Preoperative Neutrophil-to-Lymphocyte Ratio in Postmenopausal Breast Cancer Patients.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a marker of systemic inflammation with a prognostic impact in patients with various cancers, including breast cancer. The aim of this study was to investigate the relationships between the preoperative NLR and breast cancer prognosis in the patients before and after menopausal age, and its relationship with other prognostic factors. METHODS: A total of 1868 patients with clinical Stage I-III primary breast cancer were enrolled. The associations between clinicopathological factors and the preoperative NLR were analyzed, and relapse-free survival (RFS) and overall survival (OS) were estimated. RESULTS: Statistical analyses stratified by the menopausal status revealed that a high NLR was significantly associated with worse RFS (P < 0.001) and OS (P = 0.001) in postmenopausal patients, but not in premenopausal patients. Although the postmenopausal patients with relapsed cancer tended to have higher NLR levels than those without relapse (P = 0.079), NLR levels of premenopausal patients with relapsed cancer were significantly lower than that of relapse-free patients (P = 0.024). In postmenopausal patients, a high NLR was only associated with worse RFS in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (P < 0.001), in those managed without adjuvant chemotherapy (P = 0.003); this association was not observed in patients who received adjuvant chemotherapy. CONCLUSIONS: The preoperative NLR can be a useful prognostic marker, especially in postmenopausal breast cancer patients. The relationships between the NLR and breast cancer prognosis may be more evident when patients are assessed according to their menopausal status.

Extracellular aaRSs drive autoimmune and inflammatory responses in rheumatoid arthritis via the release of cytokines and PAD4.

OBJECTIVES: Recent studies demonstrate that extracellular-released aminoacyl-tRNA synthetases (aaRSs) play unique roles in immune responses and diseases. This study aimed to understand the role of extracellular aaRSs in the pathogenesis of rheumatoid arthritis (RA). METHODS: Primary macrophages and fibroblast-like synoviocytes were cultured with aaRSs. aaRS-induced cytokine production including IL-6 and TNF-α was detected by ELISA. Transcriptomic features of aaRS-stimulated macrophages were examined using RNA-sequencing. Serum and synovial fluid (SF) aaRS levels in patients with RA were assessed using ELISA. Peptidyl arginine deiminase (PAD) 4 release from macrophages stimulated with aaRSs was detected by ELISA. Citrullination of aaRSs by themselves was examined by immunoprecipitation and western blotting. Furthermore, aaRS inhibitory peptides were used for inhibition of arthritis in two mouse RA models, collagen-induced arthritis and collagen antibody-induced arthritis. RESULTS: All 20 aaRSs functioned as alarmin; they induced pro-inflammatory cytokines through the CD14-MD2-TLR4 axis. Stimulation of macrophages with aaRSs displayed persistent innate inflammatory responses. Serum and SF levels of many aaRSs increased in patients with RA compared with control subjects. Furthermore, aaRSs released PAD4 from living macrophages, leading to their citrullination. We demonstrate that aaRS inhibitory peptides suppress cytokine production and PAD4 release by aaRSs and alleviate arthritic symptoms in a mouse RA model. CONCLUSIONS: Our findings uncovered the significant role of aaRSs as a novel alarmin in RA pathogenesis, indicating that their blocking agents are potent antirheumatic drugs.

PPG2EMG: Estimating Upper-Arm Muscle Activities and EMG from Wrist PPG Values.

The electromyogram (EMG) is a waveform representation of the action potential generated by muscle cells using electrodes. EMG acquired using surface electrodes is called surface EMG (sEMG), and it is the acquisition of muscle action potentials transmitted by volume conduction from the skin. Surface electrodes require disposable conductive gel or adhesive tape to be attached to the skin, which is costly to run, and the tape is hard on the skin when it is removed. Muscle activity can be evaluated by acquiring muscle potentials and analyzing quantitative, temporal, and frequency factors. It is also possible to evaluate muscle fatigue because the frequency of the EMG becomes lower as the muscle becomes fatigued. Research on human activity recognition from EMG signals has been actively conducted and applied to systems that support arm and hand functions. This paper proposes a method for recognizing the muscle activity state of the arm using pulse wave data (PPG: Photoplethysmography) and a method for estimating EMG using pulse wave data. This paper assumes that the PPG sensor is worn on the user's wrist to measure the heart rate. The user also attaches an elastic band to the upper arm, and when the user exerts a force on the arm, the muscles of the upper arm contract. The arteries are then constricted, and the pulse wave measured at the wrist becomes weak. From the change in the pulse wave, the muscle activity of the arm can be recognized and the number of action potentials of the muscle can be estimated. From the evaluation experiment with five subjects, three types of muscle activity were recognized with 80+%, and EMG was estimated with approximately 20% error rate.

