[Robot-assisted radical prostatectomy: An update].

The incidence of prostate cancer (PCa) is on a gradual rise. For localized PCa, radical prostatectomy is a main treatment option among many others, and laparoscopic radical prostatectomy is even considered as a gold treatment standard. However, with the development of robots and improvement of clinicians' surgical experience and understanding of prostatic anatomy, robot-assisted radical prostatectomy has been gaining a wide application. This review focuses on the development, advantages and disadvantages of robot-assisted radical prostatectomy with a view to providing some reference for clinicians.

Laparoscopic resection of a huge mature cystic teratoma of the right adrenal gland through retroperitoneal approach: a case report and literature review.

BACKGROUND: At present, the primary mature cystic teratoma in the adrenal gland is extremely rare in adults, according to the literature. In addition, a completely retroperitoneoscopic resection of mature cystic teratomas has been reported only in two cases. CASE PRESENTATION: We report a case of a large mature cystic teratoma with a regular margin in the right adrenal gland. Three months before surgery, abdominal enhanced computer tomography revealed a 5.7 × 4.9 × 4.3 cm lipoid tumour of mixed density with calcification in the tumorous centre, clinically diagnosed as adrenal myelolipoma or adenoma. Retroperitoneoscopic adrenalectomy was successfully performed; however, the tumour had increased in size to approximately 6.0 × 7.0 × 11 cm. The pathological report suggested the final diagnosis of mature cystic teratoma. The patient had an uneventful course after the surgery and was free of recurrence or metastasis within 8 months of follow-up. CONCLUSIONS: Retroperitoneoscopic adrenalectomy for large adrenal masses is safe and feasible. To the best of our knowledge, this is the first report where of a large mature cystic teratoma of the right adrenal gland has been completely resected using retroperitoneoscopic approach.

An unexpected but interesting response to a novel therapy for malignant extragastrointestinal stromal tumor of the mesoileum: a case report and review of the literature.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Extragastrointestinal stromal tumors (eGISTs) of the mesoileum are extremely rare and are usually treated with surgery combined with imatinib therapy. CASE PRESENTATION: We present the case of a 43-year-old man who developed a large eGIST in the mesoileum. Abdominal/pelvic computed tomography revealed a large heterogeneous mass with cystic and solid components that measured 20.0 × 12.0 × 8.0 cm. Three cycles of neoadjuvant chemotherapy with epirubicin, cyclophosphamide and hydroxycamptothecin; en bloc resection; and three more cycles of adjuvant chemotherapy with the same regimen and drugs resulted in five years of disease-free survival without any symptoms. CONCLUSIONS: Although imatinib treatment is usually chosen for eGISTs, resistance to imatinib remains a concern; these patients may receive neoadjuvant or adjuvant chemotherapy. In case of the former, further treatment, that is, surgery or adjuvant chemotherapy, depends on tumor response to the neoadjuvant chemotherapy. In addition, this treatment for eGIST is not only beneficial but also economical for patients compared with imatinib. A novel treatment approach that combined neoadjuvant chemotherapy, surgery and adjuvant chemotherapy resulted in long-term survival in our patient, thus showing promise as a potential therapy for eGISTs.

Single-cell transcriptome analysis reveals the key genes associated with macrophage polarization in liver cancer.

