Recurrence Pattern, Treatment Modalities, and Prognostic Factors After Definitive Chemoradiotherapy for Recurrent Esophageal Cancer.

BACKGROUND: Recurrent esophageal cancer (EC) has a poor prognosis. However, the recurrence patterns and therapeutic outcomes after definitive chemoradiotherapy (CRT) are not fully understood. We analyzed survival and prognostic factors associated with post-definitive CRT recurrent EC. METHODS: We retrospectively reviewed 71 consecutive patients with post-definitive CRT EC recurrence between 2008 and 2021 at our institution. Recurrence was locoregional, distant, and combined in 42 (59%), 18 (25%), and 11 (16%) patients, respectively. The median time from definitive CRT to recurrence was 8.3 months. Treatment modalities included local therapy, systemic therapy, and palliative care. Overall survival (OS) after recurrence was analyzed using the Kaplan-Meier and Cox proportional hazards models. RESULTS: The median follow-up time from recurrence was 7.1 months, and the median survival time (MST) was 12.5 months. In the univariate analysis, longer time to recurrence, earlier stage at initial treatment, surgical tolerance at initial diagnosis, treatment modalities, and oligo-recurrence were associated with a better prognosis. The MST of the local therapy, systemic therapy, and palliative care groups were not reached, 11.8 months and 4.1 months, respectively (P < 0.001). In the multivariate analysis, treatment modalities and oligo-recurrence emerged as independent prognostic factors (P < 0.001 and P = 0.009). CONCLUSIONS: Aggressive local therapy should be considered to improve the prognosis for patients with oligo-recurrence and/or indication of local therapy to treat recurrent EC.

Abscopal Effect after Stereotactic Body Radiotherapy with Nivolumab for Lung Metastasis of Head and Neck Cancer: A Case Report.

Introduction: The abscopal effect (AE) is a phenomenon, in which radiotherapy exerts an antitumour effect on distant lesions outside the primary irradiated area. Although immune checkpoint inhibitors have been widely studied for their potential to enhance the AE and improve patient outcomes, findings in cases of head and neck cancers remain limited. Case Presentation: We report the case of a 72-year-old man who experienced lung oligoprogression during nivolumab treatment for metastatic hypopharyngeal cancer. Stereotactic body radiotherapy (SBRT) was administered to one of the lung lesions, after which both irradiated and nonirradiated lesions regressed. Upon an 18-month follow-up period after SBRT, the patient showed no disease progression or toxicity, and continued receiving nivolumab therapy. Conclusion: The intent behind presenting this case report was to contribute to the accumulation of evidence regarding the AE in cases of head and neck cancer.

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

BACKGROUND/AIM: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy. PATIENTS AND METHODS: A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference. RESULTS: The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072). CONCLUSION: There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

Protein Kinase A Is Responsible for the Presynaptic Inhibition of Glycinergic and Glutamatergic Transmissions by Xenon in Rat Spinal Cord and Hippocampal CA3 Neurons.

The effects of a general anesthetic xenon (Xe) on spontaneous, miniature, electrically evoked synaptic transmissions were examined using the "synapse bouton preparation," with which we can clearly evaluate pure synaptic responses and accurately quantify pre- and postsynaptic transmissions. Glycinergic and glutamatergic transmissions were investigated in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xe presynaptically inhibited spontaneous glycinergic transmission, the effect of which was resistant to tetrodotoxin, Cd2+, extracellular Ca2+, thapsigargin (a selective sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor), SQ22536 (an adenylate cyclase inhibitor), 8-Br-cAMP (membrane-permeable cAMP analog), ZD7288 (an hyperpolarization-activated cyclic nucleotide-gated channel blocker), chelerythrine (a PKC inhibitor), and KN-93 (a CaMKII inhibitor) while being sensitive to PKA inhibitors (H-89, KT5720, and Rp-cAMPS). Moreover, Xe inhibited evoked glycinergic transmission, which was canceled by KT5720. Like glycinergic transmission, spontaneous and evoked glutamatergic transmissions were also inhibited by Xe in a KT5720-sensitive manner. Our results suggest that Xe decreases glycinergic and glutamatergic spontaneous and evoked transmissions at the presynaptic level in a PKA-dependent manner. These presynaptic responses are independent of Ca2+ dynamics. We conclude that PKA can be the main molecular target of Xe in the inhibitory effects on both inhibitory and excitatory neurotransmitter release. SIGNIFICANCE STATEMENT: Spontaneous and evoked glycinergic and glutamatergic transmissions were investigated using the whole-cell patch clamp technique in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xenon (Xe) significantly inhibited glycinergic and glutamatergic transmission presynaptically. As a signaling mechanism, protein kinase A was responsible for the inhibitory effects of Xe on both glycine and glutamate release. These results may help understand how Xe modulates neurotransmitter release and exerts its excellent anesthetic properties.

