Impact of relative cisplatin dose to skeletal muscle mass on adverse events in patients with head and neck cancer undergoing chemoradiotherapy.

BACKGROUND: Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0. RESULTS: Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively). CONCLUSION: The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC.

Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Instrumentation failure following pediatric spine deformity growth-sparing surgery using traditional growing rods or vertical expandable prosthetic titanium ribs.

BACKGROUND: Instrumentation failure (IF) is a major complication associated with growth-sparing surgery for pediatric spinal deformities; however, studies focusing on IF following each surgical procedure are lacking. We aimed to evaluate the incidence, timing, and rates of unplanned return to the operating room (UPROR) associated with IF following each surgical procedure in growth-sparing surgeries using traditional growing rods (TGRs) and vertical expandable prosthetic titanium ribs (VEPTRs). METHODS: We reviewed 1,139 surgical procedures documented in a Japanese multicenter database from 2015 to 2017. Of these, 544 TGR and 455 VEPTR procedures were included for evaluation on a per-surgery basis. IF was defined as the occurrence of an implant-related complication requiring revision surgery. RESULTS: The surgery-based incidences of IF requiring revision surgery in the TGR and VEPTR groups were 4.3% and 4.0%, respectively, with no significant intergroup difference. Remarkably, there was a negative correlation between IF incidence per surgical procedure and the number of lengthening surgeries in both groups. In addition, rod breakage in the TGR group and anchor-related complications in the VEPTR group tended to occur relatively early in the treatment course. The surgery-based rates of UPROR due to IF in the TGR and VEPTR groups were 2.0% and 1.5%, respectively, showing no statistically significant difference. CONCLUSIONS: We found that IF, such as anchor related-complications and rod breakage, occurs more frequently earlier in the course of lengthening surgeries. This finding may help in patient counseling and highlights the importance of close postoperative follow-up to detect IF and improve outcomes.

[Factors and Mechanisms of Pleural Dissemination in Surgically Treated Cases of Lung Metastasis Originated from Pancreatic Cancer].

Pancreatic cancer with distant metastasis typically results in a poor prognosis, but patients with only pulmonary metastasis are reported to have a relatively good prognosis. In this study, we investigated the clinicopathological data and prognosis of 15 patients who underwent surgery for lung metastasis of pancreatic cancer at our hospital between April 2010 and December 2021. The median disease-free interval after pancreatic cancer treatment was 24.5 (9.6-71.8) months. Ten of the 15 patients underwent successful radical resection, while the remaining 5 had pleural dissemination and underwent non-radical resection. The median follow-up duration was 13.5 months, with the median survival time for radical resection and non-radical resection cases being 49.5 months and 31.2 months, respectively. This indicates significantly worse prognosis for non-radical resection cases( p=0.010). Furthermore, the median CA19-9 levels before lung resection were 22 U/ml for radical resection and 2,181 U/ml for non-radical resection cases, significantly higher in the latter (p=0.049). Immunostaining of resected specimens revealed that MMP-2 was positive in 11 of 15 cases, particularly in 4 of 5 cases with pleural dissemination. CA19-9 levels before lung resection may be a predictive factor for pleural dissemination, and MMP-2 may play a role in the mechanism of pleural dissemination.

Angioscopic Comparison of Early- and Mid-Term Vascular Responses Following Treatment of ST-Elevation Acute Myocardial Infarction With Biodegradable vs. Durable Polymer Everolimus-Eluting Stents　- A Prespecified Subanalysis of the MECHANISM AMI RCT.

