Comparison of the subtotal and narrow gastric conduit for cervical esophagogastrostomy after esophagectomy in esophageal cancer patients: a propensity score-matched analysis.

BACKGROUND: Several reports have compared narrow gastric conduit (NGC) with subtotal gastric conduit (SGC) for cervical esophagogastrostomy after esophagectomy; however, whether which one is more beneficial in terms of postoperative complications remains unclear. To determine the optimal gastric conduit type, we retrospectively investigated and compared the postoperative complications between NGC and SGC used in cervical circular-tapered esophagogastrostomy after esophagectomy through a propensity score-matched analysis. METHODS: Between 2008 and 2022, 577 consecutive esophageal cancer patients who underwent esophagectomy and cervical circular-stapled esophagogastrostomy were enrolled in this study. RESULTS: Of the 577 patients, 77 were included each in the SGC and NGC groups, after propensity score matching. Clinical characteristics did not differ between the two groups. The anastomotic leakage rate was significantly lower in the SGC group than in the NGC group (5% vs. 22%, p < 0.01). The anastomotic stenosis rate was significantly higher in the SGC group (16% vs. 5%, p = 0.03). Multivariate logistic analysis showed that NGC, subcutaneous route, and age were significant independent factors associated with anastomotic leakage (odds ratios, 8.58, 6.49, and 5.21; p < 0.01, < 0.01 and 0.03, respectively) and that SGC was a significant independent factor associated with anastomotic stricture (odds ratios, 4.91; p = 0.04). CONCLUSIONS: In cervical circular-stapled esophagogastrostomy after esophagectomy, SGC was superior to NGC in terms of reducing the risk of anastomotic leakage, although the risk of anastomotic stricture needs to be resolved.

Association between combined spinal-epidural analgesia and neurodevelopment at 3 years old: The Japan Environment and Children's Study.

AIM: To investigate the association between maternal combined spinal-epidural analgesia during vaginal delivery and neurodevelopment in 3-year-old children. METHODS: Using data from the Japan Environment and Children's Study, a birth cohort study on pregnant women and their offspring, we described the background, perinatal outcomes, and neurodevelopmental outcomes of participants with a singleton pregnancy who received combined spinal-epidural analgesia during vaginal delivery and those who did not. The association between maternal combined spinal-epidural analgesia and abnormalities in five domains of the Ages and Stages Questionnaire, Third Edition, was analyzed using univariable and multivariable logistic regression analyses. Crude and adjusted odds ratios with 95% confidence intervals (95% CI) were calculated. RESULTS: Among 59 379 participants, 82 (0.1%) children (exposed group) were born to mothers who received combined spinal-epidural analgesia during vaginal delivery. In the exposed versus control groups, 1.2% versus 3.7% had communication abnormalities (adjusted odds ratio [95% CI]: 0.30 [0.04-2.19]), 6.1% versus 4.1% exhibited gross-motor abnormalities (1.36 [95% CI: 0.55-3.36]), 10.9% vs. 7.1% had fine-motor abnormalities (1.46 [95% CI: 0.72-2.96]), 6.1% vs. 6.9% showed difficulties with problem-solving (0.81 [95% CI: 0.33-2.01]), and 2.4% vs. 3.0% had personal-social problems (0.70 [95% CI: 0.17-2.85]). CONCLUSIONS: Exposure to combined spinal-epidural analgesia during vaginal delivery was not associated with the risk of neurodevelopmental abnormalities; however, the sample size of our study might not be appropriate for the study design.

Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

Longitudinal study of body mass index and percentage of overweight in Japanese children grouped by maturity.

Childhood obesity is a known risk factor for adult diseases, making its evaluation highly important. However, the evaluation is complex because there is no gold standard method. Body mass index (BMI) and percentage of overweight (POW) are widely used in Japan. However, they have the following limitations: it is difficult to set cutoffs for BMI because it dynamically varies in childhood, and POW has not been studied extensively, especially regarding its difference during maturity. Therefore, our study analyzed BMI/POW in Japanese children grouped by maturity. We used longitudinal school check-up data collected from elementary and junior high schools in 20 municipalities. We made percentile curves of BMI/POW and calculated the percentage of participants considered overweight/obese by sex, age, and maturity. Maximum increment age (MIA) was calculated using the graphical fitting method. We included 35,461 subjects aged 15 in 2018. Early-maturing children had higher BMI. The difference among maturity groups decreased by shifting the percentile curves by differences in MIA. Therefore, the use of BMI might lead to the overestimation of overweight/obesity in early-maturing children and underestimation in late-maturing children. The POW percentile curves were "N"-shaped around the MIA, indicating the inappropriate evaluation during this period. The percentile curves of children categorized as overweight/obese were also "N"-shaped, confirming that MIA affects the evaluation of childhood obesity. The possibility of overestimation/underestimation needs verification with the data of accurate age, pubertal changes, and adult diseases. In conclusion, it is difficult to evaluate childhood obesity only with height and weight.