In vivo and in silico assessments of estrogenic potencies of bisphenol A and its analogs in zebrafish (Danio rerio): Validity of in silico approaches to predict in vivo effects.

This study assessed the estrogen-like potencies of bisphenol A (BPA) and its analogs (BPs) using in vivo and in silico approaches in zebrafish. Zebrafish embryos were exposed to 16 BPs, most of which concentration-dependently induced cytochrome P450 19A1b (CYP19A1b) expression. BPs-induced CYP19A1b expression was suppressed by fulvestrant, a nonselective high affinity antagonist for estrogen receptor (Esr) subtypes. For BPs that concentration-dependently induced CYP19A1b expression, we estimated their 50 % effective concentration (EC50) and relative potencies (REPs) with respect to the potency of BPA for inducing CYP19A1b expression. BP C2, Bis-MP, and BPAF showed lower EC50 than BPA, BPE, and BPF, while BPZ and BPB showed moderate EC50. The REP order of the BPs was BP C2 (26) > Bis-MP (24) > BPAF (21) > BPZ (5.8) > BPB (2.7) > BPE (1.5) > BPF (0.63) > 2,4'-BPF (0.22), indicating that some BPs showed greater estrogenic potencies than BPA in our system. We also constructed in silico homology models of ligand binding domains for zebrafish Esr subtypes, including Esr1, Esr2a, and Esr2b. Molecular docking simulations of ligands with the Esr subtypes revealed the interaction energies of some BPs were lower than that of BPA. The interaction energies showed significant positive correlations with their EC50 values for inducing CYP19A1b expression in vivo. This study showed that some BPA analogs have greater estrogenic potencies than BPA and that in silico simulations of interactions between ligands and Esr subtypes may help predict in vivo estrogenic potencies of untested chemicals.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.

Nintedanib-Induced Delayed Mucosal Healing after Adjuvant Radiation in a Case of Oropharyngeal Carcinoma.

Since the launch of imatinib in 2001, tyrosine kinase inhibitors are being used in chemotherapy for a wide range of malignant tumors. Drugs that inactivate multiple molecular mechanisms are called multikinase inhibitors (MKIs). Nintedanib is a type of MKI that inhibits downstream cascades in three systems: vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor inhibitions. It was initially developed as an anticancer drug for non-small-cell lung carcinoma; however, it was also found to inhibit the proliferation of fibroblasts associated with chronic inflammation in the lungs. Therefore, it is being more widely used to treat idiopathic pulmonary fibrosis, a benign disease, than as an antineoplastic agent. Several studies have reported adverse events associated with the concurrent use of MKIs with surgery or radiotherapy. Specifically, there has been a report cautioning against delayed wound healing associated with the use of nintedanib in patients undergoing surgery. However, there is no specific mention of its concurrent use during irradiation. We describe a case of a 72-year-old man with severely delayed recovery from radiation mucositis when nintedanib was being administered for benign disease.

Radiation Myelopathy Caused by Palliative Radiotherapy and Intrathecal Methotrexate.

