Total Sealing Technique (TST) with a bipolar vessel sealing system reduces lymphorrhea and seroma formation for axillary lymph node dissection in primary breast cancer.

Background: The purpose of this study is to evaluate the potential of a novel surgical procedure, the Total Sealing Technique (TST), using the latest bipolar vessel sealing system (BVSS; LigaSure™ Exact Dissector) to reduce lymphatic leakage and seroma formation after electrocautery axillary lymph node dissection (ALND) in breast cancer surgery. Prolonged drainage is a common occurrence after ALND, primarily due to lymphatic leakage. In addition, the presence of seroma often leads to delays in the administration of postoperative adjuvant chemotherapy even after drain removal. Methods: We conducted a comparative analysis of 36 patients who underwent total mastectomy with ALND using conventional electrocautery technique (CONV) during the first 3 years, and 35 patients who underwent the same procedure using TST during the subsequent 3 years. The following factors were compared to assess the impact of TST: operation time, blood loss, total drainage volume, mean time to drain removal, postoperative hospital stay, mean time to initiation of postoperative chemotherapy, and postoperative complications in each group. Results: TST significantly reduced drainage volume (360.5 vs. 820.6 mL, p < 0.001), days to drain removal (4.8 vs. 6.8 days, p < 0.001), postoperative hospital stay (5.9 vs. 9.6 days, p < 0.001), the incidence of seroma (28.6 % vs. 65.9 %, p = 0.001), and time to chemotherapy initiation (33.1 vs. 61.4 days, p < 0.001) compared to CONV. Conclusions: TST in total mastectomy with ALND effectively decreases the incidence of lymphorrhea and seroma formation; thus, it can be recommended for total mastectomy with ALND.

Total neoadjuvant therapy improves survival of patients with borderline resectable pancreatic cancer with arterial involvement.

Aim: This study aimed to evaluate the prognostic impact of total neoadjuvant therapy (TNT) for borderline resectable pancreatic cancer with arterial involvement (BR-A) pancreatic cancer. Methods: We analyzed 81 patients initially diagnosed as BR-A who received initial treatments between 2007 and 2021. Among them, 18 patients who received upfront surgery were classified as the UFS group, while 30 patients who were treated with neoadjuvant chemoradiotherapy were classified as the NACRT group. Furthermore, 33 patients who planned to receive a combination treatment of over 6 months of systemic chemotherapies followed by chemoradiotherapy before surgery were classified as the TNT group. Results: There were no significant differences in the patients' backgrounds between the three groups at the time of initial treatment. The resection rates of the UFS, NACRT, and TNT groups were 89%, 77%, and 67%, respectively. NACRT had no impact on the prognosis compared to upfront surgery. In sharp contrast, the TNT group had a significantly better prognosis compared to the other groups, especially after pancreatic resection. Multivariate analysis demonstrated that TNT and resection were independent prognostic factors for the patients of BR-A. Conclusion: TNT can be a promising therapeutic strategy for patients with BR-A.

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial).

Background: Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods: This single-arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP-NAT, (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4-week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results: Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence-free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions: This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP-NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration: UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.

Clinical practice guidelines for duodenal cancer 2021.

Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

Clinically Relevant Late-Onset Biliary Complications After Pancreatoduodenectomy.

BACKGROUND: Late-onset biliary complications (LBC) after pancreatoduodenectomy (PD) can be serious. This study aimed to clarify the frequency and risk factors of severe LBC after PD. METHODS: We defined LBC as biliary complications occurring 3 months after PD and severe LBC as cases that required intensive care. A total of 318 patients who underwent PD between 2010 and 2018 with at least 1 year of postoperative follow-up were evaluated. RESULTS: Hospitalization for severe LBC was required in 59 patients (19%), of whom 20 had liver abscesses (6.3%); 18, acute cholangitis (5.7%); 12, biliary stones (3.8%); and 21, biliary strictures (6.6%). Interventional radiological or endoscopic treatment was required in 32 patients (10%), of whom 9 had a benign primary disease with biliary stones and/or strictures. Thirteen of the remaining 23 patients with a malignant primary disease had liver abscesses and cholangitis. Significant independent risk factors for severe LBC in patients with malignant primary disease were recurrence around the hepaticojejunostomy (odds ratio 6.5, P = 0.013) and chemotherapy (odds ratio 13.5, P < 0.001). CONCLUSIONS: Severe LBC after PD may occur regardless of whether the primary disease is benign or malignant. The course of severe LBC differs according to the primary disease, and therefore, appropriate follow-up and optimal treatment should be recommended according to the condition of the patient and the disease state.

