First Observation of Electron Scattering from Online-Produced Radioactive Target.

We successfully performed electron scattering off unstable nuclei which were produced online from the photofission of uranium. The target ^{137}Cs ions were trapped with a new target-forming technique that makes a high-density stationary target from a small number of ions by confining them in an electron storage ring. After developments of target generation and transportation systems and the beam stacking method to increase the ion beam intensity up to approximately 2×10^{7} ions per pulse beam, an average luminosity of 0.9×10^{26} cm^{-2} s^{-1} was achieved for ^{137}Cs. The obtained angular distribution of elastically scattered electrons is consistent with a calculation. This success marks the realization of the anticipated femtoscope which clarifies the structures of exotic and short-lived unstable nuclei.

The role of thyroid function in female and male infertility: a narrative review.

PURPOSE: We herein aimed to review the new insights into the impact of impaired thyroid function on male and female fertility, spacing from spontaneous pregnancy to ART, with the objective of providing an updated narrative revision of the literature. METHODS: This narrative review was performed for all available prospective, retrospective and review articles, published up to 2021 in PubMed. Data were extracted from the text and from the tables of the manuscript. RESULTS: Thyroid dysfunction is frequently associated with female infertility, whereas its link with male infertility is debated. Female wise, impaired function is detrimental to obstetric and fetal outcomes both in spontaneous pregnancies and in those achieved thanks to assisted reproduction technologies (ART). Furthermore, the reference range of TSH in natural pregnancy and ART procedures has recently become a matter of debate following recent reports in this field. On the other hand, the impact of thyroid function on the male reproductive system is less clear, although a possible role is suggested via modulation of Sertoli and Leydig cells function and spermatogenesis. CONCLUSION: Thyroid function should be carefully monitored in both male and female, in couples seeking spontaneous pregnancy as well as ART, as treatment is generally immediate and likely to improve chances of success.

TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma.

BACKGROUND: Tripartite motif-containing 27 (TRIM27) has been implicated in the progression of various cancers. However, the role of TRIM27 in sinonasal mucosal melanoma (SNMM) remains poorly understood. MATERIALS & METHODS: We retrospectively examined 28 patients with SNMM treated with between 2003 and 2021. We undertook immunohistochemical analysis of TRIM27, Ki-67, and p-Akt1 expression in SNMM tissues. We also investigated the relationship between TRIM27 expression and clinical characteristics, prognosis, Ki-67 as a tumor growth potential marker, and p-Akt1 as one of the prognostic factors in mucosal melanoma. RESULTS: TRIM27 expression was significantly higher in T4 disease than in T3 disease and was higher in stage IV than in stage III. Patients with high-TRIM27 SNMM had a significantly poorer prognosis in terms of overall survival (OS) and disease-free survival.There was also a significantly higher rate of distant metastasis. Univariate analysis for OS revealed that TRIM27 and T classification were significant poor prognostic factors. In addition, the Ki-67 positive score and the p-Akt1 total staining score were significantly higher in the high-TRIM27 group than in the low-TRIM27 group. CONCLUSIONS: High TRIM27 expression in SNMM was associated with advanced T classification, poor prognosis and distant metastasis. We suggest that TRIM27 has potential as a novel biomarker for prognosis in SNMM.

An Assessment of Earth's Climate Sensitivity Using Multiple Lines of Evidence.

We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S. This evidence includes feedback process understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density function (PDF) for S given all the evidence, including tests of robustness to difficult-to-quantify uncertainties and different priors. The 66% range is 2.6-3.9 K for our Baseline calculation and remains within 2.3-4.5 K under the robustness tests; corresponding 5-95% ranges are 2.3-4.7 K, bounded by 2.0-5.7 K (although such high-confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S, in particular using comprehensive models and process understanding to address limitations in the traditional forcing-feedback paradigm for interpreting past changes.