Radiation myelopathy is a rare, late-stage adverse event that develops following irradiation at or above 50 Gy. Here, we report a case of irreversible paraplegia caused by palliative radiation (20 Gy in 5 fractions) to the spinal cord combined with intrathecal methotrexate (IT-MTX). A 69-year-old man presented with back pain, prompting a diagnosis of acute myeloid leukemia. At the first visit, he complained of muscle weakness and hypoesthesia in both legs; spinal magnetic resonance imaging (MRI) revealed an epidural mass compressing the spinal cord at the fifth to seventh level of the thoracic vertebrae. This was considered to be an extramedullary lesion of leukemia, and he received remission induction therapy including IT-MTX; palliative radiation (20 Gy in 5 fractions) of the epidural mass was initiated the following day. Then, during the course of consolidation therapy, a second IT-MTX was performed after 1 month and a third after 3 months. While the consolidation therapy was complete, yielding remission, he developed sudden paraplegia, as well as bladder and bowel dysfunction (BBD), 10 months later. Spinal MRI showed extensive intramedullary high signal intensity on T2-weighted image, including the irradiation field. It was thought myelopathy was due to irradiation of the spinal cord combined with IT-MTX. He immediately received steroid pulse therapy; however, the paraplegia and BBD did not improve. It is extremely rare for irreversible radiation myelopathy to occur with IT-MTX and palliative radiation to the spinal cord. We believe that even with low-dose palliative radiation, caution is required for combined use with IT-MTX.

Ureteral reimplantation during augmentation cystoplasty is not needed for vesicoureteral reflux in patients with neurogenic bladder: a long-term retrospective study.

BACKGROUND: To investigate the need for ureteral reimplantation for vesicoureteral reflux (VUR) during augmentation cystoplasty (AC) in the long term. METHODS: A total of 19 patients with a median age at surgery of 14 years (3-38 years) who underwent AC for neurogenic bladder with VUR between 1983 and 2016 were included in this study. The changes in VUR grade and urodynamic findings were retrospectively evaluated. We evaluated the renal function by periodic inspection of serum creatinine level and estimated glomerular filtration rate; eGFR. RESULTS: The median follow-up period from AC was 14.8 years (5.7-30 years). VUR was detected in 19 patients, involving 27 ureters. Reflux grade was V in 6, IV in 9, III in 5, II in 6, and I in 1. Ureteral reimplantation was not performed in 18 patients (26 ureters), whereas it was done for 1 patient (1 ureter) in the early era of our experience. Postoperative videourodynamics showed that the reflux was radiologically not verifiable in 23 ureters (85%), was downgraded in 3 ureters (11%), and was unchanged in 1 ureter (3%). There were no cases of deterioration of VUR. CONCLUSIONS: Ureteral reimplantation is not necessary for VUR during augmentation cystoplasty.

Association of exposure to prenatal perfluoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children: The Hokkaido study.

Per- and Polyfluoroalkyl substances (PFAS) have endocrine-disrupting effects. The ratio of the lengths of the second and fourth digits (2D:4D) is a noninvasive retrospective index of prenatal exposure to sex hormones, and estrogen receptor 1 (ESR1) polymorphisms may contribute to 2D:4D determination. We investigated whether ESR1 polymorphisms modify the effects of prenatal PFAS exposure on 2D:4D. Participants (n = 1024) with complete data in a prospective birth cohort study (the Hokkaido Study) were included, and maternal plasma in the third trimester was used to examine PFAS concentrations. 2D:4D was determined from photocopies of palms of children using Vernier calipers. ESR1 polymorphisms (rs2234693, rs9340799, and rs2077647) were genotyped by TaqMan polymerase chain reaction. PFAS and 2D:4D association with ESR1 polymorphisms was assessed by multiple linear regression adjusted for potential confounding factors. A 10-fold increase in maternal perfluorooctanoic acid (PFOA) concentration was associated with a 1.54% [95% confidence interval (CI): 0.40, 2.68] increase in mean 2D:4D in children with an AA genotype at rs9340799 and a 2.24% (95% CI: 0.57, 3.92) increase in children with an AA genotype at rs2077647. A 10-fold increase in perfluorododecanoic acid (PFDoDA) was associated with a significant increase in 2D:4D in children with the AA genotype [rs9340799, 1.18% (95% CI: 0.02, 2.34); and rs2077647, 1.67% (95% CI: 0.05, 3.28)]. These associations were apparent among males. A significant gene-environment interaction between PFOA or PFDoDA and ESR1 polymorphism was detected. These findings suggest that ESR1 polymorphisms modify the effects of prenatal exposure to PFAS on sex differentiation.

Palliative Radiotherapy Provided Good Pain Relief for Painful Adrenal Metastasis.

