Effects of diphenhydramine exposure on reproduction of mature Japanese medaka (Oryzias latipes).

Diphenhydramine (DPH) is an antihistamine drug. It has been frequently detected in the environment, because it is not completely degraded in wastewater treatment plants. Recent studies have shown the adverse effects of DPH exposure to various aquatic organisms; however, its chronic effects on fish have been poorly elucidated. In this study, several pairs of mature Japanese medaka (Oryzias latipes) were exposed to DPH for a long period to determine the effects of DPH exposure on the subsequent generations, number of spawned and fertilized eggs, expression of sex-related genes, feeding behavior, embryo development, hatching rate, malformations among the hatched larvae, and mortality rate. The number of spawned eggs significantly decreased, when the parent fish were continuously exposed to 31.6 µg/L DPH for over 46 days. DPH exposure also altered the feeding behavior of medaka individuals, and increased the larval mortality rate. The effects of DPH exposure to fish may occur to some extent in the actual aquatic environment, although the risk evaluations in the field are limited.

Prevalence of Poor Sleep Quality and its Association with Lifestyle Habits, Competition-Based Activities, and Psychological Distress in Japanese Student-Athletes During the COVID-19 Pandemic.

Objectives The present study clarified the prevalence of poor sleep quality and its relation to lifestyle habits, competitive-based activities, and psychological distress among Japanese student-athletes in the initial pandemic period (2020) and 1 year later (2021). Methods In the present study, student-athletes were defined as individuals belonging to university athletic clubs. The data of two cross-sectional surveys (2020: n = 961 and 2021: n = 711) were collected from student-athletes in 6 universities in Japan. First, the prevalence of poor sleep quality (Pittsburgh sleep quality index score > 5) was investigated. Relationships between poor sleep quality and lifestyle habits, competition-based activities, and psychological distress were then explored using multivariate logistic regression analysis adjusted for age, sex, and body mass index. Results The prevalence of poor sleep quality was 33.6% in 2020 and 36.6% in 2021. Poor sleep quality in 2020 was related to late bedtime, taking supplements before bed, part-time job (no late night), stressors of expectations and pressure from others, and psychological distress, whereas that in 2021 was related to early wake-up time, skipping breakfast, taking caffeinated drinks before bed, use of smartphone/cellphone after lights out, stressors of motivation loss, and psychological distress. Conclusions In both 2020 and 2021, one-third of student-athletes had poor sleep quality and psychological distress was its common risk factor. Lifestyle habits and competition stressors associated with poor sleep quality were pandemic-specific in 2020, but similar to the prepandemic period in 2021.

A novel QTL associated with tolerance to cold-induced seed cracking in the soybean cultivar Toyomizuki.

Low temperatures after flowering cause seed cracking (SC) in soybean. Previously, we reported that proanthocyanidin accumulation on the dorsal side of the seed coat, controlled by the I locus, may lead to cracked seeds; and that homozygous IcIc alleles at the I locus confer SC tolerance in the line Toiku 248. To discover new genes related to SC tolerance, we evaluated the physical and genetic mechanisms of SC tolerance in the cultivar Toyomizuki (genotype II). Histological and texture analyses of the seed coat revealed that the ability to maintain hardness and flexibility under low temperature, regardless of proanthocyanidin accumulation in the dorsal seed coat, contributes to SC tolerance in Toyomizuki. This indicated that the SC tolerance mechanism differed between Toyomizuki and Toiku 248. A quantitative trait loci (QTL) analysis of recombinant inbred lines revealed a new, stable QTL related to SC tolerance. The relationship between this new QTL, designated as qCS8-2, and SC tolerance was confirmed in residual heterozygous lines. The distance between qCS8-2 and the previously identified QTL qCS8-1, which is likely the Ic allele, was estimated to be 2-3 Mb, so it will be possible to pyramid these regions to develop new cultivars with increased SC tolerance.

[Paclitaxel plus Bevacizumab Combination Therapy for Esophageal Metastasis of Breast Cancer-A Case Report].

