Cholangiocarcinoma: three different entities based on location.
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ABSTRACT:
SUBMITTER: Aquina CT
PROVIDER: S-EPMC7333109 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Cholangiocarcinoma: three different entities based on location.
Aquina Christopher T CT Pawlik Timothy M TM Ejaz Aslam A
Annals of translational medicine 20200601 12
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Project description:Cholangiocarcinoma (CC) is an uncommon malignancy with increasing incidence and dismal prognosis. We conducted a comprehensive analysis of the CC tumor immune microenvironment (TIME) based on tumor location to identify therapeutic targets. We hypothesized that the TIME of CC would vary by primary tumor location and that high tumor infiltration by CD8+ T cells and low infiltration by M2 macrophages would be associated with improved survival. A retrospective analysis was conducted of 99 CC tumor samples surgically resected between 2000 and 2014. Tissue microarrays were constructed from each tumor and stained by immunohistochemistry for 24 markers of immune cells, immune activation or inhibition, programmed cell death-ligand 1, and mesothelin. Most tumors were amply infiltrated with by CD4+, CD8+, and FoxP3+ T cells, as well as by myeloid cells. Mesothelin expression ≥1+ by immunohistochemistry was found in 68% of tumors. We identified higher densities of M1 macrophages in primary distal extrahepatic CC, as well as metastatic lesions. Mesothelin expression was also significantly higher in distal extrahepatic CC. There was no association with survival of infiltration by CD4+, CD8+, or FoxP3+ T cells, mesothelin expression, or programmed cell death-ligand 1 percentage expression, however, high CD14+ myeloid cells and high CD163+ M2 macrophages were associated with worse survival. In conclusion, the CC TIME is a heterogenous milieu highly infiltrated by innate and adaptive immune cells, which differs based on primary tumor location and between primary tumors and metastatic lesions. The correlation of intratumoral M2 macrophages and myeloid cells with a worse prognosis may suggest promising immunotherapeutic targets in CC.
| S-EPMC8373662 | biostudies-literature
Project description:BackgroundAnatomical location is considered in diagnostic and therapeutic approaches of cholangiocarcinoma (CCA). However, disparities and its extents in proportion of surgical candidates, prognostic factors, prognostic genetic networks, susceptibility for lymph node dissection, and disease stage at diagnosis remain to be confirmed.MethodsA total of 11,710 patients with cholangiocarcinoma from Surveillance, Epidemiology, and End Results Cancer Registries (SEER) and 45 CCA patients with paired tumor and normal specimens from The Cancer Genome Atlas were studied. Kaplan-Meier estimation, Cox proportional hazards regression, Pearson's correlation, comparison between anatomical location (distal, intrahepatic, and perihilar)-dependent CCAs, differential expressive gene stratification, potential interactive gene identification, and confirmation on pathways of the prognostic networks were carried out.ResultsSurvival outcomes were most favorable in the distal type, followed by perihilar and intrahepatic types, but postsurgical prognosis was slightly higher in intrahepatic type compared to perihilar type. Distant historic stage at diagnosis was noticed in intrahepatic type. Significant prognostic factors and their hazards ratios were dependent to the anatomical location. In addition, lymph node dissection provided significant survival benefits in perihilar type only. Furthermore, prognosis-predictive genes, as well as potential processes and pathways, were significantly among the anatomical location-dependent types that the genes barely overlapped.ConclusionsThere are disparities in almost all aspects among distal, intrahepatic, and perihilar CCAs. Anatomical location needs to be considered in treatment, prognostic estimation, identifying targets, and developing therapeutic approaches for CCA.
| S-EPMC6989985 | biostudies-literature
Project description:BackgroundHealth care-associated infective endocarditis (HAIE) and intravenous drug use-related IE (IDUIE) have emerged as major groups in infective endocarditis (IE). We studied their role and clinical picture in a population-based survey.MethodsA population-based retrospective study including all adult patients diagnosed with definite or possible IE in Southern Finland in 2013-2017. IE episodes were classified according to the mode of acquisition into 3 groups: community-acquired IE (CAIE), HAIE, and IDUIE.ResultsTotal of 313 episodes arising from 291 patients were included. Incidence of IE was 6.48/100 000 person-years. CAIE accounted for 38%, HAIE 31%, and IDUIE 31% of IE episodes. Patients in the IDUIE group were younger, and they more frequently had right-sided IE (56.7% vs 5.0%; P < .001) and S. aureus as etiology (74.2% vs 17.6%; P < .001) compared with the CAIE group. In-hospital (15.1% vs 9.3%; P = .200) and cumulative 1-year case fatality rates (18.5% vs 17.5%; P = .855) were similar in CAIE and IDUIE. Patients with HAIE had more comorbidities, prosthetic valve involvement (29.9% vs 10.9%; P = .001), enterococcal etiology (20.6% vs 5.9%; P = .002), and higher in-hospital (27.8% vs 15.1%; P = .024) and cumulative 1-year case fatality rates (43.3% vs 18.5%; P < .001) than patients with CAIE. Staphylococcus aureus caused one-fifth of IE episodes in both groups.ConclusionsOur study indicates that in areas where injection drug use is common IDUIE should be regarded as a major risk group for IE, along with HAIE, and not seen as part of CAIE. Three different risk groups, CAIE, HAIE, and IDUIE, with variable characteristics and outcome should be recognized in IE.
