Preoperative Fistula Risk Prediction Using Computed Tomography Image Before Pancreatoduodenectomy.

BACKGROUND: Although many formulas for predicting postoperative pancreatic fistula (POPF) have been introduced, POPF is generally predicted during pancreatic surgery due to pancreatic texture. This study was designed to verify the correlation between Hounsfield units (HU) and pancreatic texture and to suggest a fistula risk score (FRS) that can be used before surgery. METHODS: Data from 545 patients who underwent pancreatoduodenectomy for malignant disease between January 2008 and December 2019 were retrospectively reviewed. The HU level of the pancreas was measured, and odds ratio (OR) of the HU for POPF was analyzed. Additionally, the assessed HU was compared with the pancreatic texture (soft vs. hard) and calculated cutoff level. Finally, the preoperatively chosen pancreatic texture according to HU level was applied to the FRS formula (preoperative-FRS: p-FRS), and the results were compared with a previously reported FRS formula (updated alternative-FRS: ua-FRS). RESULTS: The Hounsfield unit levels were correlated with clinically relevant POPF (CR-POPF) (odds ratio [OR]: 1.04 (1.01-1.07), p = 0.015). In the receiver operating characteristic curve, the HU showed significant prediction potential for pancreatic texture (area under the curve [AUC]: 0.744, p < 0.001). The p-FRS also showed acceptable results in predicting CR-POPF (AUC = 0.702, p < 0.001). There was no statistically significant difference in the DeLong's test compared with the ua-FRS (p = 0.314). In the Hosmer-Lemeshow test, observed probabilities were correlated with predicted probabilities (p = 0.596). CONCLUSIONS: The HU level on preoperative computed tomography (CT) is a predictive factor for POPF and could represent for pancreatic texture.

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

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

Molecular Characterization of Biliary Tract Cancer Predicts Chemotherapy and Programmed Death 1/Programmed Death-Ligand 1 Blockade Responses.

BACKGROUND AND AIMS: Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs. APPROACH AND RESULTS: We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response. CONCLUSIONS: This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.

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.

Systemic inflammation response index correlates with survival and predicts oncological outcome of resected pancreatic cancer following neoadjuvant chemotherapy.

BACKGROUND: The Systemic Inflammation Response Index (SIRI) has been used to predict the prognosis of various cancers. This study examined SIRI as a prognostic factor in the neoadjuvant setting and determined whether it changing after chemotherapy is related to patient prognosis. METHODS: Patients who underwent pancreatic surgery following neoadjuvant chemotherapy for pancreatic cancer were retrospectively analyzed. To establish the cut-off values, SIRIpre-neoadjuvant, SIRIpost-neoadjuvant, and SIRIquotient (SIRIpost-neoadjuvant/SIRIpre-neoadjuvant) were calculated and significant SIRI values were statistically determined to examine their effects on survival rate. RESULTS: The study included 160 patients. Values of SIRIpost-neoadjuvant ≥ 0.8710 and SIRIquotient <0.9516 affected prognosis (hazard ratio [HR], 1.948; 95% confidence interval [CI], 1.210-3.135; ∗∗P = 0.006; HR, 1.548; 95% CI, 1.041-2.302; ∗∗P = 0.031). Disease-free survival differed significantly at values of SIRIpost-neoadjuvant < 0.8710 and SIRIpost-neoadjuvant ≥ 0.8710 (P = 0.0303). Overall survival differed significantly between SIRIquotient <0.9516 and SIRIquotient ≥0.9516 (P = 0.0368). CONCLUSIONS: SIRI can predict the survival of patients with pancreatic ductal adenocarcinoma after resection and neoadjuvant chemotherapy. Preoperative SIRI value was correlated with disease-free survival, while changes in SIRI values were correlated with overall survival.

Total laparoscopic versus robotic-assisted laparoscopic pancreaticoduodenectomy: which one is better?

