Divergent neurodevelopmental profiles of very-low-birth-weight infants.

BACKGROUND: Advanced perinatal medicine has decreased the mortality rate of preterm infants. Long-term neurodevelopmental outcomes of very-low-birth-weight infants (VLBWIs) remain to be investigated. METHODS: Participants were 124 VLBWIs who had in-hospital birth from 2007 to 2015. Perinatal information, developmental or intelligence quotient (DQ/IQ), and neurological comorbidities at ages 3 and 6 years were analyzed. RESULTS: Fifty-eight (47%) VLBWIs received neurodevelopmental assessments at ages 3 and 6 years. Among them, 15 (26%) showed DQ/IQ <75 at age 6 years. From age 3 to 6 years, 21 (36%) patients showed a decrease (≤-10), while 5 (9%) showed an increase (≥+10) in DQ/IQ scores. Eight (17%) with autism spectrum disorder or attention-deficit hyperactivity disorder (ASD/ADHD) showed split courses of DQ/IQ, including two with ≤-10 and one with +31 to their scores. On the other hand, all 7 VLBWIs with cerebral palsy showed DQ ≤35 at these ages. Magnetic resonance imaging detected severe brain lesions in 7 (47%) of those with DQ <75 and 1 (18%) with ASD/ADHD. CONCLUSIONS: VLBWIs show a broad spectrum of neurodevelopmental outcomes after 6 years. These divergent profiles also indicate that different risks contribute to the development of ASD/ADHD from those of cerebral palsy and epilepsy in VLBWIs. IMPACT: Very-low-birth-weight infants (VLBWIs) show divergent neurodevelopmental outcomes from age 3 to 6 years. A deep longitudinal study depicts the dynamic change in neurodevelopmental profiles of VLBWIs from age 3 to 6 years. Perinatal brain injury is associated with developmental delay, cerebral palsy and epilepsy, but not with ASD or ADHD at age 6 years.

Utility of Positional Instillation of Contrast Cystography for Diagnosing Occult Vesicoureteral Reflux in Children: A Report of Two Cases.

Positional instillation of contrast (PIC) cystography is effective for detecting occult vesicoureteral reflux (VUR), which can not be revealed by standard voiding cystourethrography (VCUG). We experienced two cases of young female patients; one had repeated urinary tract infection with a negative VUR on standard VCUG, and the other had findings suggestive of reflux hydronephrosis and intolerance of standard VCUG. They underwent PIC cystography, and occult VUR was detected in both cases. Both were successfully treated with simultaneous endoscopic injection therapy with dextranomer/hyaluronic acid. PIC cystography is useful for detecting occult VUR in children with negative VUR findings on standard VCUG or who are unable to tolerate standard VCUG.

Loss of imprinting of the human-specific imprinted gene ZNF597 causes prenatal growth retardation and dysmorphic features: implications for phenotypic overlap with Silver-Russell syndrome.

BACKGROUND: ZNF597, encoding a zinc-finger protein, is the human-specific maternally expressed imprinted gene located on 16p13.3. The parent-of-origin expression of ZNF597 is regulated by the ZNF597:TSS-DMR, of which only the paternal allele acquires methylation during postimplantation period. Overexpression of ZNF597 may contribute to some of the phenotypes associated with maternal uniparental disomy of chromosome 16 (UPD(16)mat), and some patients with UPD(16)mat presenting with Silver-Russell syndrome (SRS) phenotype have recently been reported. METHODS: A 6-year-old boy presented with prenatal growth restriction, macrocephaly at birth, forehead protrusion in infancy and clinodactyly of the fifth finger. Methylation, expression, microsatellite marker, single nucleotide polymorphism array and trio whole-exome sequencing analyses were conducted. RESULTS: Isolated hypomethylation of the ZNF597:TSS-DMR and subsequent loss of imprinting and overexpression of ZNF597 were confirmed in the patient. Epigenetic alterations, such as UPD including UPD(16)mat and other methylation defects, were excluded. Pathogenic sequence or copy number variants affecting his phenotypes were not identified, indicating that primary epimutation occurred postzygotically. CONCLUSION: We report the first case of isolated ZNF597 imprinting defect, showing phenotypic overlap with SRS despite not satisfying the clinical SRS criteria. A novel imprinting disorder entity involving the ZNF597 imprinted domain can be speculated.

