Extracranial medulloepithelioma: a review of the literature.

PURPOSE: Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region of the cerebral hemispheres or the ciliary body of the eye. Even rarer still is the extracranial manifestation of medulloepithelioma with only 12 cases reported to date. Our purpose is to report a case of an intradural, extra-medullary medulloepithelioma and review the limited literature about diagnosis and treatment of this extremely rare pathology. METHODS: PubMed was queried using search terms "peripheral medulloepithelioma" and "pre-sacral medulloepithelioma." Medulloepitheliomas which were intraocular or occurred in reproductive organs were excluded. Patients' age, sex, the symptomatic period prior to diagnosis, primary tumor site, stage, treatment regimen, pathologic description, and survival outcomes were collected. RESULTS: We present a case of extracranial medulloepithelioma in an 8-year-old male. Morphology of the neoplasm was representative of medulloepithelioma but there was no amplification of C19MC. Additionally, the neoplasm stained positive for CD99. Twelve other cases of extracranial medulloepithelioma were found in literature review. CONCLUSIONS: The rarity of extracranial medulloepithelioma makes for a challenging diagnosis. Designing an optimal treatment strategy is difficult because of a scarcity of cases and wide variety in locations and treatments. Our case provides an example of treatment including resection, intense induction chemotherapy, consolidation with high-dose chemotherapy and stem cell rescue, craniospinal proton radiation therapy, and metronomic chemotherapy.

Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a series of three cases.

BACKGROUND: We describe three children with Angelman syndrome and medically refractory epilepsy. METHODS: Case series of three pediatric patients with Angelman syndrome and medically refractory epilepsy. All three patients failed medical treatment and were recommended for vagal nerve stimulator (VNS) implantation. RESULTS: Following VNS implantation, all three patients experienced reduction in seizure frequency greater than that afforded by medication alone. CONCLUSION: We present vagal nerve stimulator implantation as a viable treatment option for medically refractory epilepsy associated with Angelman syndrome.

Head injury in heroes of the Civil War and its lasting influence.

The Civil War era was an age-defining period in the history of the United States of America, the effects of which are still seen in the nation today. In this era, the issue of head injury pervaded society. From the president of the United States, Abraham Lincoln, to the officers and soldiers of the Union and Confederate armies, and to the population at large, head injury and its ramifications gripped the nation. This article focuses on 3 individuals: Major General John Sedgwick, First Lieutenant Alonzo Cushing, and Harriet Tubman, as examples of the impact that head injury had during this era. These 3 individuals were chosen for this article because of their lasting legacies, contributions to society, and interesting connections to one another.

Genetic variants in VEGF pathway genes in neoadjuvant breast cancer patients receiving bevacizumab: Results from the randomized phase III GeparQuinto study.

Studies assessing the effect of bevacizumab (BEV) on breast cancer (BC) outcome have shown different effects on progression-free and overall survival, suggesting that a subgroup of patients may benefit from this treatment. Unfortunately, no biomarkers exist to identify these patients. Here, we investigate whether single nucleotide polymorphisms (SNPs) in VEGF pathway genes correlate with pathological complete response (pCR) in the neoadjuvant GeparQuinto trial. HER2-negative patients were randomized into treatment arms receiving either BEV combined with standard chemotherapy or chemotherapy alone. In a pre-planned biomarker study, DNA was collected from 729 and 724 patients, respectively from both treatment arms, and genotyped for 125 SNPs. Logistic regression assessed interaction between individual SNPs and both treatment arms to predict pCR. Five SNPs may be associated with a better response to BEV, but none of them remained significant after correction for multiple testing. The two SNPs most strongly associated, rs833058 and rs699947, were located upstream of the VEGF-A promoter. Odds ratios for the homozygous common, heterozygous and homozygous rare rs833058 genotypes were 2.36 (95% CI, 1.49-3.75), 1.20 (95% CI, 0.88-1.64) and 0.61 (95% CI, 0.34-1.12). Notably, some SNPs in VEGF-A exhibited a more pronounced effect in the triple-negative subgroup. Several SNPs in VEGF-A may be associated with improved pCR when receiving BEV in the neoadjuvant setting. Although none of the observed effects survived correction for multiple testing, our observations are consistent with previous studies on BEV efficacy in BC. Further research is warranted to clarify the predictive value of these markers.

