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Abstract Voluntary participation is a central yet understudied aspect of collaboration. Here, we model collaboration as people’s voluntary choices between joining an uncertain public goods provisioning in groups and pursuing a less profitable but certain individual option. First, we find that voluntariness in collaboration increases the likelihood of group success via two pathways, both contributing to form more optimistic groups: pessimistic defectors are filtered out from groups, and some individuals update their beliefs to become cooperative. Second, we reconcile these findings with existing literature that highlights the detrimental effects of an individual option. We argue that the impact of an outside individual option on collaboration depends on the “externality” of loners — the influence that those leaving the group still exert on group endeavors. Theoretically and experimentally, we show that if collaboration allows for flexible group formation, the negative externality of loners remains limited, and the presence of an individual option robustly aids collaborative success.

BackgroundThe effectiveness of a dexamethasone-sparing strategy in the treatment of breast cancer with anthracycline-cyclophosphamide therapy when combined with first-generation 5-HT3 receptor antagonists (RAs) and neurokinin-1 RAs is unclear. This is attributable to a lack of evidence from direct comparison of multiple doses of DEX to a single dose of DEX in combination with first-generation 5-HT3 RAs in anthracycline-cyclophosphamide therapy. Our goal was to clarify the impact of dexamethasone-sparing strategies that involve both first-generation 5-HT3 RAs and palonosetron when combined with neurokinin-1 RAs, using a network meta-analysis.Materials and methodsA literature search was conducted on PubMed/Medline for articles published up to July 4, 2023. We included randomized controlled trials which assessed the efficacy of antiemetic regimens which combined 5-HT3 RAs and dexamethasone, with or without neurokinin-1 RAs, for the initial dose in anthracycline-cyclophosphamide therapy for patients with breast cancer. The primary outcome was the proportion of patients achieving a complete response during the delayed phase (CR-DP).ResultsThe difference in the proportion of patients achieving CR-DP between multiple and single doses of dexamethasone was 0.1% (95%CI: -12.4 to 12.5) with palonosetron and neurokinin-1 RAs, compared to 5.3% (95%CI: -13.4 to 23.0) with a single dose of a first-generation 5-HT3 receptor antagonist. Additionally, the difference was 12.7% (95% CI: -2.8 to 28.2) when comparing palonosetron against first-generation 5-HT3 RAs in combination with a single dose of dexamethasone and neurokinin-1 RAs.ConclusionPalonosetron is recommended rather than a single dose of first-generation 5-HT3 RAs in dexamethasone-sparing strategies for anthracycline-cyclophosphamide therapy.

Abstract Background Breast ultrasound (US) is useful for dense breasts, and the introduction of artificial intelligence (AI)-assisted diagnoses of breast US images should be considered. However, the implementation of AI-based technologies in clinical practice is problematic because of the costs of introducing such approaches to hospital information systems (HISs) and the security risk of connecting HIS to the Internet to access AI services. To solve these problems, we developed a system that applies AI to the analysis of breast US images captured using a smartphone. Methods Training data were prepared using 115 images of benign lesions and 201 images of malignant lesions acquired at the Division of Breast Surgery, Gifu University Hospital. YOLOv3 (object detection models) was used to detect lesions on US images. A graphical user interface (GUI) was developed to predict an AI server. A smartphone application was also developed for capturing US images displayed on the HIS monitor with its camera and displaying the prediction results received from the AI server. The sensitivity and specificity of the prediction performed on the AI server and via the smartphone were calculated using 60 images spared from the training. Results The established AI showed 100% sensitivity and 75% specificity for malignant lesions and took 0.2 s per prediction with the AI sever. Prediction using a smartphone required 2 s per prediction and showed 100% sensitivity and 97.5% specificity for malignant lesions. Conclusions Good-quality predictions were obtained using the AI server. Moreover, the quality of the prediction via the smartphone was slightly better than that on the AI server, which can be safely and inexpensively introduced into HISs.

Time irreversibility of a time series, which can be defined as the variance of properties under the time-reversal transformation, is a cardinal property of non-equilibrium systems and is associated with predictability in the study of financial time series. Recent pieces of literature have proposed the visibility-graph-based approaches that specifically refer to topological properties of the network mapped from a time series, with which one can quantify different degrees of time irreversibility within the sets of statistically time-asymmetric series. However, all these studies have inadequacies in capturing the time irreversibility of some important classes of time series. Here, we extend the visibility-graph-based method by introducing a degree vector associated with network nodes to represent the characteristic patterns of the index motion. The newly proposed method is parameter-free and temporally local. The validation to canonical synthetic time series, in the aspect of time (ir)reversibility, illustrates that our method can differentiate a non-Markovian additive random walk from an unbiased Markovian walk, as well as a GARCH time series from an unbiased multiplicative random walk. We further apply the method to the real-world financial time series and find that the price motions occasionally equip much higher time irreversibility than the calibrated GARCH model does.

Approximately 24 cases of cytokeratin-positive interstitial reticulum cell tumors have been reported in English literature. In this paper, we report a case of cytokeratin-positive interstitial reticulum cell tumor that was localized in the parafollicular region of the axillary lymph node and was an incidental finding in a patient with breast cancer. A 50 year-old woman underwent a mastectomy and lymph node dissection following a preoperative diagnosis of bilateral breast cancer. Histopathological examination revealed that the patient had non-invasive and invasive ductal carcinoma in the right and left mammary glands. Although we could not detect breast cancer metastasis in the lymph nodes, one of eight right axillary lymph nodes harbored an 11 × 8 mm discohesive sheet of large polygonal epithelioid tumor cells in the parafollicular area. Tumor cells were immunoreactive for AE1/AE3, CAM5.2, CK18 and l-caldesmon and negative for CD1a, CD21, CD23, CD31, CD68, and S‑100 protein markers. Based on these findings, the lesion was diagnosed as a cytokeratin-positive interstitial reticulum cell tumor of the lymph node. Notably, this early-stage cytokeratin-positive interstitial reticulum cell tumor demonstrated focal nuclear YAP/TAZ proto-oncogene products, which were recently identified as critical for differentiation, maturation, and function of fibroblastic reticular cells. To the best of our knowledge, this is the first report to describe nuclear YAP/TAZ immunoreactivity in cytokeratin-positive interstitial reticulum cell tumors.

