Neurodevelopmental impairment following surgical necrotizing enterocolitis with gestational age ≥ 28 weeks: who is at risk?

PURPOSE: Surgical necrotizing enterocolitis (NEC) is a severe medical condition that, even after surgery, a portion of the survival infants may still have neurological sequelae. The objective of this study was to identify the risk factors associated with the development of permanent neurodevelopmental impairment (NDI) in neonates with surgical NEC. METHODS: Between January 2016 and June 2022, a retrospective data collection was conducted on 98 individuals who experienced surgical NEC with gestational age ≥ 28 weeks. Among these patients, 27 patients were diagnosed with NDI, while the remaining 71 patients did not have NDI. Based on this division, the patients were categorized into the NDI group and the Non-NDI group. Demographics, comorbidities, and admission lab results were analyzed using univariate and logistic regression analyses. RESULTS: Of the 98 neonates following surgical NEC, 27(27.6%) developed permanent neurodevelopmental impairment (NDI). Predictors of NDI were identified through the final multivariable logistic regression analysis, which revealed that gestational age ≤ 32 weeks (p = 0.032; odds ratio [OR], 5.673), assisted mechanical ventilation after NEC onset (p = 0.047; OR, 5.299), postoperative acute kidney injury (p = 0.040; OR, 5.106), CRP day 3 after NEC onset (p = 0.049; OR, 1.037), time from presentation to surgery (p = 0.003; OR, 1.047) were significant risk factors. CONCLUSIONS: Our study identified gestational age ≤ 32 weeks, assisted mechanical ventilation after NEC onset, postoperative acute kidney injury, CRP day 3 after NEC onset, and time from presentation to surgery as significant risk factors for NDI in neonates with surgical NEC. These factors would be helpful to refine treatment modalities for better disease outcomes. We also determined the cut-off values of CRP day 3 after NEC onset and time from presentation to surgery, allowing for the individualized evaluation of NDI risk and the implementation of earlier targeted laparotomy.

A new classification for surgical NEC during exploratory laparotomy: introduction and reproducibility assessment.

PURPOSE: Variability in necrosis patterns and operative techniques in surgical necrotizing enterocolitis (NEC) necessitates a standardized classification system for consistent assessment and comparison. This study introduces a novel intraoperative reporting system for surgical NEC, focusing on reliability and reproducibility. METHODS: Analyzing surgical NEC cases from January 2018 to June 2023 at two tertiary neonatal and pediatric surgery units, a new classification system incorporating anatomical details and intestinal involvement extent was developed. Its reproducibility was quantified using kappa coefficients (κ) for interobserver and intraobserver reliability, assessed by four specialists. Furthermore, following surgery, the occurrence of mortality and enteric autonomy were evaluated on the basis of surgical decision-making of the novel intraoperative classification system for surgical NEC. RESULTS: In total, 95 patients with surgical NEC were included in this analysis. The mean κ value of the intra-observer reliability was 0.889 (range, 0.790-0.941) for the new classification, indicating excellent agreement and the inter-observer reliability was 0.806 (range, 0.718-0.883), indicating substantial agreement. CONCLUSION: The introduced classification system for surgical NEC shows high reliability, deepening the understanding of NEC's intraoperative exploration aspects. It promises to indicate operative strategies, enhance prognosis prediction, and substantially facilitate scholarly communication in pediatric surgery. Importantly, it explores the potential for a standardized report and may represent a step forward in classifying surgical NEC, if pediatric surgeons are open to change.

Causes of recurrence of paediatric inguinal hernia after single-port laparoscopic closure.

PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.

Upregulation of CD3ζ and L-selectin in antigen-specific cytotoxic T lymphocytes by eliminating myeloid-derived suppressor cells with doxorubicin to improve killing efficacy of neuroblastoma cells in vitro.

