Role of neoadjuvant treatment in resectable pancreatic cancer according to vessel invasion and increase of CA19-9 levels.

BACKGROUND/PURPOSE: The efficacy of neoadjuvant treatment (NAT) for resectable pancreatic cancer remains debatable, particularly in patients with portal vein (PV)/superior mesenteric vein (SMV) contact and elevated serum carbohydrate antigen (CA) 19-9. This study investigated the clinical significance of PV/SMV contact and CA19-9 levels, and the role of NAT in resectable pancreatic cancer. METHODS: A total of 775 patients who underwent surgery for resectable pancreatic cancer between 2007 and 2018 were included. Propensity score-matched (PSM) analysis (1:3) was performed based on tumor size, lymph node enlargement, and PV/SMV contact. Subgroup analyses were performed according to PV/SMV contact and CA19-9 level. RESULTS: Among the patients, 52 underwent NAT and 723 underwent upfront surgery. After PSM, NAT group showed better survival than upfront surgery group (median 30.0 vs 22.0 months, P = .047). In patients with PV/SMV contact, NAT tended to have better survival (30.0 vs 22.0 months, P = .069). CA19-9 >150 U/mL was a poor prognostic factor, with NAT showing a significant survival difference compared with upfront surgery (34.0 vs 18.0 months, P = .004). CONCLUSIONS: Neoadjuvant treatment showed better survival than upfront surgery in resectable pancreatic cancer. In patients with PV/SMV contact or CA19-9 >150 U/mL, NAT showed a survival difference compared to upfront surgery; therefore, NAT could be considered in these patients.

Oncologic Benefits of Neoadjuvant Treatment versus Upfront Surgery in Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Neoadjuvant treatment (NAT) followed by surgery is the primary treatment for borderline resectable pancreatic cancer (BRPC). However, there is limited high-level evidence supporting the efficacy of NAT in BRPC. PubMed was searched to identify studies that compared the survival between BRPC patients who underwent NAT and those who underwent upfront surgery (UFS). The overall survival (OS) was compared using intention-to-treat (ITT) analysis. A total of 1204 publications were identified, and 19 publications with 21 data sets (2906 patients; NAT, 1516; UFS, 1390) were analyzed. Two randomized controlled trials and two prospective studies were included. Thirteen studies performed an ITT analysis, while six presented the data of resected patients. The NAT group had significantly better OS than the UFS group in the ITT analyses (HR: 0.63, 95% CI = 0.53-0.76) and resected patients (HR: 0.68, 95% CI = 0.60-0.78). Neoadjuvant chemotherapy with gemcitabine or S-1 and FOLFIRINOX improved the survival outcomes. Among the resected patients, the R0 resection and node-negativity rates were significantly higher in the NAT group. NAT improved the OS, R0 resection rate, and node-negativity rate compared with UFS. Standardizing treatment regimens based on high-quality evidence is fundamental for developing an optimal protocol.

The development and clinical efficacy of simulation training of open duct-to-mucosa pancreaticojejunostomy using pancreas and intestine silicone models.

Purpose: As pancreaticojejunostomy (PJ) is a challenging anastomosis, an education program is needed to train young surgeons to perform PJ. This study evaluated the effects of simulation-based training of open PJ using pancreas and intestine silicone models. Methods: Five videos pancreatobiliary clinical fellows who did not perform PJ participated in this study. After watching the master video created by a senior pancreatobiliary surgeon, each trainee performed the PJ using silicone models and recorded them 10 times using a video camera. Of these videos, 5 were randomly duplicated due to the validation of the scoring system. The scoring system developed consisted of 20 scores. Three pancreatobiliary professors scored their performance by watching videos. Results: The mean procedure time of the 5 trainees was 25.4 minutes (range, 23.5-27.3 minutes) in the first video and 15.8 minutes (range, 13.8-19.1 minutes) in the 10th video. The mean score was 12.6 (range, 5-19) and 18.3 (range, 15-20) in the first and 10th videos, respectively. The scores were similar among the duplicated videos for each supervisor. Conclusion: This education system would help pancreatobiliary trainees to overcome learning curves efficiently without ethical issues related to animal models or direct practice to human patients.

