Eribulin promotes proliferation of CD8+ T cells and potentiates T cell-mediated anti-tumor activity against triple-negative breast cancer cells.

PURPOSE: Chemotherapeutic agents exert immunomodulatory effects on triple-negative breast cancer (TNBC) cells and immune cells. Eribulin favorably affects the immunological status of patients with breast cancer. However, the effects of eribulin on the immune cells remain unexplored. The aim of this study was to investigate the effects of eribulin on immune cells. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors and mouse splenocytes were stimulated with anti-CD3 and anti-CD28 antibodies. The effects of eribulin and paclitaxel on cell proliferation and differentiation status were analyzed using flow cytometry. RNA sequencing was performed to assess alterations in gene expression in CD8+ T cells following eribulin and paclitaxel treatment. Using TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157), the anti-tumor activity of CD3/CD28-stimulated T cells combined with eribulin or paclitaxel was evaluated. RESULTS: Eribulin did not affect CD3/CD28-stimulated PBMCs proliferation. However, eribulin significantly decreased the CD4/CD8 ratio in T cells, indicating that eribulin facilitates CD8+ T cell proliferation. Furthermore, eribulin significantly increased the frequency of less differentiated CD45RA+, CCR7+, and TCF1+ subsets of CD8+ T cells. RNA sequencing revealed that eribulin enhanced the expression of gene sets related to cell proliferation and immune responses. Moreover, eribulin augmented the anti-tumor effects of CD3/CD28-stimulated T cells against TNBC cells. These results were not observed in experiments using paclitaxel. CONCLUSIONS: Eribulin promoted CD8+ T cell proliferation, repressed effector T cell differentiation, and harnessed T cell-mediated anti-tumor effects. These mechanisms may be one of the cues that eribulin can improve the immunological status of tumor-bearing hosts.

Neutrophil-to-Lymphocyte Ratio Is Associated With the Proportion of Poorly Differentiated Components in Papillary Thyroid Carcinoma.

INTRODUCTION: Diagnosis of poorly differentiated thyroid cancer (PDTC) requires ≥ 50% of poorly differentiated components (PDC) in Japan. However, the optimal cutoff percentage of PDC for PDTC diagnosis remains controversial. Although high neutrophil-to-lymphocyte ratio (NLR) correlates with the aggressiveness of papillary thyroid cancer (PTC), whether NLR is associated with the proportion of PDC in PTC remains unstudied. MATERIALS AND METHODS: Patients with the pure PTC (n = 664), PTC with < 50% PDC (n = 19), or PTC with ≥ 50% PDC (n = 26) who underwent surgery were retrospectively analyzed. Twelve-year disease-specific survival and preoperative NLR were compared among these groups. RESULTS: Twenty seven patients died from thyroid cancer. The PTC with ≥ 50% PDC group (80.7%) showed significantly worse 12-year disease-specific survival than the pure PTC group (97.2%) (P < 0.001); however, the < 50% PDC group (94.7%) did not (P = 0.91). The PTC with ≥ 50% PDC group had a significantly higher NLR than the pure PTC (P < 0.001) and the PTC with < 50% PDC groups (P < 0.001), whereas there was no significant difference in the NLR between the pure PTC and the PTC with < 50% PDC groups (P = 0.48). CONCLUSIONS: PTC with ≥ 50% PDC is more aggressive than either pure PTC or PTC with < 50% PDC, and NLR potentially reflects the PDC proportion. These results support the validity of 50% PDC as a cut-off for PDTC diagnosis and indicate the utility of NLR as a biomarker for PDC proportion.

A Rare Clinical Case of Secondary Central Nervous System Involvement without Transformation in Hairy Cell Leukemia: Case Report and Literature Review.

