Current trends and prospects of surgical techniques for hepatoblastoma.

Hepatoblastoma, a common extracranial malignant solid tumor in childhood, is often detected at an advanced stage and is difficult to treat surgically. Despite the availability of multiple comprehensive treatments that can be combined with surgery, hepatoblastoma treatment outcomes remain poor. Surgery is the main treatment strategy for hepatoblastoma, but it faces many challenges, including tumor attachment to surrounding tissues, tumor wrapping or invading of vital organs and tissues, the presence of giant or multiple tumors, distant metastasis, the formation of a tumor thrombus, and significant surgical trauma. In this review, we discuss recent research advances and propose potential strategies for overcoming these challenges. Such strategies may improve the rate of hepatoblastoma resection and local control in children, as well as reduce complications and trauma.

Validation and effect of the NASA-TLX score on the assessment of the workload of pediatric robotic operations.

OBJECTIVE: The objective of the study was to assess the validity of the NASA-TLX score in rating the workload of pediatric robotic operations. METHODS: The workload of 230 pediatric gastrointestinal and thoracic robotic operations was rated using the NASA-TLX score. The difference between the high workload group and the low workload group in each subscale of the NASA-TLX score was analyzed. The correlation of each subscale with the total workload score in the high workload group and low workload group was also analyzed. A logistic regression analysis was subsequently conducted to assess the effects of different factors (sex, age, weight, procedure duration, procedure specialties, combined malformation and blood loss) on the workload. RESULTS: The average NASA-TLX score was 56.5 ± 5.1 for the total group, 56.9 ± 5.0 for the gastrointestinal group and 54.6 ± 4.8 for the thoracic group, p = 0.007. The score of the high workload group was 62.7 ± 3.2, while it was 50.6 ± 2.7 for the low workload group (p < 0.001). The score on each subscale was also significantly different between the high and low workload groups. In the high workload group, a stronger correlation was observed between the total score and TD and Fr and a lower correlation with MD and Pe. In the low workload group, all six subscales showed a moderate correlation with the total score. A multivariate logistic regression analysis revealed that the procedure duration was an independent influencing factor for a higher workload score. CONCLUSIONS: NASA-TLX is a valid tool to rate the surgeon's workload in pediatric robotic surgery. A longer operative time contributes to a higher workload.

Robotic resection of paediatric solid tumours at a single institution.

BACKGROUND: To explore the clinical application of robotic-assisted surgery in paediatric solid tumours and to explore its feasibility. METHODS: From 2015 to 2022, 53 children with solid tumours underwent robotic-assisted surgery in our centre were retrospectively analysed. RESULTS: The mean weight of the patients was 27.7 kg, and the mean age was 6.7 years. The average tumour volume was 5.5*4.6*3.7 cm. Two procedures (3.8%) were converted. The mean total operative time was 198.5 min. The mean estimated blood loss was 27.1 ml, and no intraoperative complications occurred. Two (3.8%) patients had postoperative complications. At a median follow-up of 21.2 months, one (1.9%) patient with malignant tumours stopped treatment, and two (3.8%) patients developed tumour recurrence. CONCLUSIONS: Robotic-assisted tumour resection is feasible in highly selected cases of young age, light weight, huge tumour or malignant tumour.

Downregulation of hsa_circ_0074854 Suppresses the Migration and Invasion in Hepatocellular Carcinoma via Interacting with HuR and via Suppressing Exosomes-Mediated Macrophage M2 Polarization.

