Suggested use of empirical antibiotics in acute cholecystitis based on bile microbiology and antibiotic susceptibility.

BACKGROUND: Bacterial infection is common in acute cholecystitis (AC). To identify appropriate empirical antibiotics, we investigated AC-associated microorganisms and their susceptibilities to antibiotics. We also compared preoperative clinical findings of patients grouped according to specific microorganisms. METHODS: Patients who underwent laparoscopic cholecystectomy for AC between 2018 and 2019 were enrolled. Bile cultures and antibiotic susceptibility tests were performed, and clinical findings of patients were noted. RESULTS: A total of 282 patients were enrolled (147 culture-positive and 135 culture-negative). The most frequent microorganisms were Escherichia (n = 53, 32.7%), Enterococcus (n = 37, 22.8%), Klebsiella (n = 28, 17.3%), and Enterobacter (n = 18, 11.1%). For Gram-negative microorganisms, second-generation cephalosporin (cefotetan: 96.2%) was more effective than third-generation cephalosporin (cefotaxime: 69.8%). Vancomycin and teicoplanin (83.8%) were the most effective antibiotics for Enterococcus. Patients with Enterococcus had higher rates of CBD stones (51.4%, p = 0.001) and biliary drainage (81.1%, p = 0.002), as well as higher levels of liver enzymes, than patients with other microorganisms. Patients with ESBL-producing bacteria had higher rates of CBD stones (36.0% vs. 6.8%, p = 0.001) and biliary drainage (64.0% vs. 32.4%, p = 0.005) than those without. DISCUSSION: Preoperative clinical findings of AC are related to microorganisms in bile samples. Periodic antibiotic susceptibility tests should be conducted to select appropriate empirical antibiotics.

Incidence of bactibilia and related factors in patients who undergo cholecystectomy.

Purpose: In general, bile is normally sterile. However, there are reports bactibilia may occur in certain instances, though the causal factors are unclear. We analyzed possible preoperative predictors of bactibilia upon cholecystectomy. Methods: Bile samples were collected during cholecystectomies from November 2018 to November 2019. A total of 428 open or laparoscopic cholecystectomies were performed. Preoperative, intraoperative, and postoperative variables were compared between the culture-positive and culture-negative groups. Results: One hundred fifty-seven patients (36.7%) were culture-positive. Gram-negative bacteria (95 [61.0%]) were more common. Escherichia coli (38 [40.0%]) and Enterobacter (22 [23.2%]) were the most common species. In univariate analysis, age of ≥70 years (P < 0.001), male sex (P < 0.001), high American Society of Anesthesiologists physical status grades (P = 0.001), diabetes mellitus (P = 0.002), jaundice (P = 0.007), high Tokyo Guideline grades (P = 0.008), percutaneous transhepatic gallbladder drainage (PTGBD; P < 0.001), endoscopic retrograde cholangiopancreatography (ERCP; P < 0.001) were identified as a risk factors for bactibilia. In multivariate analysis, age of ≥70 years (hazard ratio [HR], 2.874; 95% confidence interval [CI], 1.769-4.670; P = 0.001), ERCP (HR, 9.001; 95% CI, 4.833-16.75; P < 0.001), and PTGBD (HR, 2.866; 95% CI, 1.440-4.901; P = 0.002) were independent risk factors for bactibilia. Conclusion: Among patients who underwent cholecystectomy, those who were elderly, symptomatic, and underwent preoperative drainage were more likely to have bactibilia. In such cases, surgeons should take care to prevent bile leakage during surgery and consider administering appropriate antibiotics.

Multi-biomarker panel prediction model for diagnosis of pancreatic cancer.

BACKGROUND/PURPOSE: The current study aimed to develop a prediction model using a multi-marker panel as a diagnostic screening tool for pancreatic ductal adenocarcinoma. METHODS: Multi-center cohort of 1991 blood samples were collected from January 2011 to September 2019, of which 609 were normal, 145 were other cancer (colorectal, thyroid, and breast cancer), 314 were pancreatic benign disease, and 923 were pancreatic ductal adenocarcinoma. The automated multi-biomarker Enzyme-Linked Immunosorbent Assay kit was developed using three potential biomarkers: LRG1, TTR, and CA 19-9. Using a logistic regression model on a training data set, the predicted values for pancreatic ductal adenocarcinoma were obtained, and the result was classification into one of the three risk groups: low, intermediate, and high. The five covariates used to create the model were sex, age, and three biomarkers. RESULTS: Participants were categorized into four groups as normal (n = 609), other cancer (n = 145), pancreatic benign disease (n = 314), and pancreatic ductal adenocarcinoma (n = 923). The normal, other cancer, and pancreatic benign disease groups were clubbed into the non-pancreatic ductal adenocarcinoma group (n = 1068). The positive and negative predictive value, sensitivity, and specificity were 94.12, 90.40, 93.81, and 90.86, respectively. CONCLUSIONS: This study demonstrates a significant diagnostic performance of the multi-marker panel in distinguishing pancreatic ductal adenocarcinoma from normal and benign pancreatic disease states, as well as patients with other cancers.

