Long-term clinical outcome after endoscopic resection of esophageal squamous cell carcinoma invading the muscularis mucosae without lymphovascular invasion.

BACKGROUND AND AIMS: Lymph node recurrence (LNR) after endoscopic resection (ER) in patients with esophageal squamous cell carcinoma (ESCC) pathologically invading the muscularis mucosae (pMM) without lymphovascular invasion (LVI) has been reported as non-negligible in the ER guidelines for esophageal cancer by the Japan Gastroenterological Endoscopy Society. However, these data were not regarded as high-level evidence because several retrospective case series were tabulated without sufficient long-term follow-up. Hence, this guideline stated that the administration of additional treatment after ER could not be determined for this population. This study aimed to clarify the long-term clinical outcomes after ER of pMM ESCC without LVI. METHODS: Between January 2009 and November 2017, we enrolled followed patients who underwent ER and were diagnosed with pMM ESCC without LVI with no additional treatments. We retrospectively investigated the cumulative recurrence rate and recurrence-free, overall, and disease-specific survival at 5 years after ER. RESULTS: Eighty-seven patients were enrolled. During the median follow-up period of 64 months (range, 12-117), 3 patients developed lymph node and/or distant recurrence, and 2 of these cases occurred more than 3 years after ER; all 3 patients died of the primary disease. The 5-year cumulative recurrence rate was 4.3%, and the 5-year recurrence-free, disease-specific, and overall survival rates were 88.8%, 98.2%, and 91.7%, respectively. CONCLUSIONS: The long-term outcome for patients with pMM ESCC without LVI was favorable after ER; however, this population had a risk of recurrence directly leading to death. Long-term follow-up is necessary, with attention to the timing of recurrence.

The safety and feasibility of endoscopic submucosal dissection using a flexible three-dimensional endoscope for early gastric cancer and superficial esophageal cancer: A prospective observational study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is performed as one of standard treatments for patients with early gastric cancer (EGC) and superficial esophageal squamous cancer (SESCC). A prototype of a flexible endoscope with a 3-D system has been recently developed. This study aimed to investigate the safety and feasibility of ESD using a 3-D flexible endoscope (3-D ESD) for EGC and SESCC. METHODS: This single-center, prospective, observational study enrolled patients who underwent planned 3-D ESD. The clinical outcomes, including the incidence of adverse events and treatment results, were analyzed. Visibility and manipulation during 3-D ESD were evaluated using a visual analog scale (VAS). We also evaluated the effect of the 3-D system on the endoscopist using VAS and the critical flicker fusion frequency (CFFF). RESULTS: We analyzed 47 EGC and 20 SESCC cases. There are no bleeding cases that required transfusion and perforation during 3-D ESD in both EGC and SESCC patients. However, the incidence of delayed bleeding and delayed perforation was 1.5% (one case) each. The mean VAS scores for recognizing the submucosal layer during the submucosal dissection, visual perception of blood vessel, and depth perception were 72.7 ± 22.2, 74.7 ± 21.8, and 78.2 ± 19.9, respectively. In contrast, the mean VAS score for manipulation was 25.4 ± 19.7. Among endoscopists, there was no significant difference in the VAS of eyestrain and headache before and after ESD, and there was no significant difference in the CFFF. CONCLUSION: The safety and feasibility of 3-D ESD for EGC and SESCC are acceptable in both patients and endoscopists.

Efficacy and safety of second photodynamic therapy for local failure after salvage photodynamic therapy for esophageal cancer.

