Shun Onishi

Long-term outcome of bowel function for 110 consecutive cases of Hirschsprung's disease: Comparison of the abdominal approach with transanal approach more than 30 years in a single institution – is the transanal approach truly beneficial for bowel function?

BACKGROUND We compared the long-term outcomes of the bowel function (BF) in Hirschsprungs disease (HD) patients who underwent transanal endorectal pull-through (TA) with those who underwent the Soave-Denda (SD) procedure. METHODS Patient data were collected from 1984 to 2015 from 110 HD patients who underwent definitive diagnosis and operation. The follow-up data were analyzed retrospectively. BF was evaluated according to the evacuation score (ES) of the Japan Society of Anorectal Malformation Study Group at 3, 5, 7, 9, and 11years of age. RESULTS The operative procedures performed were as follows: SD: 71 (64.5%), TA: 38 (34.5%), and Duhamel: 1 (1.0%). We compared SD with TA. The ES improved chronologically after both procedures, and patients achieved satisfactory results at least 10years after operation. There was no significant difference in the total ES at all ages. The incontinence and frequency of bowel movement scores of TA patients were significantly lower than those of SD patients at several points. CONCLUSION TA is simple, less invasive, and adaptive for neonates and small infants. However, regarding the bowel function, TA is not always superior to SD. The surgical technique of TA must be improved according to a detailed understanding of the anatomy. LEVEL OF EVIDENCE Retrospective study - level III.

Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study

BACKGROUND/PURPOSE Total parenteral nutrition (TPN) has been reported to be associated with mucosal atrophy of the small intestine. Ghrelin has hormonal, orexigenic, and metabolic activities. We investigated whether ghrelin improved intestinal mucosal atrophy using a TPN-supported rat model. METHODS Rats underwent jugular vein catheterization and were divided into four groups: TPN alone (TPN), TPN plus low-dose ghrelin (TPNLG), TPN plus high-dose ghrelin (TPNHG), and oral feeding with normal chow (OF). Ghrelin was administered continuously at dosages of 10 or 50 μg/kg/day. On day 6 rats were euthanized, and the small intestine was harvested and divided into the jejunum and ileum. Then the villus height (VH) and crypt depth (CD) were evaluated. RESULTS The jejunal and ileal VH and CD in the TPN group were significantly decreased compared with those in the OF group. TPNHG improved only VH of the jejunum. TPNLG improved VH and CD of the jejunum and CD of the ileum. The improvement of TPNLG was significantly stronger than that in CD of the jejunum and ileum. CONCLUSIONS TPN was more strongly associated with mucosal atrophy in the jejunum than in the ileum. Low-dose intravenous administration of ghrelin improved TPN-associated intestinal mucosal atrophy more effectively than high-dose administration.

Ghrelin stimulates intestinal adaptation following massive small bowel resection in parenterally fed rats

Background: Since short bowel syndrome (SBS) patients face life‐threatening conditions, the development of therapeutic strategies to induce intestinal adaptation has been investigated. Ghrelin, a ligand of growth hormone (GH) secretagogue‐receptor that stimulates the release of GH and insulin like growth factor‐1 (IGF‐1), has several pleiotropic effects. We investigated whether ghrelin induces intestinal adaptation in parenterally fed rats with SBS. Methods: Sprague‐Dawley rats underwent venous catheterization and were divided into 3 groups: those receiving 90% small bowel resection while leaving the proximal jejunum and distal ileum (90% SBR) with TPN (SBS/TPN group), those receiving 90% SBR with TPN+ghrelin (SBS/TPN/ghrelin group), and those receiving sham operation and fed chow (sham group). Ghrelin was administered intravenously at 10&mgr;g/kg/day. On Day 13, the rats were euthanized and the small intestine harvested, and the histology and crypt cell proliferation rates (CCPR), apoptosis, and nutrient transporter protein levels were analyzed and the plasma hormones were measured. Results: The villus height and crypt depth of the ileum in the SBS/TPN/ghrelin group were significantly higher than in the SBS/TPN group. The CCPR of the jejunum and the ileum significantly increased by the administration of ghrelin; however, the apoptosis rates did not significantly differ between the SBS/TPN and SBS/TPN/ghrelin groups. Significant differences did not exist in the plasma IGF‐1 and nutrient transporter protein levels among three groups. Conclusions: The intravenous administration of ghrelin stimulated the morphological intestinal adaptation of the ileum to a greater degree than the jejunum due to the direct effect of ghrelin. HIGHLIGHTSVillus height and crypt depth of the ileum were increased by ghrelin.Crypt cell proliferation rates of the small intestine were increased by ghrelin.Plasma IGF‐1 concentrations were not altered with or without ghrelin.The nutrient transporter protein levels were not changed with or without ghrelin.

The bowel function and quality of life of Hirschsprung disease patients who have reached 18 years of age or older – the long-term outcomes after undergoing the transabdominal soave procedure

BACKGROUND/PURPOSE Hirschsprung disease (HD) is considered curable, but the postoperative bowel function is not always satisfactory. In this study, we evaluated the general condition, bowel function, and social performance in adults who were older than 17years of age who had undergone definitive operations in childhood. METHOD From 1984 to 2016, 110 patients with HD underwent definitive surgery at our institute. Sixty-three patients who had undergone the transabdominal Soave procedure reached 18years of age. Their present status and symptoms, anorectal function, genitourinary function, and social performance were evaluated during the clinical follow-up via a questionnaire survey. RESULT The mean age of the questionnaire respondents was 25.0 (19-37) years. The bowel function was mostly good. However, 56% of patients had abdominal pain more than once a week. Regarding evacuation symptoms, incontinence and soiling occurred in 18.7%. Among the respondents 33.3% were married, and 60% of those who were married had children. The respondents had achieved success in their education and professional careers. CONCLUSION The bowel function of most patients was satisfactory, although some had chronic abdominal symptoms. Pediatric surgeons should continue trying to achieve complete bowel function after definitive surgery of HD. TYPE OF STUDY Prospective Cohort Study. LEVEL OF EVIDENCE Level III.