Risk factors deteriorating severe exocrine pancreatic insufficiency measured by stool elastase after pancreatoduodenectomy and the risk factors for weight loss.

PURPOSE: The measurement of stool elastase (SE) level is useful for evaluating pancreatic exocrine function. This study aimed to determine the risk factors for severe exocrine pancreatic insufficiency (EPI) after pancreatoduodenectomy (PD), and analyze serial changes in nutritional markers and weight based on the SE level. METHODS: Among patients who underwent PD for periampullary disease, patients whose preoperative and postoperative SE levels were measured were included in the study. The deteriorated (exocrine function) group comprised patients whose SE levels decreased from ≥100 µg/g preoperatively to <100 µg/g postoperatively. Patients whose weight 12 months postoperatively was greater than that 3 months postoperatively were classified into the weight-recovery group. RESULTS: Of the 202 included patients, the deteriorated group had a higher incidence of preoperative SE level above 200 µg/g, benign pathology, and the presence of a clinically relevant postoperative pancreatic fistula than the maintained group. Patients who did not undergo weight recovery had a higher rate of history of adjuvant radiotherapy compared to the no-recovery group. CONCLUSION: The evaluation of EPI by measuring SE alone is not sufficient because it does not reflect the nutritional status of patients, and a comprehensive approach that considers other parameters is required for EPI management.

The incidence and clinical features of familial pancreatic cancer in Korea.

BACKGROUND: A history of familial pancreatic cancer (FPC) increases the incidence of pancreatic cancer (PC) among first-degree relatives. We aimed to determine the incidence of FPC and analyze its clinical characteristics. METHODS: Between 2010 and 2014, 1159 patients with PC were included in the study. We evaluated the incidence of FPC, clinicopathological features, and survival prognosis between FPC and non-FPC patients. We further analyzed the clinical outcomes of 389 patients with PC who underwent curative-intent surgery. RESULTS: Familial pancreatic cancer incidence was 3.1% (n = 36) among all patients with PC (n = 1159). FPC was diagnosed at an advanced clinical stage compared to non-FPC (P = .041). The tested variables and 5-year survival rate (5YSR) between FPC and non-FPC after propensity score matching had no differences (5YSR: 4.6% vs 2.6%, P = .834). Among PC patients who underwent curative-intent surgery (n = 389), FPC incidence was 1.8% (n = 7). FPC patients were older than non-FPC patients (75.3 ± 4.7 years vs 64.0 ± 9.9 years, P < .001). 5YSR tended to differ between FPC and non-FPC (14.3% vs 22.5%, P = .07) groups. CONCLUSION: Familial pancreatic cancer is diagnosed at an advanced stage, and FPC that has undergone resection is associated with older age or worse prognosis. A prospective nationwide pedigree registration system was required.

Comparisons of short-term outcomes of anastomotic methods of duct-to-mucosa pancreaticojejunostomy: out-layer continuous suture versus modified Blumgart method.

Purpose: Postoperative pancreatic fistula (POPF) is the most troublesome complication after pancreaticojejunostomy (PJ). This study aimed to compare the short-term outcomes of 2 different methods of duct-to-mucosa PJ; out-layer continuous suture anastomosis (OCA) and the modified Blumgart method (mBM). Methods: This retrospective cohort study enrolled patients who underwent curative-intent, open PD between 2015 and 2020. In mBM, 2 transpancreatic U-sutures were performed between the pancreatic margin and jejunum, with reinforced sutures in the central region. Patient demographics, diagnosis, intraoperative factors, postoperative complications, and POPF defined by the International Study Group on Pancreatic Fistula were investigated. Clinically relevant POPF (CR-POPF) included grades B and C POPF. Results: A total of 184 patients underwent OCA, and 96 patients underwent mBM. The mBM group had more patients who underwent neoadjuvant therapy. The fistula risk scores were comparable between the 2 groups. Both groups showed no significant differences in CR-POPF and overall surgical complication rates. The total operation time was comparable, although the operation time for PJ was shorter in mBM. Conclusion: No significant differences were observed in the postoperative outcomes between each group; the operation time for PJ in mBM was shorter. Therefore, mBM may be considered for utilization in duct-to-mucosa PJ.

