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Abstract Bucket handle meniscal tears (BHMT) of the knee occur infrequently (approximately 10% of meniscal injuries). Simultaneous, bicompartmental BHMT are extremely rare. Previously, these have only been reported in association with a ruptured anterior cruciate ligament (ACL). The pathomechanism of this injury was thought to be due to the lack of knee stability following the ACL injury. We present a case of a 38 year old male patient with bicompartmental BHMT with a clinically competent ACL. This highlights the need for clinical and radiological suspicion of simultaneous BHMTs even in the presence of an intact ACL.

Background: Apoptosis was initially identified through transmission electron microscopy. Subsequent advances in morphological techniques for apoptosis detection have revealed its involvement in multiple pathological conditions in various tissues. This review summarizes previous experimental studies on apoptotic cell death during regressive changes in the salivary glands, with a focus on morphological observations., Highlight: Obstructive sialadenitis is histologically characterized by acinar cell loss and increased number of duct cells. Although acinar cells were previously believed to dedifferentiate into duct cells, there is evidence that they are eliminated by apoptosis. Animals fed a soft diet exhibited parotid gland atrophy, in which acinar cells decreased in size and disappeared because of apoptosis. Age-related changes in the salivary glands involved a reduced number of acinar cell through apoptosis. Additionally, apoptotic acinar cell death occurs in other pathological conditions, including the regression of hypertrophic and irradiated salivary glands., Conclusion: Apoptosis often eliminates acinar cells during atrophic alterations in the salivary glands. Unlike necrosis, apoptosis is an active form of cell death, thereby helping prevent the complete destruction of the salivary glands. However, the contribution of apoptosis to regressive changes in the salivary glands remains unclear and warrants further investigation., (Copyright © 2024. Published by Elsevier B.V.)

Gastrointestinal (GI) polyposis and cancer in pediatric patients is frequently due to an underlying hereditary cancer risk syndrome requiring ongoing cancer screening. Identification of at-risk patients through family history, clinical features of a syndrome, or symptom onset ensures appropriate cancer risk assessment and management in childhood and beyond. In this 2024 perspective, we outline updates to the hereditary GI cancer screening guidelines first published by the American Association of Cancer Research Pediatric Cancer Predisposition Workshop in 2017. These guidelines consider existing recommendations by pediatric and adult gastroenterology consortia to ensure alignment with gastroenterology practices in managing polyposis conditions. We specifically address the recommendations for pediatric screening in familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Further, we emphasize the importance of multidisciplinary care and partnership with gastroenterology, as it is crucial in management of children and families with these conditions., (©2024 American Association for Cancer Research.)

Background: Although feeding with a liquid diet does not affect the growth of rat submandibular glands, it inhibits the growth of rat parotid glands during growth periods. In these growth-inhibited parotid glands, the growth of parasympathetic nerves is also suppressed. Meanwhile, the mature parotid glands of animals maintained on a liquid diet become morphologically and functionally atrophic, however, there is no effect of a liquid diet on mature submandibular glands. The objective of the present study was to clarify whether the nerve distribution in the mature salivary glands of rats was affected by a liquid diet., Materials and Methods: Seven-week-old male Wistar rats were used in this study. Half of the rats were kept on a pellet diet, and half were kept on a liquid diet, for 3, 7, 14, or 21 days. All rats were euthanised by isoflurane at each endpoint. Then, the parotid and submandibular glands were removed, frozen in liquid nitrogen, cryosectioned, and stained with antibodies against protein gene product 9.5 (PGP 9.5; general nerve marker), tyrosine hydroxylase (TH; sympathetic nerve marker), or neuronal nitric oxide synthase (nNOS; parasympathetic nerve marker)., Results: In parotid and submandibular glands of the pellet diet group, PGP 9.5- and TH-like immunoreactivity were seen around acini and ducts, and nNOS-like immunoreactivity was lower than PGP 9.5- and TH-like immunoreactivity. In the parotid glands of the liquid diet group, similar immunoreactivities were seen throughout the experimental period. The distribution of antibody labelling in the submandibular glands of the liquid diet group was similar to that of the pellet diet group and remained unchanged during the experimental period., Conclusions: The present study demonstrated no regressive effects of a liquid diet on the distribution of sympathetic or parasympathetic nerves in mature parotid glands and submandibular glands. This differed from inhibitory effects on the growth of parotid glands seen during growth periods.