Introduction and aim. We developed a rat model of portal vein ligation (PVL) with venous congestion (PVL+C) to investigate beneficial effect PVL plus congestion for regeneration of intact liver segments.Materials and methods. In the PVL group, portal vein branches were ligated except the caudate lobe (CL). In the PVL + C group, the left lateral hepatic vein was ligated in addition to PVL. Chronological changes in the following variables were compared among the groups: CL weight to body weight ratio (CL/BW), embolized liver weight to body weight ratio (EL/BW), histological findings of the embolized/non-embolized liver, and expression of several mediators that affect liver regeneration in the non-embolized liver.Results. Weight regeneration of CL continued up to postoperative day (POD)7 in PVL + C, but terminated at POD2 in PVL. CL/BW at POD7 was significantly higher in PVL + C than in PVL (2.41 ± 0.33% vs. 1.22 ± 0.18%, P < 0.01). In contrast, EL/BW continued to decrease up to POD7 in PVL + C but reached nadir at POD2 in PVL. Furthermore, EL/BW at POD7 was significantly smaller in PVL + C than in PVL (0.35 ± 0.03% vs. 0.67 ± 0.08%, P < 0.01). Histologically-proven injury in the embolized liver was more severe in PVL + C than in PVL. Expression of Ki-67, IL-6, TNF -a, and HGF were greater and/or more prolonged in PVL + C than in PVL.Conclusions. Our rat model of PVL + C was considered useful for investigating the beneficial effect of congestion in addition to PVC. PVL + C caused increased devastation of the embolized liver, and higher and more prolonged expression of factors promoting liver regeneration in the non-embolized liver than in PVL.

Background: Bone-only metastatic breast cancer is believed to be non-life-threatening, and mild therapy is frequently selected to avoid adverse events of drug therapy. However, the prognoses of such patients are not well studied. Methods: Patients who received drug therapies for metastatic breast cancer between 2004 and 2016 at our institution were divided into the “Bone-only metastasis”, “non-visceral”, and “visceral” groups based on the mode of the first metastasis, and the efficacy of the first-line therapy and survival of these patients were compared. Results: There were 131 eligible patients, and the bone-only metastasis, non-visceral, and visceral groups included 26, 25, and 80 patients, respectively. The median survival time (MST) of the overall survival (OS) in each group was 35.1, 34.9, and 37.4 months, respectively (p=0.71). The clinical benefit rates of first-line therapy in the bone-only metastasis, non-visceral, and visceral groups were 66.7%, 45%, and 69.3%, respectively, and the MST of the time to treatment failure (TTF) in each group was 6.3, 5.5, and 5.8 months, respectively, showing that the efficacy of first-line therapy did not significantly differ among the groups. In the bone-only metastasis group, patients with

Pancreatic intraepithelial neoplasia (PanIN), the most common premalignant lesion of the pancreas, is a histologically well-defined precursor to invasive pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms underlying the progression of PanINs have not been fully elucidated. Previously, we demonstrated that the expression of collapsin response mediator protein 4 (CRMP4) in PDAC was associated with poor prognosis. The expression of CRMP4 was also augmented in a pancreatitis mouse model. However, the role of CRMP4 in the progression of PanIN lesions remains uncertain. In the present study, we examined the relationship between CRMP4 expression and progression of PanIN lesions using genetically engineered mouse models. PanIN lesions were induced by peritoneal injection of the cholecystokinin analog caerulein in LSL-KRASG12D; Pdx1-Cre (KC-Crmp4 wild-type, WT) mice and LSL-KRASG12D; Pdx1-Cre; Crmp4−/− (KC-Crmp4 knockout, KO) mice. We analyzed pancreatic tissue sections from these mice and evaluated PanIN grade by hematoxylin and eosin staining. CRMP4 expression was examined and the cellular components assessed by immunohistochemistry using antibodies against CRMP4, CD3, and α-smooth muscle actin (SMA). The incidence of high-grade PanIN in KC-Crmp4 WT mice was higher than that in KC-Crmp4 KO animals. CRMP4 was expressed not only in epithelial cells but also in αSMA-positive cells in stromal areas of PanIN lesions. The CRMP4 expression in stromal areas correlated with PanIN grade in WT mice. These results suggested that the expression of CRMP4 in stromal cells may underlie the incidence or progression of PanIN.

Abstract Background According to the Response Evaluation Criteria in Solid Tumors (RECIST), progressive disease (PD) is diagnosed under two conditions: an increase in size of pre-existing lesions (IS) and the appearance of new lesions (NL). We retrospectively investigated the difference in the prognosis between IS and NL. Methods Patients receiving drug therapies for metastatic breast cancer between 2004 and 2015 at our institution were reviewed. The survival time after NL and IS was compared and the frequency of NL with each drug calculated. Results For the 107 eligible patients, the survival time after NL at second-line chemotherapy was significantly worse than after IS (median survival time 4.3 months vs. 20.3 months, p = 0.0048). Maintenance therapy with bevacizumab or trastuzumab had a high frequency of NL (88.9%), and third-line eribulin had a low frequency of NL (16.7%). A multivariate analysis showed that NL at second-line chemotherapy was not an independent risk factor (hazard ratio 1.02, 95%; confidence interval 0.54–1.93, p = 0.95) for the total survival time. Conclusions Patients with IS had a better survival after PD than those with NL. We may be able to avoid changing drug therapy for patients without NL and allow them to continue drug therapy for longer.

