Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other nonviral cau...Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other nonviral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection.展开更多
Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neopl...Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, endoscopic ultrasound(EUS)-guided fine-needle aspiration(FNA) has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion, diagnose malignancy and collect cyst fluid for further diagnostic studies, such as pancreatic enzyme levels, molecular analysis and other tumor biomarkers. The current review will focus on EUSguided FNA and the cytological diagnosis for pancreatic cysts.展开更多
Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification ...Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.展开更多
Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic.However,approaches for its analysis by use of reverse transcription quantitative polymer...Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic.However,approaches for its analysis by use of reverse transcription quantitative polymerase chain reaction(RT-q PCR)are still far from standardized globally.To characterize inter-and intra-laboratory variability among results when using various methods deployed across Canada,aliquots from a real wastewater sample were spiked with surrogates of SARS-CoV-2(gamma-radiation inactivated SARS-CoV-2 and human coronavirus strain 229E[HCoV-229E])at low and high levels then provided"blind"to eight laboratories.Concentration estimates reported by individual laboratories were consistently within a 1.0-log_(10) range for aliquots of the same spiked condition.All laboratories distinguished between low-and high-spikes for both surrogates.As expected,greater variability was observed in the results amongst laboratories than within individual laboratories,but SARS-CoV-2 RNA concentration estimates for each spiked condition remained mostly within 1.0-log_(10) ranges.The no-spike wastewater aliquots provided yielded non-detects or trace levels(<20 gene copies/mL)of SARS-CoV-2 RNA.Detections appear linked to methods that included or focused on the solids fraction of the wastewater matrix and might represent in-situ SARS-CoV-2 to the wastewater sample.HCoV-229E RNA was not detected in the no-spike aliquots.Overall,all methods yielded comparable results at the conditions tested.Partitioning behavior of SARS-CoV-2 and spiked surrogates in wastewater should be considered to evaluate method effectiveness.A consistent method and laboratory to explore wastewater SARS-CoV-2 temporal trends for a given system,with appropriate quality control protocols and documented in adequate detail should succeed.展开更多
BACKGROUND Neuroendocrine tumors(NETs)are rare malignancies arising from the diffuse neuroendocrine system,often in the gastroenteropancreatic(GEP)tract.GEP-NETs,primarily involving the intestines(50%)and pancreas(30%...BACKGROUND Neuroendocrine tumors(NETs)are rare malignancies arising from the diffuse neuroendocrine system,often in the gastroenteropancreatic(GEP)tract.GEP-NETs,primarily involving the intestines(50%)and pancreas(30%),may occa-sionally secrete hormones,causing syndromes.Diagnosis relies on markers like chromogranin A,synaptophysin,and Ki-67,along with imaging modalities.Ri-sing NETs incidence is attributed to advancements in diagnostic modalities,parti-cularly endoscopic ultrasonography(EUS).EUS demonstrates high accuracy in detecting small lesions,assessing tumor depth,and identifying locoregional lymph nodes.Despite its proven diagnostic utility,there is limited data on EUS's role in evaluating GEP-NETs in resource-constrained settings like Pakistan.AIM To evaluate the diagnostic role of EUS in characterizing GEP-NETs based on clinical,histopathological,tumor grading,and site-specific differences.METHODS This single-center retrospective descriptive study was conducted at Aga Khan University Hospital,Karachi,a tertiary care hospital,from January 2021 to December 2023.Fourteen adult patients(≥18 years)with suspected NETs who underwent EUS and were diagnosed via histopathology were included.Data on demographics,clinical features,radiological findings,and histopathological characteristics were collected.Descriptive analysis was performed using SPSS version 23,with descriptive statistics expressed as means±SD for continuous variables and frequencies/percentages for categorical data.RESULTS A total of 14 adult GEP-NETs patients who underwent EUS were included,with a mean age of 52±14 years and the majority being male(71.4%).Common clinical presentations included weight loss(85.7%)and abdominal pain(78.6%).Computed tomography scans were performed in 92.9%of cases,with pancreatic masses detected in 42.9%of patients.EUS-guided fine needle biopsy(FNB)had a 100%diagnostic yield.The pancreas was the most common tumor site(57.1%).Histopathology revealed 78.6%of cases as well-differentiated NETs with 42.9%being grade II.Metastases were seen in 57.1%of patients,with the liver being the most common site.Surgical interventions were performed in 28.6%of patients,and all patients were alive at the time of study analysis.CONCLUSION EUS,with accurate imaging and effective EUS-FNB,is the gold standard for GEP-NET diagnosis,aiding tumor assessment and prognosis.Larger studies are needed to validate its impact on management outcomes.展开更多
