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Purpose: In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the 'delayed local treatment (DL)' policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL. Patients: From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed. Results: Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation. Conclusions: Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter. [ABSTRACT FROM AUTHOR]

The metabolic profiles of urine and blood plasma in drug-addicted rat models based on morphine (MOR), methamphetamine (MA), and cocaine (COC)-induced conditioned place preference (CPP) were investigated. Rewarding effects induced by each drug were assessed by use of the CPP model. A mass spectrometry (MS)-based metabolomics approach was applied to urine and plasma of MOR, MA, and COC-addicted rats. In total, 57 metabolites in plasma and 70 metabolites in urine were identified by gas chromatography-MS. The metabolomics approach revealed that amounts of some metabolites, including tricarboxylic acid cycle intermediates, significantly changed in the urine of MOR-addicted rats. This result indicated that disruption of energy metabolism is deeply relevant to MOR addiction. In addition, 3-hydroxybutyric acid, l-tryptophan, cystine, and n-propylamine levels were significantly changed in the plasma of MOR-addicted rats. Lactose, spermidine, and stearic acid levels were significantly changed in the urine of MA-addicted rats. Threonine, cystine, and spermidine levels were significantly increased in the plasma of COC-addicted rats. In conclusion, differences in the metabolic profiles were suggestive of different biological states of MOR, MA, and COC addiction; these may be attributed to the different actions of the drugs on the brain reward circuitry and the resulting adaptation. In addition, the results showed possibility of predict the extent of MOR addiction by metabolic profiling. This is the first study to apply metabolomics to CPP models of drug addiction, and we demonstrated that metabolomics can be a multilateral approach to investigating the mechanism of drug addiction. [ABSTRACT FROM AUTHOR]

This review describes the pathological classification of pediatric liver cancer types and subtypes proposed at the recent international symposium (March 2011, Los Angeles, USA) and meetings involving pathologists serving as central reviewers for the Children's Oncology Group, Société Internationale d'Oncologie Pédiatrique, Gesellschaft für Pädiatrische Onkologie und Hämatologie, or Japanese Study Group for Pediatric Liver Tumors, and pediatric oncologists/surgeons specializing in liver cancers, as well as immunohistochemical panels, recommendations for submission, sampling and evaluation of diagnostic specimens. The pathological classification is intended to be standardized and clinically meaningful, thus improving future patient management and prognosis. The most common pediatric liver cancer is hepatoblastoma (HBL). HBL has two types, the wholly epithelial type and the mixed epithelial and mesenchymal (MEM) type. The wholly epithelial type was subdivided into well-differentiated fetal (pure fetal with low mitotic activity), crowded fetal (mitotically active), embryonal, epithelial mixed, small cell undifferentiated, and cholangioblastic. A macrotrabecular pattern and a pleomorphic epithelial pattern were recognized as supplemental features of epithelial components. The MEM type was subdivided into MEM without teratoid features and MEM with teratoid features. Other liver cancers in children were divided into hepatocellular carcinoma (classic hepatocellular carcinoma and fibrolamellar carcinoma) and hepatocellular malignant tumor not otherwise specified. This classification is basically applied to pretreatment specimens; the evaluation of post-chemotherapy specimens will be the subject of further studies. [ABSTRACT FROM AUTHOR]

Background: In the recent years, surgical resection with pre- and/or postoperative chemotherapy has markedly improved the survival rate of hepatoblastoma patients. We herein report the results of patients treated with the current protocol of the Japanese Study Group for Pediatric Liver Tumor, JPLT-2.Methods: A total of 279 patients with malignant liver tumor were enrolled in JPLT-2. Data from 212 hepatoblastoma cases were analyzed. PRETEXT I patients were treated with primary resection followed by low doses of cisplatin-pirarubicin (tetrahydropyranyl-adriamycin). Otherwise, patients received preoperative cisplatin-pirarubicin (CITA), followed by surgery and postoperative chemotherapy. Ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC) were given as a salvage treatment. High-dose chemotherapy with hematopoietic stem cell transplantation (SCT) was reserved for patients with metastatic diseases.Results: The 5-year overall survival rate (OS) in non-metastatic cases was 100% for PRETEXT I, 87.1% for PRETEXT II, 89.7% for PRETEXT III, and 78.3% for PRETEXT IV. The 5-year OS in metastatic cases was 43.9%. The outcome in non-metastatic PRETEXT IV cases was markedly improved, while the results of metastatic tumors remained poor.Conclusions: JPLT-2 protocol achieved satisfactory survival among children with non-metastatic hepatoblastoma. New approaches are needed for patients with metastatic diseases. [ABSTRACT FROM AUTHOR]