The protective effect of fish oil lipid emulsions on intestinal failure-associated liver disease in a rat model of short-bowel syndrome

PurposePediatric patients with intestinal failure need long-term parenteral nutrition (PN), but this nutritional support causes liver dysfunction, such as intestinal failure-associated liver disease (IFALD). Several studies have shown that the lipid emulsion produced by soybean oil (SO) is associated with the occurrence of IFALD. In this study, we evaluated the effect of SO and fish oil (FO) lipid emulsion on hepatic steatosis.MethodsSprague-Dawley rats underwent jugular vein catheterization and were divided into three groups: sham operation with normal chow (Sham group), 80% small bowel resection (80% SBR) + TPN with SO lipid emulsion (SO group), and 80% SBR + TPN with FO lipid emulsion (FO group). All rats were euthanized and the serum biochemistry and hepatic histology analyzed.ResultsNo significant differences in the serum liver or biliary enzymes were noted between the SO and FO groups. The pathological findings and NAFLD score in the FO group did not show steatosis and were significantly lower than in the SO group. An analysis of the fatty acids profile in the both the SO and FO groups did not indicate essential fatty acid deficiency (EFAD).ConclusionFO lipid emulsion may have a protective role against steatosis of IFALD without EFAD.

The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection

AIMS AND OBJECTIVES Fish oil (FO) lipid emulsion and a new lipid emulsion (SMOF) are important treatments for intestinal failure-associated liver disease. We evaluated the efficacy of FO and SMOF lipid emulsion on intestinal mucosal adaptation using a total parenteral nutrition (TPN)-supported rat model of short bowel syndrome. MATERIAL & METHODS Sprague-Dawley rats underwent jugular vein catheterization and 90% small bowel resection and were divided into three groups: TPN with soy bean oil lipid emulsion (SO group), FO lipid emulsion (FO group), or SMOF (SMOF group). On day 13, the rats were euthanized, and the small intestine was harvested. The microscopic morphology and crypt cell proliferation rate (CCPR) were then evaluated. RESULTS The villus height of the ileum in the SMOF group was significantly higher than in the SO group. The crypt depth of the intestine in the SMOF group was significantly lower than in the SO group. The CCPRs of the intestine in the FO and SMOF groups were both higher than in the SO group. CONCLUSIONS Lipid emulsion affected the bowel morphology, such as the mucosa as well as the intestinal smooth muscle. Further studies are needed to clarify the mechanisms.

Identification of a novel variant of the RET proto-oncogene in a novel family with Hirschsprung’s disease

AbstractPurposeHirschsprung’s disease (HSCR) is a congenital disorder of the enteric nervous system characterized by the absence of ganglion cells in the Auerbach’s and Meissner’s plexuses. Although about 7% of cases are hereditary, the causal mutations have not been completely characterized. We encountered a novel family with inherited HSCR and screened them for causal mutations. MethodsA Japanese family of five female patients and six unaffected individuals was subjected to a whole-exome analysis with a next-generation sequencer.ResultsAfter exome sequencing and the annotation of mutations, we identified co-segregated mutations with sequential filtering steps via a standard protocol. Eight mutations were identified: two on chromosome 10 and six on chromosome 11. We used pathogenicity prediction tools such as Genomic Evolutionary Rate Profiling, SIFT, and PolyPhen2 to predict the impact of mutations on the protein activity. S922Y, a novel mutation of RET, was identified as a likely causal mutation. In addition, a mutation of rs2435357T, known as enhancer of RET located in intron 1 of RET, was detected in this family.ConclusionThe coexistence of RET mutations in both the exon (S922Y) and intron1 (rs2435357T) indicated a risk of HSCR in this family.

The changing profile of safe techniques for the insertion of a central venous catheter in pediatric patients – improvement in the outcome with the experiences of 500 insertions in a single institution

BACKGROUND The ability to safely insert a central venous catheter (CVC) is critical to avoid associated complications. The aim of this study was to explore appropriate technique to maintain the safety of pediatric patients during CVC. METHODS We reviewed the surgical records of CVC insertion techniques and associated complications of 503 tunneled CVC insertions performed from 2000 to 2015. RESULTS Two hundred thirty CVCs (45.7%) were inserted into the subclavian vein using the landmark technique for 10years (first period). Only two pneumothoraxes (0.9%) were experienced. In 2009, we adopted ultrasound-guided venous catheterization from the internal jugular vein, and 103 CVCs (20.5%) were inserted (second period). This procedure led to penetration into the innominate vein (1.0%) by dilater sheath. Patient underwent repair of the penetrated vessel. After this serious complication, 170 CVCs (33.8%) were inserted using the venous cutdown procedure except two catheters. We had two cases whose accessible veins were occluded because of frequent catheterization using venous cutdown technique. No mechanical complications were experienced. CONCLUSIONS The venous cutdown method is the safest technique for inserting a tunneled CVC in pediatric patients. However, multiple vein occlusions because of repeated catheterizaion by venous cutdown lead to the exhaustion of accessible vessels. LEVEL OF EVIDENCE Treatment Study - Level IV.