Early growth hormone treatment accelerates delayed onset of puberty in patients with growth hormone deficiency.

We investigated whether growth hormone (GH) treatment could accelerate the onset of puberty in patients with isolated GH deficiency (GHD). Of the 135 boys and 89 girls who started GH treatment before the onset of puberty and were followed up at Tanaka Growth Clinic, 83 boys and 51 girls who started GH treatment sufficiently earlier than the average age at onset of puberty of GHD patients (<10 years vs. 11.7 years for boys; <9.5 years vs. 11.4 years for girls) were analyzed. Age at onset of puberty significantly positively correlated to age at the start of GH treatment (boys: r = 0.427, p < 0.0001; girls: r = 0.302, p < 0.05). When the subjects were divided into two groups each: for boys, Groups A (n = 45) and B (n = 39), treatment was started at age <8 and 8 to <10 years, respectively; for girls, Groups A (n = 26) and B (n = 21), treatment was started at age <7 and 7 to <9.5 years, respectively, age at the onset of puberty was significantly lower in Groups A than in Groups B by the Mann-Whitney U test (boys: p < 0.01; girls: p < 0.05) and Kaplan-Meier log-rank test (boys: p < 0.01; girls: p < 0.05). These results indicate that GH treatment accelerates the delayed onset of puberty in patients with GHD. Heights at the onset of puberty in Groups A and B were not significantly different, suggesting that early treatment does not increase adult height.

A comparison of the surgical invasiveness and short-term outcomes between thoracoscopic and pneumatic mediastinoscopic esophagectomy for esophageal cancer.

PURPOSE: Minimally invasive esophagectomy (MIE) has been widely accepted as a treatment for esophageal cancer. This retrospective study compared the short-term outcomes and surgical invasiveness between thoracoscopic esophagectomy (TE) and mediastinoscopic esophagectomy with pneumomediastinum (pneumatic mediastinoscopic esophagectomy [PME]). METHODS: A total of 72 patients who underwent TE or PME were included and assessed for their surgical findings, postoperative complications, and inflammatory responses on postoperative day (POD) 1, 3, 5, and 7. RESULTS: The PME group exhibited a significantly shorter operative time and fewer lymph nodes retrieved than the TE group. Furthermore, the PME group tended to have greater incidences of recurrent laryngeal nerve palsy and lower incidences of atelectasis than the TE group. The PME group had significantly lower white blood cell counts on POD 5, serum C-reactive protein (CRP) levels on POD 3 than the TE group. CONCLUSION: PME seems to be less invasive than TE and can be considered the preferred option for patients with lower-stage esophageal cancer expected to have severe pleural adhesion or who cannot tolerate TE.

Clinical Impact of the Prognostic Nutritional Index as a Predictor of Outcomes in Patients with Stage II/III Gastric Cancer: A Retrospective Cohort Study.

BACKGROUND: The Japanese Gastric Cancer Treatment Guidelines recommend S-1 and S-1 plus docetaxel as postoperative chemotherapy for pathological stage II and III gastric cancer (GC). There is currently no strategy for using chemotherapy to treat high-risk recurrent pathological stage II/III. Previous studies reported that the several nutritional, immunological, and inflammatory markers examined the association with clinical outcomes after surgery for GC. METHODS: Ninety patients with GC (stage II, n = 48; stage III, n = 42) for whom gastrectomy was performed at our institution between November 2009 and September 2018 were examined. Nutritional, immunological, and inflammatory markers were calculated from blood samples within 1 week before surgery. RESULTS: The prognostic nutritional index (PNI) status correlated with the pathological stage and disease recurrence after surgery (p = 0.015 and p < 0.0001, respectively). Thirty-three patients had disease recurrence after gastrectomy (stage II, n = 11; stage III, n = 22). The PNI was significantly lower in the recurrent group than in the non-recurrent group (p = 0.0003). The PNI correlated with overall survival and recurrence-free survival after gastrectomy (p = 0.0021 and p = 0.0001, respectively). A multivariate analysis identified the PNI as an independent prognostic factor (p = 0.006). CONCLUSION: The PNI may be useful for predicting the outcomes of patients with pathological stage II/III GC and may contribute to the selection of an appropriate adjuvant chemotherapy regimen.