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.

Impact of surgery on survival outcomes for Bismuth type IV Klatskin tumors.

BACKGROUND: Bismuth-Corlette type IV Klatskin tumors have conventionally been considered unresectable. This retrospective study aimed to demonstrate the survival improvement of patients with type IV Klatskin tumors when resected and suggest possible radiological features for R0 resectability. METHODS: Data on type IV Klatskin tumors diagnosed between 2008 and 2019 were reviewed retrospectively. Patients with distant metastasis, concomitant other cancers at the initial state, extensive vascular invasions, poor liver function, and poor general condition were excluded. The survival outcomes of patients and radiologic parameters of bile duct tumors were compared between the curative resection (R0, 1 resection) and non-resection groups. RESULTS: The demographic findings of patients with curative resection (n = 48) and non-resection (n = 111) were comparable. Both were potentially resectable in the initial state. The postoperative morbidity was 22.9% and the 90-day mortality 4.2%. There was a significant difference in the median survival among the curative-intended resection, palliative treatment, and supportive care groups (35, 16, and 12 months, respectively; P < 0.001). DISCUSSION: In patients with type IV Klatskin tumor without extensive tumor invasion into adjacent tissues, including major vessels, surgical resection can be considered for better survival. CLINICAL REGISTRATION NUMBER: IRB No. 2009-100-1157.

In vivo study for the hemostatic efficacy and foreign body reaction of a new powder-type polysaccharide hemostatic agent.

PURPOSE: Various hemostatic agents have been introduced in therapy as postoperative bleeding is a poor prognostic factor for postoperative outcomes. These products can be divided into those that directly promote the hemostatic cascade and those that physically form a barrier by absorbing blood. The latter, powder-type hemostatic agents have the advantages of being inexpensive and more absorbable with less foreign body reactions (FBRs) and are applicable to a relatively wide area. This study was conducted to verify the safety and efficacy of a newly invented polysaccharide product (OOZFIX, Theracion Biomedical), which improves blood absorption and hemostatic effects. METHODS: Two separate animal experiments were performed. The first evaluated FBRs histologically at 3 days, 2 weeks, and 4 weeks, after implantation of OOZFIX in rats, and the second compared hemostatic performance of OOZFIX and Arista AH (Bard) in the porcine liver punch biopsy model. RESULTS: We found minimal FBRs in the 3-day group and no reactions in both the 2-week and 4-week groups after implantation of hemostatic agents. The time to hemostasis of OOZFIX was not significantly different from that of Arista AH (median [interquartile range]: 9 [6-10] minutes vs. 8 [6-10] minutes, respectively; P = 0.522). When comparing the serial bleeding grade tendency, there was no statistical difference between OOZFIX and Arista AH (P = 0.656). CONCLUSION: OOZFIX caused a minimal FBR that disappeared within 2 weeks in vivo, and its hemostatic performance was comparable with that of an existing agent, Arista AH. Further clinical studies are required in the future.

