Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer.

BACKGROUND: We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). METHODS: A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. RESULTS: Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). CONCLUSIONS: Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.

A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Clinical significance of metastatic tumor deposit foci in rectal cancer in the lateral pelvic lymph node area.

BACKGROUND: Although previous studies have demonstrated that tumor deposits (TDs) are associated with worse prognosis in colon cancer, their clinical significance in rectal cancer has not been fully elucidated, especially in the lateral pelvic lymph node (LPLN) area. This study aimed to clarify the clinical significance of TDs, focusing on the number of metastatic foci, including lymph node metastases (LNMs) and TDs, in the LPLN area. METHODS: This retrospective study involved 226 consecutive patients with cStage II/III low rectal cancer who underwent LPLN dissection. Metastatic foci, including LNM and TD, in the LPLN area were defined as lateral pelvic metastases (LP-M) and were evaluated according to LP-M status: presence (absence vs. presence), histopathological classification (LNM vs. TD), and number (one to three vs. four or more). We evaluated the relapse-free survival of each model and compared them using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). RESULTS: Forty-nine of 226 patients (22%) had LP-M, and 15 patients (7%) had TDs. The median number of LP-M per patient was one (range, 1-9). The best risk stratification power was observed for number (AIC, 758; c-index, 0.668) compared with presence (AIC, 759; c-index, 0.665) and histopathological classification (AIC, 761; c-index, 0.664). The number of LP-M was an independent prognostic factor for both relapse-free and overall survival, and was significantly associated with cumulative local recurrence. CONCLUSION: The number of metastatic foci, including LNMs and TDs, in the LPLN area is useful for risk stratification of patients with low rectal cancer.

Development of a novel drug information provision system for Kampo medicine using natural language processing technology.

BACKGROUND: Kampo medicine is widely used in Japan; however, most physicians and pharmacists have insufficient knowledge and experience in it. Although a chatbot-style system using machine learning and natural language processing has been used in some clinical settings and proven useful, the system developed specifically for the Japanese language using this method has not been validated by research. The purpose of this study is to develop a novel drug information provision system for Kampo medicines using a natural language classifier® (NLC®) based on IBM Watson. METHODS: The target Kampo formulas were 33 formulas listed in the 17th revision of the Japanese Pharmacopoeia. The information included in the system comes from the package inserts of Kampo medicines, Manuals for Management of Individual Serious Adverse Drug Reactions, and data on off-label usage. The system developed in this study classifies questions about the drug information of Kampo formulas input by natural language into preset questions and outputs preset answers for the questions. The system uses morphological analysis, synonym conversion by thesaurus, and NLC®. We fine-tuned the information registered into NLC® and increased the thesaurus. To validate the system, 900 validation questions were provided by six pharmacists who were classified into high or low levels of knowledge and experience of Kampo medicines and three pharmacy students. RESULTS: The precision, recall, and F-measure of the system performance were 0.986, 0.915, and 0.949, respectively. The results were stable even with differences in the amount of expertise of the question authors. CONCLUSIONS: We developed a system using natural language classification that can give appropriate answers to most of the validation questions.

Diurnal rhythms in testicular blood flow, testicular morphometry and reproductive hormones in Shiba goats.