Adrenal metastases often occur in patients with metastasized lung cancer, but symptoms rarely develop. A 45-year-old man presented with right abdominal pain requiring strong opioids due to large right adrenal metastasis of lung adenocarcinoma. The tumor was 7.3 × 5.6 × 8.4 cm in size. He was treated with palliative radiotherapy (RT) up to 39 Gy in 13 fractions for this lesion without severe adverse effects. After RT, he had good pain relief, and opioids were no longer needed. Palliative RT for a large adrenal tumor can provide a good analgesic effect without relevant toxicity.

Girls and renal scarring as risk factors for febrile urinary tract infection after stopping antibiotic prophylaxis in children with vesicoureteral reflux.

PURPOSE: To clarify the incidence of and risk factors for febrile urinary tract infection in children with persistent vesicoureteral reflux (VUR) after the discontinuation of continuous antibiotic prophylaxis (CAP), retrospective chart review was performed. PATIENTS AND METHODS: Among children with primary VUR at 10 years of age or younger at presentation, those who had persistent VUR despite conservative management with CAP and who were subsequently followed after discontinuation of CAP were included. Kaplan-Meier curve and Cox's proportional hazard regression model were used for evaluation of the incidence of and risk factors for febrile urinary tract infection (fUTI) after stopping CAP. RESULTS: Among 144 children (99 boys and 45 girls), fUTI developed in 34. The 5-year fUTI-free rate after discontinuation of CAP was 69.4%. On multivariate analyses, girls (p = 0.008) and abnormalities on nuclear renal scans (p = 0.0019), especially focal defect (p = 0.0471), were significant factors for fUTI. Although the fUTI-free rate was not different between children who had no or 1 risk factor, it was significantly lower in children with 2 risk factors than in those with no or 1 risk factor. CONCLUSIONS: The present study revealed that girls and abnormal renal scan, especially focal defect, are risk factors for fUTI. Active surveillance without CAP for persistent VUR seems to be a safe option for children with no or 1 risk factor. Prophylactic surgery or careful conservative follow-up may be an option for girls with abnormal renal scan results if VUR persists under CAP.

Serotonin in the rat prefrontal cortex controls the micturition reflex through 5-hydroxytryptamine 2A and 5-hydroxytryptamine 7 receptors.

OBJECTIVES: To identify the types of serotonin (5-hydroxytryptamine) receptors of the prefrontal cortex related to the micturition reflex. METHODS: Female Sprague-Dawley rats and a microinjection method were used for this study. Stainless steel guide cannulas were implanted bilaterally into the prefrontal cortex, and a polyethylene catheter was inserted into the bladder. Cystometric parameters (intercontraction interval and maximum voiding pressure) were measured before and after injection of any one of six specific antagonists of 5-hydroxytriptamine receptors (5-hydroxytryptamine 1A, 5-hydroxytryptamine 2A, 5-hydroxytryptamine 2C, 5-hydroxytryptamine 3, 5-hydroxytryptamine 4 and 5-hydroxytryptamine 7) into the prefrontal cortex. The prefrontal cortex was divided into two regions, namely the prelimbic cortex and the infralimbic cortex. The experiments were carried out in conscious and free-moving rats. RESULTS: The intercontraction interval value increased significantly after injection of the 5-hydroxytriptamine 2A receptor antagonist, MDL11939, into the prelimbic cortex of the rat prefrontal cortex (7.68 ± 1.28 vs 9.02 ± 1.41 min, P < 0.05), whereas the intercontraction interval value decreased significantly after injection of the 5-hydroxytriptamine 7 antagonist SB269970 into the prelimbic cortex (9.42 ± 0.39 vs 8.14 ± 0.71 min, P < 0.05). The intercontraction interval was unaffected by injection of either of these two antagonists into the infralimbic cortex. The other four antagonists (5-hydroxytryptamine 1A, 5-hydroxytryptamine 2C, 5-hydroxytryptamine 3 and 5-hydroxytryptamine 4) had no effect on the intercontraction interval after injection into the prelimbic cortex and the infralimbic cortex. The maximum voiding pressure was unaffected by injection of any one of the six 5-hydroxytriptamine antagonists into the prelimbic cortex and infralimbic cortex. CONCLUSIONS: In the rat prefrontal cortex5-hydroxytryptamine 2A receptors excite the micturition reflex, whereas 5-hydroxytryptamine 7 receptors inhibit this reflex.

Association of exposure to prenatal phthalate esters and bisphenol A and polymorphisms in the ESR1 gene with the second to fourth digit ratio in school-aged children: Data from the Hokkaido study.