Physical Noninvasive Attacks on Photoplethysmogram by Computer Controlled Blood Pressure Cuff.

Sensor data has been used in social security and welfare infrastructures such as insurance and medical care to provide personalized products and services; there is a risk that attackers can alter sensor data to obtain unfair benefits. We consider that one of the attack methods to modify sensor data is to attack the wearer's body to modify biometric information. In this study, we propose a noninvasive attack method to modify the sensor value of a photoplethysmogram. The proposed method can disappear pulse wave peaks by pressurizing the upper arm with air pressure to control blood volume. Seven subjects experiencing a rest environment and five subjects experiencing an after-exercise environment wore five different models of smartwatches, and three pressure patterns were performed. It was confirmed in both situations that the displayed heart rate decreased from the true heart rate.

Exercise-Induced Adrenocorticotropic Hormone Response Is Cooperatively Regulated by Hypothalamic Arginine Vasopressin and Corticotrophin-Releasing Hormone.

INTRODUCTION: Exercise becomes a stress when performed at an intensity above the lactate threshold (LT) because at that point the plasma adrenocorticotropic hormone (ACTH), a marker of stress response, increases. It is possible that the exercise-induced ACTH response is regulated at least by arginine vasopressin (AVP) and possibly by corticotropin-releasing hormone (CRH), but this remains unclear. To clarify the involvement of these factors, it is useful to intervene pharmacologically in the regulatory mechanisms, with a physiologically acceptable exercise model. METHODS: We used a special stress model of treadmill running (aerobic exercise) for male Wistar rats, which mimic the human physiological response, where plasma ACTH levels increase at just above the LT for 30 min. Animals were administered the AVP V1b receptor antagonist SSR149415 (SSR) and/or the CRH type 1 receptor antagonist CP154526 (CP) intraperitoneally before the exercise, which allowed the monitoring of exercise-induced ACTH response. Immunohistochemical evaluation of activated AVP and CRH neurons with exercise was performed for the animals' hypothalami. RESULTS: A single injection of either antagonist, SSR or CP, resulted in inhibited ACTH levels after exercise stress. Moreover, the combined injection of SSR and CP strongly suppressed ACTH secretion during treadmill running to a greater extent than each alone. The running-exercise-induced activation of both AVP and CRH neurons in the hypothalamus was also confirmed. CONCLUSION: These results lead us to hypothesize that AVP and CRH are cooperatively involved in exercise-induced ACTH response just above the LT. This may also reflect the stress response with moderate-intensity exercise in humans.

High-intensity Intermittent Training Enhances Spatial Memory and Hippocampal Neurogenesis Associated with BDNF Signaling in Rats.

High-intensity intermittent (or interval) training (HIIT) has started to gain popularity as a time-effective approach to providing beneficial effects to the brain and to peripheral organs. However, it still remains uncertain whether HIIT enhances hippocampal functions in terms of neurogenesis and spatial memory due to unconsidered HIIT protocol for rodents. Here, we established the HIIT regimen for rats with reference to human study. Adult male Wistar rats were assigned randomly to Control, moderate-intensity continuous training (MICT; 20 m/min, 30 min/day, 5 times/week), and HIIT (60 m/min, 10 30-s bouts of exercise, interspaced with 2.5 min of recovery, 5 times/week) groups. The ratios of exercise time and volume between MICT and HIIT were set as 6:1 and 2:1-4:1, respectively. After 4 weeks of training, all-out time in the incremental exercise test was prolonged for exercise training. In skeletal muscle, the plantaris citrate synthase activity significantly increased only in the HIIT group. Simultaneously, both HIIT and MICT led to enhanced spatial memory and adult hippocampal neurogenesis (AHN) as well as enhanced protein levels of hippocampal brain-derived neurotrophic factor (BDNF) signaling. Collectively, we suggest that HIIT could be a time-efficient exercise protocol that enhances hippocampal memory and neurogenesis in rats and is associated with hippocampal BDNF signaling.

