Effectiveness of clip-and-thread traction-assisted duodenal endoscopic submucosal dissection: a propensity score-matched study (with video).

BACKGROUND AND AIMS: The indications for endoscopic submucosal dissection (ESD) in superficial nonampullary duodenal epithelial tumors (SNADETs) remain controversial because the procedure is technically challenging. Moreover, the effectiveness of clip-and-thread traction-assisted ESD (TA-ESD) for SNADETs has not been assessed. The aim of the current study was to compare the effectiveness of duodenal TA-ESD and conventional ESD for SNADETs. METHODS: SNADETs treated with conventional ESD or TA-ESD between April 2017 and March 2021 at Saitama Medical University International Medical Center were evaluated retrospectively. RESULTS: There were 49 cases of conventional ESD and 32 cases of TA-ESD for SNADETs. Using a propensity score-matched design, we selected 26 pairs of cases with conventional ESD and TA-ESD. In the unmatched cohort, patients treated with TA-ESD were characterized by a higher R0 (no tumor identified at the lateral or vertical margins) resection rate (P = .004), more frequent poor submucosal lifting because of fibrosis (P = .014), and shorter follow-up period (P = .0004) than patients treated with conventional ESD. In the propensity score-matched pairs, patients treated with TA-ESD were characterized by a higher rate of R0 resection (P = .021) and a shorter follow-up period (P = .0061). The findings regarding R0 resection rates were confirmed by multivariate logistic regression models, which found a higher odds ratio (OR) for R0 resection in patients who underwent TA-ESD than in patients who underwent conventional ESD both in the unmatched cohort (OR, 17.0; 95% confidence interval, 1.6-178.8; P = .018) and in the propensity score-matched pairs (OR, 26.7; 95% confidence interval, 1.5-460.2; P = .024). CONCLUSIONS: Our findings suggest TA-ESD may increase the rate of R0 resection in patients with SNADETs in comparison with conventional ESD.

Experience using donor human milk: A single-center cohort study in Japan.

BACKGROUND: Donor human milk (DHM) became available in Japan when the first human milk bank was established in 2017. This study investigated the effects of DHM on enteral nutrition (EN) in very low birth weight (VLBW) infants in the single center in Japan. METHODS: Seventy-six VLBW infants hospitalized between April 2017 and March 2020 at Showa University Hospital were included in the study. We retrospectively evaluated age (hours) at which EN was initiated and age (days) until complete feeding (EN > 100 mL/kg/day) was achieved. We compared the DHM and non-DHM groups, or the early human milk (EHM) and non-EHM groups. The EHM group was defined as those in which EN was initiated with the mother's own milk or DHM within 12 h of birth. RESULTS: In 30 extremely low birth weight (ELBW) infants, EN was initiated at significantly earlier postnatal hours in the DHM group compared to those in the non-DHM group. Complete feeding was achieved at significantly earlier ages in the EHM group after adjusting for gastrointestinal complications and gestational age. Additionally, the changes in body weight z-scores from birth to term-equivalent age were significantly greater in the EHM group after adjusting for exclusive breastfeeding and small for gestational age, compared to the non-EHM group. Statistical significance was not noted in 46 subjects (birth weight, 1000-1500 g). CONCLUSION: The use of DHM may contribute to earlier initiation and achievement of EN, resulting in greater early postnatal growth in ELBW infants in Japan.

Birth Weight Standard Deviation Score is a Significant Determinant of Serum Urotensin-II Levels at Term-Equivalent Age in Preterm Infants.

OBJECTIVE: Urotensin II (U-II) is a potent vasoconstrictor peptide, and increased U-II levels are associated with atherosclerosis and hypertension in adults. Low birth weight (LBW) infants have higher risks of such diseases in the future. A small number of nephrons is one of possible mechanism underlying these risks in LBW infants, while vascular elasticity and cardiac function might be another important factor. The objective of this study is to evaluate U-II levels in preterm LBW infants at an early stage of life and determine perinatal factors associated with U-II levels. STUDY DESIGN: The study population consisted of 57 preterm LBW infants (26 males and 31 females), including 49 appropriate for gestational age (AGA) and 8 small for gestational age (SGA) infants, born at a gestational age of ≤34 weeks with a mean birth weight of 1,589 g. Serum U-II levels were measured at term-equivalent age to evaluate perinatal factors related to serum U-II levels. RESULTS: Preterm SGA infants had significantly higher serum U-II levels than preterm AGA infants at term-equivalent age (p = 0.019). Serum U-II levels in preterm LBW infants at term-equivalent age were inversely correlated with birth weight standard deviation (SD) score in a simple regression analysis (r = - 0.395, p = 0,002) and the correlation was maintained in the multiple regression analysis. CONCLUSION: Our results indicate that birth weight SD score might be associated with serum U-II levels in preterm LBW infants at term-equivalent age. Further studies are required to determine whether U-II levels at an early stage of life might influence the risk of atherosclerosis and hypertension. KEY POINTS: · U-II is a potent vasoconstrictor.. · We evaluated serum U-II levels in preterm infants.. · Fetal growth is negatively related to serum U-II levels..

