Early and late outcomes of congenital biliary dilatation in pediatric patients.

BACKGROUND: This study aimed to reveal the early and late postoperative complications and outcomes after surgery for congenital biliary dilatation (CBD) by reviewing cases over the past 40 years. METHODS: We retrospectively evaluated 59 patients with CBD who underwent radical surgery for complications and outcomes, based on medical records. Early complications were defined as those requiring treatment within 5 years of the initial operation. Late complications were defined as those treated more than 5 years later. RESULTS: The median age at the first surgery was 37 months. Regarding biliary reconstruction, 54 of the 59 patients (91.5%) underwent hepaticojejunostomy. Although three patients underwent cholecystoduodenostomy and one patient underwent hepaticoduodenostomy, all were converted to hepaticojejunostomy after a median of 12.5 years. One patient developed synchronous biliary carcinoma and underwent pancreaticoduodenectomy. Early complications occurred in seven patients with 10 events (surgical site infection, n = 3 bile leakage, n = 3; ileus, n = 3; bile duct obstruction, n = 1 and intussusception, n = 1). Late complications occurred in nine patients with 12 events (ileus, n = 3; anastomotic stricture, n = 3; hepatolithiasis, n = 3; asynchronous biliary carcinoma, n = 2; pancreatolithiasis, n = 1). Two of the three patients with hepatolithiasis underwent hepatectomy refractory to the endoscopic approach. Two patients developed asynchronous biliary carcinoma at 34 and 13 years after last operation; both ultimately died of the carcinoma. Only 35 patients (61.4%) underwent a follow-up examination. A total of 11 female patients (45.8%) eventually married, and all successfully gave birth. CONCLUSION: Although the long-term prognosis is excellent with complete cyst excision and hepaticojejunostomy, we emphasize the importance of long-term follow-up.

Management of refractory chylothorax in the neonatal intensive care unit: A 22-year experience.

BACKGROUND: The aim was to assess the therapeutic strategy of patients with chylothorax in a neonatal intensive care unit. METHODS: Twenty-eight infants with chylothorax were included in this study. Their clinical characteristics and outcomes were reviewed retrospectively. RESULTS: The male-to-female ratio was 1:1. The mean gestational age and birthweight were 35.1 ± 3.5 weeks and 2,692 ± 791 g, respectively. Eighteen patients were diagnosed with congenital chylothorax; chylothorax occurred postoperatively in 10 patients. Chromosomal anomalies were diagnosed in 8 patients. Six patients received surgical therapy, such as pleurodesis, thoracic duct ligation, or lymphaticovenous anastomosis. Two patients required surgery due to resistance to pleurodesis. In surgically managed patients, the daily maximum amount of pleural effusion (mL)/bodyweight (kg) ratio was significantly larger than in non-surgically managed patients: 229.0 ± 180.5 versus 59.7 ± 49.2 mL/kg. In the receiver operating characteristic analysis of the daily maximum amount of pleural effusion/bodyweight ratio, the area under the curve was 0.889 when the cut-off value was 101 mL/kg, and the sensitivity was 0.8333 and the specificity was 0.8095 (P = 0.0059). CONCLUSIONS: Pleurodesis using OK432 could become a surgical first-line therapy for chylothorax even for neonates. It was important to initiate pleurodesis for refractory chylothorax at an earlier stage. A daily chylous effusion/bodyweight ratio of >101 mL/kg was a good predictor and seemed to be a useful parameter for prompt surgical intervention.

Epidermal growth factor receptor/heme oxygenase-1 axis is involved in chemoresistance to cisplatin and pirarubicin in HepG2 cell lines and hepatoblastoma specimens.