[Comparative Safety Study of Original and Generic Docetaxel without Alcohol in the Treatment of Breast Cancer].

Docetaxel(DTX)is a key drug for breast cancer treatment; however, its formulation contains alcohol, which can cause several problems. We have been preparing original DTX without using its accompanying alcohol-solubilizing solution since 2013 and switched to generic DTX without alcohol in 2015. In this study, we compared adverse events between the original and generic DTX, both of which did not contain alcohol. We retrospectively investigated the occurrence of adverse events in breast cancer patients who were treated with DTX(75 mg/m2)as neoadjuvant or adjuvant chemotherapy from January 2013 to December 2017. 201 patients participated in the study(75/126 in the original/generic groups). The incidence of febrile neutropenia, hypersensitivity reactions, and skin toxicities did not differ between the groups(p=0.620, 0.066, 0.205). The severity of edema and peripheral neuropathy was significantly worse in the patients receiving the generic DTX (p<0.01, <0.01). The findings suggest a difference in the incidence of edema and peripheral neuropathy following treatment with the original and generic DTX, regardless of the inclusion of alcohol.

Preventive role of regular low-intensity exercise during adolescence in schizophrenia model mice with abnormal behaviors.

Schizophrenia is probably ascribed to perinatal neurodevelopmental deficits, and its onset might be affected by environmental factors. Hypofrontality with glutamatergic and dopaminergic neuronal dysfunction are known factors, but a way to mitigate abnormalities remains unfound. An early enriched environment such as a wheel running in rodents may contribute to the prevention, but its clinical applicability is very limited. From our studies, low-intensity exercise training (LET) based on physiological indices, such as lactate threshold, easily translates to humans and positively affects the brains. Hence, LET during adolescence may ameliorate abnormalities in neurodevelopment and prevent the development of schizophrenia. In the current study, LET prevented sensitization to phencyclidine (PCP) treatment, impairment of cognition, and affective behavioral abnormalities in an animal model of schizophrenia induced by prenatal PCP treatment. Further, LET increased dopamine turnover and attenuated the impairment of phosphorylation of ERK1/2 after exposure to a novel object in the prenatal PCP-treated mice. These results suggest that LET during adolescence completely improves schizophrenia-like abnormal behaviors associated with improved glutamate uptake and the dopamine-induced ERK1/2 signaling pathway in the PFC.

Sympathetic ophthalmia after 27-G pars plana vitrectomy.

BACKGROUND: Sympathetic ophthalmia (SO) is a bilateral diffuse uveitis that can arise after ocular trauma or ocular surgery in the inciting eye. Pars plana vitrectomy (PPV) is one of the risk factors for SO. Several reports have described SO developing after 23- and 25-G PPV, but none have described SO occurring after 27-G PPV. We describe herein a case of SO after 27-G PPV for rhegmatogenous retinal detachment. CASE PRESENTATION: A 42-year-old woman presented with visual disturbance in the right eye. Best-corrected visual acuity (BCVA) was 6/200 in the right eye. Fundus examination revealed off-macula retinal detachment with retinal tears at both ends of retinal lattice degeneration at the temporal-oven peripheral retina of the right eye. We therefore performed 27-G sutureless PPV on the right eye. After 12 days, the retina was reattached, and BCVA improved to 6/30 in the right eye. Fifteen days postoperatively, she experienced headache and reduced vision in both eyes. Symptoms gradually worsened, and she visited our hospital 21 days postoperatively. BCVA was 6/30 in the right eye and 6/15 in the left eye. Slit-lamp examination revealed uveitis in the anterior chambers of both eyes, and fundus examination showed papillitis and subretinal detachment at the posterior poles of both eyes. Optical coherence tomography revealed subretinal fluid in the maculae of both eyes and fluorescein angiography showed multiple hyperfluorescent leakage sites in the retinal pigment epithelium. Cerebrospinal fluid examination showed pleocytosis and human leukocyte antigen testing showed expression of the DR04 phenotype; therefore, the patient was diagnosed with SO. She was treated with steroid therapy, and her visual disturbance subsided and the subretinal fluid improved as well. Her BCVA was 6/15 for the right eye and 6/5 for the left eye 93 days after the initial surgery. CONCLUSION: The present case shows that even if the sclerotomy site of 27-G PPV is small, there is still a risk of SO occurring in the eyes of patients who underwent transconjunctival vitrectomy. Ophthalmologists should recognize SO as complication of 27-G PPV and carry out proper management as early as possible.