A retrospective cohort study of factors influencing long procedure times in colorectal endoscopic submucosal dissection.

OBJECTIVE: To evaluate the outcomes and factors influencing colorectal endoscopic submucosal dissection (ESD) with a long procedure time. MATERIALS AND METHODS: In this single-center, retrospective study, we included 1,100 patients with 1,199 lesions who underwent colorectal ESD between April 2016 and December 2020. ESD was performed using an advanced system knife for lesions >20 mm. An S-O clip was used as the traction device. The long-time group (LP; procedure time >120 min) and normal-time group (NP; procedure time <120 min) were compared. RESULTS: The procedure times were 166.86 and 44.72 min in the LP and NP groups, respectively. The completion rate was higher in the NP group (96.5% vs. 83.5%, p = .001); the completed lesions were resected en bloc. Multivariate analysis revealed 18.8% and 7.8% of submucosal fibrosis in the LP and NP groups, respectively (odds ratio [OR] = 2.410, p = .026). Compared to the NP group, the LP group presented larger maximum lesion sizes and higher rates of R1 resection, and traction device use. Time to introduction of traction device use was longer in the LP than in the NP group (126.05 vs. 21.72 min; p < .001). Fibrosis tends to occur cecal lesions (OR 2.436, p = .011) and laterally spreading tumor-non-granular-pseudo-depressed (LST-NG-PD) (OR 2.6181, p = .001). CONCLUSIONS: Lesion size and fibrosis were factors associated with a long procedure time in colonic ESD. For fibrotic lesions (LST-NG-PD and cecal lesions), it is necessary to consider early use of traction devices and advisable to plan a strategy for the use of traction devices.

Distribution of serum adiponectin isoforms in pediatric patients with steroid-sensitive nephrotic syndrome.

BACKGROUND: Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. METHODS: We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. RESULTS: The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 µg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. CONCLUSIONS: In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.

Survey of a nutrition management method for very low birthweight infants: Status before wide use of breast milk banks in Japan.

BACKGROUND: The importance of breast-feeding for very low birthweight (VLBW) infants has been pointed out. Some overseas studies suggested that the standardization of enteral nutrition (EN) leads to improved prognosis in VLBW infants. In Japan, however, physicians in charge of infants are responsible for making nutrition management decisions on an individual basis. We conducted an online survey to clarify the course of nutrition management of VLBW infants currently implemented in Japan. METHODS: We mailed a notice to 300 representative neonatologists throughout Japan requesting their participation in the online survey. On the survey website, neonatologists responded to questions regarding the nutritional strategy for five birthweight groups (less than 500 g, 500-749 g, 750-999 g, 1,000-1,249 g and 1,250-1,499 g). RESULTS: Responses were recieved from 137 neonatologists. The first choice for EN up to 1 week after birth was breast milk regardless of birthweight (92.0% for 1,250-1,499 g to 95.6% for 500-999 g). More than 30% of the respondents answered that they fast infants who weigh <750 g at birth or feed them with other mothers' breast milk until their own mother's milk becomes available. The lower the birthweight, the later EN is started, and the greater the number of days to establish EN. CONCLUSION: The lower the birthweight, the more difficult it is to feed infants their own mother's milk and the later the EN is started. If donor milk is supplied in a stable manner, it takes fewer days to establish EN.

Body length and occipitofrontal circumference may be good indicators of neurodevelopment in very low birthweight infants - secondary publication.