An 80-year-old woman with a history of left breast cancer complained of dysphagia. At the age of 67 years, she had undergone a left modified radical mastectomy, chemotherapy, and endocrine therapy for left breast cancer. Six years after adjuvant therapy completion, she developed dysphagia. Chest CT showed only midesophageal stenosis. Endoscopic examination revealed whole circumferential stenosis without mucosal abnormality located 25 cm from the incisors, and a biopsy showed histologically normal mucosa. Endoscopic balloon dilatation was performed 5 times in 1 year and 3 months. Subsequently, a biopsy specimen revealed adenocarcinoma, which suggested metastasis from the previous breast cancer. One month after the initiation of tamoxifen administration, dyspnea due to pleural effusion was encountered. We treated this via pleural adhesion therapy and changed the treatment to paclitaxel plus bevacizumab combination therapy. She continued paclitaxel plus bevacizumab therapy for 1 year and 4 months without any signs of recurrence.

[A Case of Intraductal Apocrine Carcinoma of the Breast].

A female in her 60s who complained of nipple discharge in her left breast for 1 year. A soft mass ill-defined margin in the border of AB area was observed. Mammography showed a focal asymmetric density. Ultrasonography disclosed an irregular heterogenous low echoic lesion in the AB area of her left breast. MRI image showed an enhanced lesion in the inner area. The pathological diagnosis by core needle biopsy was non-invasive ductal carcinoma with apocrine metaplasia. Mastectomy with sentinel lymph node biopsy of the left breast was performed. Post operative histopathological examination revealed intraductal apocrine carcinoma without lymph node metastasis. Estrogen and progesterone receptors were negative. Three years after operation without any adjuvant treatment, she has no recurrence of lesion.

[A Case of Metastatic Pancreatic Ductal Adenocarcinoma Successfully Treated with Modified FOLFIRINOX and Concurrent Radiotherapy].

A 70-year-old man with metastatic pancreatic ductal adenocarcinoma(cT4N1bM1, cStage Ⅳ)underwent chemotherapy with modified FOLFIRINOX without any severe adverse event to 20 cycles. In the middle of that, concurrent irradiation toward primary lesion(total dose, 43.2 Gy)was administered. Grade 1 adverse events include anemia, thrombocytopenia, hypoalbuminemia, hypokalemia, alkaline phosphatase increased, hypertension, peripheral sensory neuropathy, fatigue, anorexia and nausea. The relative dose intensities of oxaliplatin, irinotecan and fluorouracil at 6 months after beginning of treatment were 77.6, 84.0 and 88.3 percent, respectively. The total dose of administered oxaliplatin was 825 mg to the square meter. The primary lesion had been stable for the 20 cycles, although peritoneal dissemination had progressively increased in size. For 17 months, opioid was not necessary for the control of abdominal or back pain to the end of third-line treatment. Though safety or clinical benefits of modified FOLFIRINOX plus concurrent radiotherapy for metastatic pancreatic ductal adenocarcinoma have not been reported, in this case, such treatment might contribute to prolong prognosis or prevent developing abdominal or back pain.

[Two Cases of Stage â £ Occult Breast Cancer].

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.

[A Case of Breast Metastasis of Gastric Cancer after an Eight Year Latency Period].

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.

[Incidence of Catheter-Related Thrombosis in Patients with Long-Term Indwelling Central Venous Port Who Received Chemotherapies for Unresectable Advanced Digestive Cancers].

BACKGROUND: Most patients with unresectable advanced digestive cancers require placement of a fully implantable venous access port to facilitate safe delivery of anti-cancer drugs. Anti-VEGF therapies are commonly used even though they increase the risk of thrombosis. The objective of this study was to assess the incidence of radiologically confirmed catheter-related thrombosis(CRT)in patients with advanced digestive cancers. METHODS: We retrospectively reviewed 88 patients with advanced digestive cancers who had adapted implantable ports placed in our institution for chemotherapy. RESULTS: Thirty-nine patients were diagnosed with colorectal cancer, 26 with gastric cancer, 12 with pancreatic cancer, 8 with esophageal cancer, and 3 with other cancers. During follow-up, 22 patients(25%)received anti-VEGF therapies, while 66 patients(75%)did not. Four out of 88 patients(4.5%)had asymptomatic CRT. The incidence of CRT was the same(4.5%)regardless of whether the patient received anti-VEGF therapy. CONCLUSIONS: In patients with digestive cancers who had implantable venous access ports, the incidence of the CRT was 4.5% with no association with anti-VEGF therapies.