OBJECTIVES: Photodynamic therapy (PDT) is an optional salvage treatment for local failure of esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy; however, local failure after PDT sometimes occurs. In such cases, second PDT is sometimes attempted, but its outcomes remain unclear. This study aimed to evaluate the efficacy and safety of second PDT. METHODS: We enrolled patients who underwent PDT for local failure of ESCC after chemoradiotherapy. We retrospectively evaluated local-complete response (L-CR) rate and clinical outcomes of first and second PDT. The indications for PDT were lesions within the muscle layer, <3 cm in size, and <3/4 of the esophageal circumference; not suitable for salvage surgery; and absence of metastasis. Second PDT was avoided when lesions were apparently refractory to first PDT, e.g. persistence of submucosal tumor-like protruded component or rapid regrowth of tumor at the ulceration after first PDT. L-CR was defined as endoscopic disappearance of tumor and post-PDT ulcer and absence of cancer cells histologically. RESULTS: Among 82 patients who underwent first PDT, 27 underwent second PDT. The L-CR rates with first and second PDT were 63.0% and 40.7%, respectively. The 2-year overall survival rates after second PDT in patients with L-CR and local-nonCR were 79.5% and 40.5%, respectively. Five of 11 patients with L-CR survived without any recurrence. No grade ≥3 adverse events occurred. CONCLUSIONS: Second PDT demonstrated excellent safety and acceptable efficacy; therefore, it could be a useful treatment for local failure after first PDT.

Factors of technical difficulty in conventional and traction-assisted esophageal endoscopic submucosal dissection.

BACKGROUND: The traction assisted (TA) method has reduced the technical difficulty associated with esophageal endoscopic submucosal dissection (ESD). However, it is unclear which factors associated with difficulty have been improved by the TA-ESD method. We aimed to evaluate and compare difficulty factors between conventional and TA-ESD. METHODS: We retrospectively enrolled patients treated by ESD from Apr 2010 to Jun 2014 for the conventional ESD cohort and from Jan 2016 to Dec 2019 for the TA-ESD cohort. Difficult cases were defined as; (1) ≥ 120 min ESD procedure time, (2) intraoperative perforation, or (3) piecemeal resection. We explored and compared the factors associated with technical difficulty in each cohort. RESULTS: The conventional and TA-ESD cohorts included 285 (299 lesions) and 387 (421 lesions) patients, respectively. For difficult cases, the conventional and TA-ESD cohorts had 91 (30%) and 71 (17%) lesions, respectively. Multivariate logistic regression showed that ≥ 30 mm lesion length (odds ratio (OR) 6.85, 95% confidence interval (CI) 3.47-13.50), lower esophagus (OR 2.37, 95% Cl 1.34-4.21), > 1/2 circumference (OR 2.26, 95% CI 1.28-3.99), and left wall (OR 2.72, 95% CI 1.42-5.20) in the conventional ESD cohort, and ≥ 30 mm lesion length (21.30, 95% CI 4.75-95.30), lower esophagus (OR 3.05, 95% CI 1.52-6.13), and > 1/2 circumference (OR 6.40, 95% CI 3.06-13.40) in the TA-ESD cohort, were independently associated with technical difficulty. CONCLUSIONS: TA-ESD can reduce the difficulty in cases including lesions in the left wall; however, cases in the lower esophagus and large lesions were still difficult to simplify.

Long-term clinical outcomes of patients diagnosed with pT1a-muscularis mucosae with lymphovascular invasion or pT1b after endoscopic resection for cT1N0M0 esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments. METHODS: We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated. RESULTS: Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at > 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P < 0.001). CONCLUSIONS: Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at > 4 years after ER, careful long-term follow-up examinations are needed.

Over 1000 nm Near-Infrared Multispectral Imaging System for Laparoscopic In Vivo Imaging.

In this study, a laparoscopic imaging device and a light source able to select wavelengths by bandpass filters were developed to perform multispectral imaging (MSI) using over 1000 nm near-infrared (OTN-NIR) on regions under a laparoscope. Subsequently, MSI (wavelengths: 1000-1400 nm) was performed using the built device on nine live mice before and after tumor implantation. The normal and tumor pixels captured within the mice were used as teaching data sets, and the tumor-implanted mice data were classified using a neural network applied following a leave-one-out cross-validation procedure. The system provided a specificity of 89.5%, a sensitivity of 53.5%, and an accuracy of 87.8% for subcutaneous tumor discrimination. Aggregated true-positive (TP) pixels were confirmed in all tumor-implanted mice, which indicated that the laparoscopic OTN-NIR MSI could potentially be applied in vivo for classifying target lesions such as cancer in deep tissues.

[Mobile Thrombus in the Ascending Aorta Detected Incidentally in the Patient with Fever before Surgery for Esophageal Cancer:Report of a Case].