Endothelial-to-hematopoietic transition (EHT) is crucial for hematopoietic stem cell (HSC) generation. During EHT, the morphology of hemogenic endothelial cells (HECs) changes from flat and adherent to spherical hematopoietic cells, which detach from the dorsal aorta. HECs attain a rounded shape in a mitosis-independent manner before cell adhesion termination, suggesting an atypical cell-rounding mechanism. However, the direct mechanisms underlying this change in cell morphology during EHT remain unclear. Here, we show that large vacuoles were transiently formed in avian HECs, and that aquaporin 1 (AQP1) was localized in the vacuole and plasma membranes. Overexpression of AQP1 in non-HECs induced ectopic vacuole expansion, cell rounding and subsequent cell detachment from the endothelium into the bloodstream, mimicking EHT. Loss of redundant AQP functions by CRISPR/Cas9 gene editing in HECs impeded the morphological EHT. Our findings provide the first evidence to indicate that morphological segregation of hematopoietic cells from endothelial cells is regulated by water influx into vacuoles. These findings provide important insights for further exploration of the mechanisms underlying cell/tissue morphogenesis through water-adoptive cellular responses., Competing Interests: Competing interests M.S. is an employee of the Japan Science and Technology Agency. M.S.-K. is an employee of Daiichisankyo RD Novare. The remaining authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Introduction: Metastasectomy of oligometastatic prostate cancer has the potential to contribute to improving prognosis. We report on a case of metastasectomy of solitary liver tumor after radical prostatectomy., Case Presentation: An 80-year-old man underwent radical prostatectomy for prostate cancer, followed by radiotherapy after the operation because of increased serum prostate-specific antigen levels of 0.529 ng/mL. Levels increased further to 0.997 ng/mL even after salvage therapy. The patient then received androgen deprivation therapy. Levels remained stable for 3 years, but rapidly increased to 19.781 ng/mL in the following 6 months. Abdominal computed tomography revealed a solitary liver tumor, and no metastasis to other sites was identified. The patient underwent liver segmentectomy. Microscopic examination of excised specimens revealed prostate cancer cells. Five years after surgery, serum prostate-specific antigen maintained to the lowest level so far., Conclusion: Metastasectomy might be a beneficial therapeutic option to improve the prognosis for solitary metastasis from prostate cancer., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Rock and sediment samples were collected from petit-spots in the northwestern Pacific. The sampling was conducted using deep-submergence vehicle (DSV) Shinkai 6500 and its mother ship, research vessel (RV) Yokosuka during YK20-14S and YK21-07S cruises. The collected rock samples are basalt and peperite. Some of the basalts include small mantle xenoliths (∼3 cm in diameter). The dataset of rock and sediment samples from the petit-spots located on >130 Ma northwestern Pacific plate are presented herein. The peperites are a reaction product between petit-spot magma and wet sediment, and the mantle xenoliths are fragmented mantle materials transported by the petit-spot magmas. Therefore, the petit-spot samples are of significant importance to elucidate modification process of the surface condition by petit-spot magma and to characterize the deep lithospheric mantle. The dataset presented herein provides in a sense a unique insight into the whole Pacific plate just before its subduction beneath the Japan arc., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Biliary tract cancer (BTC) is a Lynch syndrome (LS)-associated cancer with a high mortality rate. This study aimed to clarify the clinical features of BTC in individuals with LS and to discuss its management., Methods: We obtained data from genetically verified Japanese individuals with LS who were diagnosed at a single institution, between January 2003 and April 2021. Moreover, 21 individuals with sporadic BTC (n=15) and LS associated BTC (n=6) underwent microsatellite instability (MSI) testing., Results: Among 92 individuals with LS, 6 individuals with MLH1 variants developed BTCs (10 lesions, male/female, 2:1). The median age at diagnosis of initial BTC was 69 years (range, 34-78 years). Histological examination revealed a predominance of differentiated adenocarcinoma (89%). Then, 2 individuals had multiple BTCs. All available 7 BTC lesions showed high-frequency of microsatellite instability (MSI-H). MLH1 carriers showed a 7.2% cumulative risk of BTC development at an age of 70 years. Five of the six individuals died of BTC., Conclusions: MSI analysis could facilitate LS identification in individuals with BTC. Surveillance for BTC should be considered for MLH1 carriers in Japan., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-165/coif). KA had lecture fee from Merck Sharp & Dohme (MSD). The other authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

