Amyloid-beta pathology-induced nanoscale synaptic disruption:the case of the GABA_B-GIRK assembly

Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.

Cavitary Pulmonary Metastases: CT Features and Their Correlation with the Pathology of the Primary Malignancy

Objective: To study CT features of cavitary pulmonary metastases and to investigate the pos- sible relationship between CT features and the pathology of the primary lesions. Methods: CT ?ndings of 131 cavitary metastatic nodules in 40 patients with pathologically-proved pulmonary metastases were retrospectively analyzed. A comparison between CT signs and the pathologic types of the primary tumors was made. Results: Cavitary metastases and multiple solid nodules coexisted in all patients. Cavitary metastases presented as bubble (n=41), irregular (n=33), cystic (n=26) or small circular (n=31) cavities, with even (n=61) or uneven (n=70) thickness of the cavity wall. Of 131 cavitary nodules, diameter less than 15 mm was seen in 44, between 15–25 mm in 66, 25–40 mm in 17 and larger than 40 mm in 4 respectively. And the wall thickness of the cavity below 4 mm, between 4–15 mm and over 15 mm was respectively seen in 69, 44 and 18 metastatic nodules. Cavitary pulmonary metastases mainly occurred in patients whose primary malignancy was squamous cell carcinoma (n=13) or adenocarcinoma (n=22). Both squamous cell carcinoma and adenocarcinoma had its own CT characteristics. The occurrence of cavity bore no relationship to its site in the lung. Conclusion: Cavitary pulmonary metastases carries certain CT features and its occurrence is related to the pathologic type of the primary malignancy.

NLRP3-mediated autophagy dysfunction links gut microbiota dysbiosis to tau pathology in chronic sleep deprivation

Emerging evidence indicates that sleep deprivation(SD)can lead to Alzheimer’s disease(AD)-related pathological changes and cognitive decline.However,the underlying mechanisms remain obscure.In the present study,we identified the existence of a microbiota-gut-brain axis in cognitive deficits resulting from chronic SD and revealed a potential pathway by which gut microbiota affects cognitive functioning in chronic SD.Our findings demonstrated that chronic SD in mice not only led to cognitive decline but also induced gut microbiota dysbiosis,elevated NLRP3 inflammasome expression,GSK-3βactivation,autophagy dysfunction,and tau hyperphosphorylation in the hippocampus.Colonization with the“SD microbiota”replicated the pathological and behavioral abnormalities observed in chronic sleep-deprived mice.Remarkably,both the deletion of NLRP3 in NLRP3-/-mice and specific knockdown of NLRP3 in the hippocampus restored autophagic flux,suppressed tau hyperphosphorylation,and ameliorated cognitive deficits induced by chronic SD,while GSK-3βactivity was not regulated by the NLRP3 inflammasome in chronic SD.Notably,deletion of NLRP3 reversed NLRP3 inflammasome activation,autophagy deficits,and tau hyperphosphorylation induced by GSK-3βactivation in primary hippocampal neurons,suggesting that GSK-3β,as a regulator of NLRP3-mediated autophagy dysfunction,plays a significant role in promoting tau hyperphosphorylation.Thus,gut microbiota dysbiosis was identified as a contributor to chronic SD-induced tau pathology via NLRP3-mediated autophagy dysfunction,ultimately leading to cognitive deficits.Overall,these findings highlight GSK-3βas a regulator of NLRP3-mediated autophagy dysfunction,playing a critical role in promoting tau hyperphosphorylation.

Identification of pathological characteristics in pulmonary tuberculosis using polarization-sensitive optical coherence tomography

The low detection rate of Mycobacterium tuberculosis in clinical practice leads to a high rate of missed diagnosis for pulmonary tuberculosis(PTB).As a noninvasive,high-resolution,real-time imaging technology,polarization-sensitive optical coherence tomography(PS-OCT)may be feasible for the rapid identification of pathological feature.This study aimed to explore the feasibility of using PS-OCT to identify pathological features of PTB.In the experiments,PTB samples containing some surrounding lung tissues were imaged using PS-OCT.It is demonstrated that PS-OCT images showed good consistency with the corresponding pathological images and were able to identify PTB-related characteristic pathological regions.We think PS-OCT can serve as an effective supplement for the diagnosis of PTB,enabling rapid and accurate diagnosis,and aiding in the understanding of the pathological characteristics and pathophysiological processes of PTB.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease

This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.