Electrophysiological insights into the relationship between calcium dynamics and cardiomyocyte beating function in chronic hemodialysis treatment.

For patients in which the Ca2+ concentration of dialysis fluid is lower than that in plasma, chronic hemodialysis treatment often leads to cardiac beating dysfunction. By applying these conditions to an electrophysiological mathematical model, we evaluated the impact of body fluid Ca2+ dynamics during treatment on cardiomyocyte beating and, moreover, explored measures that may prevent cardiomyocyte beating dysfunction. First, Ca2+ concentrations in both plasma and interstitial fluid were decreased with treatment time, which induced both a slight decline in beating rhythm on a sinoatrial nodal cell and a wane in contraction force on a ventricular cell. These simulated results were in agreement with clinical observations. Next, a relationship between the intracellular Ca2+ concentration and ion current dynamics of ion transporters were examined to elucidate the mechanism underlying cardiomyocyte beating dysfunction. The inward current of the Na/Ca exchanger (NCX) increased with a decrease in Ca2+ concentration in interstitial fluid and induced a reduction in intracellular Ca2+ concentration during treatment. Furthermore, the decline in intracellular Ca2+ concentration reduced the contraction force. These findings implied that ion transport through the NCX is a dominant factor that induces cardiomyocyte beating dysfunction during hemodialysis. Finally, the replenishment of Ca2+ or application of an NCX inhibitor during treatment suppressed the decrease in intracellular Ca2+ concentration and contributed to the stabilization of cardiomyocyte beating function. In summary, the clinical implementation of hepatically cleared NCX inhibitor may be a suitable approach to improving the quality of life for patients on chronic hemodialysis.

Case of primary intraocular lymphoproliferative disorder caused by Epstein-Barr Virus.

BACKGROUND: Cases of panuveitis caused by Epstein-Barr virus (EBV) associated with primary intraocular lymphoproliferative disorder (LPD) are rare in immunocompetent individuals. CASE PRESENTATION: A 67-year-old man noted blurred vision in both eyes and was referred to our hospital. His best-corrected visual acuity (BCVA) was 20/20 in both eyes. He had mild inflammation in the anterior chamber but not in the vitreous of both eyes. The inflammation was resolved with topical corticosteroid but 10 months later both eyes presented recurrence. Treatment with a sub-Tenon's injection of steroid was effective for OS but not for OD and 2 months after, the inflammation in the anterior chamber and vitreous opacities got worsen in OD and BCVA decreased to 6/20 OD. Thus, pars plana vitrectomy was performed on OD, and EBV was detected in the aqueous humor by multiplex polymerase chain reaction, and an infiltration of CD19κ positive B cells was revealed in the vitreous specimens by flow cytometry. Systemic workup revealed no other sites of lymphoproliferation, no active EBV infection, or underlying immunodeficiency. CONCLUSION: Panuveitis caused by EBV associated with primary intraocular LPD can occur in patients with no history of congenital or acquired immunodeficiencies.

The Motor Network Reduces Multisensory Illusory Perception.

Observing mouth movements has strikingly effects on the perception of speech. Any mismatch between sound and mouth movements will result in listeners perceiving illusory consonants (McGurk effect), whereas matching mouth movements assist with the correct recognition of speech sounds. Recent neuroimaging studies have yielded evidence that the motor areas are involved in speech processing, yet their contributions to multisensory illusion remain unclear. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in an event-related design, we aimed to identify the functional roles of the motor network in the occurrence of multisensory illusion in female and male brains. fMRI showed bilateral activation of the inferior frontal gyrus (IFG) in audiovisually incongruent trials. Activity in the left IFG was negatively correlated with occurrence of the McGurk effect. The effective connectivity between the left IFG and the bilateral precentral gyri was stronger in incongruent than in congruent trials. The McGurk effect was reduced in incongruent trials by applying single-pulse TMS to motor cortex (M1) lip areas, indicating that TMS facilitates the left IFG-precentral motor network to reduce the McGurk effect. TMS of the M1 lip areas was effective in reducing the McGurk effect within the specific temporal range from 100 ms before to 200 ms after the auditory onset, and TMS of the M1 foot area did not influence the McGurk effect, suggesting topographical specificity. These results provide direct evidence that the motor network makes specific temporal and topographical contributions to the processing of multisensory integration of speech to avoid illusion.SIGNIFICANCE STATEMENT The human motor network, including the inferior frontal gyrus and primary motor cortex lip area, appears to be involved in speech perception, but the functional contribution to the McGurk effect is unknown. Functional magnetic resonance imaging revealed that activity in these areas of the motor network increased when the audiovisual stimuli were incongruent, and that the increased activity was negatively correlated with perception of the McGurk effect. Furthermore, applying transcranial magnetic stimulation to the motor areas reduced the McGurk effect. These two observations provide evidence that the motor network contributes to the avoidance of multisensory illusory perception.