A mobile thrombus in the ascending aorta is extremely rare. A 57-year-old man was referred to our hospital with suspected esophageal cancer. Following thorough evaluation, he was diagnosed with esophageal cancer( UtMt type0-Ⅱa T1b, Mt type0-Ⅱc T1a N0M0 cStageⅠ) and tongue cancer in situ. He was administered preoperative chemotherapy comprising fluorouracil and cisplatin. The patient developed fever on day four of the first course of the chemotherapy. Contrast-enhanced chest and abdominal computed tomography revealed a mobile thrombus in the ascending aorta with bilateral partial renal infarction. We initiated intravenous unfractionated heparin and oral warfarin as anticoagulant therapy. The thrombus did not disappear despite ten-day treatment;therefore, he underwent aortic thrombectomy under hypothermic circulatory arrest with retrograde cerebral perfusion. Intraoperatively, we detected a pedunculated mobile thrombus attached to the aorta. His postoperative course was uneventful and he was treated at discharge with warfarin. He underwent video-assisted thoracoscopic esophagectomy postoperatively and was discharged without any complication. Currently, he showed no recurrent thrombus or cancer.

Clinical features and risk factors of gastric cancer detected by esophagogastroduodenoscopy in esophageal cancer patients.

BACKGROUND: Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. METHODS: We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. RESULTS: Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. CONCLUSIONS: The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients.

Effect of the cation structure on cellulose dissolution in aqueous solutions of organic onium hydroxides.

The solubility of cellulose was systematically assessed in organic onium/inium hydroxide aqueous solutions (OHAS) having assorted cations, such as phosphonium, ammonium, piperidinium, morpholinium, pyrrolidinium, and cholinium. From a dissolution test of cellulose in OHAS, it was confirmed that the single most important factor in the dissolution is the high concentration of OHAS. In addition, having a weaker hydrogen bond network around OH and H2O was found to be important to facilitate the cellulose dissolution. In NMR analysis, the OHAS with an excellent cellulose solubility, such as tetrabutylphosphonium hydroxide ([P4444]OH), exhibited a chemical shift of water (δH2O) integrated with that of OH in the low frequency region (∼4.9 ppm), while choline hydroxide ([Ch]OH) with poor cellulose solubility showed δH2O higher than 5.2 ppm. A higher δH2O means that the protons are deshielded due to a stronger hydrogen bond network around H2O and OH, which indicates a strong self-associating property of OHAS that is unfavourable for the cellulose dissolution. Assuming that the strong self-associating property can be reduced by improving the hydrophobicity of organic cations, the methyl group in N-butyl-N-methylmorpholinium hydroxide ([Mor14]OH) was replaced by a butyl chain to shield the positive charge. While [Mor14]OH dissolved only 5 wt% of cellulose, the solubility in the synthesised OHAS, N,N-dibutylmorpholinium hydroxide ([Mor44]OH), was successfully improved to 20 wt%. In the present paper, cellulose solubility was also analysed in relation to the Kamlet-Taft parameters.

Comparison Between Linked Color Imaging and Blue Laser Imaging for Improving the Visibility of Flat Colorectal Polyps: A Multicenter Pilot Study.

INTRODUCTION: Linked color imaging (LCI) and blue laser imaging-bright (BLI-b) improve the visibility of gastrointestinal lesions. In this multicenter study, we compared the effects of LCI and BLI-b on the visibility of flat polyps with visibility scores and color difference (CD) values, including fast-withdrawal and large-monitor observation. METHODS: We recorded 120 videos of 40 consecutive flat polyps (2-20 mm), adenoma, and sessile serrated adenoma and polyp (SSA/P), using white light imaging (WLI), BLI-b, and LCI from July 2017 to December 2017. All videos were evaluated by eight endoscopists according to a published polyp visibility score of 4 (excellent) to 1 (poor). Additionally, 1.5 ×faster and 1.7 ×sized videos were evaluated. Moreover, we calculated the CD values for each polyp in three modes. RESULTS: The mean LCI scores (3.1 ± 0.9) were significantly higher than the WLI scores (2.5 ± 1.0, p < 0.001) but not significantly higher than the BLI-b scores (3.0 ± 1.0). The scores of faster videos on LCI (3.0 ± 1.1) were significantly higher than WLI (2.0 ± 1.0, p < 0.001) and BLI-b (2.8 ± 1.1, p = 0.03). The scores of larger-sized videos on LCI were not significantly higher than those of WLI or BLI-b. The CD value of LCI (18.0 ± 7.7) was higher than that of WLI (11.7 ± 7.0, p < 0.001), but was not significantly higher than that of BLI-b (16.6 ± 9.6). The CD value of LCI was significantly higher than that of BLI-b for adenoma, but the CD value of BLI-b was significantly higher than that of LCI for SSA/P. CONCLUSIONS: The superiority of LCI to BLI-b was proven for the visibility of adenoma and fast observation.

