Surgical Outcomes and Comparative Analysis of Transduodenal Ampullectomy and Pancreaticoduodenectomy: A Single-Center Study.

BACKGROUND: Transduodenal ampullectomy (TDA) is performed for adenoma or early cancer of the ampulla of Vater (AoV). This study aimed to analyze the short- and long-term outcomes of TDA (TDA group) when compared with conventional pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PD group). METHODS: Patients who underwent TDA between January 2006 and December 2019, and PD cases performed for AoV malignancy with carcinoma in-situ (Tis) (high-grade dysplasia, HGD) and T1 and T2 stage from January 2010 to December 2019 were reviewed. RESULTS: Forty-six patients underwent TDA; 21 had a benign tumor, and 25 cases with malignant tumors were compared with PD cases (n = 133). Operation time (p < 0.001), estimated blood loss (p < 0.001), length of hospital stays (p = 0.003), and overall complication rate (p < 0.001) were lower in the TDA group than in the PD group. Lymph node metastasis rates were 14.6% in pT1 and 28.9% in pT2 patients. The 5-year disease-free survival and 5-year overall survival rates for HGD/Tis and T1 tumor between the two groups were similar (TDA group vs PD group, 72.2% vs 77.7%, p = 0.550; 85.6% vs 79.2%, p = 0.816, respectively). CONCLUSION: TDA accompanied with lymph node dissection is advisable in HGD/Tis and T1 AoV cancers in view of superior perioperative outcomes and similar long-term survival rates compared with PD.

The Impact of Neoadjuvant Treatment on Survival in Patients Undergoing Pancreatoduodenectomy With Concomitant Portomesenteric Venous Resection: An International Multicenter Analysis.

OBJECTIVE: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers. SUMMARY OF BACKGROUND DATA: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients. METHODS: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018. RESULTS: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS. CONCLUSION: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT.

Radical antegrade modular pancreatosplenectomy (RAMPS) versus conventional distal pancreatectomy for left-sided pancreatic cancer: findings of a multicenter, retrospective, propensity score matching study.

PURPOSE: Radical antegrade modular pancreatosplenectomy (RAMPS) has been reported to achieve high rates of a negative margin and resected metastatic lymph nodes. However, many studies have used historical controls and the results remain controversial. We conducted this study to compare the surgical and long-term outcomes of RAMPS vs. conventional distal pancreatectomy (DP). METHODS: The subjects of this multicenter retrospective study were 106 patients who underwent curative resection for left-sided pancreatic cancer between 2012 and 2017. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using Kaplan-Meier estimates. RESULTS: The RAMPS group had more advanced T (T3/T4) and N stages (N1/N2) and a larger tumor size than the conventional group (T stage, p = 0.04; N stage, p = 0.02; tumor size, p = 0.04). The RAMPS group had more harvested metastatic lymph nodes (p = 0.02). After propensity-score matching, 37 patients from each group were included in the final analysis. There was no significant difference in RFS (p = 0.463) or OS (p = 0.383) between the groups. Multivariate analyses revealed the completion of chemotherapy to be an independent factor for RFS and OS (both p < 0.001). CONCLUSIONS: There was no difference in the RFS or OS between RAMPS and conventional DP in this series. RAMPS may be an option for R0 resection of advanced tumors; however, postoperative chemotherapy has a greater influence than the surgical procedure on the prognosis of patients with pancreatic cancer.

Defining Benchmark Outcomes for Pancreatoduodenectomy With Portomesenteric Venous Resection.

OBJECTIVE: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers. SUMMARY BACKGROUND DATA: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection. METHODS: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998). RESULTS: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%. CONCLUSION: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Effects of Pancreatic Enzyme Replacement Therapy on Body Weight and Nutritional Assessments After Pancreatoduodenectomy in a Randomized Trial.