Famous head injuries of the first aerial war: deaths of the "Knights of the Air".

World War I advanced the development of aviation from the concept of flight to the use of aircraft on the battlefield. Fighter planes advanced technologically as the war progressed. Fighter pilot aces Francesco Baracca and Manfred von Richthofen (the Red Baron) were two of the most famous pilots of this time period. These courageous fighter aces skillfully maneuvered their SPAD and Albatros planes, respectively, while battling enemies and scoring aerial victories that contributed to the course of the war. The media thrilled the public with their depictions of the heroic feats of fighter pilots such as Baracca and the Red Baron. Despite their aerial prowess, both pilots would eventually be shot down in combat. Although the accounts of their deaths are debated, it is undeniable that both were victims of traumatic head injury.

Changes in serum levels of miR-21, miR-210, and miR-373 in HER2-positive breast cancer patients undergoing neoadjuvant therapy: a translational research project within the Geparquinto trial.

Trastuzumab and lapatinib are established treatments for patients with HER2 (human epidermal growth factor receptor 2)-positive breast cancer with different mechanisms of action. The focus of this study is to investigate, whether altered expression levels of potentially relevant microRNAs (miRs) in serum are associated with response to trastuzumab or lapatinib. Circulating miR-21, miR-210, and miR-373 were quantified with TaqMan MicroRNA assays in serum of 127 HER2-postive breast cancer patients before and after neoadjuvant therapy and in 19 healthy controls. Patients received chemotherapy combined with either trastuzumab or lapatinib within the prospectively randomized Geparquinto trial. The association between miR levels and pathological response (pCR) to therapy and type of therapy was examined. Serum levels of miR-21 (p = 5.04e-08, p = 1.43e-10), miR-210 (p = 0.00151, p = 1.6e-05), and miR-373 (p = 7.87e-06, p = 1.75e-07) were significantly higher in patients before and after chemotherapy than in healthy women. Concentrations of miR-21 (p = 5.73e-08), miR-210 (p = 0.000724), and miR-373 (p = 0.00209) increased further after chemotherapy. A significant association of higher serum levels of miR-373 with advanced clinical tumor stage could be detected (p < 0.002). An association of miR-21 levels before (p = 0.0091) and after (p = 0.037) chemotherapy with overall survival of the patients could be detected, independent of type of anti-HER2 therapy. No association of circulating miRs with pCR was found. Our findings demonstrate a specific influence of neoadjuvant therapy on the serum levels of miR-21, miR-210, and miR-373 in breast cancer patients together with a prognostic value of miR-21.

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma.

Invasive lobular carcinomas (ILC) show better clinical behaviour compared with other histological types, but significantly lower pathological complete response (pCR) rates after neoadjuvant chemotherapy (NACT). We investigated whether factors influencing pCR rate in ILC after NACT can be identified and whether clinical outcome is different. 9,020 breast cancer patients from nine German neoadjuvant trials with known histological type were pooled. 11.7 % of tumours were ILC. Endpoints were: pCR rate, surgery type and survival. ILC was associated with older age, larger tumour size, lymph node negativity, lower grade and positive hormone-receptor-status (HR). Patients with ILC achieved a significantly lower pCR rate compared with non-ILC patients (6.2 vs. 17.4 %, P < 0.001). The pCR rate was 4.2 % in ILC/HR+/G1-2, 7.0 % in ILC with either HR- or G3, and 17.8 % in ILC/HR-/G3. Mastectomy rate was higher in ILC compared with non-ILC patients irrespective of response to NACT (pCR: 27.4 vs. 16.6 %, P = 0.037 and non-pCR: 41.8 % vs. 31.5 %, P < 0.0001). Age and HR independently predicted pCR in ILC. In ILC patients, pCR did not predict distant disease free (DDFS) and loco-regional disease free survival (LRFS), but overall survival (OS). Non-pCR patients with ILC had significantly better DDFS (P = 0.018), LRFS (P < 0.0001) and OS (P = 0.044) compared with non-ILC patients. Patients with ILC had a low chance of obtaining a pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours.

