Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Versatile chondroitin sulfate-based nanoplatform for chemo-photodynamic therapy against triple-negative breast cancer.

Versatile nanoplatform equipped with chemo-photodynamic therapeutic attributes play an important role in improving the effectiveness of tumor treatments. Herein, we developed multifunctional nanoparticles based on chondroitin sulfate A (CSA) for the targeted delivery of chlorin e6 (Ce6) and doxorubicin (DOX), in a combined chemo-photodynamic therapy against triple-negative breast cancer. CSA was chosen for its hydrophilic properties and its affinity to CD44 receptor-overexpressed tumor cells. The CSA-ss-Ce6 (CSSC) conjugate was synthesized utilizing a disulfide linker. Subsequently, DOX-loaded CSSC (CSSC-D) nanoparticles were fabricated, showcasing a nearly spherical shape with an average particle size of 267 nm. In the CSSC-D nanoparticles, the chemically attached Ce6 constituted 1.53 %, while the physically encapsulated DOX accounted for 8.11 %. Both CSSC-D and CSSC nanoparticles demonstrated a reduction-sensitive release of DOX or Ce6 in vitro. Under near-infrared (NIR) laser irradiation, CSSC-D showed the enhanced generation of reactive oxygen species (ROS), improving cytotoxic effects against triple-negative breast cancer 4T1 and MDA-MB-231 cells. Remarkably, the CSSC-D with NIR exhibited the most potent tumor growth inhibition in comparison to other groups in the 4T1-bearing Balb/c mice model. Overall, this CSSC-D nanoplatform shows significant promise as a powerful tool for a synergetic approach in chemo-photodynamic therapy in triple-negative breast cancer.

Unveiling the State Transition Mechanisms of Ras Proteins through Enhanced Sampling and QM/MM Simulations.

In cells, wild-type RasGTP complexes exist in two distinct states: active State 2 and inactive State 1. These complexes regulate their functions by transitioning between the two states. However, the mechanisms underlying this state transition have not been clearly elucidated. To address this, we conducted a detailed simulation study to characterize the energetics of the stable states involved in the state transitions of the HRasGTP complex, specifically from State 2 to State 1. This was achieved by employing multiscale quantum mechanics/molecular mechanics and enhanced sampling molecular dynamics methods. Based on the simulation results, we constructed the two-dimensional free energy landscapes that provide crucial information about the conformational changes of the HRasGTP complex from State 2 to State 1. Furthermore, we also explored the conformational changes from the intermediate state to the product state during guanosine triphosphate hydrolysis. This study on the conformational changes involved in the HRas state transitions serves as a valuable reference for understanding the corresponding events of both KRas and NRas as well.

Progress in the treatment of malignant ascites.

Malignant ascites occurs as a symptom of the terminal stage of cancer, affecting the quality of life through abdominal distension, pain, nausea, anorexia, dyspnea and other symptoms. We describe the current main drug treatments in addition to surgery according to the traditional and new strategies. Traditional treatments were based on anti-tumor chemotherapy and traditional Chinese medicine treatments, as well as diuretics to relieve the patient's symptoms. New treatments mainly involve photothermal therapy, intestinal therapy and targeted immunity. This study emphasizes that both traditional and new therapies have certain advantages and disadvantages, and medication should be adjusted according to different periods of use and different patients. In conclusion, this article reviews the literature to systematically describe the primary treatment modalities for malignant ascites.

[Pollution Characteristics and Source Apportionment of VOCs in Urban Areas of Liaocheng in Summer].

