Traditional laparoscopic radical prostatectomy is a treatment choice in many developing countries and regions for most patients with localized prostate cancer; however, no system for predicting surgical difficulty and...Traditional laparoscopic radical prostatectomy is a treatment choice in many developing countries and regions for most patients with localized prostate cancer; however, no system for predicting surgical difficulty and risk has been established. This study aimed to propose a simple and standard preoperative classification system of prostate cancer using preoperative data to predict surgical difficulty and risk and to evaluate the relationship between the data and postoperative complications. We collected data from 236 patients and divided them into three groups to evaluate and validate the relationships among preoperative, operative, and postoperative data. This new scoring system is based on the body mass index, ultrasonic prostate volume, preoperative prostate-specific antigen level, middle lobe protrusion, and clinical stage. In the scoring group, we classified 89 patients into two groups: the low-risk group (score of 〈4) and high-risk group (score of ~4), and then compared the postoperative data between the two groups. The positive surgical margin rate was higher in the high-risk group than low-risk group. The results in validation Groups A and B were similar to those in the scoring group. The focus of our scoring system is to allow for preliminary assessment of surgical difficulty by collecting the patients' basic information. Urologists can easily use the scoring system to evaluate the surgical difficulty and predict the risks of a positive surgical margin and urinary incontinence in patients undergoing laparoscopic radical prostatectomy.展开更多
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial con...A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.展开更多
Variceal bleed represents an important complication of cirrhosis,with its presence reflecting the severity of liver disease.Gastric varices,though less frequently seen than esophageal varices,present a distinct clinic...Variceal bleed represents an important complication of cirrhosis,with its presence reflecting the severity of liver disease.Gastric varices,though less frequently seen than esophageal varices,present a distinct clinical challenge due to its higher intensity of bleeding and associated mortality.Based upon the Sarin classification,GOV1 is the most common subtype of gastric varices seen in clinical practice.展开更多
Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This lit...Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This literature review aims to examine the current state of knowledge on fURS treatment of kidney stones, with a particular focus on the impact of the latest laser technologies on clinical outcomes and patient safety.Methods: We conducted a search of the PubMed/PMC, Web of Science Core Collection, Scopus, Embase (Ovid), and Cochrane Databases for all randomized controlled trial articles on laser lithotripsy in September 2023 without time restriction.Results: We found a total of 22 relevant pieces of literature. Holmium laser has been used for intracavitary laser lithotripsy for nearly 30 years and has become the golden standard for the treatment of urinary stones. However, the existing holmium laser cannot completely powder the stone, and the retropulsion of the stone after the laser emission and the thermal damage to the tissue have caused many problems for clinicians. The introduction of thulium fiber laser and Moses technology brings highly efficient dusting lithotripsy effect through laser innovation, limiting pulse energy and broadening pulse frequency.Conclusion: While the holmium:yttrium-aluminum-garnet laser remains the primary choice for endoscopic laser lithotripsy, recent technological advancements hint at a potential new gold standard. Parameter range, retropulsion effect, laser fiber adaptability, and overall system performance demand comprehensive attention. The ablation efficacy of high-pulse-frequency devices relies on precise targeting, which may pose practical challenges.展开更多
Objectives:To highlight critical preoperative and intraoperative considerations in approaching fistula repair robotically.Methods:A search of the literature was conducted to identify relevant articles pertaining to ro...Objectives:To highlight critical preoperative and intraoperative considerations in approaching fistula repair robotically.Methods:A search of the literature was conducted to identify relevant articles pertaining to robotic management of urinary fistulae.Results:Fistulae of the genitourinary tract can be a challenging dilemma for urologists,as definitive management may require surgical intervention.Pathogenesis of both enteric and non-enteric fistulae are multifactorial,and successful repair hinges on the meticulous perioperative evaluation,planning,and execution.Traditional open techniques can subject patients to increased morbidity and prolonged hospitalizations.Since its introduction,the robotic surgical platform has continued to expand its indications.Its three-dimensional visualization and tremor free wristed instrument movements have made the robotic platform an attractive option for genitourinary fistula reconstruction.Conclusion:Robotic management of complex urinary fistulae is feasible in expert hands;more studies are needed to define its role in the treatment algorithm of this devastating conditions.展开更多
BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for ...BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.展开更多
BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative...BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.展开更多
BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is ...BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.展开更多
The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer ...The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.展开更多
