Intravascular placement and migration of a colonic stent into the inferior mesenteric vein.

Colonic self-expanding metal stents (SEMSs) are commonly used to treat large bowel obstruction due to gastrointestinal malignancy with great success. While mortality is negligible, morbidity from both early and late complications can be significant. Stent perforation, erosion and migration are the most feared complications. We present the first reported case of wire-associated colon perforation with placement and migration of an SEMS into the inferior mesenteric vein (IMV). A man in his early 60s presented with a large bowel obstruction due to a colorectal mass. He underwent endoscopic colonic SEMS placement for colonic decompression. The stent was later found to be within the IMV, requiring a colon resection and retrieval of the stent.

Resurrecting the Hospital Autopsy: Impact of an Office of Decedent Affairs on Consent Rates, Providers, and Next-of-Kin.

CONTEXT.­: Autopsy rates have decreased dramatically despite providing important clinical information to medical practices and social benefits to decedents' families. OBJECTIVE.­: To assess the impact of an institutional Office of Decedent Affairs (ODA), a direct communication link between pathology and decedents' families, on hospital autopsy consent rates, autopsy-related communication, practitioner views, and next-of-kin experiences. DESIGN.­: A before and after study involving all hospital decedents whose deaths did not fall within the jurisdiction of the medical examiner's office from 2013 to 2018. A pathology-run ODA launched in May 2016 to guide next-of-kin through the hospital death process (including autopsy-related decisions) and serve as the next-of-kin's contact for any subsequent autopsy-related communication. Critical care and hematology/oncology practitioners were assessed for their autopsy-related views and decedents' next-of-kin were assessed for their autopsy-related experiences. Autopsy consent rates for non-medical examiner hospital deaths, autopsy-related communication rates, practitioner views on the role and value of autopsy, and next-of-kin autopsy experiences and decisions factors were compared prior to and after ODA launch. RESULTS.­: Autopsy consent rates significantly increased from 13.2% to 17.3% (480 of 3647 deaths versus 544 of 3148 deaths; P < .001). There were significant increases in the rate of autopsy-related discussions and bereavement counseling provided to decedents' families. Practitioner views on the positive role of autopsy for any hospital death and those with advanced stage cancer also significantly increased. Next-of-kin indicated more consistent autopsy-related discussions with the potential benefits of autopsy discussed becoming key decision factors. CONCLUSIONS.­: An ODA improves hospital autopsy consent rates, autopsy-related communication, providers' autopsy-related views, and next-of-kins autopsy experiences.

Pick's disease: clinicopathologic characterization of 21 cases.

BACKGROUND: Pick's disease (PiD) is a unique subtype of frontotemporal lobar degeneration characterized pathologically by aggregates of 3-Repeat tau. Few studies have examined the clinical variability and disease progression in PiD. We describe the clinical features, neuropsychological profiles and coexistent pathologies in 21 cases of autopsy-confirmed PiD. METHODS: This study was a retrospective analysis of patients with Pick's disease evaluated at Mayo Clinic, Rochester or Jacksonville (1995-2018), and identified through an existing database. RESULTS: Twenty-one cases with sufficient clinical data were identified. Behavioral variant FTD (bvFTD; 12/21) was the most common phenotype, followed by primary progressive aphasia (PPA; 7/21), corticobasal syndrome (CBS; 1/21) and amnestic dementia (1/21). Median age at disease onset was 54 years, with PPA cases (median = 52 years) presenting earlier than bvFTD (median = 59). Median disease duration (onset-death) overall was 10 years and did not differ significantly between bvFTD (median = 9.5 years) and PPA (median = 13). Age at death was not significantly different in PPA (median = 66) compared to bvFTD (median = 68.5). A third of the cases (n = 7/21) demonstrated pure PiD pathology, while the remainder showed co-existent other pathologies including Alzheimer's type (n = 6), cerebral amyloid angiopathy (n = 3), combined Alzheimer's and amyloid angiopathy (n = 4), and Lewy body disease (n = 1). CONCLUSIONS: Our study shows that bvFTD and PPA are the most common clinical phenotypes associated with PiD, although rare presentations such as CBS were also seen. Coexisting non-Pick's pathology was also present in many cases. Our study highlights the clinical and pathologic heterogeneity in PiD.

New insights into calcifying pseudoneoplasm of the neuraxis (CAPNON): a 20-year radiological-pathological study of 37 cases.