Spinal cord involvement by atrophy and associations with disability are different between multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: The cervical and thoracic cross-sectional spinal cord area (CS-SCA) in multiple sclerosis (MS) correlates with disability, whilst such a correlation remains to be established in neuromyelitis optica spectrum disorder (NMOSD). Our aim was to clarify differences between MS and NMOSD in spinal cord segments where CS-SCA is associated with disability. METHODS: The CS-SCA at C2/C3, C3/C4, T8/T9 and T9/T10 vertebral disc levels was measured in 140 MS patients (111 with relapsing-remitting MS and 29 with progressive MS) and 42 NMOSD patients with anti-aquaporin-4 immunoglobulin G. Disability was evaluated by Expanded Disability Status Scale (EDSS) scores. Multivariate associations between CS-SCA and disability were assessed by stepwise forward multiple linear regression. RESULTS: Thoracic CS-SCA was significantly smaller in NMOSD patients than in MS patients even after adjusting for age, sex and disease duration (P = 0.002 at T8/T9), whilst there was no difference in cervical CS-SCA between the two diseases. Cervical and thoracic CS-SCA had a negative correlation with EDSS scores in MS patients (P < 0.0001 at C3/C4 and P = 0.0002 at T8/T9) whereas only thoracic CS-SCA correlated with EDSS scores in NMOSD patients (P = 0.0006 at T8/T9). By multiple regression analyses, predictive factors for disability in MS were smaller cervical CS-SCA, progressive course, older age and a higher number of relapses, whilst those in NMOSD were smaller thoracic CS-SCA and older age. CONCLUSIONS: Thoracic CS-SCA is a useful predictive marker for disability in patients with NMOSD whilst cervical CS-SCA is associated with disability in patients with MS.

Neighbourhood relationships moderate the positive association between family caregiver burden and psychological distress in Japanese adults: a cross-sectional study.

OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

Morphological lymphocytic reaction, patient prognosis and PD-1 expression after surgical resection for oesophageal cancer.

BACKGROUND: Immune checkpoint inhibitors, such as antibody against programmed cell death protein (PD-1), have demonstrated antitumour effects in patients with malignancies, including oesophageal cancer. A lymphocytic reaction observed by pathological examination is a manifestation of the host immune response to tumour cells. It was hypothesized that a stronger lymphocytic reaction to tumours might be associated with favourable prognosis in oesophageal cancer. METHODS: Using a database of resected oesophageal cancers, four morphological components of lymphocytic reactions (peritumoral, intranest, lymphoid and stromal) to tumours were evaluated in relation to clinical outcome, PD-1 expression by immunohistochemistry and total lymphocyte count in blood. RESULTS: Resected oesophageal cancer specimens from 436 patients were included in the study. Among the four morphological components, only peritumoral reaction was associated with patient prognosis (multivariable P for trend <0·001); patients with a higher peritumoral reaction had significantly longer overall survival than those with a lower reaction (multivariable hazard ratio 0·48, 95 per cent c.i. 0·34 to 0·67). The prognostic effect of peritumoral reaction was not significantly modified by other clinical variables (all P for interaction >0·050). Peritumoral reaction was associated with total lymphocyte count in the blood (P < 0·001), supporting the relationship between local immune response and systemic immune competence. In addition, higher morphological peritumoral reaction was associated with high PD-1 expression on lymphocytes in tumours (P = 0·034). CONCLUSION: These findings should help to improve risk-adapted therapeutic strategies and help stratify patients in the future clinical setting of immunotherapy for oesophageal cancer.

ANTECEDENTES: Los inhibidores de los puntos de control inmunitario (checkpoints) (p.ej. los anticuerpos anti-PD-1) han demostrado efectos antitumorales en pacientes con tumores malignos, incluido el cáncer de esófago. La reacción linfocítica detectada en estudios anatomopatológicos es una manifestación de la respuesta inmune del huésped a las células tumorales. Se estableció la hipótesis de que una mayor reacción linfocítica a los tumores podría asociarse con un mejor pronóstico en el cáncer de esófago. MÉTODOS: Usando una base de datos de 436 cánceres de esófago resecados, se evaluaron cuatro componentes morfológicos (peritumoral, intra-epitelial, linfoide y estromal) de las reacciones linfocíticas a tumores en relación con los resultados clínicos, la expresión inmunohistoquímica de PD-1 y el recuento total de linfocitos en sangre. RESULTADOS: De los cuatro componentes, solamente la reacción peritumoral se asoció con el pronóstico del paciente (P multivariable para tendencia < 0,001): los pacientes con mayor reacción peritumoral presentaron una supervivencia global significativamente más prolongada que aquellos pacientes con menor reacción peritumoral (cociente de riesgos instantáneos multivariable, hazard ratio, HR: 0,48; i.c. del 95%: 0,34 -0,67; P <0,001). El efecto pronóstico de la reacción peritumoral no se modificó significativamente por otras variables clínicas (todas las P para la interacción > 0,05). La reacción peritumoral se asoció con el recuento total de linfocitos en la sangre (P < 0,001), lo que respalda la relación entre la respuesta inmune local y la competencia inmune sistémica. Además, una elevada reacción morfológica peritumoral se asoció con una alta expresión de PD-1 en linfocitos tumorales (P = 0,034). CONCLUSIÓN: Estos hallazgos deberían ayudar a mejorar las estrategias terapéuticas adaptadas al riesgo y contribuir a estratificar a los pacientes en el entorno clínico futuro de la inmunoterapia para los pacientes con cáncer de esófago.