Effects of intravitreal injection of ranibizumab on choroidal structure and blood flow in eyes with diabetic macular edema.

PURPOSE: To determine the effects of an intravitreal injection of ranibizumab (IVR) on the choroidal structure and blood flow in eyes with diabetic macular edema (DME). METHODS: Twenty-eight consecutive patients with DME who received an IVR and 20 non-diabetic, age-matched controls were followed for 1 month. The eyes with DME were divided into those with prior panretinal photocoagulation (PRP, n = 16) and those without prior PRP (no-PRP, n = 12). The enhanced depth imaging optical coherence tomography (EDI-OCT) scans and Niblack's image binarization were performed to determine the choroidal structure. The choroidal blood flow was determined by laser speckle flowgraphy. RESULTS: The subfoveal choroidal thickness at the baseline was significantly thicker in the no-PRP group than in the PRP-treated group. After IVR, the best-corrected visual acuity (BCVA) and central retinal thickness in eyes with DME were significantly improved compared to the baseline values. There were significant differences in the choroidal thickness, total choroidal area, and choroidal vascularity index between the groups after IVR. Choroidal vascular index and choroidal blood flow were significantly reduced only in the no-PRP group and not in the PRP-treated group. In addition, the correlation between the central retinal thickness and the choroidal blood flow was significant in the no-PRP group (r = 0.47, P < 0.05). CONCLUSIONS: A single IVR will reduce the central retinal thickness and improve the BCVA in eyes with DME in both the no-PRP and PRP-treated group. IVR affected the choroidal vasculature and blood flow significantly, and a significant correlation was found between the central retinal thickness and the choroidal blood flow in eyes without PRP.

CHOROIDAL BLOOD FLOW AND THICKNESS AS PREDICTORS FOR RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To determine the choroidal blood flow and subfoveal choroidal thickness (SCT) in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). METHODS: Thirty-two eyes of 32 patients with macular edema secondary to a BRVO were treated with a single intravitreal injection of ranibizumab (IVR) and were followed for 2 months. The central retinal thickness and SCT, and the retinal and choroidal blood flows were evaluated, and they were compared between the recurrent and resolved groups. RESULTS: At the baseline, the SCT of eyes with a BRVO was significantly thicker than that of the fellow eye (P < 0.01). It was also significantly thicker in the recurrent group than in the resolved group (P = 0.03). The reduction of the retinal blood flow was found only after 1 week in the resolved group. The SCT and choroidal blood flow were significantly reduced during the follow-up period in the resolved group but not in the recurrent group. CONCLUSION: The choroid is involved in the pathology of BRVO and the SCT at the baseline may be a predictive factor in the treatment of intravitreal injection of ranibizumab for macular edema secondary to BRVO.

Association Between Optic Nerve Head Blood Flow Measured Using Laser Speckle Flowgraphy and Radial Arterial Pressure During Aortic Arch Surgery.