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a challenging procedure. Laparoscopic pancreaticoduodenectomy (LPD) is feasible and safe. Since the development of robotic platforms, the number of reports on robot-assisted pancreatic surgery has increased. We compared the technical feasibility and safety between LPD and robot-assisted LPD (RALPD). METHODS: From September 2012 to August 2020, 257 patients who underwent MIPD for periampullary tumors were enrolled. Of these, 207 underwent LPD and 50 underwent RALPD. We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographics and surgical outcomes. RESULTS: After PSM analysis, no difference was noted in demographics. Operation times and estimated blood loss were similar, as was the incidence of complications (p > 0.05). In subgroup analysis in patients with soft pancreas with pancreatic duct ≤ 2 mm, no significant between-group difference was noted regarding short-term surgical outcomes, including clinically relevant POPF (CR-POPF) (p > 0.05). In multivariable analysis, the only soft pancreatic texture was a predictive factor (HR 3.887, 95% confidence interval 1.121-13.480, p = 0.032). CONCLUSION: RALPD and LPD are safe and effective for MIPD and can compensate each other to achieve the goal of minimally invasive surgery.

Minimally invasive (laparoscopic and robot-assisted) versus open approach for central pancreatectomies: a single-center experience.

BACKGROUND: There continues to be an interest in minimally invasive approaches to pancreatic surgery. At our institution, there has been a progressive change from an open to minimally invasive surgery (MIS) (laparoscopic, robotic, or laparoscopic-robotic) approach for central pancreatectomies (CP). The aim of this study was to evaluate surgical outcomes with open CP (O-CP) versus minimally invasive CP (MI-CP). METHODS: A retrospective medical review of patients who underwent CP between 1993 and 2018 at Yonsei University Health System, Seoul, Korea was performed. Short-term perioperative outcomes were compared between O-CP and MI-CP. RESULTS: Thirty-one CPs (11 open, 20 MIS) were identified during the study period. No difference was observed in admission days between O-CP and MI-CP (21.2 vs. 16.7 days, p = 0.340), although operating time was significantly increased in the MI-CP group (296.8 vs. 374.8 min, p = 0.036). Blood loss was significantly less in MI-CP vs. O-CP (807.1 vs. 214.0 mls, p = 0.001), with no difference in post-operative new-onset diabetes (9% vs. 5%). The overall post-operative pancreatic fistula rate was 25.8%, and no significant difference between O-CP and MI-CP or complication rates (45% vs. 40%) was observed. CONCLUSION: Despite increased operative time, MI-CP is feasible and comparable to conventional O-CP with regard to surgical outcomes in well-selected patients.

Wrapping the pancreas with a polyglycolic acid sheet before stapling reduces the risk of fluid collection on the pancreatic stump after distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) and postoperative fluid collection (POFC) are common complications after distal pancreatectomy (DP). The previous method of reducing the risk of POPF was the application of a polyglycolic acid (PGA) sheet to the pancreatic stump after cutting the pancreas with a stapler (After-stapling); the new method involves wrapping the pancreatic resection line with a PGA sheet before stapling (Before-stapling). The study aimed to compare the incidence of POPF and POFC between two methods. METHODS: Data of patients who underwent open or laparoscopic DPs by a single surgeon from October 2010 to February 2020 in a tertiary referral hospital were retrospectively analyzed. POPF was defined according to the updated International Study Group of Pancreatic Fistula criteria. POFC was measured by postoperative computed tomography (CT). RESULTS: Altogether, 182 patients were enrolled (After-stapling group, n = 138; Before-stapling group, n = 44). Clinicopathologic and intraoperative findings between the two groups were similar. Clinically relevant POPF rates were similar between both groups (4.3% vs. 4.5%, p = 0.989). POFC was significantly lesser in the Before-stapling group on postoperative day 7 (p < 0.001). CONCLUSIONS: Wrapping the pancreas with PGA sheet before stapling was a simple and effective way to reduce POFC.

Comparison of oncologic outcomes between open and laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma using data from the KOTUS-BP national database: overcoming selection bias and the necessity of definite indications.

