Forced expression of NR4A3 induced the differentiation of human neuroblastoma-derived NB1 cells.

Nuclear receptor subfamily 4, group A, member 3 (NR4A3) is a member of the NR4A subgroup of orphan nuclear receptors, implicated in the regulation of diverse biological functions, including metabolism, angiogenesis, inflammation, cell proliferation, and apoptosis. Although many reports have suggested the involvement of NR4A3 in the development and/or progression of tumors, its role varies among tumor types. Previously, we reported that DNA hypomethylation at NR4A3 exon 3 is associated with lower survival rate of neuroblastoma (NB) patients. As hypomethylation of this region results in reduced expression of NR4A3, our observations suggested that NR4A3 functions as a tumor suppressor in NB. However, the exact mechanisms underlying its functions have not been clarified. In the present study, we analyzed public databases and showed that reduced NR4A3 expression was associated with shorter survival period of NB in two out of three datasets. An in vitro study revealed that forced expression of NR4A3 in human NB-derived cell line NB1 resulted in elongation of neurites along with overexpression of GAP43, one of the differentiation markers of NB. On the other hand, siRNA-mediated knockdown of NR4A3 suppressed the expression level of GAP43. Interestingly, the forced expression of NR4A3 induced only the GAP43 but not the other molecules involved in NB cell differentiation, such as MYCN, TRKA, and PHOX2B. These results indicated that NR4A3 directly activates the expression of GAP43 and induces differentiated phenotypes of NB cells, without affecting the upstream signals regulating GAP43 expression and NB differentiation.

NRP1 knockdown promotes the migration and invasion of human neuroblastoma-derived SK­N­AS cells via the activation of ß1 integrin expression.

Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which regulates many aspects of cellular function by functioning as co-receptor of various ligands. Recent studies have suggested that NRP1 promotes tumorigenesis, not only by activating the growth of tumor vessels, but also by activating the growth or migration of tumor cells themselves. The present study was performed to elucidate the roles of NRP1 in the development and/or progression of neuroblastoma (NB). In contrast to previous observations in various types of cancer, the analysis of public datasets indicated that lower levels of NRP1 expression were significantly associated with a shorter survival period of patients with NB. Consistent with this finding, wound-healing assay and Matrigel invasion assay revealed that NB cells in which NRP1 was knocked down exhibited increased migratory and invasive abilities. Further analyses indicated that ß1 integrin expression was markedly increased in NB cells in which NRP1 was knocked down, and NB cells in which ß1 integrin was knocked down exhibited decreased migratory and invasive abilities. The results presented herein indicate that NRP1 exerts tumor suppressive effects in NB, at least in part by regulating the expression of ß1 integrin.

ZAR1 knockdown promotes the differentiation of human neuroblastoma cells by suppression of MYCN expression.

Although DNA hypermethylation at non-promoter region of the Zygote arrest 1 (ZAR1) gene has been observed in many types of tumor, including neuroblastoma (NB), the role of this gene in tumor development and/or progression is unclear. One reason is that knowledge about the function of ZAR1 protein is limited. Although it has been reported that ZAR1 plays a crucial role in early embryogenesis and may act as a transcriptional repressor for some transcripts, the detailed mechanism is still elusive. In the present study, we analyzed public data of NB patients and found that higher expression levels of ZAR1 were significantly associated with a shorter survival period. Consistent with this result, ZAR1-depleted NB cells showed well-differentiated phenotypes with elongated neurites and upregulated expression of TRKA and RET, which are markers for differentiated NB. Moreover, the expression level of MYCN protein was markedly suppressed in ZAR1-depleted NB cells. MYCN-depleted cells showed similar phenotypes to ZAR1-depleted cells. The present findings indicate that ZAR1 has oncogenic effects in NB by suppressing cell differentiation via regulation of MYCN expression.

Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells.

Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system and accounts for approximately 15% of all pediatric cancer-related deaths. To newly identify gene(s) implicated in the progression of neuroblastoma, we investigated aberrantly methylated genomic regions in mouse skin tumors. Previously, we reported that TFAP2E, a member of activator protein-2 transcription factor family, is highly methylated within its intron and its expression is strongly suppressed in mouse skin tumors compared with the normal skin. In the present study, we analyzed public data of neuroblastoma patients and found that lower expression levels of TFAP2E are significantly associated with a shorter survival. The data indicate that TFAP2E acts as a tumor suppressor of neuroblastoma. Consistent with this notion, TFAP2E-depleted neuroblastoma NB1 and NB9 cells displayed a substantial resistance to DNA damage arising from adriamycin (ADR), cisplatin (CDDP) and ionizing radiation (IR). Silencing of TFAP2E caused a reduced ADR-induced proteolytic cleavage of caspase-3 and PARP. Of note, compared with the untransfected control cells, ADR-mediated stimulation of CDK inhibitor p21WAF1 was markedly upregulated in TFAP2E­knocked down cells. Therefore, our present findings strongly suggest that TFAP2E has a pivotal role in the regulation of DNA damage response in NB cells through the induction of p21WAF1.

Pyrrole-imidazole polyamide-mediated silencing of KCNQ1OT1 expression induces cell death in Wilms' tumor cells.

KvDMR (an intronic CpG island within the KCNQ1 gene) is one of the imprinting control regions on human chromosome 11p15.5. Since KvDMR exists within the promoter region of KCNQ1OT1 (antisense transcript of KCNQ1), it is likely that genomic alterations of this region including deletion, paternal uniparental disomy and de-methylation in maternal allele lead to aberrant overexpression of KCNQ1OT1. Indeed, de-methylation of KvDMR accompanied by uncontrolled overexpression of KCNQ1OT1 occurs frequently in Beckwith-Wiedemann syndrome (BWS), and around 10% of BWS patients developed embryonal tumors (Wilms' tumor or hepatoblastoma). These observations strongly suggest that silencing of KCNQ1OT1 expression might suppress its oncogenic potential. In the present study, we designed two pyrrole-imidazole (PI) polyamides, termed PI-a and PI-b, which might have the ability to bind to CCAAT boxes of the KCNQ1OT1 promoter region, and investigated their possible antitumor effect on Wilms' tumor-derived G401 cells. Gel retardation assay demonstrated that PI-a and PI-b specifically bind to their target sequences. Microscopic observations showed the efficient nuclear access of these PI polyamides. Quantitative real-time PCR analysis revealed that the expression level of KCNQ1OT1 was significantly decreased when treated with PI-a and PI-b simultaneously but not with either PI-a or PI-b single treatment. Consistent with these results, the combination of PI-a and PI-b resulted in a significant reduction in viability of G401 cells in a dose-dependent manner. Furthermore, FACS analysis demonstrated that combinatory treatment with PI-a and PI-b induces cell death as compared with control cells. Taken together, our present observations strongly suggest that the combinatory treatment with PI polyamides targeting KCNQ1OT1 might be a novel therapeutic strategy to cure patients with tumors over-expressing KCNQ1OT1.

Effectiveness of Interval Appendectomy After Conservative Treatment of Pediatric Ruptured Appendicitis with Abscess.

The management of patients with acute perforated appendicitis with abscess is controversial. The aim of the present study was to assess the outcomes of treatment in patients with this condition. We retrospectively analyzed 31 patients (16 men and 15 women with a mean age of 8.4 years) with appendicitis presenting with abscess. Patients were divided into two groups (emergency operation group and interval operation group), and clinical characteristics and outcomes of treatment were investigated. On presentation, no differences in gender, age, body weight, duration of symptoms, temperature, white blood cell count, C-reactive protein level, or maximum size of the abscess in the axial view were detected between the two groups. Fifteen patients (48.4 %) underwent emergency surgery. The remaining 16 patients (51.6 %) were initially treated conservatively with antibiotics. All 16 patients underwent planned operations after receiving conservative treatment, and two (12.5 %) of these patients underwent appendectomy before the planned operation day because of recurrent appendicitis without abscess. There were no differences in the length of hospital stay. In the emergency operation group, six (40 %) patients presented with wound infection and four (26.7 %) developed a postoperative intra-abdominal abscess. No infective complications were reported in the interval operation group. Interval appendectomy after conservative treatment of pediatric ruptured appendicitis with abscess significantly reduced postoperative infection rates.

Evaluation of the efficacy of incision and drainage versus hainosankyuto treatment for perianal abscess in infants: a multicenter study.

PURPOSE: We retrospectively compared the short-term outcomes between incision and drainage (ID) and hainosankyuto (TJ-122, Tsumura & Co, Tokyo, Japan) treatment for perianal abscess (PA) in infants. METHODS: We retrospectively examined 48 consecutive patients (median age 129 days; range 19-330 days) who presented with PA over a 3 year period. Group 1 comprised 26 patients who were treated with ID at presentation, and Group 2 comprised 22 patients who were treated with oral TJ-122 at presentation; oral treatment was continued until the disappearance of purulent discharge and resolution of induration at the abscess site. RESULTS: PAs were identified in all 48 patients at presentation. The median duration of follow-up was 26 months (range 13-40 months). At presentation, there were no differences in the gender, age, birth weight, duration of symptoms, skin erosion or prevalence of diarrhea between the two groups. Purulent discharge resolved within a median period of 26 days (range 7-42 days) in Group 2, but persisted for 40 days (range 4-196 days) in Group 1. The induration resolved within a median period of 39 days (range 7-91 days) in Group 2, but persisted for 70 days (range 4-308 days) in Group 1 (p = 0.04). CONCLUSIONS: TJ-122 treatment was more beneficial than ID in treating PA in infants.

Sacral nerve function in child patients after ileal J-pouch-anal anastomosis for ulcerative colitis.

To clarify the neurological function of the puborectalis muscle (PM) in child patients with soiling after ileal J-pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), we examined the terminal motor latency in the sacral nerves that regulate the PM. Eight patients after IPAA for UC were studied (6 males and 2 females aged 11 to 13 years with a mean age of 12.8 years). All patients 6 months after IPAA showed soiling (group A) and these patients showed continence at 2 years after IPAA (group B). Group C serving as controls consisted of 16 subjects (10 males and 6 females aged 12 to 17 years with a mean age of 14.4 years). Left- and right-sided sacral nerve terminal motor latency (SNTML) tests were performed at 6 months and 2 years after IPAA in order to measure the latency of the response in the bilateral PM following magnetic stimulation of sacral nerve root segments 2 to 4 (S2-S4) of the spinal column overlying the cauda equina. The following results were obtained. (1) Right-sided SNTML: group A exhibited significant prolongation compared with groups B and C (P < 0.0001 and P < 0.0001, respectively). There was no significant difference between groups B and C (P = 0.2329). (2) Left-sided SNTML: group A exhibited significant prolongation compared with groups B and C (P = 0.0002 and P < 0.0001, respectively). There was no significant difference between groups B and C (P = 0.2315). Note that significant differences were not established between SNTML values measured on the right and left sides. Soiling in child patients 6 months after IPAA may be caused by damage to the bilateral sacral nerves during the operation. However, the damage to the sacral motor nerve improves within 2 years after IPAA.

Nr4a3, a possibile oncogenic factor for neuroblastoma associated with CpGi methylation within the third exon.