OBJECTIVE: This study was designed to investigate the association between ocular blood flow measured using laser speckle flowgraphy (LSFG) and radial arterial pressure during aortic arch surgery. DESIGN: A prospective study. SETTING: A single university hospital. PARTICIPANTS: This study included 24 patients undergoing aortic arch surgery with cardiopulmonary bypass (CPB) using antegrade selective cerebral perfusion (SCP). INTERVENTIONS: Measurement of optic nerve head blood flow using LSFG and radial arterial pressure via a catheter in the radial artery METHODS AND MAIN RESULTS: Antegrade SCP was managed with 24℃ and 40-to-60 mmHg at the right radial artery, which usually corresponds to a flow rate of 10 mL/kg/min. Optic nerve head blood flow using LSFG and radial arterial blood pressure were evaluated simultaneously at the right side and recorded at the following 4 points: after the induction of anesthesia (phase 1), after the beginning of CPB (phase 2), after the beginning of antegrade SCP (phase 3), and after cessation of CPB (phase 4). A moderate positive correlation between %change of mean blur rate in the optic nerve head measured using LSFG and %change of radial mean arterial pressure was identified (r = 0.604, p < 0.001). Bland-Altman analysis showed that the bias (mean difference) was -1.2% (95% limits of agreement -47.4% to 45.0%), indicating good agreement between %changes of the values recorded using the 2 measurements. CONCLUSIONS: Intraoperative monitoring of optic nerve head blood flow using LSFG can be used as an additional cerebral perfusion parameter during aortic arch surgery with CPB using antegrade SCP.

Moderate exercise ameliorates dysregulated hippocampal glycometabolism and memory function in a rat model of type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is likely to be an independent risk factor for hippocampal-based memory dysfunction, although this complication has yet to be investigated in detail. As dysregulated glycometabolism in peripheral tissues is a key symptom of type 2 diabetes, it is hypothesised that diabetes-mediated memory dysfunction is also caused by hippocampal glycometabolic dysfunction. If so, such dysfunction should also be ameliorated with moderate exercise by normalising hippocampal glycometabolism, since 4 weeks of moderate exercise enhances memory function and local hippocampal glycogen levels in normal animals. METHODS: The hippocampal glycometabolism in OLETF rats (model of human type 2 diabetes) was assessed and, subsequently, the effects of exercise on memory function and hippocampal glycometabolism were investigated. RESULTS: OLETF rats, which have memory dysfunction, exhibited higher levels of glycogen in the hippocampus than did control rats, and breakdown of hippocampal glycogen with a single bout of exercise remained unimpaired. However, OLETF rats expressed lower levels of hippocampal monocarboxylate transporter 2 (MCT2, a transporter for lactate to neurons). Four weeks of moderate exercise improved spatial memory accompanied by further increase in hippocampal glycogen levels and restoration of MCT2 expression independent of neurotrophic factor and clinical symptoms in OLETF rats. CONCLUSIONS/INTERPRETATION: Our findings are the first to describe detailed profiles of glycometabolism in the type 2 diabetic hippocampus and to show that 4 weeks of moderate exercise improves memory dysfunction in type 2 diabetes via amelioration of dysregulated hippocampal glycometabolism. Dysregulated hippocampal lactate-transport-related glycometabolism is a possible aetiology of type-2-diabetes-mediated memory dysfunction.

Final report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japan.

BACKGROUND: The impact of oral capecitabine as adjuvant chemotherapy for Japanese patients with resected colon cancer was unclear. We previously planned and conducted a prospective feasibility study (KSCC0803) and reported on the safety of oral capecitabine as adjuvant chemotherapy for Japanese patients with resected stage III colon cancer. The purpose of the current study was to assess the survival results from that study. METHODS: The study subjects were Japanese patients with resected stage III colon cancer. The protocol adjuvant regimen consisted of oral capecitabine 1250 mg/m2 twice daily on days 1-14 of a 3-week cycle for a total of eight cycles. The 3- and 5-year disease free survival (DFS) rates and overall survival (OS) rates were analyzed in the eligible cohort. RESULTS: Ninety-seven patients were registered between September 2008 and August 2009 and treated with the protocol regimen. The median follow-up time was 60.7 months. The 3- and 5-year DFS rates were 71.2% [95% confidence interval (CI): 61.7-79.8%] and 69.7% (95% CI: 59.4-77.8%), respectively. The 3- and 5-year OS rates were 92.6% (95% CI: 85.2-96.4%) and 84.5% (95% CI: 75.1-90.5%), respectively. CONCLUSIONS: The survival results in this study are in line with those of previously reported, reliable, studies. The safety and tolerability of the protocol regimen have already been confirmed. Oral capecitabine is acceptable as adjuvant chemotherapy for Japanese patients with resected stage III colon cancer.

Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction of Tongue Cancer: A Case Report.