Surgical results of non-ampullary duodenal cancer: a nationwide survey in Japan.

BACKGROUND: As non-ampullary duodenal cancer is relatively rare, the optimal treatment strategy, including the appropriate surgical procedure and efficacy of adjuvant chemotherapy, remains unclear. This nationwide survey aimed to clarify the actual lymph node spread pattern and determine the optimal treatment strategy for this disease, using a large-scale database. METHODS: We used a questionnaire and a retrospective registry of 1083 patients with non-ampullary duodenal cancer who had undergone surgery during 2008-2017 in 114 high-volume Japanese Society of Hepatobiliary and Pancreatic Surgery-certified training institutions. Propensity score-matched analyses were conducted to minimise background bias. Cox regression was performed to identify covariates associated with recurrence-free survival. There were distinct disparities in the nodal dissection rate according to the predominant tumor location and tumor invasion depth. Metastases were frequently observed in the peripancreatic nodes and those along the superior mesenteric artery, irrespective of tumor location. Their dissection seemed to be beneficial for improved survival. In the overall cohort, no survival benefit was observed in patients who received adjuvant chemotherapy when compared with that in patients who underwent surgery alone. Nevertheless, in the matched cohort, adjuvant chemotherapy for > 6 months was associated with a significant improvement in recurrence-free survival (median: 43.5 vs. 22.5 months, p = 0.016), particularly in patients with tumor invasion of the subserosa or deeper tumor invasion, lymph node metastasis, or elevated serum carbohydrate antigen 19-9 levels. CONCLUSION: Pancreatoduodenectomy should be the standard procedure for advanced non-ampullary duodenal cancer. Adjuvant chemotherapy for > 6 months, especially for advanced tumors, significantly improves survival.

Transcriptomic Profiling Identifies an Exosomal microRNA Signature for Predicting Recurrence Following Surgery in Patients With Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: We performed genome-wide expression profiling to develop an exosomal miRNA panel for predicting recurrence following surgery in patients with PDAC. SUMMARY OF BACKGROUND DATA: Pretreatment risk stratification is essential for offering individualized treatments to patients with PDAC, but predicting recurrence following surgery remains clinically challenging. METHODS: We analyzed 210 plasma and serum specimens from 4 cohorts of PDAC patients. Using a discovery cohort (n = 25), we performed genome-wide sequencing to identify candidate exosomal miRNAs (exo-miRNAs). Subsequently, we trained and validated the predictive performance of the exo-miRNAs in two clinical cohorts (training cohort: n = 82, validation cohort: n = 57) without neoadjuvant therapy (NAT), followed by a post-NAT clinical cohort (n = 46) as additional validation. RESULTS: We performed exo-miRNA expression profiling in plasma specimens obtained before any treatment in a discovery cohort. Subsequently we optimized and trained a 6-exo-miRNA risk-prediction model, which robustly discriminated patients with recurrence [area under the curve (AUC): 0.81, 95% confidence interval (CI): 0.70-0.89] and relapse-free survival (RFS, P < 0.01) in the training cohort. The identified exo-miRNA panel was successfully validated in an independent validation cohort (AUC: 0.78, 95% CI: 0.65- 0.88, RFS: P < 0.01), where it exhibited comparable performance in the post-NAT cohort (AUC: 0.72, 95% CI: 0.57-0.85, RFS: P < 0.01) and emerged as an independent predictor for RFS (hazard ratio: 2.84, 95% CI: 1.30-6.20). CONCLUSIONS: We identified a novel, noninvasive exo-miRNA signature that robustly predicts recurrence following surgery in patients with PDAC; highlighting its potential clinical impact for optimized patient selection and improved individualized treatment strategies.