Aberrant methylation of Nr4a3 exon 3 CpG island (CpGi) was initially identified during multistep mouse skin carcinogenesis. Nr4a3 is also known as a critical gene for neuronal development. Thus, we examined the Nr4a3 exon 3 CpGi methylation in mouse brain tissues from 15-day embryos, newborns and 12-week-old adults and found significant increase of its methylation and Nr4a3 expression during mouse brain development after birth. In addition, homologous region in human genome was frequently and aberrantly methylated in neuroblastoma specimens. A quantitative analysis of DNA methylation revealed that hypomethylation of CpG islands on Nr4a3 exon 3, but not on exon 1 was identified in three neuroblastomas compared with matched adrenal glands. Additional analysis for 20 neuroblastoma patients was performed and 8 of 20 showed hypomethylation of the CpGi on Nr4a3 exon 3. The survival rate of those 8 patients was significantly lower compared with those in patients with hypermethylation. Immunohistochemical Nr4a3 expression was generally faint in neuroblastoma tissues compared with normal tissues. Moreover, the MYCN amplified NB9 cell line showed hypomethylation and low expression of Nr4a3, while the non-MYCN amplified NB69 cell line showed hypermethylation and high expression. These results indicate that DNA hypomethylation of the CpGi at Nr4a3 exon 3 is associated with low Nr4a3 expression, and correlates with poor prognosis of neuroblastoma. Since Nr4a3 upregulation associated with the hypermethylation and neuronal differentiation in mice, poor prognosis of neuroblastoma associated with Nr4a3 low expression may be partly explained by dysregulation of its differentiation.

Long-term results of seton placement for fistula-in-ano in infants.

BACKGROUND: The present study aimed to assess the long-term results of seton placement for fistula-in-ano (FIA) in infants. METHODS: Data of patients aged <1 year who presented to our department with perianal abscess (PA) between January 2006 and February 2010 were retrospectively reviewed. Our standard initial treatment for PA was incision and drainage. Patients with systemic diseases and inflammatory bowel diseases were excluded. RESULTS: Ninety-five patients were treated for PA and/or FIA during the 5-year period, and follow-up data were available for 90 patients. The mean follow-up duration in these patients was 49.8 ± 11.4 months, and mean age at presentation was 3.1 ± 2.7 months. Of the 90 patients, 36 (40%) developed FIA (39 lesions) and underwent seton placement. The condition healed in a mean period of 6.3 ± 4.0 weeks after the placement of a cutting seton. Healing of the fistula was achieved in 35 (97.2%) of 36 patients after the initial seton procedure, and one patient who showed recurrence underwent a second seton placement, resulting in successful healing of the FIA after 5 weeks. CONCLUSIONS: The long-term success of seton placement indicates that this procedure should be a treatment option for FIA in infants.

[Malignant small bowel ileus due to recurrent colorectal cancer with peritoneal metastasis].

PURPOSE: To investigate the clinical findings of patients who underwent surgery for small bowel obstruction following a previous operation for colorectal cancer. We assessed consecutive patients operated on for peritoneal metastasis with small bowel ileus. PATIENTS AND METHODS: We evaluated the clinical characteristics of 7 consecutive patients with malignant small bowel ileus due to recurrent colorectal cancer with peritoneal metastasis. RESULTS: 1) Primary cancer location: descending colon, 2 cases (28.6%); sigmoid colon, 1 case (14.3%); and rectum, 4 cases (57.1%). 2) Peritoneal dissemination grade: P2, 1 case (14.3%); and P3, 6 cases (85.7%). 3) Liver metastasis grade: H1, 1 case (14.3%); H2, 5 cases (71.4%); and H3, 1 case (14.3%). 4) Lymph node metastasis grade: N2, 1 case (14.3%); and N3, 6 cases (85.7%). 5) Extra-abdominal metastasis: multiple lung metastases were detected in 3 cases (42.9%). 6) Pathological type: moderately differentiated tubular adenocarcinoma (tub2), 3 cases (42.3%); poorly differentiated adenocarcinoma (por), 1 case (14.3%); and mucinous adenocarcinoma (muc), 3 cases (42.3%). The differentiated type (tub2) was more common than the undifferentiated types(por and muc). 7) Malignant small bowel stenosis and/or obstruction: there were 3 or more cases with stenosis and/or obstruction in jejunum and ileum. 8) OPERATIVE PROCEDURE: gastrostomy was performed in 2 cases (28.6%); nephrostomy was performed in 1 case (14.3%); gastrostomy with nephrostomy was performed in 1 case (14.3%); and probe laparotomy was performed in 3 cases (42.9%). 9) Survival time of patients with recurrent colorectal cancer, from readmission to death: 0.5-1 month, 3 cases (42.9%); 1-1.5 months, 3 cases (42.9%); and 1.5-3 months, 1 case (14.3%). All patients died in less than 3 months. CONCLUSIONS: The prognosis of the malignant small bowel ileus due to recurrent colorectal cancer with peritoneal metastasis is very bad.

Anaplastic sarcoma of the kidney: case report and literature review.

Anaplastic sarcoma of the kidney (ASK) is a relatively newly recognized pediatric renal tumor. The present patient, a 13-year-old boy with a large renal mass, underwent surgery. Pathological findings showed proliferation of short spindle-shaped cells with anaplastic features including multiple foci in hyaline cartilage. Complex chromosomal abnormalities were detected in the tumor cells. Postoperative chemotherapy with the regimen for Ewing's sarcoma achieved complete remission but the tumor recurred and the patient died during re-induction chemotherapy. Autopsy indicated the cause of death as duodenal hemorrhage. Because there were no viable tumor cells, the recurrent tumor was considered to have been completely cured by chemotherapy. ASK is a very rare tumor, of unknown pathogenesis, and no standard treatment has yet been established, but the tumor cells may be responsive to chemotherapy. Further study is needed to establish the optimal treatment strategy.

Non-promoter DNA hypermethylation of Zygote Arrest 1 (ZAR1) in neuroblastomas.

BACKGROUND: The comprehensive methylation analysis of tumor-specific differently methylated regions in malignant melanomas and brain tumors has led to the identification of non-promoter hypermethylation of zygote arrest 1 (ZAR1). To search the non-promoter ZAR1 hypermethylation in neuroblastomas, we analyzed the levels of the methylation and transcript expression of ZAR1. METHODS: The MassARRAY® EpiTYPER (Sequenom Inc., San Diego, CA, USA) system was optimized to determine the quantitative methylation levels of ZAR1 for 12 neuroblastoma cell lines, 23 neuroblastoma samples and four adrenal samples. ZAR1 expression levels were evaluated through a quantitative, real-time reverse transcription-polymerase chain reaction. The quantitative methylation levels of ZAR1 were subjected to correlation studies with the established markers of progressive disease and outcome. RESULTS: Strikingly, the hypermethylation of ZAR1 regions and ZAR1 expression levels was observed in the neuroblastoma cell lines and neuroblastoma samples, compared to the adrenal samples. Somatic changes in ZAR1 methylation and ZAR1 expression were found in all three neuroblastoma patients. In the ZAR1 regions, poor-outcome tumors that were MYCN-amplified and/or Stage 3 or 4 and/or the age at diagnosis was≥18months, and/or showed an unfavorable histology were frequently hypermethylated. CONCLUSION: Our results indicate that the hypermethylation of ZAR1 regions is extremely frequent in neuroblastomas and correlates with established markers of progressive disease and outcome.

Identification of aberrant methylation regions in neuroblastoma by screening of tissue-specific differentially methylated regions.

BACKGROUND: The identification of tissue-specific differentially methylated regions (tDMRs) is key to our understanding of mammalian development. Research has indicated that tDMRs are aberrantly methylated in cancer and may affect the oncogenic process. PROCEDURE: We used the MassARRAY EpiTYPER system to determine the quantitative methylation levels of seven neuroblastomas (NBs) and two control adrenal medullas at 12 conserved tDMRs. A second sample set of 19 NBs was also analyzed. Statistical analysis was carried out to determine the relationship of the quantitative methylation levels to other prognostic factors in these sample sets. RESULTS: Screening of 12 tDMRs revealed 2 genomic regions (SLC16A5 and ZNF206) with frequent aberrant methylation patterns in NB. The methylation levels of SLC16A5 and ZNF206 were low compared to the control adrenal medullas. The SLC16A5 methylation level (cut-off point, 13.25%) was associated with age at diagnosis, disease stage, and Shimada classification but not with MYCN amplification. The ZNF206 methylation level (cut-off point, 68.80%) was associated with all of the prognostic factors analyzed. Although the methylation levels at these regions did not reach statistical significance in their association with prognosis in mono-variant analysis, patients with both hypomethylation of SLC16A5 and hypermethylation of ZNF206 had a significantly prolonged event-free survival, when these two variables were analyzed together. CONCLUSIONS: We demonstrated that two tDMRs frequently displayed altered methylation patterns in the NB genome, suggesting their distinct involvement in NB development/differentiation. The combined analysis of these two regions could serve as a diagnostic biomarker for poor clinical outcome.

[Malignant small bowel ileus caused by local recurrence after colorectal cancer surgery].

We assessed 5 consecutive patients operated for local recurrence of small bowel obstruction after previous operation for colorectal cancer. Case 1 involved a 71-year-old man who presented with local recurrence with invasion of the ileum after low anterior resection( D3) for rectal cancer( Rb[rectum/below the peritoneal reflection]). Case 2 involved a 51-year-old woman; case 3, a 54-year-old woman; and case 4, a 60-year-old woman, all showing local recurrence with invasion of the jejunum and ureter after high anterior resection (D3) for rectal cancer (Ra[rectum/above the peritoneal reflection]). Case 5 involved a 58-year-old man who showed local recurrence of descending colon cancer with invasion of the jejunum, liver metastasis, and brain metastasis after left hemicolectomy( D3) for descending colon cancer. For the treatment of local recurrence in the patient referred to in case 1, amputation recti with partial resection of the ileum was performed. Partial resection of the ileum was performed in the patients referred to in cases 2 and 3. Nephrostomy was performed in patients referred to in cases 2, 3, and 4. Partial resection of the anastomotic colon and jejunum was performed in the patient referred to in case 5. The patient involved in case 5 underwent radiotherapy for brain metastasis. In the patient referred to in case 1, only radical surgery was performed, which is associated with a good prognosis. The estimated survival after the operation for local recurrence, except for the patient referred to in case 1, was 2 to 15 months( mean, 11.5 months). Oral intake periods, except for the patient referred to in case 1, were 0 to 4 months (mean, 2.3 months). Postoperative complication rates were 80%( 4/5). Our findings suggest that radical operation leads to a good quality of life( QOL) in patients with malignant small bowel obstruction.

Surgical technique for the transperineal approach of anterior levatorplasty and recto-vaginal septum reinforcement in rectocele patients with soiling and postoperative clinical outcomes.

BACKGROUND/AIMS: To clarify the significance of a transperineal approach of anterior levatorplasty (ALP) and recto-vaginal septum reinforcement in rectocele patients with soiling, we reported the surgical technique and clinical outcomes two years after this operation. METHODOLOGY: Twelve female patients (33-82 years, average 63.3) complaining of defecation disorders (disturbed defecation including excessive straining during defecation, sensation of incomplete defecation and manual assistance of digitation of the vagina) with soiling underwent the following surgical technique: under spinal anesthesia, rectal wall was opened up to the end of the rectal wall weakness. Rectocele in the weak rectal wall was horizontally sutured. Before closing wound ALP was fashioned. RESULTS: In clinical outcomes, excessive straining during defecation, sensation of incomplete evacuation and defecation by manual assistance were statistically significantly reduced postoperatively after a follow-up of 2 years (p<0.01, p<0.01, p<0.0001, p<0.01, respectively). As an early postoperative complication, perineal wound infection was noted in one patient. Late postoperative complications were not noted in any patient. In overall patient satisfaction 2 years after operation, half of the patients were excellent and no patients were poor. CONCLUSIONS: Combined repair of rectocele and ALP by transperineal approach may be a useful procedure for correcting rectocele with soiling. This procedure is also easy and safe.