ROBOT-assisted pancreatoduodenectomy in 300 consecutive cases: Annual trend analysis and propensity score-matched comparison of perioperative and long-term oncologic outcomes with the open method.

BACKGROUND/PURPOSE: We previously reported perioperative and oncologic outcomes of robot-assisted pancreatoduodenectomy (RAPD); however, the follow-up period in RAPD was relatively short, and disease-matched survival analyses were lacking. Therefore, this study investigated time trends of perioperative and long-term disease-matched outcomes of RAPD. METHODS: Annual clinicopathologic outcomes of 328 patients with RAPD between 2015 and 2020 were analyzed and compared with 929 patients with open PD using the propensity score-matched (PSM) analysis based on postoperative pancreatic fistula (POPF) risk and oncologic variables in malignant patients. RESULTS: Robot-assisted pancreatoduodenectomy cases increased from 10 (6.3%) in 2015 to 116 (50.2% of total PD) in 2020, with malignancy proportion increasing from 50.0% to 80.2%. POPF risk-based PSM analysis showed that compared with open PD, RAPD had younger patients (63.7 vs 65.6 years, P = .018), longer operation time (339.1 vs 290.0 min, P < .001); however, estimated blood loss (P = .275), complications (17.1% vs 18.3%, P = .702), and clinically relevant POPF (9.8% vs 11.1%, P = .584) were similar with shorter postoperative hospital stay (10.8 vs 15.6 days, P < .001). In disease and stage-matched malignant patients, R0 resection (93.9% vs 91.2%, P = .376), total retrieved lymph node (18.2 vs 19.9, P = .058), and 5-year survival rate (57.3% vs 60.6%, P = .406) were similar between RAPD and open PD, also in pancreatic cancer patients (31.6% vs 26.3%, P = .068). CONCLUSIONS: Robot-assisted pancreatoduodenectomy demonstrated similar perioperative outcomes with earlier recovery and equivalent long-term survival with open PD. RAPD is safe and feasible for periampullary lesions, including pancreatic cancers, and its role will expand in the era of minimally invasive surgery.

A retrospective multicentre study on the evaluation of perioperative outcomes of single-port robotic cholecystectomy comparing the Xi and SP versions of the da Vinci robotic surgical system.

BACKGROUND: Single-incision robotic cholecystectomy (SIRC) is widely performed with both the da Vinci Xi system (Xi) and the da Vinci SP system (SP). But there are limited numbers of studies comparing these platforms. METHODS: Patients who underwent SIRC between 2019 and 2020 were enrolled. Patient demographics, intraoperative factors, postoperative complications, postoperative pain were compared using a one-to-one propensity score matching (PSM). RESULTS: Overall, 258 patients underwent SIRC with Xi and 72 with SP. After PSM, there were significant differences between the Xi and SP in operation time at console and numeric rating scale for postoperative pain, but no difference in total operation time and postoperative complications. The SP group showed more estimated blood loss. CONCLUSIONS: Despite the statistical difference, clinical benefit was not significant. Both platforms can be safe and feasible to perform SIRC, but further investigation including the surgeon's workload and ergonomics is needed as a prospective study.

Clinical characteristics of patients with malignancy and long-term outcomes of surgical treatment of patients with choledochal cyst.