[A Case of Long-Term Survival after Para-Aortic Lymph Node Recurrence Following the Curative Resection of Gastric Cancer Treated Using Multimodality Therapy Including Salvage Surgery].

This case was observed in a man in his 70s. Although symptomatic treatment was performed for epigastralgia, endoscopic examination revealed a type 3 tumor on the fornix of the stomach to the lesser curvature of the body just above the esophagogastric junction, and the patient was diagnosed with moderately differentiated tubular adenocarcinoma(cT4bN3aM0, cStage ⅣA). As esophageal and diaphragmatic invasion was suspected based on CT findings, S-1 plus CDDP was started as preoperative chemotherapy. Although the primary lesion and lymph node metastasis decreased in size, chemotherapy was discontinued after one course due to stenosis symptoms, and total gastrectomy and D2 dissection were performed. Postoperative adjuvant chemotherapy with S-1 was started. However, 6 months after starting the treatment, para-aortic lymph node recurrence was observed, and the treatment strategy was changed to weekly PTX. After 5 courses of weekly PTX, the lymph nodes continued to increase in size, and chemotherapy was discontinued per the patient's request. The patient was followed up with CT and PET-CT; however, no new recurrent lesions were found in other sites for approximately 1 year. Therefore, para-aortic lymph node dissection was performed as the salvage surgery. Pathological findings showed that gastric cancer metastasis was present in 1 swollen lymph node only, as confirmed by PET. At present, 6 years have passed since the first operation, and there has been no recurrence. In general, para-aortic lymph node metastasis is considered to result in poor prognosis in gastric cancer. However, in the absence of other noncurative factors, a good prognosis may be obtained with combined therapeutic modalities.

Cetuximab retreatment in patients with metastatic colorectal cancer who exhibited a clinical benefit in response to prior cetuximab: A retrospective study.

Clinical benefits of cetuximab retreatment in patients with metastatic colorectal (mCRC) have been reported. In the present study, the effect of cetuximab retreatment on predictive markers was investigated by evaluating the clinical benefit of initial cetuximab treatment prior to cetuximab retreatment. Between November 2012 and March 2017, 14 patients with KRAS proto-oncogene GTPase exon 2 wild-type mCRC who exhibited a clinical benefit (confirmed stable disease for at least 6 months or a clinical response) to an initial cetuximab-based regimen, who received multiple lines of chemotherapy following disease progression and ultimately received a second cetuximab and irinotecan regimen, were retrospectively analyzed. For retreatment, patients received bi-weekly irinotecan (120-150 mg/m2) combined with cetuximab (400 mg/m2 as an initial dose, followed by 250 mg/m2, weekly). The median age of the 14 patients (11 males, 3 females) was 68 years (32-77). The median progression-free survival (PFS) following prior cetuximab-based therapy was 6.6 months (range, 4.1-18.4). Initial cetuximab treatment was administered as a first-line treatment in 11 patients, a second-line treatment in 1 patient and a third-line treatment in 2 patients. The median interval time between the last cycle of initial cetuximab-based therapy and the first cycle of cetuximab retreatment was 13.1 months (range, 6.0-37.1). The objective response rate of cetuximab retreatment was 21.4% and the median PFS was 4.4 months (95% confidence interval, 1.4-5.6). The Spearman's correlation coefficient for the PFS following retreatment and duration of initial cetuximab-based regimens demonstrated a more marked correlation compared with that between the PFS following retreatment and the interval time between the two regimens (r=0.45, P=0.11 vs. r=0.08, P=0.79). Cetuximab retreatment may provide clinical benefit to patients with mCRC who were good responders with longer periods of initial cetuximab-based therapy.

Occurrence and tolerance mechanisms of seed cracking under low temperatures in soybean (Glycine max).