BACKGROUND: The vessel healing process after implantation of biodegradable polymer (BP) and durable polymer (DP) everolimus-eluting stent (EES) in ST-elevation myocardial infarction (STEMI) lesions remains unclear.Methods and Results: We conducted a multicenter prospective randomized controlled trial to compare early (2 weeks) and mid-term (12 months) vascular responses after implantation of BP-EES vs. DP-EES in STEMI patients. In this prespecified subanalysis, serial coronary angioscopy (CAS) analysis was performed in 15 stents in the BP-EES arm (n=10 patients) and 14 stents in the DP-EES arm (n=10 patients). At the 2-week follow-up, there was no significant difference in the estimated marginal means of the neointimal coverage grade (primary endpoint) between the 2 arms (mean [±SE] 0.00±0.00 in both arms; P>0.999). There were no significant differences between the BP-EES and DP-EES groups in the yellow color grade (1.046±0.106 vs. 0.844±0.114, respectively; P=0.201) or the presence of thrombus (77.8% vs. 88.8%, respectively; P=0.205). At 12 months, competent strut coverage, defined as yellow color grade ≤1, no thrombus, and a neointimal coverage grade ≥1 was achieved more frequently in the BP-EES than DP-EES arm (85.2% vs. 53.1%; adjusted odds ratio 2.11 [95% confidence interval 1.26-3.53]; P=0.023). CONCLUSIONS: Neointimal coverage 2 weeks after implantation of BP-EES and DP-EES in STEMI lesions was comparable on CAS evaluation. However, at 1 year, BP-EES was independently associated with competent strut coverage.

Predicting dry weight change in Hemodialysis patients using machine learning.

BACKGROUND: Machine Learning has been increasingly used in the medical field, including managing patients undergoing hemodialysis. The random forest classifier is a Machine Learning method that can generate high accuracy and interpretability in the data analysis of various diseases. We attempted to apply Machine Learning to adjust dry weight, the appropriate volume status of patients undergoing hemodialysis, which requires a complex decision-making process considering multiple indicators and the patient's physical conditions. METHODS: All medical data and 69,375 dialysis records of 314 Asian patients undergoing hemodialysis at a single dialysis center in Japan between July 2018 and April 2020 were collected from the electronic medical record system. Using the random forest classifier, we developed models to predict the probabilities of adjusting the dry weight at each dialysis session. RESULTS: The areas under the receiver-operating-characteristic curves of the models for adjusting the dry weight upward and downward were 0.70 and 0.74, respectively. The average probability of upward adjustment of the dry weight had sharp a peak around the actual change over time, while the average probability of downward adjustment of the dry weight formed a gradual peak. Feature importance analysis revealed that median blood pressure decline was a strong predictor for adjusting the dry weight upward. In contrast, elevated serum levels of C-reactive protein and hypoalbuminemia were important indicators for adjusting the dry weight downward. CONCLUSIONS: The random forest classifier should provide a helpful guide to predict the optimal changes to the dry weight with relative accuracy and may be useful in clinical practice.

Natural history and surgical outcomes of idiopathic spinal cord herniation.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: Although surgery is frequently selected for the treatment of idiopathic spinal cord herniation (ISCH), its impact on functional outcomes has yet to be fully understood given the limited number of patients in previous studies. This study aims to evaluate the symptomatic history and surgical outcomes of ISCH. SETTING: Three institutions in Japan. METHODS: A total of 34 subjects with ISCH were retrospectively enrolled and followed up for at least 2 years. Demographic information, imaging findings, and clinical outcomes were collected. Functional status was assessed using the JOA score. RESULTS: The types of neurologic deficit were monoparesis, Brown-Sequard, and paraparesis in 5, 17, and 12 cases, with their mean disease duration being 1.2, 4.2, and 5.8 years, respectively. Significant differences in disease duration were observed between the monoparesis and Brown-Sequard groups (p < 0.01) and between the monoparesis and paraparesis groups (p = 0.04). Surgery promoted significantly better recovery rates from baseline. Correlations were observed between age at surgery and recovery rate (p < 0.01) and between disease duration and recovery rate (p = 0.04). The mean recovery rates were 82.6%, 51.6%, and 29.1% in the monoparesis, Brown-Sequard, and paraparesis groups, respectively. The monoparesis group had a significantly higher recovery rate than did the Brown-Sequard (p = 0.045) and paraparesis groups (p < 0.01). CONCLUSIONS: Longer disease duration was correlated with the progression of neurologic deficit. Older age, and worse preoperative neurologic status hindered postoperative functional recovery. These results highlight the need to consider surgical timing before neurologic symptoms deteriorate.