Phthalates and bisphenol A (BPA) are estrogenic endocrine disruptors. Polymorphisms in the gene encoding estrogen receptor 1 (ESR1) may contribute to the ratio of the lengths of the second and fourth digits (2D:4D), which is considered an index of prenatal exposure to sex hormones. Thus, we investigated whether ESR1 polymorphisms modify the effects of prenatal exposure to phthalates and BPA on 2D:4D in a birth cohort. Maternal serum in the first trimester was used to determine prenatal exposure to these compounds. Six hundred twenty-three children (7 years of age) provided mean 2D:4D from photocopies and were genotyped for single nucleotide polymorphisms in ESR1, particularly PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The associations among compound exposure, mean 2D:4D, and ESR1 polymorphisms were assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the AG/GG genotype at rs2077647 in the group exposed to high levels of mono(2-ethylhexyl) phthalate (MEHP) or Σ Di(2-ethylhexyl) phthalate (DEHP) showed feminized 2D:4D compared with boys with the AA genotype at rs2077647 who had low exposure to MEHP or ΣDEHP (MEHP: increase in mean 2D:4D of 1.51%, 95% confidence interval [CI]: 0.40-2.63; ΣDEHP: increase in mean 2D:4D of 1.37%, 95% CI: 0.25-2.49). No significant differences were found among girls. There were no associations between mean 2D:4D and metabolites other than MEHP or BPA. These data suggest that ESR1 polymorphisms modify the effects of prenatal exposure to DEHP on mean 2D:4D among boys.

[PUBERTAL TESTICULAR TORSION OF POLYORCHIDISM DIAGNOSED IN INFANCY: A CASE REPORT].

Left polyorchidism was found in a 2-month-old boy with a left scrotal mass. As he was asymptomatic and all testes were in the scrotum, he was conservatively followed up. At 17 years of age, he presented with left acute scrotum due to testicular torsion of the left supernumerary testis. Counterclockwise 720-degree rotation of the left supernumerary testis was noted during emergency surgery, and orchidopexy of the 3 testes (2 left testes and 1 right testis) was performed. Biopsy of the left supernumerary testis demonstrated spermatogenesis and no malignancy. One and a half years after surgery, all testes were viable without atrophy.Polyorchidism is a rare condition and there is no consensus on the management of asymptomatic cases detected early in life. The position of the supernumerary testis (intrascrotal or extrascrotal) is important when deciding the management strategy because of the risk of malignancy. If conservative management is selected initially, elective surgery, such as prophylactic orchiectomy or orchidopexy, may be needed because of the risk of malignancy and torsion.

Therapeutic Potential of AAV1-Rheb(S16H) Transduction Against Alzheimer's Disease.

We recently reported that adeno-associated virus serotype 1-constitutively active Ras homolog enriched in brain [AAV1-Rheb(S16H)] transduction of hippocampal neurons could induce neuron-astroglia interactions in the rat hippocampus in vivo, resulting in neuroprotection. However, it remains uncertain whether AAV1-Rheb(S16H) transduction induces neurotrophic effects and preserves the cognitive memory in an animal model of Alzheimer's disease (AD) with characteristic phenotypic features, such as ß-amyloid (Aß) accumulation and cognitive impairments. To assess the therapeutic potential of Rheb(S16H) in AD, we have examined the beneficial effects of AAV1-Rheb(S16H) administration in the 5XFAD mouse model. Rheb(S16H) transduction of hippocampal neurons in the 5XFAD mice increased the levels of neurotrophic signaling molecules, including brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), and their corresponding receptors, tropomyosin receptor kinase B (TrkB) and CNTF receptor α subunit (CNTFRα), respectively. In addition, Rheb(S16H) transduction inhibited Aß production and accumulation in the hippocampus of 5XFAD mice and protected the decline of long-term potentiation (LTP), resulting in the prevention of cognitive impairments, which was demonstrated using novel object recognition testing. These results indicate that Rheb(S16H) transduction of hippocampal neurons may have therapeutic potential in AD by inhibiting Aß accumulation and preserving LTP associated with cognitive memory.

Laparoscopic nephroureterectomy using the stoma site of cutaneous ureterostomy as a multi-channel port site in a 15-month-old child with megaureter: A case report.