Introduction Hairy cell leukemia (HCL) is an indolent B-cell lymphoma characterized by a specific genetic mutation, BRAF V600E, which affects the specific morphology and oncogenesis. For HCL, few reports regarding secondary central nervous system involvement (SCNSI) are available. Herein, we present the case of an 80-year-old woman who had a relapse of HCL with SCNSI. Case presentation The diagnosis of HCL was made in June 2015 after identifying BRAF V600E proteins by immunohistochemical analysis, and the disease was then controlled for 6 years by employing chemoimmunotherapy. In February 2021, the patient was admitted with neurological symptoms such as dizziness. Magnetic resonance imaging of the brain showed abnormal enhancement in the cerebrum, and cerebrospinal fluid analysis revealed neoplastic cells without transformation into large cells. Thus, the patient was diagnosed as having SCNSI in HCL. Conclusion We report a case of a rare clinical presentation of SCNSI in HCL with literature review.

Epidemiological and therapeutic profiles of lung cancer patients in the Hokushin Region Japan: a retrospective hospital administrative database study.

OBJECTIVE: This study was performed to validate the epidemiology, initial treatment, and clinical practice of lung cancer patients in the Hokushin region, Japan. METHODS: We retrospectively surveyed data of 5503 newly diagnosed and registered lung cancer patients in 22 principal hospital-based cancer registries in Hokushin region linked with health insurance claims data for registered patients between 2016 and 2017. RESULTS: The patients consisted of 3677 (66.8%) men and 1826 (33.2%) women with a mean (range) age of 72.2 (27-103) years). Diagnoses were small cell lung cancer (n = 512, 9.4%), squamous cell carcinoma (n = 1083, 19.7%), and non-squamous non-small cell lung cancer (NSCLC; n = 3906, 70.9%). The population with stage I disease in Toyama prefecture (41.1%) was smaller than in the other three prefectures associated with reduced selection of initial surgical therapy and increased frequencies of stage IV disease (33.2%) and best supportive care (18.6%). Initial chemotherapy for stage IV non-squamous NSCLC consisted of tyrosine kinase inhibitors in 39.3% of cases for EGFR and 4% of cases for ALK-positive non-squamous NSCLC, followed by platinum compounds (25.9%) non-platinum compounds (12.9%), and immune checkpoint inhibitors (10.2%). Carboplatin was the commonly prescribed first-line cytotoxic chemotherapeutic agent (65.4% of patients under 75 years and in 96.7% of patients over 75 years). CONCLUSION: This study revealed real-world data on epidemiological and treatment status in lung cancer in four prefectures in Hokushin region, Japan. Simultaneous analysis of nationwide registry and insurance data could provide valuable insights for the development of lung cancer screening and medical treatment strategies. In addition, the comparative data analysis with other lesions or countries will be useful for evaluating the differences in clinical practice of cancer managements.

Myofibroblast-dominant proliferation associated with severe fibrosis in bulbar urethral strictures.

OBJECTIVES: Myofibroblast-dominant proliferation (relative to fibroblast proliferation) is the key process in urethral fibrosis, but its association with clinical features is not understood. We conducted a histological analysis of urethral strictures and examined the association between myofibroblast proliferation and stricture characteristics. METHODS: Formalin-fixed, paraffin-embedded urethral sections sliced axially from 175 male patients with bulbar urethral strictures were retrospectively analyzed. All patients underwent excision and primary anastomosis between September 2008 and January 2021 by a surgeon (AH). Masson's trichrome stain was used to estimate the area of fibrosis. Corresponding unstained slides with the largest area of fibrosis were selected and double-immunostained with anti-smooth muscle actin (SMA) and anti-TE-7 mouse monoclonal antibodies for the assessment of myofibroblasts and fibroblasts, respectively. The ratio of the number of SMA-positive cells to the number of TE-7-positive cells (SMA/TE-7 ratio) was calculated. RESULTS: The area of fibrosis in strictures due to perineal trauma (n = 85, median 108.9 mm2 ) was significantly larger than that in non-traumatic strictures (n = 90, median 42.9 mm2 , p < 0.0001). The area of fibrosis positively correlated with SMA expression (r = 0.35, p < 0.0001) and the SMA/TE-7 ratio (r = 0.36, p < 0.0001), but not with TE-7 expression (r = -0.01, p = 0.75). In a multivariate linear regression model, traumatic etiology (standard coefficient 0.37, t value 3.9, p < 0.0001) and increased SMA expression (standard coefficient 0.17, t value 2.1, p = 0.03) were the predictors of wide fibrosis area. CONCLUSIONS: Myofibroblast-dominant proliferation may contribute to the pathogenesis of severe urethral fibrosis.