Based on the online monitoring data of volatile organic compounds(VOCs) and ozone(O3) in Liaocheng in June 2021, the concentration levels, compositional characteristics, daily variation characteristics, and ozone formation potential(OFP) of VOCs on polluted days and clean days were systematically analyzed. Potential source areas of VOCs were identified by the potential source contribution function(PSCF) and concentration-weighted trajectory(CWT). The sources of VOCs in Liaocheng were analyzed using the characteristic species ratio and positive matrix factorization(PMF). The results showed that the hourly mean values of VOCs concentrations on polluted days and clean days in Liaocheng in June 2021 were(115.38±59.12) µg·m-3 and(88.10±33.04) µg·m-3, respectively, and the concentration levels of VOCs in each category showed that oxygenated volatile organic compounds(OVOCs)>alkanes>halogenated hydrocarbons>aromatic hydrocarbons>alkenes>alkynes>organosulfur. VOCs species with large differences in concentrations between polluted and clean days were among the top ten species of the hourly mean VOCs concentrations. The daily trends of concentrations of total VOCs, alkanes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons, and organosulfur showed that the daytime concentrations were lower than the nighttime concentrations, and the daily changes in OVOCs concentrations showed the characteristics of high in the daytime and low at nighttime. The OFP was 285.29 µg·m-3 on polluted days and 212.00 µg·m-3 on clean days, and OVOCs, alkenes, and aromatic hydrocarbons contributed significantly to ozone formation. The PSCF and CWT results found that the potential source areas of VOCs in Liaocheng were concentrated in the northern and northeastern part of Dongchangfu District and the central and southwestern part of Chiping District. The results of the characteristic species ratio indicated that the VOCs in Liaocheng might have been more from coal combustion, gasoline volatilization, and motor vehicle exhaust. The results of PMF showed that industrial emission sources(30.57%), motor vehicle exhaust and oil and gas volatilization sources(19.44%), combustion sources(17.23%), air aging and secondary generation sources(13.69%), solvent usage sources(12.75%), and natural sources(6.32%) were the main sources of VOCs in Liaocheng.

Loss of MIR503HG facilitates papillary renal cell carcinoma associated lymphatic metastasis by triggering NOTCH1/VEGFC signaling.

Clinical lymphatic metastasis indicates an extremely poor prognosis. Patients with papillary renal cell carcinoma (pRCC) have a high probability of progressing to lymphatic metastasis. However, the molecular mechanism of pRCC-associated lymphatic metastasis has not been elucidated. In this study, we found a downregulated long non-coding RNA (lncRNA) MIR503HG in pRCC primary tumor tissues due to hypermethylation at the CpG islands within its transcriptional start site. Decreased MIR503HG expression could stimulate tube formation and migration of human lymphatic endothelial cell (HLEC) and play a central role to promote lymphatic metastasis in vivo by enhancing tumor lymphangiogenesis. MIR503HG, located in the nucleus, bound with histone variant H2A.Z and affected the recruitment of histone variant H2A.Z to chromatin. Subsequently, increasing the H3K27 trimethylation caused by MIR503HG-overexpression epigenetically downregulated the NOTCH1 expression, which ultimately resulted in decreasing VEGFC secretion and lymphangiogenesis. Additionally, downregulated MIR503HG facilitated the HNRNPC expression, which ultimately promoted the maturation of NOTCH1 mRNA. Notably, upregulating MIR503HG expression might decrease pRCC resistance to the mTOR inhibitor. Together, these findings highlighted a VEGFC-independent mechanism of MIR503HG-mediated lymphatic metastasis. MIR503HG, identified as a novel pRCC-suppressor, would serve as the potentially biomarker for lymphatic metastasis.

Surface-Enhanced Raman Spectroscopy of Pretreated Plasma Samples Predicts Disease Recurrence in Muscle-Invasive Bladder Cancer Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy.

Objective: To explore the value of surface-enhanced Raman spectroscopy analysis of pretreated plasma samples in prediction of bladder cancer (BCa) recurrence after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Patients and Methods: SERS was used to analyze plasma samples collected before biopsy and treatment in BCa patients undergoing NAC and RC. The value of clinicopathological parameters and distinctive SERS peaks in the prediction of disease recurrence were analyzed in Cox regression proportional hazard analysis and Log rank test. Principal component analysis and linear discriminant analysis (PCA-LDA) were employed to process spectral data and construct diagnostic algorithms. Results: A total of 88 patients with 440 plasma SERS spectra were collected. The SRES spectra from recurrent patients were compared with patients who remained recurrence free. The SERS demonstrated higher levels of circulating free nucleic acid components in recurrent population, which is represented by significantly higher intensities at SERS peaks of 725 cm-1, 1328 cm-1 and 1455 cm-1. The SERS also detected significantly lower levels of tryptophan shown as lower significantly intensities at the 1558 cm-1, which is proved to be an independent predictor of BCa recurrence. The addition of SERS peaks of 1558 cm-1 to classic clinicopathological predictors including pathological tumor stage, lymph node metastasis and pathological downstaging can significantly enhance the power of the predictive model from 0.66 to 0.76 in the area under curve (AUC) of receiver operating characteristic (ROC) curves. Meanwhile, the PCA-LDA diagnostic model based on SERS spectra reveals a high accuracy of 85.2% in prediction of disease recurrence and the AUC of 0.92 in the ROC curve. When validated in the leave-one-out cross-validation method, the accuracy of the model remained 84.1%. Conclusion: We show that SERS analysis of plasma before NAC treatment can accurately classify patients with different risks of disease recurrence after surgery and improve the power of clinicopathological predictive models, thus refining clinical decision-making.