BACKGROUND Primary immunoglobulin(Ig)-associated mesangiocapillary glomerulonephritis(Ig-MCGN)is an immune complex glomerulonephritis of unknown etiology.It is a common cause of chronic kidney disease in developing co...BACKGROUND Primary immunoglobulin(Ig)-associated mesangiocapillary glomerulonephritis(Ig-MCGN)is an immune complex glomerulonephritis of unknown etiology.It is a common cause of chronic kidney disease in developing countries.There is limited data available on renal and patient outcomes of this disease from developing countries.AIM To determine the short-term renal and patient outcomes of adults with a tissueconfirmed diagnosis of primary Ig-MCGN at a single center in Pakistan.METHODS A retrospective cohort study of adult patients was conducted on biopsy-proven Ig-MCGN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation,Karachi,Pakistan.Secondary causes were excluded.The primary endpoint was renal survival without end-stage kidney disease(ESKD)or mortality.The secondary endpoint was the rate of remission during the 2-year follow-up period.Survival curves were made with the use of Kaplan-Meier estimates.RESULTS A total of 163 patients were included in the study and their mean follow-up duration was 29.45 months±21.28 months.Among baseline characteristics,young age,lower estimated glomerular filtration rate,requirement of kidney replacement therapy,presence of crescents,and severity of interstitial fibrosis and tubular atrophy were found to have a significant association with renal outcomes.The renal outcomes were negatively correlated with the presence of hypertension,level of complements,and degree of proteinuria.In all,63(37.4%)patients were treated with steroids and 21(13%)received combination therapy(cyclophosphamide with steroids).At 2 years,124(76.07%)patients were in complete remission or partial remission[56(34.3%)and 68(41.71%),respectively],while 32(19.63%)patients progressed to ESKD and 7(4.29%)patients died.CONCLUSION The outcomes of primary Ig-MCGN are guarded in Pakistan and require further prospective studies to improve our understanding of this relatively common disease so that more personalized treatment approaches can be developed.展开更多
Pregnancy in women with lupus,particularly those with lupus nephritis(LN),carries an increased risk of adverse outcomes.Women with active LN at the time of conception are at a high risk of poor maternal and fetal outc...Pregnancy in women with lupus,particularly those with lupus nephritis(LN),carries an increased risk of adverse outcomes.Women with active LN at the time of conception are at a high risk of poor maternal and fetal outcomes.Recent studies indicate that even in the presence of quiescent disease,factors such as hypertension and positive lupus anticoagulant are predictors of worse pregnancy outcomes.Consequently,pre-conception evaluation is essential to ensure that pursuing pregnancy is safe and timely,and to facilitate proper planning for optimizing medical regimens,discontinuing teratogenic agents,and treating active disease.Additionally,pre-existing LN is associated with higher rates of preeclampsia and hemolysis,elevated liver enzymes,and low platelet count syndrome.Women with lupus and prior LN can have successful pregnancies,but a multidisciplinary approach with close monitoring is essential for optimal outcomes.By systematically reviewing the available evidence,this narrative review aims to provide a comprehensive update on the complex interaction between LN and pregnancy,offering insights to guide clinical practice and future research in this field.展开更多
BACKGROUND Kidney function loss or renal insufficiency indicated by elevated creatinine levels and/or an estimated glomerular filtration rate(eGFR)<60 mL/minute/1.73 m²at presentation in patients with primary ...BACKGROUND Kidney function loss or renal insufficiency indicated by elevated creatinine levels and/or an estimated glomerular filtration rate(eGFR)<60 mL/minute/1.73 m²at presentation in patients with primary focal segmental glomerulosclerosis(FSGS)is commonly seen as a poor prognostic marker for kidney survival.However,a pre>vious study from our center suggested this may be due to hemodynamic factors.AIM To observe the clinical and biochemical parameters,treatment response,kidney survival,and overall outcomes of adult patients with primary FSGS presenting with kidney function insufficiency.METHODS This retrospective observational study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from January 1995 to December 2017.During this period,401 biopsy-proven primary FSGS patients were identified,of which 98(24.4%)presented with kidney function loss or renal insufficiency defined as eGFR<60 mL/minute/1.73 m²at presentation and were studied in detail.RESULTS Among the 98 patients with renal function loss on presentation,the mean age was 30.9 years±13.6 years with a male-to-female ratio of 2.5:1.The mean serum creatinine level was 2.2 mg/dL±1.3 mg/dL and mean eGFR 37.1 mL/minute/1.73 m2±12.8 mL/minute/1.73 m2.The mean 24-hour urinary protein excretion was 5.9 g/day±4.0 g/day,and the mean serum albumin was 2.1 g/dL±1.0 g/dL(median:1.5 g/dL).The mean systolic blood pressure(BP)was 132.7 mmHg±19.8 mmHg,and the mean diastolic BP was 87.4 mmHg±12.7 mmHg.Steroid treatment was given to 81(82.6%)of 98 patients for an average duration of 19.9 weeks±14.4 weeks,with a mean total steroid dose of 4.4 g±1.5 g.Treatment response showed that 20(24.6%)patients achieved complete remission,9(11.1%)achieved partial remission,and 52(64.1%)did not respond.The baseline eGFR was significantly lower in the non-responsive group(P=0.006).The distribution of FSGS variants was also significantly different among steroid-responsive and non-responsive groups(P=0.012).CONCLUSION Renal function loss in FSGS patients at presentation does not necessarily indicate irreversible kidney function loss and a significant number of patients respond to appropriate treatment of the underlying disease.展开更多
Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been proble...Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been problematic since its initial recognition.Traditionally,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification issues.The two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its nomenclature.Numerous attempts were made to address these issues but none achieved universal acceptance.Just recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology.FLD has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated SLD.Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis.This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.展开更多
