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Abstract Aim The aim of this study was to clarify the significance of blood culture testing in the postoperative period of pancreatoduodectomy (PD), a highly invasive surgery. Methods Rates of blood culture sampling and positivity were investigated for febrile episodes (FEs) in patients who underwent PD (2016–2021). FEs were defined as body temperature of 38.0°C or higher occurring on or after the 4th postoperative day. Fever origin was diagnosed retrospectively, and FEs were classified as pancreatic fistula (PF)‐related or PF‐unrelated FEs. Factors correlated with blood culture positivity were explored. Results Among 339 patients who underwent PD, 99 experienced 202 FEs. Blood culture testing was performed on 160 FEs occurring in 89 patients. The sampling and positivity rates were 79.2% and 17.5%, respectively, per episode and 89.9% and 28.1%, respectively, per patient. Thirty‐six FEs were classified as PF‐related and 124 were classified as PF‐unrelated FEs. The blood culture positivity rate was significantly lower in PF‐related vs. PF‐unrelated FEs (1/36 vs. 27/124, respectively, p = 0.006). The blood culture positivity rate was significantly higher in patients with cholangitis, catheter‐related blood stream infection, and urinary tract infection than PF‐related FEs. Multivariate analysis showed that blood culture positivity was negatively associated with PF‐related FEs and positively associated with accompanying symptoms of shivering, Pitt Bacteremia Score, and preoperative biliary drainage. Conclusions Patients who underwent PD showed relatively high blood culture positivity rates. Based on these results, it may be possible to distinguish PF‐related and ‐unrelated FEs.

Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Abstract Human‐induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno‐free and robust methods for lineage‐specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high‐efficiency muscle lineage generation. HS conjugation to the C‐terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine.

Abstract Deleterious germline variants in the BRCA1-associated ring domain (BARD1) gene moderately elevate breast cancer risk; however, their potential association with other neoplasms remains unclear. Here, we present the case of a 43-year-old female patient diagnosed with sigmoid colon adenocarcinoma whose maternal family members met the Amsterdam Criteria II for Lynch syndrome. Comprehensive multigene panel testing revealed a heterozygous BARD1 exon 3 deletion.

The effects of Au addition on the acetone response of Cu2O-added porous SnO2 (pr-Cu2O-SnO2) powders, which were synthesized by ultrasonic spray pyrolysis employing polymethyl methacrylate microspheres as a template, were investigated in this study. The 3.0 wt% Au-added pr-Cu2O-SnO2 sensor showed the largest acetone response among all sensors. In addition, the magnitude of the acetone response was much larger than those of the ethanol and toluene responses. The catalytic activities of these gases over Au-added pr-Cu2O-SnO2 powders were also examined to clarify the key factors affecting their acetone-sensing properties. The Au addition increased the complete oxidation activity of all gases, and the complete oxidation activity of acetone was much higher than those of ethanol and toluene. These results indicate that the oxidation behavior during the gas-diffusion process in the sensitive Au-added pr-Cu2O-SnO2 layer of the sensors is quite important in enhancing the acetone-sensing properties.

Objectives: The present study aimed to investigate the clinical relevance of lateral pelvic lymph node dissection (LPLND) in low rectal cancer without preoperative treatment, with a focus on the presence of LPLN enlargement in preoperative imaging. Methods: Consecutive patients with cT3 to T4 low rectal cancer who underwent mesorectal excision and LPLND without preoperative treatment between 2007 and 2018 at a single dedicated cancer center were included. LPLN short-axis diameter (SAD) measured using preoperative multi-detector row computed tomography (MDCT) was evaluated retrospectively. Results: A total of 195 consecutive patients were analyzed. Overall, 101 (51.8%) and 94 (48.2%) patients had visible and no visible LPLNs in preoperative imaging, including 56 (28.7%), 28 (14.4%), and 17 (8.7%) patients had SADs of

Postoperative arterial bleeding after gastrointestinal surgery is a potentially fatal complication. Transcatheter arterial embolization is considered the first-line treatment because of efficacy and less invasiveness despite the risk of organ infarction. With the recent advances in endovascular devices, stent-graft placement, which can preserve arterial flow, has been an alternative treatment option in patients with extrahepatic artery hemorrhage. Moreover, clinical outcomes of stent-graft placement for pseudoaneurysms in relative long term have been reported recently. Herein, we review the techniques and clinical outcomes for interventional management for postoperative arterial bleeding.