Abstract Background Medullary carcinoma of the pancreas (MCP) is a rare malignant pancreatic tumor. The World Health Organization classification defines the tumor as a subtype of pancreatic ductal carcinomas. MCP is histologically characterized as having highly pleomorphic cells with syncytial morphology, expansive tumor growth, and necrosis. The pathogenesis and clinical course of MCP are largely unknown. Herein, we report an unusual case of MCP that was radiologically followed up for 9 years prior to surgical intervention. Case presentation A 73-year-old Japanese woman with a nonspecific disease history was found to have an asymptomatic cyst in the pancreatic duct by abdominal ultrasonography. Thorough radiological investigation suggested it was not an aggressive neoplasm, and she received periodic check-ups under a clinical diagnosis of “a cystic pancreatic lesion of uncertain malignancy.” Nine years after initial presentation, she experienced acute pancreatitis and underwent thorough re-evaluation. Dynamic computed tomography revealed no cyst; rather, a solid tumor was detected. Cytology of the pancreatic duct suggested adenocarcinoma. Pancreatoduodenectomy with D2 lymph node dissection was performed. The resected tumor was a non-mucinous, solid mass measuring 22 × 10 mm. Microscopically, the tumor had a well-demarcated pushing border. Lymphocytic infiltration was abundant, and stromal component was sparse. The tumor cells were composed of highly pleomorphic cells, proliferating in sheets without glandular formation. Neither lymphovascular invasion nor lymph node metastasis was detected. The histopathologic diagnosis was MCP, pT1aN0M0. The tumor carried a KRAS mutation, and MLH-1, MSH-2, MSH-6, and PMS-2 immunostaining results were normal, suggesting microsatellite stability. The patient has remained free of disease for 29 months following surgical intervention. Conclusion A review of 20 previously reported cases plus the present case suggests that subsets of MCPs have genetic aberrations such as KRAS mutation and high microsatellite instability. MCP has been suggested to have a better prognosis than common ductal adenocarcinoma; however, 15 of 20 previously reported cases died from disease. Whether the asymptomatic cyst observed over 9 years contributed to the development of MCP in this patient is a subject for future study.

Abstract Background Metastatic breast tumors from other organs are very rare. We herein describe the case of a patient with a metastatic breast tumor due to ovarian cancer who was diagnosed by the succession of a p53 mutation. Case presentation The patient was a 59-year-old woman with sigmoid colon stenosis. Diagnostic imaging revealed a pelvic mass, multiple liver tumors, ascites, and multiple swollen para-aortic lymph nodes, suggesting an advanced ovarian tumor. Transverse loop colostomy and partial resection of the greater omentum was performed followed by six cycles of paclitaxel with carboplatin chemotherapy (TC therapy). Her cancer almost disappeared, with the exception of a small tumor in her pelvis. Simple hysterectomy with bilateral salpingo-oophorectomy was performed. Two years and 5 months after the second surgery, a mass was detected in her right breast and simple mastectomy was performed. A histological examination of the tumors from the first surgery revealed infiltrating papillary adenocarcinoma and the solid nest proliferation of atypical cells with comedo necrosis and psammoma bodies. The findings of an immunohistochemical analysis were as follows: cancer antigen 125 (CA125 (+)), cytokeratin 7 (CK7 (+)), cytokeratin 20 (CK20 (−)), p53 (+) and CDX2 (−), estrogen receptor (ER (slightly +)), progesterone receptor (PR (slightly +)), and human epidermal growth factor receptor 2 (HER2 (1+)). The breast tumors presented similar morphological features (ER (−), PR (−), HER2 (−), CA125 (+), CK7 (+), CK20 (−), p53 (+), mammaglobin (−), and GCDFP15 (−)), which were not characteristic of breast cancer. A direct sequencing analysis of p53 revealed a p.V173M mutation in exon 5 in both the breast tumor and the ovarian cancer. It was not detected in normal tissue, suggesting that the breast tumors were metastatic serous adenocarcinomas from ovarian cancer. Conclusions A direct sequencing mutation analysis of p53 was useful for distinguishing the primary tumor from the metastatic tumor. We should resect metastatic breast tumors to the extent that is possible because the prognosis of such patients is relatively good.

Introduction: Hormone receptor (HR)-positive metastatic breast cancer (MBC) is usually treated with hormone therapy. In postmenopausal females, aromatase inhibitors (AIs) are usually used as first-line therapy, and fulvestrant is used subsequently. The optimal treatment beyond fulvestrant has not been established. We experienced two cases in which high-dose toremifene (hdTOR) was effective after the failure of AIs and fulvestrant. Case 1: A 73-year-old female with HR-positive left breast cancer (T2N1M0) underwent preoperative chemotherapy and mastectomy with axillary dissection. Computed tomography (CT) revealed liver tumors in S7 (23 mm) and S8 (25 mm) during adjuvant letrozole therapy, so fulvestrant was started. The tumors initially decreased in size (23 and 22 mm), but then progressed (36 and 25 mm). Treatment was changed to hdTOR, and the tumors shrunk to 26 mm (S7) and 24 mm (S8), and she was stable for 6 months while receiving hdTOR. Case 2: An 81-year-old female with HR-positive left breast cancer (T2N1M0) underwent left mastectomy and axillary dissection. CT revealed liver tumors in S7 (20 mm) and S8 (11 mm) during adjuvant letrozole therapy, so fulvestrant treatment was started. The tumor in S7 shrunk (13 mm), but the tumor in S8 slightly progressed (13 mm), and both tumors progressed (14 and 18 mm) after 6 months. Treatment was changed to hdTOR, and the tumors slightly shrunk (12 and 14 mm) after 6 months. hdTOR has been continued for 9 months. Conclusion: hdTOR was effective for MBC after multiple hormone therapies, likely because it acts via a different mechanism of action.

Introduction: Locally advanced breast cancer (LABC) deteriorates the quality of life (QOL) of the affected patients. Combination chemotherapy or extended chemotherapy is considered to help to shrink local lesions. Case 1: A 71-year-old female with a history of tympanitis and cystitis with methicillin-resistant Staphylococcus aureus (MRSA) visited our hospital. There was a tumor of 7 cm in diameter in her right breast with skin ulceration. Paclitaxel + bevacizumab therapy was started, and after five cycles of therapy, a mastectomy with axillary dissection was performed. Chemotherapy with anthracycline was avoided for fear of activating the MRSA. After the operation, the patient's wound opened. However, it naturally epithelialized. Case 2: A 41-year-old female visited our hospital due to a tumor of 8 cm in diameter in her right breast with skin ulceration. Four cycles of paclitaxel + bevacizumab therapy were started, and her tumor almost disappeared during the first cycle. Then, doxorubicin + cyclophosphamide therapy was performed for four cycles, and a mastectomy with axillary dissection was performed. Her postoperative course was good. Discussion: Chemotherapy with bevacizumab or extended chemotherapy is generally not considered to contribute to a survival improvement. However, such therapy contributes in increasing the response to chemotherapy, and should be considered for patients with LABC to shrink the local lesions and improve the QOL.

