Early imaging marker of progressing glioblastoma: a window of opportunity.

PURPOSE: Therapeutic intervention at glioblastoma (GBM) progression, as defined by current assessment criteria, is arguably too late as second-line therapies fail to extend survival. Still, most GBM trials target recurrent disease. We propose integration of a novel imaging biomarker to more confidently and promptly define progression and propose a critical timepoint for earlier intervention to extend therapeutic exposure. METHODS: A retrospective review of 609 GBM patients between 2006 and 2019 yielded 135 meeting resection, clinical, and imaging inclusion criteria. We qualitatively and quantitatively analyzed 2000+ sequential brain MRIs (initial diagnosis to first progression) for development of T2 FLAIR signal intensity (SI) within the resection cavity (RC) compared to the ventricles (V) for quantitative inter-image normalization. PFS and OS were evaluated using Kaplan-Meier curves stratified by SI. Specificity and sensitivity were determined using a 2 × 2 table and pathology confirmation at progression. Multivariate analysis evaluated SI effect on the hazard rate for death after adjusting for established prognostic covariates. Recursive partitioning determined successive quantifiers and cutoffs associated with outcomes. Neurological deficits correlated with SI. RESULTS: Seventy-five percent of patients developed SI on average 3.4 months before RANO-assessed progression with 84% sensitivity. SI-positivity portended neurological decline and significantly poorer outcomes for PFS (median, 10 vs. 15 months) and OS (median, 20 vs. 29 months) compared to SI-negative. RC/V ratio ≥ 4 was the most significant prognostic indicator of death. CONCLUSION: Implications of these data are far-reaching, potentially shifting paradigms for glioma treatment response assessment, altering timepoints for salvage therapeutic intervention, and reshaping glioma clinical trial design.

Pediatric Primary Diffuse Leptomeningeal Primitive Neuroectodermal Tumor: A Case Report and Literature Review.

BACKGROUND: Primary diffuse leptomeningeal primitive neuroectodermal tumor (PDL PNET) is extremely rare, with only 19 cases reported in the literature to date. We present a case of a child with rapidly progressive PDL PNET and a literature review. A 10-year-old boy presented with mood lability, hallucinations, generalized pain, enuresis, and headaches. Initial investigation failed to produce a diagnosis. The symptoms progressed to seizure, back pain, and papilledema. Imaging showed acute hydrocephalus and mild diffuse leptomeningeal enhancement without an identifiable primary lesion. METHODS: The hydrocephalus was managed with a ventriculostomy - later replaced by a ventriculoperitoneal shunt after ruling out infection. A dura mater biopsy obtained prior to shunt insertion was unrevealing. Repeat MRI at the 2-month follow-up showed severe interval progression of the leptomeningeal enhancement with thick lumbar spinal subdural enhancing areas. A biopsy from the inflamed arachnoid at the L3-L4 level unveiled a leptomeningeal PNET diagnosis. RESULTS: Despite adjuvant therapy with chemoradiation, the disease progressed, and the patient died 22 months after the initial presentation. Nineteen other cases of PDL PNET have been reported in the literature and were analyzed. CONCLUSION: Primary leptomeningeal PNET is an extremely rare disease. Optimal treatment is not well established, and the prognosis is very poor.

A mathematical evaluation of hemodynamic parameters after carotid eversion and conventional patch angioplasty.

Carotid endarterectomy has a long history in stroke prevention, yet controversy remains concerning optimal techniques. Two methods frequently used are endarterectomy with patch angioplasty (CEAP) and eversion endarterectomy (CEE). The objective of this study was to compare hemodynamics-related stress and strain distributions between arteries repaired using CEAP and CEE. Mathematical models were based on in vivo three-dimensional arterial geometry, pulsatile velocity profiles, and intraluminal pressure inputs obtained from 16 patients with carotid artery disease. These data were combined with experimentally derived nonlinear, anisotropic carotid artery mechanical properties to create fluid-structure interaction models of CEAP and CEE. These models were then used to calculate hemodynamic parameters thought to promote recurrent disease and restenosis. Combining calculations of stress and strain into a composite risk index, called the integral abnormality factor, allowed for an overall comparison between CEAP and CEE. CEE demonstrated lower mechanical stresses in the arterial wall, whereas CEAP straightened the artery and caused high stress and strain concentrations at the suture-artery interface. CEAP produced a larger continuous region of oscillatory, low-shear, vortical flow in the carotid bulb. There was a more than two-fold difference in the integral abnormality factor, favoring CEE. In conclusion, in a realistically simulated carotid artery, fluid-structure interaction modeling demonstrated CEE to produce less mechanical wall stress and improved flow patterns compared with CEAP. Clinical validation with larger numbers of individual patients will ultimately be required to support modeling approaches to help predict arterial disease progression and comparative effectiveness of reconstruction methods and devices.