In this study, double-multilayer monochromators that generate intense, high-energy, pink X-ray beams are designed, installed and evaluated at the SPring-8 medium-length (215 m) bending-magnet beamline BL20B2 for imaging applications. Two pairs of W/B4C multilayer mirrors are designed to utilize photon energies of 110 keV and 40 keV with bandwidths of 0.8% and 4.8%, respectively, which are more than 100 times larger when compared with the Si double-crystal monochromator (DCM) with a bandwidth of less than 0.01%. At an experimental hutch located 210 m away from the source, a large and uniform beam of size 14 mm (V) × 300 mm (H) [21 mm (V) × 300 mm (H)] was generated with a high flux density of 1.6 × 109 photons s−1 mm−2 (6.9 × 1010 photons s−1 mm−2) at 110 keV (40 keV), which marked a 300 (190) times increase in the photon flux when compared with a DCM with Si 511 (111) diffraction. The intense pink beams facilitate advanced X-ray imaging for large-sized objects such as fossils, rocks, organs and electronic devices with high speed and high spatial resolution.

Abstract Background The treatment of locally advanced colon cancer is challenging, particularly when there is invasion of the abdominal wall. In such cases, balancing the securing of margins and sufficiently repairing abdominal wall defects is important, but difficult when the extent of invasion is large. Case presentation A 34-year-old male was referred to our hospital with abdominal pain and diagnosed with obstructive transverse colon cancer. He had undergone ileo-sigmoid colostomy at his previous hospital. The tumor was massive and invaded the abdominal wall (maximum diameter: approximately 12 cm), and was accompanied by regional lymph node swelling. No distant metastasis was detected. We diagnosed the tumor as cT4bN2bM0 Stage IIIC locally advanced transverse colon cancer and planned neoadjuvant chemotherapy. After two courses of FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan), he developed an entero-cutaneous fistula due to tumor penetration and required emergency diverting ileostomy construction. After the procedure, contrast-enhanced computed tomography showed good tumor shrinkage. As a result, the planned chemotherapy was canceled and he underwent radical resection of the tumor. En bloc extended right hemicolectomy was performed with excision of the fistula, ensuring a sufficient margin. The post-excision defect at the anterior abdominal wall involved 11 × 16 cm of fascia and 6 × 9 cm of skin located in the middle of the abdomen. A free anterolateral thigh flap was harvested from the right thigh and vascular pedicle was anastomosed to the right gastroepiploic artery and vein. The fascia lata, which was included in the anterolateral thigh flap, was sutured onto the abdominal wall fascia as inlay fashion to reconstruct the abdominal wall defect. Histopathology revealed moderately differentiated adenocarcinoma of the colon with no tumor cells in the abdominal wall tissue [post-chemotherapeutic state, therapy effect: Grade 1b; Stage IIA (ypT3N0M0)]. All resected margins of the specimen were free from adenocarcinoma. He was discharged on postoperative day 16. Conclusion We report a case of colon cancer extensively invading the abdominal wall, which was completely resected. The abdominal wall defect was reconstructed with a free anterolateral thigh flap after tumor shrinkage with neoadjuvant chemotherapy. We present an efficient strategy for managing locally advanced colon cancer with extensive abdominal wall invasion.

Abstract A median sternotomy is often performed in patients with gastric tube cancer reconstructed through the retrosternal route; however, this procedure is invasive and has the risk of severe infectious complications. To overcome these problems, we created a novel method to perform the reconstructed gastric tube resection using a gastric tube inversion technique combined with a laparoscopic mediastinal approach. After the duodenum was divided, the oral side of the cut end was sutured with silken threads for traction. The gastric tube was dissected from the caudal side under a laparoscopic mediastinal approach, whereas the cervical esophagus was taped. After the adhesion between the middle side of the posterior sternum and the reconstructed gastric tube was dissected to the cervix, the gastric tube was inverted by guiding and pulling the thread toward the cervical side. Sharp dissection was facilitated between the inverted gastric tube and the surrounding organs under moderate traction and a favorable surgical view. We have performed this procedure and evaluated the short‐term outcomes in six cases. The laparoscopic mediastinal approach was completed without a median sternotomy in all six cases. Restorable intraoperative lung injury was observed in one case and no major vessel injuries were observed. The postoperative course was satisfactory with a 29.5‐day median length of hospital stay (range, 16‐60 days). The gastric tube inversion technique combined with the laparoscopic mediastinal approach for patients with retrosternal‐reconstructed gastric tube cancer was shown to be safe and less invasive and should be considered in resection of the reconstructed gastric tube.