Background and study aims: Neoadjuvant chemotherapy (NAC) may lead to a successful margin-negative resection in patients with initially unresectable locally advanced Klatskin tumor (IULAKT). Use of removable plastic stents is preferable for the safe implementation of NAC in patients with IULAKT to reduce the risk of recurrent cholangitis. Our aim was to evaluate the efficacy associated with the use of plastic stents placed across the stenosis and above the papilla (above stent) during NAC. Patients and methods: In this study, we stratified the patients into two groups chronologically with respect to the period of stent placement: above stent group (n = 17) and across stent group (n = 23) (plastic stent across the sphincter of Oddi). Results: The median stent patency period was 99 days in the above stent group and 31 days in the across stent group (P

PURPOSE: Pancreatic cancer still has one of the worst prognoses in gastrointestinal cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. In this study, we investigated the prognostic values of HIF1a, bFGF, VEGF, and PDGFA gene expressions as well as their interrelationships. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma (age, 65; range, 34–85 years). After laser capture microdissection, direct quantitative real-time reverse transcription-polymerase chain reaction assays were performed in triplicates to determine HIF1a, PDGFA, VEGF, and bFGF gene expression levels. Multivariate Cox proportional hazards regression analysis was used to assess the impact of HIF1a gene expression on prognosis. RESULTS:HIF1a was significantly correlated to every gene we tested: bFGF (P = .04), VEGF (P = .02), and PDGFA (P = .03). Tumor size, P = .04, and high HIF1a mRNA expression (cutoff, 75th percentile) had a significant impact on survival, P = .009 (overall model fit, P = .02). High HIF1a expression had a sensitivity of 87.1% and a specificity of 55.6% for the diagnosis short (

We have previously developed mouse models of HER-2-positive cervical cancer. Tumors in nude mice had histological structures similar to the original tumor and were stained by anti-HER-2 antibody in the same pattern as the patient's cancer. We have also previously developed tumor-targeting Salmonella typhimurium A1-R and have demonstrated its efficacy against patient-derived tumor mouse models, both alone and in combination. In the current study, we determined the efficacy of S. typhimurium A1-R in combination with trastuzumab on a patient-cancer nude-mouse model of HER-2 positive cervical cancer. Mice were randomized to 5 groups and treated as follows: (1) no treatment; (2) carboplatinum (30 mg/kg, ip, weekly, 5 weeks); (3) trastuzumab (20 mg/kg, ip, weekly, 5 weeks); (4) S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks); (5) S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks) + trastuzumab (20 mg/kg, ip, weekly, 5 weeks). All regimens had significant efficacy compared to the untreated mice. The relative tumor volume of S. typhimurium A1-R + trastuzumab-treated mice was smaller compared to trastuzumab alone (p = 0.007) and S. typhimurium A1-R alone (p = 0.039). No significant body weight loss was found compared to the no treatment group except for carboplatinum-treated mice (p = 0.021). Upon histological examination, viable tumor cells were not detected, and replaced by stromal cells in the tumors treated with S. typhimurium A1-R + trastuzumab. The results of the present study suggest that S. typhimurium A1-R and trastuzumab in combination are highly effective against HER-2-expressing cervical cancer.

A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) Salmonella typhimurium A1-R (5 × 10(7) CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). S. typhimurium A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). S. typhimurium A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting S. typhimurium A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma.

Objective: According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor–positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy–effective and hormone therapy–ineffective cases. Methods: Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. Results: A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2–positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy–ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. Conclusion: The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of hormone receptor–positive metastatic breast cancer, if needed.

Objectives: The recurrence of breast cancer during adjuvant hormone therapy is often targeted by second-line hormone therapy. However, there has been a lack of prior success with such treatments. We retrospectively investigated the efficacy of subsequent hormone therapy. Methods: Patients who underwent breast cancer surgery between 2006 and 2012 at our institution were investigated. Results: A total of 20 patients developed recurrence during adjuvant hormone therapy. There were four patients with luminal A, seven with luminal B and six with luminal HER2 tumors, respectively. Twelve patients received subsequent hormone therapy, and eight patients received chemotherapy. Subsequent hormone therapy produced one partial response (PR), two long stable disease (SD), one SD and five progressive disease (PD). A clinical benefit (CB) was obtained by 33%. Subsequent chemotherapy produced one complete response (CR), two PRs, one long SD and two PD, resulting in a CB in 66%. Among those who received any hormone therapy, the best responses were two PR, three long SD and one SD. A CB was obtained by 38%, while seven patients did not have any CB from hormone therapy. Meanwhile, the best responses to chemotherapy were two CRs, four PRs, three SD and two PD, thus resulting in a CB in 72%. All luminal A cases obtained a long SD or SD with hormone therapy. However, the CB of hormone therapy for non-luminal A cases was only 30%. Conclusions: The efficacy of hormone therapy for recurrence during adjuvant hormone therapy is poor, and when selecting therapy for such patients, the breast cancer subtype should be taken into account.