BACKGROUND: Agglomeration of myeloid-derived suppressor cells (MDSCs) in tumors impedes immunotherapeutic effects. Doxorubicin (DOX) is currently the most specific drug used for the selective removal of MDSCs. Here, we study the feasibility and mechanism of eliminating MDSCs by DOX to improve antigen-specific cytotoxic T lymphocyte (CTL)-killing neuroblastoma (NB) cells in vitro. METHODS: CTL and MDSC were prepared; then, CTLs, NB cells, MDSCs, and DOX were mixed and cultivated in different collocation patterns and divided into different groups. The levels of cluster of differentiation 3ζ chain (CD3ζ) and L-selectin in CTL in different groups were detected. Thereafter, the killing rate of NB cells and secretion of interleukin-2 and interferon-γ were measured and compared. RESULTS: By real-time polymerase chain reaction (PCR) and Western blot test respectively, the proliferation and killing effect of CTLs on NB cells were all inhibited by MDSC through downregulating CD3ζ (p = 0.002; p = 0.001) and L-selectin (p = 0.006; p < 0.001). However, this inhibitory effect was reversed by DOX. Significant differences were observed in the levels of interleukin-2 (p < 0.001), interferon-γ (p < 0.001), and the killing rate (p < 0.001) among the groups, except between the CTL +SK-N-SH and CTL +SK-N-SH +DOX groups (p > 0.05). CONCLUSIONS: Targeted elimination of MDSCs by DOX can improve Ag-specific CTL killing of NB cells in vitro by upregulating CD3ζ and L-selectin. This study provides a novel method to enhance the immunotherapeutic effects of NB.

Exogenous Secretin Improves Parenteral Nutrition-associated Liver Disease in Rats.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) is a feared and life-threatening complication in neonates with intestinal failure (IF) receiving long-term total parenteral nutrition (TPN). This study aims to investigate the effect of exogenous secretin on liver pathology and hepatic function in a rat model of PN-associated liver disease (PNALD). METHODS: Male Sprague-Dawley rats underwent right jugular venous catheterization to receive 14-day continuous TPN therapy. All rats were allocated into 3 groups: the Control group (n = 8) did not have surgery or TPN and was fed standard rat chow ad libitum; the TPN group (n = 8) underwent catheter insertion and TPN treatment; and the TPN/S group (n = 8) also underwent catheter insertion, TPN treatment, and exogenous secretin treatment (2.5 nmol ·â€Škg ·â€Šday) daily. Fourteen days after initial surgery, we collected the animals' liver and blood samples for further test. RESULTS: The TPN/S group had diminished direct bilirubin (TPN, 2.1 ±â€Š0.7 µmol/L; TPN/S, 1.5 ±â€Š0.2 µmol/L) and liver total bile acid levels (TPN, 144.5 ±â€Š21.2 µmol/L; TPN/S, 123.4 ±â€Š10.4 µmol/L) and improved histological outcomes compared with those in the TPN group. Exogenous secretin also enhanced the canalicular transporter (BSEP, 0.5-fold, P = 0.011) and inhibited the basolateral transporter (OSTA, -0.48-fold, P = 0.002; OSTB, -0.6-fold, P = 0.013) of liver bile acid. CONCLUSIONS: In this animal model of PNALD, secretin may improve cholestasis by enhancing canalicular transport, inhibiting the basolateral export of liver bile acid, and eventually decreasing the total bile acid level in the liver. Exogenous secretin treatment may potentially prevent and treat IFALD in IF patients relying on long-term TPN therapy.

[Transumbilical single-port laparoscopy combined with improved double hernia needles for pediatric hydrocele].

