Crohn´s disease is an independent risk factor for liver fibrosis in patients with inflammatory bowel disease and non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Controversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls. METHODS: Cross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use. RESULTS: The prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001-1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001-1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78-8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87-0.98)). CONCLUSIONS: Although we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease.

Seropositivity to Cysticercosis in School-Age Children Living in a Low-Income Municipality in the Midwest Region of Brazil.

Background: Human cysticercosis (CC) is a global public health problem, especially in Latin America, including Brazil. We aimed to analyze the seroprevalence of CC among school-age children and adolescents. Methods: We analyzed the presence of specific IgG antibodies against Taenia solium metacestodes in 500 serum samples from elementary school children and adolescents in Jataí City, state of Goiás, Brazil. IgG antibodies against the antigenic extract of the parasite were detected and analyzed by ELISA, and specific peptides were identified by confirmatory Western Blotting test. Results: Of the 500 study participants, 205 (41%) were male, and 295 (59%) were female. Participants aged between 4 and 18 years (mean age 8.4 years). The percentage of serum samples reactive by ELISA was 37.2%. These samples were analyzed by Western Blotting, which confirmed that the seropositivity rate was 6.2% (95% CI 2.4-14.7) in 31 samples reactive for CC-specific bands, determined in serum samples from 18 male (5-11 years old) and 13 female (4-12 years old) students. Conclusion: The CC seroprevalence demonstrated in schoolchildren suggests that this parasitosis is endemic in the study area. Further investigations are necessary to clarify the local epidemiology of this parasitosis.

REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial.

BACKGROUND: Approximately 15% of adult GIST patients harbor tumors that are wild-type for KIT and PDGFRα genes (KP-wtGIST). These tumors usually have SDH deficiencies, exhibit a more indolent behavior and are resistant to imatinib. Underlying oncogenic mechanisms in KP-wtGIST include overexpression of HIF1α high IGFR signaling through the MAPK pathway or BRAF activating mutation, among others. As regorafenib inhibits these signaling pathways, it was hypothesized that it could be more active as upfront therapy in advanced KP-wtGIST. METHODS: Adult patients with advanced KP-wtGIST after central confirmation by NGS, naïve of systemic treatment for advanced disease, were included in this international phase II trial. Eligible patients received regorafenib 160 mg per day for 21 days every 28 days. The primary endpoint was disease control rate (DCR), according to RECIST 1.1 at 12 weeks by central radiological assessment. RESULTS: From May 2016 to October 2020, 30 patients were identified as KP-wtGIST by Sanger sequencing and 16 were confirmed by central molecular screening with NGS. Finally, 15 were enrolled and received regorafenib. The study was prematurely closed due to the low accrual worsened by COVID outbreak. The DCR at 12 weeks was 86.7% by central assessment. A subset of 60% experienced some tumor shrinkage, with partial responses and stabilization observed in 13% and 87% respectively, by central assessment. SDH-deficient GIST showed better clinical outcome than other KP-wtGIST. CONCLUSIONS: Regorafenib activity in KP-wtGIST compares favorably with other tyrosine kinase inhibitors, especially in the SDH-deficient GIST subset and it should be taken into consideration as upfront therapy of advanced KP-wtGIST. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02638766.

Liver Fibrosis in Non-Alcoholic Fatty Liver Disease and Progression to Hepatocellular Carcinoma in Patients with Inflammatory Bowel Disease: A Systematic Review.

The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn's Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn's disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice.

Extra-meningeal solitary fibrous tumor: an evolving entity with chameleonic morphological diversity, a hallmark molecular alteration and unresolved issues in risk stratification assessment.

Solitary fibrous tumor (SFT) is a rare type of mesenchymal lesion with variable clinical presentation in which specific clinicopathologic factors have been related to patient outcome. SFT shares an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging. Although molecular studies provide significant clues, especially in the differential diagnosis with other neoplasms, a thorough hematoxylin and eosin analysis and the integration of phenotypical, clinical, and radiological features remain an essential tool in SFT diagnosis. In this review, we discuss some emerging issues still under debate in SFT.

Tumor Microenvironment and Its Clinicopathologic and Prognostic Association in Cutaneous and Noncutaneous Angiosarcomas.