A multicenter, randomized, rater-blinded, parallel-group, phase 3 study to compare the efficacy, safety, and immunogenicity of biosimilar RGB-10 and reference once-daily teriparatide in patients with osteoporosis.

The efficacy and safety of RGB-10 and reference teriparatide were evaluated in a randomized 52-week study in 250 patients with osteoporosis at high risk of fracture. RGB-10 was equivalent to reference teriparatide in efficacy and had a comparable safety profile. INTRODUCTION: RGB-10 is the first biosimilar teriparatide authorized in the European Union. This multicenter, randomized, rater-blinded, parallel-group phase 3 study evaluated equivalence in efficacy and compared safety between RGB-10 and reference teriparatide in patients with osteoporosis at high risk of fracture for registration in Japan. METHODS: Ambulatory postmenopausal women and men (≥ 55 years of age) with osteoporosis at high risk of fracture were randomized 1:1 to receive either RGB-10 or reference teriparatide 20 µg once daily via subcutaneous self-injection for 52 weeks. The primary efficacy endpoint was the percent change from baseline to 52 weeks in lumbar spine (L2-L4) bone mineral density (BMD). Safety outcomes and immunogenicity were also assessed. RESULTS: In total, 250 patients (125 in each group) were randomized. The percent change from baseline to 52 weeks in lumbar spine (L2-L4) BMD (mean ± standard deviation) was 8.94% ± 6.19% in the RGB-10 group and 9.65% ± 6.22% in the reference teriparatide group. The estimated between-group difference (95% confidence interval) was - 0.65% (- 2.17% to - 0.87%) within the pre-specified equivalence margin (± 2.8%), which indicates equivalence in efficacy between the two groups. Changes in BMD at lumbar spine (L1-L4), femoral neck, and total hip and serum procollagen type I amino-terminal propeptide were also similar between the groups. Safety profiles, including immunogenicity, were comparable. CONCLUSIONS: The therapeutic equivalence of RGB-10 to reference teriparatide was demonstrated. RGB-10 had comparable safety profile to that of reference teriparatide.

Energy of the

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

Comparison of mediastinal lymph node metastases from adenocarcinoma of the esophagogastric junction versus lower esophageal squamous cell carcinoma with involvement of the esophagogastric junction.

The distribution of mediastinal lymph node metastasis in patients with adenocarcinoma of the esophagogastric junction (AEG) remains unclear. Additionally, the distribution of nodal mediastinal metastasis from squamous cell carcinoma (SCC) of the lower esophagus with involvement of the esophagogastric junction remains unclear, given the very limited number of these patients. In this retrospective review, we compared the outcomes of radical lymphadenectomy of the mediastinum, including upper mediastinal lymphadenectomy, between patients with AEG and those with SCC. From 2005 to 2017, 69 consecutive patients underwent esophagectomy via right thoracotomy or minimally invasive esophagectomy for a Siewert type I or II tumor with esophageal invasion ≥3 cm. We analyzed the incidences of mediastinal lymph node metastasis in this group relative to those of 73 patients with SCC with involvement of the esophagogastric junction who consecutively underwent esophagectomy during the same period. Mediastinal lymph node metastasis was seen in 26 of 69 patients with AEG (38%), with upper, middle, lower mediastinal nodal metastasis instances of 20%, 17%, and 23%, respectively. Mediastinal lymph node metastasis was seen in 23 of 73 patients with SCC (32%), with upper, middle, lower mediastinal nodal metastasis instances of 12%, 16%, and 19%, respectively. This mediastinal lymph nodal metastasis distribution did not statistically differ between patients with AEG and those with SCC. The relapse-free survival outcomes were poor for patients with clinical (P < 0.01) or pathological (P < 0.01) nodal metastasis of the mediastinum with AEG. In contrast, patients with clinical or pathological mediastinal nodal metastases of SCC did not have extremely poor survival outcomes, compared to patients with AEG. Despite the limited dataset available for analysis, patients with AEG and those with SCC might exhibit similar incidences and distribution of mediastinal lymph node metastasis. However, the clinical or pathological metastasis of AEG to the mediastinum was associated with poor survival outcomes, even if radical mediastinal lymphadenectomy including the upper mediastinal lymphadenectomy was performed.

