教学课程资源库 更多>>

关键词： cerebral small vessel disease   neuroimaging   neuropathology   radiology   systematic review   vascular dementia  

摘要： Aims Sporadic human cerebral small vessel disease (SVD) commonly causes stroke and dementia but its pathogenesis is poorly understood. There are recognised neuroimaging and histopathological features. However, relatively few studies have examined the relationship between the radiological and pathological correlates of SVD;better correlation would promote greater insight into the underlying biological changes. Methods We performed a systematic review to collate and appraise the information derived from studies that correlated histological with neuroimaging-defined SVD lesions. We searched for studies describing post-mortem imaging and histological tissue examination in adults, extracted data from published studies, categorised the information and compiled this narrative. Results We identified 38 relevant studies, including at least 1146 subjects, 342 of these with SVD: 29 studies focussed on neuroradiological white matter lesions (WML), six on microinfarcts and three on dilated perivascular spaces (PVS) and lacunes. The histopathology terminology was diverse with few robust definitions. Reporting and methodology varied widely between studies, precluding formal meta-analysis. PVS and 'oedema' were frequent findings in WML, being described in at least 94 and 18 radiological WML, respectively, in addition to myelin pallor. Histopathological changes extended beyond the radiological lesion margins in at least 33 radiological WML. At least 43 radiological lesions not seen pathologically and at least 178 histological lesions were not identified on imaging. Conclusions Histopathological assessment of human SVD is hindered by inconsistent methodological approaches and unstandardised definitions. The data from this systematic review will help to develop standardised definitions to promote consistency in human SVD research.

关键词： COVID-19   neurotropism   anosmia   long COVID   neuroglial infection   immune activation  

摘要： Neurological symptoms and varying levels of central nervous system (CNS) immunopathology have been described in COVID-19. Recent reports have suggested an increased level of innate immune activation associated with CNS border areas, as well as with a compartmentalized cytokine response and a dysregulated, autoreactive cerebrospinal fluid (CSF) immune profile. However, it remains contested whether these changes reflect bystander effects of systemic inflammation or relate to CNS-specific viral infection. We summarize some of the key findings pertaining to this ongoing debate and highlight directions for future investigation.

关键词： Histopathology   Epidemiology   Death   Autoimmune Liver Disease  

摘要： BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting. METHODS: This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death. RESULTS: During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI = 31.1-33.6) for AIH individuals and 14.1% (95%CI = 13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI = 2.17-2.41), which remained elevated >= 20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR = 4.55;95%CI = 3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR = 1.27;95%CI = 1.15-1.40), liver disease (HR = 66.24;95%CI = 48.19-91.03) and extrahepatic malignancy (HR = 1.69;95%CI = 1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death. CONCLUSION: AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.

关键词： cholangiocarcinoma   thyroid-like pattern   albumin in-situ hybridization   molecular characterization  

摘要： Thyroid-like cholangiocarcinoma is a very uncommon variant of peripheral-type cholangiocarcinoma. To date, only 4 prior cases have been reported. The molecular features of this tumor have not been described. We report a case of a 60-year-old woman with a tumor that evolved over a period of 10 years. A left hepatectomy specimen showed an 11 cm tumor that on histology exhibited areas reminiscent of a thyroid tumor with follicular and insular features which were positive on immunohistochemistry for cytokeratin 7 and in-situ hybridization for albumin. A detailed molecular analysis failed to show mutations common to cholangiocarcinomas but revealed frameshift mutations in 2 chromatin-remodeling genes, CREBBP and KMNT2A. This case confirms that thyroid-like cholangiocarcinoma is a histologic variant of this tumor that is associated with relatively low growth. As most cholangiocarcinomas, it is diffusely positive for cytokeratin 7 and albumin by in-situ hybridization. Given its rarity, the molecular alterations in this specific histologic subtype remain to be fully elucidated.

关键词： biomarker   graft-versus-host disease   immunohistochemistry   maculopapular drug eruption   Stevens-Johnson syndrome   toxic epidermal necrolysis  

摘要： Graft-versus-host disease (GvHD) is a major complication following stem-cell or solid-organ transplantation. Accurate diagnosis of cutaneous GvHD is challenging, given that drug eruptions and viral rashes may present with similar clinical/histological manifestations. Specific markers are not available. We performed the histological examination of biopsy samples from acute GvHD (aGvHD;n = 54), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN;n = 27), maculopapular drug eruption (MDE;n = 26) and healthy controls (n = 26). Samples of aGvHD showed a decrease in Langerhans cells (LC, p = 0.0001) and an increase in macrophages (M phi, p = 0.0001) compared to healthy skin. Compared to SJS/TEN, MDE and healthy skin, aGvHD biopsies contained greater numbers of CD4(+) and CD8(+) T cells. The majority of CD4(+) T-helper cells were localized in the upper dermis, whereas cytotoxic CD8(+) T cells were found in the epidermis. Increased numbers of CD56(+) natural killer (NK) cells in the upper dermis of aGvHD skin (p = 0.007) were not observed in controls or SJS/TEN and MDE. There were no differences in elafin staining between aGvHD and the latter two conditions. Acute GvHD appears to have a distinct inflammatory cell profile (T cells/NK cells) that may aid establishing in a more accurate diagnosis, especially when used to rule out differential diagnoses such as SJS/TEN or MDE.