Nonlinear mechanical behavior of the human common, external, and internal carotid arteries in vivo.

BACKGROUND: The mechanical environment and properties of the carotid artery play an important role in the formation and progression of atherosclerosis in the carotid bifurcation. The purpose of this work was to measure and compare the range and variation of circumferential stress and tangent elastic moduli in the human common (CCA), external (ECA), and internal (ICA) carotid arteries over the cardiac cycle in vivo. METHODS: Measurements were performed in the surgically exposed proximal cervical CCA, distal ECA, and distal ICA of normotensive patients (n = 16) undergoing carotid endarterectomy. All measurements were completed in vivo over the cardiac cycle in the repaired carotid bifurcation after the atherosclerotic plaque was successfully removed. B-mode Duplex ultrasonography was used for measurement of arterial diameter and wall thickness, and an angiocatheter placed in the CCA was used for concurrent measurement of blood pressure. A semiautomatic segmentation algorithm was used to track changes in arterial diameter and wall thickness in response to blood pressure. These measurements were then used to calculate the variation of circumferential (hoop) stresses, tangent elastic moduli (the slope of the stress-strain curve at specified stresses), and strain-induced stiffness of the arterial wall (stiffening in response to the increase of intraluminal blood pressure) for each patient. RESULTS: The diameter and wall thickness of the segments (CCA, ECA, and ICA) of the carotid bifurcation were found to decrease and strain-induced stiffness to increase from proximal CCA to distal ECA and ICA. The circumferential stress from end-diastole (minimum pressure) to peak-systole (maximum pressure) varied nonlinearly from 25 ± 7 to 63 ± 23 kPa (CCA), from 22 ± 7 to 57 ± 19 kPa (ECA), and from 28 ± 8 to 67 ± 23 kPa (ICA). Tangent elastic moduli also varied nonlinearly from end-diastole to peak-systole as follows: from 0.40 ± 0.25 to 1.50 ± 2.05 MPa (CCA), from 0.49 ± 0.34 to 1.14 ± 0.52 MPa (ECA), and from 0.68 ± 0.31 to 1.51 ± 0.69 MPa (ICA). The strain-induced stiffness of CCA and ECA increased more than 3-fold and the stiffness of ICA increased more than 2.5-fold at peak-systole compared with end-diastole. CONCLUSIONS: The in vivo mechanical behavior of the three segments of the carotid bifurcation was qualitatively similar, but quantitatively different. All three arteries--CCA, ECA and ICA--exhibited nonlinear variations of circumferential stress and tangent elastic moduli within the normal pressure range. The variability in the properties of the three segments of the carotid bifurcation indicates a need for development of carotid models that match the in vivo properties of the carotid segments. Finally, the observed nonlinear behavior of the artery points to the need for future vascular mechanical studies to evaluate the mechanical factors of the arterial wall over the entire cardiac cycle.

Müllerian Cysts of the Posterior Mediastinum: A Case Report and Review of the Literature.

Cysts can be segregated according to their embryonic backgrounds. The cysts that were found in the mediastinum are usually divided into bronchogenic cysts, enteric cysts, esophageal cysts, and nonspecific cysts. We add to the relatively small body of literature that exists on this topic by reporting a case of a Müllerian cyst occurring in the posterior mediastinum of a 60-year-old female, showing diffuse nuclear positivity for estrogen receptor (ER) and PAX-8. We examined and summarized the findings of the unique reported cases in the literature. Lastly, an institutional retrospective review of all posterior mediastinal lesions in the last 38.5 years was performed. This revealed that out of 135 candidates within our own healthcare system, the only case consistent with the diagnosis of a mediastinal Müllerian cyst is the report included herein.

Comparative analysis of the biaxial mechanical behavior of carotid wall tissue and biological and synthetic materials used for carotid patch angioplasty.