| S-EPMC7473740 | biostudies-literature
Project description:BackgroundResistant and refractory migraine are commonly encountered in specialized headache centers. Several comorbidities, mostly psychiatric conditions, have been linked to migraine worsening; however, there is little knowledge of the comorbidity profile of individuals with resistant and refractory migraine.MethodsREFINE is a prospective observational multicenter international study involving individuals with migraine from 15 headache centers. Participants were categorized into three groups based on the European Headache Federation criteria: non-resistant and non-refractory (NRNRM), resistant (ResM), and refractory (RefM). We explored the prevalence of 20 comorbidities at baseline in the three groups.ResultsOf the 689 included patients (82.8% women), 262 (38.0%) had ResM, 73 (10.4%) had RefM and 354 (51.4%) NRNRM. A higher prevalence of psychiatric comorbidities, trigger points, temporomandibular joint disorders, thyroiditis, and cerebrovascular diseases was observed in the RefM group, followed by ResM and NRNRM. Multiple comorbidities were more common in the RefM group, followed by the ResM group and by the NRNRM group (41.6% vs. 24.5% vs. 14.1% respectively; p < 0.001). At the sensitivity analysis, exploring participants with chronic migraine, significant differences among the NRNRM, ResM, and RefM groups were found in the prevalence of anxiety (p < 0.001), asthma and rhinitis (p = 0.013), bipolar and other psychiatric disorders (p = 0.049), cerebrovascular diseases (p < 0.001), depression (p < 0.001), obesity (p = 0.002), thyroiditis (p < 0.001), and trigger points (p = 0.008).ConclusionREFINE data indicate that individuals with ResM and RefM have a higher burden of comorbidities than those with NRNRM. It can be postulated that those comorbidities may have an impact on the progression of migraine from a form that is easy to treat to a form that is resistant or refractory to treatments. Longitudinal studies are needed to understand the direction of the association between ResM or RefM and those comorbidities and if proper treatment of comorbidities might help overcome treatment resistance or refractoriness.
| S-EPMC11613769 | biostudies-literature
Project description:A common way to learn about a system's properties is to analyze temporal fluctuations in associated variables. However, conclusions based on fluctuations from a single entity can be misleading when used without proper reference to other comparable entities or when examined only on one timescale. Here we introduce a method that uses predictions from a fluctuation scaling law as a benchmark for the observed standard deviations. Differences from the benchmark (residuals) are aggregated across multiple timescales using Principal Component Analysis to reduce data dimensionality. The first component score is a calibrated measure of fluctuations-the reactivity RA of a given entity. We apply our method to activity records from the media industry using data from the Event Registry news aggregator-over 32M articles on selected topics published by over 8000 news outlets. Our approach distinguishes between different news outlet reporting styles: high reactivity points to activity fluctuations larger than expected, reflecting a bursty reporting style, whereas low reactivity suggests a relatively stable reporting style. Combining our method with the political bias detector Media Bias/Fact Check we quantify the relative reporting styles for different topics of mainly US media sources grouped by political orientation. The results suggest that news outlets with a liberal bias tended to be the least reactive while conservative news outlets were the most reactive.
| S-EPMC7691371 | biostudies-literature
Project description:PurposeExtrahepatic cholangiocarcinoma is distinguished into perihilar cholangiocarcinoma (PHC) and distal bile duct cancer (DBC). The studies for each subtype have been conducted separately. This study compared oncological outcomes between PHC and DBC.MethodsFrom 2001 to 2017, patients who underwent surgery at Seoul National University Hospital for PHC or DBC were enrolled. T stage was reclassified for tumor extent as 'confined to' or 'beyond' the bile duct (BD). In survival analysis, stage matching was performed based on tumor extent and lymph node (LN) metastasis.ResultsThere were 680 patients enrolled: 295 with PHC and 385 with DBC. The R0 resection rate was higher in DBC (77.3% vs. 89.9%, P = 0.001). Tumors confined to BD were more common in PHC (61.7% vs. 37.7%, P = 0.001). The 5-year survival rate (5YSR) was higher in DBC patients (30.8% vs. 47.8%, P = 0.001). After stage matching, DBC patients showed better 5YSR for tumors confined to BD/LN(-) (47.1% vs. 64.3%), confined to BD/LN(+) (22.0% vs. 35.0%), beyond BD/LN(-) (21.9% vs. 49.8%), and beyond BD/LN(+) (9.6% vs. 26.9%). The overall recurrence rate was higher in PHC (59.7% vs. 51.9%, P = 0.045), with no difference in the recurrence types between two groups. Radiation therapy was effective for patients with advanced stage disease (5YSR: 35.8% vs. 29.5%, P = 0.022); adjuvant chemotherapy was effective for patients receiving R1 resection (5YSR: 37.3% vs. 13.2%, P = 0.040).ConclusionDifferences were identified in oncological outcomes between PHC and DBC, including pathologic findings and survival outcomes.