AIM: The aim of this study was to predict the neurological prognosis of very low birthweight (VLBW) infants. We examined the relationship between nutritional status, brain volume measured by magnetic resonance imaging (MRI) and anthropometric measurements of VLBW infants at term-equivalent age (TEA). METHODS: We evaluated 27 VLBW infants, born at Showa University Hospital in Japan between April 2012 and August 2013, who underwent brain MRI at TEA. Based on their clinical data, we analysed their protein and energy intake. RESULTS: Median values for the 27 VLBW infants were as follows: gestational age, 29.7 weeks; birthweight 1117 g; protein intake 2.7 g/kg/day and energy intake 97.9 kcal/kg/day. At TEA, the standard deviation scores (SDSs) of body weight, body length and the occipitofrontal circumference (OFC) were -0.8, -1.4 and 0.7, respectively. Multiple regression analysis revealed that the SDSs of body length and the OFC at TEA were significant determinants of white matter volume, but that the SDS of body weight at TEA was not. CONCLUSION: Our findings suggest that the SDSs of body length and the OFC at TEA may be better indicators than body weight for predicting the development of the central nervous system in VLBW infants receiving nutritional management.

Population pharmacokinetic modelling and simulation of 5-fluorouracil incorporating a circadian rhythm in rats.

1. The aim of this study was to develop a population pharmacokinetic (PK) model for 5-fluorouracil (5-FU) and perform simulations to identify the circadian rhythm of the PK of 5-FU and the degree of circadian effects on the 5-FU plasma concentrations. 2. 5-FU plasma concentrations in rats following administration of 5-FU at varying time points throughout the day were obtained and used to develop the population PK model incorporating a circadian rhythm. The Cosinor method was used to describe the circadian variation of 5-FU clearance. 3. Our population PK model could successfully characterize the 5-FU disposition and provide reliable PK parameter estimates. The mesor, amplitude and acrophase of Cosinor model were estimated as 1.93 L/h/kg, 0.10 L/h/kg and 2.02 h, respectively. The peak clearance levels were estimated at ∼2 Hours After Light Onset (HALO) and the trough levels at ∼14 HALO. The plasma concentration-time profile of 5-FU after continuous infusion of 5-FU in rats successfully simulated the circadian variation of steady-state plasma concentrations. 4. The population PK model with individual 5-FU plasma concentrations, dose levels and sampling time points could be valuable for estimating area under the curve (AUC) levels and determining individual 5-FU dose management.

Proteinuria caused by glomerular hypertension during adolescence associated with extremely premature birth: a report of two cases.

BACKGROUND: Prematurity and low birth weight are risk factors for the future development of chronic kidney disease (CKD) and hypertension caused by fewer nephrons with limited filtration surface area. Few reports to date have evaluated their clinical backgrounds and pathological findings, including glomerular hypertension and focal segmental glomerulosclerosis. CASE-DIAGNOSIS/TREATMENT: This report describes two patients, a 15-year-old girl (patient 1), with a birth weight of 618 g and a gestational age of 24 weeks, and a 14-year-old boy (patient 2), with a birth weight of 842 g and a gestational age at 25 weeks. Both had a birth weight appropriate for gestational age. Both were first diagnosed with proteinuria during adolescence, and patient 2 also had hypertension. Pathological findings included glomerulomegaly in both and hypertrophy of the juxtaglomerular apparatus and perihilar glomerulosclerosis in patient 1, suggesting glomerular hypertension. Treatment with lisinopril resulted in the immediate disappearance of proteinuria. Renal dysfunction was observed in both patients, but neither showed evidence of severe aggravation after a follow-up of 5 or 6 years. CONCLUSIONS: Proteinuria in both patients was caused by glomerular hypertension with hyperfiltration. Extremely preterm birth itself may be a risk factor for future CKD. Long-term follow-up of patients born prematurely and at low birth weight, including urinalysis and blood pressure measurements, is necessary to diagnose and treat late renal complications.

Abdominal aortic intima-media thickness in preschool children born preterm.

Recently aortic intima-media thickness (IMT) has been used as an earlier marker of preclinical atherosclerosis in high-risk children, such as those with type 1 diabetes mellitus and hypercholesterolemia. Children who were born preterm have an early elevation in insulin resistance, which may be a risk factor for metabolic syndrome in adulthood. However, there is no optimal marker of subsequent cardiovascular disease for children born preterm. In this study, we aimed to evaluate the effect of preterm birth on aortic IMT during the preschool period. Mean aortic IMT was measured by ultrasound in 26 subjects born preterm (gestational age <37 weeks [preterm group]) and 11 control subjects born at term (term group). The mean aortic IMT of the preterm group was significantly thicker than that of the term group (preterm group: median 577 µm, interquartile range (524-599) versus term group: 517 µm (442-544); p = 0.003). Mean aortic IMT may be one of the earlier markers of subclinical vasculopathy in preschool children who were born preterm.