The mol-ecular and crystal structures of two ruthenium(II) complexes, viz. cis -aqua-[2,6-bis-(1,8-naphthyridin-2-yl)pyridine-κ 3 N , N ', N ''](thio-cyanato-κ N )ruthenium(II) hexa-fluorido-phosphate-acetone-water (1/0.5/1), [Ru(NCS)(C P )ruthenium(II) hexa-fluorido-phosphate-acetone-water (1/0.5/1), [Ru(NCS)(C 21 H 13 )(C 5 )(C 18 H 15 P)(H 2 O)]PF 6 ·0.5C 3 H 6 O·H 2 O (I) and trans -[2,6-bis-(1,8-naphthyridin-2-yl)pyridine-κ 3 ' N , N ', N '']bis-(pyridine-κ N )ruthenium(II) thio-cyanate, [Ru(NCS)(C N )ruthenium(II) thio-cyanate, [Ru(NCS)(C 21 H 13 )(C 5 )(C 5 H 5 N) 2 atom in each of the cationic complexes adopts a distorted octa-hedral coordination sphere, defined by an N atom of the thio-cyanato ligand, three N atoms from the tridentate polypyridyl ligand, and an O and P atom in (I) or two pyridine-N atoms in (II) derived from monodentate ligands. The thio-cyanato ligand in (I) coordinates in an axial manner to the {Ru-dnp} unit [dnp = 2,6-bis-(1,8-naphthyridin-2-yl)pyridine], whereas it coordinates in an equatorial manner in (II). In the crystal structure of compound (I), intra-molecular C-H⋯O, C-H⋯N and O-H⋯N hydrogen bonds as well as π-π contacts are present, in addition to inter-molecular C-H⋯F, C-H⋯O and O-H⋯O hydrogen bonds. In the crystal structure of compound (II), intra-molecular C-H⋯N hydrogen bonds are observed along with inter-molecular C-H⋯N and C-H⋯S hydrogen bonds as well as a π-π inter-action.II atom in each of the cationic complexes adopts a distorted octa-hedral coordination sphere, defined by an N atom of the thio-cyanato ligand, three N atoms from the tridentate polypyridyl ligand, and an O and P atom in (I) or two pyridine-N atoms in (II) derived from monodentate ligands. The thio-cyanato ligand in (I) coordinates in an axial manner to the {Ru-dnp} unit [dnp = 2,6-bis-(1,8-naphthyridin-2-yl)pyridine], whereas it coordinates in an equatorial manner in (II). In the crystal structure of compound (I), intra-molecular C-H⋯O, C-H⋯N and O-H⋯N hydrogen bonds as well as π-π contacts are present, in addition to inter-molecular C-H⋯F, C-H⋯O and O-H⋯O hydrogen bonds. In the crystal structure of compound (II), intra-molecular C-H⋯N hydrogen bonds are observed along with inter-molecular C-H⋯N and C-H⋯S hydrogen bonds as well as a π-π inter-action., (© Takase et al. 2022.)

Nitroxides have been widely used as a molecular probe for analysis of various diseases models. This article describes an analytical method for separation and semi-quantification of multiple paramagnetic contrast agents with simple procedure combining electrophoresis and Overhauser enhancement magnetic resonance imaging (OMRI) imaging. We used three nitroxides, 3-carbamoyl PROXYL, 3-carboxy PROXYL, and CAT-1, which have different ionic charges in the molecule. In addition, we showed that this method could apply for in vitro measurement using biological sample. The results showed the nitroxides were successfully separated with electrophoresis depending on their charge, and their separation was visualized with OMRI after electrophoresis. Vehicle media such as whole blood did not affect the electrophoresis results and OMRI enhancement factor. Thus, the method can be used to analyze the redox status of biological samples without preprocessing. This analytical method enables in vitro measurement of biological samples to determine the redox status of specific tissue layers using paramagnetic agents, which is helpful for detailed analysis of redox-related diseases., (Copyright © 2022 JCBN.)

Li-Fraumeni syndrome (LFS) is a hereditary tumor that exhibits autosomal dominant inheritance. LFS develops in individuals with a pathogenic germline variant of the cancer-suppressor gene, TP53 (individuals with TP53 pathogenic variant). The number of individuals with TP53 pathogenic variant among the general population is said to be 1 in 500 to 20,000. Meanwhile, it is found in 1.6% (median value, range of 0-6.7%) of patients with pediatric cancer and 0.2% of adult patients with cancer. LFS is diagnosed by the presence of germline TP53 pathogenic variants. However, patients can still be diagnosed with LFS even in the absence of a TP53 pathogenic variant if the familial history of cancers fit the classic LFS diagnostic criteria. It is recommended that TP53 genetic testing be promptly performed if LFS is suspected. Chompret criteria are widely used for the TP53 genetic test. However, as there are a certain number of cases of LFS that do not fit the criteria, if LFS is suspected, TP53 genetic testing should be performed regardless of the criteria. The probability of individuals with TP53 pathogenic variant developing cancer in their lifetime (penetrance) is 75% for men and almost 100% for women. The LFS core tumors (breast cancer, osteosarcoma, soft tissue sarcoma, brain tumor, and adrenocortical cancer) constitute the majority of cases; however, various types of cancers, such as hematological malignancy, epithelial cancer, and pediatric cancers, such as neuroblastoma, can also develop. Furthermore, approximately half of the cases develop simultaneous or metachronous multiple cancers. The types of TP53 pathogenic variants and factors that modify the functions of TP53 have an impact on the clinical presentation, although there are currently no definitive findings. There is currently no cancer preventive agent for individuals with TP53 pathogenic variant. Surgical treatments, such as risk-reducing bilateral mastectomy warrant further investigation. Theoretically, exposure to radiation could induce the onset of secondary cancer; therefore, imaging and treatments that use radiation should be avoided as much as possible. As a method to follow-up LFS, routine cancer surveillance comprising whole-body MRI scan, brain MRI scan, breast MRI scan, and abdominal ultrasonography (US) should be performed immediately after the diagnosis. However, the effectiveness of this surveillance is unknown, and there are problems, such as adverse events associated with a high rate of false positives, overdiagnosis, and sedation used during imaging as well as negative psychological impact. The detection rate of cancer through cancer surveillance is extremely high. Many cases are detected at an early stage, and treatments are low intensity; thus, cancer surveillance could contribute to an improvement in QOL, or at least, a reduction in complications associated with treatment. With the widespread use of genomic medicine, the diagnosis of LFS is unavoidable, and a comprehensive medical care system for LFS is necessary. Therefore, clinical trials that verify the feasibility and effectiveness of the program, comprising LFS registry, genetic counseling, and cancer surveillance, need to be prepared., (© 2021. Japan Society of Clinical Oncology.)

