Long-term outcome data from 121 patients treated with Gamma Knife stereotactic radiosurgery as salvage therapy for focally recurrent high-grade gliomas.

INTRODUCTION: We examined patient outcomes after Gamma Knife stereotactic radiosurgery (GKSRS) salvage therapy for recurrent high-grade gliomas (HGGs) to determine whether tumor grade or lesion size affected overall survival (OS) and progression-free survival (PFS). METHODS: This single-center retrospective study assessed radiographic response and clinical outcomes following GKSRS salvage treatment of recurrent malignant gliomas (January 2005-March 2014). RESULTS: A total of 121 patients (67 female) with 132 tumors were treated. Median (range) PFS was 4.7 (3.9-5.4) months for the cohort, 6.8 (4.6-8.9) months for initial grade 2 tumors, 4.2 (1.9-6.5) months for initial grade 3 tumors, and 4.3 (3.7-4.9) months for initial grade 4 tumors. Patients with small lesions (≤6.7 cm3; n = 53) had significantly longer median (range) PFS (6.8 [4.8-8.8], P=0.02). CONCLUSIONS: GKSRS offers meaningful salvage therapy with minimal morbidity in appropriately selected patients with focally recurrent HGGs.

Challenges of imaging for cancer in patients with diabetes and obesity.

A growing body of evidence supports a connection among diabetes (predominantly type 2), obesity, and cancer. Multiple meta-analyses of epidemiological data show that people with diabetes are at increased risk of developing a variety of different cancers and suffer from an increased rate of perioperative complications and cancer mortality. Computed tomography (CT) has played an important role in diagnosis and staging of cancer. Positron emission tomography is complementary to CT in the diagnosis, staging, and evaluation of treatment response for many types of cancer. Because of generally poor clinical outcome of cancers when they are detected in late stages, more research is now focused on stratifying risk to allow personalized screening of at-risk patients and cancer detection at an earlier stage. In this review, we summarize basic noninvasive imaging techniques currently in use to detect cancer with emphasis on the challenges of imaging for early cancer detection in obese patients with diabetes.

Ascending sliding arch aortoplasty: a novel technique for repair of arch hypoplasia.

BACKGROUND: Coarctation of the aorta (CoA) is often associated with clinically significant hypoplasia of the aortic arch. Historically, patch aortoplasty or bypass procedures have been the preferred techniques when arch augmentation is required in children beyond infancy. While safe and effective, these approaches require prosthetic or biologic material without the potential for growth, or normal endothelial and physiologic elastic function. This retrospective study reviews the use of a novel technique, ascending sliding arch aortoplasty, that utilizes viable autologous tissue for repair of arch obstruction in children beyond infancy. METHODS: Between April 2002 and January 2007, 8 patients ranging in age from 18 months to 15 years underwent repair of CoA with arch hypoplasia using ascending sliding arch aortoplasty. All patients were approached through median sternotomy, utilizing cardiopulmonary bypass and selective antegrade cerebral perfusion. RESULTS: There was no mortality or major morbidity. One toddler had pneumonia, resulting in an increased length of stay. Median duration of hospitalization was 5.8 days, ranging from 3 to 10 days. No patient had evidence of residual obstruction or recurrent CoA at a mean follow-up interval of 36 months. CONCLUSIONS: Ascending sliding arch aortoplasty for CoA with arch obstruction in children beyond infancy is a safe technique that can be accomplished without deep hypothermic circulatory arrest. There is no evidence of recurrence at midterm follow-up. Because the augmentation is accomplished with viable autologous aortic tissue, the potential for growth, preserved elasticity and endothelial function, and resistance to infection make this method attractive for use in the young.

Intraoperative imprint cytology of central neurocytoma: The great oligodendroglioma mimicker.

Intraoperative cytologic evaluation of brain tumors has been used either to render a preliminary interpretation or more often as a complement to frozen section examination. Central neurocytoma is a intraventricular neoplasm, typically located in the region of the foramen of Monro, affecting mostly young to middle age adults. Histologically, central neurocytomas are characterized by monotonous cells with round nuclei and neuronal differentiation within a rich capillary network. Their distinction during intraoperative consultations from oligodendroglioma, ependymoma (mainly clear cell ependymoma), and non-Hodgkin lymphoma can be a diagnostic challenge. We report a case of a 19-year-old female with an intraventricular tumor where imprint cytology preparations were crucial for the intraoperative diagnosis of central neurocytoma. Imprint cytology preparations show a round cell neoplasm associated with neuropil clumps and short straight capillaries admixed with tumor cell clusters. To the best of our knowledge, only a few cases describing the cytologic findings of central neurocytomas have been reported in the medical literature. The differential diagnosis, tissue correlation, clinical-radiologic features, and ancillary studies are discussed.

Ciliary syndromes and treatment.

Abnormal visceral patterning has been known for centuries. However, it has not been associated with ciliary dysfunction until recently. Overlapping clinical entities including situs inversus, certain infertility disorders, as well as chronic respiratory infections have their roots in abnormal ciliary function. Current research focuses on causative factors and genes involved in signal transduction pathways that define ciliary function and structure, as well as treatment. In this review, attempts are made to outline selected, yet key topics related to ciliary function in health and disease.

Granulosa cell-specific inactivation of follistatin causes female fertility defects.

Follistatin plays an important role in female physiology by regulating FSH levels through blocking activin actions. Failure to regulate FSH has been implicated as a potential cause of premature ovarian failure. Premature ovarian failure is characterized by amenorrhea, infertility, and elevated gonadotropin levels in women under the age of 40. Because follistatin is essential for postnatal viability, we designed a cre/loxP conditional knockout system to render the follistatin gene null specifically in the granulosa cells of the postnatal ovary using Amhr2cre transgenic mice. The follistatin conditional knockout females develop fertility defects, including reduced litter number and litter sizes and, in the most severe case, infertility. Reduced numbers of ovarian follicles, ovulation and fertilization defects, elevated levels of serum FSH and LH, and reduced levels of testosterone were observed in these mice. These findings demonstrate that compromising granulosa cell follistatin function leads to findings similar to those characterized in premature ovarian failure. Follistatin conditional knockouts may therefore be a useful model with which to further study this human syndrome. These studies are the first report of a granulosa cell-specific deletion of a gene in the postnatal ovary and have important implications for future endeavors to generate ovary-specific knockout mouse models.

Obox, a family of homeobox genes preferentially expressed in germ cells.

We used in silico (electronic database) subtraction to identify ESTs that are preferentially expressed in the adult mouse germ cells. During our analysis, we identified Obox1 and Obox2 transcripts as preferentially expressed in the mouse unfertilized egg libraries. Obox1 and Obox2 transcripts encode homeodomain proteins of 204 amino acids that share 97% identity with each other. Further characterization of mouse BACs encoding Obox1 and Obox2, as well as available BAC and EST sequences in GenBank, identified four closely related genes: Obox3, Obox4, Obox5, and Obox6. Northern blot analyses and RT-PCR from 10 different adult mouse tissues showed that the six Obox family transcripts are preferentially expressed in the gonads. In situ hybridization detected Obox1 and Obox6 transcripts exclusively in oocytes as early as one-layer follicles and throughout folliculogenesis. Obox1, Obox2, Obox3, Obox4, Obox5, and Obox6 map to proximal chromosome 7 in the mouse. The Obox1 and Obox2 genomic structures revealed the presence of six exons each. The Obox genes represent a new family of tissue-specific homeobox genes preferentially expressed in gonads.