Comparison of taste characteristics between koji mold-ripened cheese and Camembert cheese using an electronic tongue system.

Koji mold, classified in the genus Aspergillus, is used to produce traditional Japanese fermented foods such as miso, soy sauce, and sake. In recent years, the application of koji mold to cheese ripening has attracted attention, and cheese surface-ripened with koji mold (koji cheese) has been studied. In this study, to evaluate the taste characteristics of koji cheese, an electronic tongue system was employed to measure the taste values of cheese samples ripened using 5 strains of koji mold in comparison with commercial Camembert cheese. All koji cheese samples exhibited lower sourness and greater bitterness, astringency, saltiness, and umami richness than the Camembert cheese samples. The intensity of each taste characteristic differed depending on the koji mold strain. These results indicate that koji cheese has a different taste value than conventional mold-ripened cheese. Furthermore, the results also indicate that various taste characteristics can be achieved by selecting different koji molds.

Prolonged Double-Low Time and the Incidence of Postoperative Delirium in Surgical ICU Patients.

An intraoperative double-low condition is defined as concurrent low values for bispectral index (BIS) and mean arterial pressure (MAP), and may predict perioperative outcomes. We hypothesized that prolonged double-low times might be associated with an increased incidence of postoperative delirium. We conducted a single-center retrospective observational study on patients who had been admitted to our hospital's intensive care unit (ICU) after surgery and whose BIS and MAP data had been recorded during general anesthesia. The primary outcome was the incidence of postoperative delirium. A double-low condition was defined as BIS < 45 and MAP <75 mmHg. The total double-low time was calculated in 1-min increments and used to divide the patients into quintiles. Multiple logistic regression analyses were conducted. Among the 334 patients included in the study, the incidence of postoperative delirium was 15.6% (n=52). Multiple logistic regression analysis revealed that a prolonged double-low time, defined as a total double-low time of > 42 min (i.e., third, fourth, and fifth quintiles), was significantly associated with an increased incidence of postoperative delirium (adjusted odds ratio: 2.61, 95% confidence interval: 1.27-5.37, p=0.009). Prolonged double-low time during general anesthesia was independently associated with an increased incidence of postoperative delirium in surgical ICU patients.

Persistent low bone mineral density in adolescent idiopathic scoliosis: A longitudinal study.

BACKGROUND: Since osteopenia has been reported to potentially associated with the progression of scoliosis, bone mineral density (BMD) might have some influences on adolescent idiopathic scoliosis (AIS). However, little is known about longitudinal BMD changes in AIS patients. This study aimed to investigate whether osteopenia in preoperative AIS patients persist at bone maturity, and to evaluate the association between BMD and AIS severity. METHODS: We reviewed 61 AIS patients who underwent surgery when they were Risser grade 4 or below and less than 20 years old (16.6 ± 1.9 years), were followed until they were at least 18 years old and had a Risser grade of 5, and followed at least 2 years after the surgery (mean follow-up 4.9 ± 1.7 years). We evaluated radiographical parameters and proximal femur BMD before surgery and at the final follow-up. A BMD of less than the mean minus 1SD was considered as low BMD. Based on preoperative BMD, 37 patients were assigned to normal BMD (N) group (1.02 ± 0.08 g/cm2) and 24 patients to low BMD (L) group (0.82 ± 0.06 g/cm2). RESULTS: All patients in the N-group had normal BMD at the final follow-up. In the L group, 15 patients (62.5%) had low BMD at the final follow-up (L-L group; preoperative 0.79 ± 0.05 g/cm2 and final follow-up 0.78 ± 0.05 g/cm2). The mean preoperative Cobb angle was significantly larger in the L-L group (67.8 ± 11.2°) than in those with normal BMD at the final follow-up (L-N group, 55.6 ± 11.8°) or the N-N group (50.8 ± 7.6°). Preoperative BMD was significantly negative correlated with the preoperative Cobb angle. The age at surgery and mean preoperative BMI were similar in the L-N and L-L groups. CONCLUSIONS: Of AIS patients with low preoperative BMD, 62.5% still had low BMD after reaching bone maturity, and low BMD was associated with the severity of scoliosis.