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, and the majority of patients with LFS have been identified with germline variants in the p53 tumor suppressor (TP53) gene. In the past three decades, considerable case reports of TP53 germline variants have been published in Japan. To the best of our knowledge, there have been no large-scale studies of Japanese patients with LFS. In this study, we aimed to identify Japanese patients with TP53 germline variants and to reveal the characteristics of LFS in Japan. We collected reported cases by reviewing the medical literature and cases diagnosed at the institutions of the authors. We identified 68 individuals from 48 families with TP53 germline pathogenic or likely pathogenic variants. Of the 48 families, 35 (72.9%) had missense variants, most of which were located within the DNA-binding loop. A total of 128 tumors were identified in the 68 affected individuals. The 128 tumor sites were as follows: breast, 25; bones, 16; brain, 12; hematological, 11; soft tissues, 10; stomach, 10; lung, 10; colorectum, 10; adrenal gland, 9; liver, 4; and others, 11. Unique phenotype patterns of LFS were shown in Japan in comparison to those in a large national LFS cohort study in France. Above all, a higher frequency of patients with stomach cancer was observed in Japanese TP53 germline variant carriers. These results may provide useful information for the clinical management of LFS in Japan., (This article is protected by copyright. All rights reserved.)

A 69-year-old man presented to our hospital with chief complaints of epigastral pain and nausea, was diagnosed with intestinal obstruction after gastric surgery. Abdominal CT performed on the admission showed the tumor located on the terminal ileum. On colonoscopy, type 1 cancer was found near the Bauhin valve in the ileum, and suspected primary ileal carcinoma. Laparoscopic ileocecal resection was performed. The pathological diagnosis was moderately differentiated adenocarcinoma, and the pathological stage was T3(SS), N1(3/16), M0, Stage ⅢA. Although superficial surgical site infection was occurred, the patient was discharged 11 days after surgery. He hoped to adopt without adjuvant chemotherapy, so he has been followed as outpatient. Twenty one months since the surgery, there has been no evidence of cancer recurrence.

Background: Persistent Helicobacter pylori infection induces gastric mucosal atrophy, which is a precancerous condition. Hydrogen sulfide (H 2 S), a gaseous biological transmitter, has been implicated in both the physiological functions of the gastrointestinal tract and its diseases. To understand gastric epithelial cell response against H pylori infection, we investigated the metabolic changes of gastric cancer cells co-cultured with H pylori and observed the modulation of endogenous H 2 S production., Materials and Methods: Gastric cancer AGS cells were co-cultured with an H pylori standard strain possessing bacterial virulence factor CagA (ATCC 43504) and a strain without CagA (ATCC 51932). Three hours after inoculation, the cells were subjected to metabolomics analysis using gas chromatography-tandem mass spectrometry (GC-MS/MS). Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and pathway analysis were performed. In addition, intracellular H 2 S levels were measured by using HSip-1 fluorescent probe., Results: Results of OPLS-DA showed a significant difference between the metabolism of untreated control cells and cells inoculated with the H pylori strains ATCC 51932 or ATCC 43504, mainly due to 45 metabolites. Pathway analysis with the selected metabolites indicated that methionine metabolism, which is related to H 2 S production, was the most frequently altered pathway. H pylori-inoculated cells produced more endogenous H 2 S than control cells. Moreover, ATCC 43504-inoculated cells produced less H 2 S than ATCC 51932-inoculated cells., Conclusions: H pylori infection modulates endogenous H 2 S production in AGS cells, suggesting that H 2 S might be one of the bioactive molecules involved in the biological mechanisms of gastric mucosal disease including mucosal atrophy., (© 2020 John Wiley & Sons Ltd.)