Epidermal growth factor receptor activation confers resistance to lenvatinib in thyroid cancer cells.

Thyroid cancer is the most common endocrine malignancy. A multitargeted tyrosine kinase inhibitor, lenvatinib, has been used for the treatment of advanced thyroid cancer. To elucidate the mechanism of resistance to lenvatinib in thyroid cancer cells, we established lenvatinib-resistant sublines and analyzed the molecular mechanisms of resistance. Two thyroid cancer cell lines (TPC-1 and FRO) were used, and resistant sublines for lenvatinib (TPC-1/LR, FRO/LR) were established. In TPC-1/LR, the phosphorylation of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), and Akt was enhanced whereas in FRO/LR, the phosphorylation of EGFR and downstream signal transduction molecules was not enhanced. The addition of epidermal growth factor decreased sensitivity to lenvatinib in TPC-1 and FRO. The combination of EGFR inhibitors lapatinib and lenvatinib significantly inhibited the growth of TPC-1/LR in both in vitro and mouse xenograft models. Short-term exposure to lenvatinib enhanced the phosphorylation of EGFR in six thyroid cancer cell lines regardless of their histological origin or driver gene mutations; however, phosphorylation of ERK was enhanced in all cells except TPC-1. A synergistic growth-inhibitory effect was observed in three thyroid cancer cell lines, including intrinsically lenvatinib-resistant cells. The results indicate that signal transduction via the EGFR pathway may be involved in the development of lenvatinib resistance in thyroid cancer cells. The inhibition of the EGFR pathway simultaneously by an EGFR inhibitor may have therapeutic potential for overcoming lenvatinib resistance in thyroid cancer.

Skeletal muscle loss during neoadjuvant chemotherapy predicts poor prognosis in patients with breast cancer.

BACKGROUND: The skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level divided by height squared, has been considered a prognostic factor in patients with breast cancer. However, the prognostic impact of changes in SMI during treatment remains unclear. This study aimed to evaluate the influence of SMI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). METHODS: We reviewed patients with breast cancer who underwent NAC and subsequent surgery for breast cancer between 2010 and 2017. The rate of SMI change during NAC was calculated, and the association between SMI changes and prognosis was retrospectively analyzed. RESULTS: In total, 141 patients were evaluated. 48 (34.0%), 53 (37.6%), and 40 (28.4%) patients exhibited increased (≥ 3%), maintained (- 3% <, < 3%), and decreased (- 3% ≥) SMI during NAC, respectively. The decreased SMI group showed significantly poorer disease-free survival than the maintained and increased SMI groups (hazard ratio [HR] 8.29, p <  0.001 for the decreased vs. increased SMI groups; HR 3.49, p <  0.001 for the decreased vs. maintained SMI groups). Moreover, decreased SMI was an independent risk factor for disease-free survival in multivariate analysis (HR 3.68, p <  0.01). CONCLUSIONS: Skeletal muscle loss during NAC predicts poor prognosis. Our results underscore the importance of monitoring and maintaining skeletal muscle mass during NAC.

The protective effect of Centella asiatica and its constituent, araliadiol on neuronal cell damage and cognitive impairment.