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study.

BACKGROUND: Pancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma. METHODS: A total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively. RESULTS: Sixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival. CONCLUSION: Direct invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.

Is Neoadjuvant Treatment Justified in Clinical T1 Pancreatic Ductal Adenocarcinoma?

Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical T1 stage pancreatic cancer. Methods: Data from two centers were included in the comparative analysis, with overall and recurrence-free survival as primary outcomes, between January 2010 and December 2017. Results: In total, 45 patients were retrospectively reviewed in this study. Two patients in the neoadjuvant group were excluded because of distant metastasis during neoadjuvant treatment. Finally, 43 patients underwent a pancreatectomy for clinical T1 pancreatic cancer, of whom, 35 and 8 patients underwent upfront surgery and neoadjuvant treatment, respectively. Overall survival was similar in the two study groups (5-year overall survival rate: neoadjuvant group, 75%; upfront surgery group, 43.9%, p = 0.066). Conclusions: In our study on patients with clinical T1 stage pancreatic cancer, no significant differences were reported in the oncological outcome in the neoadjuvant therapy group. Large-scale prospective studies are needed to determine the survival benefits of neoadjuvant treatment for early-stage pancreatic cancer.

Clinical relevance of CD70 expression in resected pancreatic cancer: Prognostic value and therapeutic potential.

BACKGROUND: Aberrant expression of CD70 in several malignancies is potentially associated with poor patient prognosis and could serve as a therapeutic target. However, the clinical relevance of CD70 expression in pancreatic cancer has not been thoroughly explored. METHODS: We evaluated CD70 expression in 166 surgical specimens obtained from human patients with pancreatic cancer. We analyzed the function of CD70 in proliferation and migration using pancreatic cancer cell lines with silenced CD70 expression. RESULTS: CD70 expression was positively stained in 42 patients (25%). In the whole cohort, high CD70 expression was not associated with overall survival (OS: 33.1 vs. 40.8 months, P = 0.256), although it was significantly associated with inferior OS in a population of patients that completed adjuvant chemotherapy (OS: 45.4 vs. 63.8 months, P = 0.027). Moreover, the incidence of hematogenous metastasis was significantly higher in patients with high CD70 expression than in those with low CD70 expression (P = 0.020). This finding was also statistically significant in multivariate analyses (P = 0.001). In vitro experiments demonstrated that CD70 expression contributed to cancer cell proliferation independently of gemcitabine treatment as well as cell migration. Furthermore, real-time polymerase chain reaction analysis of frozen surgical tissues showed a correlation between the expression of CD70 and mesenchymal markers. CONCLUSIONS: CD70 expression in pancreatic cancer might be involved in hematogenous metastasis. Furthermore, our results imply that CD70 overexpression can serve as a novel prognostic factor and a potential therapeutic target in patients who have completed adjuvant chemotherapy.

Limited resection vs. pancreaticoduodenectomy for primary duodenal adenocarcinoma: a systematic review and meta-analysis.

It is well known that surgery is the mainstay treatment for duodenal adenocarcinoma. However, the optimal extent of surgery is still under debate. We aimed to systematically review and perform a meta-analysis of limited resection (LR) and pancreatoduodenectomy for patients with duodenal adenocarcinoma. A systematic electronic database search of the literature was performed using PubMed and the Cochrane Library. All studies comparing LR and pancreatoduodenectomy for patients with duodenal adenocarcinoma were selected. Long-term overall survival was considered as the primary outcome, and perioperative morbidity and mortality as the secondary outcomes. Fifteen studies with a total of 3166 patients were analyzed; 995 and 1498 patients were treated with limited resection and pancreatoduodenectomy, respectively. Eight and 7 studies scored a low and intermediate risk of publication bias, respectively. The LR group had a more favorable result than the pancreatoduodenectomy group in overall morbidity (odd ratio [OR]: 0.33, 95% confidence interval [CI] 0.17-0.65) and postoperative pancreatic fistula (OR: 0.13, 95% CI 0.04-0.43). Mortality (OR: 0.96, 95% CI 0.70-1.33) and overall survival (OR: 0.61, 95% CI 0.33-1.13) were not significantly different between the two groups, although comparison of the two groups stratified by prognostic factors, such as T categories, was not possible due to a lack of detailed data. LR showed long-term outcomes equivalent to those of pancreatoduodenectomy, while the perioperative morbidity rates were lower. LR could be an option for selected duodenal adenocarcinoma patients with appropriate location or depth of invasion, although further studies are required.