Adsorption/combustion-type gas sensors, subspecies of catalytic combustion-type gas sensors, show large dynamic responses to volatile organic compounds (VOCs) under the operation with a mode of pulsed temperature heating, because of the flash catalytic combustion of target VOCs adsorbed on the gas-sensing films. Catalytic combustion behavior of ethanol over γ-Al2O3 powders loaded with and without 1 wt% Pt and/or 10 wt% metal oxide (MO: CeO2 or Bi2O3) and their adsorption/desorption properties of ethanol (adsorption temperature: 150°C) were investigated, and then the ethanol-sensing characteristics of the sensors utilizing the gas-sensing materials (low and high temperatures under dynamic operation: 150°C and 450°C, respectively) have been discussed on the basis of the findings on both their catalytic combustion behavior and adsorption/desorption properties. Especially, the co-loading of Pt with CeO2 onto γ-Al2O3 was the most effective in enhancing the dynamic response, because the relatively small amounts of various compounds that were adsorbed on the surface at 150°C efficiently oxidized at the initial stage of the pulse-driven heating to form CO2. The effects of low and high temperatures under the pulse-heating operation on the ethanol-sensing properties of the sensor utilizing γ-Al2O3 co-loaded with Pt and CeO2 were also clarified on the basis of the above findings.

Left-sided portal hypertension following pancreaticoduodenectomy (PD) with portal vein resection and splenic vein ligation may cause ectopic variceal formation, potentially resulting in life-threatening bleeding. We report of a 79-year-old male suffering from severe anemia and melena after PD. Emergency endoscopy and contrast-enhanced computed tomography (CECT) revealed ectopic varices at the anastomosis site of pancreaticojejunostomy. An interventional radiology approach was preferred over surgical and endoscopic treatment because of the poor general condition and altered anatomy. In the first procedure, percutaneous transhepatic retrograde obliteration was performed using the coaxial double balloon-occlusion technique. Although hemostasis was obtained, re-bleeding occurred two months later. CECT revealed the development of another collateral pathway and the recurrence of varices. Insufficient embolization of the afferent vein was considered the cause of recurrence. Therefore, a percutaneous transsplenic approach was used, and complete embolization of varices was achieved. When transhepatic retrograde obliteration is not effective, transsplenic antegrade obliteration can be a useful therapeutic option.

Abstract Background Expression of human equilibrative nucleoside transporter‐1 (hENT1) is reported to predict survival of gemcitabine (GEM)‐treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. Aim We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. Methods The subjects of this study were totally 332 whose formalin‐fixed paraffin‐embedded specimens and/or unstained sections were obtained. The individual H‐scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. Results The highest concordance rate (79.8%) was obtained when the cut‐off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H‐score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p

Background : : Malignant afferent loop syndrome occurs after biliary reconstruction and is difficult to treat because of the complicated anatomical changes. The aim of this study was to investigate the safety and efficacy of percutaneous metallic stent placement for malignant afferent loop syndrome via the blind end of the jejunal limb after biliary reconstruction. Methods : : Percutaneous metallic stent placement via the jejunal limb was performed in five male patients (median age, 68 years; range, 51–88 years) with malignant afferent loop syndrome following pancreatoduodenectomy or bile duct resection with reconstruction at our institute from June 2009 to April 2019. Reconstruction was performed using a modified Child’s method or the Roux-en-Y method, and blind end of the jejunal limb was surgically fixed to the abdominal wall. Percutaneous drainage of the afferent loop was performed via the blind end of the jejunal limb. Subsequently, percutaneous metallic stent placement was performed via the same route. Technical success, clinical success, and complications were retrospectively evaluated. Results : : Percutaneous metallic stent placement via the blind end of the jejunal limb was successfully achieved in all six procedures. Additional metallic stent placement was performed due to tumor ingrowth in a patient. Drainage catheters were removed from three patients, clamped in one, and could not be removed in one. Clinical success was achieved in four patients (80%) without major complications. Conclusion : : Percutaneous metallic stent placement for malignant afferent loop syndrome via the blind end of the jejunal limb after biliary reconstruction could be a safe and effective procedure.

Porous (pr-)SnO2-based powders were synthesized by ultrasonic spray pyrolysis employing home-made polymethylmethacrylate (PMMA) microspheres (typical particle size: 70 nm in diameter), and effects of the CuxO addition to the pr-SnO2 powder on the acetone and toluene sensing properties were investigated. Well-developed spherical pores reflecting the morphology of the PMMA microsphere templates were formed in the SnO2-based powders, which were quite effective in enhancing the acetone and toluene responses. The 0.8 wt% Cu-added pr-SnO2 sensor showed the largest acetone response at 350 °C among all the sensors. Furthermore, we clarified that the addition of CuxO onto the pr-SnO2 decreased the concentration of carrier electrons and the acetone-oxidation activity, leading to the improvement of the acetone-sensing properties of the pr-SnO2 sensor.

