Multiple Brain Developmental Venous Anomalies as a Marker for Constitutional Mismatch Repair Deficiency Syndrome.

BACKGROUND AND PURPOSE: Biallelic constitutional mutations in DNA mismatch repair genes cause a distinct syndrome, constitutional mismatch repair deficiency syndrome (CMMRD), characterized by cancers from multiple organs, most commonly brain tumors, during childhood. Surveillance protocols include total and brain MR imaging among other modalities to enable early detection of tumors. Brain surveillance scans revealed prominent brain developmental venous anomalies (DVAs) in some patients. DVAs are benign vascular anomalies, and their incidence in the general population is 2.6%-6.4%. Most developmental venous anomalies are asymptomatic and are found incidentally. Our purpose was to assess the prevalence of DVAs in CMMRD patients and describe their phenotype. MATERIALS AND METHODS: A retrospective descriptive analysis of brain MR imaging studies from 10 patients from 3 families with CMMRD was performed. Analysis included the number of developmental venous anomalies, location, draining vessels, and associated vascular anomalies (ie, cavernomas), with clinical correlation of symptoms and tumors. RESULTS: All 10 patients had ≥2 developmental venous anomalies, and 2 had, in addition, non-therapy-induced cavernomas. There was no clinically symptomatic intracranial bleeding from developmental venous anomalies. Six patients had malignant brain tumors. The location of brain tumors was not adjacent to the developmental venous anomalies. No new developmental venous anomalies developed during follow-up. CONCLUSIONS: The occurrence of multiple developmental venous anomalies in all our patients with CMMRD suggests that developmental venous anomalies may be a characteristic of this syndrome that has not been previously described. If confirmed, this quantifiable feature can be added to the current scoring system and could result in early implementation of genetic testing and surveillance protocols, which can be life-saving for these patients.

Efficacy of XP-endo finisher files in the removal of calcium hydroxide paste from artificial standardized grooves in the apical third of oval root canals.

AIM: To compare the efficacy of the XP-endo finisher file (XP) (FKG Dentaire, La Chaux de Fonds, Switzerland) to that of passive ultrasonic irrigation (PUI) and conventional syringe and needle irrigation (SNI) in the removal of calcium hydroxide paste from an artificial standardized groove in the apical third of root canals. METHODOLOGY: The root canals of 68 mandibular incisors with single oval canals were prepared using Mtwo instruments (VDW GmbH, Munich, Germany) up to size 40, .04 taper. Each tooth was split longitudinally, and in one half of the root, a standardized groove was prepared in the apical part of the specimen. The grooves were filled with Ca(OH)2 , and the root halves were reassembled. The roots were randomly divided into two control groups (n = 4) and three experimental groups (n = 20) according to the Ca(OH)2 methods used: XP, PUI and SNI. The amount of remaining medicament was evaluated under X25 magnification using a 4-grade scoring system. Kappa values were calculated for intra- and interobserver agreement evaluation. The differences in the Ca(OH)2 scores amongst the different groups were analysed using the Kruskal-Wallis test. RESULTS: None of the tested methods could completely clean the Ca(OH)2 from the artificial standardized groove in the apical third of the root canals. XP and PUI removed significantly more Ca(OH)2 than SNI (P < 0.001), with no significant differences between them (P = 0.238). CONCLUSIONS: XP and PUI were more effective in removing Ca(OH)2 from artificial standardized grooves in the apical third of root canals than SNI.

The gastrointestinal manifestation of constitutional mismatch repair deficiency syndrome: from a single adenoma to polyposis-like phenotype and early onset cancer.

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20 years), three subjects had polyposis-like phenotype (13, 14, 16 years), four subjects had few adenomatous polyps (8, 12-14 years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory.

Integrated 18F-fluorodeoxyglucose positron emission tomography and computerized tomography in endodermal sinus tumor.

Application of an in-line positron emission tomography and computerized tomography (PET-CT) in endodermal sinus tumor (EST) is described in this study. CASE 1: A young female with massive ascites postovarian mass resection had elevated alpha-fetoprotein (AFP) serum levels. Following a positive PET-CT study with increased (18)F-fluorodeoxyglucose (FDG) uptake, a CT-guided core biopsy of a peritoneal mass was performed. EST was diagnosed histologically. The patient was disease free after chemotherapy. Follow-up PET-CT was negative in keeping with no viable tumor tissue. CASE 2: A large pelvic mass diagnosed histologically as primarily EST was removed in a teenage patient with elevated AFP levels. PET-CT showed diffuse abdominal spread of FDG uptake, suggesting extensive peritoneal seeding. The patient was disease free after chemotherapy. Follow-up PET-CT was negative. EST is an FDG-avid tumor. PET-CT delineated the prechemotherapy tumor extent adequately ruled out the presence of residual tumor after a successful treatment.