A gene expression signature for predicting response to neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), optimal treatment selection, including multimodality regimens such as neoadjuvant chemoradiotherapy (NACRT), can be clinically transformative. Unfortunately, currently no predictive biomarkers are available that can guide the use of NACRT in PDAC patients. Accordingly, herein we developed a novel gene signature that can preoperatively predict NACRT-sensitivity in PDAC patients. Herein, we evaluated the performance of a 10-gene panel in 749 PDAC cases, which included two public datasets (The Cancer Genome Atlas and International Cancer Genome Consortium; n = 276), and three clinical specimen cohorts (n = 417), and a pre-NACRT endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy cohort (n = 56). The potential predictive performance of this signature was evaluated and compared to CA-19-9 levels and key clinicopathological factors. We first evaluated the prognostic potential of a 10-gene panel which significantly predicted overall survival in both public datasets (P < .01, P < .01), and two in-house patient cohorts (P < .01, P = .04). In the pre-NACRT EUS-FNA cohort, we established a radio-sensitivity gene panel (RSGP) which yielded highly robust (area under the curve [AUC] = 0.91; 95% CI: 0.81-0.97) for predicting response to gemcitabine-based NACRT. Multivariate logistic regression analysis revealed that RSGP was an independent predictor for response to NACRT (OR = 2.70; 95% CI: 1.25-5.85), and this response-prediction was even more robust when CA-19-9 levels were included into the model. In conclusion, we have validated and developed a novel gene signature that is highly robust in predicting response to NACRT, even in preoperative settings, highlighting its clinical significance for optimizing and personalizing treatment strategies in PDAC patients.

No Significant Effect of Daikenchuto (TJ-100) on Peritoneal IL-9 and IFN-γ Levels After Pancreaticoduodenectomy.

AIM AND BACKGROUND: TJ-100 is a traditional Japanese medicine that affects inflammation and gastrointestinal motility, and is used as a preventive and treatment for paralytic ileus. This study aims at determining the effect of TJ-100 on the peritoneal levels of IFN-γ/IL-9, cytokines related to ileus, after pancreaticoduodenectomy (PD) in a clinical setting. METHODS: This was a subsidiary study of the clinical trial investigating the effect of TJ-100 on postoperative bowel function. Ascites was collected from 180 patients using an abdominal drainage tube on postoperative day 1 and 3 after PD (POD 1 or POD 3) and used to measure 27 cytokines. We performed univariate and multivariate analyses using several perioperative variables and administration of TJ-100/placebo to determine the effect of TJ-100 on the levels of IFN-γ and IL-9. RESULTS: Peritoneal levels of IL-9 and IFN-γ decreased between POD 1 and 3 (Wilcoxon signed-rank test p<0.001). Multivariate analysis was performed after univariate analysis to select the variables and patients with a body mass index of ≥22 kg/m2, older age, use of epidural anesthesia, and longer surgery correlated with the levels of IL-9 and IFN-γ. However, we could not detect a correlation between the use of TJ-100 and cytokine levels in ascites either on POD 1 or 3. CONCLUSION: TJ-100 did not affect peritoneal IL-9 and IFN-γ levels after PD. This was in accordance with published clinical findings showing no improvement in bowel function after PD and TJ-100 treatment.

Impact of Antithrombotic Agents on Postpancreatectomy Hemorrhage: Results from a Retrospective Multicenter Study.