The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) with gemcitabine (GEM) in combination with fluorescence-guided surgery (FGS) on a pancreatic cancer patient derived orthotopic xenograft (PDOX) model. A PDOX model was established from a CA19-9-positive, CEA-negative tumor from a patient who had undergone a pancreaticoduodenectomy for pancreatic adenocarcinoma. Mice were randomized to 4 groups: bright light surgery (BLS) only; BLS+NAC; FGS only; and FGS+NAC. An anti-CA19-9 or anti-CEA antibody conjugated to DyLight 650 was administered intravenously via the tail vein of mice with the pancreatic cancer PDOX 24 hours before surgery. The PDOX was brightly labeled with fluorophore-conjugated anti-CA19-9, but not with a fluorophore-conjugated anti-CEA antibody. FGS was performed using the fluorophore-conjugated anti-CA19-9 antibody. FGS had no benefit over BLS to prevent metastatic recurrence. NAC in combination with BLS did not convey an advantage over BLS to prevent metastatic recurrence. However, FGS+NAC significantly reduced the metastatic recurrence frequency to one of 8 mice, compared to FGS only after which metastasis recurred in 6 out of 8 mice, and BLS+NAC with metastatic recurrence in 7 out of 8 mice (p = 0.041). Thus NAC in combination with FGS can reduce or even eliminate metastatic recurrence of pancreatic cancer sensitive to NAC. The present study further emphasizes the power of the PDOX model which enables metastasis to occur and thereby identify the efficacy of NAC in combination with FGS on metastatic recurrence.

We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naïve-macrophages" (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P

CO2-Responsive CCT Protein (CRCT) is a transcription factor regulating the expression of starch synthesis-related genes in the vegetative organs of rice. Among six rice cultivars (Nipponbare, Koshihikari, Habataki, Takanari, Momiroman, Leafstar), the expression of CRCT was highly correlated with the starch content of leaf sheath in Nipponbare, but not in Koshihikari, Takanari and Momiroman during plant development. Meanwhile, the expressions of starch synthesis-related genes such as ADP-glucose pyrophosphorylase large subunit 1 was correlated with CRCT expression in Nipponbare, Momiroman, and Leafstar, but the correlations were ambiguous in Koshihikari, Habataki, and Takanari. In addition, the slopes of its regression lines in Nipponbare were larger than those cultivars. These results suggest that the influence of CRCT on starch synthesis varies among these cultivars. Additionally, the similar cultivar differences were observed when these gene expressions were analyzed after sucrose treatment in leaf blade. Some mutations in the promoter regions of the starch synthesis-related genes were identified among these cultivars. There were cultivars in which the presence of mutations correlated with decreased expression of starch synthesis genes in response to CRCT. Thus, these mutations can partially explain the responsiveness of the starch synthesis-related genes to CRCT, and difference in starch content of vegetative organs among rice cultivars.

Abstract Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme1 (UBA1) gene and characterised by an overlap between autoinflammatory and haematologic disorders. Case presentation We reported a case of a 67-year-Japanese man receiving peritoneal dialysis (PD) who had recurrent aseptic peritonitis caused by the VEXAS syndrome. He presented with unexplained fevers, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed high serum C-reactive protein concentration and increased cell count in PD effluent. He was treated with antibiotics for PD-related peritonitis, but this was unsuccessful. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography images demonstrated intense FDG uptake in his left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and he was treated with oral prednisolone (PSL) 15 mg daily with good response. However, he was unable to taper the dose to less than 10 mg daily because his symptoms flared up. Since Tocilizumab was initiated, he could taper PSL dose to 2 mg daily. Sanger sequencing of his peripheral blood sample showed a mutation of the UBA1 gene (c.122 T > C; p.Met41Thr). We made a final diagnosis of VEXAS syndrome. He suffered from flare of VEXAS syndrome at PSL of 1 mg daily with his cloudy PD effluent. PSL dose of 11 mg daily relieved the symptom within a few days. Conclusions It is crucial to recognise aseptic peritonitis as one of the symptoms of VEXAS syndrome and pay attention to the systemic findings in the patients.

ABSTRACTCO2-Responsive CCT Protein (CRCT) is suggested to be a positive regulator of starch synthesis-related genes in the vegetative organs of rice. To investigate the physiological function of CRCT, we produced CRCT knockout lines by CRISPR/Cas9 system. CRCT knockout tended to slightly reduce photosynthetic performance and had some adverse effects on growth parameters such as tiller number and straw dry weight. The starch content in the leaf sheath of CRCT knockout lines was significantly lower than that of wild-type. qRT-PCR and RNA-seq analysis showed that sucrose treatment induced the expression of CRCT, which, in turn, induced many starch synthesis-related genes in wild-type, whereas this induction did not occur in CRCT knockout lines. In conclusion, our results suggest that sugar induction of starch synthesis-related genes is almost fully dependent on CRCT, making it a necessary factor for normal photosynthesis and growth of rice.

ABSTRACTAccurate estimation of sink capacity in rice (grain number × potential grain size), independent of grain filling, is necessary for considering source – sink interactions. However, how to measure potential grain size is still a matter of debate. Here, we investigated the effect of modifying the grain-filling environment on 1000-grain weight of grains screened by specific gravity or brown rice thickness, grain projected area (‘grain area’), or husk weight as candidate indicators of potential grain size using a japonica cultivar Koshihikari and its near-isogenic line with greater spikelet number. We found grain area to be the best, followed by 1000-grain weight. We developed a novel method to calculate sink capacity from grain area; the method was developed based on the relationship between individual grain weight and grain area. Comparison with the conventional method based on 1000-grain weight showed that although the method based on grain area is more accurate, that based on 1000-grain weight is useful enough, because screening by specific gravity or brown rice thickness selected filled grains well, and the effect of the grain-filling environment on 1000-grain weight was limited.

Background/Aim: Current expert consensus recommends re-resection for incidental gallbladder cancer (IGBC) of pT1b-3. This study examined whether this consensus was reasonably applicable to patients with IGBC in one Japanese region. Patients and Methods: This was a multicenter, retrospective analysis of cholecystectomies for presumed benign diseases between January 2000 and December 2009. Results: IGBC was diagnosed in 70 (1.0%) out of 6,775 patients undergoing cholecystectomy. Five-year disease-specific cumulative survival was 100% in 19 patients with pT1a, 80.0% in five with pT1b, 49.5% in 33 with pT2, and 23.1% in 13 with pT3. Re-resection was not performed for the 24 patients with pT1a/1b disease, whereas 24 out of 46 patients with pT2/3 underwent re-resection. Regardless of re-resection, independent factors associated with a poor prognosis on multivariate analysis were grade 2 or poorer disease and bile spillage at prior cholecystectomy. In the 24 patients with pT2/3 re-resection, 11 patients without either of these two factors had significantly better 5-year disease-specific cumulative survival than the 13 patients with one or two independent factors associated with a poor prognosis (72.7% vs. 30.8%, p=0.009). Conclusion: This Japanese regional study suggests that indication of re-resection for IGBC should not be determined by pT-factor alone and that much more attention should be paid to pathological and intraoperative findings at prior cholecystectomy. [ABSTRACT FROM AUTHOR]