Endoscopic prediction of advanced histology in colorectal lesions sized <10 mm using the Japan Narrow-band imaging Expert Team classification.

BACKGROUND AND AIM: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm. METHODS: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions. RESULTS: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors. CONCLUSION: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm.

Therapeutic results of proton beam therapy with concurrent chemotherapy for cT1 esophageal cancer and salvage endoscopic therapy for local recurrence.

BACKGROUND: Proton beam therapy (PBT) with concurrent chemotherapy is promising for esophageal squamous cell carcinoma (ESCC). The aim of study was to evaluate the outcome of concurrent chemo-proton therapy (CCPT), i.e., PBT with concurrent chemotherapy for cT1 ESCC and the salvage endoscopic therapy for local recurrence. METHODS: Patients with clinical T1 ESCC who underwent CCPT (60 GyE) between April 2013 and April 2017 at the National Cancer Center Hospital East were investigated. The efficacy of CCPT at the primary site was evaluated via endoscopy; primary complete response (CR) was defined as disappearance of the tumor lesion/ulcer and absence of cancer cells on biopsy. Endoscopic evaluation was performed with the same protocol of conventional chemoradiotherapy. Local recurrence after CCPT was treated with endoscopic resection for cT1a and with esophagectomy or photodynamic therapy for cT1b+. RESULTS: Of the 44 patients (median age, 70 years) that underwent CCPT, 43 patients (98%) achieved primary CR. Among the 44 patients, the 3-year overall survival rate was 95.2%. Five patients (11%) developed local recurrence without regional lymph node or distant metastasis and received endoscopic resection or photodynamic therapy. All five patients were alive with no recurrence after a median 23 months. CONCLUSIONS: The results suggest that CCPT is an effective treatment for cT1 ESCC and careful endoscopic follow-up allows preferable local control with salvage endoscopic treatment.

Human-specific mutations in VMAT1 confer functional changes and multi-directional evolution in the regulation of monoamine circuits.

BACKGROUND: Neurochemicals like serotonin and dopamine play crucial roles in human cognitive and emotional functions. Vesicular monoamine transporter 1 (VMAT1) transports monoamine neurotransmitters, and its variant (136Thr) is associated with various psychopathological symptoms and reduced monoamine uptake relative to 136Ile. We previously showed that two human-specific amino acid substitutions (Glu130Gly and Asn136Thr/Ile) of VMAT1 were subject to positive natural selection. However, the potential functional alterations caused by these substitutions (Glu130Gly and Asn136Thr) remain unclear. To assess functional changes in VMAT1 from an evolutionary perspective, we reconstructed ancestral residues and examined the role of these substitutions in monoamine uptake in vitro using fluorescent false neurotransmitters (FFN), which are newly developed substances used to quantitatively assay VMATs. RESULTS: Immunoblotting confirmed that all the transfected YFP-VMAT1 variants are properly expressed in HEK293T cells at comparable levels, and no significant difference was seen in the density and the size of vesicles among them. Our fluorescent assays revealed a significant difference in FFN206 uptake among VMAT1 variants: 130Glu/136Asn, 130Glu/136Thr, and 130Gly/136Ile showed significantly higher levels of FFN206 uptake than 130Gly/136Asn and 130Gly/136Thr, indicating that both 130Glu and 136Ile led to increased neurotransmitter uptake, for which 136Thr and 136Asn were comparable by contrast. CONCLUSIONS: These findings suggest that monoamine uptake by VMAT1 initially declined (from 130Glu/136Asn to 130Gly/136Thr) in human evolution, possibly resulting in higher susceptibility to the external environment of our ancestors.

