Stereotactic-guided direct orbital puncture for treatment of orbital arteriovenous fistula.

The patient presented with left-sided chemosis, exophthalmos, and progressive visual loss. Cerebral angiography ed a left orbital arteriovenous malformation and an associated hematoma, with the point of fistulation between the left ophthalmic artery and the anterior section of the inferior ophthalmic vein, with retrograde flow through the superior ophthalmic vein. Transvenous embolization through the anterior facial and angular veins was unsuccessful, with residual shunting. Stereotactic-guided direct venous puncture and Onyx embolization was subsequently performed in the hybrid operating room (OR) to cure the fistula. A subciliary incision allowed for retraction of the orbital contents, creating an optimal trajectory. An endonasal endoscopic approach was performed after the embolization to decompress the orbit. This procedure is shown in video 11-11 neurintsurg;16/4/429/V1F1V1Video 1 .

Microsurgical Clipping of a Middle Cerebral Artery Aneurysm After Woven Endobridge Embolization Recurrence.

We present the case of a 67-year-old patient with a left middle cerebral artery (MCA) aneurysm treated with a Woven EndoBridge (WEB) device, who experienced neck recurrence after initial complete obliteration. The initial angiogram showed a wide-necked left MCA aneurysm that measured 8 × 7 mm with a 5-mm neck, treated with a WEB device. Post implantation, the initial follow-up angiogram showed complete obliteration. However, subsequent angiogram showed neck recurrence measuring 6.6 × 1.7 mm. The WEB device has become a popular alternative to traditional clipping and coiling procedures, with studies reporting successful treatment of 85%. However, concerns have been raised regarding the device's efficacy in achieving complete aneurysm obliteration, with a lower rate of complete aneurysm occlusion and a higher rate of recurrence compared with surgical clipping. The decision was made to retreat with clipping, and the surgery was successful in completely obliterating the aneurysm. The patient had no residual MCA aneurysm, with both M2 branches patent on postoperative angiogram. Literature review of retreatment options for WEB device failures highlights that the retreatment rate after WEB embolization is approximately 10%. For surgically accessible aneurysms, surgical clipping is an effective retreatment strategy after WEB failure given the compressibility of the device. Video 1 and our literature review provide valuable insights into a rare case of aneurysm recurrence after complete obliteration at initial follow-up after WEB embolization that was successfully treated with surgical clipping.1-8.

Third ventricular choroid plexus papilloma: a pure neuroendoscopic approach.

Pure endoscopic technique in resection of intraventricular tumors is an emerging technology. This case demonstrates resection of a multicentric choroid plexus papilloma in a 2-month-old child. This child had two district tumors: one located in the left atrium and another in the third ventricle. Initial microsurgery was performed to resect the left atrial tumor. With the tumor noted to be not very vascular at initial surgery, the third ventricle tumor was resected with a GAAB neuroendoscope and NICO Myriad. A gross-total resection was achieved. At 3 years' follow-up, the child remains tumor free and developing without any functional deficits. The video can be found here: https://stream.cadmore.media/r10.3171/2023.1.FOCVID22145.

Robotic-guided direct transtemporal embolization of an indirect carotid cavernous fistula.

A middle-aged patient presented with right-sided chemosis, exophthalmos, and progressive visual loss. Digital subtraction angiography revealed a type D carotid-cavernous fistula (CCF). Transarterial embolization through the internal maxillary artery was unsuccessful, and there was no venous access to the CCF. A robotic-guided direct transtemporal embolization of the CCF with Onyx was performed, resulting in successful fistula obliteration and symptom resolution. This is the first reported case of a robotic-guided direct transcranial CCF embolization. We include a technical video that demonstrates this procedure (Supplemental File 1).

Comparison of multimodal surgical and radiation treatment methods for pediatric craniopharyngioma: long-term analysis of progression-free survival and morbidity.

OBJECTIVE: The authors compared survival and multiple comorbidities in children diagnosed with craniopharyngioma who underwent gross-total resection (GTR) versus subtotal resection (STR) with radiation therapy (RT), either intensity-modulated radiation therapy (IMRT) or proton beam therapy (PBT). The authors hypothesized that there are differences between multimodal treatment methods with respect to morbidity and progression-free survival (PFS). METHODS: The medical records of children diagnosed with craniopharyngioma and treated surgically between February 1997 and December 2018 at Texas Children's Hospital were reviewed. Surgical treatment was stratified as GTR or STR + RT. RT was further stratified as PBT or IMRT; PBT was stratified as STR + PBT versus cyst decompression (CD) + PBT. The authors used Kaplan-Meier analysis to compare PFS and overall survival, and chi-square analysis to compare rates for hypopituitarism, vision loss, and hypothalamic obesity (HyOb). RESULTS: Sixty-three children were included in the analysis; 49% were female. The mean age was 8.16 years (95% CI 7.08-9.27). Twelve of 14 children in the IMRT cohort underwent CD. The 5-year PFS rates were as follows: 73% for GTR (n = 31), 54% for IMRT (n = 14), 100% for STR + PBT (n = 7), and 77% for CD + PBT (n = 11; p = 0.202). The overall survival rates were similar in all groups. Rates of hypopituitarism (96% GTR vs 75% IMRT vs 100% STR + PBT, 50% CD + PBT; p = 0.023) and diabetes insipidus (DI) (90% GTR vs 61% IMRT vs 85% STR + PBT, 20% CD + PBT; p = 0.004) were significantly higher in the GTR group. There was no significant difference in the HyOb or vision loss at the end of study follow-up among the different groups. Within the PBT group, 2 patients presented a progressive vasculopathy with subsequent strokes. One patient experienced a PBT-induced tumor. CONCLUSIONS: GTR and CD + PBT presented similar rates of 5-year PFS. Hypopituitarism and DI rates were higher with GTR, but the rate of HyOb was similar among different treatment modalities. PBT may reduce the burden of hypopituitarism and DI, although radiation carries a risk of potential serious complications, including progressive vasculopathy and secondary malignancy. Further prospective study comparing neurocognitive outcomes is necessary.