MAIN CONCLUSION: In soybean, occurrence of, or tolerance to, seed cracking under low temperatures may be related to the presence or absence, respectively, of proanthocyanidin accumulation in the seed coat dorsal region. Soybean seeds sometimes undergo cracking during low temperatures in summer. In this study, we focused on the occurrence and tolerance mechanisms of low-temperature-induced seed cracking in the sensitive yellow soybean cultivar Yukihomare and the tolerant yellow soybean breeding line Toiku 248. Yukihomare exhibited seed cracking when subjected to a 21-day low-temperature treatment from 10 days after flowering. In yellow soybeans, seed coat pigmentation is inhibited, leading to low proanthocyanidin levels in the seed coat. Proanthocyanidins accumulated on the dorsal side of the seed coat in Yukihomare under the 21-day low-temperature treatment. In addition, a straight seed coat split occurred on the dorsal side at the full-sized seed stage, resulting in seed cracking in this cultivar. Conversely, proanthocyanidin accumulation was suppressed throughout the seed coat in low-temperature-treated Toiku 248. We propose the following mechanism of seed cracking: proanthocyanidin accumulation and subsequent lignin deposition under low temperatures affects the physical properties of the seed coat, making it more prone to splitting. Further analyses uncovered differences in the physical properties of the seed coat between Yukihomare and Toiku 248. In particular, seed coat hardness decreased in Yukihomare, but not in Toiku 248, under the low-temperature treatment. Seed coat flexibility was higher in Toiku 248 than in Yukihomare under the low-temperature treatment, suggesting that the seed coat of low-temperature-treated Toiku 248 is more flexible than that of low-temperature-treated Yukihomare. These physical properties of the Toiku 248 seed coat observed under low-temperature conditions may contribute to its seed-cracking tolerance.

[A Case of Primary Spinddle Cell Carcinoma of the Breast].

A 76-year-old female underwent breast-conserving surgery of the right breast and sentinel lymph node biopsy for primary breast cancer. Three years later, mammography and ultrasonography showed a small nodule in the right breast. There was nothing abnormal in the left breast. Three months later, she complained of a huge and rapid growing mass in the left breast. Malignant cells were obtained on fine needle aspiration biopsy in the right breast tumor. But it was not possible to diagnose whether the left breast tumor was benign or malignant on fine needle aspiration biopsy and needle biopsy. Bilateral mastectomy and sentinel lymph node biopsy of the right side were performed. Pathological diagnosis were squamous cell carcinoma of the right breast and spindle cell carcinoma of the left breast. Although the patient was treated with adjuvant chemotherapy, she had an early relapse with pleural, lung and bone metastases. The patient died approximately 8 months after operation. Spindle cell carcinoma presents many problems about therapy and prognosis. Further accumulation analysis is necessary.

Accumulation of proanthocyanidins and/or lignin deposition in buff-pigmented soybean seed coats may lead to frequent defective cracking.

MAIN CONCLUSION: Defective cracking frequently occurs in buff-pigmented soybean seed coats, where proanthocyanidins accumulate and lignin is deposited, suggesting that proanthocyanidins and/or lignin may change physical properties and lead to defective cracking. In the seed production of many yellow soybean (Glycine max) cultivars, very low percentages of self-pigmented seeds are commonly found. This phenomenon is derived from a recessive mutation of the I gene inhibiting seed coat pigmentation. In Japan, most of these self-pigmented seeds are buff-colored, and frequently show multiple defective cracks in the seed coat. However, it is not known why cracking occurs specifically in buff seed coats. In this study, quantitative analysis was performed between yellow and buff soybean seed coats. Compared with yellow soybeans, in which defective cracking rarely occurs, contents of proanthocyanidins (PAs) and lignin were significantly higher in buff seed coats. Histochemical data of PAs and lignin in the seed coats strongly supported this result. Measurements of the physical properties of seed coats using a texture analyzer showed that a hardness value was significantly decreased in the buff seed coats. These results suggest that PA accumulation and/or lignin deposition may affect the physical properties of buff seed coats and lead to the defective cracking. This work contributes to understanding of the mechanism of defective cracking, which decreases the seed quality of soybean and related legumes.

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

BACKGROUND: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. PATIENTS AND METHODS: Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. RESULTS: Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). CONCLUSION: A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

Optimal cut-off value of alanine aminotransferase level to precisely estimate the presence of fatty liver in patients with poorly controlled type 2 diabetes.