BACKGROUND & AIMS: We studied the effects of pancreatic enzyme replacement therapy (PERT) on body weight, nutritional status, and quality of life (QoL) in patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. METHODS: We performed a randomized, double-blind trial of 304 patients who underwent pancreatoduodenectomy at 7 tertiary referral hospitals in South Korea. Patients with fecal levels of elastase of 200 µg/g or less, before and after surgery, were assigned randomly to groups that received PERT (a single capsule of 40,000 IU pancreatin, Norzyme (40,000 IU, Pankreatan; Nordmark Arzneimittel GmbH & Co, Uetersen, Germany), 3 times each day during meals for 3 months; n = 151) or placebo (n = 153). Protocol completion was defined as taking more than two thirds of the total dose without taking other digestive enzymes; the protocol was completed by 71 patients in the PERT group and 93 patients in the placebo group. Patients underwent a physical examination, oral glucose tolerance tests, and blood tests at baseline and at month 3 of the study period. The primary end point was change in body weight. Secondary end points were changes in bowel habits, nutritional parameters, and QoL. RESULTS: In the per-protocol analysis, 3 months after the study began, patients in the PERT group gained a mean of 1.09 kg in weight and patients in the placebo group lost a mean of 2.28 kg (difference between groups, 3.37 kg; P < .001). However, no difference in body weight was observed between groups in the intent-to-treat analysis. Three months after the study began, the mean serum levels of prealbumin increased by 10.9 mg/dL in the PERT group and increased by 7.8 mg/dL in the placebo group (P = .002). Poor compliance to PERT was a significant risk factor for weight loss (P < .001). There was no significant difference in QoL scores between groups. CONCLUSIONS: In the intent-to-treat analysis of data from a randomized trial, we found no significant effect of PERT on mean body weights of patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. However, with active education and monitoring, PERT could increase body weight and nutritional parameters. ClinicalTrials.gov no: NCT02127021.

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

BACKGROUND: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). METHODS: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). RESULTS: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001). CONCLUSION: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy.

Preoperative prediction of futile surgery in patients with radiologically resectable or borderline resectable pancreatic adenocarcinoma.

BACKGROUND AND AIM: The aim of this study is to identify the predictive factors for futile surgery in patients with radiologically resectable or borderline resectable pancreatic cancer and to develop a prediction model. METHODS: This retrospective study included patients who underwent pancreatic surgery for pancreatic cancer between 2006 and 2017. To identify independent risk factors for futile surgery, logistic regression and random forest analyses were performed in the training cohort, based on which a nomogram was established. The predictive accuracy and discriminative ability of the nomogram were validated in the validation cohort. RESULTS: Of 389 patients who underwent pancreatic surgery, the laparotomy was futile in 40 patients (10.3%). In the training cohort, the univariate and multivariate logistic regression analyses revealed that serum carbohydrate antigen 19-9 level of ≥ 150 U/mL (P = 0.003), the presence of suspicious lymph node (P = 0.013), and more extensive peripancreatic tumor infiltration (P < 0.001) were independent predictive factors for futile surgery. The bootstrap-corrected concordance index of the nomogram was high in the training cohort, 0.826 with a 95% confidence interval of 0.745-0.907. This model also showed a good discriminative performance in the validation cohort, with a concordance index of 0.831. CONCLUSIONS: We established and validated a novel nomogram that predicts the risk of futile surgery due to occult distant metastasis in patients with radiologically resectable or borderline resectable pancreatic cancer.

The Yonsei experience of 104 laparoscopic pancreaticoduodenectomies: a propensity score-matched analysis with open pancreaticoduodenectomy.

BACKGROUND: With continued technical advances in surgical instruments and growing expertise, several surgeons have performed laparoscopic pylorus preserving pancreaticoduodenectomy (L-PPPD) safely with good results, and the laparoscopic approach is being performed more frequently. We performed over 100 cases of L-PPPD and compared their outcomes to those of open PPPD (O-PPPD) using the large sample size. The aim of the present study was to evaluate the safety and feasibility of L-PPPD compared with O-PPPD. METHODS: From September 2012 to June 2017, PPPD was performed for 217 patients at Yonsei University Severance Hospital by a single surgeon. Patients were divided into two groups: those who underwent O-PPPD (n = 113) and those who underwent L-PPPD (n = 104). We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographic and surgical outcomes. We also reviewed all previous studies of more than 100 cases. RESULTS: The L-PPPD group had lesser intraoperative blood loss than the O-PPPD group (548.1 ml vs. 244.7 ml; p < 0.001). Both groups showed similar rates of negative resection margins (99.1% vs. 96.2%; p = 0.196). Overall complication rates did not differ significantly between O-PPPD and L-PPPD (39.8% vs. 35.6%; p = 0.519). The clinically relevant postoperative pancreatic fistula (POPF) rates in the O-PPPD and L-PPPD groups were 18.8% and 13.5%, respectively (p = 0.311). There was no difference in 30- and 90-day mortality rates between the two groups (p = 0.479). Similar results were obtained after PSM analysis. CONCLUSIONS: L-PPPD can be a good alternative option for well-selected patients with periampullary lesions requiring PPPD.

A nomogram to preoperatively predict 1-year disease-specific survival in resected pancreatic cancer following neoadjuvant chemoradiation therapy.