Abstract Background and Aim Surgical resection is the standard local therapy for patients with colorectal liver metastases (CRLM). However, elderly and vulnerable patients sometimes have various organ dysfunctions. We have to conduct nonsurgical local therapies for those patients who might not tolerate surgery or systemic chemotherapy. Methods We retrospectively reviewed medical records of 254 patients who underwent local therapies, including surgery, radiofrequency ablation (RFA), and stereotactic body radiation therapy (SBRT), for CRLM from January 2010 to December 2016, at seven tertiary‐care institutions in Japan. This study was designed to include elderly, vulnerable patients who received local therapy for CRLM. For those undergoing liver resection, only those having one or more points of the Charlson comorbidity index (CCI) were enrolled. Results Of the total 169 enrolled patients, 122 patients underwent surgery, 42 RFA, and 5 SBRT as the first local therapy for CRLM. Median overall survival from the first local therapy was 5.9 years for the surgery group, 2.7 years for the RFA group, and 3.8 years for the SBRT group. The proportion of the patients with CCI ≧3 was significantly higher in the group of RFA/SBRT than surgery (P

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Abstract Background Postoperative bleeding originating from pseudoaneurysms after radical gastrectomy is not common, but it can be fatal. In particular, delayed bleeding that occurs after the seventh postoperative day is rare. Case presentation A 54-year-old man underwent laparoscopic distal gastrectomy, D2 lymph node dissection, and Roux en-Y reconstruction for duodenal neuroendocrine tumors. Drainage was performed for a postoperative pancreatic fistula and abdominal abscess. On the 28th postoperative day, he passed a large amount of bloody stool; therefore, emergency esophagogastroduodenoscopy (EGD) and angiography were performed. However, neither examination demonstrated any bleeding foci or pseudoaneurysm. He was conservatively observed and discharged on the 50th postoperative day. Approximately 1 year after the surgery, he passed a bloody stool and experienced hemorrhagic shock. An EGD revealed exposed blood vessels at the duodenal blind end. His condition was diagnosed as a pseudoaneurysm arising from gastroduodenal artery, which ruptured into the duodenum, based on abdominal contrast-enhanced computed tomography findings. Emergency angiography was performed, and the pseudoaneurysm and artery were successfully embolized. Conclusions This case illustrates that there is a possibility of delayed bleeding even 1 year after gastrectomy. Such cases may be serious and require immediate and careful management.

Background and study aims Endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) is an alternative therapy for percutaneous transhepatic biliary drainage. Outcomes of EUS-CDS for distal biliary tract obstruction with a covered self-expandable metallic stent (SEMS) as a primary drainage technique are unclear because there are few relevant reports. This study aimed to determine outcomes in patients undergoing EUS-CDS using SEMS as the primary drainage technique for malignant distal biliary duct obstruction. Patients and methods This retrospective study was conducted at Aichi Cancer Center Hospital, from January 2010 to July 2018, using data from our database. Results EUS-CDS was performed as a primary drainage technique for 92 patients. The technical success rate was 92.8 %, and the clinical success rate was 91.6 %. The overall incidence of adverse events was 15.7 %. The median stent patency time for the EUS-CDS was 396 days. Nineteen patients required re-intervention because of cholangitis or jaundice. Conclusion EUS-CDS as a primary drainage technique using SEMS has high technical and clinical success rates. It should be considered an effective drainage method with respect to long-term stent patency, low re-intervention rates, and absence of severe complications.

Abstract Background Spontaneous esophageal rupture, also known as Boerhaave syndrome, is a very serious life-threatening benign disease of the gastrointestinal tract. It is typically caused by vomiting after heavy eating and drinking. However, in our patient, because of a combination of hypopharyngeal cancer with stenosis and chemoradiotherapy (CRT), which caused chemotherapy-induced vomiting, radiotherapy-induced edema, relaxation failure, and delayed reflexes; resistance to the release of increased pressure due to vomiting was exacerbated, thus leading to Boerhaave syndrome. To the best of our knowledge, this is the first report of a patient with esophageal rupture occurring during CRT for hypopharyngeal cancer with stenosis. Case presentation A 66-year-old man with a sore throat was referred to our hospital. He was found to have stage IVA hypopharyngeal cancer, cT2N2bM0, and underwent radical concurrent CRT consisting of weekly cisplatin (30 mg/m2) and radiation (70 Gy/35fr), for larynx preservation. On day 27 of treatment, he vomited, which was followed by severe left chest pain radiating to the back and the upper abdomen. Enhanced computed tomography (CT) revealed extensive mediastinal emphysema and a small amount of left pleural effusion. Esophagography revealed extravasation into the left thoracic cavity, and the patient was diagnosed with an intrathoracic rupture type of Boerhaave syndrome. He underwent emergency left thoracotomy 21 h after the onset. The ruptured esophageal wall was primarily repaired by closure with two-layer suturing and covered by a pedicled omentum. A jejunostomy tube was placed for postoperative enteral nutrition. On postoperative day (POD) 16, the patient was transferred to head and neck surgery to finish CRT and was discharged on POD 56. He has survived without relapse for 11 months after surgery. Conclusion Patients with head and neck cancer are at risk for developing Boerhaave syndrome during CRT. In addition, since such patients often are in poor overall condition because of immunosuppression and protracted wound healing, Boerhaave syndrome can rapidly lead to severe life-threatening infections such as empyema and mediastinitis. Therefore, awareness of this condition is important so that appropriate treatment can rapidly be implemented to increase the likelihood of a good outcome.