Preoperative carbohydrate antigen 19-9 and standard uptake value of positron emission tomography-computed tomography as prognostic markers in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Among various prognostic factors of pancreatic cancer, preoperative clinical information is obtained by imaging modality. This study aimed to evaluate clinical usefulness of preoperative carbohydrate antigen and preoperative standard uptake value in 18F-fluorodeoxyglucose positron emission tomography as predictive biological markers for resectable pancreatic ductal adenocarcinoma. METHODS: A total of 189 patients with PDAC who underwent preoperative PET-computed tomography were evaluated. Patients underwent neoadjuvant chemotherapy, and R2 resection was excluded. The correlation between SUVmax and clinicopathologic parameters was analyzed. The C-tree statistical method was used to estimate cutoff values of logCA19-9 and SUVmax for survival rate. A multivariate analysis was conducted to identify prognostic factors for overall survival. RESULTS: The median duration of OS was 26 months, and the 5-year survival rate was 22.4%. The optimal cutoff values for CA19-9 level was 150 U/mL and SUVmax was 5.5. When subjects were divided into three groups according to the combination of CA19-9 level and SUVmax from C-tree (high-risk group, CA19-9 > 150 U/mL and SUVmax > 5.5; intermediate-risk group, CA19-9 ≤ 150 U/mL and SUVmax > 5.5 or CA19-9 > 150 U/mL and SUVmax ≤ 5.5; and low-risk group, CA19-9 ≤ 150 U/mL and SUVmax ≤ 5.5), there was a significant 5YSR difference (5.6%, 24.3%, and 36.5%, P < .001). The multivariate analysis revealed high SUVmax, high preoperative CA19-9 level, venous invasion, and adjuvant chemotherapy were prognostic factors of OS. CONCLUSIONS: CA19-9 and SUVmax are strong prognostic biological factors in resectable PDAC. Moreover, patients with high CA19-9 level and SUVmax are not indicated for upfront surgery.

Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

Outcomes of 5000 pancreatectomies in Korean single referral center and literature reviews.

BACKGROUND: Pancreatic resection has higher postoperative mortality and morbidity rates than other abdominal operations. Some centers have reported remarkable postoperative outcomes of minimally invasive surgery. This study investigated the chronological trends of pancreatectomies by analyzing a large-scale database. METHODS: The medical records of 5175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were reviewed. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed. RESULTS: Patient age and the proportion with pancreatic cancer have increased over time. From 2015 to 2019, pancreatic cancer was the most common cause for resection (35.9%), followed by pancreatic cysts (24.8%) and common bile duct cancer (13.4%). The incidence of postoperative complications tended to decrease over time (26.0% from 2000 to 2004; 20.8% from 2015 to 2019). A comparison of survival outcomes of periampullary malignancies by period revealed that patients with pancreatic cancer significantly improved (5-year survival rate: 14.4% before 2000% vs 15.2% from 2000 to 2009% vs 29.0% after 2009, P < .001). CONCLUSIONS: Postoperative outcomes of pancreatic resection have improved over the past few decades. To improve outcomes in the future, an active multidisciplinary approach and postoperative management are required.

Radiological tumour invasion of splenic artery or vein in patients with pancreatic body or tail adenocarcinoma and effect on recurrence and survival.

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.

Conversion surgery for initially unresectable extrahepatic biliary tract cancer.

BACKGROUNDS/AIMS: Surgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents. METHODS: Patients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively. RESULTS: Twelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies. CONCLUSIONS: Conversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.

Comparison of perioperative short-term outcomes and oncologic long-term outcomes between open and laparoscopic distal pancreatectomy in patients with pancreatic ductal adenocarcinoma.

PURPOSE: Laparoscopic distal pancreatectomy (LDP) is widely performed but its efficacy and safety are not established for malignant lesions. This study was aimed to compare outcomes of LDP and open distal pancreatectomy (ODP) in pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients who underwent distal pancreatectomy for PDAC between 2009 and 2017 were enrolled. The preoperative clinical stage was evaluated and propensity score matching (PSM) was performed using age, sex, The American Joint Committee on Cancer 8th clinical T stage, and other organ involvement. RESULTS: In 186 patients enrolled, 35 (18.8%) received LDP. The ODP group showed larger tumor size and frequent involvement of other organs in preoperative images. However, after PSM, these differences were balanced. R0 resection (90.5% vs. 94.3%, P = 0.730), harvested lymph nodes (14.3 vs. 12.6, P = 0.380) and pathologic T stage (P = 0.474) were comparable between ODP and LDP groups, respectively. LDP demonstrated shorter operation time, less postoperative pain, and shorter hospitalization (14.4 days vs. 11.1 days, P = 0.026). In terms of long-term oncologic outcomes, median overall survival (32 months vs. 28 months, P = 0.724) and disease-free survival (18 months vs. 19 months, P = 0.926) were comparable. CONCLUSION: LDP demonstrated better short-term outcomes and comparable long-term outcomes compared with ODP. LDP is a safe and feasible procedure for PDAC.