Aim: To study the outcome of pregnancies with severely increased nuchal translucency (NT) thickness at the 11-13-week scan., Methods: This study included 162 singleton pregnancies whose fetuses had increased NT thickness ≥ 5.5 mm between September 2013 and August 2018. The cases were divided into two groups: NT ≥ 6.5 mm (n = 112) (group A); and 6.5 mm > NT ≥ 5.5 mm (n = 50) (group B). Fetal (amniotic fluid) or placental (chorionic villous) chromosome analyses were conducted. Subsequent ultrasound findings, pregnancy outcome and structural defects in the neonates were recorded and analyzed., Results: Abnormal karyotype was found in 71% (60/84) (group A) and 57% (21/37) (group B) of the cases respectively. In group A, 15 cases out of 24 with normal karyotype were born. Among these 15 cases, one case died soon after birth and 5 cases had associated abnormalities. In group B, 13 cases out of 18 with normal karyotype or negative noninvasive prenatal testing results and 1 case out of 2 cases with 47,XXY were born. All of them survived with no major anomaly., Conclusion: Incidence of chromosomal aberrations was high in the cases with severely increased NT thickness. But favorable outcome could be expected if the fetus had no chromosomal abnormality and no abnormal findings were found in second trimester ultrasound scan especially in a fetus with increased NT < 6.5 mm., (© 2020 Japan Society of Obstetrics and Gynecology.)

Purpose: To investigate the binding potential of newly developed Annexin V-conjugated ultrasmall superparamagnetic iron oxide (V-USPIO) for detection of drug-induced apoptosis in vitro and in vivo., Methods: Apoptotic cells induced by camptothecin were incubated with or without Annexin V-USPIO at a concentration of 0.089 mmol Fe/L in vitro. T 2 values of the two cell suspensions were measured by 0.47T nuclear magnetic resonance (NMR) spectrometer. Tumor-bearing mice were subjected to 1.5T MR scanner at 2 h after intraperitoneal injection of etoposide and cyclophosphamide. Following the pre-contrast T 1 - and T 2 -weighted imaging (0 h), the post-contrast scan was performed at 2, 4, 6 and 24 h after intravenous injection of Annexin V-USPIO (100 μmol Fe/kg). As a control, MRI was also obtained at 4 h after injection of USPIO without Annexin V. The ratio of tumor signal intensity (SI) on post-MRI for that on pre-MRI (Post/Pre-SI ratio) was calculated. After scanning, tumors were resected for pathological analysis to evaluate the distribution of iron and apoptotic cells., Results: The suspension of apoptotic cells incubated with Annexin V-USPIO showed shorter T 2 value than that without it. On T 1 -weighted imaging post/pre-SI ratio at 4 h after injection of Annexin V-USPIO showed 1.46, while after injection of USPIO without Annexin V was 1.17. The similar distribution of iron and apoptotic cells was observed in concordance with high signal intensity area on post-T 1 -weighted imaging., Conclusion: A newly developed Annexin V-USPIO could have the potential for detection of drug-induced apoptosis.

Interactions between human beings and the built environment are mediated by physiological and psychological stimuli, which may interfere in the perception and satisfaction related to indoor comfort variables. The study aims to explore the relationship between daylighting features and possible impacts on humans in regards to lighting preferences. The influence of different daylighting configurations, glazed façade orientation and season of the year on lighting preferences in human beings was evaluated by means of tests in a rotating climate with monitoring of environmental variables, developed by the Karlsruhe Institute of Technology, Karlsruhe, Germany. The sample, n = 16, is composed of German male students (height SD = 1.80 m, SD = 0.06; body weight SD = 80 kg, SD = 8.9; and age SD = 24.9 years, SD = 3.6). Under controlled thermal conditions (PMV approx. ±0.5), participants remained in two office-like environments over 5 h (8:00 am to 1:00 pm - local time) three days in a row, for three seasons of the year, totaling nine days of data collection per participant. Definitions of glazed façade orientations for the experimental rounds were done by means of computer simulations. Objective variables were measured by spectroradiometers at desk height, with sensor h = ca. 0.90 m, and comfortmeters. Preferences of daylighting features was assessed by a questionnaire with Likert-scale alternatives, administered online at 8:50 am, 10:30 am and 12:30 pm. Objective and subjective data were analyzed statistically (Spearman's rho, rs), suggesting possible correlations between lighting preferences and objective variables, including: E (lx), CCT (K), DWl (nm) and the circadian metric a cv (circadian action factor)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Pathogenic variants in highly penetrant genes are useful for the diagnosis, therapy, and surveillance for hereditary breast cancer. Large-scale studies are needed to inform future testing and variant classification processes in Japanese. We performed a case-control association study for variants in coding regions of 11 hereditary breast cancer genes in 7051 unselected breast cancer patients and 11,241 female controls of Japanese ancestry. Here, we identify 244 germline pathogenic variants. Pathogenic variants are found in 5.7% of patients, ranging from 15% in women diagnosed <40 years to 3.2% in patients ≥80 years, with BRCA1/2, explaining two-thirds of pathogenic variants identified at all ages. BRCA1/2, PALB2, and TP53 are significant causative genes. Patients with pathogenic variants in BRCA1/2 or PTEN have significantly younger age at diagnosis. In conclusion, BRCA1/2, PALB2, and TP53 are the major hereditary breast cancer genes, irrespective of age at diagnosis, in Japanese women.