OBJECTIVE: To compare the clinical effect of transumbilical single-port laparoscopy combined with improved double hernia needles with that of traditional open surgery in the treatment of hydrocele in children. METHODS: We retrospectively analyzed 35 cases (54 sides) of pediatric hydrocele treated by transumbilical single-port laparoscopy combined with improved double hernia needles (laparoscopy group). We recorded the operation time, intraoperative blood loss, hospital stay, scrotal edema, and postoperative complications and compared them with those of another 46 cases (58 sides) treated by traditional open surgery (open surgery group) during the same period. RESULTS: The laparoscopy group showed a significantly shorter operation time, less intraoperative blood loss, milder scrotal edema, and fewer hospital days than the open surgery group (all P<0.05). However, no statistically significant difference was found in the incidence of postoperative complications between the two groups (P>0.05). Subcutaneous emphysema developed in 2 patients in the laparoscopy group, which disappeared after 1－3 days of oxygen inhalation and other symptomatic treatment, while scrotal hematoma occurred in 1 and incision fat liquefaction in 2 patients in the open surgery group 3 days postoperatively, which healed after debridement suture and daily dressing, respectively. The patients were followed up for 3－6 months, which revealed no late complications in the laparoscopy group but 1 case of unilateral recurrence and 2 cases of offside recurrence in the open surgery group, all cured by laparoscopic internal ring ligation. CONCLUSIONS: Transumbilical single-port laparoscopy combined with improved double hernia needles is superior to traditional open surgery for the treatment of pediatric hydrocele and therefore deserves clinical generalization.

Laparoscopic cyst excision and Roux-Y hepaticojejunostomy for children with choledochal cysts in China: a multicenter study.

AIMS: Laparoscopic hepaticojejunostomy (LH) for children with choledochal cyst (CDC) has become feasible and popular recently. The purpose of this study is to evaluate the safety and efficacy of LH for CDC in a large multicenter series. PATIENTS AND METHODS: Medical records of 956 consecutive patients who underwent LH for CDC at seven academic institutions from June 2001 to May 2012 were retrospectively analyzed. Ultrasonography, upper gastrointestinal contrast studies, and laboratory tests were performed during the follow-up period. RESULTS: A total of 956 patients of CDC treated with LH were identified and included in this study. Of these patients, there were no significant differences in age, gender ratio, and the subtypes of CDC among the seven centers. The operative time of all patients decreased significantly as time went by. Interestingly, the centers that began to perform LH earlier, like cohort A, B, and C, took much more time in the initial cases than the later centers. The postoperative complications included 12 (1.3 %) intra-abdominal fluid collection, 6 (0.6 %) anastomotic stenosis, 14 (1.5 %) bile leak, 8 (0.8 %) Roux loop obstruction and 4 (0.4 %) gastrointestinal bleeding, and one case developed intrahepatic stone formation; two mortalities occurred; one died of hyperkalemia, and the other one died of postoperative bleeding. No other complication occurred during the mean follow-up of 5.7 years (ranged from 4 month to 11 years). CONCLUSIONS: We reported a multi-institutional series of LH in children with CDC. Our findings suggested that LH represents a feasible treatment option for CDC by offering reliable middle and long-term outcome, low surgical morbidity.

Laparoscopically assisted extrahepatic bile duct excision with ductoplasty and a widened hepaticojejunostomy for complicated hepatobiliary dilatation.

BACKGROUND: Complicated hepatobiliary dilatation is characterized by congenital cystic dilatation of the biliary tree extending to involve the intrahepatic biliary channels. Some studies have reported on laparoscopic excision for common choledochal cyst, yet there are little reports on laparoscopic surgery for congenital choledochal cyst with intrahepatic bile duct dilatation. In this paper, we present our experiences in laparoscopic extrahepatic bile duct excision combined with ductoplasty and hepaticojejunostomy for complicated hepatobiliary dilatation. METHODS: We retrospectively studied 153 children (age ranged between 3 months and 12 years) who had undergone laparoscopic cholangiopancreatography and radical choledochal resection in our institute from 2002 to 2012. A co-existing extra- and intra-hepatic dilatation was found in 26 patients. After resecting the extrahepatic dilated duct and widening the portohepatic or intrahepatic ductal lumen (ductoplasty) under the laparoscopic video, a widened hepaticojejunostomy at the hilum was performed using a Roux-en-Y jejunal limb. RESULTS: Laparoscopic procedures were successfully performed in all children with complicated hepatobiliary dilatation and their ductal stenoses at the hilum were corrected. In 13 patients with a stricture that converged into the common hepatic duct, the stenotic segment was incised and a wide hepaticojejunostomy was completed at the porta hepatis. A constrictive confluence of the right and left hepatic duct was observed in eight cases, a bi-ductal portojejunostomy was achieved at the bifurcation after making incision in the bilateral stenotic hepatic ducts to create a large stoma. A downstream stricture of the left hepatic duct was identified and incised from the hilum to the dilated segment along the lateral wall in three cases, so that a long hepaticojejunostomy to left intrahepatic duct lay in an oblique orientation. In two cases, a septum was found in the right hepatic ductal terminal and excised through the hilar orifice. Postoperative complications were observed in two children including temporary bile leakage and hepaticojejunal anastomotic stricture each one. The intrahepatic duct dilatation was remarkably reduced in size during the follow-up. CONCLUSIONS: Laparoscopic cholangiopancreatography is a valuable method in offering an accurate delineation of complicated hepatobiliary dilatation associated pancreaticobiliary maljunction and only necessitates simple equipments. With the aid of the magnified laparoscopic view, the radical resection of extrahepatic biliary duct and correction of the portohepatic bile ductal stenosis can be exactly performed. Laparoscopic hepaticojejunostomy at the hilum is effective and safe for children with complicated hepatobiliary dilatation.