Recommendations on screening mammography in patients with ventriculoperitoneal shunts and deep brain stimulation.

Insertion of ventriculoperitoneal (VP) shunt and deep brain stimulation (DBS) are common neurosurgical procedures. Concerns have been raised regarding the safety of mammography in this patient cohort due to the risk of damaging the VP shunt tubing or DBS implantable pulse generator, and the degradation in mammography image quality secondary to the implanted devices. Based on a review of the current literature, the authors propose that mammography is safe in patients with VP shunts and DBS, and should be performed routinely as a part of population screening.

How enhancers regulate wavelike gene expression patterns.

A key problem in development is to understand how genes turn on or off at the right place and right time during embryogenesis. Such decisions are made by non-coding sequences called 'enhancers.' Much of our models of how enhancers work rely on the assumption that genes are activated de novo as stable domains across embryonic tissues. Such a view has been strengthened by the intensive landmark studies of the early patterning of the anterior-posterior (AP) axis of the Drosophila embryo, where indeed gene expression domains seem to arise more or less stably. However, careful analysis of gene expression patterns in other model systems (including the AP patterning in vertebrates and short-germ insects like the beetle Tribolium castaneum) painted a different, very dynamic view of gene regulation, where genes are oftentimes expressed in a wavelike fashion. How such gene expression waves are mediated at the enhancer level is so far unclear. Here, we establish the AP patterning of the short-germ beetle Tribolium as a model system to study dynamic and temporal pattern formation at the enhancer level. To that end, we established an enhancer prediction system in Tribolium based on time- and tissue-specific ATAC-seq and an enhancer live reporter system based on MS2 tagging. Using this experimental framework, we discovered several Tribolium enhancers, and assessed the spatiotemporal activities of some of them in live embryos. We found our data consistent with a model in which the timing of gene expression during embryonic pattern formation is mediated by a balancing act between enhancers that induce rapid changes in gene expression patterns (that we call 'dynamic enhancers') and enhancers that stabilize gene expression patterns (that we call 'static enhancers'). However, more data is needed for a strong support for this or any other alternative models.

Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group.

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.

Effects of Neuroanatomic Structural Distances on Pituitary Function After Stereotactic Radiosurgery: A Multicenter Study.

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

Sellar Atypical Teratoid/Rhabdoid Tumors (AT/RT): A Systematic Review and Case Illustration.

INTRODUCTION: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with a median survival of 20 months. We report a case of a sellar atypical teratoid/rhabdoid tumor in a 70-year-old female treated with intraventricular chemotherapy, followed by a systematic review of the current management of sellar AT/RTs. METHODS: A comprehensive systematic literature search was conducted on Web of Science, Scopus, and PubMed Central using the key terms "sellar" and "atypical teratoid/rhabdoid tumors", following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including patient demographics, histology, treatments, and overall survival were extracted and analyzed. Kaplan-Meier survival curves and log-rank analysis were used to compare survival outcomes between different treatment regimens. RESULTS: Our literature search disclosed 123 publications. After prespecified exclusions, 41 patients with sellar AT/RT from 30 manuscripts were identified, and 38 were included in the final analysis. Including our patient, the median age was 44 (range: 20-70) with a substantial female predominance (94.7%). Collectively, patients who received combined chemoradiation therapy had a significantly increased overall survival compared to those who received single modality or no adjuvant therapies (median OS 27 vs. 1.25 months; p=0.0052). CONCLUSION: Atypical teratoid/rhabdoid tumor in the sellar region carries a poor prognosis. Adjuvant chemotherapy and radiation therapy were associated with significantly increased overall survival. Early consideration of neuro-oncology and radiation-oncology referral and management is likely beneficial in this patient population. Intrathecal chemotherapy is a treatment modality that requires further exploration given the limited options and current dismal prognosis of adult sellar AT/RT.