BACKGROUND: The aim of this study was to reveal the key genes associated with macrophage polarization in liver cancer. METHODS: Data were downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas databases (TCGA). R package Seurat 4.0 was used to preprocess the downloaded single-cell sequencing data, principal component analysis, and clustering. R package SingleR was used to annotate cell types and calculate macrophage polarization scores. Spearman correlation analysis was performed to obtain key genes highly correlated with macrophage polarization in liver cancer. The Tumor IMmune Estimation Resource algorithm was used to analyze the correlation between genes and the infiltration level of macrophages. Finally, the prognostic model was constructed based on 6 macrophage polarization-related genes by multivariate Cox regression analysis. Kaplan-Meier curves and receiver operating characteristic curves validated the prognostic value of the prognostic model. RESULTS: Two thousand highly variable genes were obtained after the normalization of single-cell profiles. In all, 16 principal components and 15 cell clusters were obtained. Monocytes and macrophages were the main immune cells in the microenvironment of liver cancer tissues. Macrophage polarization scores showed that cluster 5 had the highest degree of polarization. Spearman analysis yielded that a total of 6 key genes associated with macrophage polarization (CD53, TGFBI, S100A4, pyruvate kinase M, LSP1, SPP1), and Tumor IMmune Estimation Resource analysis showed that 6 key genes were significantly positively correlated with macrophage infiltration levels. The model constructed by 6 key genes could effectively evaluate the prognosis of patients with liver cancer. CONCLUSIONS: The key genes associated with macrophage polarization, namely CD53, TGFBI, S100A4, pyruvate kinase M, LSP1, and SPP1, may be potential therapeutic targets for liver cancer.

Application of machine learning algorithm in prediction of lymph node metastasis in patients with intermediate and high-risk prostate cancer.

PURPOSE: This study aims to establish the best prediction model of lymph node metastasis (LNM) in patients with intermediate- and high-risk prostate cancer (PCa) through machine learning (ML), and provide the guideline of accurate clinical diagnosis and precise treatment for clinicals. METHODS: A total of 24,470 patients with intermediate- and high-risk PCa were included in this study. Multivariate logistic regression model was used to screen the independent risk factors of LNM. At the same time, six algorithms, namely random forest (RF), naive Bayesian classifier (NBC), xgboost (XGB), gradient boosting machine (GBM), logistic regression (LR) and decision tree (DT) are used to establish risk prediction models. Based on the best prediction performance of ML algorithm, a prediction model is established, and the performance of the model is evaluated from three aspects: area under curve (AUC), sensitivity and specificity. RESULTS: In multivariate logistic regression analysis, T stage, PSA, Gleason score and bone metastasis were independent predictors of LNM in patients with intermediate- and high-risk PCa. By comprehensively comparing the prediction model performance of training set and test set, GBM model has the best prediction performance (F1 score = 0.838, AUROC = 0.804). Finally, we developed a preliminary calculator model that can quickly and accurately calculate the regional LNM in patients with intermediate- and high-risk PCa. CONCLUSION: T stage, PSA, Gleason and bone metastasis were independent risk factors for predicting LNM in patients with intermediate- and high-risk PCa. The prediction model established in this study performs well; however, the GBM model is the best one.

Advancements in the treatment of metastatic hormone-sensitive prostate cancer.

In the last decade, there have been substantial improvements in the outcome of the management of metastatic hormone-sensitive prostate cancer (mHSPC) following the development of several novel agents as well as by combining several therapeutic strategies. Although the overall survival (OS) of mHSPC is shown to improve with intense androgen deprivation therapy (ADT), combined with docetaxel, as well as other novel hormonal therapy agents, or alongside local intervention to the primary neoplasm. Notably, luteinizing hormone-releasing hormone (LHRH) antagonists are known to cause fewer cardiovascular side effects compared with LHRH agonists. Thus, in this mini review, we explore the different approaches in the management of mHSPC, with the aim that we may provide useful information for both basic scientists and clinicians when managing relevant clinical situations.

KLK6 mediates stemness and metabolism of gastric carcinoma cells via the PI3K/AKT/mTOR signaling pathway.