PURPOSE: There are few reports of postoperative long-term malignant risk or postoperative sequelae after surgery for choledochal cysts (CCs). This study aimed to analyze the clinical characteristics of patients with malignancy and the long-term results of operated CC. METHODS: The patients who underwent surgical treatments for CC between 2003 and 2020 at Seoul National University Hospital were enrolled. Clinicopathologic factors and pre-/postoperative computed tomography or magnetic resonance imaging were reviewed. RESULTS: Of the 153 patients, Todani classification Ic (36.6%), C-P type (43.8%) anomalous pancreaticobiliary duct union were the most common type respectively. Fourteen patients (9.2%) had biliary tract cancer and a comparison of patients with and without malignancy showed that the diameter of cyst was significantly lower in malignant patients and malignancy was observed to be significantly higher in P-C type. The incidence of long-term complications was 9.8%, and the median time interval was 30 months. The 2 most common complications were cholangitis and stricture (60.0%). There was one case of new cancer near the intrapancreatic remnant bile duct. CONCLUSION: Of the resected CCs, 9.2% had a combined malignancy on the biliary tracts. Long-term complications such as cholangitis, anastomotic stricture, and new cancers may occur. Therefore, continuous surveillance is required.

Serum carcinoembryonic antigen and carbohydrate antigen 19-9 as preoperative diagnostic biomarkers of extrahepatic bile duct cancer.

BACKGROUND: Serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been proposed as useful preoperative biomarkers of extrahepatic bile duct cancer (EBDC). This study investigated the accuracy of CEA and CA19-9 for preoperative diagnosis of EBDC. METHODS: Patients who underwent surgery for EBDC at a tertiary centre between 1995 and 2018 were studied, and those with concurrent hepatobiliary diseases (including gallbladder cancer, intraductal papillary mucinous neoplasms of pancreas), which could affect CEA or CA19-9 levels, were excluded. The control group included patients who underwent cholecystectomy for benign gallbladder diseases during the same period. Diagnostic accuracy was determined using sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: After excluding 23 patients, 687 patients (488 men and 199 women, mean age 65.8 years) were compared with the control group of 2310 patients. Median CEA and CA19-9 levels were 1.8 µg/l and 47.0 kU/l in patients with EBDC. CEA (cut-off 5.0 µg/l) showed AUC of 0.541, sensitivity 9.0 per cent and specificity 99.2 per cent, whereas CA19-9 (cut-off 37.0 kU/l) showed AUC of 0.753, sensitivity 56.2 per cent and specificity 94.5 per cent. Sensitivity of CA19-9 was lower in early (T stages 0-II) than advanced (T stages III and IV) cancer (47.0 versus 64.9 per cent), and also lower in N0 stage cancer than lymph node metastasis (50.1 versus 68.8 per cent). CONCLUSION: Serum CEA and CA19-9 showed low sensitivity limiting their usefulness as diagnostic biomarkers of EBDC.

Limits of serum carcinoembryonic antigen and carbohydrate antigen 19-9 as the diagnosis of gallbladder cancer.

PURPOSE: Although serum CEA and CA 19-9 have been widely utilized for the diagnosis of gallbladder cancer (GBC), few studies have examined the diagnostic performance of them. This study aimed to investigate the diagnostic performance of these 2 biomarkers and demonstrate their clinical usefulness in diagnosing GBC. METHODS: Between January 2000 and March 2020, a total of 751 GBC patients and 2,310 normal controls were included. Serum CEA and CA 19-9 were measured preoperatively. Receiver operating characteristic curves were obtained, and the sensitivity and specificity of each biomarker were evaluated. RESULTS: In terms of differentiating GBC from the control, the sensitivity and specificity of serum CEA at 5 ng/mL was 12.1% and 99.1%, respectively, and those of serum CA 19-9 at 37 IU/mL were 28.7% and 94.5%, respectively. The optimal cutoff values of CEA and CA 19-9 were set to 2.1 ng/mL and 26 IU/mL in the receiver operating characteristic curves, respectively. The sensitivities of CEA and CA 19-9 at new cutoff values slightly increased but remained low (CEA, 42.9%; CA 19-9, 38.2%). When differentiating early-stage GBC from advanced tumor, the sensitivity and specificity, were 14.2% and 96.1% for CEA (cutoff value, 5 ng/mL) and 33.6% and 90.1% for CA 19-9 (cutoff value, 37 IU/mL), respectively. CONCLUSION: Serum CEA and CA 19-9 levels are not suitable for screening GBC patients from controls. New promising biomarkers with higher sensitivity should be explored.