The diagnostic and prognostic values of inflammatory markers in intraductal papillary mucinous neoplasm.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an broad-spectrum disease from benign to malignant. Inflammatory markers are known as prognostic predictors in various diseases. The purpose of this study was to determine the predictive value of inflammatory markers for prognosis in IPMN. METHODS: From April 1995 to December 2016, patients who underwent pancreatectomy with pathologically confirmed IPMN at four tertiary centers were enrolled. Patients with a history of pancreatitis or cholangitis, and other malignancies were excluded. Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and advanced lung cancer inflammation index (ALI) were calculated. RESULTS: Of all, ninety-eight patients (26.8%) were diagnosed as invasive IPMN. The NLR and PLR were significantly elevated in invasive IPMN than in non-invasive disease (2.0 vs 1.8, p = 0.004; 117.1 vs 107.4, p = 0.009, respectively). ALI was significantly higher in non-invasive IPMN than in invasive disease (58.1 vs 45.9, p < 0.001). In multivariate analysis, only NLR showed significant association among the inflammatory markers studied (p = 0.044). In invasive IPMN, the five-year recurrence-free survival rate for NLR less than 3.5 was superior to the rest (59.1 vs 42.2, p = 0.023). CONCLUSION: NLR may help to rightly select IPMN patients who will require surgery and may serve as a useful prognostic factor.

Changes in postoperative long-term nutritional status and quality of life after total pancreatectomy.

PURPOSE: Quality of life (QoL) is widely known to be poor after total pancreatectomy (TP) due to the loss of pancreatic function and poor nutritional status, but prospective studies on changes in QoL over time are lacking. The aim of this study was to prospectively evaluate the short- and long-term consequences of pancreatic exocrine insufficiency, changes in nutritional status, and their associated effects on QoL after TP. METHODS: Prospective data were collected from patients who underwent TP between 2008 and 2018. Validated questionnaires (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ] Core 30, EORTC QLQ-pancreatic cancer module, and the Mini Nutritional Assessment), measured frequency of bowel movement, relative body weight (RBW), triceps skinfold thickness (TSFT), and serum levels of protein, albumin, transferrin, and hemoglobin A1c were collected serially for 1 year. RESULTS: Thirty patients who underwent TP were eligible for the study. Bowel movement frequency increased over time, and the RBW and TSFT were lowest by 1 year. The global health status score showed no significant difference over time. At 3 months, physical and role function scores as well as symptoms of fatigue, constipation, and digestive difficulties worsened significantly. Most indices recovered after 1 year, but poorer physical function scores, digestive difficulties, and altered bowel habits persisted. CONCLUSION: Because some symptoms do not recover over time, careful follow-up and supportive postoperative management are needed for TP patients, including nutritional support with pancreatic enzyme replacement and education about medication adherence and diet.

CORRIGENDUM: Addition of data source: Diagnostic model for pancreatic cancer using a multi-biomarker panel.

[This corrects the article on p. 144 in vol. 100, PMID: 33748028.].

Peritumoral lymph nodes in pancreatic cancer revisited; is it truly equivalent to lymph node metastasis?

BACKGROUND: Lymph node (LN) metastasis is a well-known poor prognostic factor of pancreatic cancer. LN metastasis, through direct invasion of tumor cell to peritumoral lymph nodes (PTLN), is treated as the same as those which spread through lymphatic channels. This study aimed to evaluate the impact of PTLN invasion on the oncologic outcome of pancreatic cancer. METHODS: Five hundred and six patients who underwent operation for pancreatic ductal adenocarcinoma from 2012 to 2018 were reviewed. PTLN invasion was defined as direct invasion of tumor cells in contact with main tumor. RESULTS: Among the 506 patients, 112 patients (22.1%) had PTLN invasion. PTLN invasion group (PTLNI) showed better disease-free survival than regional LN metastasis group (RLNM) and combined LN metastasis group (CLNM) (PTLNI 21 vs RLNM 11 vs CLNM 12 months, P = .003). There was no significant difference between N0 and PTLNI (PTLNI 21 vs N0 23 months, P = .999). In multivariate analysis, conventional LN metastasis was a significant factor compared to N0, but PTLN invasion was not (hazard ratio 0.786 [0.507-1.220], P = .283). CONCLUSION: Because PTLN invasion does not adversely affect survival in the same way as LN metastasis does, pancreatic cancer-may be overstaged if PTLN invasion were dealt in the same manner as a metastatic LN. Therefore, PTLN invasion should be disregarded from current nodal staging system.