| S-EPMC8831089 | biostudies-literature
Project description: Not available
| S-EPMC8966960 | biostudies-literature
Project description:BackgroundStudies regarding coxsackievirus A6 (CVA6) infection were limited. In Taiwan, outbreaks of CVA6 occurred in 2009 and 2010, respectively, but the clinical manifestations were markedly different. We conducted a study to compare the clinical features and genomic sequence between the two years.Methodology/principal findingsIn 2009 and 2010, 205 patients with coxsackievirus A6 (CVA6) infection were treated at Chang Gung Memorial Hospital. Detailed clinical features were obtained from 126 inpatients, 62 in 2009 and 64 in 2010. Between the inpatients in 2009 and 2010, no statistically significant difference was noted in terms of demographics, length of hospital stay and laboratory data. Significantly more patients in 2009 presented with herpangina (82%) while more patients in 2010 presented with hand-foot-mouth disease (HFMD; 67%) and skin rash beyond the typical sites for HFMD. Complete genomic sequences were determined and compared for three isolates from patients with herpangina in 2009 and three isolates from patients with HFMD in 2010. The complete sequences showed that 2009 and 2010 CVA6 isolates were indistinguishable by partial VP1 genes, but there were 5 unique nucleotide changes in 3' UTR, and 23 out of 2201 (1%) amino acids were different. 2010 viruses underwent the largest number of amino acid changes in 3CD protein, which is the precursor of both 3C protease and 3D polymerase.ConclusionsSince 2008 in Finland, outbreaks of HFMD due to CVA6 were noted internationally. CVA6 of different genetic background may cause different clinical manifestations such as herpangina and HFMD.
| S-EPMC3530459 | biostudies-literature
Project description:BackgroundPseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings.MethodsPatients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated.ResultsThirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was - 19.1 mm and - 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed.ConclusionsPsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.
| S-EPMC10249323 | biostudies-literature
Project description:Mucoepidermoid carcinoma (MEC) and adenosquamous carcinoma (ASC) have overlapping histopathological appearances and sites of occurrence, which may cause diagnostic difficulty impacting subsequent treatment. We conducted a systematic review of the scientific literature to determine whether molecular alterations were sufficiently different in MEC and ASC to aid in classifying the two entities. We searched Medline, Embase and Web of Science for studies reporting molecular determinations of ASC and/or MEC and screened retrieved records for eligibility. Two independent researchers reviewed included studies, assessed methodological quality and extracted data. Of 8623 identified records, 128 articles were included for analysis: 5 which compared the two tumors in the same investigation using the same methods and 123 which examined the tumors separately. All articles, except one were case series of moderate to poor methodological quality. The 5 publications examining both tumors showed that 52/88 (59%) MEC and 0% of 110 ASC had rearrangement of the MAML2 gene as detected by FISH and/or RT-PCR, but did not investigate other genes. In the entire series MEC had MAML2 gene rearrangement in 1337/2009 (66.6%) of tumors studied. The articles examining tumors separately found that MEC had mutations in EGFR (11/329 cases, 3.3%), KRAS (11/266, 4.1%) and ERBB2 (9/126, 7.1%) compared with ASC that had mutations in EGFR (660/1705, 38.7%), KRAS (143/625, 22.9%) and ERBB2 (6/196, 3.1%). The highest level of recurrent mutations was in pancreatic ASC where (108/126, 85.7%) reported mutations in KRAS. The EGFR mutations in ASC were similar in number and kind to those in lung adenocarcinoma. By standards of systematic review methodology and despite the large number of retrieved studies, we did not find adequate evidence for a distinctive molecular profile of either MEC or ASC that could definitively aid in its classification, especially in histologically difficult cases that are negative for MAML2 rearrangement. The case series included in this review indicate the relevance of MAML2 rearrangement to support the diagnosis of MEC, findings that should be confirmed by additional research with adequate study design.
| S-EPMC9514988 | biostudies-literature