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo.

AIM: To evaluate the dentinogenetic effects of tissue inhibitor of metalloprotease (TIMP1) on human pulp cells in vitro and rat pulp tissue in vivo. METHODOLOGY: The effect of TIMP1 on pulp cell functions related to hard tissue formation as part of the wound healing process (i.e. biocompatibility, proliferation, differentiation and mineralized nodule formation) was evaluated in vitro and using a direct pulp capping experimental animal model in vivo. The effects of different-sized cavity preparations on hard tissue formation induced by ProRoot MTA at 2 weeks were evaluated using micro-computed tomography (micro-CT). Tertiary dentine formation quality and quantity after pulp capping using TIMP1, ProRoot MTA and phosphate-buffered saline (PBS) was also evaluated after 4 weeks using micro-CT in term of dentine volume (DV), dentine mineral density (DVD) and histological analysis. The data were evaluated by Student's t-test, one-way ANOVA with Tukey's post hoc test, the Kruskal-Wallis test or the Steel-Dwass test. P values < 0.05 were considered statistically significant. RESULTS: TIMP1 significantly stimulated dental pulp stem cell proliferation, differentiation, and mineralization and was more biocompatible compared with the PBS control (P < 0.05). In the pulp capping model, the amount of tertiary dentine that formed was directly proportional to the size of the pulp exposure; greater amounts of tertiary dentine were observed in pulps with larger exposures after 2 weeks. 4-week samples of TIMP1 and ProRoot MTA had similar characteristics, but both sample significantly induced tertiary dentine formation beneath the cavity compared with PBS (P <  0.05) under standardized cavity preparations. CONCLUSIONS: TIMP1 has an important role in pulpal wound healing, which makes it a potential biological pulp capping material and candidate molecule for regenerative endodontic therapy.

Oesophagectomy with or without supraclavicular lymphadenectomy after neoadjuvant treatment for squamous cell carcinoma of the oesophagus.

BACKGROUND: Treatment of supraclavicular nodes remains controversial among patients with oesophageal squamous cell carcinoma. This study assessed the outcomes of patients who underwent oesophagectomy with or without supraclavicular lymphadenectomy after neoadjuvant treatment. METHODS: This was a single-centre retrospective cohort study. Patients with oesophageal squamous cell carcinoma and clinically negative supraclavicular nodes who underwent oesophagectomy after neoadjuvant treatment between January 2005 and December 2015 were included. Overall and relapse-free survival were compared between patients who did or did not undergo supraclavicular nodal dissection. Propensity score matching was used to correct for differences in prognostic factors between the groups. RESULTS: Some 223 patients underwent supraclavicular lymphadenectomy. The prevalence of pathologically confirmed supraclavicular metastasis was 10·3 per cent, and these patients had poor 5-year relapse-free (7 per cent) and overall (14 per cent) survival. Only two of 55 patients who did not undergo supraclavicular lymphadenectomy had recurrent disease in the supraclavicular region without distant metastasis. There was no statistically significant difference between the groups in relapse-free survival (hazard ratio (HR) 0·95, 95 per cent c.i. 0·61 to 1·47; P = 0·821) or overall survival (HR 0·86, 0·52 to 1·40; P = 0·544). Similarly, no significant difference in relapse-free or overall survival was observed between the propensity score-matched groups. CONCLUSION: For patients with clinically negative supraclavicular lymph nodes, prophylactic supraclavicular lymphadenectomy may be omitted when neoadjuvant treatment is administered.

Endocytosis following dopamine D2 receptor activation is critical for neuronal activity and dendritic spine formation via Rabex-5/PDGFRß signaling in striatopallidal medium spiny neurons.

Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-ß (PDGFRß)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation. Endosomes containing D2LR and PDGFRß are then transported to the Golgi apparatus, where those complexes trigger Gαi3-mediated ERK signaling. Loss of intracellular D2LR-mediated ERK activation decreased neuronal activity and dendritic spine density in striatopallidal medium spiny neurons (MSNs). In addition, dendritic spine density in striatopallidal MSNs significantly increased following treatment of striatal slices from wild-type mice with quinpirole, a D2R agonist, but those changes were lacking in D2LR knockout mice. Moreover, intracellular D2LR signaling mediated effects of a typical antipsychotic drug, haloperidol, in inducing catalepsy behavior. Taken together, intracellular D2LR signaling through Rabex-5/PDGFRß is critical for ERK activation, dendritic spine formation and neuronal activity in striatopallidal MSNs of mice.

Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell carcinoma patients: striving toward appropriate judgment of biopsy.

In esophageal squamous cell carcinoma (ESCC) patients who are treated with chemoradiotherapy (CRT), identification of the presence or absence of residual or recurrent carcinoma is usually pivotal in their clinical management. In addition, the extent of carcinoma invasion into the esophageal wall could determine the clinical outcome of these patients following CRT. Therefore, in this study, we evaluated the response to CRT both macroscopically and histologically in a consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy following curative esophageal resection at Tohoku University Hospital between August 2011 and December 2012. The histological grading of tumor regression was as follows: grade 3, markedly effective (no viable residual tumor cells); grade 2, moderately effective (residual tumor cells in less than one-third of the tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two-thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases because they might show a complete response with definitive CRT. We evaluated the presence of any residual in situ lesions and tumor depth in detail. The grading of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2 (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate between macroscopic and histopathological evaluation on the depth of the tumor was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions were not detected in 17 cases, and tumor nests were not detected in the lamina propria mucosae in 9 cases. The results of this study highlight the difficulties of detecting residual carcinoma cells using conventional endoscopic biopsy in patients who have received CRT. Therefore, when residual cancer is clinically suspected in patients who have received CRT, the biopsy specimen should be obtained from the deep layer of the esophagus whenever possible. Additionally, close follow-up is required using positron emission tomography/computed tomography, endoscopy, and other radiological evaluations.

Clinical utility of exhaled carbon monoxide in assessing preoperative smoking status and risks of postoperative morbidity after esophagectomy.

Whereas smoking constitutes a significant risk factor for postesophagectomy morbidity, there is no reliable method to assess the smoking status of patients prior to the procedure. Since exhaled carbon monoxide (CO) is an indicator of recent smoking, this paper hypothesizes that this is a useful parameter in assessing current smoking status and may help predict morbidity following esophagectomy. Sixty-nine patients, who had undergone elective three-incision esophagectomy with two- or three-field lymphadenectomy for esophageal cancer, were prospectively studied between February 2015 and September 2017. At surgical admission, they were asked about their smoking history, their exhaled CO levels were evaluated, and they were grouped into three based on their CO levels. These were 0 parts per million (ppm), >0 and <7 ppm, and ≥7 ppm. Their postoperative morbidity was also assessed. Approximately 13.5% of the patients showed high levels of exhaled CO ≥ 7 ppm, despite preoperatively reporting smoking cessation for over a month. Morbidities of the Clavien-Dindo classification (CDc) ≥ II increased as exhaled CO levels increased and severe morbidity of CDc ≥ IIIb frequently was observed in patients with exhaled CO levels ≥7 ppm. The logistic regression analysis showed that exhaled CO level ≥7 ppm was an independent risk factor for severe postesophagectomy morbidity. Overall, the results of this study suggest that exhaled CO levels may be useful in estimating current smoking status and that it may also help give an estimation of the risk of postesophagectomy morbidity.

Pyloroplasty may reduce weight loss 1 year after esophagectomy.

Weight loss after esophagectomy is common and is associated with unfavorable prognosis. However, the clinical features and surgical methods that influence postesophagectomy weight loss are not well characterized. This study aims to determine those features (especially the surgical methods) that may affect postoperative weight loss. We reviewed 221 esophageal cancer patients who had undergone esophagectomy at Kumamoto University Hospital (Kumamoto, Japan) between November 2012 and June 2015. Among these, we recruited 106 patients who had undergone transthoracic esophagectomy with gastric conduit reconstruction, had no cancer recurrence within 1 year, and no missing follow-up data. We tabulated the body weight changes and risk factors associated with weight loss exceeding 10% at 1-year postesophagectomy. The mean body weights at baseline and 1-year postsurgery were 60.3 kg (standard error (SE): 0.91) and 52.6 (SE: 0.91), respectively. One year postsurgery, the body weights had changed as follows: mean: -12.2%; median: -12.9%; standard deviation: 9.06; range: -36.1-18.56%; interquartile range: -10.5 to -14.0%. In the multivariate logistic regression analysis, the absence of pyloroplasty was the sole risk factor for more than 10% weight loss (OR: 3.22; 95% CI: 1.08-11.9; P = 0.036). Our data suggest that pyloroplasty with esophagectomy can overcome the post-surgical weight loss.