The relationship between urologic cancer outcomes and national Human Development Index: trend in recent years.

OBJECTIVES: To describe the influence of the socioeconomic development on worldwide age-standardized incidence and mortality rates, as well as mortality-to-incidence ratio (MIR) and 5-year net survival of urologic cancer patients in recent years. METHODS: The Human Development Index (HDI) values were obtained from the United Nations Development Programme, data on age-standardized incidence/mortality rates of prostate, bladder and kidney cancer were retrieved from the GLOBOCAN database, 5-year net survival was provided by the CONCORD-3 program. We then evaluated the association between incidence/MIR/survival and HDI, with a focus on geographic variability as well as temporal patterns during the last 6 years. RESULTS: Urologic cancer incidence rates were positively correlated with HDIs, and MIRs were negatively correlated with HDIs. Prostate cancer survival also correlated positively with HDIs, solidly confirming the interrelation among cancer indicators and socioeconomic factors. Most countries experienced incidence decline over the most recent 6 years, and a substantial reduction in MIR was observed. Survival rates of prostate cancer have simultaneously improved. CONCLUSION: Development has a prominent influence on urologic cancer outcomes. HDI values are significantly correlated with cancer incidence, MIR and survival rates. HDI values have risen along with increased incidence and improved outcomes of urologic caner in recent years.

Influence of American Society of Anesthesiologists Score on Oncologic Outcomes in Patients With Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Large-Sample Study in Two Institutions.

INTRODUCTION: As a research team of urologists and an anesthetist, we sought to investigate the prognostic significance of American Society of Anesthesiologists (ASA) score in patients with upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU). ASA physical status (ASA-PS) classification not only was found to be associated with increased comorbidities but also independently factors for predicting morbidity and mortality. Accurate risk assessment was being particularly important for patients being considered for surgery. METHODS: Records for 958 patients with UTUC who underwent RNU were reviewed. Clinicopathologic variables, including ASA-PS, were assessed at two institutions. Overall survival (OS), cancer-specific survival (CSS), intravesical recurrence-free survival (IRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method and Cox regression analyses. We measured the independent predictive value of ASA-PS for mortality by multivariate regression. Association of ASA-PS and clinicopathologic variables was assessed. RESULTS: The group of patients with ASA = 2/3 had a shorter 5-year OS (67.6% and 49.9%), CSS (72.9% and 58.1%), and MFS (75.1% and 58.5%). The median follow-up time was 39 months. Kaplan-Meier curves showed that the group with ASA = 2/3 had significantly poorer OS, CSS, and MFS. Adjusting for multiple potential confounding factors, multivariate analyses suggested that ASA score was an independent predictor of OS, CSS, and MFS (p = 0.004, p = 0.005, p < 0.001). CONCLUSION: Higher ASA scores were independently associated with lower survival rate. This capability, along with its simplicity, makes it a valuable prognostic metric. It should be seriously referenced in UTUC patients being considered for RNU.

Characteristics and sources of amine-containing particles in the urban atmosphere of Liaocheng, a seriously polluted city in North China during the COVID-19 outbreak.