First-line antibiotic prescription patterns for acute otitis media in children: A descriptive study using Japanese claims data (2014-2018).

INTRODUCTION: Acute otitis media is a highly prevalent disease in children. Although guidelines in many countries recommend amoxicillin as the first-line treatment for acute otitis media, the prescribing pattern in Japan is not clear. Our objective was to clarify the amoxicillin prescriptions as first-line antibiotics for acute otitis media and factors associated with amoxicillin prescriptions. Also, changes in amoxicillin prescriptions during the study period by medical facilities were investigated. METHODS: Using an administrative claims database, we included new episodes of acute otitis media prescribed antibiotics in children under seven years of age between 2014 and 2018. The proportion of amoxicillin prescription was described. Using multivariate logistic regression analysis, factors associated with amoxicillin prescription were evaluated. Rate differences were calculated to describe changes in amoxicillin prescription by medical facilities. RESULTS: 207,213 episodes in 149,929 patients were identified. Amoxicillin prescription was 24.0% and increased over the study period (P for trend <0.001). Characteristics of medical facilities were associated with amoxicillin prescriptions, and hospitals were more likely to prescribe amoxicillin (adjusted odds ratio: 1.71, 95% confidence intervals: 1.63 to 1.79). Compared to 2014, the range of increase in amoxicillin prescription in 2018 was greater in hospitals (14.9%) and pediatric clinics (10.5%) than in otolaryngology clinics (5.9%) and other specialty clinics (6.0%). CONCLUSIONS: During the study period, amoxicillin prescriptions had increased compared to 2014, but the proportion was still low. Clinics prescribed less amoxicillin than hospitals, and the range of increase was small. Our results suggested that some interventions focused on clinics are needed.

Prognostic impact of surgery after chemotherapy for type 4 gastric cancer.

PURPOSE: To assess the clinical indications for, and prognostic impact of surgery after, chemotherapy for type 4 gastric cancer. METHODS: The subjects of this retrospective study were 67 patients who received chemotherapy for type 4 gastric cancer. The patients were grouped into those with progressive disease (PD group) and those without PD (non-PD group), according to the tumor response to chemotherapy. RESULTS: Distant metastases developed in 58 patients. With regard to tumor response, there were 16 patients in the PD group and 51 patients in the non-PD group. The prognosis of the PD group patients was significantly poorer than that of the non-PD group patients (p < 0.0001). R0 resection was performed for 21 of 23 patients who underwent surgery after chemotherapy. Multivariate analysis revealed tumor response and surgery as independent prognostic factors (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis of the surgery group revealed that metastatic nodal status (N0-1 vs. N2-3) and residual tumor status (R0 vs. R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). CONCLUSION: The findings of this study suggest that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status, who undergo curative R0 resection.

Comparison of greater curvature and lesser curvature circular-stapled esophagogastrostomy after esophagectomy in patients with esophageal cancer: a prospective randomized controlled trial.

PURPOSE: Using a circular stapler to create an anastomosis for esophagogastrostomy after esophagectomy is well accepted; however, it remains uncertain if the greater curvature (GC) or lesser curvature (LC) of the gastric conduit is better for the anastomosis. We conducted this prospective study to compare the integrity of esophagogastrostomy between the esophagus and the GC or LC side of the gastric conduit. METHODS: The subjects of this study were 70 patients who underwent esophagectomy and were randomized to a "GC" group and an "LC" group (n = 35 each). The primary and secondary end points were anastomotic leakage (AL) and anastomotic stricture (AS), respectively. RESULTS: The overall AL rate was 22.1%, without a significant difference between the groups. Stump leakage developed in eight of nine patients in the GC group, whereas leakage developed at the esophagogastric anastomosis in five of six patients in the LC group. The rate of stump leakage was significantly higher than that of esophagogastric AL in the GC group. The overall AS rate was 4.4%, with a significant difference between the groups (0% in the GC group vs. 9.1% in the LC group). CONCLUSIONS: AL rates were comparable in the two groups, but the sites of leakage were significantly different.

RNA sequencing-based microRNA expression signature in esophageal squamous cell carcinoma: oncogenic targets by antitumor miR-143-5p and miR-143-3p regulation.