CONTEXT: Testicular blood flow (TBF) is crucial for testicular function. The pattern of TBF in Shiba goats indicates seasonal variations. AIMS: This study aimed to investigate the effect of diurnal variations on TBF, testis volume (TV), testicular echogenicity, and reproductive hormones in goats over a 24-h period. METHODS: In three trials that went for three consecutive days each, 12 bucks were scanned using Triplex ultrasonography to assess the TV, pixel intensity of testicular echotexture (PIX), and Doppler indices of TBF (resistive index: RI and pulsatility index: PI) in four-time points a day (at 6.00, 12.00, 18.00, and 00.00h). Concomitantly, the changes in circulating FSH, LH, inhibin, testosterone (T), estradiol (E2), cortisol, and melatonin were assessed. KEY RESULTS: Results revealed diurnal alterations in the calculated RI of TBF and the PIX of testicular parenchyma (P <0.05). Lower RI values of the TBF were observed at 6.00h compared to other time points. There were significant diurnal alterations in the levels of FSH (P <0.05), LH (P <0.05), T (P <0.0001), E2 (P <0.0001), cortisol (P <0.0001), and melatonin (P <0.0001). FSH attained a higher concentration at 18.00h compared to 12.00h. Concentrations of LH were significantly higher at 06.00h compared to those at 18.00h. Concentrations of T were significantly higher at 6.00 compared to other time points. E2 showed higher concentrations at 6.00h and 00.00h compared to 12.00h and 18.00h. On the contrary, concentrations of cortisol were significantly higher at 12.00h and 18.00h compared to 06.00h and 00.00h. The highest concentrations of melatonin were observed at 00.00h compared to other time points, while the lowest concentrations were at 12.00h. CONCLUSIONS: Diurnal rhythm induces significant changes in TBF, testicular PIX, and circulating FSH, LH, T, E2, cortisol, and melatonin over the 24-hday. IMPLICATIONS: The outcomes of the study are reflected in the advisability of monitoring the TBF at a fixed time a day to avoid the circadian rhythm effect.

Estrogen promotes increased breast cancer cell proliferation and migration through downregulation of CPEB1 expression.

The polyadenylation element binding protein 1 (CPEB1) plays an important role in the regulation of poly(A) tail length at the 3'UTR of mRNA during transcription. Downregulation of CPEB1 expression, which is associated with the loss of mammary epithelial polarity, has been reported in breast cancer. CPEB1 downregulation leads to an increase in tumor aggressiveness of breast cancer. Breast cancer is also known to be responsive to the treatment with steroid hormones, which promotes cancer development and progression; however, the nature of these associations remains unclear. This study aimed to investigate whether estrogen and progesterone impacted CPEB1 expression in breast cancer in order to regulate cell proliferation and migration. MCF7 cell proliferation was increased in response to estrogen treatment, and estrogen application suppressed the expression of CPEB1 mRNA. Cells treated with estrogen or those depleted for CPEB1 by shRNA showed increased wound healing capacity compared with that of control cells in migration assay. Moreover, we found that CPEB1 level of expression in human breast cancer tissue was low compared with that in the healthy tissue. CPEB1 expression was downregulated in response to estrogen activity and in turn, that caused a significantly induced cell migration in breast cancer cells. This suggests that CPEB1 is one of the estrogen responsive genes, which stimulates breast cancer progression. Increasing and/or maintaining CPEB1 expression level has the potential to control breast cancer behavior.

L-amino acid oxidase 1 in sperm is associated with reproductive performance in male mice and bulls.

Sperm quality is an important indicator of male fertility, and a suitable biomarker enables the selection of high-quality spermatozoa. We previously found that L-amino acid oxidase encoded by the L-amino acid oxidase 1 (Lao1) gene exerts biological roles in the mammary gland and brain by converting specific L-amino acids into keto acids, ammonia, and hydrogen peroxide (H2O2). Here, we describe the role of Lao1 in male reproduction. Lao1-deficient (Lao1-/-) male mice generated fewer pregnant embryos and pups as well as lower ratios of fertilized oocytes and even ovulated number was not different, suggesting that male subfertility caused the smaller litters. We found that LAO1 expressed in acrosomes is associated with high malformation ratios and low viability of Lao1-/- sperm. Wild-type (WT) sperm produced more H2O2 than Lao1-/- sperm, and 10 µM H2O2 restored knockout (KO) sperm viability in vitro. In addition, the sperm ratio of induced acrosome reaction was higher in WT than in Lao1-/- sperm incubated with the calcium ionophore A23187. Moreover, LAO1 expression was abundant in bovine sperm with high fertilization ratios. We concluded that LAO1 localized in the sperm acrosome influences sperm viability and morphology as well as the acrosome reaction, and that LAO1-deficient sperm might cause male subfertility. Thus, LAO1 might serve as a novel marker for selecting high-quality spermatozoa, especially for livestock reproduction.