Hidden blood loss in extreme lateral interbody fusion for adult spinal deformity.

BACKGROUND: Extreme lateral interbody fusion (XLIF) is often used with posterior spinal fixation (PSF) to treat adult spinal deformity (ASD). However, the amount of intraoperative blood loss (IBL) reported for XLIF may underestimate the total blood loss (TBL). The objective of this study was to determine the total perioperative blood loss in XLIF for ASD. METHODS: We assessed 30 consecutive ASD patients with Schwab-SRS type L (mean age: 68.7 ± 8.2 years; mean follow-up 2.0 ± 1.3 years) who were treated by multilevel XLIF (mean, 2.5 ± 0.6 levels) followed by PSF after 3-5 days. We calculated the TBL after XLIF by the Gross equation, by hemoglobin (Hb) balance, and by the Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) formula. We defined hidden blood loss (HBL) as the difference between the TBL and IBL. Pearson correlation, Spearman correlation, and multiple logistic regression analysis were performed to investigate the risk factors related to HBL. RESULTS: Post-XLIF blood tests showed a significant decrease in the Hb (from 11.8 ± 1.1 mg/dl to 10.6 ± 1.1 mg/dl) and hematocrit (from 36.0 ± 3.2% to 32.5 ± 3.2%). Although the mean IBL was relatively small (33 ± 52 mL), we calculated the TBL as 291 ± 171 mL (Gross equation) and the HBL as 258 ± 168 mL by Gross equation, which was 8 times greater than the IBL on average. There was no difference in the results obtained using the three methods. Multiple logistic regression analysis indicated preoperative lumber lordosis was the risk factor of high HBL (Odds ratio = 1.085, 95%CI: 1.006-1.170, p = 0.035). CONCLUSIONS: The HBL in XLIF was 8 times greater than the IBL. During the perioperative course of correction and fusion surgery for ASD with XLIF, surgeons need to pay attention not to underestimate the TBL.

A nationwide multicenter study of the cost effectiveness of five leading drugs for pharmacological management of cervicobrachial symptoms.

BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.

Impact evaluation of typhoons and remediation works on spatiotemporal evolution of air dose rate in two riverside parks in Fukushima, Japan after the Dai-ichi nuclear power plant accident.

This study elucidated the impacts of typhoon events and remediation works on the spatiotemporal evolution of the air dose rate in riverside areas frequented by residents. Spatial distribution of the air dose rate and radiocesium concentration in the sediments were measured in two riverside parks located near each other in Fukushima Prefecture, Japan, for 2015-2020. The air dose rates measured by walk surveys were interpolated using ordinary kriging to generate air dose rate maps, to facilitate a comparison between the results at different points in time during the measurement campaigns. After the typhoons that occurred during 2015-2018, the air dose rate near the riverside in one park decreased, but not in the other, because the erosion and sediment deposition patterns differed between them. This could be due to the presence of a dam upstream, which serves a flood mitigation function. However, the extreme event of typhoon Hagibis in 2019 dropped the air dose rates near the riversides in both parks. In contrast to the typhoon events which affected the riverside areas, remediation works such as decontamination undertaken during 2015-2019 reduced the air dose rates around the garden and lawn areas which are frequently used as recreational sites. Modeling the temporal evolutions in the air dose rates for the entire area of the riverside parks revealed that 35% of the reduction was caused by physical decay of radiocesium on average, 14% by vertical migration of radiocesium in the soil through precipitation, and 51% by the three typhoons and remediation works during 2015-2019. The contribution of 20% from the strongest typhoon Hagibis highlights the fact that floods resulting from large typhoons are effective in causing natural attenuation of air dose rates in riverside parks.

