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Double cantilever beam (DCB) tests were conducted by immersing the specimens in temperature-controlled water while applying a creep load using a spring. By introducing a data reduction scheme to the spring-loaded DCB test method, it was confirmed that only a single parameter measurement was sufficient to calculate the energy release rate (ERR). Aluminum alloy substrates bonded with an epoxy adhesive were used, and DCB tests were performed by changing the initial load values, spring constants, and immersion temperatures for two types of surface treatment. The initial applied load and spring constant had no effect on the ERR threshold. In contrast, the threshold decreased with the increasing immersion temperature, but even in the worst case, it was 15% of the critical ERR in the static tests. Using the creep crack growth relationship, it was revealed that there were three phases of creep immersion crack growth in the adhesive joints, and each phase was affected by the temperature. The spring-loaded DCB test method has great potential for investigating the combined effects of creep, moisture, and temperature, and this study has demonstrated the validity of the test method. The long-term durability of adhesive joints becomes increasingly important, and this test method is expected to become widespread.

OBJECTIVE We performed genome-wide expression profiling to develop an exosomal miRNA panel for predicting recurrence following surgery in patients with PDAC. SUMMARY BACKGROUND DATA Pre-treatment risk stratification is essential for offering individualized treatments to patients with pancreatic ductal adenocarcinoma (PDAC), but predicting recurrence following surgery remains clinically challenging. METHODS We analyzed 210 plasma and serum specimens from four 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 (AUC: 0.81, 95% 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 (HR: 2.84, 95% CI: 1.30-6.20). CONCLUSIONS We identified a novel, non-invasive exosomal 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.

Objective The purpose of this study is to investigate changes in autonomic activities and systemic circulation generated by surgical manipulation or electrical stimulation to the human brain stem. Methods We constructed a system that simultaneously recorded microsurgical field videos and heart rate variability (HRV) that represent autonomic activities. In 20 brain stem surgeries recorded, HRV features and sites of surgical manipulation were analyzed in 19 hypertensive epochs, defined as the periods with transient increases in the blood pressure. We analyzed the period during electrical stimulation to the ponto-medullary junction, performed for the purpose of monitoring a cranial nerve function. Results In the hypertensive epoch, HRV analysis showed that sympathetic activity predominated over the parasympathetic activity. The hypertensive epoch was more associated with surgical manipulation of the area in the caudal pons or the rostral medulla oblongata compared to controls. During the period of electrical stimulation, there were significant increases in blood pressures and heart rates, accompanied by sympathetic overdrive. Conclusions Our results provide physiological evidence that there is an important autonomic center located adjacent to the ponto-medullary junction. Significance A large study would reveal a candidate target of neuromodulation for disorders with autonomic imbalances such as drug-resistant hypertension.

BackgroundAberrant 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.MethodsWe 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.ResultsCD70 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 (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.ConclusionsCD70 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.

Approximately 30% of patients diagnosed with colorectal cancer (CRC) develop liver metastases. We evaluated the role of CD200, a potent immunosuppressive molecule, in colorectal liver metastases (CRLM). We examined 110 patients who underwent curative liver resection for CRLM at our institution between 2000 and 2016. Based on the results of immunohistochemical analysis, the patients were divided into high-CD200 (n = 47) and low-CD200 (n = 63) expression groups. The relationships between CD200 expression and various clinicopathological outcomes were investigated. The overall survival (OS) of patients in the high-CD200 group was significantly worse than that in the low-CD200 group (p = 0.009). Multivariate analysis showed that the independent prognostic factors in CRLM were maximum tumor size > 30 mm (p = 0.002), preoperative carcinoembryonic antigen level > 20 ng/mL (p