Aberrantly expressed microRNAs (miRNAs) disrupt intracellular RNA networks and contribute to malignant transformation of cancer cells. Utilizing the latest RNA sequencing technology, we newly created the miRNA expression signature of esophageal squamous cell carcinoma (ESCC). A total of 47 miRNAs were downregulated in ESCC tissues, and these miRNAs were candidates for antitumor miRNAs in ESCC cells. Analysis of the signature revealed that several passenger strands of miRNAs were significantly downregulated in ESCC, e.g., miR-28-3p, miR-30a-3p, miR-30c-3p, miR-133a-3p, miR-139-3p, miR-143-5p, and miR-145-3p. Recent studies indicate that some passenger strands of miRNAs closely involved in cancer pathogenesis. In this study, we focused on both strands of pre-miR-143, and investigated their antitumor roles and target oncogenes in ESCC. Ectopic expression of miR-143-5p and miR-143-3p significantly attenuated malignant phenotypes (e.g., proliferation, migration, and invasive abilities) in ESCC cell lines. We revealed that six genes (HN1, HMGA2, NETO2, STMN1, TCF3, and MET) were putative targets of miR-143-5p regulation, and one gene (KRT80) was a putative target of miR-143-3p regulation in ESCC cells. Our ESCC miRNA signature and analysis strategy provided important insights into the molecular pathogenesis of ESCC.

Clinical Significance of Conversion Surgery for Gastric Cancer with Peritoneal Dissemination: A Retrospective Study.

OBJECTIVE: Although chemotherapy has been clinically recommended as the initial treatment for patients with peritoneal dissemination of gastric cancer, poor prognosis has been noted among the same patients. However, the prognostic significance of conversion surgery after chemotherapy remains unclear. The present study therefore aimed to assess the clinical impact of conversion surgery among patients with peritoneal dissemination of gastric cancer. METHODS: A total of 93 patients with peritoneal dissemination of gastric cancer undergoing chemotherapy between February 2002 and October 2019 were retrospectively enrolled and subsequently divided into progressive disease (PD) and non-PD groups based on tumor response to chemotherapy. RESULTS: Among the included patients, 17 developed distant metastases at another site besides peritoneal dissemination. Based on tumor response, 24 and 69 patients were determined to have PD and non-PD, respectively, with the former having significantly poorer prognosis than the latter (p < 0.0001). A total of 19 patients underwent conversion surgery after chemotherapy, with the presence or absence of conversion surgery being significantly correlated with age, first-line chemotherapy regimen, and tumor response (p = 0.0134, p = 0.0337, and p = 0.0024, respectively). Patients in the non-PD group who underwent conversion surgery or chemotherapy alone had 3-year overall survival rates of 55.6 and 6.6%, respectively. Multivariate analysis identified conversion surgery alone as an independent prognostic factor in the non-PD group (p < 0.0001). CONCLUSION: Our retrospective study demonstrated that conversion surgery for gastric cancer with peritoneal dissemination might improve the prognosis of responders who developed no peritoneal dissemination after chemotherapy.

Indication and Prognostic Significance of Conversion Surgery in Patients with Liver Metastasis from Gastric Cancer.

OBJECTIVE: Chemotherapy is generally recommended as the first-line standard treatment in patients with liver metastasis from gastric cancer. However, the clinical impact of surgical treatment remains unclear in responders after chemotherapy. The present study aimed to investigate the tumor response and prognosis after chemotherapy and to assess the clinical indication of conversion surgery in responders. METHODS: The study retrospectively reviewed the clinical data of 44 patients with liver metastasis from gastric cancer who were treated with chemotherapy between February 2002 and January 2019. These patients were classified into progressive disease (PD) and non-PD groups according to tumor response. RESULTS: Among the 44 patients, 7 and 26 had peritoneal dissemination and ≥5 had metastatic liver nodules. Additionally, 15 and 29 patients had PD and non-PD, respectively. Surgical treatment was significantly correlated with tumor response (p < 0.0321). Prognostic differences between the PD and non-PD groups were significant (p < 0.0001). Moreover, gastrectomy and hepatectomy were significantly correlated with the number of liver metastases (≥5 vs. <5, respectively) in the non-PD group (p = 0.0025 and p = 0.0169, respectively). The 3-year survival rates among patients with non-PD undergoing both gastrectomy and hepatectomy (n = 6), gastrectomy alone (n = 7), and nonsurgical treatments (n = 16) were 100, 66.7, and 0%, respectively (p = 0.0026). Multivariate analysis identified peritoneal dissemination as an independent prognostic factor (p = 0.0225). CONCLUSION: Our preliminary results suggest that conversion surgery for gastric cancer with liver metastasis might be clinically indicated in chemotherapy responders with <5 metastatic liver nodules and without peritoneal dissemination.