BACKGROUND: Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database. METHODS: A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP). RESULTS: ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion. CONCLUSION: LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.

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.

Minimally Invasive Versus Open Pancreatectomy for Right-Sided and Left-Sided G1/G2 Nonfunctioning Pancreatic Neuroendocrine Tumors: A Multicenter Matched Analysis with an Inverse Probability of Treatment-Weighting Method.

BACKGROUND: Limited evidence exists for the safety and oncologic efficacy of minimally invasive surgery (MIS) for nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) according to tumor location. This study aimed to compare the surgical outcomes of MIS and open surgery (OS) for right- or left-sided NF-PNETs. METHODS: The study collected data on patients who underwent surgical resection (pancreatoduodenectomy, distal/total/central pancreatectomy, duodenum-preserving pancreas head resection, or enucleation) of a localized NF-PNET between January 2000 and July 2017 at 14 institutions. The inverse probability of treatment-weighting method with propensity scores was used for analysis. RESULTS: The study enrolled 859 patients: 478 OS and 381 MIS patients. A matched analysis by tumor location showed no differences in resection margin, intraoperative blood loss, or complications between MIS and OS. However, MIS was associated with a longer operation time for right-sided tumors (393.3 vs 316.7 min; P < 0.001) and a shorter postoperative hospital stay for left-sided tumors (8.9 vs 12.9 days; P < 0.01). The MIS group was associated with significantly higher survival rates than the OS group for right- and left-sided tumors, but survival did not differ for the patients divided by tumor grade and location. Multivariable analysis showed that MIS did not affect survival for any tumor location. CONCLUSION: The short-term outcomes offered by MIS were comparable with those of OS except for a longer operation time for right-sided NF-PNETs. The oncologic outcomes were not compromised by MIS regardless of tumor location or grade. These findings suggest that MIS can be performed safely for selected patients with localized NF-PNETs.

Biologic behavior of resected BRCA-mutated pancreatic cancer: Comparison with sporadic pancreatic cancer and other BRCA-related cancers.

BACKGROUND: Since margin-negative resection is essential for the cure of pancreatic cancer (PC), early detection of PC is important. Although PC is the third most common cancer associated with BRCA1/2 mutations, clinical research regarding BRCA mutations in resected PC are rare. In this study, we investigated the oncologic characteristics of resected PC with BRCA mutation to suggest management strategies. METHODS: We retrospectively reviewed data from 493 patients who were confirmed to be pathogenic BRCA1/2 mutation carriers between January 2007 and December 2019. We investigated the oncologic characteristics of PC patients by comparing them with resected sporadic PC and other BRCA-related cancer groups (breast cancer, ovarian cancer, and others). RESULTS: Ten BRCA mutation carriers (2.0%) experienced PC, and PC onset was significantly later than that of BRCA-related breast cancer (age: breast vs. pancreas, 45.0 vs. 53.5 years, p = 0.050). Six patients underwent pancreatectomy and their long-term survival outcomes did not differ from those of sporadic PC patients (disease free survival: BRCA1/2 vs. sporadic, 10.0 months vs. 9.0 months, p = 0.504; overall survival: BRCA1/2 vs. sporadic, 29.0 months vs. 35.0 months, p = 0.520). CONCLUSION: BRCA-mutated PC occurs later than BRCA-mutated breast cancer. Active genetic testing to identify BRCA1/2 mutation carriers at the onset of breast cancer and continuous long-term surveillance of these patients can provide opportunities to detect BRCA-mutated PC at a resectable stage.

Risk Factors for Recurrence in Pancreatic Neuroendocrine Tumor and Size as a Surrogate in Determining the Treatment Strategy: A Korean Nationwide Study.