Influence of the Retrocolic Versus Antecolic Route for Alimentary Tract Reconstruction on Delayed Gastric Emptying After Pancreatoduodenectomy: A Multicenter, Noninferiority Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine whether retrocolic alimentary tract reconstruction is noninferior to antecolic reconstruction in terms of DGE incidence after pancreatoduodenectomy (PD) and investigated patients' postoperative nutritional status. SUMMARY OF BACKGROUND DATA: The influence of the route of alimentary tract reconstruction on DGE after PD is controversial. METHODS: Patients from 9 participating institutions scheduled for PD were randomly allocated to the retrocolic or antecolic reconstruction groups. The primary outcome was incidence of DGE, defined according to the 2007 version of the International Study Group for Pancreatic Surgery definition. Noninferiority would be indicated if the incidence of DGE in the retrocolic group did not exceed that in the antecolic group by a margin of 10%. Patients' postoperative nutrition data were compared as secondary outcomes. RESULTS: Total, 109 and 103 patients were allocated to the retrocolic and antecolic reconstruction group, respectively (n = 212). Baseline characteristics were similar between both groups. DGE occurred in 17 (15.6%) and 13 (12.6%) patients in the retrocolic and antecolic group, respectively (risk difference; 2.97%, 95% confidence interval; -6.3% to 12.6%, which exceeded the specified margin of 10%). There were no differences in the incidence of other postoperative complications and in the duration of hospitalization. Postoperative nutritional indices were similar between both groups. CONCLUSIONS: This trial could not demonstrate the noninferiority of retrocolic to antecolic alimentary tract reconstruction in terms of DGE incidence. The alimentary tract should not be reconstructed via the retrocolic route after PD, to prevent DGE.

Trends in Bronchopulmonary Dysplasia Among Extremely Preterm Infants in Japan, 2003-2016.

OBJECTIVE: To investigate recent trends in bronchopulmonary dysplasia (BPD) and its risk factors among extremely preterm infants. STUDY DESIGN: Demographic and clinical data were reviewed for 19 370 infants born at 22-27 weeks of gestation registered in the affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2016. We investigated the overall survival and prevalence of bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age and risk factors for developing BPD among the survivors. RESULTS: Among 19 370 infants, 2244 (11.6%) died by 36 weeks' postmenstrual age. The mortality rate decreased from 19.0% (99% CI, 15.7%-22.8%) in 2003 to 8.0% (99% CI, 6.2%-10.3%) in 2016. Among 17 126 survivors, BPD developed in 7792 (45.5%) infants, and its proportion significantly increased from 41.4% (99% CI, 36.5%-46.4%) in 2003 to 52.0% (99% CI, 48.2%-55.9%) in 2016. A multivariable analysis of the survivors showed a positive association of BPD with ≥4 weeks' supplemental oxygen or invasive ventilation, birth weight <750 g, small for gestational age, ≥4 weeks' noninvasive positive pressure ventilation, chorioamnionitis, <26 weeks' gestational age, <20 cases per year of center patient volume, or treated patent ductus arteriosus. Although the median duration of invasive ventilation was shortened, the proportions of factors associated adversely with BPD generally showed increasing trends over time. CONCLUSIONS: The mortality rate of extremely preterm infants has decreased, but the rate of BPD has increased in survivors between 2003 and 2016. Despite the decreasing duration of invasive ventilation over time, increasing rates of BPD suggest that differences in the patient population or other management strategies influence the development of BPD.

[A Patient with Ascending Jejunal Mesentery Metastasis of Pancreatic Cancer after a Subtotal Stomach-Preserving Pancreaticoduodenectomy].

