Although the presence of granulomas can support a diagnosis of Crohn disease, severe inflammation and other abnormalities occur in the proximal gastrointestinal tract in Crohn disease and ulcerative colitis.

The stem cell factor (SCF)/c-kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c-kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF). Specific expression of mRNA for c-kit and ␤-actin was measured by ribonuclease protection and by immunohistochemistry to localize c-kit in tissue sections. Expression of c-kit was detected at relatively consistent levels in normal and cirrhotic (

The outcome of pediatric ependymomas is difficult to predict based on clinical and histological parameters. To address this issue, we have performed a comparative genomic hybridization screen of 42 primary and 11 recurrent pediatric ependymomas and correlated the genetic findings with clinical outcome. Three distinct genetic patterns were identified in the primary tumors and confirmed by hierarchical cluster analysis. The first group of structural tumors, showed few, mainly partial imbalances (n ‫؍‬ 19). A second numerical group showed 13 or more chromosome imbalances with a nonrandom pattern of whole chromosome gains and losses (n ‫؍‬ 5). The remaining tumors (n ‫؍‬ 18) showed a balanced genetic profile that was significantly associated with a younger age at diagnosis (P < 0.0001), suggesting that ependymomas arising in infants are biologically distinct from those occurring in older children. Multivariate analysis showed that the structural group had a significantly worse outcome compared to tumors with a numerical (P ‫؍‬ 0.05) or balanced profile (P ‫؍‬ 0.02). Moreover genetic group and extent of surgical resection contributed significantly to outcome whereas histopathology, age, and other clinical parameters did not. We conclude that patterns of genetic imbalances in pediatric intracranial ependymomas may help to predict clinical outcome. Pediatric ependymomas are enigmatic tumors whose behavior is difficult to predict based on clinical and histological factors. These tumors are thought to derive from ependymal cells lining the ventricular system and fall into the broad group of gliomas.1 Ependymomas comprise ϳ10% of all childhood intracranial neoplasms and with Ͼ50% arising in children younger than 5 years of age present a distinct management challenge.2-4 In contrast to adults in which spinal tumors predominate, Ͼ90% of all pediatric ependymomas are intracranial in origin with most tumors arising infratentorially.2,3,5

Inflammatory myofibroblastic tumours (IMFT) may arise at any anatomical site, including lung, soft tissues, retroperitoneum and bladder. Although morphologically similar, these lesions encompass a spectrum of entities with differing aetiology, ranging from reactive/regenerative proliferations to low-grade neoplasms with a risk of local recurrence, but no significant metastatic potential. Vesical IMFT usually presents as a polypoid mass with a pale firm cut surface and can be of considerable size, mimicking a malignant tumour clinically and radiologically. Its good outcome, however, warrants conservative surgical excision, emphasising the importance of identification and distinction from malignant tumours of the bladder that may require more radical surgery and/or adjuvant therapy. We conducted a preliminary retrospective, comparative immunocytochemical study of 20 bladder tumours, including nine IMFTs, five spindle cell (sarcomatoid) carcinomas, two rhabdomyosarcomas, two leiomyosarcomas and two neurofibromas. The results confirmed IMFT positivity for smooth muscle actin, desmin and cytokeratin in 78-89% cases, resulting in potential confusion with sarcomatoid carcinoma or leiomyosarcoma. In contrast, cytoplasmic anaplastic lymphoma kinase (ALK 1) staining was present in eight IMFT (89%), but was not seen in any other lesion examined. The ALK 1 staining was confirmed by fluorescence in situ hybridisation, with translocation of the ALK gene present in 15-60% tumour cells in four of six IMFT examined, but not in four cases of sarcomatoid carcinoma or three of leiomyosarcoma. In conclusion, ALK 1 staining may be of value in the distinction of vesical IMFT from morphologically similar entities, and often reflects ALK gene translocations in these lesions.