Ultra-early synostectomy and cranial remodeling orthoses in the management of craniosynostoses.

OBJECTIVE: The advent of endoscopic synostectomy has enabled early surgery for infants with craniosynostosis. Even though diagnosis is often made at birth, endoscopic synostectomy has traditionally been delayed until the infant is 3 months of age. There have been very few published reports of this procedure being performed in the early neonatal period. The authors discuss their experience with ultra-early endoscopic synostectomy, defined as an operation for infants aged 8 weeks or younger. METHODS: A retrospective analysis of infants who underwent operations at or before 8 weeks of age between 2011 and 2020 was done. RESULTS: Twenty-five infants underwent operations: 11 were 2 weeks of age or younger, 8 were between 3 and 4 weeks of age, and 6 were between 5 and 8 weeks of age. The infants weighed between 2.25 and 4.8 kg. Eighteen had single-suture synostosis, and 7 had multiple sutures involved. Of these 7, 4 had syndromic craniosynostosis. The average operative time was 35 minutes, and it was less than 40 minutes in 19 cases. The estimated operative blood loss was 25 ml or less in 19 cases; 5 infants required an intraoperative blood transfusion. In 1 child with syndromic multisuture craniosynostosis, the surgery was staged due to blood loss. Two children experienced complications related to the procedure: one had an incidental durotomy with skin infection, and the other had postoperative kernicterus. All infants were fitted for cranial remodeling orthoses following surgery. Three of the 25 infants required reoperations, with 2 patients with syndromic craniosynostosis needing repeat surgery for cranial volume expansion and cosmetic appearance. Another child with syndromic craniosynostosis is awaiting cranial expansion surgery. Follow-up varied between 6 months and 8 years. CONCLUSIONS: The data show that ultra-early synostectomy is safe and not associated with increased complications compared with surgery performed between 3 and 6 months of age. Infants with multisuture synostosis had increased operative time, required blood transfusion, and were more likely to require a second operation.

Genomic profiling guides the choice of molecular targeted therapy of pancreatic cancer.

Pancreatic cancer has the worst five-year survival rate of all malignancies due to its aggressive progression and resistance to therapy. Current therapies are limited to gemcitabine-based chemotherapeutics, surgery, and radiation. The current trend toward "personalized genomic medicine" has the potential to improve the treatment options for pancreatic cancer. Gene identification and genetic alterations like single nucleotide polymorphisms and mutations will allow physicians to predict the efficacy and toxicity of drugs, which could help diagnose pancreatic cancer, guide neoadjuvant or adjuvant treatment, and evaluate patients' prognosis. This article reviews the multifaceted roles of genomics and pharmacogenomics in pancreatic cancer.

MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab.

BACKGROUND: Epidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown. METHODS: miR-566 expression levels were detected in glioma cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate VHL as a direct target gene of miR-566. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm whether miR-566 inhibition could sensitize anti-EGFR therapy. RESULTS: In this study, we demonstrated that miR-566 is up-regulated in human glioma cell lines and inhibition of miR-566 decreased the activity of the EGFR pathway. Lentiviral mediated inhibition of miR-566 in glioblastoma cell lines significantly inhibited cell proliferation and invasion and led to cell cycle arrest in the G0/G1 phase. In addition, we identified von Hippel-Lindau (VHL) as a novel functional target of miR-566. VHL regulates the formation of the ß-catenin/hypoxia-inducible factors-1α complex under miR-566 regulation. CONCLUSIONS: miR-566 activated EGFR signaling and its inhibition sensitized glioblastoma cells to anti-EGFR therapy.

Hereditary risk of women's cancers.