OBJECTIVES: We explored features of the angiosarcoma (AS) tumor microenvironment to discover subtypes that may respond to immunotherapy. METHODS: Thirty-two ASs were included. Tumors were studied by histology, immunohistochemistry (IHC), and gene expression profile using the HTG EdgeSeq Precision Immuno-Oncology Assay. RESULTS: Comparing cutaneous and noncutaneous ASs, the second group showed 155 deregulated genes, and unsupervised hierarchical clustering (UHC) delineated two groups: the first mostly cutaneous AS and the second mainly noncutaneous AS. Cutaneous ASs showed a significantly higher proportion of T cells, natural killer cells, and naive B cells. ASs without MYC amplification revealed a higher immunoscore in comparison with ASs with MYC amplification. PD-L1 was significantly overexpressed in ASs without MYC amplification. UHC showed 135 deregulated genes differentially expressed when comparing ASs from the non-head and neck area with patients who had AS in the head and neck area. ASs from the head and neck area showed high immunoscore. PD1/PD-L1 content was significantly more highly expressed in ASs from the head and neck area. IHC and HTG gene expression profiling revealed a significant correlation between PD1, CD8, and CD20 protein expression but not PD-L1. CONCLUSIONS: Our HTG analyses confirmed a high degree of tumor and microenvironment heterogeneity. Cutaneous ASs, ASs without MYC amplification, and ASs located in the head and neck area seem to be the most immunogenic subtypes in our series.

Risk of Cancer in Patients with Inflammatory Bowel Diseases and Keys for Patient Management.

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

Combined Merkel cell carcinoma and cutaneous squamous cell carcinoma with lymph node metastases: Report of two cases.

Merkel cell carcinoma (MCC) is an infrequent, aggressive cutaneous neoplasm, that typically affects the photodamaged skin of elderly individuals, and immunosuppressed patients. Because a subset of MCC is closely related to UV radiation, MCC can develop concurrently with other tumors, most commonly, as a combined tumor with squamous cell carcinoma (SCC). These combined tumors appear to represent a distinct disease process from pure MCC, as they are mostly Merkel cell polyomavirus (MCPyV) negative, and show a more aggressive behavior. We present two additional cases of combined MCC and SCC with nodal metastases, one of which was MCPyV positive. Two different subtypes of MCC have been proposed based on their origin: a true neuroendocrine carcinoma, that is MCPyV positive and has a dermal origin, and a UV-related SCC with neuroendocrine differentiation. This theory could explain why MCC can develop concurrently with SCC, and why these combined cases are generally MCPyV negative. However, it fails to explain the minority of combined MCC and SCC tumors that are MCPyV positive. Because both our patients had a history of chronic UV exposure, we hypothesize that UV radiation probably played a major role in the pathogenesis of these tumors, while MCPyV integration probably acted as an additional trigger.

Cytotoxicity Assessment of a New Design for a Biodegradable Ureteral Mitomycin Drug-Eluting Stent in Urothelial Carcinoma Cell Culture.

Urothelial tumour of the upper urinary tract is a rare neoplasm, but unfortunately, it has a high recurrence rate. The reduction of these tumour recurrences could be achieved by the intracavitary instillation of adjuvant chemotherapy after nephron-sparing treatment in selected patients, but current instillation methods are ineffective. Therefore, the aim of this in vitro study is to evaluate the cytotoxic capacity of a new instillation technology through a biodegradable ureteral stent/scaffold coated with a silk fibroin matrix for the controlled release of mitomycin C as an anti-cancer drug. Through a comparative study, we assessed, in urothelial carcinoma cells in a human cancer T24 cell culture for 3 and 6 h, the cytotoxic capacity of mitomycin C by viability assay using the CCK-8 test (Cell counting Kit-8). Cell viability studies in the urothelial carcinoma cell line confirm that mitomycin C embedded in the polymeric matrix does not alter its cytotoxic properties and causes a significant decrease in cell viability at 6 h versus in the control groups. These findings have a clear biomedical application and could be of great use to decrease the recurrence rate in patients with upper tract urothelial carcinomas by increasing the dwell time of anti-cancer drugs.

