Otherwise, moderate or poor histological grade, lymph node positivity, positive resection margin, and elevated CA 19-9 (>median) were significantly associated with worse OS. Conclusions: Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.

Predictive Performance of Current Nodal Staging Systems in Various Categories of Pancreatic Cancer.

BACKGROUND: Nodal staging systems (NSS) for pancreatic ductal adenocarcinoma (PDAC) classify patients on the basis of number of metastatic lymph nodes (MLN), metastatic/retrieved lymph node ratio (LNR), and log odds of positive LN (LODDS). The relative prognostic performance of these NSS, however, remains unclear. PATIENTS AND METHODS: We identified 2584 patients who underwent surgery for PDAC between 2010 and 2019. Subgroups of each staging system were classified using K-adaptive partitioning method and assessed by comparing time-dependent areas under the curve (AUC) 5 years after surgery. RESULTS: Patients were subgrouped by MLN (0, 1-3, ≥ 4), LNR (0, 0-0.23, > 0.23), and LODDS (< - 3.5, - 3.5 to - 0.970, > - 0.97). All three NSS were independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS). The AUCs for OS were comparable for the MLN (0.622), LNR (0.609), and LODDS (0.596) systems. Subgroup evaluation based on 12 retrieved lymph nodes (RLN), R1 resection, and extent of resection showed that the AUCs of the MLN and LNR NSS were comparable for OS and RFS regardless of the number of RLNs, R1 resection, and extent of resection. By contrast, the AUCs of the LODDS NSS were lower. CONCLUSION: The NSS based on the number of MLN is the best prognostic indicator, with prognostic performance comparable to the other NSS and greater convenience for practical use. This NSS was applicable regardless of the numbers of RLN, R1 resection, and extent of resection.

Clinical Outcomes Between a Minimally Invasive and Open Extended Cholecystectomy for T2 Gallbladder Cancer: A Propensity Score Matching Analysis.

Background: Although a minimally invasive extended cholecystectomy (MIEC) for T2 gallbladder cancer (T2 GBC) has been performed in many experienced centers, no oncologic comparison with open extended cholecystectomy (OEC) has yet been reported. Methods: T2 GBC patients who underwent MIEC (n = 60) or OEC (n = 135) were enrolled. We used propensity score matching (PSM) using pre- and intraoperative variables. Short- and long-term outcomes were then compared before and after PSM. Results: Before PSM, OEC patients more frequently showed completion of surgery after a simple cholecystectomy (standardized mean difference [SMD] = -0.551), and lymph node enlargement on preoperative computed tomography (SMD = -0.471). PSM was used to select 56 patients from each of the 2 patient groups. MIEC patients showed comparable complication rate (7.1% versus 12.5%, P = .365) and shorter hospital stay (5.7 days versus 9.8 days, P < .001). The median follow-up period was 26.2 months, and 5-year overall survival (OS) rate (96.8% versus 91.1%, P = .464) and 5-year recurrence free survival (RFS) (54.7% versus 44.4%, P = .580) outcomes were still comparable between MIEC and OEC groups. Conclusion: MIEC have advantages such as early recovery and comparable short-term outcomes compared with OEC. MIEC showed comparable OS and RFS outcomes compared with OEC. MIEC is a safe option without oncological compromise for T2 GBC.

Comparing survival rate and appropriate surgery methods according to tumor location in T2 gallbladder cancer.

BACKGROUND: The survival outcomes and optimal extent of surgery of T2 gallbladder cancers remain controversial. We aimed to investigate the difference in overall/disease-free survival rates and assess the prognosis of T2 gallbladder cancers. METHODS: We retrospectively reviewed electronic medical records of 147 patients who underwent surgical resection for pathologically confirmed T2 gallbladder cancer between January 2003 and December 2012. Patients were categorized into two groups according to the tumor location (T2a vs. T2b) and three groups according to surgery method (simple cholecystectomy, cholecystectomy with lymph node dissection, and extended cholecystectomy). We compared the overall and disease-free survival rates according to T2 subgroups and surgery methods. Cox proportional hazard analysis was performed to evaluate prognostic factors for the overall survival of T2 gallbladder cancer. RESULTS: Of all patients, 40 (27.2%) and 107 (72.8%) were diagnosed with T2a and T2b gallbladder cancers, respectively. The 5-year overall and disease-free survival rates were 75.0% vs. 73.8% (p = 0.653) and 72.5% vs. 70.1% (p = 0.479) in T2a and T2b gallbladder cancers, respectively. There was no difference in the survival rate among T2a gallbladder cancer according to the surgery method. However, in T2b gallbladder cancer, extended cholecystectomy showed a better overall survival than simple cholecystectomy and cholecystectomy with lymph node dissection groups (p = 0.043 and p = 0.003, respectively). CONCLUSIONS: There is no difference in overall and disease-free survival rates according to the location of T2 gallbladder cancers. Extended cholecystectomy increases overall survival rate, especially in T2b gallbladder cancers.

Usefulness of Inflammation-Based Prognostic Scores in Patients with Surgically Treated Pancreatic Ductal Adenocarcinoma.