The characterization of specific genes responsible for the hereditary risk of common cancers has enabled the development of clinical tests designed to identify at-risk individuals and to significantly improve the clinical outcome of such individuals. Two of the most important syndromes associated with a hereditary risk of cancer in women are hereditary breast and ovarian cancer, resulting from the BRCA1 and BRCA2 genes, and hereditary non-polyposis colorectal cancer, caused primarily by the MLH1 and MSH2 genes. As testing for the hereditary risk of breast, ovarian, endometrial and colorectal cancer enters the clinical mainstream, physicians responsible for the health care of women are increasingly required to assess and provide guidance to healthy patients with a strong family history, cancer survivors who may be at risk of a second cancer and women who discover that a family member carries a specific mutation identified through genetic testing. Obstetricians and gynaecologists must therefore become familiar with the principles of assessing the family history for specific hereditary cancer syndromes, with the appropriate use of tests to confirm such syndromes and with the management options for women who have inherited a greatly increased risk of cancer.

BRCA1/2 genetic testing in the community setting.

PURPOSE: BRCA1/2 genetic testing has been commercially available in the United States since 1996. Most published reports described BRCA1/2 testing as research studies at large academic centers, but less is known about testing in the community. This study evaluates the process and early outcomes of BRCA1/2 genetic testing as a clinical service in the community setting. METHODS: Surveys were mailed to women in the United States whose health care providers ordered BRCA1/2 genetic testing from Myriad Genetic Laboratories from August 1998 through July 2000. Women tested at 149 large academic centers were excluded. Main outcome measures were demographic characteristics, recall of and satisfaction with the genetic testing process, and likelihood of pursuing cancer prevention strategies. RESULTS: Among the 646 respondents, 414 (64%) had a personal history of cancer and 505 (78%) had at least one first-degree relative with breast and/or ovarian cancer. Most subjects (82%) recalled discussions of informed consent before testing (median time, 30 minutes). Genetic results were conveyed during an office visit (57%), by telephone (39%), or by mail (3%). More than 75% of respondents were "very satisfied with the counseling received." Cancer-free subjects with a germline mutation were more likely to consider prevention strategies after receiving the genetic results. CONCLUSION: Virtually all respondents had a personal and/or family history of breast/ovarian cancer. Although pretest and posttest communications were not standardized, overall satisfaction with clinical breast cancer genetic testing was high. Additional follow-up will provide data on future cancer prevention practices and cancer incidence.

Characterization of common BRCA1 and BRCA2 variants.

Many missense variants identified in BRCA1 and BRCA2, two genes responsible for the majority of hereditary breast and ovarian cancer, are of unclear clinical significance. Characterizing the significance of such variants is important for medical management of patients in whom they are identified. The aim of this study was to characterize eight of the most common reported missense mutations in BRCA1 and BRCA2 occurring in patients tested for hereditary risk of breast and ovarian cancers. The prevalence of each variant in a control population, co-segregation of the variant with cancer within families, location of the variant within the gene, the nature of the amino acid substitution and conservation of the wild-type amino acid among species were considered. In a control population, the BRCA1 variants M1652I, R1347G, and S1512I, were each observed at a frequency of 4.08%, 2.04%, and 2.04%, respectively, and the BRCA2 variants A2951T, V2728I, and D1420Y, were seen at 1.02%, 0.68%, and 0.34%, respectively. Although the BRCA2 variants T598A and R2034C were not seen in this group of controls, other clinical and published observations indicate that these variants are not deleterious. Based on epidemiological and biological criteria, we therefore conclude that the BRCA1 missense mutations R1347G, S1512I and M1652I, and the BRCA2 missense mutations T598A, D1420Y, R2034C, V2728I, and A2951T, are not deleterious mutations.

Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals.

PURPOSE: To assess the characteristics that correlate best with the presence of mutations in BRCA1 and BRCA2 in individuals tested in a clinical setting. PATIENTS AND METHODS: The results of 10,000 consecutive gene sequence analyses performed to identify mutations anywhere in the BRCA1 and BRCA2 genes (7,461 analyses) or for three specific Ashkenazi Jewish founder mutations (2,539 analyses) were correlated with personal and family history of cancer, ancestry, invasive versus noninvasive breast neoplasia, and sex. RESULTS: Mutations were identified in 1,720 (17.2%) of the 10,000 individuals tested, including 968 (20%) of 4,843 women with breast cancer and 281 (34%) of 824 with ovarian cancer, and the prevalence of mutations was correlated with specific features of the personal and family histories of the individuals tested. Mutations were as prevalent in high-risk women of African (25 [19%] of 133) and other non-Ashkenazi ancestries as those of European ancestry (712 [16%] of 4379) and were significantly less prevalent in women diagnosed before 50 years of age with ductal carcinoma in situ than with invasive breast cancer (13% v 24%, P =.0007). Of the 74 mutations identified in individuals of Ashkenazi ancestry through full sequence analysis of both BRCA1 and BRCA2, 16 (21.6%) were nonfounder mutations, including seven in BRCA1 and nine in BRCA2. Twenty-one (28%) of 76 men with breast cancer carried mutations, of which more than one third occurred in BRCA1. CONCLUSION: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCA2 in individuals tested in a clinical setting.