Myxopapillary Ependymoma with Anaplastic Features: A Case Series and Review of the Literature.

BACKGROUND: Myxopapillary ependymomas (MPEs) with anaplastic features are rarely reported, with only 21 cases identified to date, and long-term recurrence is rarely presented. A case series is presented to expand understanding of this disease by describing 3 unique cases, including 2 that arose from MPE after a prolonged clinical course. METHODS: A literature review was performed, and 3 cases of MPE with anaplastic features from our institution were included. RESULTS: Patient 1 was a 13-year-old boy who presented with an avidly enhancing intradural lumbar mass. On gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and MIB-1 (Ki-67) index of 12%. Patient 2 was a woman who initially presented at age 22 with a lumbosacral tumor that was treated with surgery and radiation. A recurrent tumor was resected at age 24. At age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending into the presacral space and Ki-67 index of 8%. This was treated with complete resection. Patient 3 was a man who initially presented at age 35 with a lower thoracic, upper lumbar mass at L2 extending into the sacrum. Following resection and radiation, a metastatic focus followed an indolent course until causing pain at the age of 48. Ki-67 index was 16%. CONCLUSIONS: The presented cases of MPE with anaplastic features make a total of 24 cases on record in the medical literature and demonstrate 2 examples of late recurrence.

Brain Cancer Progression: A Retrospective Multicenter Comparison of Awake Craniotomy Versus General Anesthesia in High-grade Glioma Resection.

BACKGROUND: High-grade gliomas impose substantial morbidity and mortality due to rapid cancer progression and recurrence. Factors such as surgery, chemotherapy and radiotherapy remain the cornerstones for treatment of brain cancer and brain cancer research. The role of anesthetics on glioma progression is largely unknown. METHODS: This multicenter retrospective cohort study compared patients who underwent high-grade glioma resection with minimal sedation (awake craniotomy) and those who underwent craniotomy with general anesthesia (GA). Various perioperative factors, intraoperative and postoperative complications, and adjuvant treatment regimens were recorded. The primary outcome was progression-free survival (PFS); secondary outcomes were overall survival (OS), postoperative pain score, and length of hospital stay. RESULTS: A total of 891 patients were included; 79% received GA, and 21% underwent awake craniotomy. There was no difference in median PFS between awake craniotomy (0.54, 95% confidence interval [CI]: 0.45-0.65 y) and GA (0.53, 95% CI: 0.48-0.60 y) groups (hazard ratio 1.05; P <0.553). Median OS was significantly longer in the awake craniotomy (1.70, 95% CI: 1.30-2.32 y) compared with that in the GA (1.25, 95% CI: 1.15-1.37 y) group (hazard ratio 0.76; P <0.009) but this effect did not persist after controlling for other variables of interest. Median length of hospital stay was significantly shorter in the awake craniotomy group (2 [range: 0 to 76], interquartile range 3 d vs. 5 [0 to 98], interquartile range 5 for awake craniotomy and GA groups, respectively; P <0.001). Pain scores were comparable between groups. CONCLUSIONS: There was no difference in PFS and OS between patients who underwent surgical resection of high-grade glioma with minimal sedation (awake craniotomy) or GA. Further large prospective randomized controlled studies are needed to explore the role of anesthetics on glioma progression and patient survival.

Dose to neuroanatomical structures surrounding pituitary adenomas and the effect of stereotactic radiosurgery on neuroendocrine function: an international multicenter study.