Associations between gastrointestinal infection and urinary phthalate metabolite concentrations in US children and adolescents from NHANES 2005-2016.

The purpose of this study was to evaluate at the link between gastrointestinal illness and urine phthalate metabolite concentrations in children and adolescents in the United States between 2005 and 2016. A total of 4008 National Health and Nutrition Examination Survey (NHANES) participants had urine samples obtained during the survey and self-reported their gastrointestinal functional status over the previous week. High performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS) was used to identify twelve phthalate metabolites in urine samples. The link between PAE concentrations and gastrointestinal illnesses was investigated using logistic regression, which was controlled for possible confounders. The combined and independent effects of PAEs on gastrointestinal illnesses were investigated using Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (qgcomp). In children and adolescents, the prevalence of gastrointestinal infection was 9.0%. One log-unit increase in urinary concentrations was associated with an increased risk of gastrointestinal infection for monocarboxyoctyl phthalate (MCOP) (adjusted odd ratio (aOR) = 1.36, 95 percent confidence interval (95%ci): 1.08, 1.62), mono(2-ethylhexyl) phthalate (MEHP) (aOR = 1.18, 95 percent CI: 1.05, 1.32) and mono(2-eth The mixed exposure model findings revealed that the combined effect of PAEs was substantially linked with gastrointestinal infection; exposure to the combination of PAEs was positively associated with the risk of gastrointestinal infection. In the BKMR model, the exposure to the mixture of PAEs was positively associated with the risk of gastrointestinal infection. In qgcomp, a substantial positive correlation between PAEs and gastrointestinal illnesses was identified (OR = 1.16, 95 percent CI: 1.05, 1.28). MCOP and MEHP may be the major contributors after controlling for other PAE homologs. These associations were more pronounced in overweight and obese children and adolescents. Mixed exposure to phthalates (PAEs) in children and adolescents was significantly associated with gastrointestinal infections, with MCOP and MEHP accounting for the major proportions. These associations were more pronounced in overweight and obese children and adolescents.

Laparoscopic surgery for stage III neuroblastoma: A case report.

Laparoscopic surgery for malignant solid tumors is still in the stage of clinical exploration. Neuroblastoma is a common solid tumor in children. The present study discussed significance and feasibility of complete resection of stage III neuroblastoma by laparoscopic surgery and its safety and effectiveness was compared with traditional surgery. For children suffering from neuroblastoma with large tumor volume and vascular invasion, preoperative chemotherapy can be given and minimally invasive laparoscopic surgery can be one option to be considered when the tumor volume is <6 cm. During the operation, the tumor tissue can be removed by segmental resection and the removal of as much tumor tissue as possible is an important factor in improving the prognosis. Laparoscopic minimally invasive surgery is associated with minimal surgical trauma and quick recovery of patients, and children can receive postoperative chemotherapy as early as possible, which is conducive to good recovery. Basically, the prerequisite and requirements for performing this operation are professional laparoscopic skills and an experienced team.