A 73-year-old woman underwent a subtotal stomach-preserving pancreaticoduodenectomy, wedge resection of the portal vein, and partial resection of the transverse colon for pancreatic cancer at the age of 71. After 18 months, a computed tomography image showed an 8 mm tumor in the ascending jejunal mesentery. Six months later, the tumor grew to 20 mm and had an increased FDG uptake. The tumor was diagnosed as metastasis of pancreatic cancer to the ascending jejunal mesentery. Since no metastasis was found in the other organs, resection was performed. The pathological results showed adenocarcinoma with proximal lymph node metastasis. The patient was diagnosed with ascending jejunal mesentery metastasis of pancreatic cancer. The patient has remained healthy without recurrent disease 1 year 6 months after the resection. Ascending jejunal mesentery metastasis of pancreatic cancer is a type of distant metastasis. In the absence of metastasis to other organs, it is tolerable and radical resection is possible.

[A Case of Pancreatic Cancer with Gastric Wall Recurrence after Laparoscopic Distal Pancreatectomy Due to Needle Tract Seeding following EUS-FNA].

A woman in her 80s was diagnosed with pancreatic tail cancer by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We performed laparoscopic distal pancreatectomy followed by adjuvant chemotherapy with S-1 for 6 months. One year after surgery, contrast-enhanced computed tomography revealed a 15 mm mass in the posterior wall of the gastric body. EUS showed a hypoechoic mass in the muscular layer in the gastric wall, which was diagnosed as adenocarcinoma by FNA. We diagnosed gastric wall recurrence due to needle tract seeding(NTS)following EUS-FNA and performed partial gastrectomy. Histopathological diagnosis was gastric wall recurrence of pancreatic cancer. Since NTS following EUS-FNA can be proven only by the presence of gastric wall recurrence after surgery for pancreatic body or tail cancer, the actual risk of NTS including peritoneal dissemination is not clear and may have been underestimated. In case of resectable pancreatic body or tail cancer, indication for EUS-FNA should be carefully considered.

[Analysis of Hepatectomy for Extreme Elderly Patients with Hepatocellular Carcinoma].

Although the first-line treatment for hepatocellular carcinoma(HCC)is hepatectomy, extreme elderly(80 years or older) patients often tend to have a variety of underlying diseases and decreased cardiopulmonary function, which means that surgery involves a high risk. In this case, we examined the safety and efficacy of hepatectomy performed in an extreme elderly patient with HCC. Of the patients with HCC that underwent initial hepatectomy at Kobe University Hospital(n=348)between 2009 and 2015, 23 patients aged 80 years or older at the time of surgery(Group 1, n=23)and those younger than 80 years at the time(Group 2, n=325)were compared, based on parameters related to safety and prognosis. We did not identify differences between the 2 groups with respect to blood loss and operating time. Intraoperative blood transfusion was more common in Group 1. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲ or higher. The median survival of Group 2 patients following hepatectomy(42 months)was better than that of Group 1 patients(34 months), but there was no significant difference between the 2 groups(p=0.429). Furthermore, when the same parameters were compared after adjusting for and matching propensity scores, there were no significant differences in complications, hospitalization periods, and prognosis between the 2 groups. Through proper assessment of oncologic factors and patient risk factors, hepatectomy can be performed safely and effectively even for extreme elderly patients with HCC. If there is no other disease regulating the prognosis, we can expect to achieve similar prognosis in non-extreme elderly patients. Hence, treatments should not be limited solely based on a patient being extremely elderly; rather, proactive treatments should be considered.

Pathological and Radiological Splenic Vein Involvement are Predictors of Poor Prognosis and Early Liver Metastasis After Surgery in Patients with Pancreatic Adenocarcinoma of the Body and Tail.

BACKGROUND: The prognostic impact of pancreatic ductal adenocarcinoma (PDAC) invasion to the splenic vessel is controversial. OBJECTIVE: The aim of this study was to assess the clinical value of pathological and radiological splenic vessel invasion in PDACs of the body and tail. METHODS: Medical records of patients with resectable PDAC of the body and tail who underwent distal pancreatectomy between 2003 and 2016 at the Kobe University Hospital were retrospectively analyzed. RESULTS: Overall, 68 patients (29 female and 39 male patients) were enrolled. Pathologically determined splenic vein invasion (p-SV) and splenic artery invasion (p-SA) were identified in 21 (30.9%) and 5 (7.4%) patients, respectively. The p-SV (but not p-SA) was an independent prognostic factor in multivariate analysis (p = 0.009). On analysis of recurrence patterns, patients with PDAC positive for p-SV were at a higher risk for liver metastasis (p = 0.022); however, the associations were not significant for other recurrence patterns. Liver metastasis occurred earlier in patients who were positive for p-SV (p = 0.015). Preoperative computed tomography effectively diagnosed pathological vessel invasion (SV: sensitivity, 95.2%, specificity, 72.3%; SA: sensitivity, 100%, specificity, 84.1%). Radiological SV invasion remained significant in multivariate analysis regarding postoperative survival (p = 0.007), and was also associated with early liver metastases (p = 0.008). CONCLUSIONS: Pathological/radiological SV invasion were independent adverse prognostic factors associated with early liver metastasis in patients with PDAC of the body/tail. Assessment of these findings may be useful in determining optimal therapeutic options in these patients.