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 revol...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.展开更多
Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) u...Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.展开更多
Renal cancer is one of the most common malignancies of the urinary system,and the number of deaths continues to increase.The standardized management of the diagnosis and treatment of renal cancer is challenging due to...Renal cancer is one of the most common malignancies of the urinary system,and the number of deaths continues to increase.The standardized management of the diagnosis and treatment of renal cancer is challenging due to the great differences in the diagnosis and treatment of renal cancer in different regions.The Renal Cancer Expert Committee of the National Cancer Quality Control Center(NCQCC)identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of renal cancer.The Renal Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization,uniformity,and normalization of renal cancer diagnosis and treatment,which ultimately improved the survival rate and quality of life of renal cancer patients.A panel of experts with renal cancer surgery,renal cancer medicine,medical imaging,pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of renal cancer.The Indices includes 20 items that cover all key areas in the diagnosis and treatment of renal cancer,such as standard diagnosis,surgery treatment,systemic treatment,and prognostic evaluation.展开更多
Objective:Percutaneous nephrolithotomy is a treatment of choice for larger stones of the upper urinary tract.Currently,several nephrolithometric nomograms for prediction of post-operative surgical outcomes have been p...Objective:Percutaneous nephrolithotomy is a treatment of choice for larger stones of the upper urinary tract.Currently,several nephrolithometric nomograms for prediction of post-operative surgical outcomes have been proposed,although uncertainties still exist regarding their roles in the estimation of complications.Methods:We conducted a systematic review on PubMed and Web of Sciences databases including English studies with at least 100 cases and published between January 2010 and December 2021.We identified original articles evaluating correlations between the Guy’s stone score,the stone size(S),tract length(T),obstruction(O),number of involved calices(N),and essence or stone density(E)(S.T.O.N.E.),Clinical Research Office of the Endourological Society(CROES),and Seoul National University Renal Stone Complexity(S-ReSC)scores and post-operative complications in adult patients.We also included newly designed nomograms for prediction of specific complications.Results:After an initial search of 549 abstracts,we finally included a total of 18 papers.Of them,11 investigated traditional nephrolithometric nomograms,while seven newly designed nomograms were used to predict specific complications.Overall,7316 patients have been involved.In total,14 out of 18 papers are derived from retrospective single-center studies.Guy’s stone score obtained correlation with complications in five,S.T.O.N.E.nephrolithometry score in four,while CROES score and S-ReSC score in three and two,respectively.None of the studies investigated minimally invasive percutaneous nephrolithotomy(PCNL)and all cases have been conducted in prone position.Considering newly designed nomograms,none of them is currently externally validated;five of them predict post-operative infections;the remaining two have been designed for thromboembolic events and urinary leakage.Conclusion:This review presents all nomograms currently available in the PCNL field and highlights a certain number of concerns.Published data have appeared contradictory;more recent tools for prediction of post-operative complications are frequently based on small retrospective cohorts and lack external validations.Heterogeneity among studies has also been noticed.More rigorous validations are advisable in the future,involving larger prospective patients’series and with the comparison of different tools.展开更多
BACKGROUND Proteinuria is an important and well-known biomarker of many forms of kidney injury.Its quantitation is of particular importance in the diagnosis and management of glomerular diseases.Its quantification can...BACKGROUND Proteinuria is an important and well-known biomarker of many forms of kidney injury.Its quantitation is of particular importance in the diagnosis and management of glomerular diseases.Its quantification can be done by several methods.Among these,the measurement of 24-h urinary protein excretion is the gold standard method.However,it is cumbersome,time-consuming,and inconvenient for patients and is not completely foolproof.Many alternative methods have been tested over time albeit with conflicting results.Among the latter,the measurement of urine protein-to-creatinine ratio(uPCR)in singlevoided urinary samples is widely used.The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation,whereas others did not.AIM To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single largevolume nephrological center in Pakistan.METHODS This cross-sectional,observational study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan from September 2017 to March 2018.All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled.All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations.A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample.The data of patients were collected in a proforma.SPSS version 20.0 was used for statistical analysis.RESULTS A total of 157 patients were included.Their mean age was 30.45±12.11 years.There were 94(59.8%)males and 63(40.2%)females.The mean 24-h urinary protein excretion was 3192.78±1959.79 mg and the mean spot uPCR was 3.16±1.52 in all patients.A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion(r=0.342,P=0.01)among all patients.On subgroup analysis,a slightly better correlation was found in patients older than 47 years(r=0.78),and those with body mass index>25 kg/m2(r=0.45).The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods.CONCLUSION Overall,the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies.The agreement between the two methods was also poor.Hence,there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.展开更多