Association Between the Children's Dietary Inflammatory Index (C-DII) and Markers of Inflammation and Oxidative Stress Among Children and Adolescents: NHANES 2015-2018.

Objectives: To explore the association of Children's Dietary Inflammatory Index (C-DII) scores with inflammation and markers of inflammatory factors in children and adolescents. Methods: Data on dietary nutrient intake, markers of inflammation (ferritin, alkaline phosphatase, C-reactive protein (CRP), absolute neutrophil cell count and lymphocyte count) and oxidative stress (serum bilirubin, albumin, and iron) were available for participants aged 6-19 years (n = 1281). Each participant's C-DII score was calculated based on a 24-h diet and recall. Generalized linear models were applied to examine associations between C-DII and markers of inflammation and oxidative stress, while adjusting for covariates. Restricted cubic splines were used to explore the dose-response association of C-DII scores with indicators of inflammatory oxidative stress. Akaike's Information Criterionwas applied to compare the performance of linear and non-linear models. Results: After adjusting for potential confounders, quantile regression results showed that when comparing C-DII quartile 4 (most pro-inflammatory) and quartile 1 (most anti-inflammatory), lymphocytes, ferritin, CRP were statistically significant differences in serum bilirubin, albumin and serum iron (P < 0.05). The C-DII score showed a non-linear relationship with inflammatory oxidative stress indicators. Overweight/obese children and adolescents who ate a high pro-inflammatory diet were more likely to have higher levels of inflammatory cytokines (P = 0.002). Conclusions: The dietary inflammatory index in children is associated with markers of chronic inflammation and oxidative stress. A pro-inflammatory diet resulted in increased serum concentrations of these markers, implying that early dietary interventions have implications for reducing chronic inflammation and oxidative stress in children and adolescents.

Successful treatment of floating splenic volvulus: Two case reports and a literature review.

BACKGROUND: The floating spleen refers to the spleen moving away from the normal anatomical position to other parts of the abdominal cavity. CASE SUMMARY: In this report, we describe two cases of torsion of floating spleen, which were successfully treated by laparoscopic partial splenectomy and retroperitoneal fixation of the residual spleen. The clinical characteristics of previously reported cases are also discussed. CONCLUSION: In conclusion, laparoscopic partial resection of splenic volvulus infarction and extraperitoneal fixation of residual spleen are safe and reliable.

Targeted elimination of myeloid-derived suppressor cells via regulation of the STAT pathway alleviates tumor immunosuppression in neuroblastoma.

Neuroblastoma (NB) has high morality rates and is the most common malignant tumor found in children. High aggregation of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment results in immunosuppression and affects therapeutic effectiveness. At present, doxorubicin (DOX) and dopamine (DA) are the specific drugs used to selectively remove or mature MDSCs. The aim of the present study was to explore the feasibility and underlying mechanism of targeting elimination of MDSCs via DOX or DA administration to alleviate tumor immunosuppression in NB. In the present study, a BALB/c tumor-bearing mouse model was established, and mice were grouped into the control, DOX2.5, DOX5 and DA50 mg/kg groups. DOX or DA were injected intravenously on days 7 and 12 after inoculation, following which the parameters related to the signal transducer and activator of transcription (STAT) pathway in MDSCs, the proportion of MDSCs, T cell infiltration, programmed death-1 (PD-1) on the surface of T cells, the number of regulatory T cells (Tregs), polarization of tumor-related macrophages (TAMs) and tumor growth were compared between the groups on days 14, 17 and 23 after inoculation. The results demonstrated that following DOX or DA administration, STAT1/phosphorylated (p)-STAT1 decreased, whereas STAT3/p-STAT3, STAT5/p-STAT5 and STAT6/p-STAT6 increased, which was accompanied by a decrease in the MDSC proportion in each experimental group. Simultaneously, T cell infiltration in tumors was increased, whereas expression of PD-1, the number of Tregs, TAM polarization and tumor growth were inhibited. The most significant findings were observed in the DOX2.5 mg/kg group. To conclude, low dose DOX or DA administration could effectively regulate the STAT pathway to eliminate MDSCs, alleviate immunosuppression and improve the immune response against NB tumor cells.