Activated charcoal is known to adsorb a variety of drugs concomitantly administered and reduce their intestinal absorption, and separating the dosing is considered a practical approach to avoid this drug interaction. The aim of the present study was to develop and validate a simple method to estimate the sufficient dosing interval to avoid drug interaction using the pharmacokinetic profile of the subject drugs administered alone and the amplitude of interaction upon simultaneous administration with activated charcoal. For each subject drug, the pharmacokinetic profile and the amplitude of interaction, as assessed by AUCR (the ratio of area under the plasma concentration-time curve (AUC) in the presence of activated charcoal to that in its absence), were collected from previous reports. The AUCR value was estimated based on the compartment model under the assumption that the subject drug in the first gastrointestinal compartment is immediately adsorbed to a certain extent upon the administration of activated charcoal. The estimated AUCR (AUCRe) for each drug with certain dosing interval was compared with the respective AUCR value reported previously (AUCRobs). Among twenty concentration profiles for 14 subject drugs obtained from previous reports, 15 AUCRe values fell in the range of 80–120% of the respective AUCRobs values. The developed method enabled estimation of the amplitude of DDI by activated charcoal administered in a certain dosing interval, whereas overestimation of AUCRe was observed for drugs that undergo extensive enterohepatic circulation.

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., Much attention has been focused on the utility of a liquid biopsy as a biomarker. 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.

Pancreatic ductal adenocarcinoma (PDAC) incidence is rising worldwide, and most patients present with an unresectable disease at initial diagnosis. Measurement of carbohydrate antigen 19-9 (CA19-9) levels lacks adequate sensitivity and specificity for early detection; hence, there is an unmet need to develop alternate molecular diagnostic biomarkers for PDAC. Emerging evidence suggests that tumor-derived exosomal cargo, particularly micro RNAs (miRNAs), offer an attractive platform for the development of cancer-specific biomarkers. Herein, genomewide profiling in blood specimens was performed to develop an exosome-based transcriptomic signature for noninvasive and early detection of PDAC.Small RNA sequencing was undertaken in a cohort of 44 patients with an early-stage PDAC and 57 nondisease controls. Using machine-learning algorithms, a panel of cell-free (cf) and exosomal (exo) miRNAs were prioritized that discriminated patients with PDAC from control subjects. Subsequently, the performance of the biomarkers was trained and validated in independent cohorts (n = 191) using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays.The sequencing analysis initially identified a panel of 30 overexpressed miRNAs in PDAC. Subsequently using qRT-PCR assays, the panel was reduced to 13 markers (5 cf- and 8 exo-miRNAs), which successfully identified patients with all stages of PDAC (area under the curve [AUC] = 0.98 training cohort; AUC = 0.93 validation cohort); but more importantly, was equally robust for the identification of early-stage PDAC (stages I and II; AUC = 0.93). Furthermore, this transcriptomic signature successfully identified CA19-9 negative cases (37 U/mL; AUC = 0.96), when analyzed in combination with CA19-9 levels, significantly improved the overall diagnostic accuracy (AUC = 0.99 vs AUC = 0.86 for CA19-9 alone).In this study, an exosome-based liquid biopsy signature for the noninvasive and robust detection of patients with PDAC was developed.

Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC.A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays.In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P.001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity.Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.

The adhesion G-protein-coupled receptors (GPCRs) play crucial roles in tumour pathogenesis, however, their clinical significance in pancreatic ductal adenocarcinoma (PDAC) remains unclear.We analysed 796 PDAC patients, including 331 from public data sets (TCGA, ICGC and GSE57495) and 465 from independent cohorts (training: n = 321, validation: n = 144). Using in-vitro studies, we confirmed the biological function of the candidate GPCRs.Analysis of all 33 adhesion GPCRs, led to identify GPR115, as the only significant prognostic factor in all public data sets. The patients with high GPR115 expression exhibited significantly poorer prognosis for OS and RFS, in training (P 0.01, P 0.01) and validation cohort (P 0.01, P = 0.04). Multivariate analysis indicated that GPR115 high expression was an independent prognostic factor in both cohorts (HR = 1.43; P = 0.01, HR = 2.55; P 0.01). A risk-prediction model using Cox regression by incorporating GPR115 and clinicopathological factors accurately predicted 5-year survival following surgery. In addition, GPR115 silencing inhibited cell proliferation and migration in PDAC cells.We demonstrated that GPR115 has important prognostic significance and functional role in tumour progression; providing a rationale that this may be a potential therapeutic target in patients with PDAC.