[A Patient with Multiple Pancreatic Metastases Undergoing Total Pancreatectomy 18 Years after Renal Cell Carcinoma Resection].

A 71-year-old woman underwent right nephrectomy for the treatment of clear cell renal cell carcinoma at the age of 53. After 15 years, surgical removal of a solitary tumor was performed in the right adrenal gland and thyroid gland; both were diagnosed as metastases of renal cell carcinoma. Eighteen years after the initial resection, computed tomography(CT) showed multiple hypervascular tumors spreading across the entire area of the pancreas. She was referred to our hospital, and endoscopic ultrasound-guided fine needle aspiration biopsy(EUS-FNA)revealed that they were metastases from the renal cell carcinoma. Total pancreatectomy and splenectomy were performed, and the patient remains alive and well with no evidence of recurrent disease 7 months after the pancreatectomy. Furthermore, her blood glucose level is well controlled with insulin therapy.

Prediction of lymph node metastasis in pancreatic neuroendocrine tumors by contrast enhancement characteristics.

BACKGROUND: Iso- or hypo-attenuating areas in the arterial phase on contrast-enhanced computed tomography (CE-CT) have been reported to be negative prognostic features in pancreatic neuroendocrine tumors (PNETs). Given that the optimal indication for lymph node dissection in patients with PNET remains unclear, we sought to utilize enhancement characteristics on CE-CT as a preoperative predictor of regional lymph node metastasis in PNETs. METHODS: The medical records of patients with well-differentiated PNETs who underwent pancreatectomy along with lymphadenectomy were retrospectively analyzed. We divided PNETs into two groups based on the extent of attenuation in the late arterial phase on CE-CT imaging. PNETs that showed hyper-attenuation over the entire area compared to the adjacent normal pancreas were categorized as hyper-PNETs. PNETs that contained both hyper and iso- or hypo-attenuation regions as well as those that showed only iso- or hypo-attenuation over the entire area were categorized as hetero/hypo-PNETs. RESULTS: Forty-one patients with a median age of 64 years were enrolled, including 11 with hyper-PNETs and 30 with hetero/hypo-PNETs. Hetero/hypo-PNETs were significantly larger than hyper-PNETs (P = 0.022), and the former group more frequently comprised G2 tumors, according to the World Health Organization 2010 classification (P < 0.001). On univariate and multivariate analyses, hetero/hypo-PNETs were independently associated with regional lymph node metastasis. CONCLUSIONS: The presence of iso- or hypo-attenuating regions appears to be associated with regional lymph node metastasis in PNETs. Tumor enhancement characteristics should be assessed in patients with PNET so as not to miss those at high risk of lymph node metastasis.

[A Surgical Resected Case of VIPoma with Para-Aortic Lymph Node Involvement].

A 72-year-old woman had severe watery diarrhea and weight loss. Computed tomography demonstrated a 55mm tumor in pancreatic tail with enlargement of para-aortic lymph nodes. There was no apparent liver metastasis. Endoscopic ultrasound demonstrated a well-circumscribed heterogenous tumor, which was diagnosed neuroendocrine tumor by endoscopic ultrasound-guided fine needle aspiration biopsy. For suspected VIPoma with para-aortic lymph node involvement, distal pancreatectomy and para-aortic lymphadenectomy was performed. The tumor was diagnosed as VIPoma by immunohistochemistry. The diarrhea improved after surgery. No evidence of recurrence was detected after a follow-up of 11 months.