Ascites following ventriculoperitoneal shunting in children with chiasmatic-hypothalamic glioma.

OBJECT: Optic pathway gliomas in children can involve the optic nerve, chiasm, and hypothalamus. This uncommon, slowly growing tumor can cause hydrocephalus, which usually requires placement of a ventriculoperitoneal (VP) shunt. Symptomatic ascites may occasionally develop as a complication of the VP shunt procedure. The purpose of this study was to assess the risk factors associated with CSF ascites in children with optic pathway gliomas. METHODS: Twenty-two children (ages 4 months to 20 years) with chiasmatic-hypothalamic optic gliomas participated in this study. Four children were diagnosed with a chiasmatic glioma, 7 with a hypothalamic glioma, and 11 with a glioma involving both the optic chiasm and hypothalamus. Twelve children (55%) developed hydrocephalus and required VP shunt placement. Of the 12 shunted children, 4 (33%) developed CSF ascites. The incidence of ascites was not associated with infection, tumor metastasis, or multiple shunt revisions. There was no correlation with the size of the tumor. All 4 children with ascites had tumor involving the optic chiasm or optic nerve. None of the 5 children with pure hypothalamic glioma who underwent VP shunt placement have developed ascites. Among the 7 children suffering from chiasmatic or optic nerve gliomas who developed hydrocephalus, the risk of developing ascites as a complication of VP shunt placement was 57% (4/7). Ventriculoatrial (VA) shunt was the treatment of choice for children with VP shunt-induced ascites. After placement of a VA shunt the ascites subsided. The children did not develop further complications. CONCLUSION: We conclude that glioma involving the optic chiasm or nerve is associated with a high risk of developing ascites following VP shunt placement. VA shunt may be the treatment of choice for children with chiasmatic or optic nerve gliomas who require a CSF diversion procedure.

Amniotic fluid and plasma levels of parathyroid hormone-related protein and hormonal modulation of its secretion by amniotic fluid cells.

Parathyroid hormone-related (PTHrP), the major mediator of humoral hypercalcemia of malignancy, may also regulate placental calcium flux, uterine contraction and fetal tissue development. In the present study, we demonstrated that the mean immunoreactive PTHrP concentrations in amniotic fluid at mid-gestation (21.2 +/- 3.7 pmol/l) and at term (19.0 +/- 2.7 pmol/l) were 13-16-fold higher than levels measured in either fetal (1.6 +/- 0.1 pmol/l) or maternal plasma (1.4 +/- 0.3 pmol/l) at term and equal to levels found in plasma of patients with humoral hypercalcemia of malignancy. In vitro studies pointed to three possible sources of PTHrP in amniotic fluid: cultured amniotic fluid cells, cells derived from the amniotic membrane overlying the placenta and placental villous core mesenchymal cells. Treatment of cultured amniotic fluid cells with human prolactin, human placental lactogen (hPL) or human growth hormone (100 micrograms/l) increased PTHrP secretion after 24 h by 43%, 109% and 90%, respectively. Insulin-like growth factors I and II (100 micrograms/l), insulin (100 micrograms/l) and epidermal growth factor (EGF) (10 micrograms/l) increased PTHrP secretion by 53%, 46%, 68% and 118%, respectively. The stimulation of PTHrP secretion by EGF or by hPL was both time- and dose-dependent. In contrast, calcitriol and dexamethasone (10 nmol/l) decreased PTHrP secretion by 32% and 75%, respectively. Estradiol, progesterone, dihydrotestosterone and human chorionic gonadotropin had no effect on PTHrP secretion. These findings support the notion that PTHrP may play a physiological role in the uteroplacental unit and demonstrate that human amniotic fluid cells could be a useful model for studying the regulation of PTHrP production and secretion by hormones and growth factors.

Polyamine excretion in the urine of cancer patients.

In the human body, the production of three polyamines--putrescine, spermidine and spermine--is largely associated with tissue growth, while that of a fourth--cadaverine--seems to be the result of bacterial action. In 37 (88%) of 42 cancer patients and in 24 (44%) of 54 patients with various nonmalignant diseases, increased amounts of polyamines were found in the urine. In the nonmalignant group, which served as a control group, the increased polyamine excretion was especially evident in patients with infections. There were, however, differences in the excretion patterns of the cancer and control groups: combinations of elevated levels of putrescine, spermidine and spermine were seen exclusively in the cancer patients; spermine was not found in the urine of women in the control group. The determination of urinary polyamines appears to hold promise as an aid in the diagnosis of malignant disease and in following up the results of therapy.