OBJECTIVE: This study aimed to develop a nomogram to predict the 1-year survival of patients with pancreatic cancer who underwent pancreatectomy following neoadjuvant treatment with preoperatively detectable clinical parameters. Extended pancreatectomy is necessary to achieve complete tumor removal in borderline resectable and locally advanced pancreatic cancer. However, it increases postoperative morbidity and mortality rates, and should be balanced with potential benefit of long-term survival. METHODS: The medical records of patients who underwent pancreatectomy following neoadjuvant treatment from January 2005 to December 2016 at Severance Hospital were retrospectively reviewed. Medical records were collected from five international institutions from Japan and Singapore for external validation. RESULTS: A total of 113 patients were enrolled. The nomogram for predicting 1-year disease-specific survival was created based on 5 clinically detectable preoperative parameters as follows: age (year), symptom (no/yes), tumor size at initial diagnostic stage (cm), preoperative serum carbohydrate antigen (CA) 19-9 level after neoadjuvant treatment (<34/≥34 U/mL), and planned surgery [pancreaticoduodenectomy (PD) (pylorus-preserving PD)/distal pancreatectomy (DP)/total pancreatectomy]. Model performance was assessed for discrimination and calibration. The calibration plot showed good agreement between actual and predicted survival probabilities; the the Greenwood-Nam-D'Agostino (GND) goodness-of-fit test showed that the model was well calibrated (χ2=8.24, P=0.5099). A total of 84 patients were used for external validation. When correlating actual disease-specific survival and calculated 1-year disease-specific survival, there were significance differences according to the calculated probability of 1-year survival among the three groups (P=0.044). CONCLUSIONS: The developed nomogram had quite acceptable accuracy and clinical feasibility in the decision-making process for the management of pancreatic cancer.

Glucose to Lymphocyte Ratio as a Prognostic Marker in Patients With Resected pT2 Gallbladder Cancer.

BACKGROUND: We designed a clinical application of glucose to lymphocyte ratio (GLR) as it might be a sensitive parameter to determine the glucose metabolism and behavior of the cancer (i.e., its aggressiveness), and the immunologic status of a patient with cancer. Thus, we investigated the association of GLR with the overall survival (OS) and disease-free survival (DFS) of patients with T2 gallbladder (GB) cancer after curative-intent surgery. METHODS: The medical records of patients with T2 GB cancer who underwent surgery were retrospectively reviewed. The clinicopathologic characteristics, preoperative complete blood counts, fasting blood glucose, albumin, cholesterol, and follow-up information were collected. RESULTS: A total of 197 patients were included in the study. In multivariate analysis, high GLR (>69.3) was associated with poor OS (HR = 15.249, 95% CI: 4.090-56.849, P = 0.0001) along with R1 status (HR = 1.755, 95% CI: 0.033-0.910, P = 0.033), >3 metastatic lymph nodes (HR = 2.809, 95% CI: 1.403-5.625; P = 0.004), and lymphovascular invasion (HR = 8.041, 95% CI: 2.881-22.442; P = 0.0001). Moreover, high GLR (HR = 3.666, 95% CI: 1.145-11.737, P = 0.029), adjuvant chemotherapy (HR = 6.306, 95% CI: 1.921-20.699; P = 0.002), lymphovascular invasion (HR = 5.464, 95% CI: 1.783-16.746; P = 0.003), and high-grade tumor (HR = 2.143, 95% CI: 1.042-4.407; P = 0.038) were independently associated with DFS. CONCLUSIONS: Preoperative GLR is an independent predictor of OS and DFS in T2 GB cancer. Further studies are required to validate these findings.

True learning curve of laparoscopic spleen-preserving distal pancreatectomy with splenic vessel preservation.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is generally the treatment of choice for diseases of the pancreatic body and tail. Most surgeons prefer the spleen- and splenic vessel-preserving technique (SPVP-LDP) in benign/borderline pancreatic disease because complications of splenic infarction and gastric varices can arise after Warshaw technique. This study was aimed to determine the true learning curve of the SPVP-LDP procedure not LDP including Warshaw technique. METHODS: Data were collected retrospectively from all patients who underwent a LDP between June 2007 and April 2017 at Gangnam Severance Hospital. We used cumulative sum control chart (CUSUM) analysis to assess the learning curve for the SPVP-LDP technique. RESULTS: Eight-three patients were performed LDP and we excluded patients who underwent robotic approach (N = 10) and open conversion DP (N = 8). Patients who underwent SPVP-LDP procedures were categorized into Group 1 (primary end-point). Those who underwent LDP procedures with splenectomy and the Warshaw technique were categorized into Group 2. We found that the 16th case was the cutoff point and the mean length of hospital stay was 13.0 days in the first period and 8.7 days in the second period (p = < 0.001). CONCLUSIONS: These results indicated that the frequency of SPVP-LDPs had increased and that technological progress had been made over time. The true learning curve for SPVP-LDP was indicated as 16 cases in a group of surgeons with no experience of laparoscopic pancreatic surgery.