We herein report an interesting case in which a complete response was achieved with oral anticancer monotherapy for unresectable lymph node metastasis after surgery for cecal cancer. A 78-year-old woman was referred to our hospital to undergo a detailed examination for anemia. The examination led to a diagnosis of cecal cancer. She underwent open right hemicolectomy combined with adjacent abdominal wall resection and reconstruction of abdominal wall defects the next month. During follow-up without adjuvant therapy at her request, right iliac lymph node metastasis was detected 5 months later. A lymphadenectomy by laparotomy was attempted 6 months later but ended as only an exploratory laparotomy because the metastatic lymph node was difficult to detach from the vascular wall. Starting the next month, oral anticancer monothera- py(TS-1, 80mg/day for 2weeks followed by 1week of rest)was started at the patient's request. Abdominal ultrasonography performed in March 2011 revealed no evidence of lymphadenopathy, and subsequent imaging tests also confirmed the absence of lymphadenopathy. The anticancer monotherapy was discontinued after 4 years of medication. The patient remains alive, after 3 years and 5 months of medication to date, without recurrence.

We report here a rare case of gastric metastasis after resection ofa transverse colon cancer in which eating ability was restored following mFOLFOX6 (folinic acid plus fluorouracil plus oxaliplatin) plus cetuximab (Cet) chemotherapy. A 56-year-old man with chief complaints of constipation and abdominal fullness was referred to our hospital. In February 2013, he was diagnosed with transverse colon cancer via enema and colonoscopy. We performed transverse colon cancer resection followed by a 6-month course of capecitabine chemotherapy. In July 2014, the patient's serum carcinoembryonic antigen level increased, in October, he was again referred to our hospital with complaints of appetite loss and vomiting. He was diagnosed with multiple lymph node and gastric metastases via ultrasonography, computed tomography, and endoscopy, as well as multiple lung metastases via computed tomography. As the gastric metastases and vomiting rendered him unable to eat, a nasogastric tube was inserted and was administered mFOLFOX6 plus Cet chemotherapy. After 2 courses of chemotherapy his ability to eat was restored. As of March 2015, the patient remains alive following 12 courses of chemotherapy.

Objective: Diagnosis of anterior prostate cancer is challenging. The purpose of this study was to evaluate the diagnostic performance of T2-weighted imaging and an apparent diffusion coefficient (ADC) map in the detection of anterior prostate cancer and to compare that with the diagnostic performance in the detection of posterior prostate cancer., Materials and Methods: We retrospectively reviewed the records of 87 patients who underwent 3-T MRI that included T2-weighted imaging and diffusion-weighted imaging before radical prostatectomy. The prostate gland was divided into anterior and posterior segments, and the radiologists interpreted two protocols (T2-weighted imaging alone vs T2-weighted imaging and an ADC map) and sorted the confidence levels for the presence of prostate cancer into five grades. ROC analysis was performed to evaluate the diagnostic performance of each protocol for the detection of anterior and posterior prostate cancers. We also assessed the relative fractions of sensitivity and specificity between anterior and posterior prostate cancers. Additionally, the ADCs of noncancerous anterior fibromuscular stroma were measured and compared with the ADCs of anterior prostate cancers., Results: The AUCs with T2-weighted imaging alone and with T2-weighted imaging and an ADC map were 0.75 and 0.88 for anterior prostate cancer, respectively, and were 0.70 and 0.81 for posterior prostate cancer. The sensitivity for detecting anterior prostate cancer was 90% and was significantly higher than that for detecting posterior prostate cancer in the protocol using T2-weighted imaging and an ADC map (p = 0.003) when scores of 3-5 were considered as positive for prostate cancer. The ADC was significantly lower in anterior prostate cancer (mean, 0.80 × 10(-3) mm(2)/s) than in noncancerous anterior fibromuscular stroma (1.13 × 10(-3) mm(2)/s) (p < 0.001)., Conclusion: The protocol using T2-weighted imaging and an ADC map showed higher accuracy for the detection of anterior prostate cancer than for the detection of posterior prostate cancer.