The Chinese government issued an unprecedentedly strict lockdown policy to control the spread of the novel coronavirus disease 2019 (COVID-19), significantly mitigating air pollution because of the dramatic reduction of industrial and traffic emissions. To explore the impact of COVID-19 lockdown (LCD) on organic aerosols, the mixing states and evolution processes of amine-containing particles were studied using a single particle aerosol mass spectrometer from January to March 2020 in Liaocheng, which is a seriously polluted city in North China. The counts and percentages of amine-containing particles in total obtained particles during the pre-LCD (547832, 29.8 %) were higher than those during the LCD (283983, 20.7 %) and post-LCD (102026, 18.4 %), mainly due to the reduced emission strength of amines and suppressed gas-to-particle partitioning of amines during the LCD and post-LCD. 74(C2H5)2NH2+ was the most abundant amine marker, which accounted for 98.2 %, 98.4 %, and 96.7 % of all amine-containing particles during the pre-LCD, LCD, and post-LCD, respectively. Correlation analysis and temporal variations indicated that the gas-to-particle partitioning of amines was facilitated by the stronger acidic environment and lower temperature, while the effect of RH and aerosol liquid water content was minor. The A-OC particles were the most abundant type (accounting for ~40 %) throughout the observation period. The temporal profiles and correlation analysis suggested that the impact of the increased O3 on the amines and their oxidation products (e.g., trimethylamine oxide) was minor. The identified particle types, correlation analysis, and the potential source contribution function results implied that the amine-containing particles were mainly derived from local and surrounding sources during the LCD, while those were mainly affected by long-range transport during the pre-LCD and post-LCD. Our results could deepen the comprehension of the sources and atmospheric processing of amines in the urban area of North China during the COVID-19 outbreak.

Vortex and symmetric radiation character of nonlinear Thomson scattering in Laguerre-Gaussian circularly polarized laser pulses.

The radiation character of nonlinear Thomson scattering is investigated in the interaction of Lagueree-Gaussian circularly polarized laser pulses with a single electron in the angular plane. With theoretical analysis and numerical calculation, it is shown that the angular radiation distributions have annular structures with great fourfold or plane symmetry in pulses characterized by comparatively lower laser intensity (a0 < 6), prolonged pulse duration (τ > 50fs)or wide beam waist (b0 > 5µm). In other circumstances, a vortex radiation pattern is found for the first time on the basis of the electron dynamics. Further, by increasing the initial phase of laser pulse, the overall angular radiation has an interesting counter-clockwise rotating trend with a cycle of Δξ0 = 2π. These results would help the understanding of nonlinear Thomson scattering and push forward the research of twisted X/γ-ray generation in optical laboratory.

Regulatory B cells improve ventricular remodeling after myocardial infarction by modulating monocyte migration.

Overactivated inflammatory responses contribute to adverse ventricular remodeling after myocardial infarction (MI). Regulatory B cells (Bregs) are a newly discovered subset of B cells with immunomodulatory roles in many immune and inflammation-related diseases. Our study aims to determine whether the expansion of Bregs exerts a beneficial effect on ventricular remodeling and explore the mechanisms involved. Here, we showed that adoptive transfer of Bregs ameliorated ventricular remodeling in a murine MI model, as demonstrated by improved cardiac function, decreased scar size and attenuated interstitial fibrosis without changing the survival rate. Reduced Ly6Chi monocyte infiltration was found in the hearts of the Breg-transferred mice, while the infiltration of Ly6Clo monocytes was not affected. In addition, the replenishment of Bregs had no effect on the myocardial accumulation of T cells or neutrophils. Mechanistically, Bregs reduced the expression of C-C motif chemokine receptor 2 (CCR2) in monocytes, which inhibited proinflammatory monocyte recruitment to the heart from the peripheral blood and mobilization from the bone marrow. Breg-mediated protection against MI was abrogated by treatment with an interleukin 10 (IL-10) antibody. Finally, IL-10 neutralization reversed the effect of Bregs on monocyte migration and CCR2 expression. The present study suggests a therapeutic value of Bregs in limiting ventricular remodeling after MI through decreasing CCR2-mediated monocyte recruitment and mobilization.

The influence of LncRNA H19 polymorphic variants on susceptibility to cancer: A systematic review and updated meta-analysis of 28 case-control studies.