AIMS: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare entity that can occur anywhere within the central nervous system. Histologically, CAPNON has been characterised as a benign, calcified, fibro-osseous lesion with a characteristic chondromyxoid fibrillary matrix with dense calcification and varying degrees of spindle, epithelioid, fibrous, meningothelial and giant cells. The underlying aetiology of CAPNON is controversial and incompletely understood. The aim of this study was to perform a comprehensive radiological and histological review to further characterise this entity. METHODS AND RESULTS: In this article, we review our institutional 20-year experience including 37 cases of CAPNON with detailed pathological analysis, evaluation of concurrent lesions, correlation with radiological imaging, and critical review of the literature. The classic histological finding of chondromyxoid matrix was present in one-third of cases. Underlying or dual pathologies were frequent, and included diverse underlying conditions. Radiologically, dense calcification and dural attachment were the most common features. Enhancement was often low, but was more prominent in the setting of inflammatory changes, aggressive growth, and dual pathology. CONCLUSION: Our results suggest that CAPNON represents a spectrum of reactive processes that can arise in association with diverse underlying pathologies, including inflammatory, degenerative, vascular and neoplastic lesions.

Association between contact sports participation and chronic traumatic encephalopathy: a retrospective cohort study.

Chronic traumatic encephalopathy is a debilitating neurodegenerative disorder associated with repetitive traumatic brain injuries often sustained through prior contact sport participation. The frequency of this disorder in a diverse population, including amateur athletes, is unknown. Primary historical obituary and yearbook records were queried for 2566 autopsy cases in the Mayo Clinic Tissue Registry resulting in identification of 300 former athletes and 450 non-athletes. In these cases, neocortical tissue was screened for tau pathology with immunohistochemistry, including pathology consistent with chronic traumatic encephalopathy, blinded to exposure or demographic information. Using research infrastructure of the Rochester Epidemiology Project, a comprehensive and established medical records-linkage system of care providers in southern Minnesota and western Wisconsin, medical diagnostic billing codes pertaining to head trauma, dementia, movement disorders, substance abuse disorders and psychiatric disorders were recorded for cases and controls in a blinded manner. A total of 42 individuals had pathology consistent with, or features of, chronic traumatic encephalopathy. It was more frequent in athletes compared to non-athletes (27 cases versus 15 cases) and was largely observed in men (except for one woman). For contact sports, American football had the highest frequency of chronic traumatic encephalopathy pathology (15% of cases) and an odds ratio of 2.62 (P-value = 0.005). Cases with chronic traumatic encephalopathy pathology had higher frequencies of antemortem clinical features of dementia, psychosis, movement disorders and alcohol abuse compared to cases without chronic traumatic encephalopathy pathology. Understanding the frequency of chronic traumatic encephalopathy pathology in a large autopsy cohort with diverse exposure backgrounds provides a baseline for future prospective studies assessing the epidemiology and public health impact of chronic traumatic encephalopathy and sports-related repetitive head trauma.

Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation.

Primary high-grade infiltrating gliomas of the spinal cord are rare, with prior series including limited numbers of cases and reporting poor outcomes. Additionally, the molecular profile of high-grade infiltrating gliomas of the spinal cord has not been well characterized. We identified 13 adult patients whose surgery had been performed at our institution over a 26-year-period. Radiologically, nine cases harbored regions of post-contrast enhancement. Existing slides were reviewed, and when sufficient tissue was available, immunohistochemical stains (IDH1-R132H, H3-K27M, H3K27-me3, ATRX, p53 and BRAF-V600E), and a targeted 150-gene neuro-oncology next-generation sequencing panel were performed. The 13 patients included 11 men and 2 women with a median age of 38 years (range = 18-69). Histologically, all were consistent with an infiltrating astrocytoma corresponding to 2016 WHO grades III (n = 5) and IV (n = 8). By immunohistochemistry, six cases were positive for H3K27M, all showing concomitant loss of H3K27-me3. Next-generation sequencing was successfully performed in ten cases. Next-generation sequencing studies were successfully performed in four of the cases positive for H3K27M by immunohistochemistry, and all were confirmed as H3F3A K27M-mutant. Additional recurrent mutations identified included those of TERT promoter (n = 3), TP53 (n = 5), PPM1D (n = 3), NF1 (n = 3), ATRX (n = 2), and PIK3CA (n = 2). No HIST1H3B, HIST1H3C, IDH1, IDH2, or BRAF mutations were detected. Ten patients have died since first surgery, with a median survival of 13 months and 1 year of 46%. Median survival was 48.5 months for H3K27M-positive cases, compared to 1 month for those with TERT promoter mutation and 77 months for those harboring neither (p = 0.019). Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.

Subependymoma involving multiple spinal cord levels: A clinicopathological case series with chromosomal microarray analysis.

Subependymomas of the spinal cord are rare, do not often involve multiple levels, and very rarely recur. Here, we present a series of spinal cord subependymomas with a detailed description of the clinical, radiological and pathological features, and characterization by chromosomal microarray analysis. Briefly, the four patients included two men and two women, between the ages of 22 and 48 years. The most common presenting symptoms were neck and arm pain with upper extremity weakness. By imaging, the tumors were found to involve multiple spinal levels, including cervical/ cervico-thoracic (three patients) and thoracic (one patient), were all eccentric, and had minimal to no post-contrast enhancement. Two patients underwent gross total resection, one had a sub-total resection, and one underwent biopsy alone with a decompressive laminectomy. Follow up ranged from 6 months to 22 years. One patient (case 4) had recurrence 15 years following gross total resection and chromosomal microarray analysis revealed deletions on the long arm of chromosome 6. Our limited series suggests that spinal cord subependymomas can rarely recur, even following gross total resection, suggesting a possible role for long-term surveillance for these rare tumors.