Relationship between Being Overweight and Clinical Outcomes of Ablation Therapy for Hepatocellular Carcinoma under Ultrasound Guidance: A Retrospective Analysis.

This study aimed to investigate the effect of being overweight on the outcome of ablation therapy for patients with early-stage hepatocellular carcinoma (HCC). This retrospective study included 198 patients with HCC who underwent radiofrequency ablation or microwave ablation at Gunma Saiseikai Maebashi Hospital between April 2017 and December 2021. We divided the patients into two groups based on their body mass index (BMI): overweight (BMI ≥ 25 kg/m2, n = 74 (37.4%)) and non-overweight (BMI < 25 kg/m2, n = 124 (62.6%)). The technical success rates (TSRs) in the first session were 78.4% and 90.3% in overweight and non-overweight patients, respectively, with a significant difference (p = 0.03). Additional ablation therapy for residual tumors was required in 15 (20.3%) overweight and 11 (8.9%) non-overweight patients (p = 0.03), resulting in 95.9% and 99.2% TSRs at the final session, respectively, without a significant difference (p = 0.3). While local tumor progression and distant recurrence rates were not significantly different between the two groups, overall survival was better in overweight patients than in non-overweight patients (p < 0.001). Despite the potential adverse impact of being overweight on public health problems, the present findings showed the relationship between being overweight and improved survival. The negative aspects of being overweight might remain as minor technical issues in HCC patients receiving ablation therapy.

Comparison of Fork-tip and Franseen needles for endoscopic ultrasound-guided fine-needle biopsy in pancreatic solid lesions: A propensity-matched analysis.

Objectives: There is no unanimity regarding the most appropriate needle to use for an endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). To date, new types of FNB needles have been designed, including the Fork-tip and Franseen needles. This study primarily aimed to compare the diagnostic accuracy and histological quality between the use of the Franseen and Fork-tip needles in EUS-FNB for solid pancreatic lesions. Materials and methods: We retrospectively analyzed 147 patients at our center for solid pancreatic lesions, 75 of whom underwent EUS-FNB using a 22-G Franseen needle, and 72 using a 22-G Fork-tip needle, from December 2019 to September 2021. The present study conducted a propensity-matched analysis and confounder adjustment. Results: The diagnostic accuracy of the Fork-tip group (93.3%, 42/45) was the same as that of the Franseen group. For the core tissue and blood scores, no significant difference was observed (p = 0.58, 0.25) between the two groups. The rate of changes in the operator from that of a trainee to an expert was less in the Fork-tip group (4.4%, 2/45) than in the Franseen group (15.6%, 7/45), but not significantly different (p = 0.16). Conclusions: In both groups, the diagnostic accuracy and histological quality were not significantly different. Additionally, there were no significant differences in the rate of operator changes. As both needles are useful, the choice of using either of them is equally good.

International Consensus Guideline on Small for Gestational Age: Etiology and Management From Infancy to Early Adulthood.

This International Consensus Guideline was developed by experts in the field of small for gestational age (SGA) of 10 pediatric endocrine societies worldwide. A consensus meeting was held and 1300 articles formed the basis for discussions. All experts voted about the strengths of the recommendations. The guideline gives new and clinically relevant insights into the etiology of short stature after SGA birth, including novel knowledge about (epi)genetic causes. Further, it presents long-term consequences of SGA birth and also reviews new treatment options, including treatment with gonadotropin-releasing hormone agonist (GnRHa) in addition to growth hormone (GH) treatment, as well as the metabolic and cardiovascular health of young adults born SGA after cessation of childhood GH treatment in comparison with appropriate control groups. To diagnose SGA, accurate anthropometry and use of national growth charts are recommended. Follow-up in early life is warranted and neurodevelopment evaluation in those at risk. Excessive postnatal weight gain should be avoided, as this is associated with an unfavorable cardiometabolic health profile in adulthood. Children born SGA with persistent short stature < -2.5 SDS at age 2 years or < -2 SDS at 3 to 4 years of age, should be referred for diagnostic workup. In case of dysmorphic features, major malformations, microcephaly, developmental delay, intellectual disability, and/or signs of skeletal dysplasia, genetic testing should be considered. Treatment with 0.033 to 0.067 mg GH/kg/day is recommended in case of persistent short stature at age of 3 to 4 years. Adding GnRHa treatment could be considered when short adult height is expected at pubertal onset. All young adults born SGA require counseling to adopt a healthy lifestyle.