Purpose: To assess the adequacy of a statistical model based on the gamma distribution for diffusion signal decays of prostate cancer (PCa) using b-values ranging up to 2000 sec/mm(2) , and to evaluate the differences in gamma model parameters for PCa, benign prostatic hyperplasia (BPH), and peripheral zone (PZ)., Materials and Methods: Twenty-six patients with histologically proven PCa underwent diffusion-weighted magnetic resonance imaging using five b-values (0, 500, 1000, 1500, 2000 sec/mm(2) ). The acquired signal decay curves were fit with both gamma and truncated Gaussian models and a statistical comparison between the two fits was performed. The acquired parameters using the gamma model (mean, standard deviation, the area fraction for D < 1.0 mm(2) /s [Frac<1.0], the area fraction of D > 3.0 mm(2) /s [Frac>3.0]) were compared between PCa, BPH, and PZ., Results: The gamma model provided a statistically improved fit over the truncated Gaussian model in PCa. The mean and the standard deviation were significantly lower in PCa than in BPH and PZ (P < 0.01). Frac<1.0 was significantly higher in PCa than in BPH and PZ, and Frac>3.0 was significantly lower in PCa than in BPH and PZ (P < 0.01)., Conclusion: A statistical model based on the gamma distribution proved suitable for describing diffusion signal decay curves of PCa. This approach may provide better correlation between diffusion signal decay and histological information in the prostate gland., (© 2014 Wiley Periodicals, Inc.)

Background and Aim: In Crohn's disease (CD), assessment of disease activity and extension is important for clinical management. Endoscopy is the most reliable tool for evaluating disease activity in these patients and it distinguishes between lesions based on ulcer, erosion, and redness. Magnetic resonance imaging (MRI) is less invasive than endoscopy; however, the sensitivity of MRI in detecting lesions is believed to be lower, and whether MRI can detect milder lesions has not been studied. The aim of this study was to compare the detection ability of magnetic resonance enterocolonography (MREC) with ileocolonic endoscopy in patients with CD., Methods: A total of 27 patients with CD underwent both MREC and ileocolonoscopy. There were 55 lesions (18 ileum and 37 colon) endoscopically detected, and the findings of MREC were compared with each ileocolonoscopic finding to determine sensitivity and specificity., Results: For a positive lesion defined as having at least one of the following: wall thickness, edema, diffusion-weighted imaging (DWI) high intensity and relative contrast enhancement (RCE) on MREC, the sensitivities were 100% for ulcer, 84.6% for erosion, and 52.9% for redness, suggesting an ability to detect milder lesions such as erosion or redness. Moreover, RCE values were well correlated with the severity of endoscopically identified active lesions., Conclusion: MREC findings may be useful not only for evaluation of ulcers, but also for detection of endoscopically identified milder lesions in CD, suggesting a clinical usefulness of MREC for disease detection and monitoring., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Four cardenolide glycosides, glucodigifucoside (2), 3'-O-acetylglucoevatromonoside (9), digitoxigenin 3-O-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 4)-3-O-acetyl-β-D-digitoxopyranoside (11), and purpureaglycoside A (12), isolated from the seeds of Digitalis purpurea, exhibited potent cytotoxicity against human renal adenocarcinoma cell line ACHN. These compounds exhibited significantly lower IC50 values against ACHN than that against normal human renal proximal tubule-derived cell line HK-2. In particular, 2 exhibited the most potent and carcinoma-specific cytotoxicity, with a sixfold lower IC50 value against ACHN than that against HK-2. Measurement of cyclin-dependent kinase inhibitor levels revealed that upregulation of p21/Cip1 expression was involved in the carcinoma-specific cytotoxicity of 2. Further, compound 2 also exhibited the carcinoma-specific cytotoxicity toward hepatocellular carcinoma cell line.

Background: We previously developed a surface-controlled water-dispersible form of curcumin and named it Theracurmin(®) (Theracurmin; Theravalues, Tokyo, Japan). The area under the blood concentration-time curve of Theracurmin in humans was 27-fold higher than that of curcumin powder. We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis during 8 weeks of treatment., Methods: Fifty patients with knee osteoarthritis of Kellgren-Lawrence grade II or III and who were aged more than 40 years were enrolled in this randomized, double-blind, placebo-controlled, prospective clinical study. Placebo or Theracurmin containing 180 mg/day of curcumin was administered orally every day for 8 weeks. To monitor adverse events, blood biochemistry analyses were performed before and after 8 weeks of each intervention. The patients' knee symptoms were evaluated at 0, 2, 4, 6, and 8 weeks by the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale (VAS), the knee scoring system of the Japanese Orthopedic Association, and the need for nonsteroidal anti-inflammatory drugs., Results: At 8 weeks after treatment initiation, knee pain VAS scores were significantly lower in the Theracurmin group than in the placebo group, except in the patients with initial VAS scores of 0.15 or less. Theracurmin lowered the celecoxib dependence significantly more than placebo. No major side effects were observed with Theracurmin treatment., Conclusion: Theracurmin shows modest potential for the treatment of human knee osteoarthritis.