OBJECTIVE: Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS: This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact of doses to critical structures on clinical, radiographic, and endocrine outcomes. RESULTS: The study cohort comprised 521 pituitary adenomas treated with SRS. Tumor control was achieved in 93.9% of patients over a median follow-up period of 60.1 months, and 22.5% of patients developed new loss of pituitary function with a median treatment volume of 3.2 cm3. Median maximal radiosurgical doses to the hypothalamus, pituitary stalk, and normal pituitary gland were 1.4, 7.2, and 11.3 Gy, respectively. Nonfunctioning adenoma status, younger age, higher margin dose, and higher doses to the pituitary stalk and normal pituitary gland were independent predictors of new or worsening hypopituitarism. Neither the dose to the hypothalamus nor the ratio between doses to the pituitary stalk and gland were significant predictors. The threshold of the median dose to the pituitary stalk for new endocrinopathy was 10.7 Gy in a single fraction (OR 1.77, 95% CI 1.17-2.68, p = 0.006). CONCLUSIONS: SRS for the treatment of pituitary adenomas affords a high tumor control rate with an acceptable risk of new or worsening endocrinopathy. This evaluation of point dosimetry to adjacent neuroanatomical structures revealed that doses to the pituitary stalk, with a threshold of 10.7 Gy, and doses to the normal gland significantly increased the risk of post-SRS hypopituitarism. In patients with preserved pre-SRS neuroendocrine function, limiting the dose to the pituitary stalk and gland while still delivering an optimal dose to the tumor appears prudent.

Pituitary Metastasis From Urothelial Carcinoma: A Case Report and Review of the Diagnosis and Treatment of Pituitary Metastases.

The sellar and parasellar regions are a rare site of brain metastasis, most commonly from breast and lung cancer. Pituitary metastasis (PM) often presents as the first sign of metastatic disease but may herald early disseminated cancer. The diagnosis of PM requires differentiation from a benign pituitary adenoma. Although this may be proven definitively via surgical biopsy, a constellation of clinical findings including oculomotor palsy, visual disturbances, retroorbital pain, and diabetes insipidus is more suggestive of PM. Imaging is neither sensitive nor specific for differentiation but may inform the broader clinical picture. Due to its rarity, treatment guidelines for PM lack consensus, often including a mixture of radiation and surgery. Gross resection is challenging because of the vascular, invasive nature of these lesions. Stereotactic radiosurgery may be used to good effect either alone or in addition to resection. Even with treatment, the prognosis is poor. In this article, we present the third reported case of urothelial carcinoma metastasis to the pituitary. In addition, we review the clinical presentation, diagnosis, and treatment options including surgical resection and radiosurgery.

Arachnoiditis Ossificans in the Thoracic Spine With Associated Cyst and Syringomyelia: A Rare, Intraoperative Finding Complicating Dural Opening.

Arachnoiditis ossificans (AO) is a rare spinal pathology that develops because of bony metaplasia secondary to chronic inflammation. AO may present with debilitating myelopathy secondary to nerve root compression, making it distinct from spinal calcification commonly seen with aging. AO is extremely rare, having been reported less than 100 times, most commonly in the thoracic spine. Even rarer still, AO has been associated with syringomyelia and arachnoid cyst because of associated cerebrospinal fluid (CSF) flow disruption. In this report, we describe a case of AO that presented with right shoulder pain, right-hand numbness, and bilateral lower extremity fatigue who had syringomyelia and arachnoid cyst discovered on MRI imaging. When brought to the operating room for syrinx shunting and cyst fenestration the dural opening was complicated by severe calcification and a diagnosis of AO was made. The patient was treated with partial resection of the calcified plaques. Syringomyelia shunting was abandoned due to low volume. Post-operatively, the patient had improvement in their myelopathy though syrinx was still visualized on follow-up imaging. This report reviews the pathology, clinical and radiographic diagnosis, and treatment strategies for arachnoiditis ossificans.

The Life and Death of Lord Nelson: The Leader, the Patient, the Legend.