Effectiveness of the intraoperative magnetic resonance imaging during endoscopic endonasal approach for acromegaly.

PURPOSE: Acromegaly is an acquired disorder usually caused by growth hormone-secreting pituitary adenoma, resolution of which requires correction of the excess hormone production. Recently, intraoperative magnetic resonance imaging (iMRI) was reported to be useful during the endoscopic endonasal approach (EEA) for pituitary adenoma. The present study was performed to quantitatively assess the role of iMRI in improving surgical outcomes in EEA for acromegaly. METHODS: Twenty surgeries for acromegaly in EEA performed at Shinshu University Hospital between April 2016 and March 2020 were reviewed retrospectively. The inclusion criteria were cases without severe cavernous sinus tumor invasion (Knosp grade 0 - 3) or history of prior pituitary surgery. Fifteen consecutive patients were enrolled in this study. Clinical characteristics and postoperative clinical outcomes were compared between patients with and without use of iMRI during EEA for acromegaly. RESULTS: Conventional navigation-guided surgery was performed in nine patients, and six underwent iMRI-guided EEA for acromegaly. Gross total resection (GTR) was obtained in the six (100%) patients in the iMRI group, and in four (44.4%) patients in the conventional group without iMRI. Postoperative clinical outcomes, including hormonal remission rate and surgical complications, were comparable between the two groups. CONCLUSION: Although iMRI significantly increased the GTR rate, we found no direct evidence of increased hormonal remission rate by use of iMRI. It is important to confirm complete tumor resection carefully with not only iMRI findings, but also with intraoperative high-definition endoscopic direct visualization to increase the hormonal remission rate of acromegaly.

Correlations Among Consistency, Computed Tomography Values, and Histopathological Subtypes of Spinal Meningioma.

The consistency of spinal meningiomas is important to consider when performing tumor removal surgery. This study evaluated the correlations between spinal meningioma consistency and both preoperative computed tomography (CT) values and histopathological subtypes. Fifteen consecutive patients who underwent surgical resection of spinal meningioma at our institution were identified, and preoperative CT values and the signal intensity of T2-weighted magnetic resonance images of the tumor were determined retrospectively. The consistency of the spinal meningioma was defined based on the ultrasonic surgical aspirator output during tumor debulking. Patients were assigned to 2 groups: a soft group (n=4) and a hard group (n=11). The T2 signal intensity was significantly higher in the soft group than in the hard group (p=0.001). While the CT values were considerably higher in the hard group, the difference was not significant (p=0.19). Regarding the histopathological subtypes, psammomatous meningioma exhibited significantly higher CT values than meningothelial meningioma (p=0.019); however, there was a higher frequency of hard tumors in meningothelial meningioma cases than in psammomatous meningioma cases. Although neither robust correlations between tumor consistency and CT values nor a relationship between tumor consistency and histopathological subtype has been established, these results might help with the perioperative manegement of spinal tumors.

Circulating activin A during equine gestation and immunolocalization of its receptors system in utero-placental tissues and fetal gonads.

Although equine gestation is unique from the standpoint of fetal gonadal enlargement and regression, the activator of this process is still unknown. The present study aimed to show a possible role of activin during equine gestation. In the first experiment, weekly plasma samples from six pregnant mares were used to measure activin A. In the second experiment, eight pregnant mares carrying female (gestational days 110, 140, 180, and 270) and male fetuses (gestational days 120, 180, 225, and 314) were used for immunohistochemistry of activin receptors (IA, IB, IIA, IIB), and their intracellular mediators (Smad2, Smad3, Smad4). Activin A levels in maternal circulation remained low until fourth weeks of gestation, thereafter, started to increase, and peaked first at 11 weeks of gestation. The second significant peak was observed on the day of parturition. Activin receptors type IA, IB, IIA, and IIB were immunostained in interstitial and germ cells of fetal ovaries and testes along with utero-placental tissues. Smad2, Smad3, and Smad4 were also immunolocalized in all these organs. These results demonstrated the activin-producing capacity of utero-placental tissues, and also evidenced the existence of activin receptors and functional signaling molecules in these organs. The first increment in circulating activin A in maternal circulation coinciding with the timing of initiation of fetal gonadal enlargement suggests that activin from the utero-placental tissues may have a stimulatory role in fetal gonad enlargement and utero-placental development in mares, whereas the second peak could be important to follicular development in the maternal ovary for foal heat.