Acellular mucin refers to pools of mucin without epithelial component,oftentimes harboring inflammatory cells.Acellular mucin can be observed in both neoplastic and non-neoplastic lower gastrointestinal(GI)conditions....Acellular mucin refers to pools of mucin without epithelial component,oftentimes harboring inflammatory cells.Acellular mucin can be observed in both neoplastic and non-neoplastic lower gastrointestinal(GI)conditions.While mucinous neoplasms are classified and staged using established guidelines,interobserver variability occurs when acellular mucin pools are encountered,leading to inconsistent interpretation and staging.In particular,acellular mucin found in regional lymph nodes of colorectal adenocarcinoma patients who have not received treatment presents a diagnostic challenge,as its prognostic implication is not clearly defined.Acellular mucin is also commonly seen in treated colorectal adenocarcinoma,post neoadjuvant therapy.Although acellular mucin is not counted toward T or N staging in this setting,variation in how pathologists report and stage these cases persists.Acellular mucin can also be seen in non-neoplastic specimens,such as those from interval appendectomies,appendiceal diverticula,colonic diverticulitis,volvulus,and Crohn’s disease where it may mimic a neoplastic lesion.Acellular mucin in this setting is often a byproduct of inflammation,increased luminal pressure,and mural defect.This review highlights the clinical relevance and diagnostic complexity of acellular mucin in pathologic conditions of the lower GI tract.Further studies are needed to clarify its prognostic value and develop standardized guidelines.展开更多
Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, en...Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.展开更多
BACKGROUND Gallbladder mucocele,also known as gallbladder hydrops,is a rare condition characterized by the distention of the gallbladder due to the accumulation of fluid or mucus within its lumen,primarily attributed ...BACKGROUND Gallbladder mucocele,also known as gallbladder hydrops,is a rare condition characterized by the distention of the gallbladder due to the accumulation of fluid or mucus within its lumen,primarily attributed to obstruction arising from a gallstone in the cystic duct or gallbladder neck.CASE SUMMARY We present a case of a 67-year-old woman with an incidentally discovered gallbladder mucocele,shedding light on the clinical presentation,causes,and histopathological findings.We performed a literature review including an analysis of 27 case reports,revealing the diverse spectrum of causative factors,clinical manifestations,diagnosis,and management.CONCLUSION This study underscores the importance of considering alternative diagnoses and highlights the significance of imaging techniques in narrowing down the differential diagnosis and histopathologic examination for a definitive diagnosis.展开更多
BACKGROUND Pancreatic fibrosis,which decreases risk of postoperative pancreatic fistula(POPF),can be estimated using extracellular volume fraction(ECVf).AIM To investigate the correlation between ECVf and pancreatic h...BACKGROUND Pancreatic fibrosis,which decreases risk of postoperative pancreatic fistula(POPF),can be estimated using extracellular volume fraction(ECVf).AIM To investigate the correlation between ECVf and pancreatic histology,as well as the usefulness of ECVf in predicting POPF.METHODS In 71 patients who underwent pancreatic resection,we caluculated pancreatic ECVf by comparing absolute enhancements of the pancreas and aorta between pre-contrast and equilibrium phases.Areas of fibrosis,fat,acini,and islets were calculated based on resection specimens.RESULTS ECVf correlated with fibrosis(r=0.724;P<0.001)and negatively correlated with acini(r=-0.510;P<0.001).Among 48 patients who underwent pancreatoduoden ectomy,21 developed POPF.Main pancreatic duct diameter≤2 mm and ECVf<36%were selected as risk factors by multivariate analysis[respective odds ratios(OR)and P values,4.26 and P=0.048;OR=11.07 and P=0.036].Using these factors as a risk score(0-2 points),POPF occurred in 0%,50%,and 70%of patients with 0,1,and 2 points,respectively.CONCLUSION ECVf is useful in predicting acinar loss and pancreatic fibrosis,and ECVf<36%may be a risk factor for POPF.展开更多
Background:The Akreos®AO60 intraocular lens(IOL)has been employed for scleral fixation in eyes without capsular support,although surgical complications,including IOL opacification,have been reported.This study ai...Background:The Akreos®AO60 intraocular lens(IOL)has been employed for scleral fixation in eyes without capsular support,although surgical complications,including IOL opacification,have been reported.This study aims to evaluate the outcomes and complications associated with scleral fixation of the Akreos®AO60 IOL in vitrectomized eyes,with a particular focus on IOL opacification.Methods:Electronic medical records of consecutive eyes that underwent scleral-fixation of the Akreos®AO60 lens using Gore-tex®sutures from 2017 to 2022 were reviewed.The following parameters were collected:age,sex,laterality,past ocular/medical history,surgical indication,pre-operative visual acuity(VA)and intraocular pressure(IOP),surgical procedure,and post-operative VA and IOP.The types of complications,onset,management,and outcomes were also documented.Descriptive statistics,Wilcoxon signed-rank test,and Fisher’s exact test were employed for statistical analysis.Results:Eighty-nine eyes of 86 patients aged 31-100 years were included.The most common surgical indication was non-traumatic IOL displacement.Retinal tears and localized choroidal hemorrhage were found intraoperatively in 7.9%and 1.1%,respectively.The most common post-operative complications were vitreous hemorrhage(13.5%),corneal edema(12.4%),ocular hypotony(11.2%),and IOL opacification(11.2%).IOL opacification was associated with intra-/post-operative exposure to air/gas[odds ratio(OR):12.24;95%confidence interval(CI),1.46-103.0;P=0.006].Mean logarithm of the minimum angle of resolution(logMAR)best-reported VA(BRVA)improved from 1.22±0.77 pre-operatively to 0.56±0.67 on latest follow-up(P<0.001).Conclusions:The majority of the complications from scleral-fixation of the Akreos®AO60 lens in vitrectomized eyes were mild and transient;however,a proportion required surgical intervention.A significant risk for opacification was found in IOLs exposed to air/gas,although VA was often maintained.展开更多
Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG l...Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG linker,and the payload DXD.The antibody was engineered in 293 cells and conjugated via thiol-based chemistry,achieving a drug-to-antibody ratio(DAR)of eight.Comprehensive preclinical assessments,including in vitro and in vivo studies using BCa cells,organoids,cell-derived xenograft and patient-derived xenograft(PDX)models,were conducted to evaluate efficacy,targeting ability,mechanism,safety and tissue distribution.LZU-WZLYFG001 demonstrated high purity,targeting specificity and low endotoxin levels,and it significantly inhibited BCa cell proliferation,migration and invasion at nanomolar concentrations,with efficacy strongly associated with FGFR3 expression levels.Mechanistic studies showed binding to FGFR3,internalization and lysosomal release of LZU-WZLYFG001.In organoid and xenograft models,LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine+cisplatin(GC)regimen,particularly in GC-resistant PDX tumors,while also showing robust 3D penetration,a bystander effect,and no significant short-term toxicity.展开更多
Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained defic...Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.展开更多
Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus a...Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.展开更多
The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of...The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.展开更多
Hepatic inflammatory pseudotumors are uncommon benign lesions.Accurately diagnosing hepatic inflammatory pseudotumor can be very challenging because the clinical presentation and radiological appearances are nonspecif...Hepatic inflammatory pseudotumors are uncommon benign lesions.Accurately diagnosing hepatic inflammatory pseudotumor can be very challenging because the clinical presentation and radiological appearances are nonspecific and cannot be certainly distinguished from malignant neoplastic processes.Herein,we present a case of hepatic IPT in an 8-yearold boy who presented to clinic with a 3-mo history of a tender hepatic mass,fever of unknown origin,and9-kg weight loss.The physical examination was notable for tender hepatomegaly.Laboratory investigations were notable for a normal hepatic profile and elevated erythrocyte sedimentation rate and C-reactive protein.A T2-attenuated magnetic resonance imaging scan of the abdomen showed a 4.7 cm x 4.7 cm x 6.6cm,contrast-enhancing,hyper-intense,well-defined lesion involving the right hepatic lobe.In view of the unremitting symptoms,tender hepatomegaly,thrombosed right hepatic vein,nonspecific radiological findings,and high suspicion of a deep-seated underlying infection or malignancy,a right hepatic lobectomy was recommended.Microscopically,the hepatic lesion exhibited a mixture of inflammatory cells(histiocytes,plasma cells,mature lymphocytes,and occasional multinucleated giant cells) in a background of dense fibrous tissue.Immunohistochemically,the cells stained negative for SMA,ALK-1,CD-21 and CD-23,diffusely positive for CD-68,and focally positive for lgG4.The final histopathological diagnosis was consistent with hepatic IPT.At the postoperative 4-mo follow-up,the patient was asymptomatic without radiological evidence of recurrence.展开更多
AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and c...AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P<0.01),sporadic dysplasia(68.80±4.42,P<0.01),sporadic cancer(74.80±4.91,P<0.001),and CAC(57.50±5.11,P<0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P<0.05,P<0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P<0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P<0.001 vs normal,P<0.001 vs CAC)and sporadic CRC(0.47±0.23,P<0.001 vs normal,P<0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer.展开更多
BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal trac...BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally.Though they have been a well-documented entity in the pancreas,where the exocrine-endocrine mixed tumors have been known for a while,recognition and accurate diagnosis of these tumors in the colon and rectum,to date,remains a challenge.This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification.Therefore,dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers.Though,most of these tumors are high grade and of advanced stage,intermediate and low grade lesions of these mixed tumors are also increasingly been reported.There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape,clinicoradiological features,pathology,treatment,prognosis,the current status of the management of the primary lesions,their recurrences and metastases.METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed,MEDLINE and GOOGLE scholar.The following search terms[“mixed tumors colon”OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors]were used.Eligibility criteria were defined and all potential relevant items,including full articles and/or abstracts were independently reviewed,assessed and agreed upon items were selected for in-depth analysis.RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review.This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives,nomenclature,clinicoradiological features,pathology,treatment,prognosis and the current status of the management of both the primary lesions,their recurrences and metastases.Gaps in knowledge have also been identified and discussed.An important outcome of this manuscript is the justified proposal for a new,simple,clinically relevant,non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms(MEENs).CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high,intermediate or low grade malignant potential.This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.展开更多
The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breas...The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.展开更多
Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have tr...Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.展开更多