Alzheimer's disease (AD) is characterized by progressive cognitive decline, and the number of affected individuals has increased worldwide. However, there are no effective treatments for AD. Therefore, it is important to prevent the onset of dementia. Oxidative stress and endoplasmic reticulum (ER) stress are increased in the brains of AD patients, and are postulated to induce neuronal cell death and cognitive dysfunction. In this study, Centella asiatica, a traditional Indian medicinal herb, were fractionated and compared for their protective effects against glutamate and tunicamycin damage. Araliadiol was identified as a component from the fraction with the highest activity. Further, murine hippocampal cells (HT22) were damaged by glutamate, an oxidative stress inducer. C. asiatica and araliadiol suppressed cell death and reactive oxygen species production. HT22 cells were also injured by tunicamycin, an ER stress inducer. C. asiatica and araliadiol prevented cell death by mainly inhibiting PERK phosphorylation; additionally, C. asiatica also suppressed the expression levels of GRP94 and BiP. In Y-maze test, oral administration of araliadiol (10 mg/kg/day) for 7 days ameliorated the arm alternation ratio in mice with scopolamine-induced cognitive impairment. These results suggest that C. asiatica and its active component, araliadiol, have neuroprotective effects, which may prevent cognitive dysfunction.

Surgical resection of the primary tumor prevents an undesirable locoregional condition and improves the quality of life in patients with anaplastic thyroid cancer.

PURPOSE: Anaplastic thyroid cancer (ATC) is a highly aggressive tumor that invades surrounding tissues and rapidly metastasizes throughout the body. Growth of the primary tumor in the neck often causes serious conditions that decrease the quality of life (QOL) of patients. The objective of this study was to investigate the role of surgical resection in improving the QOL of patients with ATC. METHODS: This was a retrospective review of 62 patients with ATC treated at Shinshu University Hospital between January 2001 and June 2019. RESULTS: Fourteen patients underwent R0/R1 resection. Thirteen of the 14 patients received postoperative radiation, and 4 received chemotherapy. The mean survival period was 15.4 ± 18.2 (range, 2-75) months. Distant metastases appeared within 3.2 ± 2.3 months postoperatively in 12 patients. A permanent tracheostomy was required in six patients; however, eight patients did not show airway obstruction until death. Daily treatment for exudate or bleeding from tumors that eroded in the neck, which deteriorated the QOL, was unnecessary in 12 patients. CONCLUSIONS: As surgical resection can improve the QOL in patients with ATC, thyroid surgeons should promptly and carefully evaluate the resectability of the tumor and favor resection as much as possible.

Effects of watercress extract fraction on R-spondin 1-mediated growth of human hair.

OBJECTIVE: Hair loss and greying affect men and women of all ages, often causing psychosocial difficulties. Dickkopf-1 (DKK1), a major hair loss factor secreted from dermal papilla (DP) cells in response to the secretion of dihydrotestosterone (DHT), has been reported to induce and accelerate androgenetic alopecia (AGA). In addition, DKK1 acts as a potent suppressor of melanogenesis and is closely related to hair colour. R-spondin 1 (RSPO1) is a secretory agonist of Wnt signalling known to antagonize the effects of DKK1, including DKK1-mediated hair follicle suppression. In this study, we investigated the effect of watercress extract (WCE) on the secretion of RSPO1 and DKK1 from DP cells as well as its anti-hair loss effect in human hair follicles and patients. METHODS: The in vitro secretion of RSPO1 and DKK1 was measured by ELISA. Human hair follicles were collected from the scalp of a female donor and used for ex vivo organ culture to investigate the effects of WCE on human hair loss. Finally, a 6-month human clinical trial was conducted to examine the effect of WCE-containing lotion on hair growth in a male panel. RESULTS: WCE significantly upregulated RSPO1 secretion and suppressed DKK1 secretion in a dose-dependent manner, even in the presence of DHT. WCE-treated hair follicles elongated 1.6-fold compared with the control, and the level of RSPO1 production in DP as well as RSPO1 bound to the outer root sheath (ORS) increased. In the clinical trial, the hair lotion containing 2% WCE increased hair thickness and density to improve against hair loss symptoms. CONCLUSION: WCE exhibited a strong anti-androgenic effect through its ability to suppress DKK1 secretion and antagonize DKK1 via RSPO1. These findings highlighted the potential use of WCE for the treatment of hair loss.