He was born with markedly dilated left megaureter. Since it disturbed his oral intake after birth, left temporary cutaneous ureterostomy was created at 3 days of age. Since his left kidney was dysplastic, laparoscopic left nephroureterectomy was performed using the stoma site of cutaneous ureterostomy as a multi-channel port site at 15 months of age. He had no complications after surgery, and the postoperative wound appearance was good. This is the first report of the stoma site being used as a multi-channel port site in the urology field. This surgical approach provides good cosmetic outcomes.

Risk factors affecting post-pubertal high serum follicle-stimulating hormone in patients with hypospadias.

PURPOSE: The factors affecting spermatogenesis in adulthood in patients with hypospadias (HS) are not clearly understood. In the present study, risk factors affecting post-pubertal high serum follicle-stimulating hormone (FSH) were evaluated in patients with HS. MATERIALS AND METHODS: Among those with a history of HS surgery, patients in whom endocrinological evaluation regarding pituitary-gonadal axis was performed at 15 years of age or older between March 2004 and April 2018 were enrolled in the present study. High serum FSH was defined as greater than 10 mIU/ml. The severity of HS was divided into mild and severe. Factors affecting the post-pubertal high serum FSH were estimated. RESULTS: Seventy-nine patients were included in the present study. The severity of HS was mild in 35 and severe in 44. History of undescended testis (UDT) was confirmed in 12. High serum FSH was detected in nine. On logistic regression model analysis, a history of UDT was the only significant factor for high serum FSH. The incidence of high serum FSH in patients with UDT was significantly higher than that in those without UDT (58.3% vs 7.5%, p < 0.01). When stratified by severity of HS and the presence of UDT, high serum FSH was detected in 70% in patients with severe HS and UDT, whereas less than 10% in other groups. CONCLUSIONS: A history of UDT was a significant factor for post-pubertal high serum FSH in patients with HS. Accordingly, the presence of UDT may be a marker for impaired spermatogenesis in patients with HS, especially in severe cases.

[Home Palliative Care Setting at a Mixed-Type Clinic-What Is Necessary for Comfort of Patient, Family and Medical Person].

"Comfort set for palliative care"is narrowly defined as a set of drugs used to alleviate symptoms at the terminal stage. However, we think that the followingis important(1)The practice of advance care planning(ACP)is indispensable and it is done accordingto the situation after the start of the visit, but our clinic emphasizes careful consultation before the start as a means of team formation with the patient's family and the doctor.(2)Introduction of visitingmedicine management by pharmacist of dispensingpharmacy is preferable for the method of supply/inventory of drugs. 98% of cancer patients in our clinic use it. In addition, we have injection drugs, devices and emergency drugs in the clinic so that we can respond quickly.(3) Seamless collaboration with visitingnursingis necessary for understandingand implementingthe situation that medicines should be used. All cancer patients in our clinic are receivingvisitingnursingby in-clinic nurses. We mentioned the point that seems to be important points in past practice for "comfort of patient, family member and medical staff" in home palliative care.

Association between ESR1 polymorphisms and second to fourth digit ratio in school-aged children in the Hokkaido Study.

The ratio of the lengths of the 2nd and 4th digits (2D:4D) is considered an index of prenatal exposure to androgen. Indeed, androgen receptors have been linked to digit length, but estrogen receptors are rarely investigated in this context. Thus, we investigated the association between estrogen receptor 1 (ESR1) genetic polymorphisms and 2D:4D in school-aged children. The 2D:4D ratios were determined using Vernier calipers from photocopies of palms provided by 1800 children aged 7 years who were enrolled in an ongoing prospective cohort study in Hokkaido, Japan. The children were genotyped using cord blood collected at birth for single nucleotide polymorphisms in ESR1, specifically PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The association between ESR1 polymorphisms and 2D:4D was assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the GG genotype at rs9340799 had a significantly lower 2D:4D in the right hand than boys with the AA/AG genotype (-0.96% lower, 95% confidence interval: -1.68 to -0.24). However, this association was detected only in boys born to non-smoking mothers. No significant differences were found between rs9340799 polymorphisms and 2D:4D among girls. There was also no link between 2D:4D and polymorphisms at rs2234693 and rs2077647. These data suggest that rs9340799 polymorphisms in ESR1 may contribute to digit length and 2D:4D.