Objective evaluation of the visibility of colorectal lesions using eye tracking.

BACKGROUND AND AIM: To assess the visibility of colorectal lesions using blue laser imaging (BLI)-bright and linked-color imaging (LCI) with an eye-tracking system. METHODS: Eleven endoscopists evaluated 90 images of 30 colorectal lesions. The lesions were randomly selected. Three images of each lesion comprised white light imaging (WLI), BLI-bright, and LCI in the same position. Participants gazed at the images, and their eye movements were tracked by the eye tracker. We analyzed whether the participants could detect the lesion and how long they took to detect the lesion. We assessed the miss rate and detection time among the imaging modalities. RESULTS: One endoscopist was excluded, and 10 endoscopists were assessed. Overall, 12.6% of lesions were missed with WLI, 6.0% with BLI-bright, and 4.3% with LCI; the miss rate of BLI-bright and LCI was significantly lower than that of WLI (P < 0.01), with no significant difference between the former modalities (P = 0.54). Mean (± SD) detection times were 1.58 ± 1.60 s for WLI, 1.01 ± 1.21 s for BLI-bright, and 1.10 ± 1.16 s for LCI. Detection time for BLI-bright and LCI was significantly shorter than that for WLI (P < 0.0001), with no significant difference between the former modalities (P = 0.34). Regarding the miss rate and detection time between the expert and the non-experts, there was a significant difference with WLI but not with BLI-bright and LCI. CONCLUSION: Blue laser imaging-bright and LCI improved the detection of colorectal lesions compared with WLI using an eye-tracking system.

Reactive swelling of the regional lymph nodes in patients with stage II colorectal cancer as a prognostic factor.

The aim of this study was to examine the relationship between reactive swelling of regional lymph node (LN) and survival in colorectal carcinoma. We retrospectively studied 170 patients with surgically resected colorectal carcinoma histopathologically diagnosed as stage II (pStage II). These patients were classified into two groups:a) a "reactive LN swelling" group (clinically diagnosed as positive for LN metastasis, but pathologically negative) and b) a "no LN swelling" group. Survival analyses of the two groups showed that overall survival (OS) and disease-specific survival (DSS) were longer in the reactive LN swelling group than in the no LN swelling group in patients with total colorectal and right-sided colon cancer. Multivariate analyses revealed that reactive LN swelling was an independent prognostic factor in OS and DSS in patients with right-sided colon cancer. Reactive swelling of regional LN is regarded as an expression of local immune responses, which could explain the present results.

Effects of polarity, hydrophobicity, and density of ionic liquids on cellulose solubility.

We have synthesised novel ionic liquids (ILs) to show both cellulose dissolution ability and LCST-type phase transition after mixing with water. To realise both polar and hydrophobic properties, tetraalkylphosphonium cations and a series of carboxylate anions were employed to assume hydrophobic and highly polar properties, respectively. Effects of their alkyl chain length on the water compatibility and cellulose solubility of the corresponding ILs were systematically examined. We succeeded in synthesising novel ILs which dissolve cellulose and separable with water at moderate temperature. Through the present study, we have clarified that not only polarity but also density of ILs is an important factor in designing the ILs for cellulose dissolution.

A Case of Headache Treated by Online Telemedicine in Collaboration With a Midwifery Home.