Expanded therapeutic options are warranted for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations. The present phase 1, multicenter, open-label, dose-escalation and dose-expansion study was conducted to assess the safety, pharmacokinetics, and efficacy of multiple-dose monotherapy of the FLT3 inhibitor, quizartinib, in Japanese patients with R/R AML. Patients received oral quizartinib, once daily, under fasting conditions in 28-day cycles. Sixteen patients (median age, 68.0 years; male, 56.3%; FLT3-ITD positive, 43.8%) received quizartinib (9, 3, and 4 patients at 20, 30, and 60 mg/day, respectively; median treatment duration, 95.0 days; median relative dose intensity, 100.0%). No dose-limiting toxicities were observed. The most common treatment-emergent adverse events were electrocardiogram QT prolonged (43.8%, grade 1 or 2) followed by nausea and pyrexia (37.5% each). No quizartinib-related deaths were reported. A dose-dependent increase of quizartinib and its active metabolite AC886 levels was observed at the steady state. The composite complete remission rate was 37.5%. Quizartinib was well tolerated in Japanese R/R AML patients at doses up to 60 mg/day; quizartinib 60 mg/day was considered as the recommended dose for the Japanese patient population in a subsequent study. Trial registration ClinicalTrials.gov identifier NCT02675478.

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.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.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).Inflammation-based prognostic scores, especially PNI is useful clinical biomarker for predicting the survival time after recurrence in patients with pancreatic adenocarcinoma.

This paper examines the effects that electromagnetic fields from microwave radiation have in enzymatic reactions. Hydrolysis of proteins in beef (in vivo case) and casein (in vitro case) by the papain enzyme, a major industrial enzyme, is used herein as a model reaction to assess, under highly controlled conditions, the various parameters of microwave radiation (electric field, magnetic field, pulsed microwave irradiation, continuous microwave irradiation) as they might influence these in vivo and in vitro enzymatic reactions. The effect(s) of the microwaves’ electromagnetic fields was clearly evidenced in the in vivo case, contrary to the in vitro case where no such effect was observed, likely due to the nature of the hydrolysis reaction and to the autolysis (self-digestion) of the papain enzyme. Additionally, the effect of pulsed versus continuous microwave irradiation was further assessed by examining the catalase-assisted decomposition of hydrogen peroxide.

The development of inexpensive transition metal-based catalysts for water splitting has attracted global attention, which should be accomplished in the simplest and most scalable way feasible. In this study, nickel and iron co-incorporated tungsten oxides (NixFe1-xWO4) were synthesized using a simple polyol method, and the materials achieved a highly efficient and stable oxygen evolution reaction (OER) in an alkaline electrolyte. The product as-synthesized using the polyol method consisted of an undeveloped wolframite structure, which was converted to its complete crystal by heat treatment at 600 °C, with an increase in crystallite size. The OER properties of NixFe1-xWO4 could be controlled by the ratio of Ni and Fe present and heat treatment temperature. A ternary tungsten oxide (Ni0.5Fe0.5WO4) with a Ni:Fe:W molar ratio of 0.5:0.5:1 deposited on a glassy carbon electrode required 297 mV to reach a current density of 10 mA cm−2 in 1.0 M KOH solution. The 10 mA cm−2 electrolysis with the electrode was continued for at least 100 h. This was quite different from a similarly-synthesized NiFe oxide without W, which required an additional 47-mV overpotential to reach 10 mA cm−2 and had inferior durability.