PURPOSE: To investigate the possibility that the antioxidant stress protein Heme oxygenase-1 (HO-1) is involved in the acquisition of chemoresistance in cisplatin and pirarubicin (CITA) therapy. METHODS: Human hepatoblastoma-derived cell line (HepG2) was used to generate a knockdown cell line of HO-1 by small interfering RNA (siRNA). Expression of HO-1, epidermal growth factor receptor (EGFR), Akt, and extracellular signal-regulated kinase1/2 (ERK1/2) was examined by Western blot. The cytotoxic effect of cisplatin, pirarubicin, and EGFR inhibitor was examined by trypan blue staining. In human hepatoblastoma specimens (n = 5), changes of HO-1 expression were examined immunohistochemically before and after CITA therapy. RESULTS: HO-1 expression in HepG2 cells was increased by the treatment of cisplatin (CDDP) and pirarubicin (THP) dose-dependently. In HO-1 knockdown HepG2 cells, the HO-1 was not expressed and the percentage of trypan blue-positive cells (dead cells) was significantly increased after treatment of CDDP and THP. The EGFR inhibitor decreased the levels of HO-1, phospho-Akt and phospho-ERK1/2 in HepG2 cells. Combination treatment of EGFR inhibitor with CDDP and THP increased the cytotoxic effect in HepG2 cells. In human hepatoblastoma specimens, 4 of the 5 patients (80%) showed HO-1 expression changed much stronger in the viable tumor cells after CITA therapy. CONCLUSION: The cytotoxic effects of CDDP and THP were both enhanced under HO-1 knockdown conditions as well as under conditions that inhibit the activation pathway of HO-1 by EGFR inhibitors. EGFR/HO-1 axis may be involved in acquiring chemoresistance in HepG2 cell lines as well as in human hepatoblastoma.

A phase I/II study on stereotactic body radiotherapy with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm for lung tumors.

BACKGROUND: In this phase I/II study, we assessed the safety and initial efficacy of stereotactic body radiotherapy (SBRT) for lung tumors with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm. METHODS: Study subjects had histologically confirmed primary non-small-cell lung cancer staged as T1a-T2aN0M0 and pulmonary oligometastasis. The primary endpoint was the incidence of Grade ≥3 radiation pneumonitis (RP) within 180 days of the start of SBRT. The secondary endpoint was local control and overall survival rates. Five patients were initially enrolled at level 1 [50 Gy/4 fractions (Fr)]; during the observation period, level 0 (45 Gy/4 Fr) was opened. The dose was escalated to the next level when grade ≥3 RP was observed in 0 out of 5 or 1 out of 10 patients. Virtual quality assurance planning was performed for 60 Gy/4 Fr; however, dose constraints for the organs at risk did not appear to be within acceptable ranges. Therefore, level 2 (55 Gy/4 Fr) was regarded as the upper limit. After the recommended dose (RD) was established, 15 additional patients were enrolled at the RD. The prescribed dose was normalized at the 95% volume border of the planning target volume based on the Monte Carlo algorithm. RESULTS: Between September 2011 and September 2015, 40 patients (primary 30; metastasis 10) were enrolled. Five patients were enrolled at level 0, 15 at level 1, and 20 at level 2. Only one grade 3 RP was observed at level 1. Two-year local control and overall survival rates were 98 and 81%, respectively. CONCLUSION: The RD was 55 Gy/4 Fr. SBRT with real-time tumor tracking using CyberKnife based on the Monte Carlo algorithm was tolerated well and appeared to be effective for solitary lung tumors.

Long-term results of hypofractionated stereotactic radiotherapy with CyberKnife for growth hormone-secreting pituitary adenoma: evaluation by the Cortina consensus.

The aim of the present study was to evaluate the safety and feasibility of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for growth hormone-secreting pituitary adenoma (GH-PA). Fifty-two patients with GH-PA were treated with hypofractionated SRT between September 2001 and October 2012. Eight patients had clinically silent GH-PA and 44 were symptomatic. Only 1 patient was inoperable. The other patients had recurrent or postoperative residual tumors on MRI. All patients had received pharmacotherapy prior to SRT with a somatostatin analog, dopamine agonist, and/or GH receptor antagonist. The marginal doses were 17.4-26.8 Gy for the 3-fraction schedule and 20.0-32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed by the Cortina consensus criteria 2010 (random GH <1 ng/ml or nadir GH after an oral glucose tolerance test <0.4 ng/ml and normalization of age- and sex-adjusted insulin-like growth factor-1). The median follow-up period was 60 months (range 27-137). The 5-year overall survival, local control, and disease-free survival rates were 100, 100, and 96 %, respectively. Nine patients (5 clinically silent and 4 symptomatic patients) satisfied the Cortina criteria without receiving further pharmacotherapy, whereas the remaining 43 patients did not. No post-SRT grade 2 or higher visual disorder occurred. Symptomatic post-SRT hypopituitarism was observed in 1 patient. CyberKnife hypofractionated SRT is safe and effective when judged by imaging findings for GH-PA. However, it may be difficult to satisfy the Cortina consensus criteria in most symptomatic patients with SRT alone. Further investigations of optimal treatments are warranted.