Vitexin ameliorates glycochenodeoxycholate-induced hepatocyte injury through SIRT6 and JAK2/STAT3 pathways.

Objectives: Vitexin, a natural flavonoid, is commonly found in many foods and traditional herbal medicines and has clear health benefits. However, the role of vitexin in cholestasis is presently unclear. This study investigated whether vitexin mitigated glycochenodeoxycholate (GCDC)-induced hepatocyte injury and further elucidated the underlying mechanisms. Materials and Methods: A cell counting kit-8 (CCK-8) assay was conducted to evaluate cell viability. The mitochondrial membrane potential (MMP, Δψm), reactive oxygen species (ROS) levels, and apoptosis rate of hepatocytes exposed to GCDC were detected by flow cytometry (FCM). We then measured the cytoprotective effects of vitexin against oxidative stress. The molecular signaling pathway was further investigated by using Western blotting and signaling pathway inhibitors. Results: Here, we showed that vitexin increased cell viability and reduced cell apoptosis, necroptosis, and oxidative stress in a dose-dependent manner in GCDC-treated hepatocytes. In addition, by using selective inhibitors, we further confirmed that inhibition of the JAK2/STAT3 pathway by vitexin was mediated by prolonged activation of Sirtuin 6 (SIRT6). Conclusion: Vitexin attenuated GCDC-induced hepatocyte injury via SIRT6 and the JAK2/STAT3 pathways.

WITHDRAWN: Immunohistochemical study of inflammatory responses in septa arising from type I intestinal atresia.

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Primary laparoscopic endorectal pull-through procedure with or without a postoperative rectal tube for hirschsprung disease: a multicenter perspective study.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a significant complication of HD both in the pre- and postoperative periods. This was a large multicenter series study to determine the effect of preserving a postoperative rectal tube on preventing HAEC after primary laparoscopic endorectal pull-through procedure. METHODS: Between 2014 and 2017, a total of 383 consecutive patients with rectosigmoid segment HD were randomly divided into group A (n = 190) and group B (n = 193). All of them underwent primary laparoscopic pull-through procedure, with the same postoperative treatment protocols except for group A with a rectal tube after surgery for 5 days, while group B did not have it. The mean time of follow-up was 2.0 ±â€¯0.53 years (0.5-3.6 years). Demographics, operative data, postoperative complications, and clinical outcomes were compared between these two groups. RESULTS: Outcomes within 1 month after surgery indicated a lower incidence of abdominal distention (4% vs 15.5%, P < 0.05) and postoperative HAEC (1.2% vs 6.8%, P < 0.05) in group A compared to group B. Beyond 1 month after surgery, the overall incidence of HAEC was not significantly different (12% vs 13.1%, P = 0.54). However, further analysis revealed that the patients who suffered HAEC twice or above twice in group A were significantly less than those in group B (3.6% vs 8.3%, p = 0.02). There were no significant differences in the defecation frequency and other complications. CONCLUSIONS: Primary laparoscopic endorectal pull-through procedure with a postoperative rectal tube can reduce the early-stage postoperative incidence of abdominal distension and HAEC and the risk of HAEC recurrence in the long term, and is beneficial to postoperative management. LEVEL OF EVIDENCE: Level 2.

Targeted inhibition of myeloid-derived suppressor cells in the tumor microenvironment by low-dose doxorubicin to improve immune efficacy in murine neuroblastoma.

BACKGROUND: High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB. METHODS: Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results. RESULTS: The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups. CONCLUSIONS: Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.

Single-port laparoscopic herniorrhaphy using a two-hooked cannula device with hydrodissection.