Hysterectomies for Gynaecological Pathology: 56 Cases at the Segou Regional Hospital in Mali

Introduction: Hysterectomy is a surgical procedure involving partial or total removal of the uterus. It is the most common gynaecological surgery in the world. Objective: To describe the epidemio-clinical and prognostic aspects of gynaecological hysterectomies. Patients and methods: This was an 18-month retrospective prospective descriptive study with a six-month follow-up period from 1 December 2020 to 31 May 2022 carried out in the gynaecology department of the Segou regional hospital. Results: Fifty-six (56) hysterectomies were performed out of 118 gynaecological surgical procedures (47.45%). The mean age was 47 ± 11.77 years. Large multiparous women were the most common (50%), with an average parity of 4.58. The main indications were uterine fibroids (30.4%), precancerous lesions of the cervix (17.85%) and uterine prolapse (17.85%). The abdominal route was the most commonly used surgical route (82.14%). Hysterectomy was total in 100% of cases and associated with bilateral adnexectomy in 48.2% of cases. The intra- and post-operative prognosis was satisfactory in 94.6% of cases. No deaths were recorded. The average length of stay was 3.28 days, irrespective of the surgical approach. Three cases of dyspareunia were noted among those who had resumed sexual activity.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Evaluation of autoimmune phenomena in patients with nonalcoholic fatty liver disease on the basis of liver pathology

BACKGROUND Autoimmune phenomena can be used in some patients with nonalcoholic fatty liver disease(NAFLD)in the clinic,but these patients are not autoimmune hepatitis patients.AIM To determine whether autoimmunity is present in patients with NAFLD,this study was performed.METHODS A total of 104 patients with NAFLD diagnosed by liver biopsy at Tianjin Second People’s Hospital between 2019 and 2023 were enrolled.The patients were divided into three groups according to their biopsy results:The NAFL(n=36),nonalcoholic steatohepatitis(n=51),and liver cirrhosis groups(n=17).RESULTS The differences in IgA,an immune marker,among the three groups of patients were statistically significant(P=0.025).In all NAFLD patients,antinuclear antibody and anti-smooth muscle antibody were the most common autoantibodies.The antinuclear antibody detection rate was the highest at 48.1%.The cirrhosis group had the highest autoantibody positivity rate(64.7%).Portal enlargement is also common in NAFLD patients.The rates of positivity for portal lymphoplasmacytic infiltration,small bile duct hyperplasia and interfacial hepatitis were highest in the cirrhosis group;the differences between the cirrhosis group and the other two groups were significant(P<0.05).Hepatocellular rosettes were identified only in the cirrhosis group(11.8%).CONCLUSION Autoimmune phenomena occur in NAFLD patients,especially in patients with NAFLD-related cirrhosis,in whom this phenomenon may be more pronounced.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used classification.Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different shapes.However,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'infiltration.AIM To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'infiltration.METHODS Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023.Patients first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical treatment.Pathological images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and t-tests.RESULTS The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and B3.Statistical analyses revealed significant differences(aP<0.05)in the short and long calibers,area,location,and density between types A and B.Notably,there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3(P>0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP<0.05);no significant differences were found in the density or location(P>0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy,especially between the types A and B.

A Multi-Task Deep Learning Framework for Simultaneous Detection of Thoracic Pathology through Image Classification

Thoracic diseases pose significant risks to an individual's chest health and are among the most perilous medical diseases. They can impact either one or both lungs, which leads to a severe impairment of a person’s ability to breathe normally. Some notable examples of such diseases encompass pneumonia, lung cancer, coronavirus disease 2019 (COVID-19), tuberculosis, and chronic obstructive pulmonary disease (COPD). Consequently, early and precise detection of these diseases is paramount during the diagnostic process. Traditionally, the primary methods employed for the detection involve the use of X-ray imaging or computed tomography (CT) scans. Nevertheless, due to the scarcity of proficient radiologists and the inherent similarities between these diseases, the accuracy of detection can be compromised, leading to imprecise or erroneous results. To address this challenge, scientists have turned to computer-based solutions, aiming for swift and accurate diagnoses. The primary objective of this study is to develop two machine learning models, utilizing single-task and multi-task learning frameworks, to enhance classification accuracy. Within the multi-task learning architecture, two principal approaches exist soft parameter sharing and hard parameter sharing. Consequently, this research adopts a multi-task deep learning approach that leverages CNNs to achieve improved classification performance for the specified tasks. These tasks, focusing on pneumonia and COVID-19, are processed and learned simultaneously within a multi-task model. To assess the effectiveness of the trained model, it is rigorously validated using three different real-world datasets for training and testing.