Postoperative Serum Albumin Level is a Marker of Incomplete Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Adjuvant chemotherapy (AC) is recommended as a standard treatment after curative resection in patients with pancreatic adenocarcinoma (PA). Although patients who failed to complete AC had significantly worse survival compared with those who completed AC for cancers in various organs, the effects of complete AC on survival in patients with PA have not been investigated. The purpose of this study was to clarify the impact of complete AC on PA patient survival and to identify independent risk factors for incomplete AC. METHODS: Medical records of 236 consecutive PA patients who planned to undergo surgical resection with curative intent between January 2000 and September 2012 at Kobe University Hospital were retrospectively reviewed. Of these, the complete AC (n = 75) and the incomplete AC (n = 30) groups due to adverse events were compared. RESULTS: Patient survival was significantly better in the complete AC group than in the incomplete AC group (median survival time 48.9 vs. 17.9 months; 5-year survival rate 42.7 vs. 17.1 %; p < 0.0001). Preoperative white blood cell count and postoperative serum albumin level were identified as independent risk factors for incomplete AC. By receiver operating characteristic curve analysis, the cutoff value of postoperative serum albumin level was 3.1 mg/dL. CONCLUSIONS: PA patients who completed AC had significantly better survival than those who failed to complete AC. Postoperative serum albumin level is a marker for failure to complete AC. Further prospective studies are needed to determine whether perioperative nutritional intervention could increase AC completion rate and improve prognosis in PA patients.

Acute graft-versus-host disease following simultaneous pancreas-kidney transplantation: report of a case.

Acute graft-versus-host-disease (aGVHD) is a rare complication in the setting of pancreas-kidney transplantation (PKT). We herein describe the case of a 37-year-old male with severe type 1 diabetes with chronic renal failure who received simultaneous PKT from a female donor. Diarrhea developed on postoperative day (POD) 10. Subsequently, fever and liver dysfunction occurred on POD 32. Skin rashes appeared with pain and itching on his trunk and extremities on POD 40. As pancytopenia occurred on POD 63, bone marrow biopsies demonstrated profound hypoplastic marrow. On POD 69, we eventually made a definitive diagnosis of aGVHD because skin biopsies revealed the XX chromosome signal in a fluorescence in situ hybridization analysis. Thereafter, 100 mg of prednisolone was administered for 5 days. Although every symptom was temporarily improved, on POD 156, the patient expired from the septic pneumonia without any effects of antibiotics. Clinician should be aware that PKT has the potential to induce aGVHD.

Increased incidence of retroperitoneal teratomas and decreased incidence of sacrococcygeal teratomas in infants with Down syndrome.

Individuals with Down syndrome (DS) have a unique profile of neoplasms, with a higher incidence of leukemias and a lower incidence of solid tumors than seen in the general population. We recently encountered two cases of infants with DS with retroperitoneal teratoma. After reviewing the literature on teratomas in DS, we found that the incidence of retroperitoneal teratomas was higher and the incidence of sacrococcygeal teratomas was lower in infants with DS than in the general population.

[A case of metachronous pancreatic cancer that developed 4 years after initial pancreatectomy].

A 55-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy for pancreatic ductal adenocarcinoma( PDAC) in July 2008. The final diagnosis was Stage I PDAC according to the Union for International Cancer Control( UICC) TNM classification. After the operation, adjuvant chemotherapy with gemcitabine was administered for 6 months. The tumor marker level increased at 49 months after the operation, and 18-fluoro-deoxyglucose (FDG)-positron emission tomography( PET) showed FDG accumulation in the remnant pancreas. A hypovascular tumor was revealed in the remnant pancreas on computed tomography( CT). As PDAC was diagnosed without distant metastasis, completion pancreatectomy was performed. Histopathological investigation revealed PDAC with invasion into the muscularis propria of the anastomosed jejunum and splenic plexus. The final diagnosis was T3N0M0 UICC Stage IIA metachronous PDAC. The postoperative course was uneventful. However, multiple liver metastases and local recurrence were detected on CT 2 months after resection, and the patient died 3 months after resection. Most reported cases of metachronous PDACs were diagnosed at an advanced stage despite regular follow-ups after the initial resection. Further investigation is needed to determine the adequate surveillance time and novel therapeutic strategies.