Objectives:The study aimed to evaluate quality of nephrolithometric nomograms to predict stone-free rates(SFRs)and complication rates(CRs)in case of minimally invasive percutaneous nephrolithotomy(PNL).In the last dec...Objectives:The study aimed to evaluate quality of nephrolithometric nomograms to predict stone-free rates(SFRs)and complication rates(CRs)in case of minimally invasive percutaneous nephrolithotomy(PNL).In the last decade,nomograms have been introduced to estimate the SFRs and CRs of PNL.However,no data are available regarding their reliability in case of utilization of miniaturized devices.Herein we present a prospective multicentric study to evaluate reliability of Guy’s stone score(GSS),the stone size,tract length,obstruction,number of involved calyces,and essence of stone(S.T.O.N.E.)nephrolithometry score and Clinical Research Office of the Endourological Society(CROES)score in patients treated with minimally invasive PNL.Methods:We evaluated SFRs and CRs of 222 adult patients treated with miniaturized PNL.Patients were considered stone-free if no residual fragments of any size at post-operative unenhanced computed tomography scan.Patients demographics,SFRs,and CRs were reported and analyzed.Performances of nomograms were evaluated with the area under the curve(AUC).Results:We included 222 patients,the AUCs of GSS,CROES score,and S.T.O.N.E.nephrolithometry score were 0.69(95%confidence interval[CI]0.61-0.78),0.64(95%CI 0.56-0.73),and 0.62(95%CI 0.52-0.71),respectively.Regarding SFRs,at multivariate binomial logistic regression,only the GSS had significance with an odds ratio of 0.53(95%CI 0.31e0.95,p=0.04).We did not find significant correlation with complications,with only a trend for GSS.Conclusion:This is the first study evaluating nomograms in miniaturized PNL.They still show good reliability;however,our data showed lower performances compared to standard PNL.We emphasize the need of further studies to confirm this trend.A dedicated nomogram for minimally invasive PNL may be necessary.展开更多
文摘Traditional laparoscopic radical prostatectomy is a treatment choice in many developing countries and regions for most patients with localized prostate cancer; however, no system for predicting surgical difficulty and risk has been established. This study aimed to propose a simple and standard preoperative classification system of prostate cancer using preoperative data to predict surgical difficulty and risk and to evaluate the relationship between the data and postoperative complications. We collected data from 236 patients and divided them into three groups to evaluate and validate the relationships among preoperative, operative, and postoperative data. This new scoring system is based on the body mass index, ultrasonic prostate volume, preoperative prostate-specific antigen level, middle lobe protrusion, and clinical stage. In the scoring group, we classified 89 patients into two groups: the low-risk group (score of 〈4) and high-risk group (score of ~4), and then compared the postoperative data between the two groups. The positive surgical margin rate was higher in the high-risk group than low-risk group. The results in validation Groups A and B were similar to those in the scoring group. The focus of our scoring system is to allow for preliminary assessment of surgical difficulty by collecting the patients' basic information. Urologists can easily use the scoring system to evaluate the surgical difficulty and predict the risks of a positive surgical margin and urinary incontinence in patients undergoing laparoscopic radical prostatectomy.
文摘A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
文摘Variceal bleed represents an important complication of cirrhosis,with its presence reflecting the severity of liver disease.Gastric varices,though less frequently seen than esophageal varices,present a distinct clinical challenge due to its higher intensity of bleeding and associated mortality.Based upon the Sarin classification,GOV1 is the most common subtype of gastric varices seen in clinical practice.
基金supported by the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Grant No.ZYGD18011 and No.ZYJC18015 to Wang K).
文摘Objective: Flexible ureteroscopy (fURS) has become a widely accepted and effective technique for treating kidney stones. With the development of new laser systems, the fURS approach has evolved significantly. This literature review aims to examine the current state of knowledge on fURS treatment of kidney stones, with a particular focus on the impact of the latest laser technologies on clinical outcomes and patient safety.Methods: We conducted a search of the PubMed/PMC, Web of Science Core Collection, Scopus, Embase (Ovid), and Cochrane Databases for all randomized controlled trial articles on laser lithotripsy in September 2023 without time restriction.Results: We found a total of 22 relevant pieces of literature. Holmium laser has been used for intracavitary laser lithotripsy for nearly 30 years and has become the golden standard for the treatment of urinary stones. However, the existing holmium laser cannot completely powder the stone, and the retropulsion of the stone after the laser emission and the thermal damage to the tissue have caused many problems for clinicians. The introduction of thulium fiber laser and Moses technology brings highly efficient dusting lithotripsy effect through laser innovation, limiting pulse energy and broadening pulse frequency.Conclusion: While the holmium:yttrium-aluminum-garnet laser remains the primary choice for endoscopic laser lithotripsy, recent technological advancements hint at a potential new gold standard. Parameter range, retropulsion effect, laser fiber adaptability, and overall system performance demand comprehensive attention. The ablation efficacy of high-pulse-frequency devices relies on precise targeting, which may pose practical challenges.