Patch angioplasty is the most common technique used for the performance of carotid endarterectomy. A large number of patching materials are available for use while new materials are being continuously developed. Surprisingly little is known about the mechanical properties of these materials and how these properties compare with those of the carotid artery wall. Mismatch of the mechanical properties can produce mechanical and hemodynamic effects that may compromise the long-term patency of the endarterectomized arterial segment. The aim of this paper was to systematically evaluate and compare the biaxial mechanical behavior of the most commonly used patching materials. We compared PTFE (n = 1), Dacron (n = 2), bovine pericardium (n = 10), autogenous greater saphenous vein (n = 10), and autogenous external jugular vein (n = 9) with the wall of the common carotid artery (n = 18). All patching materials were found to be significantly stiffer than the carotid wall in both the longitudinal and circumferential directions. Synthetic patches demonstrated the most mismatch in stiffness values and vein patches the least mismatch in stiffness values compared to those of the native carotid artery. All biological materials, including the carotid artery, demonstrated substantial nonlinearity, anisotropy, and variability; however, the behavior of biological and biologically-derived patches was both qualitatively and quantitatively different from the behavior of the carotid wall. The majority of carotid arteries tested were stiffer in the circumferential direction, while the opposite anisotropy was observed for all types of vein patches and bovine pericardium. The rates of increase in the nonlinear stiffness over the physiological stress range were also different for the carotid and patching materials. Several carotid wall samples exhibited reverse anisotropy compared to the average behavior of the carotid tissue. A similar characteristic was observed for two of 19 vein patches. The obtained results quantify, for the first time, significant mechanical dissimilarity of the currently available patching materials and the carotid artery. The results can be used as guidance for designing more efficient patches with mechanical properties resembling those of the carotid wall. The presented systematic comparative mechanical analysis of the existing patching materials provides valuable information for patch selection in the daily practice of carotid surgery and can be used in future clinical studies comparing the efficacy of different patches in the performance of carotid endarterectomy.

Teratoma with malignant transformation: a case report with pathological, cytogenetic, and immunohistochemistry analysis.

Background. Teratoma with malignant transformation (TMT) is rare and most commonly encountered in adult patient with germ cell tumor (GCT). Method. We report a rare case of testicular teratoma with metastatic TMT/embryonal rhabdomyosarcoma (ERMS). A 44-year-old man underwent right orchiectomy which revealed a malignant teratoma, he subsequently had right pneumonectomy with two pulmonary masses containing a high-grade embryonal rhabdomyosarcoma. The patient developed liver metastasis three months after initial diagnosis. He was treated with a chemotherapy regimen with vincristine, dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (VI) with complete resolution of his liver lesion. The tumors were examined with a battery of cytogenetic, immunohistochemical, and molecular assays. Results. The malignant cells were immunohistochemically positive for desmin, myogenin, and MyoD1. Molecular cytogenetics of embryonal rhabdomyosarcoma tissue revealed the presence of i(12p). The tumor expressed high level of TOPO2A, TOPO1, MRP1, MGMT, BCRP, ERCC1, RRM1, and TS. Conclusion. The activity of topoisomerase inhibitors and the potential usefulness of topoisomerase expression as biomarkers should be further tested in aprospective study.

A solitary extraventricular subependymal giant cell astrocytoma in the absence of tuberous sclerosis.

Subependymal giant cell astrocytomas (SEGAs) are the most common intracranial tumors in Tuberous Sclerosis Complex (TSC). Very few cases of solitary SEGA without a diagnosis of TSC have been described. Most of these previously reported solitary SEGAs were located near the caudothalamic groove or in close proximity to the lateral ventricles. Here, we describe a unique case of solitary extraventricular SEGA in a 17-year-old boy who presented with new-onset seizures in the absence of the clinical and genetic diagnosis of TSC. This extraventricular SEGA was involving white matter and cortex of the occipital lobe and was predominantly hypointense on T1 and T2-weighted images with a markedly hypointense signal on susceptibility-weighted images likely secondary to dense internal calcifications. Solitary SEGA can occur in the extraventricular location in patients without TSC and should be included in the differential diagnosis of a densely calcified supratentorial intra-axial tumor in children, especially during the second decade of life.

Evaluating survival in subjects with astrocytic brain tumors by dynamic susceptibility-weighted perfusion MR imaging.