Influence of exercise and emotional stresses on secretion of prolactin and growth hormone in Thoroughbred horses.

The secretion of prolactin and growth hormone in response to exercise and emotional stresses was investigated in Thoroughbreds. Two experiments were performed: one with loading of only exercise stress and one with simultaneous loading of exercise and emotional stresses. Exercise stress was loaded in 4 steps using a treadmill for horses: pre-exercise period (5 min), walking period (6.5 min), galloping period (3 min), and cooling down period (10 min). Emotional stress was loaded by showing a loud video of an audience at a racetrack during the walking period. The results clearly demonstrated that exercise stress rapidly increased the secretion of prolactin and growth hormone and that secretion of them persisted for a specific period after the exercise. In addition, emotional stress promoted prolactin secretion.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Gut microbiota development in mice is affected by hydrogen peroxide produced from amino acid metabolism during lactation.

The development of gut microbiota during infancy is an important event that affects the health status of the host; however, the mechanism governing it is not fully understood. l-Amino acid oxidase 1 (LAO1) is a flavoprotein that catalyzes the oxidative deamination of particular l-amino acids and converts them into keto acids, ammonia, and H2O2. Our previous study showed that LAO1 is present in mouse milk and exerts protection against bacteria by its production of H2O2. The data led us to consider whether LAO1, H2O2, or both could impact infant gut microbiota development via mother's milk consumption in mice. Different gut microbiota profiles were observed in the wild-type (WT) and LAO1-knockout mouse pups. The WT pups' microbiota was relatively simple and composed of only a few dominant bacteria, such as Lactobacillus, whereas the lactating knockout pups had high microbiota diversity. Cross-fostering experiments indicated that WT milk (containing LAO1) has the ability to suppress the diversity of microbiota in pups. We observed that the stomach content of pups fed WT milk had LAO1 proteins and the ability to produce H2O2. Moreover, culture experiments showed that Lactobacillus was abundant in the feces of pups fed WT milk and that Lactobacillus was more resistant to H2O2 than Bifidobacterium and Escherichia. Human breast milk produces very little H2O2, which could be the reason for Lactobacillus not being dominant in the feces of breast-fed human infants. In mouse mother's milk, H2O2 is generated from the process of free amino acid metabolism, and H2O2 may be a key player in regulating the initial acquisition and development of gut microbiota, especially growth of Lactobacillus, during infancy.-Shigeno, Y., Zhang, H., Banno, T., Usuda, K., Nochi, T., Inoue, R., Watanabe, G., Jin, W., Benno, Y., Nagaoka, K. Gut microbiota development in mice is affected by hydrogen peroxide produced from amino acid metabolism during lactation.

Yolk immunoreactive corticosterone in hierarchical follicles of Japanese quail (Coturnix japonica) exposed to heat challenge.

High temperature decreases the egg number, ovarian weight, and hierarchical follicle number. In the present study, we investigated the effect of high temperature on the quality of eggs of adult female quails. Laying quail were raised under a standard thermal condition of 25 °C until exposed to an elevated temperature of 34 °C (experimental) or maintained at 25 °C (control) from 12:00 to 16:00 for 10 consecutive days. Weight and number of eggs were measured; serum and the largest follicles were collected and used for hormone measurement. Ovaries and adrenals were collected for expression analysis of 3ß- and 17ß-HSD, genes encoding steroidogenic enzymes. Egg weight slightly decreased with an increase in the treatment time in the heat-challenged group; the egg weight significantly decreased in the heat treatment group than in the control group during the last 2 days of experiment (P < 0.05). The laying rate showed no difference during the experimental period but significantly decreased on the last day in the heat treatment group. In the experimental group the ovaries and oviducts were lighter (P < 0.05) and the hierarchical follicle number and ovarian weight decreased (P < 0.05) compared to the control group. Although serum corticosterone level significantly increased after heat challenge (P < 0.05) and immediately recovered to the normal level, yolk immunoreactive corticosterone in the hierarchical follicle (F1, F2, F3) significantly increased (P < 0.05). The expression level of 17ß-HSD showed no changes in the ovary but significantly increased in adrenals (P < 0.05). Our findings indicate that the effects of heat challenge on the maternal ovary in the quail are mediated through the adrenal function.