文摘Objectives:To highlight critical preoperative and intraoperative considerations in approaching fistula repair robotically.Methods:A search of the literature was conducted to identify relevant articles pertaining to robotic management of urinary fistulae.Results:Fistulae of the genitourinary tract can be a challenging dilemma for urologists,as definitive management may require surgical intervention.Pathogenesis of both enteric and non-enteric fistulae are multifactorial,and successful repair hinges on the meticulous perioperative evaluation,planning,and execution.Traditional open techniques can subject patients to increased morbidity and prolonged hospitalizations.Since its introduction,the robotic surgical platform has continued to expand its indications.Its three-dimensional visualization and tremor free wristed instrument movements have made the robotic platform an attractive option for genitourinary fistula reconstruction.Conclusion:Robotic management of complex urinary fistulae is feasible in expert hands;more studies are needed to define its role in the treatment algorithm of this devastating conditions.
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
文摘BACKGROUND Detection of early chronic changes in the kidney allograft is important for timely intervention and long-term survival.Conventional and novel ultrasound-based investigations are being increasingly used for this purpose with variable results.AIM To compare the diagnostic performance of resistive index(RI)and shear wave elastography(SWE)in the diagnosis of chronic fibrosing changes of kidney allograft with histopathological results.METHODS This is a cross-sectional and comparative study.A total of 154 kidney transplant recipients were included in this study,which was conducted at the Departments of Transplantation and Radiology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from August 2022 to February 2023.All consecutive patients with increased serum creatinine levels and reduced glomerular filtration rate(GFR)after three months of transplantation were enrolled in this study.SWE and RI were performed and the findings of these were evaluated against the kidney allograft biopsy results to determine their diagnostic utility.RESULTS The mean age of all patients was 35.32±11.08 years.Among these,126(81.8%)were males and 28(18.2%)were females.The mean serum creatinine in all patients was 2.86±1.68 mg/dL and the mean estimated GFR was 35.38±17.27 mL/min/1.73 m2.Kidney allograft biopsy results showed chronic changes in 55(37.66%)biopsies.The sensitivity,specificity,positive predictive value(PPV),and negative predictive value(NPV)of SWE for the detection of chronic allograft damage were 93.10%,96.87%%,94.73%,and 95.87%,respectively,and the diagnostic accuracy was 95.45%.For RI,the sensitivity,specificity,PPV,and NPV were 76.92%,83.33%,70.17%,and 87.62%,respectively,and the diagnostic accuracy was 81.16%.CONCLUSION The results from this study show that SWE is more sensitive and specific as compared to RI in the evaluation of chronic allograft damage.It can be of great help during the routine follow-up of kidney transplant recipients for screening and early detection of chronic changes and selecting patients for allograft biopsy.
文摘BACKGROUND The Columbia classification identified five histological variants of focal segmental glomerulosclerosis(FSGS).The prognostic significance of these variants remains controversial.AIM To evaluate the relative frequency,clinicopathologic characteristics,and medium-term outcomes of FSGS variants at a single center in Pakistan.METHODS This retrospective study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan on all consecutive adults(≥16 years)with biopsy-proven primary FSGS from January 1995 to December 2017.Studied subjects were treated with steroids as a first-line therapy.The response rates,doubling of serum creatinine,and kidney failure(KF)with replacement therapy were compared between histological variants using ANOVA or Kruskal Wallis,and Chi-square tests as appropriate.Data were analyzed by SPSS version 22.0.P-value≤0.05 was considered significant.RESULTS A total of 401 patients were diagnosed with primary FSGS during the study period.Among these,352(87.7%)had a designated histological variant.The not otherwise specified(NOS)variant was the commonest,being found in 185(53.9%)patients,followed by the tip variant in 100(29.1%)patients.Collapsing(COL),cellular(CEL),and perihilar(PHI)variants were seen in 58(16.9%),6(1.5%),and 3(0.7%)patients,respectively.CEL and PHI variants were excluded from further analysis due to small patient numbers.The mean follow-up period was 36.5±29.2 months.Regarding response rates of variants,patients with TIP lesions achieved remission more frequently(59.5%)than patients with NOS(41.8%)and COL(24.52%)variants(P<0.001).The hazard ratio of complete response among patients with the COL variant was 0.163[95%confidence interval(CI):0.039-0.67]as compared to patients with NOS.The TIP variant showed a hazard ratio of 2.5(95%CI:1.61-3.89)for complete remission compared to the NOS variant.Overall,progressive KF was observed more frequently in patients with the COL variant,43.4%(P<0.001).Among these,24.53%of patients required kidney replacement therapy(P<0.001).The hazard ratio of doubling of serum creatinine among patients with the COL variant was 14.57(95%CI:1.87-113.49)as compared to patients with the TIP variant.CONCLUSION In conclusion,histological variants of FSGS are predictive of response to treatment with immunosuppressants and progressive KF in adults in our setup.
