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BackgroundCluttering is a speech disorder distinct from stuttering. Despite this distinction, there is no established method to clearly differentiate the two disorders. This study aimed to use objective criteria to differentiate cluttering from stuttering in Japanese speakers.MethodsParticipants were 32 consecutive native-Japanese speakers who visited the Keio University Hospital between July 2020 and January 2023 with a chief complaint of speech disfluency. One physician and two speech-language-hearing therapists concurred on a stuttering or cluttering diagnosis of the 32 patients based on recordings of the Kitsuon kensa-ho test. The frequencies of stuttering-like disfluencies (SDF) and normal disfluencies (NDF) were calculated from the Kitsuon kensa-ho, and the ratio of disfluencies (RDF) was calculated as the ratio of SDF to NDF. Differences between the cluttering and stuttering groups in the RDF and the mean articulatory rate (MAR) for oral reading and a monologue task were tested using the Mann–Whitney U test. ROC curves were used to determine the sensitivity and specificity that well-distinguished subjects with cluttering from those with stuttering; the experts’ diagnosis was the gold standard.ResultsOf the 32 participants, 12 (38%) were diagnosed with cluttering and 20 (62%) with stuttering. The cluttering and stuttering groups were comparable in demographic characteristics. The RDF on monologue task had the highest sensitivity in diagnosing cluttering, and the MAR on monologue task had the highest specificity. Adopting provisional criteria of a monologue RDF greater than 1.2 and a monologue MAR greater than 7.5 produced a sensitivity of 0.92 and a specificity of 0.95.ConclusionWe conclude that combining monologue RDF and monologue MAR well-distinguished cluttering from stuttering. This method provides new objective diagnostic criteria, which can aid clinicians, therapists, and basic researchers.

The applications of wear resistant material coatings or claddings by directed energy deposition (DED) are rapidly increasing in industrial engineering fields. DED allows us the use of non-expensive substrate materials and add functional materials such as Co-based superalloys on them. However, depending on the deposition parameters, cracks can easily occur on the workpiece. The determination of the appropriate deposition parameters is crucial because it is still difficult to predict and to control cracking. This paper discusses the effect of substrate preheating by an induction heater on the crack generation for DED of Co-based superalloys. An induction heater was adopted for its high efficiency, low waste heat and ability to quickly induce a high temperature in the workpiece directly. The material used in this study is Stellite® 1, which is widely used for die cut rolls or screw shafts. To investigate the effect of the preheating, experiments were conducted by changing the process parameters: preheating temperature and laser power. Sufficient hardness of 642 HV was obtained without cracking when the preheating temperature was 500 ℃ and the laser power was 1750 W. Although cracking did not occur when the preheating temperature or the laser power was higher, the hardness decreased. There is a trade-off between hardness and crack occurrence. This trade-off is considered to be influenced by thermal stress and the precipitation amount of chromium carbides, which are hard and brittle materials. The amount of chromium carbide precipitation is affected by the cooling rate of the deposited material. In addition, a higher cooling rate may result in greater thermal stress.

Directed energy deposition (DED), a metal additive manufacturing process, has attracted considerable attention in various industries. In the past few decades, several studies have been conducted to enhance the quality of DED-produced parts. Various studies on powder- and laser-based DED have focused on eliminating the residual pores in the fabricated parts, which decrease the mechanical strength. In contrast, this study aims at intentionally increasing the residual pores to produce a porous structure in metals called as foam metal, which realizes lightweight and excellent energy absorption properties. Despite being well-known for their attractive properties, Foam metals are rarely used due to the technical difficulties in their production, which requires special devices and entails considerable cost. The simplicity of the DED process makes it a promising approach to fabricate foam metals because it is easy to foam at the fabrication point by mixing a foaming agent, such as titanium hydride (TiH2), into the material powder. This study evaluates the DED foaming process in stainless steel alloys by changing the particle size of the TiH2 powder and the scanning path to obtain the optimal conditions for enhancing the pore dispersion. The experimental results show that, when the particle size of the foaming agent is small, the number of pores and their distribution increases. Additionally, the mechanical properties are also evaluated through compression experiments, and the energy absorption ratio is found to be higher when a smaller foaming agent is used.