Purpose: In 1996, the Japan Wilms Tumor Study (JWiTS) group was founded to elucidate the efficacy and safety of the regimen established by the National Wilms Tumor Study (NWTS) group in the USA, and a multicenter cooperative study (JWiTS-1) was started in Japan. This report reviews the results of JWiTS-1.Methods: A total of 307 patients with malignant renal tumor were enrolled in the JWiTS-1 study between 1996 and 2005. Central pathological diagnosis and follow-up data were available in 210 cases. The protocol regimens were similar to the NWTS-5 regimens. Clinical stage was classified according to the Japanese Staging System.Results: Five-year overall survival (OS) rate was 91.1% for nephroblastoma, 72.9% for clear cell sarcoma of the kidney (CCSK), and 22.2% for rhabdoid tumor of the kidney (RTK). In the nephroblastoma patients, 5-year OS was 90.5% for stage I disease, 92.2% for stage II, 90.9% for stage III, 86.7% for stage IV, and 78.7% for stage V.Conclusions: The OS of patients in the JWiTS-1 study were comparable with the results of other multicenter studies in the USA and Europe. The outcome for patients with nephroblastoma and CCSK was fair. In contrast, the cure rate for those with RTK was not satisfactory. New treatment strategies are needed for patients with RTK. [ABSTRACT FROM AUTHOR]

The etiology of secretory diarrhea in early life is often unclear. We report a Japanese boy who survived until 3 years of age, despite intractable diarrhea commencing soon after birth. The fecal sodium content was strikingly high (109 mmol/L [normal range, 27-35 mmol/L]) and the osmotic gap was decreased (15 mOsm/kg), consistent with the findings of congenital sodium diarrhea. We examined the mitochondrial respiratory chain function by blue native polyacrylamide gel electrophoresis (BN-PAGE) in-gel enzyme staining, BN-PAGE western blotting, respiratory chain enzyme activity assay, and immunohistochemistry. Liver respiratory chain complex (Co) I activity was undetectable, while other respiratory chain complex activities were increased (Co II, 138%; Co III, 153%; Co IV, 126% versus respective control activities). Liver BN-PAGE in-gel enzyme staining and western blotting showed an extremely weak complex I band, while immunohistochemistry showed extremely weak staining for the 30-kDa subunit of complex I, but normal staining for the 70-kDa subunit of complex II. The patient was, therefore, diagnosed with complex I deficiency. The overall complex I activity of the jejunum was substantially decreased (63% of the control activity). The immunohistochemistry displayed apparently decreased staining of the 30-kDa complex I subunit, together with a slightly enhanced staining of the 70-kDa complex II subunit in intestinal epithelial cells. These data imply that intestinal epithelial cells are also complex I-deficient in this patient. Complex I deficiency is a novel cause of secretory diarrhea and may act via disrupting the supply of adenosine triphosphate (ATP) needed for the maintenance of ion gradients across membranes. [ABSTRACT FROM AUTHOR]