BACKGROUND: Circular RNAs (circRNAs) have been identified as key factors in the development of hepatocellular carcinoma (HCC). However, the role and potential molecular mechanism of circRNAs in HCC remain largely unclear. In addition, exosomes are known as important messengers of the cross-talk between tumor cells and immune cells, while the role of extracellular circRNAs in the cell-to-cell communication of tumor cells and immune cells remains not unclear. METHODS: The level of hsa_circ_0074854 in HCC cell lines and HCC cell-derived exosomes was assessed using RT-qPCR assay. In addition, CCK-8 and transwell assays were used to determine the viability, migration and invasion of HCC cells. RESULTS: Hsa_circ_0074854 expression was upregulated in HCC tissues and HCC cell lines. Additionally, hsa_circ_0074854 knockdown was found to inhibit HCC growth in vitro and in vivo. Mechanistically, hsa_circ_0074854 knockdown inhibited the migration and invasion of HCC cells via interacting with human antigen R (HuR) to reduce its stability. Furthermore, hsa_circ_0074854 can be transferred from HCC cells to macrophages via exosomes. Exosomes with downregulated hsa_circ_0074854 suppressed macrophage M2 polarization, which in turn suppressing migration and invasion of HCC cells both in vitro and in vivo. CONCLUSION: Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Collectively, these findings may help to understand the diagnosis and treatment of HCC.

Runt-related transcription factor 1 promotes apoptosis and inhibits neuroblastoma progression in vitro and in vivo.

BACKGROUND: Runt-related transcription factor 1 (RUNX1) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters and can accelerate apoptosis in various tumors. However, the regulatory mechanisms underlying RUNX1 expression in neuroblastoma (NB), a highly malignant tumor in childhood, remain largely unclear. In this study, we aimed to assess the role of RUNX1 in NB and to reveal the underlying mechanisms that may contribute to finding a potential therapeutics strategy against NB. METHODS: Growth, invasion, metastasis and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8) immunocytochemistry, and studies involving soft agar, cell invasion, tube formation and whole animals. The levels of expression were measured using real-time quantitative PCR for RNA, Western blot and immunostaining analyses for proteins. Luciferase reporter and chromatin immunoprecipitation assays indicated that RUNX1 directly binds within the BIRC5, CSF2RB and NFKBIA promoter regions to facilitate transcription. The level of apoptosis was assessed by determining mitochondrial membrane potential and flow cytometry. RESULTS: RUNX1 was highly expressed in ganglioneuroma (GN) and well-differentiated (WD) tissues relative to the poorly differentiated (PD) and undifferentiated (UD) ones. Moreover, RUNX1 effectively reduced cell viability, invasion, metastasis, angiogenesis, and promoted apoptosis in vitro and in vivo. RUNX1 reduced BIRC5 transcription and increased CSF2RB and NFKBIA transcription by directly binding BIRC5, CSF2RB and NFKBIA promoters. In addition, cytotoxic drugs, especially cisplatin, significantly increased RUNX1 expression in NB cells and promoted apoptosis. CONCLUSIONS: These data show that RUNX1 is an independent surrogate marker for the progression of NB and it can be used for monitoring NB prognosis during therapy.

SNW1 regulates Notch signaling in neuroblastoma through interacting with RBPJ.

The Notch signaling pathway is highly conserved, involved in cell-cell communication, and essential for multicellular organism development. The recombination signal binding protein for immunoglobulin kappa J region (RBPJ) transcriptional regulator plays a vital role in Notch signaling. When not complexed with Notch proteins, RBPJ acts as a transcriptional repressor. However, when bound to the Notch intracellular domain (NOTCH ICD) in the nucleus, RBPJ activates the transcription of Notch target genes. However, the role of RBPJ in the Notch signaling pathway in neuroblastoma (NB) remains unclear. In this study, we show that SNW domain containing 1 (SNW1) acts as a novel RBPJ partner and regulates the expression of Notch target genes. Additionally, we show that silencing RBPJ expression can prevent SNW1-mediated Notch gene expression. Public datasets and clinical NB tissues indicate that RBPJ and SNW1 are upregulated in NB, and are associated with unfavorable patient outcomes. Taken together, our results highlight that SNW1 interacts with RBPJ to regulate the Notch signaling pathway and presents a potential therapeutic target for NB.

Hybrid Nuss Procedure for Pectus Excavatum With Severe Retrosternal Adhesions After Sternotomy.