Selective laser melting (SLM) is one of the additive manufacturing (AM) methods which is applicable to metal. This technique makes it possible to form complex internal shapes such as lattice structures. The lattice structure is expected to have weight reduction and vibration suppression effects on the product. In addition, a support structure is essential for the SLM fabrication process, which has the role of supporting the product and dissipating heat from the product. However, steep temperature gradients due to local laser irradiation and non-uniform heat conduction during the process can cause bending and cracking of the product. In particular, the support structure and lattice structure consisting of thin metal struts are greatly affected by process conditions, so it is necessary to select conditions suitable for stable and high-precision modeling. In this study, the influence of laser power and scanning speed on the mechanical characteristics of the support structure and lattice structure formed by SLM is investigated. In the tensile test of the support structure, a positive correlation with the volumetric energy density was confirmed, and suitable laser conditions were examined. In the compression test of the lattice structure, it was clear that the amount of energy absorption changed depending on the laser power, and the condition of 240 W achieved the maximum energy absorption.

Background & aims: To develop an effective and safe orally administered drug, it is important to predict its intestinal absorption rate, intestinal first-pass effect, and drug-drug interactions of orally administered drugs. However, there is no existing model to comprehensively predict the intestinal pharmacokinetics and drug-response of orally administered drugs. In this study, we attempted to generate homogenous and functional intestinal epithelial cells from human induced pluripotent stem (iPS) cells for pharmaceutical research. Methods: We generated almost-homogenous Villin- and zonula occludens-1 (ZO1)-positive intestinal epithelial cells by caudal-related homeobox transcription factor 2 (CDX2) transduction into human iPS cell-derived intestinal progenitor cells. Results: The drug absorption rates in human iPS cell-derived intestinal epithelial cell monolayers (iPS-IECM) were highly correlated with those in humans (R2=0.91). The expression levels of cytochrome P450 (CYP) 3A4, a dominant drug-metabolizing enzyme in the small intestine, in human iPS-IECM were similar to those in human small intestine in vivo. In addition, intestinal availability in human iPS-IECM (the fraction passing the gut wall: Fg=0.73) was more similar to that in the human small intestine in vivo (Fg=0.57) than to that in Caco-2 cells (Fg=0.99), a human colorectal adenocarcinoma cell line. Moreover, the drug-drug interaction and drug-food interaction could be observed by using our human iPS-IECM in the presence of an inducer and inhibitor of CYP3A4, i.e., rifampicin and grape fruit juice, respectively. Conclusion: Taking these results together, we succeeded in generating the human iPS-IECM that can be applied to various intestinal pharmacokinetics and drug-response tests of orally administered drugs. Keywords: CYP3A4, Intestinal First-Pass Effect, Differentiation, Adenovirus

Directed Energy Deposition (DED) of metal materials has been widely studied with Inconel 718 using in aerospace industry. Void generation in a deposited part causes deterioration of the mechanical strength. Hence, void should be avoided in the DED process. In this study, a mechanism of void generation was investigated through the dynamic observation by high-speed camera, the thermal observation and the evaluation of the porosity. The experimental result shows that solidification time has an influence on the void generation.