Lymphangiomas are rare benign cystic tumors of the lymphatic system.Retroperitoneal lymphangiomas account for 1%of all lymphangiomas,and approximately 186 cases have been reported.They may clinically present as a palp...Lymphangiomas are rare benign cystic tumors of the lymphatic system.Retroperitoneal lymphangiomas account for 1%of all lymphangiomas,and approximately 186 cases have been reported.They may clinically present as a palpable abdominal mass and can cause diagnostic dilemmas with other retroperitoneal cystic tumors,including those arising from the liver,kidney and pancreas.This report describes the rare case of a cystic retroperitoneal lymphangioma in a 54-year-old male patient.The lymphangioma had progressed to the point of inducing clinical symptoms of abdominal distention,abdominal pain,anorexia,fever,nausea and diarrhea.Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum and extending into the pelvis.Surgical removal of the cyst was accomplished without incident.A benign cystic retroperitoneal lymphangioma was diagnosed on histology and confirmed with immunohistochemical stains.展开更多
文摘Liver biopsy evaluation plays a critical role in management of patients with viral hepatitis C. In patients with acute viral hepatitis, a liver biopsy, though uncommonly performed, helps to rule out other nonviral causes of deranged liver function. In chronic viral hepatitis C, it is considered the gold standard in assessment of the degree of necroinflammation and the stage of fibrosis, to help guide treatment and determine prognosis. It also helps rule out any concomitant diseases such as steatohepatitis, hemochromatosis or others. In patients with chronic progressive liver disease with cirrhosis and dominant nodules, a targeted liver biopsy is helpful in differentiating a regenerative nodule from dysplastic nodule or hepatocellular carcinoma. In the setting of transplantation, the liver biopsy helps distinguish recurrent hepatitis C from acute rejection and also is invaluable in the diagnosis of fibrosing cholestatic hepatitis, a rare variant of recurrent hepatitis C. This comprehensive review discusses the entire spectrum of pathologic findings in the course of hepatitis C infection.
文摘Recent advances in imaging technology have resulted in an increase in incidental discoveries of pancreatic cystic lesions. Pancreatic cysts comprise a wide variety of lesions and include non-neoplastic cysts and neoplastic cysts. Because some pancreatic cysts have more of a malignant potential than others, it is absolutely essential that an accurate diagnosis is rendered so that effective care can be given to each patient. In many centers, endoscopic ultrasound(EUS)-guided fine-needle aspiration(FNA) has emerged as the modality of choice that enables one to distinguish between mucinous and non-mucinous lesion, diagnose malignancy and collect cyst fluid for further diagnostic studies, such as pancreatic enzyme levels, molecular analysis and other tumor biomarkers. The current review will focus on EUSguided FNA and the cytological diagnosis for pancreatic cysts.
文摘Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.
基金supported by a CHEO (Children’s Hospital of Eastern Ontario) CHAMO (Children’s Hospital Academic Medical Organization) grant, awarded to Dr.Alex E.Mac Kenziesupported by the “Next generation solutions to ensure healthy water resources for future generations” funded by the Global Water Futures program, Canada First Research Excellence Fund (#419205)+7 种基金supported by the Canada Research Chairs Program of the Natural Sciences and Engineering Research Council of Canada (NSERC)supported by funding from NSERC Discovery and Strategic Grant Programssupported by funding from an NSERC Discovery Grantsupported by the NSERC Alliance COVID-19 Grantby Mitacs through the Mitacs Accelerate programsupported by Canadian Institutes of Health Research (CIHR), Alberta Innovates, Alberta Health-Water for Life Strategysupported by the BC center for Disease Control, BC center for Disease Control Foundation for Public Health and Metro Vancouversupported by the Canada Research Chairs Program of NSERC。
文摘Detection of SARS-CoV-2 RNA in wastewater is a promising tool for informing public health decisions during the COVID-19 pandemic.However,approaches for its analysis by use of reverse transcription quantitative polymerase chain reaction(RT-q PCR)are still far from standardized globally.To characterize inter-and intra-laboratory variability among results when using various methods deployed across Canada,aliquots from a real wastewater sample were spiked with surrogates of SARS-CoV-2(gamma-radiation inactivated SARS-CoV-2 and human coronavirus strain 229E[HCoV-229E])at low and high levels then provided"blind"to eight laboratories.Concentration estimates reported by individual laboratories were consistently within a 1.0-log_(10) range for aliquots of the same spiked condition.All laboratories distinguished between low-and high-spikes for both surrogates.As expected,greater variability was observed in the results amongst laboratories than within individual laboratories,but SARS-CoV-2 RNA concentration estimates for each spiked condition remained mostly within 1.0-log_(10) ranges.The no-spike wastewater aliquots provided yielded non-detects or trace levels(<20 gene copies/mL)of SARS-CoV-2 RNA.Detections appear linked to methods that included or focused on the solids fraction of the wastewater matrix and might represent in-situ SARS-CoV-2 to the wastewater sample.HCoV-229E RNA was not detected in the no-spike aliquots.Overall,all methods yielded comparable results at the conditions tested.Partitioning behavior of SARS-CoV-2 and spiked surrogates in wastewater should be considered to evaluate method effectiveness.A consistent method and laboratory to explore wastewater SARS-CoV-2 temporal trends for a given system,with appropriate quality control protocols and documented in adequate detail should succeed.