BACKGROUND: This retrospective multicenter study aimed to evaluate the risk of postpancreatectomy hemorrhage (PPH) in patients receiving antithrombotic agents (ATAs). PPH is the most severe complication after pancreatectomy. However, there is little known about the strength of the association between ATA use, PPH, and other clinical outcomes. STUDY DESIGN: Between 2007 and 2016, 1,297 patients underwent pancreatectomy at 2 surgical centers. ATA use included aspirin, clopidogrel, ticlopidine, warfarin, direct oral anticoagulants, and intravenous unfractionated heparin. The ATA group was composed of 144 patients who were taking ATAs before surgery. RESULTS: A total of 35 patients developed PPH. The patients in the ATA group showed higher frequency (8.3% vs 2.0%, p < 0.001) of PPH compared with the control group (n = 1,153). In multivariate analysis, ATA use was an independent adverse risk factor for PPH (odds ratio [OR] 3.58, 95% CI 1.29-9.91, p = 0.014). Stratification by preoperative ATA therapy revealed a significant risk of PPH Grade C in patients receiving combined AT therapy. The median onset of late hemorrhage (>24 hours post-surgery) in the ATA group was later than in the control group (17.5 vs 8.5 days, p = 0.032), and the incidence tended to be higher in patients who restarted ATAs postoperatively. CONCLUSIONS: History of ATA use is a significant risk factor for PPH, and postoperative resumption of ATAs appears to be associated with an increased risk of PPH. Patients receiving combined antithrombotic therapy may be at particularly high risk for PPH.

Application of liquid biopsy for surgical management of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer. Although drug development over the past decade has gradually improved the prognosis of PDAC, the prognosis remains extremely poor. The predominant determinant of a poor prognosis is that patients are already at the advanced stage when they are diagnosed. Therefore, it is essential to detect early-stage PDAC to ensure a good prognosis. However, in general, being asymptomatic at the early stage makes the detection of early-stage PDAC very difficult. Recently, much attention has been focused on the utility of a liquid biopsy as a biomarker. Theoretically, early-stage tumors can be detected even under asymptomatic conditions. A number of studies on liquid biopsies have been reported so far. Several biomarkers, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCS), and exosomes, are used in liquid biopsies, with the potential to be applied to the clinical setting. Each biomarker is reported to have different utilities, such as the detection of early-stage disease, the differential diagnosis of PDAC from other types of pancreatic tumors, the prediction of the prognosis or risk of recurrence, and monitoring the treatment response. In this review, we focus on ctDNA, CTCS, and exosomes as representative liquid biopsy biomarkers and describe the specific functions of each biomarker in the treatment of PDAC. Furthermore, we discuss the application of liquid biopsies, especially for the surgical management of PDAC.

A MicroRNA Signature Identifies Pancreatic Ductal Adenocarcinoma Patients at Risk for Lymph Node Metastases.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinomas (PDACs) frequently metastasize to the lymph nodes; strategies are needed to identify patients at highest risk for lymph node metastases. We performed genome-wide expression profile analyses of PDAC specimens, collected during surgery or endoscopic ultrasound-guided fine-need aspiration (EUS-FNA), to identify a microRNA (miRNA) signature associated with metastasis to lymph nodes. METHODS: For biomarker discovery, we analyzed miRNA expression profiles of primary pancreatic tumors from 3 public data sets (The Cancer Genome Atlas, GSE24279, and GSE32688). We then analyzed 157 PDAC specimens (83 from patients with lymph node metastases and 74 without) from Japan, collected from 2001 through 2017, for the training cohort and 107 PDAC specimens (63 from patients with lymph node metastases and 44 without) from a different medical center in Japan, from 2002 through 2016, for the validation cohort. We also analyzed samples collected by EUS-FNA before surgery from 47 patients (22 patients with lymph node metastases and 25 without; 17 for the training cohort and 30 from the validation cohort) and 62 specimens before any treatment from patients who received neoadjuvant chemotherapy (9 patients with lymph node metastasis and 53 without) for additional validation. Multivariate logistic regression analyses were used to evaluate the statistical differences in miRNA expression between patients with vs without metastases. RESULTS: We identified an miRNA expression pattern associated with diagnosis of PDAC metastasis to lymph nodes. Using logistic regression analysis, we optimized and trained a 6-miRNA risk prediction model for the training cohort; this model discriminated patients with vs without lymph node metastases with an area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.77-0.89). In the validation cohort, the model identified patients with vs without lymph node metastases with an AUC of 0.73 (95% CI, 0.64-0.81). In EUS-FNA biopsy samples, the model identified patients with vs without lymph node metastases with an AUC of 0.78 (95% CI, 0.63-0.89). The miRNA expression pattern was an independent predictor of PDAC metastasis to lymph nodes in the validation cohort (odds ratio, 17.05; 95% CI, 2.43-119.57) and in the EUS-FNA cohort (95% CI, 0.65-0.87). CONCLUSIONS: Using data and tumor samples from 3 independent cohorts, we identified an miRNA signature that identifies patients at risk for PDAC metastasis to lymph nodes. The signature has similar levels of accuracy in the analysis of resected tumor specimens and EUS-FNA biopsy specimens. This model might be used to select treatment and management strategies for patients with PDAC.