关键词： Surgical Oncology   Oncology   Surgery  

摘要： Background Axillary pathologic complete response (pCR) confers higher overall and recurrence-free survival than residual axillary disease. Although breast pCR (ypT0) is associated with a pathologically negative axilla (ypN0) in human epidermal growth factor receptor 2-positive (HER2+) and triple-negative breast cancer (TNBC), how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes is incompletely understood. Methods A single-institution cancer registry was retrospectively reviewed for patients receiving neoadjuvant chemotherapy (NAC) followed by surgery from 2010 to 2018. Fisher's exact tests compared proportion of breast and axillary pCR by tumor subtype (hormone receptor [HR]-positive /HER2-,HR+/HER2+,HR-/HER2+,HR-/HER2-). Logistic regression determined factors associated with ypN0. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. Results The study enrolled 1348 patients. The median age was 54 years (interquartile range [IQR], 44-63 years), and 55% of the patients (n = 736) were postmenopausal. The tumor subtypes were HR+/HER2- (12%, n = 155), HR+/HER2+ (48%, n = 653), HR-/HER2+ (25%, n = 343), and TNBC (15%, n = 197). In the study, cT included T0 (1%, n = 18), T1 (20%, n = 272), T2 (53%, n = 713), T3 (17%, n = 230), and T4 (9%, n = 111), and cN included cN0 (51%, n = 687), cN1 (41%, n = 549), cN2 (5%, n = 61), and cN3 (3%, n = 43). Breast pCR and ypN0 occurred most in the HER2+ and TNBC subtypes. A negative association was found between ypN0 and age at diagnosis (odds ratio [OR], 0.98;95% confidence interval [CI], 0.97-0.99;p < 0.001), cT4 stage (OR, 0.29;95% CI, 0.09-0.91;p = 0.034), and HR+ subtypes (HR+/HER2-: OR, 0.54;95% CI, 0.31-0.94;p = 0.028;HR+/HER2+: OR, 0.60;95% CI, 0.39-0.93;p = 0.024). The HR-/HER2+ subtype was associated with ypN0 (OR, 1.70;95% CI, 1.05-2.73;p = 0.030), and cN2/cN3 was negatively associated with ypN0 in HR+/HER2+ disease (OR, 0.26;95% CI, 0.11-0.61;p = 0.002), HR-/HE

关键词： Surgical Oncology   Oncology   Surgery  

摘要： Background Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response;Group B, high response ratio, and Group C, low response ratio. Results The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio;the estimated median disease-free survival of Group C was 9.1 months (5.97-12.23), 14.9 months (4.72-25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69-43.31), and was not reached in Groups A and B (p = 0.001). Conclusions The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

关键词： Ga-68-PSMA   PET   CT   PET   MRI   primary staging   prostate cancer  

摘要： Background The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on Ga-68-PSMA PET images. Methods Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent Ga-68-PSMA-11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as "PET positive" and "PET negative" according to the presence of pathologic extraprostatic PSMA involvement. "PET positive" patients were additionally divided into two groups: oligometastatic (1-3 metastatic lesion) and multimetastatic (>3 metastatic lesions). Results The mean age of patients was 66.8 +/- 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in "PET positive" group compared to "PET negative" group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low-intermediate risk groups (ISUP 1-3 and total PSA <= 20 ng/ml and PSAD < 0.15 ng/ml/cc). This ratio was 46% in the high-risk group (ISUP 4-5 or total PSA > 20 ng/ml or PSAD >= 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively;with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05). Conclusions In this study, Ga-68-PSMA-11 PET positivity was significantly higher in the high-risk patient group than in the low-intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP

关键词： 1p   19q codeletion   Neoadjuvant chemotherapy   M2 macrophage   Glioma stem cell   PAV chemotherapy  

摘要： Purpose Lower grade gliomas with 1p/19q codeletion are often responsive to chemotherapy, and several of these have been treated using upfront chemotherapy and subsequent resection following tumor volume decrease. This study aimed to elucidate the histological changes and the mechanism of recurrence after alkylating agent chemotherapy in 1p/19-codeleted gliomas. Methods Fourteen 1p/19q-codeleted gliomas resected following tumor volume decrease after alkylating agent chemotherapy were included and compared with their pre-chemotherapy specimens. Histological changes were investigated using hematoxylin-eosin staining, and changes in proliferative activity, status of glioma stem cells (GSCs), and tumor-infiltrating macrophages were assessed using immunohistochemistry for Ki-67/MIB-1, CD68 as a pan-macrophage/monocyte marker, CD163 as a presumed marker of M2 polarity, and nestin and CD133 as markers of GSCs. Results The most frequent histological findings following chemotherapy included a sparse glial background and abundant foamy cell infiltration. The Ki-67/MIB-1 index decreased and the number of CD68 + cells increased after chemotherapy. The increasing rate of CD68 + cells in the post-/pre-chemotherapy specimens was inversely correlated with patient prognosis but not tumor response. The number of CD163 + cells, M2/M1 + M2 ratio, and the ratio of GSCs to total tumor cells increased after chemotherapy, and those in the post-chemotherapy specimens were negatively correlated with patient prognosis. There was a correlation between the M2/M1 + M2 ratio and the ratio of GSCs in both pre- and post-chemotherapy specimens. Conclusion GSCs in conjunction with M2 macrophages constitute the mechanism of resistance to and recurrence after alkylating agent chemotherapy in 1p/19q-codeleted gliomas.