Minimally invasive esophagectomy may contribute to long-term respiratory function after esophagectomy for esophageal cancer.

Evidence suggests that minimally invasive esophagectomy has several advantages with regard to short-term outcomes, compared to open esophagectomy in esophageal cancer patients. However, the impact of minimally invasive esophagectomy on long-term respiratory function remains unknown. The objective of this study is to assess the association between use of the minimally invasive esophagectomy and long-term respiratory dysfunction in esophageal cancer patients after esophagectomy. This retrospective single institution study using prospectively collected data included 87 consecutive esophageal cancer patients who had undergone esophagectomy. All patients underwent a respiratory function test before, and one year after esophagectomy. Logistic regression analysis was used to compute the hazard ratio for long-term respiratory dysfunction. Minimally invasive esophagectomies were performed in 53 patients, and open esophagectomies in 34 patients. The two groups showed no significant differences in terms of postoperative complications and postoperative course. Nor were any differences observed between the two groups in terms of volume capacity (L) and forced expiratory volume 1.0 (L) before esophagectomy (P > 0.34). However, one year after esophagectomy, the decreases in volume capacity and forced expiratory volume 1.0 were significantly less in the minimally invasive esophagectomy group than in the open esophagectomy group (P = 0.04 and P = 0.007, respectively). Multivariate analyses revealed that minimally invasive esophagectomy was an independent favorable factor for maintenance of forced expiratory volume 1.0 (hazard ratio = 0.17, 95% confidence interval 0.04-0.71; P = 0.01). Minimally invasive esophagectomy may be an independent favorable factor for maintenance of long-term respiratory function in esophageal cancer patients after esophagectomy.

Analysis of masticatory muscle coordination during unilateral single-tooth clenching using muscle functional magnetic resonance imaging.

In a previous study, we used muscle functional magnetic resonance imaging to show that the anterior movement of the occlusal point increased the activity of the superior head of the ipsilateral lateral pterygoid muscle (ipsilateral SHLP) during unilateral single-tooth clenching. The purpose of this study was to verify the hypothesis that the increased activity of the ipsilateral SHLP described above serves to antagonise the occlusal force acting on the condyle. In total, 9 healthy volunteers were requested to perform left unilateral clenching at the first molar or first premolar region for 1 minute at 20% or 40% maximum voluntary clenching force. Changes in the mean proton transverse relaxation time (∆T2) were examined from the magnetic resonance images obtained before and after each clenching act as an index of the activity in all masticatory muscles. Correlation analyses of the mean ΔT2 for each volume of interest were performed with the first molar or premolar clenches to analyse the correlation between the activities in each muscle. A statistically significant correlation was exhibited between the ipsilateral temporal and ipsilateral SHLP (r = .651, P = .003) during first premolar clenching. However, no significant correlations were observed in the ipsilateral SHLP during first molar clenching. The results of this study suggest that the ipsilateral SHLP may contribute to the pulling of the mandibular condyle forward against the occlusal force generated by the ipsilateral temporal muscle.

Comprehensive molecular exploration identified promoter DNA methylation of the CRBP1 gene as a determinant of radiation sensitivity in rectal cancer.

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS: We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant. Using a microarray, we selected candidate radiation sensitivity marker genes by choosing genes whose expression was consistent with a radiation-resistant or sensitive cell phenotype. RESULTS: Among candidate genes, cellular retinol binding protein 1 (CRBP1) was of particular interest because it was not only induced in HCT116 cells by tentative 10 Gy radiation treatments, but also its expression was increased in HCT116-derived radiation-resistant cells vs parental cells. Forced expression of CRBP1 decreased the viability of both HCT15 and DLD-1 cells in response to radiation therapy. We also confirmed that CRBP1 was epigenetically silenced by hypermethylation of its promoter DNA, and that the quantitative methylation value of CRBP1 significantly correlated with histological response in RC patients with NCRT (P=0.031). CONCLUSIONS: Our study identified CRBP1 as a radiation-sensitive predictor in RC.

Estrogen receptor-beta genetic variations and overall survival in patients with locally advanced gastric cancer.

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.