Hypofractionated Stereotactic Radiotherapy for Auditory Canal or Middle Ear Cancer.

BACKGROUND: Stereotactic radiotherapy (SRT) may represent a new treatment option for individuals with auditory canal or middle ear cancer. METHODS: Study participants with pathologically proven ear cancer were treated with SRT (35 Gy for 3 fractions or 40 Gy for 5 fractions) as first-line therapy. When local tumor recurrence developed following SRT, subtotal temporal bone resection and postoperative chemoradiotherapy were performed as salvage treatment. Boluses were used for the initial 14 study patients. RESULTS: Twenty-nine study participants were enrolled and staged with T1 (n = 3), T2 (n = 7), T3 (n = 14), or T4 disease (n = 5). Three-year overall survival rates were 69% for T1/2 disease, 79% for T3 disease, and 0% for T4 disease. Three-year local control rates were 70% for T1/2 disease, 50% for T3 disease, and 20% for T4 disease. Grade 2 or higher dermatitis or soft-tissue necrosis occurred more frequently in study patients treated with boluses (8/14 vs 2/15; P = .02). Salvage treatment was safely performed for 12 recurrent cases. CONCLUSIONS: These results suggest that SRT outcomes are promising for patients with ear cancer (? T3 disease). The rate of toxicity was acceptable in the study patients treated without boluses. Outcomes of salvage surgery and postoperative radiotherapy following SRT were also encouraging.

Photomobile polymer materials: photoresponsive behavior of cross-linked liquid-crystalline polymers with mesomorphic diarylethenes.

Cross-linked liquid-crystalline (LC) polymers with a mesomorphic diarylethene were prepared to demonstrate a versatile strategy for cross-linked photochromic LC polymers as photomobile materials. Upon exposure to UV light to cause photocyclization of the diarylethene chromophore, the cross-linked polymer films bend toward an actinic light source. By irradiation with visible light to cause a closed-ring to open-ring isomerization, the bent films revert to the initial flat state. Without visible-light irradiation, the bent films remain bent even at 120 °C, indicating high thermal stability of the cross-linked diarylethene LC polymers.

The area and attachment abnormalities of the gubernaculum in patients with undescended testes in comparison with those with retractile testes.

PURPOSE: In order to evaluate the gubernaculum (GN) abnormalities quantitatively in patients with undescended testes (UDT), the area and attachment site of the gubernaculum were evaluated. PATIENTS AND METHODS: Sixty-seven testes from 61 patients with an undescended testis treated in the past 11 years at our institution were examined. Using intraoperative photographs or DVDs, the area of the GN inside the processus vaginalis was measured, and the ratio to that of the testis was determined. When the GN was attached to the vas deferens, the GN distance from the testis was also measured, and the ratio to that of the transverse length of the testis (deviation index) was calculated. Reference values were obtained from 23 testes from 15 patients with mobile testes. RESULTS: In cases with mobile testes, the GN attached to the bottom of the testis, and involved the lower pole of the epididymis. Even though the GN was attached to the bottom of the testis in 43 testes in the UDT patients (64 %), the GN was found to be elongated. The mean GN area ratio was 1.58 (1SD, 0.6) in the UDT cases, in comparison to 0.47 (0.2) in the cases with mobile testes. The GN was attached to the vas deferens in 24 testes (36 %). The deviation index was 1.34 (1.0), but the GN area ratio of these cases was 1.56 (0.7), which was similar to that of the GN attached to the bottom of the testis. CONCLUSION: The present study revealed that an increase in the GN area ratio was the most common imaging abnormality in cases with UDT.

Double Microballoon-occluded Ethanol Embolization for Pelvic Arteriovenous Malformation: A Case Report.