Admiral Lord Horatio Nelson is perhaps the most renowned naval commander, who allowed Britain to have dominion over the sea for 100 years after his victory at the Battle of Trafalgar. He was able to do so despite suffering from a multitude of communicable diseases and traumatic injuries, including the functional loss of his right eye, amputation of his right arm, scalp laceration, head injury, and finally a spinal injury. These injuries had permanent consequences but did not stop him from leading the charge and allowing the British to defeat the French and Spanish fleets in the decisive Battle of Trafalgar.

Malignant spindle cell tumors of the posterior fossa in children: case series and review of management.

OBJECTIVE: The WHO Classification of Tumours of the Central Nervous System (2016) classifies nonmeningothelial malignant spindle cell tumors involving the extraaxial tissues of the posterior fossa as melanocytic tumors and malignant mesenchymal tumors (sarcomas). The objective of this study was to conduct a review of the literature pertaining to the management strategies of posterior fossa malignant spindle cell tumors in the pediatric population. METHODS: The authors performed an institutional search of their pathology database for patients younger than 18 years of age who presented with posterior fossa malignant spindle cell tumors. A literature review was also performed using the PubMed database, with "posterior fossa" or "spindle cell tumors" or "Ewing sarcoma" or "high-grade" or "spindle cell sarcoma" or "leptomeningeal melanocytoma" as keywords. The database search was restricted to pediatric patients (age ≤ 18 years). Parameters reported from the literature review included patient age, tumor location, presenting symptoms, treatment modalities (resection, chemotherapy, and/or radiotherapy), leptomeningeal spread at or after the time of treatment, and follow-up length and resulting outcome. RESULTS: The authors report 3 rare cases of posterior fossa malignant spindle cell tumors, including Ewing sarcoma in a 13-year-old male; high-grade spindle cell sarcoma, not otherwise specified in a 10-year-old male; and primary leptomeningeal melanocytoma in a 16-year-old female. All 3 patients underwent resection and radiotherapy and either chemotherapy or targeted immunotherapy. At the last follow-up, all patients were alive with either resolution or stable disease. CONCLUSIONS: A review of these 3 cases and the existing literature support managing patients with intracranial malignant spindle cell tumors with multimodal therapy that can include a combination of resection, radiotherapy, and chemotherapy or immunotherapy to prolong progression-free and overall survival.

Human Acellular Dermal Matrix (Epiflex®) in Immediate Implant-Based Breast Reconstruction after Skin- and Nipple-Sparing Mastectomy and Treatment of Capsular Fibrosis: Results of a Multicenter, Prospective, Observational NOGGO-AWOGyn Study.

BACKGROUND: Over the last decades, the number of acellular dermal matrix (ADM)-assisted implant-based breast reconstructions (IBBR) has substantially increased. However, there is still a lack of prospective data on complication rates. METHODS: We performed a non-interventional, multicenter, prospective cohort study to evaluate complication rates of a human ADM in patients undergoing an IBBR after skin- and nipple-sparing mastectomies. Patients with primary reconstruction (cohort A) and patients undergoing a secondary reconstruction after capsular fibrosis (cohort B) using the human ADM Epiflex® (DIZG gGmbH, Berlin, Germany) were enrolled in this study. Patients were followed-up for 12 months after surgery. RESULTS: Eighty-four eligible patients were included in this study of whom 28 women underwent a bilateral breast reconstruction, leading to 112 human ADM-assisted reconstructions in total (cohort A: 73, cohort B: 39). In 33.0% of the reconstructed breasts at least one of the complications of primary interest occurred, including implant loss 7.1%, seroma 15.2%; infection 5.4%, rash 8.0%, and Baker grade III/IV capsular fibrosis 2.7%, with no statistically significant differences between the cohorts. Previous radiation therapy was significantly associated with occurrence of any postoperative complication (OR 20.41; p value 0.027). CONCLUSION: The rates of most complications were comparable to the rates reported for other ADMs with relatively low rates of capsular fibrosis and infections. The rate of seroma was increased in our study. Prior radiation therapy increased the risk of any postoperative complications. Therefore, the use of ADM in these patients should be considered carefully.