Limited information is available for guiding the management of upper urinary tract (UUT) urothelial carcinoma with squamous differentiation (UC-SqD). We did not even know about the difference between ...pure urothelial carcinoma (UC) and UC-SqD in the UUT regardless of treatment policy and prognosis. Instead of direct comparisons against each other, we included the third UUT malignancy, squamous cell carcinoma (SCC). This three-way-race model allows us to more clearly demonstrate the impact of squamous cell transformation on patient outcomes in UUT malignancy.
We retrospectively analysed 327 patients with UC, UC-SqD, or SCC who underwent radical nephroureterectomy with bladder cuff excision (RNU) at Taichung Veterans General Hospital, Taichung, Taiwan, between January 2006 and December 2013. A Kaplan-Meier survival analysis was used to evaluate the relationship between patient outcomes and histology. Multivariate Cox proportional hazards modelling was also used to predict patient prognoses.
The five-year postoperative cancer-specific survival (CSS) rates were 83.6% (UC), 74.4% (UC-SqD), and 55.6% (SCC), and the 5-year recurrence-free survival (RFS) rates were 87.7% (UC), 61.5% (UC-SqD), and 51.9% (SCC). UC patients had significantly better 5-year RFS than UC-SqD and SCC patients (P = 0.001 and P < 0.0001, respectively). Patients with pure UC had significantly better 5-year CSS than SCC patients (P = 0.0045). SCC or UC-SqD did not independently predict disease-specific mortality (HR 0.999, p = 0.999; HR 0.775, p = 0.632, respectively) or disease recurrence compared to pure UC (HR 2.934, p = 0.239; HR 1.422, p = 0.525, respectively). Age, lymphovascular invasion (LVI), and lymph node (LN) status independently predicted CSS, while pathological tumour stage, LN status, and LVI predicted RFS.
SCC and UC-SqD are not independent predictors of survival outcomes in patients with UUT tumours. However, they are associated with other worse prognostic factors. Hence, different treatments are needed for these two conditions, especially for SCC.
Metformin may offer benefits to certain cancer populations experiencing metabolic abnormalities. To extend the anticancer studies of metformin, a tumor model was established through the implantation ...of murine Lewis Lung Carcinoma (LLC) cells to Normal Diet (ND)-fed and High-Fat Diet (HFD)-fed C57BL/6 mice. The HFD-fed mice displayed metabolic and pro-inflammatory alterations together with accompanying aggressive tumor growth. Metformin mitigated tumor growth in HFD-fed mice, paralleled by reductions in circulating glucose, insulin, soluble P-selectin, TGF-β1 and High Mobility Group Box-1 (HMGB1), as well as tumor expression of cell proliferation, aerobic glycolysis, glutaminolysis, platelets and neutrophils molecules. The suppressive effects of metformin on cell proliferation, migration and oncogenic signaling molecules were confirmed in cell study. Moreover, tumor-bearing HFD-fed mice had higher contents of circulating and tumor immunopositivity of Neutrophil Extracellular Traps (NETs)-associated molecules, with a suppressive effect from metformin. Data taken from neutrophil studies confirmed the inhibitory effect that metformin has on NET formation induced by HMGB1. Furthermore, HMGB1 was identified as a promoting molecule to boost the transition process towards NETs. The current study shows that metabolic, pro-inflammatory and NET alterations appear to play roles in the obesity-driven aggressiveness of cancer, while also representing candidate targets for anticancer potential of metformin.
The prognostic and therapeutic values of fibronectin have been reported in patients with renal cell carcinoma (RCC). However, the underlying mechanisms of malignancy in RCC are not completely ...understood. We found that silencing of fibronectin expression attenuated human RCC 786-O and Caki-1 cell growth and migration. Silencing of potential fibronectin receptor integrin α5 and integrin β1 decreased 786-O cell ability in movement and chemotactic migration. Biochemical examination revealed a reduction of cyclin D1 and vimentin expression, transforming growth factor-β1 (TGF-β1) production, as well as Src and Smad phosphorylation in fibronectin-silenced 786-O and Caki-1 cells. Pharmacological inhibition of Src decreased 786-O cell growth and migration accompanied by a reduction of cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. In 786-O cells, higher activities in cell growth and migration than in Caki-1 cells were noted, along with elevated fibronectin and TGF-β1 expression. The additions of exogenous fibronectin and TGF-β1 promoted Caki-1 cell growth and migration, and increased cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. These findings highlight the role of fibronectin in RCC cell growth and migration involving Src and TGF-β1 signaling.
Study Type – Therapy (case series)
Level of Evidence 4
What’s known on the subject? and What does the study add?
Between December 2005 and January 2010, 200 consecutive patients with prostate cancer ...received RALP performed by a single surgeon. Only one case with Clavien grade II complication due to gouty arthritis. The complication rate was 1%. We suggested that patient with history of gouty arthritis need to prescribe preventive colchicine.
OBJECTIVE
•
To analyse the learning curve for reducing complications of robotic‐assisted laparoscopic radical prostatectomy (RALP) performed by a single surgeon in Taiwan.