Background: As part of our efforts to develop practical intervention applications for cancer prevention, we investigated a risk prediction model for gastric cancer based on genetic, biological, and lifestyle-related risk factors. Methods: We conducted two independent age- and sex-matched case–control studies, the first for model derivation (696 cases and 1392 controls) and the second (795 and 795) for external validation. Using the derivation study data, we developed a prediction model by fitting a conditional logistic regression model using the predictors age, ABCD classification defined by H. pylori infection and gastric atrophy, smoking, alcohol consumption, fruit and vegetable intake, and 3 GWAS-identified polymorphisms. Performance was assessed with regard to discrimination (area under the curve (AUC)) and calibration (calibration plots and Hosmer–Lemeshow test). Results: A combination of selected GWAS-identified polymorphisms and the other predictors provided high discriminatory accuracy and good calibration in both the derivation and validation studies, with AUCs of 0.77 (95% confidence intervals: 0.75–0.79) and 0.78 (0.77–0.81), respectively. The calibration plots of both studies stayed close to the ideal calibration line. In the validation study, the environmental model (nongenetic model) was significantly more discriminative than the inclusive model, with an AUC value of 0.80 (0.77–0.82). Conclusion: The contribution of genetic factors to risk prediction was limited, and the ABCD classification (H. pylori infection-related factor) contributes most to risk prediction of gastric cancer.

The current standard of care for patients with locally advanced rectal cancer (LARC) is neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision surgery. However, the response to nCRT varies among patients and only about 20% of LARC patients achieve a pathologic complete response (pCR) at the time of surgery. Therefore, there is an unmet need for biomarkers that could predict the response to nCRT at an early time point, allowing for the selection of LARC patients who would or would not benefit from nCRT. To identify blood-based biomarkers for prediction of nCRT response, we performed in-depth quantitative proteomic analysis of pretreatment plasma from mice bearing rectal tumors treated with concurrent chemoradiation, resulting in the quantification of 567 proteins. Among the plasma proteins that increased in mice with residual rectal tumor after chemoradiation compared to mice that achieved regression, we selected three proteins (Vascular endothelial growth factor receptor 3 [VEGFR3], Insulin like growth factor binding protein 4 [IGFBP4], and Cathepsin B [CTSB]) for validation in human plasma samples. In addition, we explored whether four tissue protein biomarkers previously shown to predict response to nCRT (Epidermal growth factor receptor [EGFR], Ki-67, E-cadherin, and Prostaglandin G/H synthase 2 [COX2]) also act as potential blood biomarkers. Using immunoassays for these seven biomarker candidates as well as Carcinoembryonic antigen [CEA] levels on plasma collected before nCRT from 34 patients with LARC (6 pCR and 28 non-pCR), we observed that levels of VEGFR3 (p = 0.0451, AUC = 0.720), EGFR (p = 0.0128, AUC = 0.679), and COX2 (p = 0.0397, AUC = 0.679) were significantly increased in the plasma of non-pCR LARC patients compared to those of pCR LARC patients. The performance of the logistic regression model combining VEGFR3, EGFR, and COX2 was significantly improved compared with the performance of each biomarker, yielding an AUC of 0.869 (sensitivity 43% at 95% specificity). Levels of VEGFR3 and EGFR were significantly decreased 5 to 7 months after tumor resection in plasma from 18 surgically resected rectal cancer patients, suggesting that VEGFR3 and EGFR may emanate from tumors. These findings suggest that circulating VEGFR3 can contribute to the prediction of the nCRT response in LARC patients together with circulating EGFR and COX2.

A molecular Mott insulator κ-(ET)_{2}B(CN)_{4} [ET = bis(ethylenedithio)tetrathiafulvalene] with a distorted triangular lattice exhibits a quantum disordered state with gapped spin excitation in the ground state. ^{13}C nuclear magnetic resonance, magnetization, and magnetic torque measurements reveal that magnetic field suppresses valence bond order and induces long-range magnetic order above a critical field ∼8 T. The nuclear spin-lattice relaxation rate 1/T_{1} shows persistent evolution of antiferromagnetic correlation above the transition temperature, highlighting a quantum spin liquid state with fractional excitations. The field-induced transition as observed in the spin-Peierls phase suggests that the valence bond order transition is driven through renormalized one-dimensionality and spin-lattice coupling.