We report a rare case of long -term survival after laparoscopic resection of sigmoid colon cancer with multiple liver metastases, followed by 5-fluorouracil Leucovorin irinotecan with bevacizumab (FOLFIRI+Bev) chemotherapy. A 61-year-old woman was referred to our hospital with a principal complaint of bloody stools. She was diagnosed with sigmoid colon cancer by colonoscopy and multiple liver metastases by ultrasonography. In October 2008, we performed laparoscopic resection of the sigmoid colon cancer with multiple liver metastases, followed by 4 courses of modified 5-fluorouracil Leucovorin oxaliplatin ( mFOLFOX6) chemotherapy. In February 2009, abdominal ultrasonography showed progressive disease, and as a result the patient was administered 73 courses of FOLFIRI +Bev chemotherapy. As of March 2014, the patient has survived for more than 5 years following treatment, but still has liver metastases. The possibility of resecting multiple liver metastases from colorectal cancer should be considered, and in some cases, chemotherapy may enhance survival.

Primordial germ cells (PGCs) are germ cell progenitors in the fetal genital ridge; female PGCs give rise to definitive oocytes that contribute to the next generation. Artificial PGCs have been induced in vitro from pluripotent stem cells and gonad-like tissue has been induced in vivo by cotransplantation of PGCs with PGC-free gonadal cells. To apply these technologies to human infertility treatment or conservation of rare species, PGC transplantation must be established in xenogenic animals. Here, we established a xenogeneic transplantation model by inducing ovary-like tissue from PGCs in xenogenic animals. We transplanted enzymatically dispersed PGCs with PGC-free gonadal cells under the kidney capsule of xenogenic immunodeficient animals. The transplanted cells formed ovary-like tissues under the kidney capsule. These tissues were histologically similar to the normal gonad and expressed the oocyte markers Vasa and Stella. In addition, mouse germinal vesicle-stage oocyte-like cells collected from ovary-like tissue in rats matured to metaphase II via in vitro maturation and gave rise to offspring by intracytoplasmic sperm injection. Our studies show that rat/mouse female PGCs and PGC-free gonadal cells can develop and reconstruct ovary-like tissue containing functional oocytes in an ectopic xenogenic microenvironment., (© 2014 by the Society for the Study of Reproduction, Inc.)

Purpose: To evaluate the differences in parameters of diffusion kurtosis imaging (DKI) between prostate cancer, benign prostatic hyperplasia (BPH), and benign peripheral zone (PZ)., Materials and Methods: Twenty-four foci of prostate cancer, 41 BPH nodules (14 stromal and 27 nonstromal hyperplasia), and 20 benign PZ from 20 patients who underwent radical prostatectomy were investigated. Diffusion-weighted imaging (DWI) was performed using 11 b-values (0-1500 s/mm(2) ). DKI model relates DWI signal decay to parameters that reflect non-Gaussian diffusion coefficient (D) and deviations from normal distribution (K). A mixed model analysis of variance and receiver operating characteristic (ROC) analyses were performed to assess the statistical significance of the metrics of DKI and apparent diffusion coefficient (ADC)., Results: K was significantly higher in prostate cancer and stromal BPH than in benign PZ (1.19 ± 0.24 and 0.99 ± 0.28 versus 0.63 ± 0.23, P < 0.001 and P < 0.001, respectively). K showed a trend toward higher levels in prostate cancer than in stromal BPH (1.19 ± 0.24 versus 0.99 ± 0.28, P = 0.051). On the ROC analyses, a significant difference in area under the curve was not observed between K and ADC, however, K showed the highest sensitivity among three parameters., Conclusion: DKI may contribute to the imaging diagnosis of prostate cancer, especially in the differential diagnosis of prostate cancer and BPH., (© 2013 Wiley Periodicals, Inc.)

This study was designed to investigate whether supplementation of 2i medium with leukemia inhibitory factor (LIF) and/or forskolin would support establishment of germline-competent rat embryonic stem (ES) cell lines. Due to the higher likelihood of outgrowth rates, supplementation of forskolin with or without LIF contributed to the higher establishment efficiency of ES cell lines in the WDB strain. Germline transmission competency of the chimeric rats was not influenced by the profile of ES cell lines until their establishment. When the LIF/forskolin-supplemented 2i medium was used, the rat strain used as the blastocyst donor, such as the WI strain, was a possible factor negatively influencing the establishment efficiency of ES cell lines. Once ES cell lines were established, all lines were found to be germline-competent by a progeny test in chimeric rats. In conclusion, both LIF and forskolin are not essential but can play a beneficial role in the establishment of "genuine" rat ES cell lines.