Breast cancers are the most common cancers in women. However, breast cancer occurring in a pectoralis major myocutaneous flap is extremely rare. This article describes a case of breast cancer occurring in such a flap used for reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a fine-needle aspiration biopsy specimen taken from the lesion suggested glandular carcinoma. The patient was diagnosed with breast cancer in the neck area of the flap and tumor excision was performed. Histologic examination of the excised tumor showed tumor cells arranged in cords, with tubular and cribriform carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to the neck with a total radiation dose of 50 Gy. Furthermore, the patient received oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor-positive breast malignancy. One year after surgery, the patient was alive with no evidence of disease. Including this case, only 2 cases of breast cancer in a pectoralis major myocutaneous flap used for reconstruction in the head and neck region have been reported.

L-Serine Deficiency Elicits Intracellular Accumulation of Cytotoxic Deoxysphingolipids and Lipid Body Formation.

L-serine is required to synthesize membrane lipids such as phosphatidylserine and sphingolipids. Nevertheless, it remains largely unknown how a diminished capacity to synthesize L-serine affects lipid homeostasis in cells and tissues. Here, we show that deprivation of external L-serine leads to the generation of 1-deoxysphingolipids (doxSLs), including 1-deoxysphinganine, in mouse embryonic fibroblasts (KO-MEFs) lacking D-3-phosphoglycerate dehydrogenase (Phgdh), which catalyzes the first step in the de novo synthesis of L-serine. A novel mass spectrometry-based lipidomic approach demonstrated that 1-deoxydihydroceramide was the most abundant species of doxSLs accumulated in L-serine-deprived KO-MEFs. Among normal sphingolipid species in KO-MEFs, levels of sphinganine, dihydroceramide, ceramide, and hexosylceramide were significantly reduced after deprivation of external L-serine, whereas those of sphingomyelin, sphingosine, and sphingosine 1-phosphate were retained. The synthesis of doxSLs was suppressed by supplementing the culture medium with L-serine but was potentiated by increasing the ratio of L-alanine to L-serine in the medium. Unlike with L-serine, depriving cells of external L-leucine did not promote the occurrence of doxSLs. Consistent with results obtained from KO-MEFs, brain-specific deletion of Phgdh in mice also resulted in accumulation of doxSLs in the brain. Furthermore, L-serine-deprived KO-MEFs exhibited increased formation of cytosolic lipid bodies containing doxSLs and other sphingolipids. These in vitro and in vivo studies indicate that doxSLs are generated in the presence of a high ratio of L-alanine to L-serine in cells and tissues lacking Phgdh, and de novo synthesis of L-serine is necessary to maintain normal sphingolipid homeostasis when the external supply of this amino acid is limited.

EFFECTS OF PANRETINAL PHOTOCOAGULATION ON CHOROIDAL THICKNESS AND CHOROIDAL BLOOD FLOW IN PATIENTS WITH SEVERE NONPROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the choroidal thickness and choroidal blood flow in the subfoveal region quantitatively after panretinal photocoagulation (PRP) in eyes with severe nonproliferative diabetic retinopathy. METHODS: This was a prospective comparative study of 24 eyes of 24 patients with type II diabetes and severe nonproliferative diabetic retinopathy with no macula edema. The foveal retinal thickness and choroidal thickness were measured by enhanced depth imaging optical coherence tomography. The subfoveal choroidal blood flow was represented by the mean blur rate obtained by laser speckle flowgraphy. The intraocular pressure, blood pressure, pulse rate, and hemoglobin A1c level (HbA1c) were also measured before and after PRP. RESULTS: The mean foveal retinal thickness did not change significantly during the follow-up period. The mean subfoveal choroidal thickness was reduced significantly from 327.4 µm at the baseline to 286.3 µm at 1 month and 285.0 µm at 3 months after PRP. The mean blur rate ratio decreased significantly to 87.5% at 1 month and 86.0% at 3 months of the baseline values. There was a significant correlation between the subfoveal choroidal thickness and subfoveal choroidal blood flow after PRP. After PRP, the best-corrected visual acuity, intraocular pressure, mean arterial pressure, ocular perfusion pressure, pulse rate, and HbA1c did not change significantly. CONCLUSION: The success of PRP in treating eyes with severe nonproliferative diabetic retinopathy is probably due to the significant reduction of the subfoveal choroidal thickness and subfoveal choroidal blood flow after PRP.