Background/Aim: At present, there are no biomarkers to predict the effects of molecular targeted drugs in patients with CRC with liver metastasis. Thus, we performed this study to explore potential biomarkers for these patients. Materials and Methods: We obtained cancer tissue specimens from liver metastasis-bearing CRC patients who received the following preoperative neoadjuvant chemotherapies with molecular targeted drugs: i) no therapy (n=3), ii) 5-FU+oxaliplatin+anti-EGFR (n=3), iii) and 5- FU+oxaliplatin+anti-VEGF (n=3). Results: We investigated the RNA expression of 84 genes related to cancer drug resistance using an RT-PCR array. The MYC gene was the only gene that was significantly up-regulated in CRC tissue specimens from anti-EGFR group in comparison to the anti- VEGF group. Conclusion: MYC up-regulation in the primary CRC tissues may be a potentially useful biomarker for selecting anti-EGFR combination therapy in neoadjuvant chemotherapy for CRC with liver metastasis. [ABSTRACT FROM AUTHOR]

Background: We sought a diagnostic tool using perioperative variables that might predict post-hepatectomy liver failure (PHLF). Patients and Methods: In 68 patients undergoing major hepatectomy, data on inflammatory markers and coagulation factors were prospectively collected and were compared between patients with International Study Group of Liver Surgery definition grade B/C PHLF (LF group) and those without LF (non-LF group). Results: Preoperatively, the LF group (n=9; 13.2%) had a lower platelet count and a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity and a higher prothrombin time-International Normalized Ratio (PT-INR) than the non-LF group. On postoperative day 1, the LF group had significantly higher serum interleukin 6 (IL6), C-C motif chemokine ligand 2 (CCL2), and IL10 levels than the non-LF group. The logistic regression model that included preoperative PT-INR and CCL2 on postoperative day 1 predicted grade B/C PHLF with 100% sensitivity and 89.8% specificity. Conclusion: Our findings suggest that the combination of preoperative PT-INR and CCL2 on postoperative day 1 can predict PHLF earlier and precisely after major hepatectomy. [ABSTRACT FROM AUTHOR]

The non-structural carbohydrate (NSC) stored in rice stems (culm plus leaf sheaths) at pre-heading stage is one of the major carbon sources for grain filling. In this study, we conducted field experiments in 2018 and 2019 using two varieties, Momiroman (japonica-dominant) and Teqing (indica), which have different accumulation and remobilization patterns of NSC in the stems. We analyzed NSC dynamics of each of the five nodal segments of internodes and leaf sheaths at pre- and post-heading stages. The dynamics of NSC at pre- and post-heading stages differed among segments. The lower segments of internodes and leaf sheaths accumulated more NSC at pre-heading stage compared to the upper segments in both varieties. The lower internodes in Teqing were morphologically larger than in Momiroman and would be able to store more NSC. However, the upper parts of the stems required biomass for development and formation at the stage of NSC accumulation in stems. Momiroman had longer upper internodes and leaf sheaths and required more biomass than Teqing. The NSC remobilization was later in the upper than the lower internodes for both varieties, which led to the delay of NSC remobilization in the entire culm after heading. These results indicated that ideal morphology of stems, to maximize the potential contribution of stem NSC as the carbon source for grain filling, is large lower internodes and short upper internodes and leaf sheaths.

The mechanism of 5-fluorouracil (5FU) resistance was investigated, focusing on the level of thymidylate synthase (TS) ternary complex formed with fluoro-deoxyuridine monophosphate (FdUMP). MKN45 and 5FU-resistant MKN45/F2R cells were treated with 5FU and fluoro-deoxyuridine (FdU) in combination with deoxyuridine (dU) and thymidine (dT). Subsequently, the levels of ternary complex were determined by western blotting and the cell viability was calculated using an MTT assay. MKN45/F2R cells exhibited 5FU resistance (56.2-fold relative to MKN45 cells), and demonstrated decreased orotate phosphoribosyltransferase (OPRT) and increased TS levels, requiring a higher concentration of 5FU to induce ternary complex formation than MKN45 cells. Following transfection of small interfering RNA against OPRT, MKN45 exhibited increased resistance to 5FU and decreased ternary complex formation subsequent to treatment with 5FU, indicating that decreased OPRT led to increased 5FU resistance. However, MKN45/F2R also exhibited resistance to FdU, which can be converted to FdUMP without OPRT, and there was decreased ternary complex formation after treatment with FdU, indicating that the 5FU-resistant cells had the ability to decrease intracellular FdUMP. The addition of dU and thymidine dT to 5FU promoted the formation of ternary complexes and reversed 5FU resistance in MKN45/F2R cells, although dT inhibited the efficacy of raltitrexed (another TS inhibitor). These results suggested that 5FU-resistant cells had the ability to reduce intracellular FdUMP irrespective of decreased OPRT, which led to resistance to 5FU. This resistance was then inhibited by treatment with dT or dU. [ABSTRACT FROM AUTHOR]

GPR120 is a long-chain fatty acid (LCFA) receptor that is specifically expressed in gonadotropes in the anterior pituitary gland in mice. The aim of this study was to investigate whether GPR120 is activated by free fatty acids in the pituitary of mice and mouse immortalized gonadotrope LβT2 cells. First, the effects of palmitate on GPR120, gonadotropic hormone b-subunits, and GnRH-receptor expression in gonadotropes were investigated in vitro. We observed palmitate-induced an increase in Gpr120 mRNA expression and a decrease in follicle-stimulating hormone b-subunit (Fshb) expression in LβT2 cells. Furthermore, palmitate exposure caused the phosphorylation of ERK1/2 in LβT2 cells, but no significant changes were observed in the expression levels of luteinizing hormone b-subunit (Lhb) and gonadotropin releasing hormone-receptor (Gnrh-r) mRNA and number of GPR120 immunoreactive cells. Next, diurnal variation in Gpr120 mRNA expression in the male mouse pituitary gland was investigated using ad libitum and night-time restricted feeding (active phase from 1900 to 0700 h) treatments. In ad libitum feeding group mice, Gpr120 mRNA expression at 1700 h was transiently higher than that measured at other times, and the peak blood non-esterified fatty acid (NEFA) levels were observed from 1300 to 1500 h. These results were not observed in night-time-restricted feeding group mice. These results suggest that GPR120 is activated by LCFAs to regulate follicle stimulating hormone (FSH) synthesis in the mouse gonadotropes.