No abstract

We report a case of a female infant with a de novo deletion of the short arm of chromosome 9, sex reversal, and an apparently intact SRY gene. Sex reversal has been reported in a number of subjects with a normal Y chromosome and a deletion of the terminal segment of the short arm of chromosome 9. The factors controlling early development of the male testes are unknown. There are likely to be many genes involved and we present additional evidence that one of these is situated on the end of the short arm of chromosome 9. (J Med Genet 1993;30:518-20) The primary event in the determination of male and female sex is dependent on the presence or absence of the sex determining region of the Y chromosome (SRY).1 Sex reversal has been reported in a number of subjects with a Y chromosome and a terminal deletion of the short arm of chromosome 9.2-6 These cases involved translocation of chromosome 9 with other chromosomes and therefore they were trisomic for part of another chromosome in addition to being monosomic for terminal 9p. We report a case of a sex reversed female infant with a de novo deletion of the distal short arm of chromosome 9, sex reversal, and an apparently intact SRY gene. Figure 1 Partial G banded metaphase to show deleted chromosome 9 with apparently terminal deletion of the short arm del (9) (p2305). Frozen fibroblasts from the proband are banked at Guy's Hospital, reference 90/3077.The SRY gene was amplified by the polymerase chain reaction, cloned, and sequenced and no mutations found.' Endocrine investigations Endocrine investigation was consistent with gonadal failure with a raised FSH of > 40 mU/l (normal range < 2 mU/l). The LH rose markedly after LHRH stimulation from 11 IU/l to > 50 IU/l (resting normal range 1-6 IU/1). The testosterone rose only minimally from 0*9 to 1-5 nmol/l (resting normal range A1Onmol/l) after three injections of HCG (1000 units x 3).~~- Docherty, Robb, Ramani, Hawkins, Grant Summary of patients with sex reversal and deletions of the distal short arm of chromosome 9.

The immunoreactivity of a new monoclonal antibody to endothelium. QBEND/10, in formalin-fixed, paraffin-embedded sections from a variety of vascular and lymphatic tumours is described and compared to that of two other endothelial markers, von Willebrand factor and Ulex europaeus agglutinin, type 1. All the benign tumours of blood vascular origin showed immunoreactivity whereas only five out of eight lymphangiomas demonstrated a weak focal reaction with QBEND/10. Primitive lumina in epithelioid and spindle cell haemangioendotheliomas were highlighted in all the cases. Tumour cells in angiosarcoma forming vasoformative areas and solid areas showed immunopositivity to QBEND/10 in 17/23 and 13/24 cases respectively, and complementary immunoreactivity for von Willebrand factor was observed. Proliferating vessels and the majority of spindle cells in Kaposi's sarcoma were positive in all 40 cases. Only one of 54 cases of carcinoma showed luminal reaction to QBEND/10. However, 17 of 45 spindle cell tumours displayed a positive reaction. QBEND/10 is an additional marker for demonstrating endothelial differentiation and has some advantages over currently available antibodies.

PURPOSE Bevacizumab improves survival for metastatic colorectal cancer patients with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF165b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF165b levels treated with bevacizumab. METHODS Blinded tumor samples from the phase-III trial of FOLFOX4±bevacizumab were assessed for VEGF165b and VEGFtotal by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF165b:VEGFtotal for 44 samples from patients treated with FOLFOX+bevacizumab (Arm A) and 53 samples from patients treated with FOLFOX4 (Arm B), and PFS, and overall survival (OS) analysed based on PI relative to median ratio. RESULTS Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF165b:VEGFtotal ratio scores below median treated with FOLFOX4+bevacizumab compared to FOLFOX4 alone (median 8.0 months vs 5.2 months, p<0.02), but no effect of bevacizumab on PFS in patients with VEGF165b:VEGFtotal ratio >median (5.9 months vs 6.3 months). These findings held after adjustment for other clinical and demographic features. Overall survival (OS) was increased in Arm A (median 13.6 months) compared with Arm B (10.6 months) in the low VEGF165b group, but this did not reach statistical significance. There was no difference in the high VEGF165b:VEGFtotal group between FOLFOX+bevacizumab (10.8 months) and FOLFOX alone (11.3months). CONCLUSION Low VEGF165b:VEGFtotal ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit.