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.

[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.

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.

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.

[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.

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.

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.

The clinical course in pediatric solid tumor patients with focal nodular hyperplasia of the liver.

BACKGROUND: Focal nodular hyperplasia (FNH) of the liver is a rare benign lesion that may be related to the vascular and hepatic damage induced by completion of tumor therapy and a reaction to localized vascular abnormality. The aim of this study was to analyze the clinical course in pediatric solid tumor patients with FNH. METHODS: We analyzed thirty-two patients with pediatric solid tumors who received multiagent chemotherapy (15 advanced neuroblastomas, 7 hepatoblastomas, 5 rhabdomyosarcomas, 2 nephroblastomas, 1 rhabdoid tumor of the kidney, 1 clear cell sarcoma of the kidney and 1 pancreatoblastoma). All of them had been previously treated at our hospital, and have been alive for over 3 years without recurrence. RESULTS: FNH lesions were discovered in three (9.4%) of 32 patients, and were neuroblastoma (NB) stage 4. All 3 patients received induction chemotherapy and high-dose alkylating agents, and developed grade 3 (National Cancer Institute Common Toxicity Criteria; NCI-CTC) liver dysfunction during completion of tumor therapy without veno-occlusive disease. Two of the 3 patients received the same induction chemotherapy and high doses of alkylating agents with total body irradiation for cytoreductive agents prior to peripheral blood cell transplantation. FNH lesions in both female patients who received estrogen replacement therapy after completion of tumor therapy have expanded and are increasing. CONCLUSION: FNH appears to be a late complication of iatrogenic disease in NB stage 4 patients. The therapeutic agents for NB stage 4 and estrogen replacement therapy should be considered as risk factors for the development of FNH.

Therapeutic strategies of meconium obstruction of the small bowel in very-low-birthweight neonates.

BACKGROUND: Meconium obstruction without cystic fibrosis in low-birthweight neonates is a distinct clinical entity. We aimed to determine what therapeutic strategies work best in very-low-birthweight neonates with meconium obstruction of the small bowel under varied clinical conditions caused by the associated diseases of prematurity. METHODS: Medical records of very-low-birthweight neonates with meconium obstruction of the small bowel treated from 1998 to 2008 were retrospectively reviewed. Pre- and postnatal data, treatments, and clinical outcomes were assessed. RESULTS: Nine patients with perinatal complications were identified. Mean gestational age and birthweight were 26.9 weeks and 863 g, respectively. Abdominal distension developed from 1 to 7 days of life. Five patients were initially treated with Gastrografin enema, three of whom had successful outcomes. Two hemodynamically unstable patients failed to respond to Gastrografin treatment; they ultimately died of sepsis. The remaining four without Gastrografin treatment underwent enterostomy to resolve the obstructions with good results. CONCLUSIONS: Gastrografin and surgical treatments should be appropriately selected based on the underlying pathologies of meconium obstruction of the small bowel. Therapeutic Gastrografin enema is effective, safe and repeatable; however, it is not recommended for hemodynamically unstable patients. Surgical intervention is reserved for those who develop rapid abdominal distension that risks perforation.

Study of segmental colonic transit time in healthy men.

BACKGROUND/AIMS: There are few reports of the segmental colonic transit time (SCTT) in healthy men. To clarify the SCTT for healthy men, the author measured the SCTT of healty men using radiopaque markers (RM). METHODOLOGY: The author analyzed the SCTT of 26 healthy men, who were aged from 24 to 60 years and had a mean age of 48.8 years, with RM (20 radiopaque polyvinyl chloride 0-rings). The criteria for participation included a usual stool frequency of between three per week and three per day, no history of gastrointestinal disease, and no use of medications known to affect gastrointestinal motility. RESULTS: The overall gastrointestinal transit time was 36.2±5.1 hours, and the transit time from the mouth to the cecum was 6.8±1.4 hours. The half-dose transit times of the ileocecal valve, hepatic flexure, splenic flexure, descending-sigmoid line, and evacuation were 6.9±1.6, 15.9±1.7, 18.8±1.7, 24.3±4.4 and 36.4±5.3 hours, respectively. The ascending (9.5±2.3 hours) and descending colon (5.5±4.1 hours) had shorter transit times than the sigmoid-rectum section (12.7±2.1 hours) (p<0.001, p<0.01, respectively), and the transverse colon (4.2±2.1 hours) had a shorter transit time than the ascending colon (p<0.05). There were no significant differences in transit time between the descending and transverse colon. CONCLUSIONS: Measuring the SCTT using RM may be effective for detecting the SCTT of specific sections of the bowel. This method is simple and can be easily performed at any radiology department.