DNA hypomethylation at the ZNF206-exon 5 CpG island associated with neuronal differentiation in mice and development of neuroblastoma in humans.

Differentiation of human neuroblastoma recapitulates neural crest development. In our whole genome DNA methylation screening of tissue-specific differentially methylated regions (T-DMRs) and developmental stage specific differentially methylated regions (DS-DMRs) we reported that the exon 5 CpG island (CpGi) of Zfp206 (human: ZNF206), which was required to maintain embryonic stem cells in a pluripotent state, was one of potent brain and testis-specific T-DMRs in mice. In this study methylation level of the CpG sites at Zfp206-exon 5 CpGi in mouse brain samples at three different developmental stages (15-day-old embryo; E15, new born; NB, 12-week adult; AD) were quantitatively analyzed and it was identified that Zfp206-exon 5 CpGi was the DS-DMRs in mouse brain. In AD brains, Zfp206-exon 5 CpGi was significantly hypomethylated and Zfp206 expression was repressed, compared with E15 and NB brains. Hence, methylation level of human 5'-end of CpGi at ZNF206-exon 5, which is homologous CpGi to mice, was analyzed in neuroblastomas. Although all four adrenal samples showed complete methylation at the homologous region, we found the hypomethylation in 7 out of 26 neuroblastomas and a significant association between the hypomethylation and poor prognosis. In neuroblastoma cell lines and specimens, the hypomethylation was also associated with ZNF206 expression. These data indicated that the changes in DNA methylation levels at the Zfp206-exon 5 might be one of the important factors during neuronal development in mice and that the hypomethylation of the homologous region induced ZNF206 expression in humans and was associated with human neuroblastomagenesis. Even though the function of ZNF206 and its expression regulation in neuroblastoma remain elusive, ZNF206 might be a candidate differentiation suppressor and prognosis marker in neuroblastoma.

Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

OBJECTIVES: The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. METHODS: The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. RESULTS: The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. CONCLUSION: Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

Ano-neorectal function using manometry on patients after restorative proctocolectomy and ileal J-pouch anal anastomosis for ulcerative colitis in children.

BACKGROUND/AIMS: The purpose of this study was to clarify the ano-neorectal functions in pediatric patients with soiling at a short period and without soiling at a long period after restorative colectomy and ileal J-pouch anal anastomosis (IPAA) for ulcerative colitis (UC). METHODOLOGY: Ten patients after IPAA for UC in childhood were mamometrically studied, aged 10 to 16 years (mean, 13.9 years). Patients after IPAA with ileostomy closure were studied at 6 months (Group A; all patients had soiling) and 3 years after ileostomy closure (Group B; all patients showed continence). Group C served as controls and consisted of 12 subjects (aged 12 to 16 years, mean, 14.8). RESULTS: Maximum anal sphincter pressure at rest and maximum anal sphincter pressure during voluntary contraction were significantly lower in group A than in groups B and C. Minimum neorectal sensory threshold volume in group A was significantly higher than in groups B and C (p<0.01). Maximum neorectal tolerated threshold volumes and neorectal compliances, and positive rates of neorectoanal inhibitory reflex, showed no significant difference among the groups. CONCLUSIONS: Patients with soiling at 6 months after IPAA showed anal sphincter dysfunction and neorectal sensory dysfunction. The IPAA may cause damage to the ano-neorectal apparatus during rectal mobilization due to the short rectal cuff and mucosectomy.