文摘BACKGROUND Neuroendocrine tumors(NETs)are rare malignancies arising from the diffuse neuroendocrine system,often in the gastroenteropancreatic(GEP)tract.GEP-NETs,primarily involving the intestines(50%)and pancreas(30%),may occa-sionally secrete hormones,causing syndromes.Diagnosis relies on markers like chromogranin A,synaptophysin,and Ki-67,along with imaging modalities.Ri-sing NETs incidence is attributed to advancements in diagnostic modalities,parti-cularly endoscopic ultrasonography(EUS).EUS demonstrates high accuracy in detecting small lesions,assessing tumor depth,and identifying locoregional lymph nodes.Despite its proven diagnostic utility,there is limited data on EUS's role in evaluating GEP-NETs in resource-constrained settings like Pakistan.AIM To evaluate the diagnostic role of EUS in characterizing GEP-NETs based on clinical,histopathological,tumor grading,and site-specific differences.METHODS This single-center retrospective descriptive study was conducted at Aga Khan University Hospital,Karachi,a tertiary care hospital,from January 2021 to December 2023.Fourteen adult patients(≥18 years)with suspected NETs who underwent EUS and were diagnosed via histopathology were included.Data on demographics,clinical features,radiological findings,and histopathological characteristics were collected.Descriptive analysis was performed using SPSS version 23,with descriptive statistics expressed as means±SD for continuous variables and frequencies/percentages for categorical data.RESULTS A total of 14 adult GEP-NETs patients who underwent EUS were included,with a mean age of 52±14 years and the majority being male(71.4%).Common clinical presentations included weight loss(85.7%)and abdominal pain(78.6%).Computed tomography scans were performed in 92.9%of cases,with pancreatic masses detected in 42.9%of patients.EUS-guided fine needle biopsy(FNB)had a 100%diagnostic yield.The pancreas was the most common tumor site(57.1%).Histopathology revealed 78.6%of cases as well-differentiated NETs with 42.9%being grade II.Metastases were seen in 57.1%of patients,with the liver being the most common site.Surgical interventions were performed in 28.6%of patients,and all patients were alive at the time of study analysis.CONCLUSION EUS,with accurate imaging and effective EUS-FNB,is the gold standard for GEP-NET diagnosis,aiding tumor assessment and prognosis.Larger studies are needed to validate its impact on management outcomes.
文摘Acellular mucin refers to pools of mucin without epithelial component,oftentimes harboring inflammatory cells.Acellular mucin can be observed in both neoplastic and non-neoplastic lower gastrointestinal(GI)conditions.While mucinous neoplasms are classified and staged using established guidelines,interobserver variability occurs when acellular mucin pools are encountered,leading to inconsistent interpretation and staging.In particular,acellular mucin found in regional lymph nodes of colorectal adenocarcinoma patients who have not received treatment presents a diagnostic challenge,as its prognostic implication is not clearly defined.Acellular mucin is also commonly seen in treated colorectal adenocarcinoma,post neoadjuvant therapy.Although acellular mucin is not counted toward T or N staging in this setting,variation in how pathologists report and stage these cases persists.Acellular mucin can also be seen in non-neoplastic specimens,such as those from interval appendectomies,appendiceal diverticula,colonic diverticulitis,volvulus,and Crohn’s disease where it may mimic a neoplastic lesion.Acellular mucin in this setting is often a byproduct of inflammation,increased luminal pressure,and mural defect.This review highlights the clinical relevance and diagnostic complexity of acellular mucin in pathologic conditions of the lower GI tract.Further studies are needed to clarify its prognostic value and develop standardized guidelines.
文摘Background: Neurodevelopmental abnormalities in experimental fetal alcohol spectrum disorder (FASD) are associated with impaired signaling through complex pathways that mediate neuronal survival, growth, migration, energy metabolism, and plasticity. Gestational dietary soy prevents alcohol-related impairments in placentation and FASD-associated fetal anomalies. Objective: This study was designed to determine if gestational dietary soy would be sufficient to normalize cognitive function in young adolescent offspring after chronic in utero exposure to alcohol. In addition, efforts were made to characterize the mechanisms of FASD prevention by maternal dietary soy. Methods: Pregnant Long Evans rats were fed isocaloric liquid diets containing 0% or 26% caloric ethanol with casein or soy isolate as the protein source from gestation day 6 through delivery/postnatal day 0 (P0). From P24 - P28, the offspring were subjected to Morris water maze (MWM) testing, and on P35, they were sacrificed to harvest temporal lobes for histopathologic and molecular studies. Results: The in-utero ethanol-exposed offspring exhibited significant performance impairments on the MWM test, and they had a significantly reduced mean brain weight with neuronal loss in the CA1 hippocampal region and evidence of white matter myelin loss. Gestational dietary soy nearly normalized MWM performance and preserved brain weight, hippocampal CA1 architecture, and white matter myelin staining in alcohol-exposed offspring. Mechanistically, the main positive effects of soy included increased temporal lobe expression of HES-1 and HIF-1α, reflecting enhanced Notch signaling, and broadly increased expression of GnRH network molecules, including Erb1, Gper1, GnRH, GnRH-R, KiSS, and KiSS-R, irrespective of gestational ethanol exposure. Conclusions: Dietary soy intervention early in pregnancy may reduce FASD-associated cognitive deficits. The findings suggest that targeting Notch and GnRH-related networks may help reduce long-term disability with FASD. Additional mechanistic and experimental research is needed to determine if longer-duration, postnatal dietary soy could prevent the adverse neurobehavioral effects of FASD.