OBJECTIVE: Although myriad researches upon the associations between LncRNA H19 polymorphic variants (rs2839698 G>A, rs217727 G>A, rs2107425 C>T, rs2735971 A>G and rs3024270 C>G) and the susceptibility to cancer have been conducted, these results remained contradictory and perplexing. Basing on that, a systematic review and updated meta-analysis was performed to anticipate a fairly precise assessment about such associations. METHODS: We retrieved the electronic databases EMBASE, PubMed and Web of Science for valuable academic studies before February 28, 2021. Ultimately, 28 of which were encompassed after screening in this meta-analysis, and the available data was extracted and integrated. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) was used to evaluate such associations. For multi-level investigation, subgroup analysis derived from source of controls together with genotypic method was preformed. RESULTS: Eventually, 28 articles altogether embodying 57 studies were included in this meta-analysis. The results illuminated that LncRNA H19 polymorphisms mentioned above were all irrelevant to cancer susceptibility. Nevertheless, crucial results were found concentrated in population-based control group when subgroup analysis by source of controls were performed in H19 mutation rs2839698 and rs2735971. Meanwhile, in the stratification analysis by genotypic method, apparent cancer risks were discovered by TaqMan method in H19 mutation rs2107425 and rs3024270. Then, trial sequential analysis demonstrated that the results about such associations were firm evidence of effect. CONCLUSION: Therefore, this meta-analysis indicated that LncRNA H19 polymorphisms were not associated with the susceptibility to human cancer. However, after the stratification analysis, inconsistent results still existed in different genotypic method and source of control. Thus, more high-quality studies on cancer patients of different factors were needed to confirm these findings.

Urinary Molecular Pathology for Patients with Newly Diagnosed Urothelial Bladder Cancer.

PURPOSE: Next-generation sequencing (NGS)-based profiling of both urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) shows promise for noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, the analytical performance of these assays remains undefined in the real-world setting. Here, we sought to evaluate the concordance between tumor DNA (tDNA) profiling and utDNA or ctDNA assays using a UBC patient cohort from the intended-use population. MATERIALS AND METHODS: Fifty-nine cases with pathologically confirmed disease and matching tissue/urine pairs were prospectively enrolled. Baseline peripheral blood mononuclear cell and plasma specimens were collected during clinic visits. The PredicineCARETM NGS assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tDNA, utDNA and ctDNA. RESULTS: Diverse quantitative metrics including cancer cell fraction, variant allele frequency and tumor mutation burden were invariably concordant between tDNA and utDNA, but not ctDNA. The mutational landscapes captured by tDNA or utDNA were highly similar, whereas a considerable proportion of ctDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed somatic events as reference, utDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value of 67.2%, a negative predictive value of 99.8% and a diagnostic accuracy of 99.1%. Higher preoperative utDNA or tDNA abundance correlated with worse relapse-free survival. Actionable variants including FGFR3 alteration and ERBB2 amplification were identified in utDNA. CONCLUSIONS: Urine-based molecular pathology provides a valid and complete genetic profile of bladder cancer, and represents a faithful surrogate for genotyping and monitoring newly diagnosed UBC.

A perioperative management to reduce rate of urinary tract infection for patient underwent radical cystectomy with ileal conduit diversion.

BACKGROUND: Although radical cystectomy, as the standard surgical treatment for muscle-invasive bladder cancer patients, prolongs survival remarkably, there are postoperative complications associated with urinary diversion. This study aimed to explore the antibiotic prophylaxis, according to culture of single J stent and urine from patients underwent urinary diversion (ileal conduit), its capacity to reduce the rate of urinary tract infection (UTI). METHODS: A total of 179 patients at Renji Hospital were reviewed in the study between Jan 2016 and June 2019. All patients included in this study were underwent radical cystectomy and ileal conduit. In Jan 2018, we enacted a quality initiative of urologic department to create a modified management. Following this initiative, antibiotic prophylaxis began to be used according to postoperative urine culture and stub of J-stent culture, which were obtained in 3rd days and 7th days after surgery, respectively. All consecutive patients treated with this process were compared with a conventional group. The clinicopathologic features of the two groups were compared using the t test and Chi square test. Multivariable logistic regression analysis was performed to determine the odds of developing 30-day UTI in two groups. RESULTS: 112 and 67 patients underwent the modified and conventional postoperative management, respectively. Two groups were comparable with regard to all demographic, clinical variables. The most common organism in urine culture and stub of J-stent culture was Candida albicans (38.46% and 31.7%). The rate of UTI was significantly lower in the modified group than in the conventional group (4.5% vs 13.4%, P = 0.031). In multivariable analyses, the conventional management was significantly more likely to develop UTI (OR = 4.992, 95% confidence interval [CI] 1.432-17.398 P = 0.012) than modified management. CONCLUSION: This procedure is associated with a significant decrease in UTI after surgery. During perioperative period, urine/single J stent culture with drug sensitivity test is necessary.