Stroke volume variation and dynamic arterial elastance predict fluid responsiveness even in thoracoscopic esophagectomy: a prospective observational study.

PURPOSE: It remains unknown whether stroke volume variation (SVV), pulse pressure variation (PPV), and dynamic arterial elastance (Eadyn) are suitable for monitoring fluid management during thoracoscopic esophagectomy (TE) in the prone position with one-lung ventilation and artificial pneumothorax. Our study aimed to evaluate the accuracy of SVV, PVV, and Eadyn in predicting the fluid responsiveness in these patients. METHODS: We recruited 24 patients who had undergone TE. Patients with a mean arterial blood pressure ≤ 65 mmHg received a 200-ml bolus of 6% hydroxyethyl starch over 10 min. Fluid responders showed the stroke volume index ≥ 15% 5 min after the fluid bolus. Receiver operating characteristic (ROC) curves were generated and area under the ROC curve (AUROC) was calculated. RESULTS: We obtained 61 fluid bolus data points, of which 20 were responders and 41 were non-responders. The median SVV before the fluid bolus in responders was significantly higher than that in non-responders (18% [interquartile range (IQR) 13-21] vs. 12% [IQR 8-15], P = 0.001). Eadyn was significantly lower in responders than in non-responders (0.55 [IQR 0.45-0.78] vs. 0.91 [IQR 0.67-1.00], P < 0.001). There was no difference in the PPV between the groups. The AUROC was 0.76 for SVV (95% confidence interval [CI] 0.62-0.89, P = 0.001), 0.56 for PPV (95% CI 0.41-0.71, P = 0.44), and 0.82 for Eadyn (95% CI 0.69-0.95, P < 0.001). CONCLUSIONS: SVV and Eadyn are reliable parameters for predicting fluid responsiveness in patients undergoing TE.

Determination of dietary essential fatty acids in a deep-sea fish, the splendid alfonsino Beryx splendens: functional characterization of enzymes involved in long-chain polyunsaturated fatty acid biosynthesis.

The splendid alfonsino Beryx splendens is a commercially important deep-sea fish in East Asian countries. Because the wild stock of this species has been declining, there is an urgent need to develop aquaculture systems. In the present study, we investigated the long-chain polyunsaturated fatty acid (LC-PUFA) requirements of B. splendens, which are known as essential dietary components in many carnivorous marine fish species. The fatty acid profiles of the muscles, liver, and stomach contents of B. splendens suggested that it acquires substantial levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from its natural diet. The functional characterization of a fatty acid desaturase (Fads2) and three elongases (Elovl5, Elovl4a, and Elovl4b) from B. splendens confirmed their enzymatic capabilities in LC-PUFA biosynthesis. Fads2 showed Δ6 and Δ8 bifunctional desaturase activities. Elovl5 showed preferential elongase activities toward C18 and C20 PUFA substrates, whereas Elovl4a and Elovl4b showed activities toward various C18-22 substrates. Given that Fads2 showed no Δ5 desaturase activity and no other fads-like sequence was found in the B. splendens genome, EPA and arachidonic acid cannot be synthesized from C18 precursors; hence, they can be categorized as dietary essential fatty acids in B. splendens. EPA can be converted into DHA in B. splendens via the so-called Sprecher pathway. However, given that fads2 is only expressed in the brain, it is unlikely that the capacity of B. splendens to biosynthesize DHA from EPA can fulfill its physiological requirements. These results will be useful to researchers developing B. splendens aquaculture methods.

[Eight mm Port-Site Hernia Following Robot-Assisted Abdominoperineal Resection for Rectal Cancer-A Case Report].