INTRODUCTION: The prognostic factors of pancreatic neuroendocrine tumor (PNET) are unclear, and the treatment guidelines are insufficient. This study aimed to suggest a treatment algorithm for PNET based on risk factors for recurrence in a large cohort. METHODS: Data of 918 patients who underwent curative intent surgery for PNET were collected from 14 tertiary centers. Risk factors for recurrence and survival analyses were performed. RESULTS: The 5-year disease-free survival (DFS) rate was 86.5%. Risk factors for recurrence included margin status (R1, hazard ratio [HR] 2.438; R2, HR 3.721), 2010 WHO grade (G2, HR 3.864; G3, HR 7.352), and N category (N1, HR 2.273). A size of 2 cm was significant in the univariate analysis (HR 8.511) but not in the multivariate analysis (p = 0.407). Tumor size was not a risk factor for recurrence, but strongly reflected 2010 WHO grade and lymph node (LN) status. Tumors ≤2 cm had lower 2010 WHO grade, less LN metastasis (p < 0.001), and significantly longer 5-year DFS (77.9 vs. 98.2%, p < 0.001) than tumors >2 cm. The clinicopathologic features of tumors <1 and 1-2 cm were similar. However, the LN metastasis rate was 10.3% in 1-2-cm sized tumors and recurrence occurred in 3.0%. Tumors <1 cm in size did not have any LN metastasis or recurrence. DISCUSSION/CONCLUSION: Radical surgery is needed in suspected LN metastasis or G3 PNET or tumors >2 cm. Surveillance for <1-cm PNETs should be sufficient. Tumors sized 1-2 cm require limited surgery with LN resection, but should be converted to radical surgery in cases of doubtful margins or LN metastasis.

Total laparoscopic pancreaticoduodenectomy in patients with periampullary tumors: a learning curve analysis.

BACKGROUND: With continued technical advances in surgical instruments and growing expertise, many surgeons have safely performed laparoscopic pylorus-preserving pancreaticoduodenectomies (LPDs) with good results, and the laparoscopic approach is being performed more frequently. However, this complex procedure requires a relatively long training period to ensure technical competence. The present study aimed to analyze the learning curve for LPD. METHODS: From September 2012 to May 2019, LPDs were performed for 171 patients at the Yonsei University Severance Hospital by a single surgeon. We retrospectively analyzed the demographic and surgical outcomes. The learning curve for LPD was evaluated using both the cumulative sum (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) methods. All variables among the learning curve phases were compared. RESULTS: Based on the CUSUM and the RA-CUSUM analyses, the learning curve for LPD was grouped into three phases: phase I was the initial learning period (cases 1-40), phase II represented the technical competence period (cases 41-100), and phase III was regarded as the challenging period (cases 101-171). CONCLUSIONS: According to the learning curve analysis, 40 cases are required to achieve technical competence in LPD and 100 cases are required to address highly challenging cases.

Laparoscopic pancreaticoduodenectomy reduces incidence of clinically relevant postoperative pancreatic fistula in soft pancreas with a smaller than 2 mm pancreatic duct.

BACKGROUND: Soft pancreas with small pancreatic duct is a known risk factor for postoperative pancreatic fistula (POPF). This study demonstrated the safety and feasibility of laparoscopic duct-to-mucosa pancreaticojejunostomy (PJ) and compared perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with soft pancreas and small pancreatic duct. METHODS: From January 2014 to December 2019, 183 patients underwent LPD and 91 patients underwent OPD by a single surgeon. Data on patients with soft pancreas and combined small pancreatic duct (≤ 2 mm) were retrospectively reviewed. Clinicopathologic characteristics, and perioperative outcomes were compared between LPD and OPD. We evaluated risk factors affecting clinically relevant POPF (CR-POPF). We also correlated calculated risks of POPF and CR-POPF between the two groups. RESULTS: We compared 62 patients in the LPD group and 34 patients in the OPD group. Perioperative outcomes showed less blood loss, shorter hospital stays, and less postoperative pain score on postoperative day (POD)#1 and #5 in LPD compared with OPD. Postoperative complications showed no differences between LPD and OPD. LPD group showed significantly reduced CR-POPF rates compared to the OPD group (LPD 11.3% vs. OPD 29.4%, p = 0.026). Multivariate analysis identified obesity (BMI ≥ 25), thick pancreas parenchyma and open surgery as independent predicting factors for CR-POPF. The LPD group showed less CR-POPF than the OPD group according to POPF risk groups. This difference was more prominent in a high-risk group. CONCLUSION: With appropriate laparoscopic technique, LPD is feasible and safe and reduces CR-POPF in soft pancreas with a small pancreatic duct.