Rotura de Pseudoaneurisma tras Pancreatitis Aguda Necrotizante que debuta como Hemorragia Digestiva Alta por Fistulización del Duodeno

Presentamos el caso de un varón de 64 años quien, tras un primer episodio de pancreatitis aguda necrotizante, reingresa a los 20 días por cuadro de dolor epigástrico intenso y posteriormente episodio de hemorragia digestiva alta en forma de hematemesis y melenas con inestabilización hemodinámica. Se realiza en ese momento gastroscopia urgente objetivándose probable fistula gastrointestinal en bulbo duodenal con coágulo adherido sin sangrado activo en ese momento por lo que se realiza angio-TC urgente que revela colección peripancreática necrótica con presencia de sangrado activo en su interior, procedente de la arteria pancreatoduodenal. La arteriografía urgente identificó imagen compatible con pseudoaneurisma arterial dependiente de la rama de arteria pancreatoduodenal, que fue embolizada con éxito. Desgraciadamente el paciente falleció en las horas posteriores, como consecuencia de un shock séptico secundario a colección pancreática infectada.

We present the case of a 64-year-old man who, after a first episode of acute pancreatitis, was readmitted 20 days later due to severe epigastric pain and later an episode of upper gastrointestinal bleeding in the form of hematemesis and melena with hemodynamic instability. An urgent gastroscopy was performed at that time, revealing a probable gastrointestinal fistula in the duodenal bulb with an adherent clot without active bleeding at that time, so an urgent CT angiography was performed that revealed a necrotic peripancreatic collection with the presence of active bleeding inside from the pancreatoduodenal artery. Urgent arteriography identified an image compatible with arterial pseudoaneurysm dependent on the pancreaticoduodenal artery branch, which was successfully embolized. Unfortunately, the patient died a few hours later as a result of septic shock secondary to an infected pancreatic collection.

Assessment of a Coated Mitomycin-Releasing Biodegradable Ureteral Stent as an Adjuvant Therapy in Upper Urothelial Carcinoma: A Comparative In Vitro Study.

A major limitation of the treatment of low-grade upper tract urothelial carcinoma is the difficulty of intracavitary instillation of adjuvant therapy. Therefore, the aim of this in vitro study was to develop and to assess a new design of biodegradable ureteral stent coated with a silk fibroin matrix for the controlled release of mitomycin C as a chemotherapeutic drug. For this purpose, we assessed the coating of a biodegradable ureteral stent, BraidStent®, with silk fibroin and subsequently loaded the polymeric matrix with two formulations of mitomycin to evaluate its degradation rate, the concentration of mitomycin released, and changes in the pH and the weight of the stent. Our results confirm that the silk fibroin matrix is able to coat the biodegradable stent and release mitomycin for between 6 and 12 h in the urinary environment. There was a significant delay in the degradation rate of silk fibroin and mitomycin-coated stents compared to bare biodegradable stents, from 6-7 weeks to 13-14 weeks. The present study has shown the feasibility of using mitomycin C-loaded silk fibroin for the coating of biodegradable urinary stents. The addition of mitomycin C to the coating of silk fibroin biodegradable stents could be an attractive approach for intracavitary instillation in the upper urinary tract.

Evaluation of Alternative Risk Stratification Systems in a Large Series of Solitary Fibrous Tumors with Molecular Findings and Ki-67 Index Data: Do They Improve Risk Assessment?