In this study, we evaluated the prognostic value of inflammation-based prognostic scores in patients undergoing curative surgery for pancreatic ductal adenocarcinoma (PDAC). A retrospective analysis was conducted for 914 patients undergoing curative surgical resection for PDAC between January 2011 and April 2016. Inflammation-based scores of modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio were assessed. mGPS was classified as high (1 or 2) or low (0). Median age was 63 (range, 33-88) years; 538 patients (58.9%) were male. A high mGPS was independently associated with poor overall survival (OS) and disease-free survival (DFS) (median OS: 25.4 months vs. 20.4 months, p = 0.001; median DFS: 11.6 months vs. 9.3 months, p = 0.002), poor OS in patients with TNM stage I PDAC (44 months vs. 24.8 months, p = 0.001), and poor OS and DFS in patients with tumors located at the pancreatic head or uncinate process (OS: 25.4 months vs. 20.4 months; p = 0.007, DFS: 11.4 months vs. 8.87 months; p = 0.005). Preoperative mGPS was a significant prognostic factor for PDAC after curative resection; thus, mGPS can be a useful prognostic predictive factor in patients with TNM stage I PDAC, especially for tumors located at the head and uncinate.

Comparison of Characteristics and Survival Rates of Resectable Pancreatic Ductal Adenocarcinoma according to Tumor Location.

The impact of tumor location on patient survival in pancreatic ductal adenocarcinoma (PDAC) remains controversial. This study investigated the association between primary tumor location and survival rates for resectable PDAC. Additionally, we assessed if this association remains consistent across categories of the Tumor-Node-Metastasis staging system. We analyzed 2471 patients who underwent surgical resection between 2000 and 2018 at a single center. Subgroup analysis was performed according to the Tumor-Node-Metastasis staging system. Among the group, 67.9% (1677 patients) had pancreatic head cancer (PHC) and 32.1% (794 patients) had pancreatic body/tail cancer (PBTC). Patients with PHC had worse overall survival and worse disease-free survival than those with PBTC. Patients with PHC had worse survival in stage IB and stage IIB than those with PBTC. No significant difference was observed for stages IA, IIA, and III. Multivariate analysis showed that elevated CA 19-9, mGPS, a longer hospital stay, complication, accompanying vein resection, larger tumor size, worse differentiation, higher TNM stage (stage IIB, III, IV), presence of LVI, and positive resection margin were risk factors for poor survival after resection. In resectable PDAC, patients with PHC had worse overall and disease-free survival than those with PBTC. However, tumor location was not an independent prognostic factor for PDAC.

Surgical outcomes are hampered after endoscopic ultrasonography-guided ethanol lavage and/or Taxol injection in cystic lesions of the pancreas.

BACKGROUNDS/AIMS: Endoscopic ultrasonography-guided ethanol lavage and Taxol injection (EUS-ELTI) for pancreatic cystic lesions have been recently performed in some medical centers. The aim of this study was to optimize patient selection and analyze outcomes of patients who underwent surgeries after EUS-ELTI for pancreatic cystic lesions. METHODS: Among 310 patients who underwent EUS-ELTI between January 2007 and December 2014, 23 underwent surgeries after EUS-ELTI owing to incomplete treatment and/or adverse events. Surgical outcomes of patients who underwent surgeries after EUSELTI were evaluated. Clinical outcomes of patients who underwent surgeries after EUS-ELTI were then retrospectively compared with those of patients who underwent upfront surgery for left-sided pancreatic lesions without an EUS-ELTI procedure. RESULTS: The pathology revealed degenerated cysts in 12 patients, mucinous cyst neoplasms in five, neuroendocrine tumors in two, intraductal papillary mucinous neoplasm (IPMN) in one, solid pseudopapillary tumor in one, pancreatic ductal adenocarcinoma arising from an IPMN in one, and hepatoid carcinoma in one. Twelve patients underwent laparoscopic distal pancreatectomy and five patients underwent open distal pancreatectomy. When clinical outcomes were retrospectively compared between patients who underwent laparoscopic distal pancreatectomy after EUS-ELTI and those who did not receive an EUS-ELTI procedure, the spleen-preserving rate was 0% in the EUS-ELTI group and 61.7% (365/592) in the control group (p < 0.001). CONCLUSIONS: Surgical outcomes are compromised after EUS-ELTI for cystic tumor of the pancreas. Further studies are needed to investigate the efficacy and safety of the EUS-ELTI procedure.

PGC-1α is downregulated in a mouse model of obstructive cholestasis but not in a model of liver fibrosis.

Several studies have indicated that cholestatic liver damage involves mitochondria dysfunction. However, the precise mechanism by which hydrophobic bile salts cause mitochondrial dysfunction is not clear. In this study, we intended to determine the pathogenesis of cholestatic liver injury associated with peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α). A mouse model of cholestatic liver disease was generated by surgical ligation of the bile duct (BDL), and a mouse model of fibrosis was developed through serial administration of thioacetamide. After obtaining liver specimens on scheduled days, we compared the expression of the antioxidant enzymes (superoxide dismutase 2 [SOD2], catalase, and glutathione peroxidase-1[GPx-1]) and PGC-1α in livers from mice with fibrosis and cholestasis using western blotting, immunohistochemistry, and immunofluorescence. We found that cholestatic livers exhibit lower expression of antioxidant enzymes, such as SOD2, catalase, and PGC-1α. In contrast, fibrotic livers exhibit higher expression of antioxidant enzymes and PGC-1α. In addition, cholestatic livers exhibited significantly lower expression of pro-apoptotic markers (Bax) as compared to fibrotic livers. It is well known that overexpression of PGC-1α increases mitochondrial antioxidant enzyme expression, and vice versa. Thus, we concluded that obstructive cholestasis decreases expression of PGC-1α, which may lead to decreased expression of mitochondrial antioxidant enzymes, thereby rendering mice with cholestatic livers vulnerable to ROS-induced cell death.