BACKGROUND: The most striking feature of pectus excavatum (PE) after previous congenital heart disease (CHD) surgery through a median sternotomy is the postsurgical adhesions between the sternum and heart. For patients with severe adhesions, passing the introducer can be difficult and hazardous when performing a Nuss repair. We describe a hybrid Nuss procedure using a small subxiphoid incision for blunt and sharp anterior mediastinal dissection and using a thoracoscope to ensure the whole process of dissection is under direct visualization. METHODS: A retrospective case review was conducted of PE patients (previous CHD operation) who had undergone the hybrid Nuss procedure between January 2012 and June 2015. Demographic, treatment, and outcome variables were recorded. RESULTS: Eleven patients were included. The mean age was 4.7 ± 1.7 years (range, 3.2 to 8.9). The mean Haller index based on computed tomography was 4.15 ± 0.78 (range, 3.2 to 5.8). All cases were the symmetric type. Mean operating time was 95.5 ± 8.4 minutes (range, 80 to 110); mean blood loss was 15 ± 2.3 mL; and mean length of hospitalization was 6.0 ± 1.4 days (range, 4 to 8). There was no pneumothorax, cardiac injury, wound infection, discomfort requiring removal, or bar rotation at the average 27-month (range, 9 to 50) follow-up. Two patients had the bars removed. No reoperations were performed owing to recurrence. CONCLUSIONS: The hybrid Nuss procedure is a safe, simple modification of the Nuss repair for patients with severe retrosternal adhesions. This procedure achieves dissection with direct visualization. Hence, the risk of death due to cardiac perforation can be prevented.

Smad4 suppresses the tumorigenesis and aggressiveness of neuroblastoma through repressing the expression of heparanase.

Heparanase (HPSE) is the only endo-ß-D-glucuronidase that is correlated with the progression of neuroblastoma (NB), the most common extracranial malignancy in childhood. However, the mechanisms underlying HPSE expression in NB still remain largely unknown. Herein, through analyzing cis-regulatory elements and mining public microarray datasets, we identified SMAD family member 4 (Smad4) as a crucial transcription regulator of HPSE in NB. We demonstrated that Smad4 repressed the HPSE expression at the transcriptional levels in NB cells. Mechanistically, Smad4 suppressed the HPSE expression through directly binding to its promoter and repressing the lymphoid enhancer binding factor 1 (LEF1)-facilitated transcription of HPSE via physical interaction. Gain- and loss-of-function studies demonstrated that Smad4 inhibited the growth, invasion, metastasis, and angiogenesis of NB cells in vitro and in vivo. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by Smad4. In clinical NB specimens, Smad4 was under-expressed and inversely correlated with HPSE levels, while LEF1 was highly expressed and positively correlated with HPSE expression. Patients with high Smad4 expression, low LEF1 or HPSE levels had greater survival probability. These results demonstrate that Smad4 suppresses the tumorigenesis and aggressiveness of NB through repressing the HPSE expression.

A Modified Approach for Inguinal Hernias in Children: Hybrid Single-Incision Laparoscopic Intraperitoneal Ligation.

PURPOSE: To report a laparoscopic approach for pediatric inguinal hernia repair using a hybrid single-incision laparoscopic (H-SIL) technique and its clinical outcomes. MATERIALS AND METHODS: A retrospective study was carried out in inguinal hernia cases treated with the new H-SIL approach using intracorporeal jumping purse-string sutures. The operative time, length of postoperative hospital stay, efficiency of the operation, and complications were analyzed. RESULTS: In total, 157 inguinal high ligations were performed in 106 children (89 boys, 17 girls). The median age was 1.5 years (range, 25 days-11.6 years). The mean operative time was 15.8±3.4 minutes for the single-side procedure and 20.3±2.5 minutes for bilateral procedures. The mean postoperative hospital stay was 0.99±0.52 (range, 0.25-3 days). No postoperative bleeding, abdominal wall emphysema, abdominal viscera injury, or scrotal edema was found, and there were no known cases of postoperative testicular atrophy or hypotrophy. Ninety-three percent of the patients became fully mobile on the first postsurgical day. The median follow-up period was 17 months (range, 9-21 months), with no recurrence, no visible scars on the abdominal wall, and no foreign body felt in the inguinal region. CONCLUSIONS: This H-SIL approach is a safe and efficient method for pediatric inguinal hernia repair. The maneuverability is the same as that in the triport laparoscopic technique, and the cosmetic results are similar to those of single-port laparoscopic surgery.

miRNA-558 promotes tumorigenesis and aggressiveness of neuroblastoma cells through activating the transcription of heparanase.