Abstract Background Loss of expression of the gene ataxia-telangiectasia mutated (ATM), occurring in patients with multiple primary malignancies, including pancreatic cancer, is associated with poor prognosis. In this study, we investigated the detailed molecular mechanism through which ATM expression affects the prognosis of patients with pancreatic cancer. Methods The levels of expression of ATM and phosphorylated ATM in patients with pancreatic cancer who had undergone surgical resection were analyzed using immunohistochemistry staining. RNA sequencing was performed on ATM-knockdown pancreatic-cancer cells to elucidate the mechanism underlying the invlovement of ATM in pancreatic cancer. Results Immunohistochemical analysis showed that 15.3% and 27.8% of clinical samples had low levels of ATM and phosphorylated ATM, respectively. Low expression of phosphorylated ATM substantially reduced overall and disease-free survival in patients with pancreatic cancer. In the pancreatic cancer cell lines with ATM low expression, resistance to gemcitabine was demonstrated. The RNA sequence demonstrated that ATM knockdown induced the expression of MET and NTN1. In ATM knockdown cells, it was also revealed that the protein expression levels of HIF-1α and antiapoptotic BCL-2/BAD were upregulated. Conclusions These findings demonstrate that loss of ATM expression increases tumor development, suppresses apoptosis, and reduces gemcitabine sensitivity. Additionally, loss of phosphorylated ATM is associated with a poor prognosis in patients with pancreatic cancer. Thus, phosphorylated ATM could be a possible target for pancreatic cancer treatment as well as a molecular marker to track patient prognosis.

Abstract Aim This study aimed to clarify the usefulness of tumor markers from peritoneal lavage in selecting patients with a high risk of recurrence and predicting site‐specific recurrence in patients with pancreatic cancer. Methods The levels of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19–9 (sCEA/sCA 19–9) and paired peritoneal lavage CEA and CA 19–9 (pCEA/pCA 19–9) were measured in 90 patients with pancreatic cancer who underwent surgery. Using the cutoff values determined by maximally selected rank statistics for disease‐free survival (DFS), the risk of recurrence and its patterns were evaluated in combination with different markers and different test specimens. Results In univariate and multivariate analysis, an elevated pCA 19–9 level (>1.3 U/mL) was an independent prognostic marker for both DFS (hazard ratio [HR], 2.391; P = .018) and overall survival (HR, 3.194; P = .033). Combination analyses contributed to further stratification of a very high risk of recurrence. Of the 58 patients with resectable pancreatic cancer who underwent curative resection, elevated pCA19–9 was also associated with inferior DFS and overall survival (OS). Patients with elevated pCA 19–9 levels were more likely to have an earlier onset of peritoneal recurrence than those with normal pCA 19–9 levels (P = .048, Gehan–Breslow–Wilcoxon test). Conclusion pCA 19–9 is a reliable marker for predicting postoperative recurrence in patients with pancreatic cancer after surgery. Further risk stratification can be achieved by using combination assays. The combination of pCA 19–9 and sCA19–9 also serves as a predictor of recurrence site‐specific recurrence.

Abstract Background Cavernous transformation of the portal vein (CTPV) due to extrahepatic portal vein obstruction is a rare vascular anomaly. Since its symptoms usually appear in childhood, most of the adult cases are detected unexpectedly with other diseases. Only a few reports have described surgical difficulties in patients with CTPV. We report a case of pancreatic head cancer with CTPV in a patient who underwent pancreaticoduodenectomy. Case presentation A 77-year-old man with epigastric and back pain was referred to our hospital. Computed tomography revealed a tumor in the pancreatic head and a CTPV near the hepatic hilum. CTPV consisted of two main collateral vessels connected by multiple surrounding small vessels. Also, portal vein obstruction was observed near the hepatic hilum, which was far from the pancreatic head tumor. After confirming that there was no distant metastasis by a thorough whole-body search, we performed a pancreaticoduodenectomy following neoadjuvant chemotherapy. During the operation, we carefully manipulated the area of the CTPV and omitted lymph node dissection in the hepatoduodenal ligament to prevent massive venous bleeding and intestinal congestion. Pancreaticoduodenectomy was performed without any intraoperative complications and the postoperative course was uneventful. Complete tumor resection was histologically confirmed. Conclusion Although pancreaticoduodenectomy for patients with CTPV involves many surgical difficulties, we successfully performed it by determining specific treatment strategies tailored to the patient and following careful and delicate surgical procedures.