Response Rate and Prognostic Impact of Salvage Chemotherapy after Nivolumab in Patients with Advanced Gastric Cancer.

OBJECTIVE: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. METHODS: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. RESULTS: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. CONCLUSION: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.

Evaluation of postoperative quality of life by PGSAS-45 following local gastrectomy based on the sentinel lymph node concept in early gastric cancer.

BACKGROUND: The usefulness of sentinel node navigation surgery (SNNS) for early gastric cancer has been demonstrated in a multicenter prospective study. However, quality of life (QOL) after local resection remains unclear. This present study investigated QOL after local resection and distal gastrectomy. METHODS: We examined 69 patients who underwent laparoscopic distal gastrectomy (LADG) (n = 44) and laparoscopic local resection (LLR) (n = 25) in our hospital between September 2011 and May 2018. We conducted a combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) with SNNS as LLR. All patients had pStage I or II and none had received adjuvant chemotherapy. We evaluated QOL using the postgastrectomy syndrome assessment scale questionnaire (PGSAS-45) 1, 6, and 12 months after surgery. RESULTS: In PGSAS-45, no significant differences were observed between LLR and LADG at 1 and 6 months after surgery. At 12 months, the LLR group scored better for some of the subscales (SS). In the endoscopic evaluation, the LLR group showed significant improvements in residual gastritis at 6 months (P = 0.006) and esophageal reflux and residual gastritis at 12 months (P = 0.021 and P = 0.017). A significant difference was observed in the prognostic nutritional index, which was assessed using serum samples, between the two groups at 6 months (P = 0.028). The body weight ratio was better in the LLR group than in the LADG group at 6 and 12 months (P = 0.041 and P = 0.007, respectively). CONCLUSIONS: CLEAN-NET with SNNS preserved a better QOL and nutrition status than LADG in patients with early gastric cancer.

Conversion surgery for stage IV gastric cancer with a complete pathological response to nivolumab: a case report.

BACKGROUND: Patients with stage IV gastric cancer have a poor prognosis despite the recent development of multidisciplinary treatments that include chemotherapy. However, conversion surgery has emerged as a promising strategy to improve the prognosis in responders with unresectable gastric cancer after chemotherapy. Moreover, nivolumab is currently recommended as a third-line treatment in patients with unresectable advanced gastric cancer. However, there are few reports of conversion surgery after nivolumab in patients with stage IV gastric cancer. CASE PRESENTATION: A 68-year-old woman complaining of nausea was diagnosed with stage I gastric cancer (T2N0M0). Although we planned gastrectomy with lymphadenectomy, multiple liver metastases were detected during the surgery. After staging laparoscopy, we diagnosed this patient as having stage IV unresectable gastric cancer, and we administered chemotherapy and immunotherapy for 39 months (first-line regimen: 6 courses of S-1 plus oxaliplatin; second-line regimen: 6 courses of ramucirumab plus paclitaxel; and third-line regimen: 20 courses of nivolumab). Although the liver metastases completely disappeared after the second-line chemotherapy, lung metastases and a rapid enlargement of the primary tumor were confirmed. Consequently, the patient received nivolumab at a dose of 3 mg/kg intravenously every 2 weeks, then a dose of 240 mg/kg intravenously every 2 weeks from September 2018. After 20 courses of nivolumab, the primary tumor dramatically shrank and the lung metastases disappeared. The patient had a partial primary tumor response to nivolumab. Therefore, the patient underwent laparoscopic distal gastrectomy with D2 lymph node dissection. The macroscopic examination of the resected specimen showed an ulcer scar in the primary tumor site. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of the primary tumor was categorized as grade 3. The postoperative course was uneventful, and the patient is receiving nivolumab to control potential liver and lung metastases. CONCLUSIONS: Conversion surgery might help control tumor progression in responders after chemotherapy and immunotherapy.

Pyridoxal 5'-phosphate and related metabolites in hypophosphatasia: Effects of enzyme replacement therapy.

OBJECTIVE: To investigate the utility of serum pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT. METHODS: Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT. RESULTS: Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients. CONCLUSIONS: The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT.