Expanding role and scope of artificial intelligence in the field of gastrointestinal pathology

Digital pathology(DP)and its subsidiaries including artificial intelligence(AI)are rapidly making inroads into the area of diagnostic anatomic pathology(AP)including gastrointestinal(GI)pathology.It is poised to revolutionize the field of diagnostic AP.Historically,AP has been slow to adopt digital technology,but this is changing rapidly,with many centers worldwide transitioning to DP.Coupled with advanced techniques of AI such as deep learning and machine learning,DP is likely to transform histopathology from a subjective field to an objective,efficient,and transparent discipline.AI is increasingly integrated into GI pathology,offering numerous advancements and improvements in overall diagnostic accuracy,efficiency,and patient care.Specifically,AI in GI pathology enhances diagnostic accuracy,streamlines workflows,provides predictive insights,integrates multimodal data,supports research,and aids in education and training,ultimately improving patient care and outcomes.This review summarized the latest developments in the role and scope of AI in AP with a focus on GI pathology.The main aim was to provide updates and create awareness among the pathology community.

Pulmonary artery stent thrombosis and symptomatic pulmonary hypertension following COVID-19 infection in Alagille patient:A case report

BACKGROUND Alagille syndrome is a multisystem disease that results in various vascular anomalies,commonly involving the cardiac and pulmonary systems.To the best of our knowledge,there is no literature regarding the cardiovascular outcomes of these patients in association with coronavirus disease 2019(COVID-19).CASE SUMMARY A 34-year-old woman with a history of Alagille syndrome who underwent successful atrial septal defect with partial anomalous pulmonary veins and patent ductus arteriosus repair,as well as left pulmonary artery catheterization and stenting in childhood due to pulmonary stenosis.The patient was without any respiratory symptoms and was a dancer prior to contracting COVID-19.Several weeks after her COVID-19 infection,she developed left pulmonary artery stent thrombosis and subsequent symptomatic pulmonary hypertension.A treatment strategy of anticoagulation alongside pharmacological agents for pulmonary hypertension for 3 months followed by balloon pulmonary artery angioplasty to reopen the stenosis was unsuccessful.CONCLUSION In the era of COVID-19,patients with pulmonary vascular malformations and endovascular stents are at an increased risk for chronic thromboembolic disease.Patients may benefit from prophylactic antiplatelet or anticoagulation therapy.Stent thrombosis is a devastating phenomenon and should be treated urgently and aggressively with balloon pulmonary angioplasty,and/or a thrombolytic agent.

Retrospective analysis of pathological types and imaging features in pancreatic cancer: A comprehensive study

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies worldwide,with a poor prognosis often attributed to late diagnosis.Understanding the correlation between pathological type and imaging features is crucial for early detection and appropriate treatment planning.AIM To retrospectively analyze the relationship between different pathological types of pancreatic cancer and their corresponding imaging features.METHODS We retrospectively analyzed the data of 500 patients diagnosed with pancreatic cancer between January 2010 and December 2020 at our institution.Pathological types were determined by histopathological examination of the surgical spe-cimens or biopsy samples.The imaging features were assessed using computed tomography,magnetic resonance imaging,and endoscopic ultrasound.Statistical analyses were performed to identify significant associations between pathological types and specific imaging characteristics.RESULTS There were 320(64%)cases of pancreatic ductal adenocarcinoma,75(15%)of intraductal papillary mucinous neoplasms,50(10%)of neuroendocrine tumors,and 55(11%)of other rare types.Distinct imaging features were identified in each pathological type.Pancreatic ductal adenocarcinoma typically presents as a hypodense mass with poorly defined borders on computed tomography,whereas intraductal papillary mucinous neoplasms present as characteristic cystic lesions with mural nodules.Neuroendocrine tumors often appear as hypervascular lesions in contrast-enhanced imaging.Statistical analysis revealed significant correlations between specific imaging features and pathological types(P<0.001).CONCLUSION This study demonstrated a strong association between the pathological types of pancreatic cancer and imaging features.These findings can enhance the accuracy of noninvasive diagnosis and guide personalized treatment approaches.