The clinical evolution of solitary fibrous tumors (SFTs) is often uncertain and several risk stratification systems (RSS) have been proposed. The Demicco et al. RSS is the most frequently implemented. In this study we aim to validate two alternative RSS (Sugita et al. and G-Score) using results for the Demicco RSS from a previous study of 97 SFTs. In addition, we aim to determine whether reclassified cases had any distinctive molecular features. As the Sugita et al. system substitutes mitotic count with Ki-67 index we also investigated whether Ki-67 results for tissue microarrays are comparable to those obtained using whole tissue sections. In the present study we detected that many cases classified by Demicco RSS as low-risk were reclassified as intermediate risk using the new system (G-score RSS). Kaplan-Meier survival plots for G-Score RSS showed that the low-risk and intermediate-risk SFTs had a similar evolution that contrasted with the more aggressive high-risk group. Moreover, the similar evolution in both low and intermediate-risk groups occurred despite the G-score system being stricter in classifying low-risk tumors. We observed that Sugita RSS does not provide any better risk stratification in comparison with the Demicco RSS, and testing both RSS in our series produced similar Kaplan-Meier survival data. We found some discordant results when comparing whole sections and the corresponding tissue microarrays samples, finding the hotspot areas easier to locate in whole sections. Forty-one SFTs with initial low-risk assigned by the Demicco RSS were reclassified as intermediate-risk by G-score finding both TP53 and HTER mutations in four cases, only HTER mutation in 11 cases, and only TP53 mutation in 2 cases. All six cases of SFT classified as high-risk by both the Demicco and G-score RSS suffered recurrence/metastasis, and half showed both TP53 and HTER mutations. Five SFTs were categorized as low-risk by both Demicco and G-score, of which 4 cases revealed HTER mutation. Regarding the outcome of these 5 patients, two were lost to follow-up, and one of the remaining three patients suffered recurrence. We believe that although the presence of both TP53 and HTER mutations may confer or be related to poor evolution, the isolated presence of HTER mutation alone would not necessarily be related to poor outcome. The G-score RSS more accurately identified low-risk patients than the other two risk models evaluated in the present series. Late recurrence/metastasis may occasionally be observed even in low-risk SFTs categorized by stricter classification systems such as the G-score RSS. These findings support the possibility that additional, as yet unknown factors may influence the clinical evolution of SFTs. In conclusion, given the possibility of late recurrence, long-term follow-up is recommended for all SFT patients, even in cases classified as low risk by the stricter G-score system. An integration of clinical, radiological, pathological, and molecular findings may improve SFT risk stratification and better predict patient outcome.

Hiperplasia de hipófise secundária a hipotireoidismo primário - relato de caso / Pituitary hyperplasia secondary to primary hypothyroidism - case report

A hiperplasia hipofisária é definida como um aumento não neoplásico no número de um dos tipos de células presentes na hipófise. Ela pode ocorrer por um processo fisiológico ou patológico. O hipotireoidismo primário prolongado é uma das causas patológicas desta condição, e ocorre devido a perda do feedback negativo. O objetivo desse relato foi demonstrar a presença de hiperplasia hipofisária em um paciente masculino com características corporais sugestivas de acromegalia. A investigação laboratorial confirmou a presença de hipotireoidismo primário e descartou a acromegalia. Foi instituído tratamento com levotiroxina, levando a regressão da hiperplasia hipofisária. Esse caso ilustra a importância de uma investigação apropriada em pacientes com hiperplasia hipofisária, bem como discute a fisiopatologia e o tratamento dessa doença.

Pituitary hyperplasia is defined as a non-neoplastic increase in the number of one of the cell types present in the pituitary gland. It can occur by a physiological or pathological process. Prolonged primary hypothyroidism is one of the pathological causes of this condition and occurs due to the lack of negative feedback. The objective of this report was to demonstrate the presence of pituitary hyperplasia in a male patient with body characteristics suggestive of acromegaly. Laboratory investigation confirmed the presence of primary hypothyroidism and ruled out acromegaly. Treatment with levothyroxine was instituted, leading to regression of pituitary hyperplasia. This case illustrates the importance of an appropriate investigation in patients with pituitary hyperplasia, as well as discussing the pathophysiology and treatment of this disease.

Solitary Fibrous Tumor: Integration of Clinical, Morphologic, Immunohistochemical and Molecular Findings in Risk Stratification and Classification May Better Predict Patient outcome.