Ovarian follicular changes and hemodynamics in Egyptian buffaloes under CIDR-PGF2α and Ovsynch-CIDR estrus synchronization treatments.

This study aimed at investigating the efficacy of two protocols of estrous synchronization on follicular changes and hemodynamics. Pluriparous Egyptian buffaloes (n = 36) were synchronized either with controlled internal drug release (CIDR)-PGF2α (7-days CIDR insert with PGF2α injected on the 6th day; n = 18) or Ovsynch-CIDR (Ovsynch protocol concurrent with 7-days CIDR insert; n = 18). Blood sampling and ovarian ultrasound examinations (Grayscale, color and power Doppler modes) were conducted on the Day of CIDR removal, estrus, and luteal phase. Mean follicle diameter (MFD), first (1st-LF) and second (2nd-LF) largest follicle diameters, and E2 levels significantly increased in the CIDR-PGF2α group at CIDR withdrawal. Ovsynch-CIDR markedly fortified higher follicle population, MFD, and 1st-LF diameter at estrus and corpus luteum (CL) volume at the luteal phase in concomitant with increases (P < 0.05) in E2 (at estrus) and P4 (at luteal phase). At CIDR removal, the blue pixels in the dominant follicle (DF) were higher (1.5 times; P = 0.054) in the Ovsynch-CIDR than in the CIDR-PGF2α. At estrus, total blood flow (TBF) and power Doppler pixels (PDP) to DF(s) were noticeably higher (seven and 1.6 times; respectively) in the Ovsynch-CIDR than in CIDR-PGF2α (5906 ± 237 vs. 830 ± 60 pixels, P < 0.01 and 5479 ± 322 vs. 3377 ± 19 pixels, P < 0.05; respectively). At the luteal phase, TBF and PDP to the CL increased in the Ovsynch-CIDR group than in the CIDR-PGF2α group (11060 ± 965 vs. 7963 ± 480 pixels, 1.4 times, P = 0.05 and 18900 ± 1350 vs. 13220 ± 568 pixels, 1.1 times, P = 0.005; respectively). In conclusion, based on the improvement in synchronized follicular activity and hemodynamics, the Ovsynch-CIDR regimen is persuaded in Egyptian buffaloes.

Discovery of novel spiro[chromane-2,4'-piperidine] derivatives as potent and orally bioavailable G-protein-coupled receptor 119 agonists.

Herein, we describe the discovery, synthesis, and evaluation of a novel series of spiro[chromane-2,4'-piperidine] derivatives as G-protein-coupled receptor 119 agonists. Their initial design exploited the conformational restriction in the linker-to-tail moiety, which was a key concept in this study, to give lead compound 11 (EC50 = 369 nM, Emax = 82%). An extensive structure-activity relationship study resulted in the identification of the optimized drug candidate (R)-29 (EC50 = 54 nM, Emax = 181%). The defining structural features of the series were a terminal benzyl-type bulky substituent and a methylene linker between the sulfonyl and phenyl groups, both of which were in the head moiety as well as the spiro-type scaffold in the linker-to-tail moiety. An in vivo oral glucose-tolerance test using C57BL/6N mice showed that (R)-29 reduced glucose excursion at a dose of 3 mg/kg in a dose-dependent manner.

Endoscopic and clinicopathological features of intramucosal, histologically mixed-type, low-grade, well-differentiated gastric tubular adenocarcinoma with the potential for late-onset lymph node metastasis.