Abstract Aim Cancer patients with personal/family histories of pancreatic/breast/ovarian/prostate cancer are associated with a higher likelihood of harboring DNA damage repair (DDR)‐related germline mutations. Here, we aimed to obtain a better understanding of DDR‐related germline mutations in Japanese pancreatic ductal adenocarcinoma (PDAC) patients with personal and/or family histories of BRCA‐related cancers of the pancreas, breast, ovary, and prostate. Methods We performed next‐generation sequencing (NGS) and evaluated germline mutations in nine DDR‐related genes (BRCA1, BRCA2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, and PMS2) in PDAC patients with personal and/or family histories. Results Of 196 patients with PDAC, 39 (19.9%) fulfilled the criteria for at least one family history of pancreatic/breast/ovarian/prostate cancer in first‐degree relatives (sibling–sibling or parent‐child) or the personal history of these malignancies. Targeted NGS revealed that four (10.2%) of 39 patients with personal/family histories harbored deleterious germline mutations—two in BRCA2, one in ATM, and one in MLH1. Both the BRCA2 variants showed frameshift mutations due to short insertion/deletions. In the 39 patients undergoing NGS, a similar distribution of the clinicopathological characteristics was observed between those with deleterious mutations/variants of unknown significance (VUSs) and with benign/wild types. Patients with deleterious germline mutations/VUSs in DDR‐related genes showed a significantly more favorable prognosis than those with benign mutations/wild‐type genes (hazard ratio: 0.160, P = .040). Conclusions A significant fraction of PDAC patients with personal/family histories of BRCA‐related cancers harbored deleterious germline mutations in DDR‐related genes. DDR‐related germline gene mutations might be a favorable prognostic factor in patients with pancreatic cancer.

Abstract Background Pancreatic serous cystic neoplasm (SCN) is an uncommon exocrine neoplasm, which is believed to be a benign entity. However, some of these neoplasms may occasionally attain metastatic ability. Von Hippel–Lindau disease (VHL) manifests a dominantly inherited systemic syndrome accompanied by several benign or malignant tumors, including cystic tumors, in various organs. We describe here a long-term survival case who underwent surgical resection for metachronous liver metastases of pancreatic SCN associated with VHL disease. Case presentation A 35-year-old woman with VHL underwent total pancreatectomy and right nephrectomy for pancreatic SCN and renal cell carcinoma, respectively. At the 4th year follow-up examination after the resection, contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) showed arterially hyper-enhanced neoplastic lesions in the segment VI and VIII of the liver. Partial resections of the liver were performed 53 months after the initial surgery. At the 6th month follow-up examination from the second surgery, one and two tumors located in the liver segment III, and VIII, respectively, were detected by contrast-enhanced CT and Gd-EOB-DTPA-enhanced MRI. Anterior segmentectomy and partial resection of the segment III were performed 66 months after the initial surgery and 13 months after the second, respectively. The tumors were pathologically diagnosed as liver metastases of pancreatic SCN synonymous with serous cystadenocarcinoma. She remains disease-free without recurrence 6.5 years after the last operation. Conclusions This is the first report of a case of metastatic SCN associated with VHL. Surgical resection might confer a favorable prognosis in patients of pancreatic SCN with liver metastases.