Hepatoblastoma is one of the most common malignant liver tumors in young children. Recent evidences have suggested that the abnormalities in Wnt signaling pathway, as seen in frequent mutation of the ß-catenin gene, may play a role in the genesis of hepatoblastoma. However, the precise mechanism to cause the tumor has been elusive. To identify novel hepatoblastoma-related genes for unveiling the molecular mechanism of the tumorigenesis, a large-scale cloning of cDNAs and differential screening of their expression between hepatoblastomas and the corresponding normal livers were performed. We constructed four full-length-enriched cDNA libraries using an oligo-capping method from the primary tissues which included two hepatoblastomas with high levels of alpha-fetoprotein (AFP), a hepatoblastoma without production of AFP, and a normal liver tissue corresponded to the tumor. Among the 10?431 cDNAs randomly picked up and successfully sequenced, 847 (8.1%) were the genes with unknown function. Of interest, the expression profile among the two subsets of hepatoblastoma and a normal liver was extremely different. A semiquantitative RT-PCR analysis showed that 86 out of 1188 genes tested were differentially expressed between hepatoblastomas and the corresponding normal livers, but that only 11 of those were expressed at high levels in the tumors. Notably, PLK1 oncogene was expressed at very high levels in hepatoblastomas as compared to the normal infant's livers. Quantitative real-time RT-PCR analysis for the PLK1 mRNA levels in 74 primary hepatoblastomas and 29 corresponding nontumorous livers indicated that the patients with hepatoblastoma with high expression of PLK1 represented significantly poorer outcome than those with its low expression (5-year survival rate: 55.9 vs 87.0%, respectively, p=0.042), suggesting that the level of PLK1 expression is a novel marker to predict the prognosis of hepatoblastoma. Thus, the differentially expressed genes we have identified may become a useful tool to develop new diagnostic as well as therapeutic strategies of hepatoblastoma.Oncogene (2004) 23, 5901-5911. doi:10.1038/sj.onc.1207782 Published online 28 June 2004 [ABSTRACT FROM AUTHOR]

We report herein a case of a 46 year old man presenting with a gastric ulcer in whom an endoscopy happened to detect an elevated lesion in the lower esophagus. Endoscopic biopsy proved sufficient for determining the diagnosis of a granular cell tumor (GCT). Electron and microscopic studies suggest that GCT are derived from Schwann cells. Although commonly found in the tongue and skin, GCT are rarely seen in the gastrointestinal tract, especially in the esophagus. However, advances in endoscopic techniques will increase the opportunity of detecting GCT of the esophagus. [ABSTRACT FROM AUTHOR]

A clinical trial of a novel modality consisting of preoperative irradiation and intraluminal hyperthermia therapy, with or without 5-fluorouracil (5-FU) suppositories, was conducted on 30 patients with rectal cancer. To create hyperthermia in rectal cancer, an intraluminal electrode connected to a radiofrequency system was devised. Patients were treated preoperatively with a total irradiation dose of 30 Gy, being 3 Gy every 2 days, and 5 applications of hyperthermia given twice a week, with or without 5-FU suppositories, given as 100 mg a day to a total of 2,000 mg. Twenty patients received irradiation, intraluminal hyperthermia, and 5-FU suppositories, being the three-combination treatment, and the remaining 10 received irradiation and intraluminal hyperthermia, being the two-combination treatment. Shrinkage of the rectal cancer was observed macroscopically in 26 patients, resulting in a flattened cancerous crater or shallow ulcer. Microscopic examination revealed a marked decrease in the number of cancer cells. In fact, three resected specimens showed no evidence of cancer cells microscopically. These striking reductions in cancer size enabled us to successfully perform super-low anterior resections in four patients, with anastomoses being made just above the dentate line with a sufficiently safe margin. No serious complications were encountered in this series. [ABSTRACT FROM AUTHOR]

An 11-year-old girl with a malignant intra-abdominal desmoplastic small-round-cell tumor (DSRCT) and a high serum level of the tumor marker CA 125 is reported. A high serum CA 125 level may be a specific marker for DSRCT, and thus may permit early diagnosis and treatment of this fast-growing tumor. [ABSTRACT FROM AUTHOR]

Describes a method of hemostasis and intraoperative control of hemorrhage during resection of giant mesothelioma in the pelvic cavity by snaring the feeding arteries. Reasons behind the difficulty of resecting mesotheliomas; Findings of the physical examination of the patient; Outcome of the surgery.