Glypican-3 (GPC3), a 65 kD protein consisting of 580 amino acids, is a heparan sulfate proteoglycan bound to the cell membrane by glycosylphosphatidylinositol. This protein is expressed in the liver and the kidney of healthy fetuses but is hardly expressed in adults, except in the placenta. Contrarily, GPC3 is specifically expressed in hepatocellular carcinoma (HCC), ovarian clear cell carcinoma, melanoma, squamous cell carcinoma of the lung, hepatoblastoma, nephroblastoma (Wilms tumor), yolk sac tumor, and some pediatric cancers. Although the precise function of GPC3 remains unclear, it has been strongly suggested that it is related to the malignant transformation of HCC. We identified GPC3 as a promising target for cancer immunotherapy and have been working on the development of cancer immunotherapeutic agents targeting it through clinical trials. In some trials, it was revealed that the GPC3 peptide vaccines we developed using human leukocyte antigen-A24- and A2-restricted GPC3-derived peptides could induce GPC3-specific cytotoxic T cells in most vaccinated patients and thereby improve their prognosis. To further improve the clinical efficacy of cancer immunotherapy targeting GPC3, we are also developing next-generation therapeutic strategies using T cells engineered to express antigen-specific T-cell receptor or chimeric antigen receptor. In addition, we have successfully monitored the levels of serum full-length GPC3 protein, which is somehow secreted in the blood. The utility of GPC3 as a biomarker for predicting tumor recurrence and treatment efficacy is now being considered. In this review article, we summarize the results of clinical trials carried out by our team and describe the novel agent targeting the cancer-specific shared antigen, GPC3.

Porous (pr-) In2O3 powders loaded with and without noble metals (Au, Pd, or Pt) were prepared by ultrasonic spray pyrolysis employing the PMMA microspheres as a template (typical particle size (ps): 28 or 70 nm with a diameter), and their NO2 sensing properties were examined. The Au loading on the pr-In2O3 was effective to increase the NO2 response at lower operating temperature (≤200°C), while the metal loading of Pd or Pt were hardly effective. In addition, a decrease in the PMMA microspheres (from 70 to 28 nm in ps) largely increased the NO2 response, and an optimized amount of Au loaded on the pr-In2O3 sensor was 1.0 wt%. The decrease in the thickness of the sensing layer improved the NO2 response and response speed. It was suggested that the Au loading enhanced the amount of the negatively adsorbed NO2 on the bottom part of the sensing layer, leading to the increase in the NO2 response. Furthermore, the introduction of additional macropores (ps: 150 nm) to the 1.0 wt% Au loaded pr-In2O3 sensor increased the response to a low concentration of NO2 (0.025 ppm) at 30°C. Therefore, it was found that easy gas diffusion from the surface to the bottom part of the sensing layer increased the effective concentration of NO2, and thus the NO2 response was increased.

Numerous technologies exist to detect circulating tumor cells (CTCs), although reports on cytological detection of CTCs remain limited. We recently developed a cytology-based CTC detection device using glass slides and light microscopy. In this study, we automated this previously manual device to improve its efficiency and cost effectiveness for clinical applications. We conducted a pilot study using this device to compare CTCs in peripheral blood (PB) and draining venous blood (DVB) from patients with colorectal cancer (CRC). The cytology-based automated CTC detection platform consisted of a disposable filtration device with a three-dimensional (3D) metal filter and multichannel automated CTC enrichment device. This platform allowed rapid and gentle filtration of CTCs and their efficient transfer from the filter to glass slides for subsequent Papanicolaou (Pap) and immunocytochemical (ICC) staining. Cytological diagnosis of CTCs was performed by observing permanent glass slide specimens by light microscopy. The current pilot clinical study enrolled CRC patients (n = 26) with stage I-IV tumors, who underwent surgery. PB was collected before surgery, and DVB was obtained from the mesenteric vein immediately after resection. Based on the CTC morphology obtained from PB and DVB samples, we proposed the following cytological criteria for the diagnosis of CTCs: pan-cytokeratin-positive, atypical cells with malignant morphological features identified by Pap staining. The numbers of CTCs defined by these criteria were significantly higher in DVB than PB from CRC patients (p

We studied the ferrimagnet La_{5}Mo_{4}O_{16} with Mo ions on quasisquare lattices both experimentally and theoretically. We found that in addition to the antiferromagnetic ordering at T_{N}=200 K, a magnetic phase transition into a ferrimagnetic phase occurs at T_{s1}=60 K, which is caused by the orbital ordering of the Mo 4d states. We also found that the relatively small size of ferrimagnetic domains despite the large Ising anisotropy of the Mo spins are formed below T_{s1}, which are responsible for the relaxation behavior and the memory effect in the magnetization. Nonvolatile positive magnetoresistance observed in this compound below T_{s1} can be attributed to the fact that such magnetic domains and the electrical conduction along the domain walls disappear with the applied magnetic field.