Heparanase (HPSE) is the endogenous endoglycosidase that degrades heparan sulfate proteoglycans and promotes the tumor growth, invasion, metastasis and angiogenesis. Our previous studies have shown that HPSE is highly expressed in neuroblastoma (NB), the most common extracranial solid tumor in childhood. However, the underlying regulatory mechanisms remain largely unknown. In this study, we identified one binding site of microRNA-558 (miR-558) within the HPSE promoter. In NB tissues and cell lines, miR-558 was up-regulated and positively correlated with HPSE expression. Gain- and loss-of-function studies demonstrated that miR-558 facilitated the transcript and protein levels of HPSE and its downstream gene, vascular endothelial growth factor, in NB cell lines. In addition, miR-558 enhanced the promoter activities of HPSE, and these effects were abolished by the mutation of the miR-558-binding site. Mechanistically, miR-558 induced the enrichment of the active epigenetic marker and RNA polymerase II on the HPSE promoter in NB cells in an Argonaute 1-dependent manner, which was abolished by repressing the miR-558-promoter interaction. Knockdown of endogenous miR-558 decreased the growth, invasion, metastasis and angiogenesis of NB cells in vitro and in vivo. In contrast, over-expression of miR-558 promoted the growth, invasion, metastasis and angiogenesis of SH-SY5Y and SK-N-SH cells. Restoration of HPSE expression prevented the NB cells from changes in these biological features induced by knockdown or over-expression of miR-558. These data indicate that miR-558 induces the transcriptional activation of HPSE via the binding site within promoter, thus facilitating the tumorigenesis and aggressiveness of NB.

Nuss repair of pectus excavatum after surgery for congenital heart disease: experience from a single institution.

OBJECTIVE: Pectus excavatum developing after surgery for congenital heart disease has its own clinical characteristics. The present study aimed to present our technique and outcomes for the Nuss procedure in the repair of these cases. METHODS: We conducted a retrospective study of all patients who had not been diagnosed as pectus excavatum preoperatively but subsequently had developed pectus excavatum after surgery for congenital heart disease from February 2005 to November 2012. The Nuss procedure was applied using a series of perioperative management techniques. The data relating to the surgical technique, complications, and outcomes were analyzed. The clinical evaluation was performed using the Nuss criteria. RESULTS: A total of 30 cases (14 boys and 16 girls) were included. The mean operative time was 73.5 minutes (range, 58-82). The mean length of hospital stay was 6.0 days. Complications occurred in 5 patients (16.7%), including asymptomatic pneumothorax, hematoma in the wound, pericardial penetration, and bar displacement. The mean follow-up period was 32 months (range, 9-60). Initially, 29 patients (96.7%) had excellent results, and 1 patient had a good result. The mean point of bar removal was 35.8 months (range, 30-39) after implantation. The postoperative results after bar removal in 17 patients were also recorded, including excellent results in 14 (82.4%), good results in 2 (11.7%), and a fair result in 1 patient. CONCLUSIONS: The Nuss procedure has been shown to be a safe and effective approach for the repair of pectus excavatum after surgery for congenital heart disease, although dissection of substernal adhesions can increase the risk of heart injury.

Single-incision laparoscopic versus conventional laparoscopic endorectal pull-through for Hirschsprung's disease: a comparison of short-term surgical results.