BACKGROUND: Intramucosal, histologically mixed-type, low-grade (LG), well-differentiated gastric tubular adenocarcinomas (tub1s; LG-tub1s) have larger mean diameters and exhibit a higher frequency of the gastric mucin phenotype (G-phenotype) than pure LG-tub1s. In proportion to their increases in diameter, G-phenotype differentiated-type early gastric cancer (EGC) tumours reportedly grow to eventually contain (an) undifferentiated-type component(s) and LG-tub1s, which are included in differentiated-type EGCs, reportedly exhibit changes in their glandular architectural and cytological atypia grades from LG to high-grade (HG) and can grow to contain a moderately differentiated tubular adenocarcinoma (tub2) component and undifferentiated components. Because they generally show a higher frequency of malignancy relative to tumours with a higher atypia grade and lower differentiation degree, it is suggested that, among mixed-type LG-tub1s, G-phenotype LG-tub1s containing an HG-tub2 component (LG-tub1s > HG-tub2) with undifferentiated components might lead to late-onset metastasis to lymph nodes even after a successful endoscopic submucosal dissection (ESD). We aimed to clarify the endoscopic and clinicopathological features of these G-phenotype LG-tub1s > HG-tub2. METHODS: Of the 13,217 oesophagogastroduodenoscopies performed at our institutions between September 2008 and March 2016, 185 EGC lesions were evaluated in this retrospective observational study. Among these EGC lesions, 60 intramucosal LG-tub1s were divided into 53 tub1 (44 pure LG-tub1s and nine LG-tub1s containing HG-tub1) lesions and seven LG-tub1 > tub2 (LG-tub1 containing LG- and HG-tub2) lesions. RESULTS: The frequencies of the superficial depressed type (P = 0.026), reddish colour (P = 0.006), HG of contained tub2s (P = 0.006), and G-phenotype (P = 0.028) were significantly higher in the LG-tub1 > tub2 group than those in the tub1 group. However, the largest lesion of the LG-tub1 > tub2 group had a superficial flat appearance, an isochromatic colour, an HG-tub2 and an undifferentiated component, and a large diameter greater than 30 mm, and it exhibited a G-phenotype. CONCLUSIONS: Intramucosal G-phenotype LG-tub1s > HG-tub2 are potential premalignant stomach neoplasms that may have specific endoscopic and clinicopathological features. However, G-phenotype LG-tub1s > HG-tub2 with undifferentiated component, which potentially show higher malignancy than those without undifferentiated components might change from a reddish to isochromatic colour. Accurately diagnosing, treating, and following-up G-phenotype LG-tub1s > HG-tub2 might decrease the number of patients who experience late-onset metastasis after ESD.

Accumulation of steroid hormones in the eggshells of Japanese quail (Coturnix coturnix japonica).

Oviparous mother transfer significant amounts of steroid to egg yolk during oviposition and the amounts may vary throughout the embryonic development. Eggshell may contain steroid hormones and the amounts could be different during embryonic development inside the egg. This study was designed to quantify the steroid concentrations in the eggshells of Japanese quail. We hypothesized that the steroids would be accumulated in the eggshells in a sex-dependent manner. Eggshells were obtained from three different stages (after laying, 15 days of incubation, and after hatching). The internal contents of the shells were carefully removed, completely dried and pulverized. The steroid contents of the eggshells were then measured by RIA. Physiologic variations in steroids were analyzed according to the amounts accumulated in the eggshells with the different embryonic stages. Results indicate that eggshell testosterone concentrations were high after laying. However, the concentrations were decreased during embryonic development and hatching and no difference was found in eggshell testosterone levels between male and female. However, eggshell estradiol concentrations were undetectable at laying time and the amounts were significantly increased at 15 days of incubation and slightly after hatching. Eggshell estradiol levels were significantly high in female eggshells than male during embryonic development. In contrast, eggshell corticosterone levels were significantly higher in males than in females after hatching. These results clearly demonstrated that eggshells accumulated steroid hormones, and the amounts varied during embryonic development concomitant with changes the internal contents of the eggs.