Abstract Background Probiotics have been reported to be beneficial for the prevention of postoperative complications and are often used during the perioperative period. Among the probiotic-related adverse events, bacteremia is rare. Here, we report two cases of probiotic-related bacteremia after major hepatectomy for biliary cancer. Case presentation 1 A 74-year-old man was referred to our hospital to be treated for gallbladder cancer. Neoadjuvant chemotherapy, two courses of gemcitabine plus S-1 combination therapy, was administered. Extended right hepatectomy with caudate lobectomy, extrahepatic bile duct resection and biliary reconstruction were performed 3 weeks after chemotherapy. Probiotics, Clostridium butyricum (C. butyricum) MIYAIRI 588, were administered 6 days before surgery and continued after surgery. Sepsis of unknown origin occurred 17 days after surgery and developed into septic shock. C. butyricum was detected in blood cultures at postoperative day 26 and 45. After stopping the probiotic agent, C. butyricum was undetectable in the blood cultures. The patient died due to an uncontrollable sepsis 66 days after surgery. Case presentation 2 A 63-year-old man with diabetes mellitus whose past history included total colectomy, papillectomy, and Frey’s operation at the age of 19, 34 and 48, respectively, was referred to our hospital to be treated for perihilar cholangiocarcinoma. Extended left hepatectomy with caudate lobectomy, extrahepatic bile duct resection and reconstruction of bile duct were performed. Probiotics were administered during the perioperative period. Combined probiotics that included lactomin, amylolytic bacillus and C. butyricum, were given before surgery. C. butyricum MIYAIRI 588 was given after surgery. Sepsis occurred 16 days after surgery and developed to respiratory failure 8 days later. Blood culture at postoperative day 25 revealed Enterococcus faecalis and C. butyricum. After the probiotics were stopped at postoperative day 27, C. butyricum was not detected in the blood culture. The general condition improved with intensive care. The patient was transferred to another hospital for rehabilitation at postoperative day 156. Conclusion It should be noted that the administration of probiotics in severe postoperative complications can lead to probiotic-related bacteremia.

Abstract Background The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the ability to predict the recurrence of such markers after curative resection in patients with these neoplasms. Methods Circulating/systemic neutrophil–lymphocyte, monocyte–lymphocyte, platelet–lymphocyte, and platelet–white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan–Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals. Results Univariate analysis demonstrated that preoperative neutrophil–lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil–lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil–lymphocyte ratio (HR = 3.49 95% CI 1.05–11.7; P = 0.042) and 2017 World Health Organization classification (HR = 8.81, 95% CI 1.46–168.2; P = 0.015) were independent recurrence predictors. Conclusions The circulating/systemic neutrophil–lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

Abstract Background Ovarian cancer typically spreads along the peritoneum or metastasizes through the blood or lymphatic stream. The bile duct is an extremely rare site of ovarian cancer-associated metastases. Case presentation A 55-year-old female underwent surgery for advanced left ovarian cancer 2 years ago. She was diagnosed with ovarian serous adenocarcinoma with multiple peritoneal metastases. She received chemotherapy for the residual peritoneal metastases. She achieved a clinical complete response and was followed up with imaging examinations for 1 year. She then complained of dark urine, yellowish discoloration of the eyes, and weight loss. Computed tomography showed an approximately 10-mm solid tumor at the hepatic hilum. Simultaneously, multiple peritoneal metastases were detected in the abdominal and pelvic cavity. Intraductal ultrasonography suggested that the hepatic hilum tumor was located in the bile duct wall. Tumor biopsy and brush cytology of the bile duct indicated atypical cells suspicious for carcinoma. After percutaneous transhepatic portal embolization, she underwent right hepatectomy and extrahepatic bile duct resection for the hepato-hilar tumor. The histopathological features were dysplastic cells with hyperchromatic nuclei and no dysplastic cells in the native biliary epithelium. Immunohistochemical staining revealed that the tumor cells were positive for CK-7 and WT-1 and negative for CK-20 and ER. These results suggested that the tumor was a metastasis of the ovarian serous adenocarcinoma. Conclusion This may be the first case of ovarian cancer metastasis to the bile duct. While it is extremely rare, ovarian cancer may metastasize to the hepatic duct, mimicking hilar cholangiocarcinoma.