BACKGROUND: Single-incision laparoscopy has recently become a popular procedure in pediatric surgery. The current series is the largest study to evaluate the operative complications and results of single-incision laparoscopic endorectal pull-through (SILEP) for the treatment of HD through a retrospective comparison with conventional laparoscopic endorectal pull-through (CLEP). METHODS: Twenty eight patients who underwent single-incision laparoscopic endorectal pull-through for HD between July 2010 and August 2011 were compared to thirty patients who underwent CLEP. Patient age, gender, transitional zone, operative time, blood loss, intraoperative and postoperative complications, as well as short-term results, were assessed. RESULTS: A total of 28 patients were included for SILEP, and historical reported 30 patients were completed by CLEP. The SILEP and CLEP groups were similar in regard to age, gender, transition zone, operative time, blood loss, hospital stay, and intraoperative complications. Postoperative results were not different, including equal daily defecation frequency and early postoperative complications. No patients with recurrent constipation were seen. Two patients with the transitional zone in the descending colon in the SILEP group had a 3mm trocar added in the left abdomen, and there were no conversions in the conventional laparoscopic group. CONCLUSION: We have shown that in selected HD patients, the SILEP technique was safe and technically feasible in experienced hands. It results in similar operative results compared with conventional laparoscopic endorectal pull-through. However, the operation is more difficult if the transition zone was higher than the rectosigmoid.

Noscapine induced apoptosis via downregulation of survivin in human neuroblastoma cells having wild type or null p53.

Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Chemotherapy is the mainstay of treatment in children with advanced neuroblastoma. Noscapine, a nontoxic natural compound, can trigger apoptosis in many cancer types. We now show that p53 is dispensable for Noscapine-induced cell death in neuroblastoma cell lines, proapoptotic response to this promising chemopreventive agent is mediated by suppression of survivin protein expression. The Noscapine treatment increased levels of total and Ser(15)-phosphorylated p53 protein in SK-SY5Y cells, but the proapoptotic response to this agent was maintained even after knockdown of the p53 protein level. Exposure of SK-SY5Y and LA1-5S cells to Noscapine resulted in a marked decrease in protein and mRNA level of survivin as early as 12 hours after treatment. Ectopic expression of survivin conferred statistically significant protection against Noscapine-mediated cytoplasmic histone-associated apoptotic DNA fragmentation. Also, the Noscapine-induced apoptosis was modestly but statistically significantly augmented by RNA interference of survivin in both cell lines. Furthermore, Noscapine-induced apoptotic cell death was associated with activation of caspase-3 and cleavage of PARP. In conclusion, the present study provides novel insight into the molecular circuitry of Noscapine-induced apoptosis to indicate suppression of survivin expression as a critical mediator of this process.

microRNA-9 targets matrix metalloproteinase 14 to inhibit invasion, metastasis, and angiogenesis of neuroblastoma cells.

Matrix metalloproteinase (MMP)-14 is the only membrane-anchored MMP that plays a critical role in tumor metastasis and angiogenesis. However, the mechanisms underlying MMP-14 expression in tumors still remain largely unknown. In this study, MMP-14 immunostaining was identified in 29/42 neuroblastoma tissues, which was correlated with clinicopathologic features and shorter patients' survival. In subtotal 20 neuroblastoma cases, microRNA 9 (miR-9) was downregulated and inversely correlated with MMP-14 expression. Bioinformatics analysis revealed a putative miR-9-binding site in the 3'-untranslated region (3'-UTR) of MMP-14 mRNA. Overexpression or knockdown of miR-9 responsively altered both the mRNA and protein levels of MMP-14 and its downstream gene, vascular endothelial growth factor, in cultured neuroblastoma cell lines SH-SY5Y and SK-N-SH. In an MMP-14 3'-UTR luciferase reporter system, miR-9 downregulated the luciferase activity, and these effects were abolished by a mutation in the putative miR-9-binding site. Overexpression of miR-9 suppressed the invasion, metastasis, and angiogenesis of SH-SY5Y and SK-N-SH cells in vitro and in vivo. In addition, the effects of miR-9 on MMP-14 expression, adhesion, migration, invasion, and angiogenesis were rescued by overexpression of MMP-14 in these cells. Furthermore, anti-miR-9 inhibitor or knockdown of MMP-14 respectively increased or inhibited the migration, invasion, and angiogenesis of neuroblastoma cells. These data indicate that miR-9 suppresses MMP-14 expression via the binding site in the 3'-UTR, thus inhibiting the invasion, metastasis, and angiogenesis of neuroblastoma.