Effect of combined treatment with FK506, FTY720, and ex vivo graft irradiation in rat small bowel transplantation: expression of mucosal addressin cell adhesion molecule-1.

We studied the effect of the combined treatment with FK506, FTY720, and ex vivo graft irradiation. Five groups of SBT animals were studied on days 3, 5, and 7 after operation (untreated, FK506, FTY720, FK506 + FTY720, FK506 + FTY720 + irradiation). Indirect immunoperoxidase staining was performed against CD4 and MAdCAM-1. The numbers of CD4 positive cells in allografts were also analyzed by flow cytometry. The graft survival was prolonged in all of the FK506- and FTY720-treated groups. SBT allografts treated by FK506 and FTY720 demonstrated less infiltration of CD4 positive cells, but the irradiation group did not show any effects on its expression. In FK506- and FTY720-treated groups, MAdCAM-1 expression on the HEVs in PPs was up-regulated, and its expression on the ECVs in the LP was down-regulated compared with other allograft groups. Irradiation did not show any effects on MAdCAM-1 expression on both HEVs in PPs and ECVs in LP. FK506 and FTY720 prevented the infiltration of CD4 positive cells, the down-regulation of MAdCAM-1 expression on HEVs in PPs, and the up-regulation of MAdCAM-1 expression on ECVs in LP during the early phase of SBT.

Mesenchymal hamartoma of the liver originating in the caudate lobe with t(11;19)(q13;q13.4): report of a case.

We herein report the case of a 35-month-old female child presenting with mesenchymal hamartoma of the liver (MHL), with t(11;19)(q13;q13.4) originating in the caudate lobe. This case is the eighth known description of a cytogenetic abnormality in mesenchymal hamartoma of the liver. It is similar to the seven cases previously reported, in that one of the breakpoints involves the chromosome band 19q13.3 or 19q13.4, but it is the first report of an abnormality originating in the caudate lobe.

Usefulness of power Doppler ultrasonography and superparamagnetic iron oxide enhanced magnetic resonance imaging for diagnosis of focal nodular hyperplasia of the liver after treatment of neuroblastoma.

Focal nodular hyperplasia (FNH) of the liver is rare in children, and it is usually diagnosed through a biopsy of the liver or hepatectomy. The authors report a case of a 10-year-old girl with multiple focal nodular hyperplasia lesions of the liver after the completion of tumor therapy for advanced neuroblastoma, and review the usefulness of the combination of power Doppler ultrasonography (US) and superparamagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI) for the diagnosis of FNH without a biopsy of the liver or hepatectomy.

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.

A rare case of multiple duodenal perforations in early infancy.

Duodenal perforation in early infancy is an uncommon condition. We describe a case of duodenal perforation from suspected ulcer. A premature boy was born at the gestational age of 26 weeks with a birth weight of 764 g. The Apgar score at 1 min was 3 and at 5 min had decreased to 2. He was given intermittent mandatory ventilation for one month after the birth. Ninety-eight days after birth, the infant's abdomen became distended. A supine and cross-table lateral radiograph of the abdomen revealed massive pneumoperitoneum. An exploratory laparotomy was performed, which revealed two perforations in the anterior wall of the first portion of the duodenum. The operation procedure was direct closure and intra-abdominal drainage. On the postoperative first day, he had central urorrhagia from hematencephalon. The patient's growth after surgery has been normal, with no recurrence of duodenal ulcer.

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.

Cytogenetic abnormalities in hepatoblastoma: report of two new cases and review of the literature suggesting imbalance of chromosomal regions on chromosomes 1, 4, and 12.

Two cases of hepatoblastoma with unique karyotypic changes are described. One case was that of a 2-year-old boy with an unbalanced chromosomal translocation involving 4q35 as the sole chromosomal abnormality. The clonal karyotype of this tumor was 46,XY,add(4)(q35)[3]/46,XY[9]. In the other case, that of a 2-year-old boy, karyotypic analyses revealed the clonal karyotype as 57,XY,+del(1)(p22),+2,+5,+6,+7,+8,+del(12)(p12),+18,+19,+20,+22[4]/46,XY[12]. Review of these two cases, together with previous reports, underscored the significance of numerical and/or structural chromosomal abnormalities of 1q, 4q, 2, 8, and 20 in the development of hepatoblastoma. The present results show that imbalance of the terminal region of 4q could be the sole chromosomal abnormality in a hepatoblastoma. We also found that imbalance of chromosomal regions on chromosomes 1 and 12 may contribute to the development of hepatoblastoma.