A 40-year-old man was incidentally found to have right-sided pelvic arteriovenous malformation (AVM) with an aneurysmal dominant outflow vein (DOV). The AVM had two main feeding arteries forming a cluster of fine vessels shunt to the DOV. As transvenous approach was impossible due to anatomical difficulty, transarterial ethanol embolization was performed under simultaneous double microballoon occlusion of the two feeding arteries in combination with protective coil embolization of the prostatic branches. Ethanol (13 mL) was intermittently injected from both microballoon catheters until the AV shunt was completely occluded. At 1-year follow-up, contrast-enhanced CT revealed shrinkage of the thrombosed DOV without any symptom. Our case demonstrated the usefulness of simultaneous double microballoon-occluded ethanol embolization for treating a localized pelvic AVM with a few feeding arteries.

A rare case of pyosalpinx in adolescent girl with Hirschsprung's disease who underwent transvaginal ultrasound-guided drainage.

BACKGROUND: Hydrosalpinx and pyosalpinx are rare gynecologic problems during adolescence, especially in girls without a history of sexual activity. They are even rarer in women with Hirschsprung's disease (HD). We herein report a case of pyosalpinx in an adolescent girl with HD treated by transvaginal ultrasound-guided drainage. CASE PRESENTATION: The present patient was a 12-year-old girl (weight 83 kg; height 159 cm; body mass index 32.8 kg/m2). She had undergone five laparotomies for long-segment HD by 2 years. Her menarche had occurred at 10 years. She was admitted with lower abdominal and anal pain. Computed tomography (CT), magnetic resonance imaging (MRI), and transvaginal ultrasound showed left pyosalpinx and abdominal abscess. Surgical drainage was necessary; however, she had a history of polysurgery and was severely obese, so laparotomy was considered to carry a high risk. Transvaginal ultrasound was deemed more likely to reach the abscess safely. Therefore, she was treated with transvaginal ultrasound-guided drainage by a gynecologist skilled in the procedure. She was discharged home after 52 days. One year and nine months after discharge, there was no reformation of either the abscess or pyosalpinx. CONCLUSIONS: Adolescent girls with HD are at risk of developing hydrosalpinx. Depending on the defecation status, pyosalpinx may also develop. As a less-invasive surgical treatment, transvaginal ultrasound-guided drainage can avoid laparotomy. Collaboration with a gynecologist is essential for the diagnosis and treatment of this clinical condition. Pediatric surgeons should communicate with gynecologists for such cases beginning around puberty for continuous follow-up.

Single and hypofractionated stereotactic radiotherapy with CyberKnife for craniopharyngioma.

Craniopharyngiomas are slow-growing tumors found in the suprasellar region, with especially high incidence in Japanese children. Due to the location, proximity and adhesiveness of the tumor to adjacent critical structures, these tumors remain a significant clinical challenge. The purpose of this study was to evaluate the clinical outcome of single and hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for craniopharyngioma. Forty-three patients (21 men and 22 women; median age 44 years; range 3-85 years) were treated at two institutions. Three cases were treated in a single fraction to a marginal dose of 13-16 Gy. The other 40 cases were treated in 2-5 fractions to a marginal dose of 13-25 Gy. Tumor volumes ranged from 0.09 to 20.8 cm(3) (median 2.0 cm(3)). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up period was 40 months (range 12-92 months). The 3-year overall survival and local control rates were 100 and 85%, respectively. In-field cyst enlargement was observed in 9 patients. These tumors had significantly larger volumes (mean 6.9 cm(3); 95% confidence interval, CI, 2.8-10.9 cm(3)) than the 34 controlled tumors (2.9 cm(3); CI 1.5-4.3 cm(3)) (P = 0.02). Out-field tumor regrowth was observed in 4 patients. No radiation-induced symptomatic visual disorder or brain necrosis was observed. Hypopituitarism was observed in only 1 patient. Single and hypofractionated SRT using CyberKnife produced high tumor control rates with minimal complications. Hypofractionated SRT may be useful for protecting the visual nerve and neuroendocrine function, especially for tumors located near the optic pathways and for large tumors.

Concentrative Nucleoside Transporter, CNT, Results in Selective Toxicity of Toyocamycin against Candida albicans.