10 years of experience with laparoscopic-assisted endorectal Soave pull-through procedure for Hirschsprung's disease in China.

OBJECTIVE: To report early and late results of laparoscopic-assisted endorectal Soave pull-through (LAEPT) with a short and V-shaped partial resection muscular cuff for Hirschsprung's disease (HD) over a 10-year period. METHODS: The clinical courses of 218 patients who underwent modified LAEPT for HD were reviewed. LAEPT was described by the Georgeson technique. The main modifications included less dissection of the bottom of the pelvis, rectal mucosa dissection with a long cuff, coloanal anastomosis with a short cuff, and a V-shaped partial resection in the posterior wall of the muscular cuff. RESULTS: From September 1999 to July 2009, 218 patients were operated on by the same surgeon. Ages ranged from 15 days to 12 years old. The aganglionic segment was located in the rectum or sigmoid colon in 176 patients, in the left colon in 38 children, and in the transverse colon in 4 patients. The median operating time was 176 minutes. Conversion to open surgery was required in 2 patients. Bleeding of the left iliac vein occurred in 1 patient, and a 180° twist of the neorectum occurred in 2 cases. Median first bowel movement time was 23 hours, and median postoperative hospital stay was 10.4 days. Median daily defecation frequency was 4.6 within 2 weeks and 2.3 at 3 months postoperatively. The immediate postoperative complications included intestine herniation from the trocar site in 2 patients, perianal excoriation in 32 patients, and anastomotic leakage in 3 patients. Follow-up ranging from 6 to 120 months was obtained for 182 patients. Late postoperative complications included postoperative adhesive bowel obstruction (1.1%), enterocolitis (7.7%), anasomostic stenosis (2.2%), constipation (1.6%), and soiling (3.6%). Eighty-seven percent had excellent and good bowel function. CONCLUSION: LAEPT with a short muscular cuff with a V-shaped partial resection in the posterior wall is a safe and effective procedure for HD.

Transanal endorectal pull-through for Hirschsprung's disease using long cuff dissection and short V-shaped partially resected cuff anastomosis: early and late outcomes.

BACKGROUND: Transanal endorectal pull-through was described by De la Torre-Mondragon's technique. In the original transanal pull-through procedure, a long rectal muscular cuff was dissected and left for anocolic anastomosis, which would sometimes lead to postoperative obstructive symptoms and enterocolitis. While a modified short mucosal dissection may increase the risk of injury to pelvic and perirectal nerves and other structures when dissected on the outside of the rectum deep in the pelvis. We report early and late results of the modified transanal procedure for Hirschsprung's disease (HD) over 8 years. METHODS: The clinical course of all children with aganglionic rectum or sigmoid colon receiving the modified transanal pull-through between May 2003 and April 2011 were reviewed. The main modifications were rectal mucosa dissection with a long cuff, coloanal anastomosis with a short cuff and a V-shaped partial resection in the posterior wall of the muscular cuff. Children with preliminary stoma or total colonic disease were excluded. RESULTS: Short- and long-term follow-up was obtained in 137 patients with HD operated upon by the same surgeon. The aganglionic segment was located in the rectum or sigmoid colon in all patients. The mean age at surgery was 165 ± 74 days. The mean operating time was 108 ± 38 min. Mean intra-operative blood loss was estimated to be 15 ± 10 ml. No patient required a blood transfusion. Mean postoperative hospital stay was 7 ± 2 days. Early postoperative complications included perianal excoriation in 38 patients (27.7 %), enterocolitis in two patients (1.4 %), and anastomotic leak in two patients (1.4 %). Late postoperative complications included perianal excoriation in 16 patients (11.7 %), anal stricture in two patients (1.4 %), constipation in four patients (2.8 %), enterocolitis in 10 patients (7.3 %), and soiling problems in six patients (4.4 %). Mean follow-up was 56 months (6 months-9 years). In patients older than 4 years, 85.4 % of them had excellent/good bowel function, 9.4 % had fair bowel function, and 5.2 % of patients had bad bowel function. CONCLUSION: Transanal endorectal pull-through with a long cuff dissection and a short V-shaped resected cuff anastomosis is a safe and effective procedure for HD. It reduced incidence of anastomotic stricture and constipation without an increased soiling incidence.