Negative energy balance in domestic animals suppresses their reproductive function. These animals commonly use long-chain fatty acids (LCFAs) from adipocytes as an energy source under states of malnutrition. The G-protein coupled receptor, GPR120, is a specific receptor for LCFAs, but its role in reproductive function remains unknown in domestic animals. The purpose of this study was to examine whether GPR120 is involved in the reproductive system of cattle. GPR120 mRNA expression was evaluated in brain, pituitary, and ovarian tissue samples by RT-PCR. GPR120 gene expression was detected with high intensity only in the anterior pituitary sample, and GPR120-immunoreactive cells were found in the anterior pituitary gland. Double immunohistochemistry of GPR120 in the anterior pituitary hormone-producing cells, such as gonadotropes, thyrotropes, lactotropes, somatotropes, and corticotropes, was performed to clarify the distribution of GPR120 in the anterior pituitary gland of ovariectomized heifers. Luteinizing hormone β subunit (LHβ)- and follicle-stimulating hormone β subunit (FSHβ)-immunoreactive cells demonstrated GPR120 immunoreactivity at 80.7% and 85.9%, respectively. Thyrotropes, lactotropes, somatotropes, and corticotropes coexpressed GPR120 at 21.1%, 5.4%, 13.6%, and 14.5%, respectively. In conclusion, the present study suggests that GPR120 in the anterior pituitary gland might mediate LCFA signaling to regulate gonadotrope functions, such as hormone secretion or production, in cattle.

Malnutrition is one of the factors that induces reproductive disorders. However, the underlying biological processes are unclear. AMP-activated protein kinase (AMPK) is an enzyme that plays crucial role as a cellular energy sensor. In the present study, we examined the effects of AMPK activation on the transcription of the murine gonadotropin subunit genes Cga, Lhb, and Fshb, and the gonadotropin-releasing hormone receptor Gnrh-r. Real-time PCR and transcription assay using LβT2 cells demonstrated that 5-amino-imidazole carboxamide riboside (AICAR), a cell-permeable AMP analog, repressed the expression of Lhb. Next, we examined deletion mutants of the upstream region of Lhb and found that the upstream regulatory region of Lhb (–2527 to –2198 b) was responsible for the repression by AICAR. Furthermore, putative transcription factors (SP1, STAT5a, and TEF) that might mediate transcriptional control of the Lhb repression induced by AICAR were identified. In addition, it was confirmed that both AICAR and a competitive inhibitor of glucose metabolism, 2-deoxy-D-glucose, induced AMPK phosphorylation in LβT2 cells. Therefore, the upstream region of Lhb is one of the target sites for glucoprivation inducing AMPK activation. In addition, AMPK plays a role in repressing Lhb expression through the distal –2527 to –2198 b region.

High-fat diet (HFD) is associated with the regulation of reproductive functions. This study aimed to investigate the effects of short-term HFD on the mRNA expression levels of follicle-stimulating hormone β subunit (FSHβ), luteinizing hormone β subunit (LHβ), gonadotropin-releasing hormone receptor, and long-chain fatty acid receptor, GPR120, in the matured male mouse pituitary gland. Adult male mice were fed either control chow or HFD for 1, 2, 5, 10, 30 and 150 days. Fshb and Gpr120 mRNA expression levels in the pituitary glands were significantly increased during 2 to 30 days of HFD feeding. Gnrh-r mRNA in the 30 days HFD fed group and body weight in the 30 and 150 days HFD fed groups were higher than control. However, there were no significant differences in plasma non-esterified fatty acids or glucose levels during the 150 days of HFD feeding. These results suggest that male mice feeding a short-term HFD induces FSHβ synthesis and GPR120 expression in their pituitary gonadotropes.

Background: Accumulation of tumor-infiltrating mast cells (MCs) predicts poor survival in several cancers after resection. However, its effect on the prognosis of patients with colorectal liver metastases (CRLM) is not known.Methods: Our retrospective study included 135 patients who underwent potentially curative resection for CRLM between 2001 and 2010. Expression of tryptase, MAC387, CD83, and CD31, which are markers for MCs, macrophages, mature dendritic cells, and vascular endothelial cells, respectively, was determined via immunohistochemistry of resected tumor specimens. The relationship between immune cell infiltration and long-term outcome was investigated.Results: The median follow-up time was 48.4 months for all patients and 57.5 months for survivors. Overall survival (OS) rates at 1, 3, and 5 years were 91.0, 62.4, and 37.4 %, respectively. Five-year disease-free survival (DFS) and OS rates were 21.6 and 38.1 %, respectively, in patients with high MC infiltration, and 42.6 and 55.6 %, respectively, in patients with low MC infiltration (p < 0.01 for both DFS and OS). Infiltration of other types of immune cells did not correlate with survival. Multivariate analyses indicated that hypoalbuminemia and high peritumoral MC infiltration were significant predictors of unfavorable OS.Conclusion: High peritumoral MC infiltration predicts poor prognosis in patients who underwent hepatectomy for CRLM. The number of MCs in metastatic lesions is important for predicting the prognosis of CRLM patients and as an indication of therapy. [ABSTRACT FROM AUTHOR]

Overexpression of Rubisco small subunit (RbcS) of C4 plant, sorghum (sorghum bicolor) was shown to enhance the catalytic turnover rate (kcat) of Rubisco in rice (Oryza sativa). In this study, the effects of other Rubisco small subunits of C4 plants, Napier grass (Pennisetum purpureum) and guinea grass (Megathyrsus maximus) on kinetic properties of Rubisco in rice were studied. The expression levels of Napier grass RbcS (NgRbcS) and guinea grass RbcS (GgRbcS) proteins accounted for 41% and 45% of total RbcS, respectively in homozygous overexpression lines. The kcat and Km for CO2 (Kc) of Rubisco were increased in all transgenic lines. Interestingly, the kcat was markedly higher in NgRbcS homozygous line, whereas Kc was notably higher in GgRbcS homozygous line. Although its effects depend on species, these results suggest that the introduction of C4 RbcS are effective approaches to alter the catalytic properties of Rubisco in rice. Abbreviation GgRbcS: guinea grass RbcS; Kc: Km for CO2; kcat: catalytic turnover rate; NpRbcS: Napier grass RbcS; RbcL: Rubisco large subunit; RbcS: Rubisco small subunit; Sc/o: CO2/O2 specificity.