Toyocamycin (TM) is an adenosine-analog antibiotic isolated from Streptomyces toyocaensis. It inhibits Candida albicans, several plant fungal pathogens, and human cells, but many fungi, including Saccharomyces cerevisiae, are much less susceptible to TM. Aiming to clarify why TM and its analogs tubercidin and 5-iodotubercidin are active against C. albicans but not S. cerevisiae, this study focused on the absence of purine nucleoside transport activity from S. cerevisiae. When the concentrative nucleoside transporter (CNT) of C. albicans was expressed in S. cerevisiae, the recombinant strain became sensitive to TM and its analogs. The expression of C. albicans purine nucleoside permease in S. cerevisiae did not result in sensitivity to TM. Clustered regularly interspaced short palindromic repeat-mediated disruption of CNT was performed in C. albicans. The CNTΔ strain of C. albicans became insensitive to TM and its analogs. These data suggest that the toxicity of TM and its analogs toward C. albicans results from their transport via CNT. Interestingly, S. cerevisiae also became sensitive to TM and its analogs if human CNT3 was introduced into cells. These findings enhance our understanding of the mechanisms of action of adenosine analogs toward Candida pathogens and human cells. IMPORTANCE We investigated the mechanism of toxicity of TM and its analogs to C. albicans. Inspired by the effect of the copresence of TM and purine nucleosides on cell growth of C. albicans, we investigated the involvement of CNT in the toxicity mechanism by expressing CNT of C. albicans (CaCNT) in S. cerevisiae and deleting CaCNT in C. albicans. Our examinations clearly demonstrated that CaCNT is responsible for the toxicity of TM to C. albicans. S. cerevisiae expressing the human ortholog of CaCNT also became sensitive to TM and its analogs, and the order of effects of the TM analogs was a little different between CaCNT- and hCNT3-expressing S. cerevisiae. These findings are beneficial for an understanding of the mechanisms of action of adenosine analogs toward Candida pathogens and human cells and also the development of new antifungal drugs.

The usefulness of OK-432 for the treatment of postoperative chylothorax in a low-birth-weight infant with trisomy 18.

Chylothorax is a rare but life-threatening condition in neonates. We herein report the successful use of OK-432 for a low-birth-weight infant with trisomy 18 who developed refractory chylothorax after thoracic surgery. Increasing the concentration of OK-432 seems useful in cases with a lot of pleural effusion.

Usefulness of Living Donor Liver Transplantation for Patients After Undergoing the Kasai Operation for Biliary Atresia.

BACKGROUND: Living donor liver transplantation (LDLT) has been actively performed for patients with poor clearance of jaundice after the Kasai operation for biliary atresia (BA). The present study clarified the usefulness of LDLT for BA. MATERIALS AND METHODS: Between 2000 and 2020, 24 patients (late group) underwent radical surgery for BA in our institute. The overall survival rate, native liver survival rate, and proportion of LDLT in the late group were retrospectively compared with those of 47 patients treated before 1999 (early group). P values <.05 was considered statistically significant. RESULTS: The overall survival rates at 5, 10, and 15 years were 57%, 54%, and 49%, respectively, in the early group and 100%, 100%, and 100% in the late group (P < .001). The native liver survival rates at 5, 10, and 15 years were 57%, 52%, and 39%, respectively, in the early group and 57%, 49%, and 42% (P = .993) in the late group. In the early group, LDLT was performed in 7 of 47 patients (15%), and the overall survival rate after LDLT was 71%. In the late group, LDLT was performed in 11 of 24 patients (46%), and the overall survival rate after LDLT was 100%. CONCLUSIONS: The long-term outcomes after the Kasai operation for BA have improved in recent years. There were no marked differences in long-term native liver survival before and after 2000. LDLT was actively introduced for patients with poor clearance of jaundice after the Kasai operation, and the survival rate significantly improved.

A rare case of eosinophilic gastrointestinal disorders with short bowel syndrome after strangulated bowel obstruction.

BACKGROUND: Short bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction. CASE PRESENTATION: A 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence. CONCLUSION: The risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination.

Evaluating ß-1,3-glucan synthesis inhibition using emulsion formation as an indicator.

