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 (PET) with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-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 was administered in 166 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 [hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.73–5.58, P<0.001] based on cutoff value of 2.4. Patients with decreased MTV had significantly better survival than those with elevated MTV among individuals with CA19-9 levels less than 37 IU/l (median survival; 35.5 vs. 20.9 months, P<0.001) and CA19-9 levels at least 37 IU/l (median survival; 34.3 vs. 17.8 months, P=0.03). In patients suspected to be Lewis antigen negative, the 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.
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.
17 August 2023 in International Journal of Surgery
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/m2, 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.
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.
1 January 2024 in Journal of Laparoendoscopic & Advanced Surgical Techniques
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.