文摘BACKGROUND Gallbladder mucocele,also known as gallbladder hydrops,is a rare condition characterized by the distention of the gallbladder due to the accumulation of fluid or mucus within its lumen,primarily attributed to obstruction arising from a gallstone in the cystic duct or gallbladder neck.CASE SUMMARY We present a case of a 67-year-old woman with an incidentally discovered gallbladder mucocele,shedding light on the clinical presentation,causes,and histopathological findings.We performed a literature review including an analysis of 27 case reports,revealing the diverse spectrum of causative factors,clinical manifestations,diagnosis,and management.CONCLUSION This study underscores the importance of considering alternative diagnoses and highlights the significance of imaging techniques in narrowing down the differential diagnosis and histopathologic examination for a definitive diagnosis.
文摘BACKGROUND Pancreatic fibrosis,which decreases risk of postoperative pancreatic fistula(POPF),can be estimated using extracellular volume fraction(ECVf).AIM To investigate the correlation between ECVf and pancreatic histology,as well as the usefulness of ECVf in predicting POPF.METHODS In 71 patients who underwent pancreatic resection,we caluculated pancreatic ECVf by comparing absolute enhancements of the pancreas and aorta between pre-contrast and equilibrium phases.Areas of fibrosis,fat,acini,and islets were calculated based on resection specimens.RESULTS ECVf correlated with fibrosis(r=0.724;P<0.001)and negatively correlated with acini(r=-0.510;P<0.001).Among 48 patients who underwent pancreatoduoden ectomy,21 developed POPF.Main pancreatic duct diameter≤2 mm and ECVf<36%were selected as risk factors by multivariate analysis[respective odds ratios(OR)and P values,4.26 and P=0.048;OR=11.07 and P=0.036].Using these factors as a risk score(0-2 points),POPF occurred in 0%,50%,and 70%of patients with 0,1,and 2 points,respectively.CONCLUSION ECVf is useful in predicting acinar loss and pancreatic fibrosis,and ECVf<36%may be a risk factor for POPF.
文摘Background:The Akreos®AO60 intraocular lens(IOL)has been employed for scleral fixation in eyes without capsular support,although surgical complications,including IOL opacification,have been reported.This study aims to evaluate the outcomes and complications associated with scleral fixation of the Akreos®AO60 IOL in vitrectomized eyes,with a particular focus on IOL opacification.Methods:Electronic medical records of consecutive eyes that underwent scleral-fixation of the Akreos®AO60 lens using Gore-tex®sutures from 2017 to 2022 were reviewed.The following parameters were collected:age,sex,laterality,past ocular/medical history,surgical indication,pre-operative visual acuity(VA)and intraocular pressure(IOP),surgical procedure,and post-operative VA and IOP.The types of complications,onset,management,and outcomes were also documented.Descriptive statistics,Wilcoxon signed-rank test,and Fisher’s exact test were employed for statistical analysis.Results:Eighty-nine eyes of 86 patients aged 31-100 years were included.The most common surgical indication was non-traumatic IOL displacement.Retinal tears and localized choroidal hemorrhage were found intraoperatively in 7.9%and 1.1%,respectively.The most common post-operative complications were vitreous hemorrhage(13.5%),corneal edema(12.4%),ocular hypotony(11.2%),and IOL opacification(11.2%).IOL opacification was associated with intra-/post-operative exposure to air/gas[odds ratio(OR):12.24;95%confidence interval(CI),1.46-103.0;P=0.006].Mean logarithm of the minimum angle of resolution(logMAR)best-reported VA(BRVA)improved from 1.22±0.77 pre-operatively to 0.56±0.67 on latest follow-up(P<0.001).Conclusions:The majority of the complications from scleral-fixation of the Akreos®AO60 lens in vitrectomized eyes were mild and transient;however,a proportion required surgical intervention.A significant risk for opacification was found in IOLs exposed to air/gas,although VA was often maintained.