Comprehensive Complication Index or Clavien-Dindo Classification: Which is Better for Evaluating the Severity of Postoperative Complications Following Pancreatectomy?

BACKGROUND: Complications are important indicators of immediate postoperative outcomes. The Clavien-Dindo classification (CDC) is a widely used index for the classification of surgical complications. More recently, the comprehensive complication index (CCI) has also been introduced for classifying postoperative complications. The aim of this study was to compare the relationship of CCI and CDC with clinical or economic parameters. METHODS: The study prospectively enrolled patients from April 2015 to October 2016. Two hundred and twenty-two patients underwent pancreatectomy during the enrolled period. Complications were ranked according to CDC and CCI indices. After analyzing the correlation between CCI and CDC, the correlations of length of stay (LOS) and cost with CCI and CDC were compared. Finally, differences between the correlation coefficients of CDC and CCI parameters were calculated. RESULTS: Complications occurred in 211 patients (95.0%). The correlation between CDC and CCI was r = 0.938. (p < 0.001) Compared to the CDC, CCI showed significantly stronger correlations with LOS and cost of complications (LOS: CCI vs. CDC, r = 0.725 vs. r = 0.630, p < 0.001; cost: CCI vs. CDC, r = 0.774 vs. r = 0.723, p < 0.001). CONCLUSION: CCI is a more accurate classification index, compared to CDC, for evaluating the risk of postoperative complications.

Quality of Recovery of Patients Who Underwent Curative Pancreatectomy: Comparison of Total Intravenous Anesthesia Versus Inhalation Anesthesia Using the QOR-40 Questionnaire.

BACKGROUND: There has been increasing attention on the subjective recovery of patients undergoing cancer surgery. Total intravenous anesthesia (TIVA) and inhaled anesthesia with volatile anesthetics (INHA) are safe and common anesthetic techniques. Currently, TIVA and INHA have only been compared for less invasive and less complex surgeries. This prospective randomized trial aimed to compare the quality of recovery between TIVA and INHA in patients undergoing pancreatoduodenectomy (PD) or distal pancreatectomy (DP) using the Quality of Recovery (QOR)-40 questionnaire. METHODS: We enrolled 132 patients who were randomly assigned to either the desflurane (DES) (INHA, balanced anesthesia with DES and remifentanil infusion) or TIVA (effect-site target-controlled infusion of propofol and remifentanil) groups and completed the QOR-40 questionnaire postoperatively. RESULTS: The mean global QOR-40 score on postoperative day 3 was significantly higher in the TIVA group than in the DES group. In the PD group, the total QOR-40 score was significantly higher in the TIVA group than in the DES group. Moreover, the TIVA group had significantly higher scores in the physical comfort and psychological support QOR-40 dimensions than the DES group. CONCLUSION: TIVA provides better quality of recovery scores on POD 3 for patients undergoing curative pancreatectomy. CLINICAL TRIAL REGISTRATION NUMBER: NCT03447691.

Correlation of Intraoperative End-Tidal Carbon Dioxide Concentration on Postoperative Hospital Stay in Patients Undergoing Pylorus-Preserving Pancreaticoduodenectomy.