Chemoprevention of familial adenomatous polyposis by bromo-noscapine (EM011) in the Apc(Min/+) mouse model.

Germline mutation of the tumor suppressor gene, adenomatous polyposis coli (APC), is responsible for familial adenomatous polyposis (FAP) with nearly 100% risk for colon cancer at an early age. Although FAP is involved in only 1% of all colon cancer cases, over 80% of sporadic cancers harbor somatic mutations of APC. We show here that bromo-noscapine (EM011), a rationally designed synthetic derivative of a natural nontoxic tubulin-binding alkaloid-noscapine, that reduces the dynamics of microtubules, causes a reversible G(2) /M arrest in wild type murine embryonic fibroblasts (MEFs), but an aberrant exit from a brief mitotic block, followed by apoptosis in MEFs after APC deletion with small interfering RNA. Furthermore, both ß-catenin levels and activity fell to half the original levels with a concomitant reduction of cell proliferation-inducing cyclin D1, c-Myc, and induction of cytostatic protein p21 before caspase-3 activation. Additionally, we show a statistically significant reduction in the number of newly emerging intestinal polyps (to 35% compared with untreated mice) as well as the mean size of polyps (to 42% compared with untreated mice) in EM011-treated Apc(Min/+) mice as compared to their sham-treated control littermates. The remaining polyps in the EM011 treated group of Apc(Min/+) mice showed evidence of elevated apoptosis as revealed by immunohistochemistry. We failed to detect any evidence of histopathological and hematological toxicities following EM011 treatment. Taken together, our data are persuasive that a clinical trial of EM011 is possible for the prevention/amelioration of polyposis in FAP patients.

Laparoscopically assisted anorectal pull-through for high imperforate anus in infants: intermediate results.

PURPOSE: The aim of this study was to evaluate the clinical outcomes and postoperative anal function in infants with congenital high imperforate anus treated with laparoscopically assisted anorectal pull-through (LAARP). METHODS: From January 2004 to July 2007, 33 patients (28 boys and 5 girls, age ranging from 3 to 10 months) with high imperforate anus underwent LAARP. Clinical data of the LAARP group were retrospectively compared with those treated by posterior sagittal anorectoplasty (PSARP; n = 28) during the same time period. Anorectal function of these patients was evaluated using the following 3 methods: the Kelly score, anorectal vector volume manometry, and magnetic resonance imaging between the ages of 3.1 and 4.4 years. RESULTS: The mean operative time in LAARP and PSARP groups was 112.5 ± 12.4 and 120.4 ± 18.5 minutes (P > .05), respectively. The mean length of hospital stay in the LAARP group was shorter than that of PSARP group (11.3 ± 2.1 vs 14.6 ± 2.3 days, P < .01). No significant difference was observed between LAARP and PSARP groups regarding the Kelly score (3.52 ± 1.42 vs 3.49 ± 0.82). Although magnetic resonance imaging revealed lower malposition rates of rectum in the LAARP group than those of the PSARP group at both I-line (3.0% vs 14.3%) and M-line (3.0% vs 10.7%) levels, this was not statistically different (P > .05). Compared with the PSARP group, lower asymmetric index, larger vector volume, and higher anal canal pressure at rest and during voluntary squeeze were observed in LAARP group (P < .05). However, there were no significant differences in the length of high-pressure zone (15.2 ± 5.8 vs 15.1 ± 6.2 mm) and the presence of rectoanal relaxation reflex (84.8% vs 85.7%). CONCLUSIONS: Satisfactory fecal continence can be achieved in patients with high-type imperforate anus after LAARP. Laparoscopically assisted anorectal pull-through has advantages over PSARP, including shorter hospital stay and better position of rectum. However, long-term follow-up is necessary to compare the benefits of LAARP against PSARP.