Abstract Background The differentiation between pancreatic head cancer (PHC) and distal cholangiocarcinoma (DCC) can be challenging because of their anatomical and histopathological similarity. This is an important problem, because the distinction has important implications for the treatment of these malignancies. However, there are no biomarkers for the differential diagnosis of PHC and DCC. The present study aimed to identify novel diagnostic immunohistochemical biomarkers to distinguish PHC from DCC. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to detect candidate proteins. Ten PHC and 8 DCC specimens were analyzed by LC-MS/MS. Selected proteins were evaluated, using immunohistochemical analysis, to determine whether they would be appropriate biomarkers. Finally, we generated biomarker panels to improve diagnostic accuracy. We applied these panels to clinically difficult cases (cases in which different diagnoses were made before and after operation). Results Consequently, 1820 proteins were detected using LC-MS/MS. Fifteen differentially expressed proteins were selected as candidates based on semi-quantitative comparison. We first performed immunohistochemical staining on samples from the small cohort group (12 PHCs and 12 DCCs) using 15 candidates. KRT17, ANXA10, TMEM109, PTMS, and ATP1B1 showed favorable performances and were tested in the next large cohort group (72 PHCs and 74 DCCs). Based on immunohistochemical analysis, KRT17 performed best for the diagnosis of PHC as a single marker; additionally, PTMS exhibited good performance for the diagnosis of DCCs. Moreover, we indicated the KRT17+/ANXA10+/PTMS- staining pattern as a biomarker panel for the correct diagnosis of PHC and KRT17−/ANXA10−/PTMS+ for the diagnosis of DCC. After immunohistochemical staining for examining samples from the clinically difficult cases, these panels showed satisfactory diagnostic performance with 85.7% (6/7) accuracy. Conclusions We conclude that 5 proteins and 2 biomarker panels are promising for distinguishing PHC from DCC, and patients with an equivocal diagnosis would benefit from the application of these biomarkers. Confirmatory studies are needed to generalize these findings to other populations.

In this study, the authors synthesized a-C:H films by filamentary dielectric barrier discharge (FDBD) to improve their mechanical properties compared to the films synthesized by glow DBD (GDBD), which is generally used for atmospheric pressure plasma enhanced chemical vapor deposition. The discharge type was transited from GDBD to FDBD by increasing the gap between the electrodes from 1 to 4 mm. The hydrogen concentration of the a-C:H films synthesized by FDBD was reduced compared to that of the films synthesized by GDBD. The hardness of the films increased from 3.7 to 11.9 GPa by using FDBD. These results show that the hard a-C:H films can be synthesized at room temperature in a large area by FDBD. [ABSTRACT FROM AUTHOR]

Abstract Background Pancreatic cancer with distant metastases is classified as “unresectable,” for which the standard treatment is systemic chemotherapy. The effectiveness of radical resection for pancreatic cancer with distant metastases is unknown. Here, we report a case of long term survival treated with conversion surgery following chemotherapy after diagnostic metastasectomy for pancreatic cancer with synchronous liver metastasis. Case presentation A 73-year-old man was referred to our hospital to examine and treat for cancer of the pancreatic body. Computed tomography (CT) scan revealed a 26-mm hypovascular tumor in contact with the common hepatic artery (CHA) (> 180°), the celiac artery (

Abstract Background The Tokyo Guidelines 2013 classifies acute cholecystitis (AC) into three grades and recommends appropriate therapy for each grade. For grade II AC, either early laparoscopic cholecystectomy (LC) or percutaneous transhepatic gallbladder drainage (PTGBD) should be performed. This study aimed to identify the risk factors for difficulty of LC for treating grade II AC. Methods Totally, 122 patients who underwent LC for grade II AC were enrolled and divided into difficult LC (DLC) and nondifficult LC (NDLC) groups. The DLC group included patients who experienced one of the following conditions: conversion from LC to open cholecystectomy, operating time ≥ 180 min, or blood loss ≥300 ml. Preoperative characteristics and postoperative outcomes were analyzed. Results In univariate analysis, risk factors included male sex, interval between symptom onset and admission, interval between symptom onset and LC, and anticoagulant therapy. The incidence of postoperative complications was higher in the DLC group than in the NDLC group (23.5% vs. 4.6%, p = 0.0016). According to receiver operating characteristic curves, the optimal cutoff value was calculated, and multivariate analysis showed that male sex [odds ratio (OR), 5.76; 95% confidence interval (CI), 1.979–19.51; p = 0.0009) and interval between symptom onset and LC of over 96 h (OR, 6.32; 95% CI, 2.126–20.15; p = 0.0009) were independent risk factors for difficulty of LC. Conclusions In patients with grade II AC, LC was technically difficult when performed over 96 h after symptom onset. Moreover, male sex was a risk factor. Therefore, PTGBD should be considered in these patients.