Background: Endoscopic biliary stenting (EBS) is one of the most important palliative treatments for biliary tract cancer. However, reflux cholangitis arising from bacterial adherence to the inner wall of the stent must be avoided. We evaluated the use of EBS above the sphincter of Oddi to determine whether reflux cholangitis could be prevented in preoperative cases. Methods: Fifty-seven patients with primary biliary tract cancer were retrospectively recruited for the evaluation of stent placement either above (n = 25; inside stent group) or across (n = 32; conventional stent group) the sphincter of Oddi. We compared the stent patency periods prior to the time of surgical resection. Results: The preoperative periods were 96.3 days in the conventional stent group and 96.8 days in the inside stent group (P = 0.979). Obstructive jaundice and/or acute cholangitis occurred in 7 patients (28.0%) in the inside stent group and in 15 patients (46.9%) in the conventional stent group during the preoperative period (P = 0.150). The average patency periods of the stents were 85.2 days (range, 13-387 days) for the inside stent group and 49.1 days (range, 9-136 days) for the conventional stent group (log-rank test: P = 0.009). The mean numbers of re-interventions because of stent occlusion were 0.32 for the inside stent group and 1.03 for the conventional stent group (P = 0.026). Post-endoscopic retrograde cholangiopancreatography complications occurred in 2 patients in the inside stent group and 4 patients in the conventional stent group (P = 0.516). Postoperative liver abscess occurred in 1 patient in the inside stent group and 5 patients in the conventional stent group (P = 0.968). Inside stent placement was the only significant preventative factor associated with stent obstruction based on univariate (hazard ratio [HR], 0.286; 95% confidence interval [CI], 0.114-0.719; P = 0.008) and multivariate (HR, 0.292; 95% CI, 0.114-0.750; P = 0.011) analyses. Conclusion: Temporary plastic stent placement above the sphincter of Oddi is a better bridging treatment than conventional stent placement in preoperative primary biliary tract cancer. [ABSTRACT FROM AUTHOR]

Production of bioethanol from rice straw has attracted attention from the point of effective use of agricultural residue. Starch content is an important determinant for bioethanol production from rice straw. The overexpression of CO2-responsive CCT protein (CRCT), which is the positive regulator of starch synthesis in vegetative organs, notably increased the starch content in rice straw. To produce the bioethanol from rice straw, the dilute acid pretreatment is a general pretreatment method. Importantly, the glucose yields in liquid hydrolyzate after dilute acid pretreatment was markedly increased in the CRCT overexpression lines compared with non-transgenic rice. In addition, the overexpression of CRCT enhanced the biomass production. In contrast, CRCT did not affect on the glucose yields from cellulose in acid-insoluble residue obtained after dilute acid pretreatment. With respect to byproduct in liquid hydrolyzate which inhibits the fermentation, the formic acid content was increased, whereas the furfural, 5-hydroxymethylfurfural and acetic acid contents were unchanged by the overexpression of CRCT. These results demonstrate that genetic engineering of CRCT is an effective method to increase the bioethanol production from rice straw.

Background and study aims We developed an e-learning program for endoscopic diagnosis of invasion depth of early gastric cancer (EGC) using a simple diagnostic criterion called non-extension sign, and the contribution of self-study quizzes to improvement of diagnostic accuracy was evaluated. Methods We conducted a prospective randomized controlled study that recruited endoscopists throughout Japan. After completing a pretest, the participants watched video lectures and undertook post-test 1. The participants were then randomly allocated to either the self-study or non-self-study group, and participants in the first group completed the self-study program that comprised 100-case quizzes. Finally, participants in both groups undertook post-test 2. The primary endpoint was the difference in post-test 2 scores between the groups. The perfect score for the tests was set as 100 points. Results A total of 423 endoscopists completed the pretest and were enrolled. Post-test 1 was completed by 415 endoscopists and 208 were allocated to the self-study group and 207 to the non-self-study group. Two hundred and four in the self-study group and 205 in the non-self-study group were included in the analysis. Video lectures improved the mean score of post-test 1 from 72 to 77 points. Participants who completed the self-study quizzes showed significantly better post-test 2 scores compared with the non-self-study group (80 vs. 76 points, respectively, P

Abstract  We report a case of hepatic mesenchymal hamartoma in an adult; this condition is extremely rare, with only 15 cases having been reported in the English-language literature worldwide. The patient was a 36-year-old woman who was seen at her local hospital for upper abdominal distension. A giant multilocular cystic tumor, which had almost entirely replaced the normal parenchyma of the right lobe of the liver, was diagnosed. She was referred to our hospital, where, with a diagnosis of biliary cystadenoma, the tumor was successfully removed by right hemihepatectomy. After an uneventful postoperative course, the patient was discharged from our hospital. On histological examination, the tumor consisted of numerous cystic lesions without epithelial lining cells; hepatocytes, bile duct, and vascular components, without either lobular structure or atypia, were observed in the pseudocyst wall, leading to a diagnosis of hepatic mesenchymal hamartoma. There have been a few previously reported cases of multifocal hepatic mesenchymal hamartoma reappearing in the remaining liver after hepatectomy, although these cases are considered to be extremely rare. Therefore, periodic follow-up will be necessary for the patient. [ABSTRACT FROM AUTHOR]