基金supported by the Major Science and Technology Special Project of Gansu Province(24ZDFA002)the National Natural Science Foundation of China(82060459)+1 种基金the Key Research and Development Program of Gansu Province(23YFFA0007)the Joint Research Fund of Gansu Province(23JRRA1511)。
文摘Given the critical shortage of antibody-drug conjugates(ADCs)for bladder cancer(BCa),we developed a novel FGFR3-targeted ADC,LZU-WZLYFG001,composed of a humanized anti-FGFR3 IgG1 monoclonal antibody,a cleavable GGFG linker,and the payload DXD.The antibody was engineered in 293 cells and conjugated via thiol-based chemistry,achieving a drug-to-antibody ratio(DAR)of eight.Comprehensive preclinical assessments,including in vitro and in vivo studies using BCa cells,organoids,cell-derived xenograft and patient-derived xenograft(PDX)models,were conducted to evaluate efficacy,targeting ability,mechanism,safety and tissue distribution.LZU-WZLYFG001 demonstrated high purity,targeting specificity and low endotoxin levels,and it significantly inhibited BCa cell proliferation,migration and invasion at nanomolar concentrations,with efficacy strongly associated with FGFR3 expression levels.Mechanistic studies showed binding to FGFR3,internalization and lysosomal release of LZU-WZLYFG001.In organoid and xenograft models,LZU-WZLYFG001 exhibited superior efficacy compared with the gemcitabine+cisplatin(GC)regimen,particularly in GC-resistant PDX tumors,while also showing robust 3D penetration,a bystander effect,and no significant short-term toxicity.
文摘Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.
基金supported by grants from AOTrauma, Clinical Priority Program (Davos, Switzerland)NIH NIAMS (P50 AR072000 and P30 AR069655)+9 种基金supported by grants from NIH NIAMS P30 AR069655 pilotAO Trauma Research Fellowship (Davos, Switzerland)supported by grants from the NIH (R01 AR43510 and R01 AG049994)supported by grants from the NIH (P30 AR061307 and T32 AR53459)the NIH (R21 AR074571 and R21 AR073321)supported by grants from the NIH (R21 AR073321, R21 AR500710 and P30 AR06965501 Pilot)supported by grants from the NIH (R21 AI119646)supported by grants from Amedica Incsupported by grants from Bristol-Myers, Astellas, and Asahi-Kaseisupported by the Goldstein Award from the Department of Orthopaedics, University of Rochester, Rochester, NY
文摘Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, S.aureus intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.
文摘The identification of novel biomarkers for early prostate cancer diagnosis is highly important because early detection and treatment are critical for the medical management of patients. Disruption in the continuity of both the basal cell layer and basement membrane is essential for the progression of high-grade prostatic intraepithelial neoplasia （HGPIN） to invasive adenocarcinoma in human prostate. The molecules involved in the conversion to an invasive phenotype are the subject of intense scrutiny. We have previously reported that matrix metalloproteinase-26 （MMP-26） promotes the invasion of human prostate cancer cells via the cleavage of basement membrane proteins and by activating the zymogen form of MMP-9. Furthermore, we have found that tissue inhibitor of metalloproteinases-4 （TIMP-4） is the most potent endogenous inhibitor of MMP-26. Here we demonstrate higher （p〈0.0001） MMP-26 and TIMP-4 expression in HGPIN and cancer, compared to non-neoplastic acini. Their expression levels are highest in HGPIN, but decline in invasive cancer （p〈0.001 for each） in the same tissues. Immunohistochemical staining of serial prostate cancer tissue sections suggests colocalization of MMP-26 and TIMP-4. The present study indicates that MMP-26 and TIMP-4 may play an integral role during the conversion of HGPIN to invasive cancer and may also serve as markers for early prostate cancer diagnosis.
文摘Hepatic inflammatory pseudotumors are uncommon benign lesions.Accurately diagnosing hepatic inflammatory pseudotumor can be very challenging because the clinical presentation and radiological appearances are nonspecific and cannot be certainly distinguished from malignant neoplastic processes.Herein,we present a case of hepatic IPT in an 8-yearold boy who presented to clinic with a 3-mo history of a tender hepatic mass,fever of unknown origin,and9-kg weight loss.The physical examination was notable for tender hepatomegaly.Laboratory investigations were notable for a normal hepatic profile and elevated erythrocyte sedimentation rate and C-reactive protein.A T2-attenuated magnetic resonance imaging scan of the abdomen showed a 4.7 cm x 4.7 cm x 6.6cm,contrast-enhancing,hyper-intense,well-defined lesion involving the right hepatic lobe.In view of the unremitting symptoms,tender hepatomegaly,thrombosed right hepatic vein,nonspecific radiological findings,and high suspicion of a deep-seated underlying infection or malignancy,a right hepatic lobectomy was recommended.Microscopically,the hepatic lesion exhibited a mixture of inflammatory cells(histiocytes,plasma cells,mature lymphocytes,and occasional multinucleated giant cells) in a background of dense fibrous tissue.Immunohistochemically,the cells stained negative for SMA,ALK-1,CD-21 and CD-23,diffusely positive for CD-68,and focally positive for lgG4.The final histopathological diagnosis was consistent with hepatic IPT.At the postoperative 4-mo follow-up,the patient was asymptomatic without radiological evidence of recurrence.