基金Supported by National Natural Science Foundation of China,No.81470982.
文摘BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of ADSCs.The mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain reaction.Culture supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent assay.RESULTS Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and IL-17A.Additionally,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release levels.This was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+alone.CONCLUSION The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg responses.Thus,ADSC-based cell therapy could be a beneficial approach for patients with severe COVID-19 who fail to respond to conventional therapies.
基金the Chinese Scholarship Council(Grant No.202206240086)the National Natural Science Foundation of China(Grant No.82170432)programs from Science and Technology Department of Sichuan Province(Grant No.2020YFSY0024).
文摘The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.
文摘BACKGROUND Primary immunoglobulin(Ig)-associated mesangiocapillary glomerulonephritis(Ig-MCGN)is an immune complex glomerulonephritis of unknown etiology.It is a common cause of chronic kidney disease in developing countries.There is limited data available on renal and patient outcomes of this disease from developing countries.AIM To determine the short-term renal and patient outcomes of adults with a tissueconfirmed diagnosis of primary Ig-MCGN at a single center in Pakistan.METHODS A retrospective cohort study of adult patients was conducted on biopsy-proven Ig-MCGN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation,Karachi,Pakistan.Secondary causes were excluded.The primary endpoint was renal survival without end-stage kidney disease(ESKD)or mortality.The secondary endpoint was the rate of remission during the 2-year follow-up period.Survival curves were made with the use of Kaplan-Meier estimates.RESULTS A total of 163 patients were included in the study and their mean follow-up duration was 29.45 months±21.28 months.Among baseline characteristics,young age,lower estimated glomerular filtration rate,requirement of kidney replacement therapy,presence of crescents,and severity of interstitial fibrosis and tubular atrophy were found to have a significant association with renal outcomes.The renal outcomes were negatively correlated with the presence of hypertension,level of complements,and degree of proteinuria.In all,63(37.4%)patients were treated with steroids and 21(13%)received combination therapy(cyclophosphamide with steroids).At 2 years,124(76.07%)patients were in complete remission or partial remission[56(34.3%)and 68(41.71%),respectively],while 32(19.63%)patients progressed to ESKD and 7(4.29%)patients died.CONCLUSION The outcomes of primary Ig-MCGN are guarded in Pakistan and require further prospective studies to improve our understanding of this relatively common disease so that more personalized treatment approaches can be developed.
文摘Pregnancy in women with lupus,particularly those with lupus nephritis(LN),carries an increased risk of adverse outcomes.Women with active LN at the time of conception are at a high risk of poor maternal and fetal outcomes.Recent studies indicate that even in the presence of quiescent disease,factors such as hypertension and positive lupus anticoagulant are predictors of worse pregnancy outcomes.Consequently,pre-conception evaluation is essential to ensure that pursuing pregnancy is safe and timely,and to facilitate proper planning for optimizing medical regimens,discontinuing teratogenic agents,and treating active disease.Additionally,pre-existing LN is associated with higher rates of preeclampsia and hemolysis,elevated liver enzymes,and low platelet count syndrome.Women with lupus and prior LN can have successful pregnancies,but a multidisciplinary approach with close monitoring is essential for optimal outcomes.By systematically reviewing the available evidence,this narrative review aims to provide a comprehensive update on the complex interaction between LN and pregnancy,offering insights to guide clinical practice and future research in this field.
文摘BACKGROUND Kidney function loss or renal insufficiency indicated by elevated creatinine levels and/or an estimated glomerular filtration rate(eGFR)<60 mL/minute/1.73 m²at presentation in patients with primary focal segmental glomerulosclerosis(FSGS)is commonly seen as a poor prognostic marker for kidney survival.However,a pre>vious study from our center suggested this may be due to hemodynamic factors.AIM To observe the clinical and biochemical parameters,treatment response,kidney survival,and overall outcomes of adult patients with primary FSGS presenting with kidney function insufficiency.METHODS This retrospective observational study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan,from January 1995 to December 2017.During this period,401 biopsy-proven primary FSGS patients were identified,of which 98(24.4%)presented with kidney function loss or renal insufficiency defined as eGFR<60 mL/minute/1.73 m²at presentation and were studied in detail.RESULTS Among the 98 patients with renal function loss on presentation,the mean age was 30.9 years±13.6 years with a male-to-female ratio of 2.5:1.The mean serum creatinine level was 2.2 mg/dL±1.3 mg/dL and mean eGFR 37.1 mL/minute/1.73 m2±12.8 mL/minute/1.73 m2.The mean 24-hour urinary protein excretion was 5.9 g/day±4.0 g/day,and the mean serum albumin was 2.1 g/dL±1.0 g/dL(median:1.5 g/dL).The mean systolic blood pressure(BP)was 132.7 mmHg±19.8 mmHg,and the mean diastolic BP was 87.4 mmHg±12.7 mmHg.Steroid treatment was given to 81(82.6%)of 98 patients for an average duration of 19.9 weeks±14.4 weeks,with a mean total steroid dose of 4.4 g±1.5 g.Treatment response showed that 20(24.6%)patients achieved complete remission,9(11.1%)achieved partial remission,and 52(64.1%)did not respond.The baseline eGFR was significantly lower in the non-responsive group(P=0.006).The distribution of FSGS variants was also significantly different among steroid-responsive and non-responsive groups(P=0.012).CONCLUSION Renal function loss in FSGS patients at presentation does not necessarily indicate irreversible kidney function loss and a significant number of patients respond to appropriate treatment of the underlying disease.