PURPOSE: Studies have evaluated the application of perfusion MR for predicting survival in patients with astrocytic brain tumors, but few of them statistically adjust their results to reflect the impact of the variability of treatment administered in the patients. Our aim was to analyze the association between the perfusion values and overall survival time, with adjustment for various clinical factors, including initial treatments and follow-up treatments. MATERIALS AND METHODS: This study consisted of 51 patients with astrocytic brain tumors who underwent perfusion-weighted MRI with MultiHance® at a dose of 0.1 mmol/kg prior to initial surgery. We measured the mean rCBV, the 5% & 10% maximum rCBV, and the variation of rCBV in the tumors. Comparisons were made between patients with and without 2-year survival using two-sample t-test or Wilcoxon rank-sum test for the continuous data, or chi-square and Fisher exact tests for categorical data. The multivariate cox-proportional hazard regression was fit to evaluate the association between rCBV and overall survival time, with adjustment for clinical factors. RESULTS: Patients who survived less than 2 years after diagnosis had a higher mean and maximum rCBV and a larger variation of rCBV. After adjusting for clinical factors including therapeutic measures, we found no significant association of overall survival time within 2 years with any of these rCBV values. CONCLUSIONS: Although patients who survived less than 2 years had a higher mean and maximum rCBV and a larger variation of rCBV, rCBV itself may not be used independently for predicting 2-year survival of patients with astrocytic brain tumors.

Neuroinvasion of SARS-CoV-2 in human and mouse brain.

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Stage-specific Conditional Survival Among Young (Age Below 50 y) Versus Older (Age 50 y and Above) Adults With Colorectal Cancer in the United States.

BACKGROUND: Conditional survival (CS) is a relevant prognostic measure and may be particularly important for young adult patients with colorectal cancer (CRC), whose incidence is rising. We sought to compare CS among young versus older adults with CRC. METHODS: Patients diagnosed with CRC between 2004 and 2010 were identified from the Surveillance, Epidemiology, and End Results registry. Smoothed yearly hazards of death due to CRC, other causes and any cause were estimated, stratified by age at diagnosis (below 50 vs. 50 y and above) and stage (I-III vs. IV). Stage-specific conditional 5-year overall survival and cancer-specific survival given that patients had already survived 1 to 5 years after diagnosis was calculated. RESULTS: Among 161,859 patients with median follow-up of 54 months, 35,411 (21.9%) were aged below 50 years. For older adults with nonmetastatic CRC, hazards of death due to noncancer causes exceeded that of rectal and colon cancer ∼6.1 and 3.8 years after diagnosis, respectively. Patients experienced improved CS over time with greater improvement seen for more advanced stages. However, young adults had less CS improvement over time than older adults. For example, the 5-year cancer-specific survival for stage IV colon cancer improved from 15.6% to 77.2% (change=61.6%) 0 to 5 years after diagnosis for older adults but only 20.3% to 67.7% (change=47.4%) for young adults. CONCLUSIONS: Prognosis for CRC improves over time for all patients, although the increase in survival appears to be less for young than older adults. Up to 10 years after diagnosis, the primary cause of death in young adults with CRC remains their incident cancer.

Recent Trends and Overall Survival of Young Versus Older Adults With Stage II to III Rectal Cancer Treated With and Without Surgery in the United States, 2010-2015.

BACKGROUND: The omission of surgery via nonoperative management (NOM) for rectal cancer may be increasing, and this strategy could be particularly attractive for younger patients, whose incidence of rectal cancer has been rising. We sought to assess trends in NOM in young (younger than 55 y) versus older adult (55 y and older) rectal cancer cohorts. METHODS: The National Cancer Database was used to identify patients diagnosed with stage II to III rectal cancer between 2010 and 2015. Multivariable logistic regression defined the association between sociodemographic variables and odds of NOM, including an age (18 to 54 vs. 55+ y)×surgery (surgery vs. NOM) interaction term. Adjusted Cox regression models compared overall survival between NOM versus surgery. RESULTS: Among 22,561 patients with a median follow-up of 37.5 months, the utilization rate of NOM increased from 10.7% (2010) to 15.2% (2015). Older patients were more likely to receive NOM, although rates also increased among young (7.1% to 10.6%). Black patients were also more likely to receive NOM (P<0.001). Among the entire cohort, NOM was associated with worse overall survival (adjusted hazard ratio [AHR]=2.90, 95% confidence interval [CI]: 2.67-3.15) and there was a statistically significant age×NOM interaction (P=0.01) such that the effect of NOM on survival was worse for younger (AHR=3.37, 95% CI: 2.82-4.02) as compared with older patients (AHR=2.49, 95% CI: 2.27-2.74). CONCLUSIONS: The increasing trend for NOM in stage II to III rectal cancer may be driven by disparities in treatment. Management with NOM appears to be associated with poorer survival, particularly in younger patients and could worsen outcomes for groups already at risk for suboptimal cancer care.