Sellar Region Atypical Teratoid/Rhabdoid Tumors in Adults: Clinicopathological Characterization of Five Cases and Review of the Literature.

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant CNS neoplasms that typically occur in children <2 years of age. These are characterized by high-grade histologic features and mutations of the INI1/SMARCB1 gene readily detected by loss of expression by immunohistochemistry. Among adults, the majority of AT/RTs occurs in the cerebral hemispheres. A small number of adult AT/RTs involving the sellar and suprasellar region reported in the literature suggest a distinct clinical course for this group. Here, we describe detailed clinical and genetic characterization of 5 adult patients with AT/RTs involving the sellar and suprasellar region, and provide a review of the available clinical and genetic features of 22 previously reported cases in order to help increase our understanding of this unusual entity.

Supratentorial CAPNON associated with WHO grade II meningioma: A case report.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare benign tumor of uncertain etiology, arising in the craniospinal axis. CAPNON typically arises in isolation, with only two prior reports of a concurrent second neoplasm. Here, we report the case of a male 17-year-old who presented with new-onset seizures. MRIs revealed a 2 cm extra-axial solid-cystic mass, arising at the left temporo-occipital junction and abutting the dura with marked surrounding parenchymal vasogenic edema. The solid components demonstrated dense calcification and avid enhancement. Gross total surgical resection was performed. Histopathological examination revealed central regions showing characteristic features of CAPNON. Toward the periphery, the CAPNON was intimately associated with and sharply demarcated from a meningioma, which showed up to five mitoses per 10 high-power fields and had invasion into the adjacent brain parenchyma, warranting a WHO grade II designation. This is the first report of CAPNON arising in association with a meningioma. The coexistence of these two tumors raises the possibility of a reactive/dysplastic etiology for CAPNON.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 µg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m2) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. © RSNA, 2017.

Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer.

Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40Gy (V20, V30, or V40) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within < 2.5cm of the CW. We found 260 cases; of these, chronic grade ≥ 2 CW pain was identified in 23 patients. We then selected 10 representative patients from this group and generated proton SBRT treatment plans, using the identical dose of 50Gy in 4 fractions, and assessed potential differences in CW dose between the 2 plans. The proton SBRT plans reduced the CW doses at all dose levels measured. The median CW V20 was 364.0cm(3) and 160.0cm(3) (p < 0.0001), V30 was 144.6cm(3)vs 77.0cm(3) (p = 0.0012), V35 was 93.9cm(3)vs 57.9cm(3) (p = 0.005), V40 was 66.5cm(3)vs 45.4cm(3) (p = 0.0112), and mean lung dose was 5.9Gy vs 3.8Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures.

Mechanistic insights into nicotine withdrawal.

Smoking is responsible for over 400,000 premature deaths in the United States every year, making it the leading cause of preventable death. In addition, smoking-related illness leads to billions of dollars in healthcare expenditures and lost productivity annually. The public is increasingly aware that successfully abstaining from smoking at any age can add years to one's life and reduce many of the harmful effects of smoking. Although the majority of smokers desire to quit, only a small fraction of attempts to quit are actually successful. The symptoms associated with nicotine withdrawal are a primary deterrent to cessation and they need to be quelled to avoid early relapse. This review will focus on the neuroadaptations caused by chronic nicotine exposure and discuss how those changes lead to a withdrawal syndrome upon smoking cessation. Besides examining how nicotine usurps the endogenous reward system, we will discuss how the habenula is part of a circuit that plays a critical role in the aversive effects of high nicotine doses and nicotine withdrawal. We will also provide an updated summary of the role of various nicotinic receptor subtypes in the mechanisms of withdrawal. This growing knowledge provides mechanistic insights into current and future smoking cessation therapies.

Pulmonary alveolar proteinosis in a kidney transplant: a rare complication of sirolimus.

Pulmonary alveolar proteinosis (PAP) has been associated with the immunosuppressant sirolimus in transplant patients. PAP is a progressive lung disease characterized by the accumulation of surfactant-like material in the lungs leading to decreased pulmonary function with shortness of breath and cough as common symptoms. We report a rare case of sirolimus-associated PAP in a kidney transplant recipient with a history of end-stage renal disease secondary to haemolytic uraemic syndrome (HUS) and review of the literature. Discontinuation of sirolimus and initiation of tacrolimus led to resolution of PAP without recurrence of HUS.