OBJECTIF: La perte de cheveux et le grisonnement touchent des hommes et des femmes de tous âges, ce qui entraîne souvent des difficultés psychosociales. Selon des rapports, Dickkopf-1 (DKK1), un facteur de perte de cheveux majeur sécrété par les cellules de la papille dermique (PD) en réponse à la sécrétion de dihydrotestostérone (DHT), induit et accélère l'alopécie androgénétique (AAG). En outre, DKK1 agit comme un puissant suppresseur de la mélanogenèse et est étroitement lié à la couleur des cheveux. La protéine R-spondin 1 (RSPO1) est un agoniste sécrétoire de la voie de signalisation Wnt connue pour antagoniser les effets de DKK1, notamment la suppression des follicules pileux médiée par DKK1. Dans cette étude, nous avons étudié l'effet de l'extrait de cresson sur la sécrétion de RSPO1 et de DKK1 à partir des cellules de la PD, ainsi que son effet anti-perte de cheveux sur les follicules pileux humains et chez les patients. MÉTHODES: La sécrétion in vitro de RSPO1 et de DKK1 a été mesurée à l'aide de la méthode ELISA. Des follicules pileux humains ont été prélevés sur le cuir chevelu d'une femme et utilisés pour une culture d'organes ex vivo afin d'étudier les effets de l'extrait de cresson sur la perte de cheveux humains. Enfin, un essai clinique de 6 mois chez l'être humain a été mené pour examiner l'effet d'une lotion contenant de l'extrait de cresson sur la croissance des cheveux au sein d'un panel d'hommes. RÉSULTATS: L'extrait de cresson a significativement régulé à la hausse la sécrétion de RSPO1 et a supprimé la sécrétion de DKK1 de manière dose-dépendante, même en présence de DHT. Les follicules pileux traités avec de l'extrait de cresson ont été multipliés par 1,6 par rapport au groupe témoin, et le niveau de production de RSPO1 dans la PD ainsi que le taux de RSPO1 lié à la gaine externe de la racine ont augmenté. Dans l'essai clinique, la lotion pour cheveux contenant 2 % d'extrait de cresson a augmenté l'épaisseur et la densité des cheveux, améliorant ainsi les symptômes de perte de cheveux. CONCLUSION: La capacité de l'extrait de cresson à supprimer la sécrétion de DKK1 et à antagoniser DKK1 via la protéine RSPO1 lui a conféré un effet anti-androgénique puissant. Ces résultats ont mis en évidence le potentiel de l'extrait de cresson pour le traitement de la perte de cheveux.

HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple-negative breast cancer cells.

PURPOSE: Improved prognosis for triple-negative breast cancer (TNBC) has plateaued and the development of novel therapeutic strategies is required. This study aimed to explore the anti-tumor effect of combined eribulin and HDAC inhibitor (vorinostat: VOR, pan-HDAC inhibitor and ricolinostat: RICO, selective HDAC6 inhibitor) treatment for TNBC. METHODS: The effect of eribulin in combination with an HDAC inhibitor was tested in three TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157) and their eribulin-resistant derivatives. The expression of acetylated α-tubulin was analyzed by Western blotting for TNBC cells and immunohistochemical analyses for clinical specimens obtained from breast cancer patients who were treated with eribulin. RESULTS: The simultaneous administration of low concentrations (0.2 µM) of VOR or RICO enhanced the anti-tumor effect of eribulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. Meanwhile, pretreatment with 5 µM of VOR or RICO enhanced eribulin sensitivity in all three cell lines. Low concentration of VOR or RICO increased acetylated α-tubulin expression in MDA-MB-231 and Hs578T cells. In contrast, whereas 5 µM of VOR or RICO increased the expression of acetylated α-tubulin in MDA-MB-157 cells, low concentrations did not. Eribulin increased the expression of acetylated α-tubulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. These phenomena were also observed in eribulin-resistant cells. Immunohistochemical analyses revealed that the expression of acetylated α-tubulin was increased after eribulin treatment in TNBC. CONCLUSIONS: HDAC6 inhibition enhances the anti-tumor effect of eribulin through the acetylation of α-tubulin. This combination therapy could represent a novel therapeutic strategy for TNBC.