Co-Expression of Stem Cell and Epithelial Mesenchymal Transition Markers in Circulating Tumor Cells of Bladder Cancer Patients.

OBJECTIVE: Cancer cells with stemness and epithelial-to-mesenchymal transition (EMT) features display enhanced malignant and metastatic potential. This study aimed to introduce a new methodology developed in order to investigate the co-expression of a stemness (OCT4) and EMT markers on single circulating tumor cells (CTCs) of patients with localized urinary bladder cancer and their potential prognostic prediction value. METHODS AND MATERIALS: Between April 2015 and July 2015, blood samples of 51 consecutive patients diagnosed with high risk bladder cancer (cT1-3N0M0) were prospectively investigated for CTCs. Peripheral blood (5 mL) was drawn before primary transurethral resection. Detection of CTCs was performed using the CanPatrolTM system. Nucleic acid probes were used to identify CTCs, and expression levels of epithelial and mesenchymal genes in CTCs were examined by situ hybridization assay. RESULTS: All patients received radical cystectomy with pelvic lymph nodes dissection. CTCs were detected in 44 of 51 (86.3%) patients, respectively. The overall mean number of CTCs was 6.1 (range: 0~29; median: 4). A total of 311 CTCs were detected in PB. High OCT4 expression (OCT4high) was detected more frequently in Epi-Mes+ cells (p=0.001). Patients with pathological confirmed muscle-invasive bladder cancer (MIBC) had higher Epi-Mes+ CTCs positive rates (p=0.001) and OCT4high CTCs positive rates (p=0.019) than pathological confirmed non muscle-invasive bladder cancer (NMIBC). Regarding co-expression of these markers, Epi-Mes+/OCT4high CTCs were more frequently evident in the MIBC setting (30.4% vs 3.6% of patients, p = 0.016). CONCLUSION: A differential expression pattern for these markers was observed both in NMIBC and MIBC disease. A subgroup of CTCs showed a CTCs expressing high OCT4, along with Mes were more frequently detected in patients with MIBC, suggesting that these cells may prevail during tumor muscle invasion and disease progression.

Prediction of lymph node metastatic status in superficial esophageal squamous cell carcinoma using an assessment model combining clinical characteristics and pathologic results: A retrospective cohort study.

BACKGROUND: It is important to identify the risk of lymph node metastasis (LNM) in patients with superficial esophageal squamous carcinoma (SESC) who have received endoscopic resection (ER). We aimed to develop a risk-predicting model for metastasis of SESC to lymph nodes using clinicopathological features and pathological results. METHODS: Clinical data on 539 consecutive patients who underwent esophagectomy for SESC in our hospital were collected. Their post-surgical pathological results were assessed and analyzed. Multivariate logistic regression was used to identify all independent risk factors associated with LNM that then were incorporated into the prediction model. RESULTS: LNM was identified in 53 of 366 patients and 30 of 173 patients by positive histopathological results in the training and validation cohorts. The risk factors associated with LNM were large tumor size, poor tumor grade, deep invasion, and presence of angiolymphatic invasion. The model achieved good discriminatory ability of 0.80 (95%CI, 0.74-0.86) and 0.81 (95%CI, 0.75-0.86) in predicting LNM in the training and validation cohorts respectively. A LNM-predicting nomogram was formed with an area under curve of 0.80 (95% CI, 0.74-0.86), which had well-fitted calibration curves. CONCLUSIONS: A prediction model was constructed to generates 3 categories for estimated LNM risk in SESC patients. It provides a practical way of estimation of LNM risk in SESC patients who had received ER.

Inflammatory myofibroblastic tumors in the kidney and abdominal wall mimicking malignancy: A case report.