Background: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second leading cause of cancer-related deaths in the United States by 2030. Most of the PDAC patients are diagnosed with advanced disease, and less than 20% of patients are resectable at the time of diagnosis. The current imaging tools and blood markers (e.g. CA 19-9), are inadequate for early disease detection due to their poor specificity and sensitivity. This highlights the need to develop robust, noninvasive biomarkers for early detection of PDAC. While a large body of literature supports the use of cell-free miRNAs (cf-miRNAs) as potential diagnostic biomarkers in cancer, their tumor specificity is often debatable. Given the emerging evidence that exosomal cargo is a more robust representation of individual tumor types, in this study we sought to explore the diagnostic potential of cf-miRNAs along with exosomal miRNAs (exo-miRNAs), to establish a non-invasive miRNA signature for the early detection of PDAC. Methods: As part of the NCI’s Pancreatic Cancer Detection Consortium (PCDC) funded project, in this study, small RNA-sequencing was performed in exosome and cell-free (cf) samples from a cohort of 57 PDAC cases and 57 non-disease controls. Using rigorous bioinformatic and biostatistical approaches, we prioritized a panel of cf- and exo-miRNAs and evaluated its diagnostic performance in the sequencing-based discovery and validation cohorts. Subsequently, the performance of the discovered miRNA panel was validated using qRT-PCR assays in an independent clinical validation cohort of PDAC patients and non-disease controls (n=48/each group). The results were examined by ROC curve analysis to determine the diagnostic power of the biomarker panel individually and in combination for their ability to discriminate PDAC from controls. Results: The genomewide transcriptomic analyses led to the identification of a panel of 13 cf-miRNA and 17 exo-miRNA candidates. Sequencing validation in an independent cohort revealed that a combined panel of cf and exo-miRNAs exhibited an area under curve (AUC) of 0.89. Subsequent risk score analysis demonstrated that our biomarker signature was also robust in the identification of PDAC patients with early-stage cancers (stage I & II) vs. controls (p Conclusions: In conclusion, we report a novel, exosome-based miRNA signature for the early detection of patients with PDAC; which could potentially improve early-detection efforts for this fatal malignancy. Citation Format: Kota Nakamura, Souvick Roy, Zhongxu Zhu, Eunsung Jun, Haiyong Han, Ruben M. Munoz, Satoshi Nishiwada, Geeta Sharma, Derek Cridebring, Frederic Zenhausern, Seungchan Kim, Denise Roe, Sourat Darabi, In Woong Han, Douglas Evans, Suguru Yamada, Michael Demure, Scott A. Celinski, Erkut Borazanci, Susan Tsai, John Bolton, Yasuhiro Kodera, Joon Oh Park, Song Cheol Kim, Xin Wang, Daniel Von Hoff, Ajay Goel. An exosomal miRNA-based liquid biopsy signature for the noninvasive early detection of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3389.

Background Primary omental tumors are extremely rare. Herein, we report the first case of a primary omental neuroendocrine tumor (NET). Case presentation A 59-year-old woman was referred to our hospital for the treatment of an 18-mm tumor located at the ventral side of the duodenum. No other tumor was detected. The preoperative imaging diagnosis was omental tumor. A laparoscopic tumor resection was performed. Histopathological examination revealed that the tumor consisted of cuboidal cells with eosinophilic, granular cytoplasm showing trabecular or ribbon architecture. No other component was seen. The mitotic count was of 5 per 10 high-power fields. Immunohistochemical staining was positive for chromogranin A, synaptophysin, and CD56. Her Ki-67 index was 5%. These results led to the diagnosis of grade 2 omental NET. The patient was discharged on the 3rd postoperative day without any complications and did not develop any recurrence for 3 years. Conclusions We encountered a very rare case of omental NET. Complete resection is recommended with minimally invasive surgery for the diagnosis of NET.

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.

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.

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.

Granulocyte-colony stimulating factor (G-CSF) producing tumors are rare diseases and occur in various organs. However, due to the rarity of these tumors, the precise biologic characteristics and optimal therapeutic strategies are largely unknown. Previous studies have shown the extremely high malignant potential and aggressive clinical features of G-CSF producing tumors, regardless of the histologic type and tumor location. We present the case of a 59-year-old female who had large tumor in extrahepatic bile duct. She underwent surgery and adjuvant chemotherapy. Then, she also received gemcitabine and cisplatin combination chemotherapy for metastatic lesions. The therapy showed a certain effect and she survived for 17 months after surgery. To the best of our knowledge, this is the first report of multidisciplinary treatment with surgery and systemic chemotherapy for G-CSF producing extrahepatic bile duct cancer. This study highlights the potential of multidisciplinary treatment even for this lethal disease condition.