Multicenter retrospective study on the use of Curebest™ 95GC Breast for estrogen receptor-positive and node-negative early breast cancer.

BACKGROUND: The benefits of postoperative chemotherapy in patients with estrogen receptor (ER)-positive breast cancer remain unclear. The use of tumor grade, Ki-67, or ER expression failed to provide an accurate prognosis of the risk of relapse after surgery in patients. This study aimed to evaluate whether a multigene assay Curebest™ 95GC Breast (95GC) can identify the risk of recurrence and provide more insights into the requirements for chemotherapy in patients. METHODS: This single-arm retrospective multicenter joint study included patients with ER-positive, node-negative breast cancer who were treated at five facilities in Japan and had received endocrine therapy alone as adjuvant therapy. The primary lesion specimens obtained during surgery were analyzed using the 95GC breast cancer multigene assay. Based on the 95GC results, patients were classified into low-risk (95GC-L) and high-risk (95GC-H) groups. RESULTS: The 10-year relapse-free survival rates were 88.4 and 59.6% for the 95GC-L and 95GC-H groups, respectively. Histologic grade, Ki-67, and PAM50 exhibited a significant relationship with the 95GC results. The segregation into 95GC-L and 95GC-H groups within established clinical factors can identify subgroups of patients using histologic grade or PAM50 classification with good prognosis without receiving chemotherapy. CONCLUSIONS: Based on the results of our retrospective study, 95GC could be used to evaluate the long-term prognosis of ER-positive, node-negative breast cancer. Even though further prospective validation is necessary, the inclusion of 95GC in clinical practice could help to select optimal treatments for breast cancer patients and identify those who do not benefit from the addition of chemotherapy, thus avoiding unnecessary treatment.

Acorus calamus extract and its component α-asarone attenuate murine hippocampal neuronal cell death induced by l-glutamate and tunicamycin.

The Asian traditional medicinal plant Acorus calamus and its component α-asarone exhibited various biological activities, such as antiinflammation and antioxidant effects. In the present study, we investigated the in vitro effects of A. calamus extract and α-asarone on oxidative stress- and endoplasmic reticulum (ER) stress-induced cell death in hippocampal HT22 cells. A. calamus extract and α-asarone both significantly suppressed cell death induced by the oxidative stress inducer l-glutamate and ER stress inducer tunicamycin. A. calamus extract and α-asarone also significantly reduced reactive oxygen species (ROS) production induced by l-glutamate. Moreover, A. calamus extract and α-asarone suppressed the phosphorylation of protein kinase RNA-like ER kinase (PERK) induced by tunicamycin. These results suggest that A. calamus extract and α-asarone protect hippocampal cells from oxidative stress and ER stress by decreasing ROS production and suppressing PERK signaling, respectively. α-Asarone has potential as a potent therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease.

Multi-institutional survey of cancer disparities in disabled patients in the region of northwestern Japan.

BACKGROUND: Potential disparities between cancer patients with and without disabilities remained to be validate in Japan. METHODS: We surveyed retrospective data on hospital cancer registration as well as information on disability certificates obtained through the Hokushin Ganpro database. In total, 93,545 cancer patients in 10 principal hospitals covering the region of northwestern Japan were registered with the Hokushin Ganpro database between 2010 and 2015. The database included the following data: diagnosis date, cancer type, staging, treatment, cancer detection process, and possession of a disability certificate. RESULTS: We found that 2983 patients, which accounted for 3.2% of the total patients, had disabilities. No significant differences in gender, age at diagnosis, cancer stage distribution, and cancer incidence rates were observed between the disabled and non-disabled patients. Even though the proportion of early-stage cancer among disabled patients differed only slightly from that in non-disabled patients, early-stage cancer was more frequently diagnosed in patients with disabilities during their regular hospital visits than in those without disabilities, who had more opportunity for early cancer detection during cancer screening. According to in-house data reflecting treatment period and process from a single hospital, all 16 disabled patients treated with chemotherapy completed the treatment until disease progression or end of predetermined cycles. CONCLUSION: These results indicate that deep disparities between cancer patients with and without disabilities are not apparent and that the disabled patients in the region of northwestern Japan receive appropriate hospital follow-up.