BACKGROUND: Hypocapnia has been traditionally advocated during general anesthesia, even though it may induce deleterious physiological effects that result in unfavorable outcomes in patients. This study investigated the association between intraoperative end-tidal carbon dioxide (EtCO2) and length of hospital stay (LOS) in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The medical records of 759 patients from 2006 to 2015 were reviewed. The patients were divided into two groups based on the mean EtCO2 value during general anesthesia: the hypocapnia group (< 35 mmHg) and the normocapnia group (≥ 35 mmHg). The primary outcome was LOS between the groups. Secondary outcomes included the length of intensive care unit (ICU) stay, postoperative 30-day, 1-year, and 2-year mortality, and perioperative factors associated with LOS. RESULTS: A total of 727 patients were finally analyzed. The median LOS of the hypocapnia group was significantly longer than that of the normocapnia group (22 days vs. 18 days, respectively; p < 0.001). Postoperative mortality did not differ between the groups. Cox regression analysis revealed that hypocapnia was an independent risk factor for longer LOS (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.37-1.89; p < 0.001). Age and postoperative pancreatic fistula were also risk factors for a longer LOS. CONCLUSIONS: It was concluded that low levels of intraoperative EtCO2 during general anesthesia were associated with an increased LOS for patients undergoing PPPD.

Initial experience of irreversible electroporation for locally advanced pancreatic cancer in a Korean population.

BACKGROUND: Locally advanced pancreatic cancer (LAPC) is one of the most aggressive malignancies. Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid vessel or duct injury. PURPOSE: To investigate the safety and efficacy of IRE for the management of LAPC in a Korean population. MATERIAL AND METHODS: Twelve patients (median age 64 years; age range 46-73 years) treated between December 2015 and March 2017 underwent intraoperative IRE for LAPC. Technical success and clinical outcomes, including complications, serum pancreatic enzyme levels, overall survival (OS), and progression-free survival (PFS), were evaluated. RESULTS: Tumors were located in the pancreas head in 7 (58.3%) patients and in the body/tail in 5 (41.7%) patients. The median tumor diameter in the longest axis was 3.1 cm. Vascular invasion was observed in all patients and bowel abutment in 3 (25%) patients. Technical success was achieved in all patients. The median serum levels of amylase and lipase were 55 U/L and 31 U/L, respectively, at baseline, increased to 141.5 U/L (P = 0.008) and 53 U/L (P = 0.505), respectively, one day after IRE, and normalized after one week. The rate of 30-day mortality of unknown relation was 8.3% (one individual experienced massive hematemesis 12 days after IRE). The median OS from diagnosis and IRE was 24.5 months and 13.5 months, respectively. The median PFS from diagnosis and IRE was 19.2 months and 8.6 months, respectively. CONCLUSION: For patients with LAPC, IRE appears to be a promising treatment modality with an acceptable safety profile.

Tumor-Specific miRNA Signatures in Combination with CA19-9 for Liquid Biopsy-Based Detection of PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive malignancies and has high mortality and poor survival rates. Therefore, there is an urgent need to discover non-invasive biomarkers for early detection before PDAC reaches the incurable stage. We hypothesized that liquid biopsy of PDAC-derived extracellular vesicles (PDEs) containing abundant microRNAs (miRNAs) could be used for early diagnosis of PDAC because they can be selectively enriched and because they are biologically stable. We isolated PDEs by immunocapture using magnetic beads, and we identified 13 miRNA candidates in 20 pancreatic cancer patients and 20 normal controls. We found that expression of five miRNAs, including miR-10b, miR-16, miR-155, miR-429, and miR-1290, was markedly higher in PDEs. Furthermore, the miRNA signatures along with serum carbohydrate antigen 19-9 (CA19-9) were optimized by logistic regression, and the miRNA signature and CA19-9 combination markers (CMs) were effective at differentiating PDAC patients from normal controls. As a result, the CMs represented a high sensitivity (AUC, 0.964; sensitivity, 100%; specificity, 80%) and a high specificity (AUC, 0.962; sensitivity, 85.71%; specificity, 100%). These findings suggest that five miRNAs expressed in PDEs and CA19-9 are valuable biomarkers for screening and diagnosis of pancreatic cancer by liquid biopsy.