Optimal cut-off value of ALT level to precisely estimate the presence of fatty liver was as low as 28.0 U/L. We should consider the possibility of fatty liver even when ALT level is within normal range in subjects with poorly controlled type 2 diabetes.

[A Case of Primary Acinic Cell Carcinoma(ACC)of the Breast].

A49 -year-old woman presented with a 3.5 cm mass in her right breast. Mammography revealed a lobular mass with poorly defined margins and no microcalcification. Ultrasonography showed a hypoechoic mass with an irregular margin. The tumor was diagnosed as breast carcinoma using a core needle biopsy. The patient underwent a modified radical mastectomy with sentinel lymph node biopsy, and received adjuvant chemotherapy. The tumor consisted of 2 types of carcinoma. The center of the tumor was solid-tubular carcinoma, and the periphery was acinic cell carcinoma(ACC). Histopathologically, the neoplastic cells of the periphery were characterized by widespread acinic cell-like differentiation with a eosinophilic granular or clear cytoplasm, resembling acinic cells of the parotid gland(t3, f[+], ly0, v0, n0, stage II B). Immunohistochemically, the specimens tested positive for salivary gland amylase, and negative for collagen type IV , ER, PgR, and HER2. We administered UFT as adjuvant chemotherapy. Eight months after surgery, local recurrence was observed. ACC of the breast is rare, and has been reported to have a good prognosis. Further investigations are needed to elucidate its true histogenesis the appropriate treatment.

[A Case of Mediastinal Dissection by Video-Assisted Thoracoscopic Surgery (VATS)in a Patient with Mediastinal Nodal Recurrence from Thyroid Carcinoma after Primary Surgery via Median Sternotomy].

A70 's male was diagnosed with advanced papillary thyroid carcinoma and underwent total thyroidectomy with left lymph node dissection(T4a, N1b, M0, stage IV A). Six years after the surgery, subclavicular and mediastinal lymph node recurrence was observed. Radioiodine therapy was not successful for those lesions. Lymph node dissection was performed via the cervical and transsternal approaches. One year after the second surgery, cervical and mediastinal lymph node recurrence was again observed. We removed the cervical lymph nodes via the cervical approach. One month after cervical dissection, we removed the mediastinal lymph nodes via video-assisted thoracoscopic surgery(VATS). The lymph nodes were relatively easily dissected by VATS under excellent surgical views. Repeat mediastinal dissection via median sternotomy could be associated with significant complications. VATS is expected to reduce the risk of reoperation and enhance surgical outcomes.

[A Case of Minimal Thyroid Carcinoma Diagnosed by a Solitary Pulmonary Metastasis].

We report a case of minimal thyroid carcinoma diagnosed by a solitary pulmonary metastasis. A 70's man visited a medical practitioner because of chest discomfort, and there was an abnormality on the chest X-ray. Chest computed tomography(CT) showed a nodule in the right middle lobe of the lung. Positron emission tomography with 18-fluorodeoxyglucose(FDG)-PET revealed increased FDG uptake in that tumor, but did not reveal any other lesion. The tumor was clinically suspected to be a carcinoid tumor, primary lung cancer, metastatic lung cancer, or a benign tumor. Right middle lobe lobectomy was performed, and the tumor was diagnosed as a metastasis from a thyroid papillary carcinoma by pathological diagnosis during surgery. After surgery, we found a tumor in the left lobe of the thyroid by CT and US. Because the patient did not desire 131I therapy, he underwent a left hemithyroidectomy and neck dissection. There was a papillary carcinoma 1.0 cm in the thyroid gland and there were 3 cervical lymph node metastases. There has been no recurrence for 11 years after surgery.

[Repair of a huge Bochdalek hernia by direct suture and mesh reconstruction].

A 72-year-old man presented with complaints of sudden abdominal pain and vomiting. After a thorough examination, the patient was diagnosed with a left-sided Bochdalek hernia with strangulation of the stomach and spleen. The impaction was cleared by drainage of the stomach contents by a nasogastric tube;then, surgical repair through thoracic approach was performed. The herinia port size was large, and the defect of diaphragm was successfully repaired by both direct closure and mesh reconstruction.