A pulmonary metastatic breast phyllodes tumor and clinicopathology analysis

Objective Breast phyllodes tumors(PTs) are rare fibroepithelial tumors that are characterized by formation of foliation patterns. Behaviorally, only relatively poor prediction of PTs is possible based on their histological appearance. PTs are frequently misdiagnosed because they are difficult to differentiate from soft tissue tumors. In this report, we describe the pathological features of a rare case of PT and review the relevant literature, summarizing the essentials of the diagnosis and differential diagnosis, while attempting to avoid misdiagnosis or missed diagnosis of the tumor to the best of our abilities.Methods We present a case of pulmonary metastatic lobular tumor, analyzing the morphological [hematoxylin-eosin(HE) staining] and immunohistochemical(streptavidin perosidase method, SP) features of the tissue.Results Long spindle-shaped tumor cells were observed using microscopy. The cells were arranged in bundles, with a whirlpool pattern, and braided. The proliferation of the spindle cells was markedly atypical and karyokinesis was elevated. Residual ductal epithelium was detected in some areas, and the margins of the tumor tissues showed invasive growth. Immunohistochemical studies of the spindle-shaped tumor cells were positive for actin, PR, CD10, SMA, Bcl-2, and negative for CKP, S-100, CD34, ER. The Ki-67 index was 40%.Conclusion The spindle cell tumor identified in the lung should first be considered as a metastatic neosplasm, because most soft-tissue sarcomas commonly metastasize through the bloodstream to the lungs. Although malignant breast PTs are rare, a detailed medical history that includes prior surgical history is required to avoid wrongful or missed diagnosis.

Pulmonary embolism after shoulder surgery:Is it a real threat?

Pulmonary embolism(PE)is a rare but devastating complication of shoulder surgery.Apart from increased morbidity and mortality rates,it may significantly impair postoperative recovery and functional outcome.Its frequency accounts for up to 5.7%of all shoulder surgery procedures with a higher occurrence in women and patients older than 70 years.It is most commonly associated with thrombophilia,diabetes mellitus,obesity,smoking,hypertension,and a history of malignancy.PE usually occurs secondary to upper or lower-extremity deep vein thrombosis(DVT).However,in rare cases,the source of the thrombi cannot be determined.Prophylaxis for PE following shoulder surgery remains a topic of debate,and the standard of care does not routinely require prophylactic medication for DVT prophylaxis.Early ambulation and elastic stockings are important preventative measures for DVT of the lower extremity and medical agents such as aspirin,low-molecular-weight heparin,and vitamin K antagonists are indicated for high-risk patients,long-lasting operations,or concomitant severe acute respiratory syndrome coronavirus 2 infection.The most common symptoms of PE include chest pain and shortness of breath,but PE can also be asymptomatic in patients with intrinsic tolerance of hypoxia.Patients with DVT may also present with swelling and pain of the respective extremity.The treatment of PE includes inpatient or outpatient anticoagulant therapy if the patient is hemodynamically unstable or stable,respectively.Hemodynamic instability may require transfer to the intensive care unit,and cardiovascular arrest can be implicated in fatal events.An important issue for patients with PE in the postoperative period after shoulder surgery is residual stiffness due to a delay in rehabilitation and a prolonged hospital stay.Early physiotherapy and range-of-motion exercises do not adversely affect the prognosis of PE and are highly recommended to preserve shoulder mobility and function.

A Novel Perspective on Histopathology Provides Novel Insights into Surgical Effects in Pulmonary Atresia,Ventricular Septal Defect,and Major Aortopulmonary Collateral Arteries:A Case-Series Study