Cord serum adiponectin is positively related to postnatal body mass index gain.

BACKGROUND: The roles of adiponectin and leptin in the early stages of life are poorly understood. We previously studied longitudinal changes in these adipocytokines from birth to 12 months of age. The aim of this investigation was to evaluate the correlation between cord serum adipocytokine levels and postnatal growth by 3 years of age. METHODS: A questionnaire was sent to obtain the general physical measurements of 3-year-olds from 56 healthy newborn infants born at a gestational age of 35 weeks or more; 45 valid responses were obtained. The correlations between variables, including cord serum adipocytokine levels at birth and general physical measurements at 3 years, were investigated. RESULTS: Body mass index (BMI) Z-score gain from birth to 3 years was negatively correlated with birthweight SD scores (ß=-0.395, P= 0.019) and gestational age (ß=-0.557, P= 0.016), and positively correlated with cord serum adiponectin levels (ß= 0.253, P= 0.043). BMI Z-score gain from birth to 6 months was negatively correlated with only birthweight SD score (ß=-0.442, P= 0.017). Cord serum leptin levels were not a significant predictor of BMI Z-scores gain in our subjects. BMI Z-scores at 6 months, 12 months, and 3 years of age were not related to cord serum adiponectin or leptin levels. CONCLUSIONS: Birthweight SD score, gestational age, and cord serum adiponectin levels are significant predictors of BMI Z-score gain from birth to 3 years of age in Japanese infants.

Gel immersion endoscopic submucosal dissection: clinical experience with 13 cases of superficial esophageal cancer.

Esophageal endoscopic submucosal dissection (ESD) of tumors located on the gravity side is technically challenging. Given that gel immersion ESD (GIESD) is performed by immersing lesions in gel, we hypothesized that it could be used to eliminate the disadvantage associated with submerging the gravity side. Here, we performed GIESD using VISCOCLEAR for superficial esophageal cancer on the gravity side of the esophagus, with monopolar devices. This study aimed to evaluate the short-term outcomes of GIESD for superficial esophageal cancer. Fifteen patients with 16 superficial esophageal cancers underwent GIESD by a single operator, and 13 cases were evaluated. All patients were male, and GIESD was performed in the middle (12/13, 92.3 %) and lower (1/13, 7.7 %) thoracic esophagus. The lesions were located on the left (7/13, 53.8 %), posterior (5/13, 38.5 %), and right (1/13, 7.7 %) esophageal walls. The median procedure time was 27 minutes (interquartile range [IQR], 14-68), and the median dissection speed was 20 mm 2 /min (IQR, 14-25.7). The median amount of gel used was 400 mL (IQR, 360-580), and no gel-related adverse events were observed. The median total dose of midazolam was 3 mg (IQR, 2-5). GIESD was completed with en bloc and R0 resections achieved in 100 % of the 13 cases. Delayed adverse events, such as bleeding or perforation, did not occur (0/13, 0 %).

Effectiveness of a multi-loop traction device for colorectal endoscopic submucosal dissection performed by trainees: a pilot study.

Colorectal endoscopic submucosal dissection (ESD) is a difficult procedure, and its introduction to trainees has been debated. Although the criteria for performing colorectal ESD vary among institutions, it is often allowed after gaining experience performing surgeries in animals and upper gastrointestinal ESD. This pilot study aimed to compare the treatment outcomes of ESD performed by trainees using the multi-loop traction device (MLTD group) and those of conventional ESD performed by experts (control group). It also aimed to determine whether the MLTD can be used to safely introduce colorectal ESD to trainees. We included 26 colorectal ESD patients (13 in the MLTD group and 13 in the control group) treated at our hospital from October to December 2021. There were no significant differences in the procedure time (50 min vs. 30 min), dissection speed (19.9 mm2/min vs. 28.7 mm2/min), and intraoperative perforation (0% vs. 0%) of the two groups. Furthermore, the rate of ESD self-completion in the MLTD group was 100%. Therefore, the use of the MLTD allowed the safe introduction of colorectal ESD, even among endoscopists with no experience performing colorectal ESD. Consequently, the use of the MLTD may replace animal and upper gastrointestinal ESD when introducing colorectal ESD to trainees.