文摘Fatty liver disease(FLD)is a highly prevalent pathological liver disorder.It has many and varied etiologies and has heterogeneous clinical course and outcome.Its proper nomenclature and classification have been problematic since its initial recognition.Traditionally,it was divided into two main categories:Alcoholassociated liver disease and nonalcoholic FLD(NAFLD).Among these,the latter condition has been plagued with nomenclature and classification issues.The two main objections to its use have been the use of negative(non-alcoholic)and stigmatizing(fatty)terms in its nomenclature.Numerous attempts were made to address these issues but none achieved universal acceptance.Just recently,NAFLD has received a new nomenclature from an international collaborative effort based on a rigorous scientific methodology.FLD has been renamed steatotic liver disease(SLD),and NAFLD as metabolic dysfunction-associated SLD.Metabolic dysfunction-associated steatohepatitis was chosen as the replacement terminology for non-alcoholic steatohepatitis.This is a significant positive change in the nomenclature and categorization of FLD and will likely have a major impact on research,diagnosis,treatment,and prognosis of the disease in the future.
文摘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.
文摘Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.
基金supported by Peking University First Hospital Domestic Multicenter Clinical Research Special Fund-Central High Level Hospital Clinical Research Business Fund(grant number:2022CR54)Peking University Medical Innovation Translation Special Fund(grant number:2022FY03)+2 种基金Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund(grant number:2022CX02)2020 Capital Health Development Research Spe-cial Project(grant number:2020-2Z-40713)National Key Research and Development Program Scheme(grant number:2023YFC2415500)。
文摘Renal cancer is one of the most common malignancies of the urinary system,and the number of deaths continues to increase.The standardized management of the diagnosis and treatment of renal cancer is challenging due to the great differences in the diagnosis and treatment of renal cancer in different regions.The Renal Cancer Expert Committee of the National Cancer Quality Control Center(NCQCC)identified a lack of authoritative quality control standards as an opportunity to utilize its multidisciplinary membership to improve the standardized diagnosis and treatment of renal cancer.The Renal Cancer Expert Committee of the NCQCC aims to promote quality control and national standardization,uniformity,and normalization of renal cancer diagnosis and treatment,which ultimately improved the survival rate and quality of life of renal cancer patients.A panel of experts with renal cancer surgery,renal cancer medicine,medical imaging,pathology and radiotherapy were drawn together and determined the quality control standards for the standardized diagnosis and treatment of renal cancer.The Indices includes 20 items that cover all key areas in the diagnosis and treatment of renal cancer,such as standard diagnosis,surgery treatment,systemic treatment,and prognostic evaluation.
文摘Objective:Percutaneous nephrolithotomy is a treatment of choice for larger stones of the upper urinary tract.Currently,several nephrolithometric nomograms for prediction of post-operative surgical outcomes have been proposed,although uncertainties still exist regarding their roles in the estimation of complications.Methods:We conducted a systematic review on PubMed and Web of Sciences databases including English studies with at least 100 cases and published between January 2010 and December 2021.We identified original articles evaluating correlations between the Guy’s stone score,the stone size(S),tract length(T),obstruction(O),number of involved calices(N),and essence or stone density(E)(S.T.O.N.E.),Clinical Research Office of the Endourological Society(CROES),and Seoul National University Renal Stone Complexity(S-ReSC)scores and post-operative complications in adult patients.We also included newly designed nomograms for prediction of specific complications.Results:After an initial search of 549 abstracts,we finally included a total of 18 papers.Of them,11 investigated traditional nephrolithometric nomograms,while seven newly designed nomograms were used to predict specific complications.Overall,7316 patients have been involved.In total,14 out of 18 papers are derived from retrospective single-center studies.Guy’s stone score obtained correlation with complications in five,S.T.O.N.E.nephrolithometry score in four,while CROES score and S-ReSC score in three and two,respectively.None of the studies investigated minimally invasive percutaneous nephrolithotomy(PCNL)and all cases have been conducted in prone position.Considering newly designed nomograms,none of them is currently externally validated;five of them predict post-operative infections;the remaining two have been designed for thromboembolic events and urinary leakage.Conclusion:This review presents all nomograms currently available in the PCNL field and highlights a certain number of concerns.Published data have appeared contradictory;more recent tools for prediction of post-operative complications are frequently based on small retrospective cohorts and lack external validations.Heterogeneity among studies has also been noticed.More rigorous validations are advisable in the future,involving larger prospective patients’series and with the comparison of different tools.