Prognostic significance of neutrophil-to-lymphocyte ratio for long-term outcomes in patients with poorly differentiated thyroid cancer.

Poorly differentiated thyroid cancer (PDTC) is a distinct but rare type of thyroid cancer with intermediate biological behavior between differentiated and anaplastic thyroid cancers. PDTC was first defined in 2005 in Japan, but the diagnostic criteria changed in 2015, requiring the tumor to have more than 50% of poorly differentiated components for diagnosis. Because only six years have passed since the PDTC definition change, prognostic factors for long-term survival who meet the latest criteria have not been determined. Neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in various solid malignancies. However, its impact on PDTC remains unclear. This study aimed to evaluate the significance of NLR as a prognostic factor for patients with PDTC diagnosed based on the latest criteria. In total, 28 PDTC cases (4.4%) of 637 thyroid cancer patients who underwent surgery between 2002 and 2012 were retrospectively analyzed. The median follow-up period was 120 months (range, 7-216 months). Of the 13 deaths (46.4%), 9 patients (32.1%) died from PDTC. The median preoperative NLR was 2.7 (0.67-8.62), and the NLR cut-off value determined by the receiver operating characteristic curve was 2.88. Patients with a high NLR (>2.88) showed significantly worse disease-specific survival (hazard ratio [HR] 4.67, p = 0.036) and overall survival (HR 4.94, p = 0.007) than those with a low NLR (≤2.88). Multivariate analysis revealed that a high NLR independently predicted a worse prognosis (HR 6.06, p = 0.0087). In conclusion, NLR is a useful prognostic marker for patients with PDTC.

Effects of Deep Learning Reconstruction Technique in High-Resolution Non-contrast Magnetic Resonance Coronary Angiography at a 3-Tesla Machine.

PURPOSE: To evaluate the effects of deep learning reconstruction (DLR) in qualitative and quantitative image quality of non-contrast magnetic resonance coronary angiography (MRCA). METHODS: Ten healthy volunteers underwent conventional MRCA (C-MRCA) and high-resolution (HR) MRCA on a 3T magnetic resonance imaging with a voxel size of 1.8 × 1.1 × 1.7 mm3 and 1.8 × 0.6 × 1.0 mm3, respectively, for C-MRCA and HR-MRCA. High-resolution magnetic resonance coronary angiography was also reconstructed with the DLR technique (DLR-HR-MRCA). We compared the contrast-to-noise ratio (CNR) and visual evaluation scores for vessel sharpness and traceability of proximal and distal coronary vessels on a 4-point scale among 3 image series. RESULTS: The vascular CNR value on the C-MRCA and the DLR-HR-MRCA was significantly higher than that on the HR-MRCA in the proximal and distal coronary arteries (13.9 ± 6.4, 11.3 ± 4.4, and 7.8 ± 2.6 for C-MRCA, DLR-HR-MRCA, and HR-MRCA, P < .05, respectively). Mean visual evaluation scores for the vessel sharpness and traceability of proximal and distal coronary vessels were significantly higher on the HR-DLR-MRCA than the C-MRCA (P < .05, respectively). CONCLUSION: Deep learning reconstruction significantly improved the CNR of coronary arteries on HR-MRCA, resulting in both higher visual image quality and better vessel traceability compared with C-MRCA.