Trends in Primary Surgical Resection and Chemotherapy for Metastatic Colorectal Cancer, 2000-2016.

BACKGROUND: When, whether, and in whom primary tumor resection (PTR) for patients with metastatic colorectal cancer (CRC) is indicated remains unknown. With advances in multiagent systemic chemotherapy, PTR may be undertaken less frequently. The aim of this study was to obtain estimates of changes in the utilization of PTR and chemotherapy for metastatic CRC. METHODS: Patients diagnosed with metastatic CRC between 2000 and 2016 were identified from Surveillance Epidemiology, and End Results (SEER) registry. Multivariable logistic regression defined odds of undergoing PTR. The analysis was also stratified by primary site (colon vs. rectum), age (younger than 50 vs. 50 y and older), and whether patients also underwent resection of metastatic sites (yes vs. no). The secondary endpoint of interest was the receipt of any chemotherapy, also assessed by multivariable logistic regression. RESULTS: Among 99,835 patients with metastatic CRC, 55,527 (55.7%) underwent PTR. The odds of undergoing PTR decreased with a later year of diagnosis, with patients diagnosed in 2016 being 61.1% less likely to undergo surgery than those diagnosed in 2000 (adjusted odds ratio=0.39, 95% confidence interval: 0.36-0.42, P<0.0001; absolute percentage: 62.3% to 43.8%). Similar trends by year for PTR were observed among each of the subgroups, although patients with colon primary, young adults (age younger than 50 y), and patients also undergoing metastasectomy were more likely to undergo PTR (P<0.001 for all). In contrast, the odds of receiving chemotherapy increased dramatically with a later year of diagnosis (adjusted odds ratio=2.21, 95% confidence interval: 2.04-2.40, P<0.0001). CONCLUSIONS: From 2000 to 2016, there was a sharp decline in the rate of PTR for patients with metastatic CRC, while the use of chemotherapy increased over the same period. Prospective studies are needed to define the optimal local treatment for patients with metastatic CRC.

Feasibility and Outcome of Routine Use of Concurrent Chemoradiation in HIV-positive Patients With Squamous Cell Anal Cancer.

OBJECTIVES: Clinical concerns about hematologic toxicities in human immunodeficiency virus (HIV)+ patients with squamous cell anal cancer (SCAC) may lead to de-escalation of treatment intensity. The objective of this study is to evaluate clinical outcomes including toxicity following standard concurrent curative-intent chemoradiation for HIV+ and HIV- patients with SCAC. MATERIALS AND METHODS: Among 97 evaluable patients treated between 2009 and 2016 (median age 52.2 y), 43 (44.3%) were HIV+ and 54 (55.7%) HIV-. The majority of the radiation was delivered using intensity-modulated radiation therapy and chemotherapy consisting primarily (93%) of 5-fluorouracil and mitomycin C. Clinical outcomes assessed included toxicity, locoregional control (LRC), distant metastasis (DM), progression-free survival (PFS), colostomy-free survival (CFS), overall survival (OS), and cause-specific survival (CSS). RESULTS: With a median follow-up of 45 months, HIV+ patients exhibited a trend toward reduced OS compared with HIV- patients (4 y OS 61.2% vs. 78.3%; HR 2.09; 95% CI, 0.97-4.52; P=0.055) on univariable analysis, but HIV status was not significant after adjusting for additional parameters on multivariable analysis. Toxicity rates, LRC, CFS, PFS, freedom from DM, and CSS were similar between the 2 cohorts. On multivariable analysis, tumor size >5 cm impacted all clinical outcomes (trend for LRC) except CFS. Radiation treatment extension beyond 7 days was found to negatively impact LRC and CSS. Male sex was associated with worse CFS. CONCLUSIONS: Radiation therapy with concurrent 5-fluorouracil and mitomycin C chemotherapy is reasonably well-tolerated as curative treatment for HIV+ patients with SCAC, and no significant difference in outcomes was noted relative to HIV- patients.