Survey Results of the Expert Meeting on Laparoscopic Surgery for Gallbladder Cancer and a Review of Relevant Literature.

BACKGROUND: Favorable outcomes of laparoscopic surgery for gallbladder cancer (GBC) have been reported; yet consensus on the indications and surgical techniques for laparoscopic surgery for GBC is lacking. OBJECTIVE: To evaluate the current status of laparoscopic surgery for GBC by analyzing the results of a survey of experts and by reviewing the relevant published literature. METHODS: Before an expert meeting was held on September 10, 2016 in Seoul, Korea, an international survey was undertaken of expert surgeons in the field of GBC surgery. RESULTS: The majority of surgeons who responded agreed that laparoscopic surgery has an acceptable role for suspicious or early GBC, and that laparoscopic extended cholecystectomy has a value comparable to that of open surgery in selected patients with GBC. However, the selection criteria for laparoscopic surgery for overt GBC and the details of the surgical techniques varied among surgeons. CONCLUSIONS: This survey and literature review revealed that laparoscopic surgery for GBC is performed in highly selected cases. However, the favorable outcomes in the published reports and the positive view of experienced surgeons for this operative procedure suggest a high likelihood that laparoscopic surgery will be more frequently performed for GBC in the future.

Laparoscopic Surgery for Gallbladder Cancer: An Expert Consensus Statement.

BACKGROUND: Despite the increasing number of reports on the favorable outcomes of laparoscopic surgery for gallbladder cancer (GBC), there is no consensus regarding this surgical procedure. OBJECTIVE: The study aimed to develop a consensus statement on the application of laparoscopic surgery for GBC based on expert opinions. METHODS: A consensus meeting among experts was held on September 10, 2016, in Seoul, Korea. RESULTS: Early concerns regarding port site/peritoneal metastasis after laparoscopic surgery have been abated by improved preoperative recognition of GBC and careful manipulation to avoid bile spillage. There is no evidence that laparoscopic surgery is associated with decreased survival compared with open surgery in patients with early-stage GBC if definitive resection during/after laparoscopic cholecystectomy is performed. Although experience with laparoscopic extended cholecystectomy for GBC has been limited to a few experts, the postoperative and survival outcomes were similar between laparoscopic and open surgeries. Laparoscopic reoperation for postoperatively diagnosed GBC is technically challenging, but its feasibility has been demonstrated by a few experts. CONCLUSIONS: Laparoscopic surgery for GBC is still in the early phase of the adoption curve, and more evidence is required to assess this procedure.

Surgical approach to solid pseudopapillary neoplasms of the proximal pancreas: minimally invasive vs. open.

BACKGROUND: Solid pseudopapillary neoplasms (SPN) of the pancreas are rare pancreatic neoplasms where complete resection is the cornerstone in management. It has been demonstrated in previous studies that minimally invasive surgical approaches are effective management options in treating SPNs of the distal pancreas. The purpose of this study is to evaluate the feasibility of minimally invasive surgery in treating SPNs of the uncinate, head, and neck of the pancreas. METHODS: Data from 2005 to 2017 at Severance Hospital of the Yonsei University Health systems in Seoul, South Korea, were retrospectively collected for 25 patients who were diagnosed with SPN of the uncinate, head, and neck of the pancreas and who underwent curative resection. Three groups of patients were considered, depending on the year of surgery, in order to determine trends in the surgical management of SPN. The patients were also divided into two groups corresponding to the type of operation done (minimally invasive surgery vs. open surgery). Perioperative patient data, including age, gender, body mass index (BMI), tumor size, and operation done, were compared and analyzed statistically. Long-term nutritional effects were measured using the Controlling Nutritional Status (CONUT) scoring system. RESULTS: There were no statistically significant differences in age, gender, BMI, symptomatic presentation, operation type, tumor size, and tumor stage between the three time periods. In comparing between minimally invasive and open surgery, there were no statistically significant differences in age, gender, symptomatic presentation, BMI, tumor size, preoperative stage, type of operation, operation time, pancreatic duct size, post-operative pancreatic fistula (POPF) grade, death associated with disease, recurrence, pathological parameters, and change in CONUT score. There was a significant difference in tumor size (4.5 ± 1.8 vs. 2.6 ± 1.0 cm, p = 0.004), blood loss (664.2 ± 512.4 vs. 277.7 ± 250.8 mL, p = 0.024), need to transfuse (33% vs. 0%, p = 0.023), hospital length of stay (27.4 ± 15.3 vs. 11.5 ± 5.3 days, p = 0.002), and complication rate (75% vs. 30.8%, p = 0.027) between the two groups. CONCLUSIONS: In appropriately selected patients with SPNs of the uncinate, head, and neck of the pancreas, a minimally invasive surgical approach offers at least equal oncologic and nutritional outcomes, while demonstrating decreased complications and decreased hospital length of stay compared with that of an open surgical approach.