Abstract Background von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. Case presentation A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. Conclusions A pancreas-sparing resection should be considered for patients with pancreatic neuroendocrine tumors and complete cystic replacement of the pancreas to preserve quality of life after surgery.

Pancreatic ductal adenocarcinoma is one of the most aggressive types of cancer. Certain proteins in the tumor microenvironment have attracted considerable attention owing to their association with tumor invasion and metastasis. Here, we used proteomics to identify proteins associated with lymph-node metastasis, which is one of the prognostic factors. We selected lymph node metastasis-positive and -negative patients (n = 5 each) who underwent pancreatectomy between 2005 and 2015 and subjected to comprehensive proteomic profiling of tumor stroma. A total of 490 proteins were detected by mass spectrometry. Software analysis revealed that nine of these proteins were differentially expressed between the two patient groups. We focused on hemopexin and ferritin light chain based on immunohistochemistry results. We assessed the clinicopathological data of 163 patients and found that hemopexin expression was associated with UICC N2 (p = 0.0399), lymph node ratio (p = 0.0252), venous invasion (p = 0.0096), and lymphatic invasion (p = 0.0232). Notably, in vitro assays showed that hemopexin promotes invasion of the pancreatic cancer cells. Our findings suggest that hemopexin is a lymph node metastasis-associated protein that could potentially serve as a useful therapeutic target or biomarker of pancreatic ductal adenocarcinoma.

Soluble royal jelly protein is a candidate factor responsible for mammiferous cell proliferation. Major royal jelly protein 1 (MRJP1), which consists of oligomeric and monomeric forms, is an abundant proliferative protein in royal jelly. We previously reported that MRJP1 oligomer has biochemical heat resistance. Therefore, in the present study, we investigated the effects of several heat treatments (56, 65 and 96°C) on the proliferative activity of MRJP1 oligomer. Heat resistance studies showed that the oligomer molecular forms were slightly maintained until 56℃, but the molecular forms were converted to macromolecular heat-aggregated MRJP1 oligomer at 65℃ and 96℃. But, the growth activity of MRJP1 oligomer treated with 96°C was slightly attenuated when compared to unheated MRJP1 oligomer. On the other hand, the cell proliferation activity was preserved until 96℃ by the cell culture analysis of Jurkat cells. In contrast, those of IEC-6 cells were not preserved even at 56°C. The present observations suggest that the bioactive heat-resistance properties were different by the origin of the cells. The cell proliferation analysis showed that MRJP1 oligomer, but not MRJP2 and MRJP3, significantly increased cell numbers, suggesting that MRJP1 oligomer is the predominant proliferation factor for mammiferous cells.

Label-free detection of single-nucleotides was performed by fast tunneling current measurements in a polar solvent at 1 MHz sampling rate using SiO2-protected Au nanoprobes. Short current spikes were observed, suggestive of trapping/detrapping of individual nucleotides between the nanoelectrodes. The fall and rise features of the electrical signatures indicated signal retardation by capacitance effects with a time constant of about 10 microseconds. The high temporal resolution revealed current fluctuations, reflecting the molecular conformation degrees of freedom in the electrode gap. The method presented in this work may enable direct characterizations of dynamic changes in single-molecule conformations in an electrode gap in liquid.

Hydrogenated amorphous carbon films with various thicknesses were synthesized by dielectric barrier discharge-based plasma deposition under atmospheric pressure diluted with nitrogen (N2) and helium (He) at various pulse frequencies. The C2H2/N2 film showed cauliflower-like-particles that grew bigger with the increase in film’s thickness. At 5 kHz, the film with a thickness of 2.7 µm and smooth surface was synthesized. On the other hand, the films synthesized from C2H2/He had a smooth surface and was densely packed with domed particles. The domed particles extended with the increase in the film thickness, enabling it to grow successfully to 37 µm with a smooth surface. [ABSTRACT FROM AUTHOR]