Neuroinvasion of SARS-CoV-2 in human and mouse brain.

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus whether the virus can infect the brain, or what the consequences of CNS infection are. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in the infected and neighboring neurons. However, no evidence for the type I interferon responses was detected. We demonstrate that neuronal infection can be prevented either by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate in vivo that SARS-CoV-2 neuroinvasion, but not respiratory infection, is associated with mortality. Finally, in brain autopsy from patients who died of COVID-19, we detect SARS-CoV-2 in the cortical neurons, and note pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV2, and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Post-operative perfusion and diffusion MR imaging and tumor progression in high-grade gliomas.

PURPOSE: Perfusion and diffusion magnetic resonance imaging (MRI) provide important biomarkers for brain tumor analysis. Our aim was to investigate if regions of increased perfusion or tumor with restricted diffusion on the immediate post-operative MRI examination would be predictive of time to tumor progression in patients with high-grade gliomas. MATERIALS AND METHODS: Twenty-three patients with high-grade gliomas were retrospectively analyzed. We measured the perfusion at the resection area and evaluated the presence or absence of the restricted diffusion in residual tumor masses. The associations of the perfusion, diffusion and contrast enhancement (delayed static enhancement (DSE)) characteristics with time to tumor progression were statistically calculated. We also evaluated if the location of the tumor progression was concordant to the areas of the elevated perfusion, tumor type restricted diffusion and enhancement. RESULTS: Patients with >200 days to progression are more likely to have no elevated relative cerebral blood volume (rCBV) ratio (p = 0.0004), no tumor restriction (p = 0.024), and no DSE (p = 0.052). The elevated mean rCBV ratio (p<0.001) and tumor type restricted diffusion (p = 0.002) were significantly associated with a higher risk of progression. All cases with rCBV ratio of >1.5 progressed in 275 days or earlier. Tumors tended to progress at the area where patients with post-operative MRIs showed elevated perfusion (p = 0.006), tumor-type restricted diffusion (p = 0.005) and DSE (p = 0.008). CONCLUSIONS: Post-operative analysis of rCBV, tumor type restricted diffusion and enhancement characteristics are predictive of time to progression, risk of progression and where tumor progression is likely to occur.

Cladophialophora Bantiana : A Rare Intracerebral Fungal Abscess-Case Series and Review of Literature.

Background Intracerebral Cladophialophora bantiana may carry up to a 70% mortality rate despite advances in surgical resection capabilities and the use of both systemic and intrathecal antifungal treatments. Objectives The authors examined a retrospective case series of two patients with intracerebral infection from the rare, neurotropic fungus Cladophialophora bantiana and conducted a literature review to evaluate optimal therapies. Patients/Methods At our institution, the patients' cases presented with raised intracranial features of headache, visual field cut, and/or memory loss, with a correspondingly wide variety of radiological differential diagnoses. It was the microbiological, histopathological, and genomic identification of C. bantiana that ensured targeted, individualized patient therapies. Results and Conclusions Successful treatment depends on obtaining a complete surgical resection, an accurate microbiological diagnoses for mold identification, and an effective long-term, personalized antifungal treatment. Close radiographic surveillance is necessary to ensure complete eradication of pheoid fungi.

Multifocal histologically malignant Epstein-Barr virus-associated smooth muscle tumor in a pediatric transplant patient with an indolent course.

Epstein-Barr virus-associated smooth muscle tumors (EBV-SMTs) are rare lesions that occur in immunocompromised patients. Dural involvement appears to be less common in organ transplant recipients than in HIV patients. Due to the paucity of reported cases following organ transplantation, the natural history of these lesions is unclear. We describe an 8-year-old female who presented with adrenal, small bowel, and intracranial tumors 6 years following renal transplantation. Histopathological analysis revealed a highly cellular, mitotically active, smooth muscle neoplasm without necrosis. The tumor stained diffusely for smooth muscle actin and myosin. In situ hybridization for EBV-encoded RNA was diffusely positive. Following gross total resection, antiviral therapy, and a reduction in immunosuppression, the patient is tumor-free at 3 years follow-up. In patients with compromised immune systems, it is important to recognize this unique form of SMT because, even when there are multiple lesions, the prognosis may be excellent.