A pancreatic mucinous cystic neoplasm undergoing intriguing morphological changes over time and associated with recurrent pancreatitis: A case report.

RATIONALE: Mucinous cystic neoplasms (MCNs) are pancreatic mucin-producing cystic lesions with a distinctive ovarian-type stroma. The diagnosis is generally easy in typical cases; however, differential diagnosis is difficult in others such as in the case we report herein. PATIENT CONCERNS: A 27-year-old woman with sudden onset of epigastric pain was referred to our hospital for suspected acute pancreatitis. Contrast-enhanced computed tomography revealed a 25-mm cystic lesion in the pancreas and a low density area with delayed enhancement at the right upper side of the cystic lesion. DIAGNOSES: During its clinical course, the cystic lesion underwent various morphological changes. Eventually, it presented typical findings of MCNs, and could be accurately diagnosed. INTERVENTIONS: Laparoscopic distal pancreatectomy was performed on the patient by preserving the spleen. OUTCOMES: The patient revealed no symptoms till 1 year after the operation. LESSONS: This case of MCN with intriguing short-term morphological changes was associated with recurrent pancreatitis. A combination of imaging modalities is essential for accurate diagnosis of MCNs, and follow-up with serial imaging might be useful for certain unusual lesions.

Significance of the inflammation-based prognostic score in recurrent pancreatic cancer.

BACKGROUND: Although the prognosis of recurrent pancreatic cancer (RPC) is improving with the appearance of new anticancer drugs, prognostic indicators for RPC are still poorly understood. The aim of this study was to evaluate significance of the inflammation-based prognostic score, including modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and Prognostic Nutritional Index (PNI), in patients with RPC. METHODS: This study reviewed 263 patients of pancreatic ductal adenocarcinoma at our institution between 2006 and 2015. A receiver operating characteristics curve analysis was performed to determine the cut-off values. The prognostic significance of the inflammation-based prognostic scores were evaluated by a multivariate analysis. RESULTS: 172 patients (65.4%) who had recurrence was included in this study. The optimal PNI for predicting 1-year survival after recurrence was 40 with higher area under receiver operating characteristics curve value (0.704) in comparison with other inflammation-based prognostic scores. A univariate and multivariate analysis revealed that liver metastasis (P < 0.001) and PNI < 40 (P < 0.001) were independently associated with the survival time after recurrence. When each of the two predictors was counted as one point and the points were calculated for all cases, a good stratified survival curve was obtained, showing the shorter survival in the higher points: median survival times of 2, 1, and 0 points were 4.3, 11.1, and 21.2 months, respectively (P < 0.001). CONCLUSIONS: Inflammation-based prognostic scores, especially PNI is useful clinical biomarker for predicting the survival time after recurrence in patients with pancreatic adenocarcinoma.

A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy.

BACKGROUND: Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms' tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. METHODS: This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. DISCUSSION: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.