A 70s woman with a history of asthma and dyslipidemia underwent a robot-assisted abdominoperineal resection for rectal cancer. The ports were placed as per the method of Shizuoka Cancer Center and no intraoperative complications were observed. The colostomy was constructed in the left lower abdomen by the retroperitoneal route. The 12-mm port part was closed in 2 layers, the fascia and dermis, and the 8-mm port part was closed only in the dermis. The postoperative course was good; however, the patient vomited 10 days after surgery. Abdominal computed tomography revealed an incarcerated small intestine in the 8-mm port of the left abdomen, and it was diagnosed as port-site hernia incarceration. Emergency laparotomy hernia repair was performed on the day. A part of the 8-mm port was incised to 30-mm and the fascia dilatation to 30-mm was observed. The color tone of the incarcerated small intestine was good. Only adhesion peeling was performed, the small intestine was returned, and the fascia was closed. The postoperative course was uneventful and the patient was discharged 17 days after the second surgery. At the 1 year postoperative follow-up, recurrence of hernia or rectal cancer was not observed.

SPECC1L regulates palate development downstream of IRF6.

SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.

A retrospective 5-year survival analysis of surgically resected gastric cancer cases from the Japanese Gastric Cancer Association nationwide registry (2001-2013).

BACKGROUND: The nationwide registry of the Japanese Gastric Cancer Association collected data of surgically resected cases of gastric cancer between 2001 and 2013. These retrospective analyses aimed to delineate tumor characteristics, surgical history, and survival distribution. METHODS: Data from 254,706 patients with primary gastric cancer were included. The 5-year survival rates were calculated for various subsets of prognostic factors. RESULTS: The number of patients over 70 years old increased from 2001 to 2013. The frequency with which laparoscopic gastrectomy was opted for increased dramatically (from 3.5 to 40.8%) in 13 years. We focused on the patients registered between 2010 and 2013, for whom data collection was based on the 3rd edition of the Japanese classification and guidelines. Five-year overall survival (OS) rate among 92,305 patients with resected tumors was 70.6%. The 5-year OS rates of patients with pathological stage IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV disease were 89.6%, 83.2%, 77.6%, 68.1%, 59.3%, 45.6%, 29.9%, and 14.0%, respectively. CONCLUSION: Our detailed analysis highlights the historical changes in outcomes of surgically treated gastric malignancies in Japan, and provides robust dataset for future analysis.

A Comprehensive Review of the Progress and Evaluation of the Thyroid Ultrasound Examination Program, the Fukushima Health Management Survey.

The Great East Japan Earthquake on March 11, 2011, and the subsequent tsunami caused an accident at the Fukushima Daiichi Nuclear Power Plant, in which extensive damage to the nuclear power reactors resulted in massive radioactive contamination. Fukushima Prefecture implemented the Thyroid Ultrasound Examination (TUE) program as part of the Fukushima Health Management Survey project in response to residents' anxieties about health risks due to radiation exposure for residents aged 0-18 years at the time of the nuclear accident. This program consisted of the primary examination and the confirmatory examination. In the primary examination, thyroid nodules and cysts were examined using portable ultrasound apparatuses. The confirmatory examination was performed to have clinical or cytological diagnosis. As of June 30, 2021, 116, 71, 31, 36, and 9 examinees in the first, second, third, and fourth round of surveys, and the survey at age 25 years, respectively, were determined to have nodules cytologically diagnosed as malignant or suspicious for malignancy. The confirmatory examination of the fourth-round survey and the primary and confirmatory examination of fifth-round survey are currently in progress. Together with the low thyroid absorbed radiation dose estimated in the United Nations Scientific Committee on the Effects of Atomic Radiation 2020 report, our results suggested that the increased incidence of childhood thyroid cancer in Fukushima Prefecture was not caused by radiation exposure, but rather by the highly sensitive detection method. As detailed in this review, there were ongoing challenges in our program, such as actions against the risk of overdiagnosis and psychological support for participants and their families.

Revisiting the Geographical Distribution of Thyroid Cancer Incidence in Fukushima Prefecture: Analysis of Data From the Second- and Third-round Thyroid Ultrasound Examination.

BACKGROUND: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. METHODS: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. RESULTS: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52-2.59), 0.55 (95% CI, 0.31-0.97), 1.05 (95% CI, 0.79-1.40), and 1.24 (95% CI, 0.89-1.74). CONCLUSION: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016-2017) in Fukushima Prefecture.