Diagnostic model for pancreatic cancer using a multi-biomarker panel.

PURPOSE: Diagnostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) have been used for early detection to reduce its dismal survival rate. However, clinically feasible biomarkers are still rare. Therefore, in this study, we developed an automated multi-marker enzyme-linked immunosorbent assay (ELISA) kit using 3 biomarkers (leucine-rich alpha-2-glycoprotein [LRG1], transthyretin [TTR], and CA 19-9) that were previously discovered and proposed a diagnostic model for PDAC based on this kit for clinical usage. METHODS: Individual LRG1, TTR, and CA 19-9 panels were combined into a single automated ELISA panel and tested on 728 plasma samples, including PDAC (n = 381) and normal samples (n = 347). The consistency between individual panels of 3 biomarkers and the automated multi-panel ELISA kit were accessed by correlation. The diagnostic model was developed using logistic regression according to the automated ELISA kit to predict the risk of pancreatic cancer (high-, intermediate-, and low-risk groups). RESULTS: The Pearson correlation coefficient of predicted values between the triple-marker automated ELISA panel and the former individual ELISA was 0.865. The proposed model provided reliable prediction results with a positive predictive value of 92.05%, negative predictive value of 90.69%, specificity of 90.69%, and sensitivity of 92.05%, which all simultaneously exceed 90% cutoff value. CONCLUSION: This diagnostic model based on the triple ELISA kit showed better diagnostic performance than previous markers for PDAC. In the future, it needs external validation to be used in the clinic.

Comparison of Clinical Outcomes of Borderline Resectable Pancreatic Cancer According to the Neoadjuvant Chemo-Regimens: Gemcitabine versus FOLFIRINOX.

Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p<0.001). The 2- and 5-year survival rates (YSRs) were significantly higher after FOLFIRINOX (2YSR, 72.2%; 5YSR, 46.0%) than after gemcitabine (2YSR, 58.4%; 5YSR, 19.1%; p=0.041). The margin negative rate was comparable (gemcitabine, 94.1%; FOLFIRINOX, 92.4%; p=0.753), and the tumor size change in percentage showed only a marginal difference (gemcitabine, 20.5%; FOLFIRINOX, 29.0%; p=0.069). Notably, the metastatic recurrence rate was significantly lower in the FOLFIRINOX group (n=20, 52.6%) than in the gemcitabine group (n=22, 78.6%; p=0.001). The rate of adverse events after chemotherapy was significantly higher with FOLFIRINOX than with gemcitabine (43.9%, 20.6%, respectively; p=0.037). Conclusions: FOLFIRINOX provided more clinical and oncological benefit than gemcitabine, with significantly higher overall survival and lower cumulative recurrence rates in BRPC. However, since FOLFIRINOX causes more adverse effects, the regimen should be individualized based on patient's general condition and clinical status.

Adverse oncologic effects of preoperative biliary drainage on early stage ampulla of Vater cancer.

BACKGROUND: The preoperative biliary drainage (PBD) in ampulla of Vater (AoV) cancer is indiscriminately performed without logical backgrounds. This study was performed to evaluate the effect of PBD on short and long-term outcomes in AoV cancer. METHODS: 313 patients who underwent pancreaticoduodenectomy and were pathologically diagnosed as AoV cancer between January 2000 and December 2014 were reviewed. RESULTS: 167 patients (53.4%) underwent PBD: Endoscopic drainage was performed in 106 patients (33.9%) and percutaneous drainage in 61 (19.5%). The postoperative complication rate of PBD group was significantly higher than that of upfront surgery group (48.5% vs. 38.4%, p = 0.045). The 5-year disease-free survival rate (5Y-DFSR) was significantly lower in PBD group compared to upfront surgery group (53.8% vs. 74.3%, p < 0.001). Worse 5Y-DFSR of PBD group was more evident in T1/T2 stage (59.2% vs. 84.1%, p < 0.001). In multivariate analysis with T1/T2 staged patients, PBD was independently associated with worse outcome (hazard ratio 2.145 [95% confidence interval, 1.202-3.826], p = 0.010). CONCLUSION: For T1/T2 AoV cancer, PBD adversely affected the short-term postoperative complication rate as well as the long-term oncologic outcomes. Therefore, especially in patients with T1/T2 AoV cancer, routine practice of PBD should be refrained and be reserved for selected cases such as cholangitis.