Background:Never had literatures characterized the relationship between the property of major aortopulmonary collateral arteries(MAPCAs)and outcomes of selective unifocalization of pulmonary atresia with ventricular septal defects and MAPCAs.Methods:This is a case-series study.Thirteen patients were included.Angiographybased assessment was conducted to determine whether collateral arteries should be unifocalized or treated with intraoperative ligature.Specimens were collected and stained by HE and ET+VG.Results:Twelve patients underwent one-stage unifocalization at a median age of 37 months(range:6–228 months)and a median weight of 14.0 kg(range:5.0–49.0 kg),which produced a favorable right ventricle to aortic systolic pressure ratio of no more than 0.5 except in one patient who died.Patients were divided into three groups:Group 1(n=6),had no native pulmonary arteries,and collateral arteries supplied all pulmonary blood;Group 2(n=6)presented dysplastic native pulmonary arteries on one or both sides,and in some lung lobes or segments,blood was supplied only by collateral arteries;Group 3(n=1)had well-developed left and right pulmonary arteries,and collateral arteries,and pulmonary arteries provided blood flow to the same segments.Pathological reports demonstrated two types of collateral arteries:Elastic arteries presented an arborization distribution similar to native pulmonary artery walls,while muscular arteries showed high resistance and distortion.We selectively unifocalized single-supply collateral arteries with morphologic features based on the arborization distribution.Conclusions:We found that there were two kinds of MAPCAs with different histology,and we performed selective UF for MAPCAs that might belong to the elastic artery.Selective unifocalization achieved a low right ventricle to aortic systolic pressure ratio and favorable surgical effects.

Thrombolysis and extracorporeal cardiopulmonary resuscitation for cardiac arrest due to pulmonary embolism:A case report

BACKGROUND Cardiac arrest caused by acute pulmonary embolism(PE)is the most serious clinical circumstance,necessitating rapid identification,immediate cardiopulmonary resuscitation(CPR),and systemic thrombolytic therapy.Extracorporeal CPR(ECPR)is typically employed as a rescue therapy for selected patients when conventional CPR is failing in settings where it can be implemented.CASE SUMMARY We present a case of a 69-year-old male who experienced a prolonged cardiac arrest in an ambulance with pulseless electrical activity.Upon arrival at the emergency department with ongoing manual chest compressions,bedside pointof-care ultrasound revealed an enlarged right ventricle without contractility.Acute PE was suspected as the cause of cardiac arrest,and intravenous thrombolytic therapy with 50 mg tissue plasminogen activator was administered during mechanical chest compressions.Despite 31 minutes of CPR,return of spontaneous circulation was not achieved until 8 minutes after initiation of Veno-arterial extracorporeal membrane oxygenation(ECMO)support.Under ECMO support,the hemodynamic status and myocardial contractility significantly improved.However,the patient ultimately did not survive due to intracerebral hemorrhagic complications,leading to death a few days later in the hospital.CONCLUSION This case illustrates the potential of combining systemic thrombolysis with ECPR for refractory cardiac arrest caused by acute PE,but it also highlights the increased risk of significant bleeding complications,including fatal intracranial hemorrhage.

Histopathology of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide.Its etiology is usually linked to environmental,dietary or lifestyle factors.HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed.Although this process is yet to be completely understood,this changing scenario also has impact on the material seen by pathologists,presenting them with new diagnostic dilemmas.Histopathologic criteria for diagnosing classical,progressed HCC are well established and known,but with an increase in detection of small and early HCCs due to routine screening programs,the diagnosis of these small lesions in core needle biopsies poses a difficult challenge.These lesions can be far more difficult to distinguish from one another than progressed HCC,which is usually a clear cut hematoxylin and eosin diagnosis.Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO.This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification.Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

Helicobacter pylori and oral pathology:Relationship with the gastric infection

Helicobacter pylori(H.pylori)has been found in the oral cavity and stomach,and its infection is one of the most frequent worldwide.We reviewed the literature and conducted a Topic Highlight,which identified studies reporting an association between H.pylori-infection in the oral cavity and H.pylori-positive stomach bacterium.This work was designed to determine whether H.pylori is the etiologic agent in periodontal disease,recurrent aphthous stomatitis(RAS),squamous cell carcinoma,burning and halitosis.Record selection focused on the highest quality studies and meta-analyses.We selected 48 articles reporting on the association between saliva and plaque and H.pylori-infection.In order to assess periodontal disease data,we included 12 clinical trials and 1 meta-analysis.We evaluated 13 published articles that addressed the potential association with RAS,and 6 with squamous cell carcinoma.Fourteen publications focused on our questions on burning and halitosis.There is a close relation between H.pylori infection in the oral cavity and the stomach.The mouth is the first extra-gastric reservoir.Regarding the role of H.pylori in the etiology of squamous cell carcinoma,no evidence is still available.