Online/offline self-disclosure to offline friends and relational outcomes in a diary study: The moderating role of self-esteem and relational closeness.

Previous work suggests that the experiences of online and offline self-disclosure are heterogeneous among individuals. Yet little work has been done to identify the moderating role of individual characteristics and pre-existing relationship characteristics on the diverse relational outcomes. The present study using a 7-day diary design examined whether individuals' self-esteem level and relational closeness would moderate the relationships between online and offline self-disclosure to offline friends and two relational outcomes, that is, relationship satisfaction and trust in friendships. The analyses on 686 diary responses from 98 participants revealed that offline self-disclosure generally predicted greater relationship satisfaction and trust in friendships, whereas the role of online self-disclosure was not statistically significant. More importantly, self-esteem moderated the pattern associated with offline self-disclosure but not that with online self-disclosure. Specifically, offline self-disclosure predicted greater benefits to people with lower self-esteem relative to people with higher self-esteem. Moreover, pre-existing relational closeness moderated the relationship between offline self-disclosure and trust in friendships such that casual friendships benefited more from offline self-disclosure than close friendships did. The present study highlights the importance of personal characteristics and relationship characteristics in understanding the heterogeneous relational influence of different communication modes.

Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer.

BACKGROUND: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). METHODS: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed. RESULTS: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042). CONCLUSIONS: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

Comparative efficacy and safety of tyrosine kinase inhibitors for thyroid cancer: a systematic review and meta-analysis.

The tyrosine kinase inhibitors (TKIs) sorafenib, lenvatinib, vandetanib, and cabozantinib are currently used for thyroid cancer treatment; however, the differences in their clinical efficacy and toxicity remain unclear. This meta-analysis assessed the efficacy and toxicity of these four TKIs based on 34 studies. The pooled incidence of partial response (PR), stable disease (SD), TKI-related adverse events (AEs), and pooled median progression-free survival (PFS) were calculated with 95% confidence intervals (CI). Complete response to TKIs was extremely rare (0.3%). The highest PR rate and longest PFS were observed for lenvatinib in differentiated thyroid cancer (69%, 95% CI: 57-81 and 19 months, 95% CI: 9-29, respectively) and vandetanib in medullary thyroid cancer (40%, 95% CI: 25-56 and 31 months, 95% CI: 19-43, respectively). Although the discontinuation rate due to AEs was similar for each TKI, there was a difference in the most frequently observed AE for each TKI (hand-foot syndrome for sorafenib, hypertension and proteinuria for lenvatinib, and QTc prolongation for vandetanib). The identified differences in the TKI efficacy and AE profiles may provide a better understanding of thyroid cancer treatment. Although TKIs are promising agents for thyroid cancer treatment, they are unlikely to lead to a cure. Thus, even in the TKI era, a multimodal treatment including surgery, radioiodine therapy, external beam radiotherapy, and TKIs is required to optimize patient chances of improved survival.

Where do you insert a drain tube during breast reconstruction?

PURPOSE: A drain tube is commonly inserted during breast reconstruction surgery. This leads to a scar in addition to the scar on the breast. This study was performed to investigate how patients feel about the drain scar and to clarify its ideal location. METHODS: A questionnaire survey about the drain scar was distributed to 38 consecutive breast reconstruction patients and a total of 104 female doctors and nurses engaged in breast reconstruction. The drain scars were evaluated using the Japan Scar Workshop (JSW) Scar Scale. RESULTS: A total of 32% of the patients expressed some anxiety about the drain scar. Patients who were anxious about the drain scar had higher scores on the JSW Scar Scale than those who were not anxious. Younger doctors and nurses preferred the drain scar to be on the side of the chest, while older doctors and nurses preferred the drain scars to be at the axilla. CONCLUSIONS: About a third of the patients had some anxiety associated with their drain scar after breast reconstruction surgery, and this anxiety level was correlated with objective assessment of the scar. Thus, more patient involvement or the provision of more information regarding drain placement is required.