Correlation Between Biomarker Candidate Proteins with the Effect of Neoadjuvant Chemoradiation Therapy on Esophageal Squamous Cell Carcinoma.

BACKGROUND: While chemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC), it is important to predict response prior to treatment by using markers because some patients respond well and others do not. METHODS: Fifty-nine patients with ESCC were treated with neoadjuvant CRT at the Kagoshima University Hospital. The expression of seven types of biomarker candidate proteins in biopsy specimens of untreated primary tumors was evaluated to determine whether it correlated with response and prognosis. RESULTS: The positive expression rates were 47% for p53, 83% for CDC25B, 68% for 14-3-3sigma, 76% for p53R2, 75% for ERCC1, 32% for Gli-1, and 54% for Nrf2. In terms of histological response, tumor grade of the 59 patients was 48.8% for grade 1 as the non-responder, 29.2% for grade 2, and 22.0% for grade 3 as the responder. CRT was significantly effective in p53(-), p53R2(-), ERCC1(-), and Nrf2(-) tumors, while p53(-), p53R2(-), and ERCC1(-) were factors independently correlated with effective histological response. Their combined expression of two or three negative expressions had 100% effective response and was a significant prognostic factor. CONCLUSION: Our results suggest that two or three negative expressions of p53, p53R2, and ERCC1 in biopsy specimens of primary tumors were associated with a favorable response to CRT for ESCC. Assessment of tumor suppressor and DNA repair protein expressions in biopsy specimens may be useful for the potential utility of CRT therapy for patients with ESCC prior to treatment.

Optimal suture anchor direction in arthroscopic lateral ankle ligament repair.

PURPOSE: In this study, the distance between the insertion point of the suture anchors and posterior surface of the fibula during arthroscopic lateral ankle ligament repair was investigated on computed tomography (CT) images. The hypothesis of this study was that there is an optimal insertional direction of the suture anchor to avoid anchor-related complications. METHODS: One hundred eleven ankles of 98 patients who had undergone three-dimensional CT scans for foot or ankle disorders without deformity of the fibula were assessed (59 males, 52 females; median age 25.5 years; age range 12-78 years). The shortest distance from the insertion point of the suture anchor to the deepest point of the fossa/top of the convex aspect of the fibula was measured on the axial plane, tilting from the longitudinal axis of the fibula at 90°, 75°, 60°, and 45°. The distance from the insertion point of the suture anchor to the posterior surface of the fibula was also measured in a direction parallel to the sagittal plane of the lateral surface of the talus on the axial plane, tilting from the longitudinal axis of the fibula at 90°, 75°, 60°, and 45°. RESULTS: The posterior fossa was observed in all cases on the 90° and 75° images. The distance from the insertion point to the posterior surface of the fibula in the parallel direction was 15.0 ± 3.4 mm at 90°, 17.5 ± 3.2 mm at 75°, 21.7 ± 3.3 mm at 60°, and 25.7 ± 3.6 mm at 45°. The posterior points in the parallel direction were located on the posterior fossa in 36.0% of cases at 90°, in 12.6% at 75°, and in 0.0% at 60° and 45°. CONCLUSIONS: The suture anchor should be directed from anterior to posterior at an angle of <45° to the longitudinal axis of the fibula, parallel to the lateral surface of the talus, to avoid passing through the fibula. LEVEL OF EVIDENCE: Cohort study, Level III.

Streptococcal toxic shock syndrome caused by the dissemination of an invasive emm3/ST15 strain of Streptococcus pyogenes.

BACKGROUND: Streptococcus pyogenes (group A Streptococcus [GAS]) is a major human pathogen that causes a wide spectrum of clinical manifestations. Although invasive GAS (iGAS) infections are relatively uncommon, emm3/ST15 GAS is a highly virulent, invasive, and pathogenic strain. Global molecular epidemiology analysis has suggested that the frequency of emm3 GAS has been recently increasing. CASE PRESENTATION: A 14-year-old patient was diagnosed with streptococcal toxic shock syndrome and severe pneumonia, impaired renal function, and rhabdomyolysis. GAS was isolated from a culture of endotracheal aspirates and designated as KS030. Comparative genome analysis suggested that KS030 is classified as emm3 (emm-type) and ST15 (multilocus sequencing typing [MLST]), which is similar to iGAS isolates identified in the UK (2013) and Switzerland (2015). CONCLUSIONS: We conclude that the global dissemination of emm3/ST15 GAS strain has the potential to cause invasive disease.