INTRODUCTION: The cell wall ß-1,3-glucan of fungal pathogen Candida albicans is an attractive antifungal target. ß-1,3-Glucan is the skeletal structure in the cell wall and the major scaffold for cell wall proteins. In previous studies using Saccharomyces cerevisiae, strong emulsification was detected by mixing cell wall proteins with oil. To date, there have been no reports of applying an emulsification phenomenon to assessing ß-1,3-glucan synthesis inhibition. OBJECTIVE: The aim of this study was to clarify that emulsification is useful as an indicator for evaluating ß-1,3-glucan synthesis inhibition in C. albicans. METHODS: At first, whether cell wall proteins released from cells by ß-1,3-glucanase treatment worked as an effective emulsifier in C. albicans was examined. Next, whether emulsification occurred even in the culture supernatant brought about by treating with bioactive compounds, including ß-1,3-glucan synthesis inhibitors, under osmotic protection was investigated. In addition, the release of cell wall proteins into the culture medium by treating with those compounds was examined. Finally, a simpler evaluation method using emulsion formation was examined for application to screening of inhibitors. RESULTS: Emulsification occurred by cell wall proteins obtained by treating with ß-1,3-glucanase in C. albicans. In addition, cell wall proteins were released into the culture medium by treating with ß-1,3-glucan synthesis inhibitors, resulting in emulsification. However, such phenomena were not observed in the case of other bioactive compounds. Furthermore, emulsification could be detected in the culture broth obtained by static culture on a small scale. CONCLUSIONS: The obtained results strongly implied that emulsification results from decreased ß-1,3-glucan levels in the cell wall. As emulsification can be simply evaluated by mixing the culture broth with oil, in the future application to the initial assessment and screening of ß-1,3-glucan synthesis inhibitors is expected.

Usefulness of the Monti-Malone procedure as a reconstruction of the antegrade continence enema procedure: a case report.

BACKGROUND: The antegrade continence enema (ACE) procedure is effective for severe constipation in patients with spina bifida and can improve quality of life (QOL). The Monti-Malone procedure (MM), which is a method of creating an enema tract from the colon, has been reported as an alternative to the ACE procedure when the appendix cannot be used. We report the usefulness of MM as a reconstruction of the antegrade continence enema procedure. CASE PRESENTATION: Our patient was a 22-year-old man with congenital spina bifida and hydrocephalus. Ventriculoperitoneal (VP) shunt surgery was performed immediately after birth, and preventative appendectomy was carried out during VP shunt repair when 4 months old. At 5 years of age, the ACE procedure using a balloon-button gastrostomy tube was performed for intractable chronic constipation. Simple management was expected, but after 17 years of age, he experienced increased stool leakage around the gastrostomy tube and his QOL declined due to difficulty in managing the ACE. Therefore, reconstruction of the ACE procedure by MM was performed. After reconstruction, the ACE performed well without any complications. The patient is currently satisfied because management of the ACE is easier than before, and his QOL has markedly improved without stool leakage and dermatitis. CONCLUSIONS: MM is less likely to cause complications and is useful as a reconstruction of the ACE procedure.

Expression of ZIC family genes in meningiomas and other brain tumors.

BACKGROUND: Zic zinc finger proteins are present in the developing rodent meninges and are required for cell proliferation and differentiation of meningeal progenitors. Although human ZIC genes are known to be molecular markers for medulloblastomas, their expression in meningioma has not been addressed to date. METHODS: We examined the mRNA and protein expression of human ZIC1, ZIC2, ZIC3, ZIC4 and ZIC5 genes in meningiomas in comparison to other brain tumors, using RT-PCR, analysis of published microarray data, and immunostaining. RESULTS: ZIC1, ZIC2 and ZIC5 transcript levels in meningiomas were higher than those in whole brain or normal dura mater, whereas all five ZIC genes were abundantly expressed in medulloblastomas. The expression level of ZIC1 in public microarray data was greater in meningiomas classified as World Health Organization Grade II (atypical) than those classified as Grade I (benign). Immunoscreening using anti-ZIC antibodies revealed that 23 out of 23 meningioma cases were ZIC1/2/3/5-immunopositive. By comparison, nuclear staining by the anti-ZIC4 antibody was not observed in any meningioma case, but was strongly detected in all four medulloblastomas. ZIC-positive meningiomas included meningothelial, fibrous, transitional, and psammomatous histological subtypes. In normal meninges, ZIC-like immunoreactivities were detected in vimentin-expressing arachnoid cells both in human and mouse. CONCLUSIONS: ZIC1, ZIC2, and ZIC5 are novel molecular markers for meningiomas whereas ZIC4 expression is highly selective for medulloblastomas. The pattern of ZIC expression in both of these tumor types may reflect the properties of the tissues from which the tumors are derived.