A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient’s abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient’s condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations.

We suggest a natural split mechanism for sfermions based on N=2 supersymmetry (SUSY). N=2 SUSY protects a sfermion in an N=2 multiplet from gaining weight by SUSY breaking. Therefore, if partly N=2 SUSY is effectively obtained, a split spectrum can be realized naturally. As an example of the natural split mechanism, we build a gauge-mediated SUSY breaking-like model assuming N=2 SUSY is partly broken in an underlying theory. The model explains the Higgs boson mass and muon anomalous magnetic dipole moment within 1 σ level with a splitting sfermion spectrum. The model has seven light sparticles described by three free parameters and predicts a new chiral multiplet, sb: the N=2 partner of the N=1 U(1)Y vector multiplet. The bini, the fermion component of the sb, weighs MeVs. We mention the experimental and cosmological aspects of the model.

NO2-sensing properties of semiconductor gas sensors using porous In2O3 powders loaded with and without 0.5 wt% Au (Au/In2O3 and In2O3 sensors, respectively) were examined in wet air (70% relative humidity at 25 °C). In addition, the effects of Au loading on the increased NO2 response were discussed on the basis of NO2 adsorption/desorption properties on the oxide surface. The NO2 response of the Au/In2O3 sensor monotonically increased with a decrease in the operating temperature, and the Au/In2O3 sensor showed higher NO2 responses than those of the In2O3 sensor at a temperature of 100 °C or lower. In addition, the response time of the Au/In2O3 sensor was much shorter than that of the In2O3 sensor at 30 °C. The analysis based on the Freundlich adsorption mechanism suggested that the Au loading increased the adsorption strength of NO2 on the In2O3 surface. Moreover, the Au loading was also quite effective in decreasing the baseline resistance of the In2O3 sensor in wet air (i.e., increasing the number of free electrons in the In2O3), which resulted in an increase in the number of negatively charged NO2 species on the In2O3 surface. The Au/In2O3 sensor showed high response to the low concentration of NO2 (ratio of resistance in target gas to that in air: ca. 133 to 0.1 ppm) and excellent NO2 selectivity against CO and ethanol, especially at 100 °C.

Background and study aims We report a case of amelanotic malignant melanoma of the esophagus (AMME), an exceedingly rare disease. A 77-year-old Japanese woman presented to our hospital with features suggestive of a middle esophageal submucosal tumor, which was diagnosed pathologically as AMME. The patient underwent thoracoscopic resection of the esophagus and laparoscopic gastric tube reconstruction. Three years after surgery, computed tomography showed no recurrence. Generally, the prognosis of malignant melanoma of the esophagus is very poor. However, our patient had no recurrence, and is alive 3 years after surgery and 5 years after the tumor was first detected.

We report the case of a 60-year-old male who was diagnosed with gastric cancer. Upper gastrointestinal endoscopy indicated advanced cancer in the posterior wall of the gastric body. Biopsy revealed poorly differentiated adenocarcinoma. Abdominal computed tomography demonstrated thickening of the gastric wall and enlargement of the regional lymph nodes and of the para-aortic lymph nodes (PAN). The involvement of the PAN extended from the celiac axis to the caudal area of the inferior mesenteric artery [cT3N3aH0P0M1(LYM), stage IV]. Systemic chemotherapy was initiated. After 3 courses of S-1 plus cisplatin combination chemotherapy, the primary lesion and the enlarged lymph nodes revealed marked regression except for a minute residual lesion in the lymph nodes. Upon obtaining informed consent, open distal gastrectomy, D2 lymphadenectomy with PAN dissection, and Roux-en-Y reconstruction were performed. The patient was discharged from the hospital 35 days after the operation. Histopathological examination of the resected samples revealed malignant cells only in the PAN, not in the stomach or in the regional lymph nodes [ypT0N0M1(LYM), stage IV]. Currently, the patient is undergoing postoperative adjuvant chemotherapy with S-1 and has remained well without any recurrence after 6 months following surgery.

We propose a new method to measure a theoretically well-defined top quark mass at the LHC. This method is based on the “weight function method,” which we proposed in our preceding paper. It requires only lepton energy distribution and is basically independent of the production process of the top quark. We perform a simulation analysis of the top quark mass reconstruction with tt¯ pair production and lepton + jets decay channel at the leading order. The estimated statistical error of the top quark mass is about 0.4 GeV with an integrated luminosity of 100 fb−1 at s=14 TeV. We also estimate some of the major systematic uncertainties and find that they are under good control.