PATIENTS AND METHODS
•
Complication rates were prospectively assessed in 200 consecutive patients undergoing RALP (Group I: cases 1–50; Group II: cases 51–100; Group III: cases 101–150 and Group IV: cases 151–200).
•
Complications were classified using the Clavien system: grade I: deviation normal postoperative course without treatment; grade II: drug or bedside treatment; grade III: endoscopic or surgical intervention; grade IV: life‐threatening problem; and grade V: death.
•
Operative parameters and peri‐operative complications were evaluated, including operative and console time, blood loss and transfusion rate, Gleason scores, positive surgical margin (PSM) rate, specimen volume, tumour size, tumour percentage, node positive rate and intra‐ and postoperative complications.
RESULTS
•
RALP console time was gradually lowered from Group I to Group IV (P < 0.05). Significantly less blood loss occurred after every 50 cases of RALP (Group I 275 mL, Group II 179 mL, Group III 145 mL, Group IV 102 mL, P < 0.001).
•
Blood transfusion incidence was 8%, 4%, 2% and 0% in Groups I, II, III and IV, respectively.
•
Complication rates were 18%, 12%, 18% and 0% in Groups I, II, III and IV, respectively.
•
Major complications (grade III–IV) were 6%, 2%, 4% and 0% in Groups I, II, III and IV, respectively.
•
Bowel injury occurred in three cases (Group II: 1; Group III: 2); one received intra‐operative repair without sequelae and two received a transient colostomy and later colostomy closure.
CONCLUSIONS
•
The learning curve for every 50 cases of RALP showed significantly less blood loss and blood transfusion rate.
•
The learning curve for significantly decreasing complications is 150 cases.
Background
The Paris System for Reporting Urinary Cytology (TPS) has been shown to improve bladder cancer diagnosis. Advances in artificial intelligence (AI) may assist and improve the clinical ...workflow by applying TPS in routine diagnostic services.
Methods
A deep‐learning–based algorithm was developed to identify urothelial cancer candidate cells using whole‐slide images (WSIs). In the testing cohort, 131 urine cytology slides were retrospectively retrieved and analyzed using this AI algorithm. The authors compared the performance of one cytopathologist and two cytotechnologists using AI‐assisted digital urine cytology. Then, the AI‐assisted WSIs were evaluated in the clinical workflow. The cytopathologist first made a diagnosis by reviewing the AI‐inferred WSIs and quantitative data (nuclear‐to‐cytoplasmic ratio and nuclear size) for each sample. After a washout period, the same cytopathologist made a diagnosis for the same samples using direct microscopy. All diagnosis results were compared with the expert panel consensus.
Results
The AI‐assisted diagnosis by the two cytotechnologists and the one cytopathologist demonstrated performance results that were comparable to the expert panel consensus (sensitivity, 79.5% and 82.1% vs. 92.3%, respectively; specificity, 100% and 98.9% vs. 100%, respectively). Furthermore, the performance of the AI‐assisted WSIs compared with the microscopic diagnosis by the cytopathologist demonstrated superior sensitivity (92.3% vs. 87.2%) and negative predictive value (96.8% vs. 94.8%). In addition, the AI‐assisted reporting demonstrated near perfect agreement with the expert panel consensus (κ = 0.944) and the microscopic diagnosis (κ = 0.862).
Conclusions
The AI algorithm developed by the authors effectively assisted TPS‐based reporting by providing AI‐inferred WSIs and quantitative data.
A deep‐learning–based algorithm was developed to assist the Paris System‐based urine cytology reporting using whole‐slice imaging with automatic annotation of urothelial cells at risk and quantitative information, such as nuclear‐to‐cytoplasmic ratios. Compared with conventional microscopic examination, the algorithm‐assisted method displayed superior sensitivity (87.2% vs. 92.3%), better negative predictive value (94.8% vs. 96.8%), and nearly perfect agreement with the expert panel consensus (k = 0.862).
To investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with upper tract urothelial cell carcinoma (UTUC) receiving radical nephroureterectomy (RNU). Between ...January 2001 and December 2015, we enrolled 488 patients with UTUC underwent RNU in Taichung Veterans General Hospital. GNRI before radical surgery was calculated based on serum albumin level and body mass index. The malnutritional status was defined as GNRI < 92.0. Using Kaplan-Meier analyses and Cox proportional hazards models to analyze the risk factors on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). 386 patients were categorized as normal nutritional status (GNRI ≥ 92) and 102 patients as malnutritional status (GNRI < 92). We used the receiver operating characteristic (ROC) curve for determined the association between GNRI and OS, with area under the curve (AUC) being 0.69. The 5-year survival rate of DFS, CSS and OS were 48.6%, 80.5% and 80.5% in the normal nutritional group and 28.0%, 53.2% and 40% in the malnutritional group. Using the multivariate analysis, malnutritional status was found as an independent risk factor for OS (hazard ratio HR = 3.94, 95% confidence interval CI 2.70-5.74), together with age (HR = 1.04, 95% CI 1.02-1.06), surgical margin positive (HR = 1.78, 95% CI 1.13-2.82), pathological T3 (HR = 2.54, 95% CI 1.53-4.21), pathological T4 (HR = 6.75, 95% CI 3.17-14.37) and lymphovascular invasion (HR = 1.81, 95% CI 1.16-2.81). We also found GNRI index as independent risk factor in DFS (HR = 1.90, 95% CI 1.42-2.54) and CSS (HR = 5.42, 95% CI 3.24-9.06). Preoperative malnutritional status with low GNRI is an independent marker in predicting DFS, CSS and OS in UTUC patients underwent RNU.