Midwifery centers are places where midwives not only provide antenatal checkups and delivery care but also offer a wide range of health guidance to pregnant women, postpartum mothers, newborns, and older women. In recent years, midwives have also provided onsite and online health guidance. However, diagnosis and prescribing medication are impossible in midwifery centers because no doctor is present. If the midwife determines that the patient should consult doctors, the patient may have to go to a hospital and see doctors in person, which can be burdensome. Online telemedicine facilitates midwife-doctor collaboration and may solve this problem. We report a case of headache management by telemedicine that minimized the patient's travel burden by collaborating with a midwifery center that provides onsite, visiting, and online health guidance for patients who have difficulty visiting a hospital due to postpartum period, childcare, and breastfeeding. A 29-year-old woman and her husband were raising an infant in Sado City (a remote island across the sea), Niigata Prefecture. She developed acute back pain and was bedridden for several days due to immobility. She consulted a midwife because of stress and anxiety caused by childcare and acute back pain, as well as newly occurring headaches. The midwife visited her and provided on-site health guidance. The midwife decided that a doctor's diagnosis and treatment with painkillers were desirable for the headache and back pain, so she contacted a doctor based on the patient's request. The doctor provided online telemedicine across the sea, diagnosed her headache as a tension-type headache, and prescribed acetaminophen 500 mg as an abortive prescription. The prescription was faxed to a pharmacy on the island, and the original was sent by post. The midwife picked up the medication and delivered it to the patient. After taking the medication, the patient's back pain and headache went into remission. Collaboration between midwifery centers that provide onsite, visiting, and online health guidance and medical institutions that offer online telemedicine can potentially improve accessibility to medical care. It differs from conventional online telemedicine in the midwife's coordination practice by monitoring the patient's condition and requesting the physician based on the patient's request.

Long-Term Results of Gamma Knife Radiosurgery for Trigeminal Neuralgia.

OBJECTIVE: Although the short- to medium-term efficacy of Gamma Knife therapy for drug-resistant essential trigeminal neuralgia has been reported, long-term evaluations are limited. We evaluated patient data obtained at least 10 years post-treatment and examined the significance of this treatment using new end points. METHODS: Among 249 consecutive patients with essential trigeminal neuralgia who were treated with Gamma Knife radiosurgery (retrogasserian target/4-mm single isocenter/90 Gy at 100%) at our institution between January 2003 and October 2011, 103 patients who were followed up for at least 10 years (mean, 174 [120-219] months) after treatment and whose data were amenable to accurate evaluation, were included in this retrospective study. Herein, we used the Barrow Neurological Institute (BNI) pain intensity scale as a clinical evaluation method for pain and the BNI numbness scale to evaluate complications (namely facial dysesthesia). RESULTS: The initial and final follow-up pain attack cessation (BNI pain intensity score I-IIIa) rate was 82.5% (85 of 103) and 58.2% (60 of 103), respectively. Furthermore, sensory impairment (BNI numbness score ≥ II) at the last follow-up was observed in 24.3% (25 of 103) of the cases, while very bothersome status (BNI numbness score IV) was observed in 2.9% of the cases. CONCLUSIONS: Gamma Knife radiosurgery for essential trigeminal neuralgia showed good therapeutic effects during long-term follow-up. Serious complications of significant concern in the short- to mid-term follow-up, resolved spontaneously. Therefore, the indications for treatment should be expanded to include patients who strongly desire Gamma Knife therapy.

Genomic adaptive potential to cold environments in the invasive red swamp crayfish.

Biological invasion refers to the introduction, spread, and establishment of non-native species in a novel habitat. The ways in which invasive species successfully colonize new and different environments remain a fundamental topic of research in ecology and evolutionary biology. Here, we investigated the genomic and transcriptomic characteristics of the red swamp crayfish (Procambarus clarkii), a widespread invader in freshwater environments. Targeting a recently colonized population in Sapporo, Japan that appears to have acquired a high degree of cold tolerance, RNA-seq analysis revealed differentially expressed genes in response to cold exposure, and those involved in protease inhibitors and cuticle development were considered top candidates. We also found remarkable duplications for these gene families during evolution and their concerted expression patterns, suggesting functional amplification against low temperatures. Our study thus provides clues to the unique genetic characteristics of P. clarkii, possibly related to cold adaptation.

Late-stage macrolactonisation enabled by tandem acyl transfers followed by desulphurisation.

Intramolecular S-acylation of a thiol-installed threonine with a thioester unit, followed by S-O acyl transfer and subsequent desulphurisation, allows the synthesis of lactone peptides. A protocol has been developed enabling the cyclisation of a linear peptide, a reaction which has not been achieved by conventional methods.