BACKGROUND: Laparoscopic percutaneous extraperitoneal closure (LPEC) with variable devices seems to be one of the most simple and reliable methods. We described our modifications of single-port laparoscopic herniorrhaphy using an inner two-hooked cannula device with preperitoneal hydrodissection. PATIENTS AND METHODS: 1568 children with 2114 inguinal hernias were treated by single-port LPEC. Under laparoscopic visualization, the two-hooked cannula device carrying a silk suture was inserted at the point of the internal ring and could be readily kept in an identical path. The hernia orifice was completely lassoed extraperitoneally by the suture with the assistance of hydrodissection. Any huge hernias of more than 1.5 cm were repaired with the incorporation of medial umbilical fold flap as reinforcement. RESULTS: All hernia repairs were successfully performed by LPEC. 1022 patients had unilateral inguinal hernia repair, and 546 patients underwent bilateral inguinal hernia repair. Of these, additional medial umbilical flap reinforcement was necessary in 68 cases, and an assisted grasping instrument was used in 19 cases owing to omental adhesion or sliding hernia. Mean operating times for unilateral and bilateral inguinal hernia repairs were 9.8 ±â€¯2.1 min and 13.6 ±â€¯2.2 min, respectively. There were no operative complications. Two recurrences and three hydroceles were observed during 6 to 30 months of follow-up. CONCLUSIONS: One-puncture LPEC using the two-hooked cannula device with preperitoneal hydrodissection has proved to be a safe and effective procedure with excellent cosmetic results. LEVEL OF EVIDENCE: IV.

Single-Port Laparoscopic Assisted Transcrotal Orchidopexy for Palpable Inguinal Canalicular Cryptorchidism Accompany With Indirect Inguinal Hernia.

Purpose: To assess the outcomes of a novel laparoscopic assisted transcrotal orchidopexy (LATO) combined with percutaneous extraperitoneal closure (PEC) for palpable inguinal canalicular cryptorchidism accompany with indirect inguinal hernia, and evaluate its safety and efficiency. Materials and Methods: A retrospective cohort study for single-port LATO-PEC and traditional inguinal orchidopexy (TIO) was performed between 2011 and 2014. Totally 53 children with both palpable inguinal canalicular testes and indirect inguinal hernia were included. Median patient age was 15month (range, 6 months to 4 years). Of them, 35 patients underwent LATO-PEC procedure, utilizing an umbilical trocar for laparoscope, transcrotal dissection for orchidopexy, and an inner two-hooked cannula for ligation of the patent processus at the level of the internal ring. Three of them were bilateral, 12 on the left side and 20 on the right. Eighteen patients received TIO, seven of them on the left side and 11 on the right. Patient demographics, surgical technique, complications, and clinical outcomes were reviewed. Follow-up visits were performed to reassess position and size of the testes. Results: All 56 undescended testes were delivered into the scrotum successfully. In the LATO-PEC group, nine contralateral herniorrhaphy were accomplished simultaneously. Fifteen contralateral patent processus vaginalis (PPVs) in 32 unilateral undescended testis (UDT) were newly confirmed during the laparoscopy, while 6 of them received percutaneous extra-peritoneal herniorrhaphy for visible inguinal bubble in pneumoperitoneum condition. No additional port placement or conversion to open procedure was needed. Mean operative time for unilateral and bilateral LATO-PEC in this study was (37.81 ± 5.23) min and (53.33 ± 2.98) min, respectively. In TIO group, mean operative time was (41.11 ± 8.67) min. There was no statistical difference in operative time between the two approaches for unilateral UDTs (p = 0.098). Median follow-up interval was 24 months (range, 12-84 months). No operative complications were found in either group to date. Conclusions: Singe-port LATO-PEC is a safe, effective, and cosmetic choice for inguinal canalicular cryptorchidism accompany with indirect inguinal hernia, minimizing injuries to the vas deferens and testicular vessels. Laparoscopy can provide a diagnostic and therapeutic solution of contralateral PPV.

Role of Thrombospondin-1 and Nuclear Factor-κB Signaling Pathways in Antiangiogenesis of Infantile Hemangioma.

BACKGROUND: Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of thrombospondin-1 and nuclear factor-κB signaling pathways in the treatment of hemangioma with propranolol. METHODS: The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo. RESULTS: The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKß) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKß (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways. CONCLUSION: The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1-mediated antiangiogenesis and to block nuclear factor-κB-mediated angiogenesis.