基金Supported by National Institutes of Health Grants,No.U56 CA126379(to Isidro AA and Appleyard CB)and No.R25-GM082406(to Isidro RA)National Science Foundation:Puerto Rico Louis Stokes Alliance for Minority Participation,NSF Project No.0601843(to Isidro RA)The PSMHS Molecular Biology Core Lab,RCMI Grant No.RR003050/MD007579
文摘AIM:To determine the expression of neurokinin-1receptor(NK-1R),phosphorylated epidermal growth factor receptor(p EGFR),cyclooxygenase-2(Cox-2),and vitamin D receptor(VDR)in normal,inflammatory bowel disease(IBD),and colorectal neoplasia tissues from Puerto Ricans.METHODS:Tissues from patients with IBD,colitisassociated colorectal cancer(CAC),sporadic dysplasia,and sporadic colorectal cancer(CRC),as well as normal controls,were identified at several centers in Puerto Rico.Archival formalin-fixed,paraffin-embedded tissues were de-identified and processed by immunohistochemistry for NK-1R,p EGFR,Cox-2,and VDR.Pictures of representative areas of each tissues diagnosis were taken and scored by three observers using a4-point scale that assessed intensity of staining.Tissues with CAC were further analyzed by photographing representative areas of IBD and the different grades of dysplasia,in addition to the areas of cancer,within each tissue.Differences in the average age between the five patient groups were assessed with one-way analysis of variance and Tukey-Kramer multiple comparisons test.The mean scores for normal tissues and tissues with IBD,dysplasia,CRC,and CAC were calculatedand statistically compared using one-way analysis of variance and Dunnett’s multiple comparisons test.Correlations between protein expression patterns were analyzed with the Pearson’s product-moment correlation coefficient.Data are presented as mean±SE.RESULTS:On average,patients with IBD were younger(34.60±5.81)than normal(63.20±6.13,P<0.01),sporadic dysplasia(68.80±4.42,P<0.01),sporadic cancer(74.80±4.91,P<0.001),and CAC(57.50±5.11,P<0.05)patients.NK-1R in cancer tissue(sporadic CRC,1.73±0.34;CAC,1.57±0.53)and sporadic dysplasia(2.00±0.45)were higher than in normal tissues(0.73±0.19).p EGFR was significantly increased in sporadic CRC(1.53±0.43)and CAC(2.25±0.47)when compared to normal tissue(0.07±0.25,P<0.05,P<0.001,respectively).Cox-2 was significantly increased in sporadic colorectal cancer(2.20±0.23 vs 0.80±0.37 for normal tissues,P<0.05).In comparison to normal(2.80±0.13)and CAC(2.50±0.33)tissues,VDR was significantly decreased in sporadic dysplasia(0.00±0.00,P<0.001 vs normal,P<0.001 vs CAC)and sporadic CRC(0.47±0.23,P<0.001 vs normal,P<0.001 vs CAC).VDR levels negatively correlated with NK-1R(r=-0.48)and p EGFR(r=-0.56)in normal,IBD,sporadic dysplasia and sporadic CRC tissue,but not in CAC.CONCLUSION:Immunohistochemical NK-1R and p EGFR positivity with VDR negativity can be used to identify areas of sporadic colorectal neoplasia.VDR immunoreactivity can distinguish CAC from sporadic cancer.
文摘BACKGROUND Mixed tumors of the colon and rectum,composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms.These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally.Though they have been a well-documented entity in the pancreas,where the exocrine-endocrine mixed tumors have been known for a while,recognition and accurate diagnosis of these tumors in the colon and rectum,to date,remains a challenge.This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification.Therefore,dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers.Though,most of these tumors are high grade and of advanced stage,intermediate and low grade lesions of these mixed tumors are also increasingly been reported.There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions.AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape,clinicoradiological features,pathology,treatment,prognosis,the current status of the management of the primary lesions,their recurrences and metastases.METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed,MEDLINE and GOOGLE scholar.The following search terms[“mixed tumors colon”OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors]were used.Eligibility criteria were defined and all potential relevant items,including full articles and/or abstracts were independently reviewed,assessed and agreed upon items were selected for in-depth analysis.RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review.This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives,nomenclature,clinicoradiological features,pathology,treatment,prognosis and the current status of the management of both the primary lesions,their recurrences and metastases.Gaps in knowledge have also been identified and discussed.An important outcome of this manuscript is the justified proposal for a new,simple,clinically relevant,non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms(MEENs).CONCLUSION MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high,intermediate or low grade malignant potential.This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.
基金supported by the National Natural Science Foundation of China(No.30930038)National"973"Program of China(No.2009CB521700+1 种基金2009CB918903)Program for Changjiang Scholars and Innovative Research Team in University(No.IRT0743)
文摘The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.
文摘Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.
文摘Lymphangiomas are rare benign cystic tumors of the lymphatic system.Retroperitoneal lymphangiomas account for 1%of all lymphangiomas,and approximately 186 cases have been reported.They may clinically present as a palpable abdominal mass and can cause diagnostic dilemmas with other retroperitoneal cystic tumors,including those arising from the liver,kidney and pancreas.This report describes the rare case of a cystic retroperitoneal lymphangioma in a 54-year-old male patient.The lymphangioma had progressed to the point of inducing clinical symptoms of abdominal distention,abdominal pain,anorexia,fever,nausea and diarrhea.Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum and extending into the pelvis.Surgical removal of the cyst was accomplished without incident.A benign cystic retroperitoneal lymphangioma was diagnosed on histology and confirmed with immunohistochemical stains.