Laparoscopic choledochal cyst excision, hepaticojejunostomy, and extracorporeal Roux-en-Y anastomosis: a technical skill and intermediate-term report in 62 cases.

BACKGROUND: This study aimed to present the authors' technique and the intermediate-term outcome for laparoscopic choledochal cyst excision with Roux-en-Y hepatoenterostomy. METHODS: This retrospective study investigated 62 children (39 girls and 23 boys) who had undergone laparoscopic resection of choledochal cyst. The average age of the children was 2.3 years. The retrospective data and the following investigations about type of choledochal cyst, surgical technique, conversion rate, morbidity, and mortality were analyzed. RESULTS: Of the 62 patients, 43 (69.4%) showed type 1a choledochal cysts, 16 (25.8%) showed type 1c, 2 (3.2%) showed type 4a, and 1 (1.6%) showed type 4b. Total cyst excision could be performed for 51 of the patients (82.3%). The large cysts were opened on the front wall, then divided circumferentially in 29 cases. The small cysts did not need to be opened before excision in 22 cases. For 11 patients (17.7%), Lilly's (Surg Gynecol Obstet 146:254-256, 1978) technique was adopted, and for 5 patients with a huge cyst, the duodenum together with the head of the pancreas had to be mobilized for visualization of the cyst's lower limit. The hepatic duct was excised, and plastic operation of bile duct was performed for two patients. The mean operative time was 226±41.2 min. Eight patients needed blood transfusion, and conversion was required for one patient. The mean hospital stay was 8±1.5 days, and the mean follow-up period was 38 months. The overall morbidity rate was 8.2% (5/61) including bile leakage (n=1), adhesive small bowel obstruction (n=1), intestinal necrosis (n=1), and cholangitis (n=1). Inflammatory edema anastomotic narrowing occurred in one patient. None of the patients needed surgery due to anastomotic stricture. CONCLUSIONS: Laparoscopic choledochal cyst excision, hepaticojejunostomy, and extracorporeal Roux-en-Y anastomosis can be safely and quickly performed for children, with satisfactory intermediate-term results. Extracorporeal Roux-en-Y anastomosis could shorten the operative time.

Endoscopic transaxillary approach for congenital muscular torticollis.

BACKGROUND: Surgical correction of the congenital muscular torticollis (CMT) is recommended for patients with unsuccessful conservative treatment. Open operative techniques all leave noticeable scars. We proposed a modified endoscopic 1-trocar transaxillary and neck microincision approach for the treatment of CMT. METHODS: Endoscopic release of the sternocleidomastoid (SCM) muscle was performed in 45 infants and children aged 6 months to 15 years. One 5-mm incision was made in the anterior axillary fold, and a subcutaneous tunnel over the clavicular and sternal heads of the SCM muscle was made. A subcutaneous space was established by CO2 inflation at a pressure of 8 mm Hg and then endoscopically using a 5-mm endoscope. Two additional 1.5- to 2-mm supraclavicular mini-incisions were made beside the SCM muscle for the introduction of miniforceps and electrocautery, respectively. The sternal and clavicular attachments were dissected and divided by electrocautery. Clinical evaluation was performed using the Lee scoring system. RESULTS: The operation was successfully completed endoscopically in all 45 children. The mean operative time was 40 minutes. No injuries of major blood vessels or nerves were encountered. A small bleed was noted in 1 child owing to reoperation. Follow-up for 6 months to 3 years in 42 patients showed complete muscular release and satisfactory cosmetic appearance with no recurrence. The results were classified as excellent in 88.1% (37/42), good in 9.5% (4/42), fair in 2.4% (1/42), and poor in 0 using the Lee scoring system. The neck scars were not visible 1 month after the procedure. CONCLUSIONS: The subcutaneous endoscopic transaxillary and micro-neck incision approach for the treatment of CMT is a safe, practical procedure that provides good functional and cosmetic outcomes without vascular or neural injury.