Oncological Benefits of Neoadjuvant Chemoradiation With Gemcitabine Versus Upfront Surgery in Patients With Borderline Resectable Pancreatic Cancer: A Prospective, Randomized, Open-label, Multicenter Phase 2/3 Trial.

OBJECTIVE: This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC. SUMMARY BACKGROUND DATA: Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment. METHODS: This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment. RESULTS: After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66-3.36), P = 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P = 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy. CONCLUSION: This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC.

Effects of Preoperative Oral Carbohydrates on Quality of Recovery in Laparoscopic Cholecystectomy: A Randomized, Double Blind, Placebo-Controlled Trial.

BACKGROUND: While carbohydrate loading is an important component of enhanced patient recovery after surgery, no study has evaluated the effects of preoperative carbohydrate loading after laparoscopic cholecystectomy (LC) on patient satisfaction and overall recovery. Thus, we aimed to investigate the impact of preoperative oral carbohydrates on scores from the quality of recovery 40-item (QoR-40) questionnaire after LC. METHODS: A total of 153 adults who underwent LC were randomized into three groups. Group MN-NPO was fasted from midnight until surgery. Group No-NPO received 400 mL of a carbohydrate beverage on the evening before surgery, and a morning dose of 400 mL was ingested at least 2 h before surgery. Group Placebo received the same quantity of flavored water as for group No-NPO. The quality of recovery after general anesthesia was evaluated using QoR-40 questionnaire. Intraoperative hemodynamics were also evaluated. RESULTS: There were no significant differences among the groups in terms of the pre- and postoperative global QoR-40 scores (P = 0.257). Group MN-NPO had an elevated heart rate compared to patients who ingested a preoperative beverage (groups No-NPO and Placebo; P = 0.0412). CONCLUSIONS: The preoperative carbohydrate beverage did not improve quality of recovery using the QoR-40 questionnaire after general anesthesia for laparoscopic cholecystectomy compared to placebo or conventional fasting. However, the preoperative fasting group had a consistently increased heart rate during changes in body position that induced hypotension, which is likely a result of depletion of effective intravascular volume caused by traditional fasting over 8 h. TRIAL REGISTRATION: Clinical trial.gov identifier: NCT02555020.

Surgical Strategy for T2 Gallbladder Cancer: Nationwide Multicenter Survey in Korea.

BACKGROUND: Although all guidelines suggest that T2 gallbladder (GB) cancer should be treated by extended cholecystectomy (ECx), high-level scientific evidence is lacking because there has been no randomized controlled trial on GB cancer. METHODS: A nationwide multicenter study between 2000 and 2009 from 14 university hospitals enrolled a total of 410 patients with T2 GB cancer. The clinicopathologic findings and long-term follow-up results were analyzed after consensus meeting of Korean Pancreas Surgery Club. RESULTS: The 5-year cumulative survival rate (5YSR) for the patients who underwent curative resection was 61.2%. ECx group showed significantly better 5YSR than simple cholecystectomy (SCx) group (65.4% vs. 54.0%, P = 0.016). For N0 patients, there was no significant difference in 5YSR between SCx and ECx groups (68.7% vs. 73.6%, P = 0.173). Systemic recurrence was more common than locoregional recurrence (78.5% vs. 21.5%). Elevation of cancer antigen 19-9 level preoperatively and lymph node (LN) metastasis were significantly poor prognostic factors in a multivariate analysis. CONCLUSION: ECx including wedge resection of GB bed should be recommended for T2 GB cancer. Because systemic recurrence was more common and recurrence occurred more frequently in patients with LN metastasis, postoperative adjuvant therapy should be considered especially for the patients with LN metastasis.

ANO9/TMEM16J promotes tumourigenesis via EGFR and is a novel therapeutic target for pancreatic cancer.

BACKGROUND: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer. METHODS: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer. RESULTS: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer. CONCLUSIONS: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.