文摘BACKGROUND Proteinuria is an important and well-known biomarker of many forms of kidney injury.Its quantitation is of particular importance in the diagnosis and management of glomerular diseases.Its quantification can be done by several methods.Among these,the measurement of 24-h urinary protein excretion is the gold standard method.However,it is cumbersome,time-consuming,and inconvenient for patients and is not completely foolproof.Many alternative methods have been tested over time albeit with conflicting results.Among the latter,the measurement of urine protein-to-creatinine ratio(uPCR)in singlevoided urinary samples is widely used.The majority of studies found a good correlation between uPCR in single urine samples with 24-h urinary protein estimation,whereas others did not.AIM To investigate the correlation of spot uPCR with 24-h urinary protein estimation in patients suffering from different forms of glomerulopathies at a single largevolume nephrological center in Pakistan.METHODS This cross-sectional,observational study was conducted at the Department of Nephrology,Sindh Institute of Urology and Transplantation,Karachi,Pakistan from September 2017 to March 2018.All newly presenting adult patients with proteinuria who were being investigated for suspected glomerulonephritis and persistent proteinuria with ages between 18 to 60 years were enrolled.All patients were given detailed advice regarding 24-h urine collection starting at 7:00 AM for total protein and creatinine excretion estimations.A spot urine sample was collected the next day at the time of submission of a 24-h urine sample for measuring uPCR along with a blood sample.The data of patients were collected in a proforma.SPSS version 20.0 was used for statistical analysis.RESULTS A total of 157 patients were included.Their mean age was 30.45±12.11 years.There were 94(59.8%)males and 63(40.2%)females.The mean 24-h urinary protein excretion was 3192.78±1959.79 mg and the mean spot uPCR was 3.16±1.52 in all patients.A weak but significant correlation was observed between spot uPCR and 24-h urinary protein excretion(r=0.342,P=0.01)among all patients.On subgroup analysis,a slightly better correlation was found in patients older than 47 years(r=0.78),and those with body mass index>25 kg/m2(r=0.45).The Bland and Altman's plot analysis comparing the differences between spot uPCR and 24-h protein measurement also showed a wide range of the limits of agreement between the two methods.CONCLUSION Overall,the results from this study showed a significant and weakly positive correlation between spot uPCR and 24-h urinary protein estimation in different forms of glomerulopathies.The agreement between the two methods was also poor.Hence,there is a need for careful interpretation of the ratio in an unselected group of patients with kidney disease.
文摘Objectives:The study aimed to evaluate quality of nephrolithometric nomograms to predict stone-free rates(SFRs)and complication rates(CRs)in case of minimally invasive percutaneous nephrolithotomy(PNL).In the last decade,nomograms have been introduced to estimate the SFRs and CRs of PNL.However,no data are available regarding their reliability in case of utilization of miniaturized devices.Herein we present a prospective multicentric study to evaluate reliability of Guy’s stone score(GSS),the stone size,tract length,obstruction,number of involved calyces,and essence of stone(S.T.O.N.E.)nephrolithometry score and Clinical Research Office of the Endourological Society(CROES)score in patients treated with minimally invasive PNL.Methods:We evaluated SFRs and CRs of 222 adult patients treated with miniaturized PNL.Patients were considered stone-free if no residual fragments of any size at post-operative unenhanced computed tomography scan.Patients demographics,SFRs,and CRs were reported and analyzed.Performances of nomograms were evaluated with the area under the curve(AUC).Results:We included 222 patients,the AUCs of GSS,CROES score,and S.T.O.N.E.nephrolithometry score were 0.69(95%confidence interval[CI]0.61-0.78),0.64(95%CI 0.56-0.73),and 0.62(95%CI 0.52-0.71),respectively.Regarding SFRs,at multivariate binomial logistic regression,only the GSS had significance with an odds ratio of 0.53(95%CI 0.31e0.95,p=0.04).We did not find significant correlation with complications,with only a trend for GSS.Conclusion:This is the first study evaluating nomograms in miniaturized PNL.They still show good reliability;however,our data showed lower performances compared to standard PNL.We emphasize the need of further studies to confirm this trend.A dedicated nomogram for minimally invasive PNL may be necessary.