RATIONALE: Inflammatory myofibroblastic tumor (IMT) is uncommon, coexistence of IMTs in the kidney and abdominal wall are more uncommon. PATIENT CONCERNS AND DIAGNOSIS: We report a 74-year-old female who presented with 6 months history of left flank pain and approximately 5 kg weight loss that were diagnosed as renal cell carcinoma and locally metastatic abdominal wall tumor. INTERVENTIONS AND OUTCOMES: A left radical nephrectomy and excision of the abdominal wall tumor were done. The pathologic result was IMTs. After follow-up for 66 months, the patient showed no signs of tumor recurrence. LESSONS: Coexistence of IMTs in the kidney and abdominal wall is extremely rare and is often diagnosed as malignancy. Therefore, IMTs should be considered in the diagnosis of the patient with both kidney and abdominal wall tumors.

Expression of vitamin D receptor in clear cell papillary renal cell carcinoma.

Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized subtype of renal cell carcinoma. In this study, we investigated the clinicopathological and immunohistochemical features in a group of 26 cases of ccpRCC, with a special emphasis on the expression of vitamin D receptor (VDR). The mean age of patients was 53.3 years (range 36-74 years), and the mean tumor size was 2.5 cm (range 0.5 to 6.5 cm). During follow-up (range 12-121 months, median 50 months), no recurrence or metastasis was observed. Histopathologically, all cases of ccpRCC exhibited a tubular and papillary architecture, covered by tumor cells with clear cytoplasm. Immunohistochemistry showed intermediate (5/26, 19%) to diffuse (21/26, 81%) and moderate (2/26, 8%) to strong (24/26, 92%) membranous staining for VDR in each case. All cases (26/26, 100%) were diffuse and strong cytoplasmic and fibrillar staining for cytokeratin 7 (CK7), but negative forα-methylacyl-CoA-racemase (AMACR). Each case showed diffuse (26/26, 100%) and moderate (4/26, 15%) to strong (22/26, 85%) membranous staining for carbonic anhydrase IX (CA IX). In addition, the majority of cases showed negative for cluster of differentiation 10 (CD10) (20/26, 77%) and renal cell carcinoma maker (RCC-Ma) (24/26, 92%). This unique staining pattern is helpful for distinguishing ccpRCC from its mimics. Furthermore, VDR positive expression suggests that ccpRCC originates from the precursor epithelium of distal nephron.

Clinical features and survival analysis of clear cell papillary renal cell carcinoma: A 10-year retrospective study from two institutions.

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity, however, little is known about its clinical features. In the present study, 26 cases of CCPRCC were screened out from two institutions. The patient data, tissue pathology, immunohistochemical phenotype, computed tomographic images and survival analysis were studied. The mean age was 53.3 years and the average tumor size was 2.5 cm. A total of 17 patients' body mass indexes were higher than the normal level. A total of 11 patients had hypertension and 6 patients had a smoking history. Histopathologically, all cases of CCPRCC exhibited a tubular and papillary architecture, small to medium-sized cuboidal tumor cells with clear cytoplasms, and a low Fuhrman nuclear grade. All tumors were encapsulated by variably thick fibrous capsules. Immunohistochemistry showed diffuse and moderate to strong cytoplasmic staining for CK7, CA IX and vimentin, but negative for AMACR and CD10 (sometimes focally positive) in all cases. According to the results of Ki67 labeling index, the expression of Ki67 in CCPRCC was much lower than that in clear cell renal cell carcinoma (CCRCC) (2.19 vs. 7.07%, P<0.001) and that in papillary renal cell carcinoma (PRCC) (2.19 vs. 6.65%, P<0.001). Radiographically, the tumors were shown as small masses with smooth contour and mixed enhancement pattern. The multiphasic attenuation curve for CCPRCC, like that for CCRCC, increased in the corticomedullary phase markedly and decreased in the nephrographic phase and excretory phase gradually. At a median follow-up period of 50 months, no cancer-specific death or tumor recurrence was observed. Considering the favorable prognosis of CCPRCC, preoperative biopsy in order to make clear the diagnosis is particularly important. In light of the present findings, partial nephrectomy for patients with CCPRCC is recommended. If the patients cannot tolerate surgery, closed monitoring or radiofrequency ablation may be considered.