Effectiveness of umbilical culture for surveillance of methicillin-resistant Staphylococcus aureus among neonates admitted to neonatal intensive care units.

To compare the culture sensitivities of MRSA detection, we collected 988 paired umbilical and nasal cultures from screened neonates. MRSA positivity rates were 79.1% from umbilicus and 41.9% from nares (P = .01). The umbilicus was a more useful culture site than the nares for surveillance of MRSA among neonates upon admission.

Low placental weight may be involved in the etiology of congenital cryptorchidism in neonatal boys.

INTRODUCTION: Several factors have been reported to be associated with the etiology of cryptorchidism; however, clear evidence regarding the risk factors for cryptorchidism is elusive. In the present study, we evaluated the clinical characteristics of cryptorchidism using the common neonatal intensive-care unit (NICU) database of the National Hospital Organization and explored one of possible factors associated with the development of cryptorchidism. METHODS: A total of 7882 male neonates were included in this study. We separated them into two groups: those without cryptorchidism (n = 7852) and those with cryptorchidism (n = 30) at the time of discharge from the NICU. Cryptorchidism was defined as a condition in which the testis was located out of the scrotum on the route of descent at the time of NICU discharge. The associations between cryptorchidism and the maternal, placental, and neonatal information were analyzed. Analyses were performed statistically to compare nominal variables between the groups using Fisher's direct establishment calculation method and logistic regression analyses. RESULTS: Univariate analyses showed the placental weight <10% tile (odds ratio 3.31, 95% confidence interval [CI] 1.18-8.64), birth height <-2 standard deviations (SD) (odds ratio 3.65, 95% CI 0.92-10.6), birth weight <-2SD (odds ratio 4.06, 95% CI 1.55-9.51), and small for gestational age (odds ratio 3.82, 95% CI 1.46-8.97) were significantly associated with the development of cryptorchidism. Multivariate analyses showed that placental weight <10th percentile (odds ratio 2.86, 95% CI 1.11-7.44) was significantly associated with the development of cryptorchidism. DISCUSSION: Although, this study population was limited to infants admitted to the ICU, the data indicated a possible association between low placental weight and the development of cryptorchidism in neonatal boys.

Changing risk factors for postpartum depression in mothers admitted to a perinatal center.

BACKGROUND: The Edinburgh postnatal depression scale (EPDS) is commonly used in screening for major postpartum depression (PPD). We explored the clinical factors associated with score changes. METHODS: Mothers (n=1,287) who delivered a single live-born infant in Kokura Medical Center in Japan during 2018-2019 were analyzed. The EPDS-Japanese version was conducted at the first and fourth weeks after childbirth. Scores of ≥9 were considered to indicate an increased risk of PPD. RESULTS: The scores improved during the four-week period (5.03±0.12 to 3.79±0.10). Primiparity, Cesarean section (CS), and a low Apgar score were identified as initial risk factors, however, primiparity remained in the multivariate analysis (aOR 2.02, 95% CI 1.37-2.97). Age ≥35 years was associated with worsened scores (aOR 1.88, 95%CI 1.01-3.51), but CS improved (aOR 0.38, 95%CI 0.21-0.70). Primiparity, CS, and neonatal respiratory support were the initial risk factors, while infant anomaly was a late risk factor in mothers whose infants were admitted to the neonatal intensive care unit (NICU) (aOR 3.35, 95%CI 1.31-8.56). In mothers of infants with an NICU stay of ≥4 weeks, infant anomaly was associated with worsened scores (aOR 6.61, 95%CI 1.11-39.3), while respiratory support was associated with improved scores (aOR 0.09, 95%CI 0.01-0.65). Twenty-six mothrs with worsened scores received psychiatric support; three developed PPD. Two of the three were ≥35 years of age, neither of their infants had anomalies. CONCLUSION: Maternal aging and infant anomaly were risk factors for PPD. PPD occurred in mothers with worsened EPDS scores after mental care. Puerperants with worsening risk factors should be targeted to control PPD.