Although solitary fibrous tumors (SFTs) have an unpredictable evolution, some specific clinicopathologic factors have been associated with the final outcome. We retrieved clinical, pathological and molecular data of 97 patients with a histological diagnosis of SFT and Signal transducer and activator of transcription 6 (STAT6) positivity. We retrospectively studied the pathological factors predictive of recurrence/metastasis and compared them with the clinical outcome. A wide immunohistochemical study and molecular analysis to detect NAB2/STAT6 gene fusion, tumor protein-53 (TP53) and/or (telomerase reverse transcriptase) TERT promotor mutation were performed. The risk of metastasis was calculated using the Demicco risk stratification system (RSS). The results were combined and examined to assess the accuracy of risk stratification and classification. The most common location was in non-extremities; 66% were located in soft tissue or subcutaneous areas and 92.8% in deep locations. On microscopic analysis, 38.1% of tumors revealed hypercellularity with a predominant patternless and/or hemangiopericytic growth pattern; 13.4% had ≥4 mitoses/10HPF; 16.5% showed necrosis, and almost half the tumors showed at least focal myxoid areas. Dedifferentiation was observed in three tumors. Immunomarker expression in SFTs was as follows: CD34 92.9%, CD99 57.1%, Bcl2 67.9%, neuroendocrine markers (at least 1) 25.7%, Desmin 14.3%, CK(AE1/AE3) 3%, Apoptotic Protease Activating Factor (APAF-1) 87% and finally Ki-67 ≥ 10% in 14.4%. The NAB2/STAT6 gene fusion was detected in 50 tumors. After a median follow-up of 90 months, 9.3% recurred, 11.3% metastasized, 10.3% died of disease and 76.2% were free of disease. TERT mutations were detected in 40.6% of the SFTs; the TP53 mutation was detected in 17%, and only 9.3% showed both mutations. According to the Demicco RSS, 6.1%, 11.3% and 82.4% of the tumors were classified as high, intermediate or low-risk of metastasis, respectively. All high-risk tumors had ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10, HTER and/or TP53 mutation and poor evolution. The intermediate risk SFTs with worse evolution displayed the HTER mutation. Almost all low-risk tumors had a favorable evolution, although four showed at least one adverse factor (Ki-67 ≥ 10, ≥4 mitoses/10HPF or high tumor size) and had a worse evolution. An integration of clinical, morphologic, immunohistochemical and molecular findings may improve risk stratification and classification and better predict patient outcome. The unfavorable course seems to be more frequent in high-risk SFTs, although it is not exceptional in low-risk SFTs either; hence, a long-term follow-up is required independently of the assigned risk stratification score. The inclusion of molecular findings in risk stratification systems could improve the precision in the classification of SFTs, especially those of intermediate risk. Future studies will be required to determine the most effective way to incorporate molecular analyses into RSS on SFTs. The coexistence of several adverse factors such as ≥4 mitoses/10HPF, necrosis, Ki-67 ≥ 10%, mutations in HTER and/or p53 may suggest a closer clinical follow-up regardless of the histological appearance of the tumor.

Emerging Applications of Bacteriocins as Antimicrobials, Anticancer Drugs, and Modulators of The Gastrointestinal Microbiota.

The use of bacteriocins holds great promise in different areas such as health, food, nutrition, veterinary, nanotechnology, among others. Many research groups worldwide continue to advance the knowledge to unravel a novel range of therapeutic agents and food preservatives. This review addresses the advances of bacteriocins and their producer organisms as biocontrol agents for applications in the medical industry and agriculture. Furthermore, the bacteriocin mechanism of action and structural characteristics will be reviewed. Finally, the potential role of bacteriocins to modulate the signaling in host-associated microbial communities will be discussed.

Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study.

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

Assessment of the Grades of Vesicoureteral Reflux in Stented Ureters: An Experimental Study.

INTRODUCTION: The aim of this experimental study is to assess, in a porcine model, the onset and grades of vesicoureteral reflux associated with ureteral stents. METHODS: Twenty-four female porcine models were used. A 4.7-Fr ureteral stent was placed in all right ureters and kept in place for 6 weeks. Follow-ups were performed on weeks 1, 3, 6, and 12. Ultrasonography, cystoscopy, and fluoroscopy were used to analyze grade of hydronephrosis, presence and grade of vesicoureteral reflux, bacteriuria, and macroscopic changes of the ureteral orifices. Vesicoureteral reflux was classified using a modification of the International Reflux Study Committee grades. RESULTS: 91.7% animals present vesicoureteral reflux, 89.5% grade IA, 3.5% grade IB, and 7% grade II. There is a significant increase in reflux during follow-ups at 3 and 6 weeks, whereas 6 weeks after removal, 26.3% of the ureters still present vesicoureteral reflux. Hydronephrosis and macroscopic changes of the ureteral orifice increase significantly with stenting, but there is no significant association between them and vesicoureteral reflux; the relationship between bacteriuria and the presence of vesicoureteral reflux is not significant either. CONCLUSION: Vesicoureteral reflux caused by ureteral stents in an animal model is mostly low grade and mainly affects the distal ureter.

Angiosarcomas: histology, immunohistochemistry and molecular insights with implications for differential diagnosis.

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.