The optimal stent type in patients receiving preoperative neoadjuvant chemoradiotherapy (NACRT) is uncertain. The present study aimed to compare the clinical effectiveness of biliary metallic stent (MS) and plastic stent (PS) in patients undergoing preoperative NACRT for resectable pancreatic cancer. This retrospective study included 43 patients who required either biliary MS or PS before initiating NACRT for resectable or borderline resectable pancreatic head cancer. Seventeen patients had MS (MS group), while 23 patients had PS (PS group). All patients received preoperative NACRT, including gemcitabine and concomitant three-dimensional radiation of 54 Gy, and underwent pancreatectomy. Stent patency, surgery postponement, postoperative outcomes, and cost-effectiveness were compared between these groups. There were no significant differences in baseline demographic or tumor characteristics between the groups. Stent patency was significantly longer in the MS group than in the PS group (p = 0.042). There were no differences in time to surgery, intraoperative characteristics, surgical complications, margin positivity, and pathological response between the groups. Furthermore, the medical cost of maintenance of biliary drainage during NACRT was similar between the groups. MS placement compared to PS in patients receiving preoperative NACRT provided no significant benefits during the postoperative course of pancreatectomy. However, MS placement was associated with long stent patency while showing no economic disadvantage. Therefore, MS placement may be recommended in patients receiving preoperative NACRT for resectable pancreatic cancer.

Recent advances in multidisciplinary treatments are improving the postoperative prognosis of pancreatic ductal adenocarcinoma (PDAC). However, the prognosis even after potentially curative resection remains poor. The aim of this study was to identify the clinical and pathological features of actual 5-year survivors under current circumstances. A total of 128 patients who underwent pancreatectomy for PDAC at our institution between January 2006 and December 2011 were retrospectively analyzed. The actual 5-year overall survival rate for all patients was 30.9%, with a median survival time of 33.1 months. Of 128 patients, 25 (19.5%) survived for 5 years after surgery without disease recurrence. A univariate analysis showed that the pretreatment serum CA19–9 value, tumor depth, lymph node metastasis, and UICC stage at resection were significant predictive factors for the actual long-term survival. A multivariate analysis showed that a pretreatment serum CA19–9 value ≥ 110 U/mL was a significant unfavorable prognostic indicator. In addition, all subjects in the 5-year survival group completed adjuvant chemotherapy. The recurrence rate in the liver was significantly lower and that in the lung significantly higher in the long-term survival group than in the short-term survival group. The factors contributing to the long-term survival of PDAC were the pretreatment CA19–9 value and the completion of adjuvant chemotherapy. To achieve the actual long-term survival and cure after pancreatectomy for pancreatic cancer, further treatment strategies enhancing the completion rate of adjuvant chemotherapy are required.

Objective: The study objective is to investigate the impact of unilateral nephrectomy on the complications after pancreatoduodenectomy (PD). Summary of background data: Preoperative renal insufficiency is a risk factor for postoperative complications and mortality after various types of surgery. However, the specific postoperative risks in uninephrectomized (UN) patients are largely unknown. Methods: Between January 2010 and June 2014, a total of 177 patients underwent PD at the Department of Surgery, Nara Medical University. Among them, 7 patients (4.0%) were UN. We retrospectively evaluated the influence of the UN status on the postoperative complications. Results: The rate of acute kidney injury in the UN group was significantly higher than that in the control group (28.6% versus 1.2%; P = 0.017). In addition, the rates of surgical site infection of the organ/space (57.1% versus 9.0%; P = 0.006) and sepsis (42.9% versus 3.5%; P = 0.003) in UN group were significantly higher. Even on a reanalysis of only patients with soft pancreas, the significance remained. Conclusions: The UN status has a significant impact on the rate of morbidities, such as acute kidney injury and various infectious complications, including surgical site infections of organ/space, sepsis, and cholangitis after PD. Appropriate intervention should be implemented to decrease the morbidity rate for UN patients.