Clinically, high cyclooxygenase-2 expression in malignant glioma correlates well with poor prognosis and the use of aspirin is associated with a reduced risk of glioma. To extend the current ...understanding of the apoptotic potential of aspirin in most cell types, this study provides evidence showing that aspirin induced glioma cell apoptosis and inhibited tumor growth, in vitro and in vivo. We found that the human H4 glioma cell-killing effects of aspirin involved mitochondria-mediated apoptosis accompanied by endoplasmic reticulum (ER) stress, Noxa upregulation, Mcl-1 downregulation, Bax mitochondrial distribution and oligomerization, and caspase 3/caspase 8/caspase 9 activation. Genetic silencing of Noxa or Bax attenuated aspirin-induced viability loss and apoptosis, while silencing Mcl-1 augmented the effects of aspirin. Data from genetic and pharmacological studies revealed that the axis of ER stress comprised an apoptotic cascade leading to Noxa upregulation and apoptosis. The apoptotic programs and mediators triggered by aspirin in H4 cells were duplicated in human U87 glioma cell line as well as in tumor-bearing BALB/c nude mice. The involvement of ER stress in indomethacin-induced Mcl-1 downregulation was reported in our previous study on glioma cells. Therefore, the aforementioned phenomena indicate that ER stress may be a valuable target for intervention in glioma apoptosis.
Objective: This study aimed to explore the benefits of theranostic robot-assisted radical prostatectomy (T-RARP) for clinically highly suspicious prostate cancer (PCa) without proven biopsies. ...Material and Methods: Between February 2016 and December 2020, we included men with clinically highly suspicious PCa in this study. They were assessed to have possible localized PCa without any initial treatments, and were categorized into previous benign biopsies or without biopsies. Furthermore, another group of malignant biopsies with RARP in the same time frame was adopted as the control group. The endpoints were to compare the oncological outcome and functional outcome between malignant biopsies with RARP and T-RARP. p < 0.05 was considered to be significant. Results: We included 164 men with proven malignant biopsies treated with RARP as the control group. For T-RARP, we included 192 men. Among them, 129 were preoperatively benign biopsies, and 63 had no biopsies before T-RARP. Approximately 75% of men in the T-RARP group had malignant pathology in their final reports, and the other 25% had benign pathology. T-RARP provides several oncological advantages, such as a higher initial pathological T stage, lower Gleason grade, and lower odds of positive surgical margins. However, the biochemical recurrence rates were not significantly decreased. From our cohort, T-RARP (odds ratio with 95% confidence interval; erectile recovery: 3.19 (1.84–5.52), p < 0.001; continence recovery: 2.25 (1.46–3.48), p < 0.001) could result in better recovery of functional outcomes than malignant biopsies with RARP. Conclusions: For clinically highly suspicious PCa, T-RARP was able to detect around 75% of PCa cases and preserved their functional outcomes maximally. However, in 25% of men with benign pathology, approximately 6% would have incontinence and 10% would have erectile impairment. This part should be sufficiently informed of the potential groups considering T-RARP.
Cell transplantation using bone marrow stromal cells (BMSCs) to alleviate neurological deficits has recently become the focus of research in regenerative medicine. Evidence suggests that secretion of ...various growth-promoting substances likely plays an important role in functional recovery against neurological diseases. In an attempt to identify a possible mechanism underlying the regenerative potential of BMSCs, this study investigated the production and possible contribution of neurotrophic factors by transected sciatic nerve defect in a rat model with a 15 mm gap. Cultured BMSCs became morphologically homogeneous with fibroblast-like shape after
ex vivo expansion. We provided several pieces of evidence for the beneficial effects of implanted fibroblast-like BMSCs on sciatic nerve regeneration. When compared to silicone tube control animals, this treatment led to (i) improved walking behavior as measured by footprint analysis, (ii) reduced loss of gastrocnemius muscle weight and EMG magnitude, and (iii) greater number of regenerating axons within the tube. Cultured fibroblast-like BMSCs constitutively expressed trophic factors and supporting substances, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), collagen, fibronectin, and laminin. The progression of the regenerative process after BMSC implantation was accompanied by elevated expression of neurotrophic factors at both early and later phases. These results taken together, in addition to documented Schwann cell-like differentiation, provide evidence indicating the strong association of neurotrophic factor production and the regenerative potential of implanted BMSCs.
PDF