Periodontitis is a chronic infectious disease for which the fundamental treatment is to reduce the load of subgingival pathogenic bacteria by debridement. However, previous investigators attempted to implement a nuclear factor kappa B (NF-κB) decoy oligodeoxynucleotide (ODN) as a suppressor of periodontitis progression. Although we recently reported the effectiveness of the ultrasound-microbubble method as a tool for transfecting the NF-κB decoy ODN into healthy rodent gingival tissue, this technique has not yet been applied to the pathological gingiva of periodontitis animal models. Therefore, the aim of this study was to investigate the effectiveness of the technique in transfecting the NF-κB decoy ODN into rats with ligature-induced periodontitis. Micro computed tomography (micro-CT) analysis demonstrated a significant reduction in alveolar bone loss following treatment with the NF-κB decoy ODN in the experimental group. RT-PCR showed that NF-κB decoy ODN treatment resulted in significantly reduced expression of inflammatory cytokine transcripts within rat gingival tissues. Thus, we established a transcutaneous transfection model of NF-κB decoy ODN treatment of periodontal tissues using the ultrasound-microbubble technique. Our findings suggest that the NF-κB decoy ODN could be used as a significant suppressor of gingival inflammation and periodontal disease progression.

BackgroundProton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC.Material and methodsPatients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area.ResultsFLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months.ConclusionThis study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

OBJECTIVE: To our knowledge, no study has compared the facial and dental morphology of adult Latin and Japanese populations. The purpose of this study was to assess differences in the facial and dental morphology between adult Spanish and Japanese women with Class I malocclusion using lateral cephalograms. MATERIALS AND METHODS: The lateral cephalograms of 33 adult Spanish and 33 adult Japanese women were traced and digitized by a single investigator. All patients satisfied the following criteria: female sex; age 18–35 years; skeletal Class I malocclusion (ANB angle, 2°–5°; angle Class I malocclusion; arch length discrepancy, −10 to + 10 mm; overjet, 1–5 mm; overbite, 1–5 mm); absence of congenital anomalies, significant facial asymmetry, or congenitally missing teeth, with the exception of the third molars; significant temporomandibular joint problems; severe crowding; and no history of orthodontic treatment. RESULTS: Eleven and six angular measurements for the skeletal and dental hard tissues, respectively, were computed in accordance with previous studies. The results showed that Japanese women had significant maxillary and mandibular protrusion, clockwise mandibular rotation, greater labial tipping of incisors, and a smaller interincisal angle compared with Spanish women. CONCLUSION: At the time of orthodontic treatment planning, it is important to consider the facial and dental morphological characteristics of individual ethnic groups to achieve satisfactory outcomes and retention. The findings of this study provide valuable information that will aid in orthodontic treatment planning for adult Spanish and Japanese women.

CO-sensing properties of diode-type sensors employing an anodized TiO2 film and noble-metal (M) electrodes (M/TiO2 sensor, M: Pd, Pt, and Pd-nPt, n: the amount of Pt (wt %) in the Pd-nPt electrode) were investigated at 50–250 °C in dry or wet H2. All the M/TiO2 sensors showed nonlinear I–V characteristics as a diode device in air and N2, but the I–V characteristics of the sensors were actually linear in H2 because of the negligible small height of Schottky barrier at their M/TiO2 interface. The Pd/TiO2 sensor showed no CO response in H2, but the Pt/TiO2 and Pd-nPt/TiO2 sensors responded to CO in H2. Among them, the Pd-64Pt/TiO2 sensor showed the largest CO response at 100 °C in H2. The reason why the mixing of Pd with Pt was effective in improving the CO response is probably because of a decrease in the amount of dissolved hydrogen species, an increase in the amount of dissociatively adsorbed hydrogen species, and an increase in the amount of adsorbed CO species in CO balanced with H2 by the mixing of Pt into Pd. The interference from moisture in the target gas on the CO response should be largely improved from a practical application perspective.

Although KCNJ11 mutation is the main cause of neonatal diabetes mellitus, reports of maturity-onset diabetes in the young (MODY) related to KCNJ11 are rare. Here, we report a case of KCNJ11-MODY in a 12-yrold Japanese female. Hyperglycemia was initially detected during a school urine screening program. Subsequent laboratory examinations revealed impaired insulin secretion; however, no islet autoantibodies were detected. Genetic testing of KCNJ11 revealed a novel heterozygous variant, c.153G>C, p.Glu51Asp. The patient's father had the same mutation and was diagnosed with diabetes at 46 yr of age. KCNJ11-MODY was suspected, and sulfonylurea administration resulted in adequate glycemic control in the patient. The American College of Medical Genetics and Genomics guidelines classify this variant as likely pathogenic, and the effectiveness of sulfonylureas supports its pathogenicity. The patient could be treated with 0.02-0.03 mg/kg/d of glibenclamide, as this mutation may be responsive to only a small amount of sulfonylurea. A detailed family history and sequencing of causative genes, including KCNJ11, may help diagnose diabetes in school-aged patients. [ABSTRACT FROM AUTHOR]