Gastric cancer is a common tumor of the digestive system, which can occur in any part of the stomach. Kallikrein 6 (KLK6) is a trypsin-like serine protease and has been found to be involved in extracellular matrix remodeling, tumor invasion and nervous system plasticity. Our previous study reported that KLK6 suppressed HGC-27 gastric cancer cell growth by inhibiting epithelial-mesenchymal transition; however, the mechanism of action underlying the effect of KLK6 still remains unclear. The aim of the present study was to investigate the effect and the underlying mechanism of KLK6 on stem cell-like properties and metabolism in gastric carcinoma cells. The HGC-27 cell line was transfected with KLK6 overexpression (OV-KLK6) and interference (short hairpin-KLK6) vectors, then the transfection efficiency was confirmed using western blot analysis and reverse transcription-quantitative PCR. The percentage of CD133+ and CD44+ cells was detected using flow cytometry, while the protein expression levels of the stem-associated genes, Nanog, Oct-4, SOX2 and Notch1, the metabolic markers, hexokinase (HK)1, HK2, GLUT1, and the proteins within the PI3K signaling pathway, phosphorylated (p)-PI3K, p-AKT and p-mTOR, were determined using western blot analysis. Biochemical kits were used to measure ATP production, lactic acid content and glucose uptake. A tumorigenicity assay was performed with nude mice to detect gastric tumor volume, and the protein expression level of Oct-4, Nanog, HK1, HK2 and GLUT1, and the mRNA expression level of KLK6 was also determined in gastric tumor tissues of mice. Compared with that in the control group, KLK6 protein and mRNA expression levels were significantly decreased in the four sh-RNA groups (P<0.05). Among them, sh-RNA-3 induced the lowest KLK6 expression and was used to silence KLK6 in subsequent experiments. Compared with that in the control and negative control groups, the percentage of CD133+ and CD44+ cells, the protein expression level of Oct-4, Nanog, HK1, HK2, GLUT1, p-PI3K, p-AKT and p-mTOR, and ATP content, lactic acid production, glucose uptake and gastric tumor volume were significantly decreased by sh-KLK6 (P<0.05), whereas KLK6 overexpression induced the opposite effect (P<0.05). In conclusion, KLK6 modulated stemness properties and cell metabolic profile in gastric carcinoma cells and the mechanism may be associated with the PI3K/AKT/mTOR signaling pathway.

Silencing of kallikrein-related peptidase 6 attenuates the proliferation, migration, and invasion of gastric cancer cells through inhibition of epithelial-mesenchymal transition.

Kallikrein-related peptidase 6 (KLK6), a member of the kallikrein-related peptidase family, is involved in the regulation of epithelial-mesenchymal transition (EMT) in cancer cells and is highly expressed in gastric cancer tissues. The aim of the present study was to investigate the effect of KLK6 on the proliferation, migration and invasion of gastric cancer cells and to determine the underlying mechanism of its actions. The expression of KLK6 was measured in metastatic gastric cancer cells using western blotting and reverse transcription-quantitative PCR, and KLK6 was overexpressed or inhibited in HGC-27 cells using plasmid transfection. Cell proliferation, migration, invasion and EMT were also evaluated using Cell Counting Kit 8, Transwell and western blot analysis, respectively. In addition, a mouse xenograft model was constructed by injection of HGC-27 cells. The xenograft was treated with KLK6 interference or overexpression plasmids to study the in vivo effects of KLK6 on tumor development. The results demonstrated that KLK6 was highly expressed in HGC-27 cells and that KLK6 inhibition attenuated cell proliferation, migration and invasion and prevented gastric cancer tumor development. In addition, KLK6 inhibition reduced the expression of epithelial cell adhesion molecule and vimentin, reduced the phosphorylation of SMAD2 and SMAD3 and upregulated epithelial-cadherin expression. In conclusion, KLK6 inhibition suppressed the proliferation, migration and invasion of gastric cancer cells both in vitro and in vivo through the inhibition of EMT. These findings indicate that KLK6 a potential therapeutic target for gastric cancer therapy.

Robot-assisted Cavectomy Versus Thrombectomy for Level II Inferior Vena Cava Thrombus: Decision-making Scheme and Multi-institutional Analysis.

BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described. OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT. DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019. SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals. MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed. RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed. CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation. PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

A comparative study on endoscopic submucosal dissection and laparoscopy-assisted radical gastrectomy in the treatment of early gastric carcinoma.

PURPOSE: To compare the clinical efficacy and safety of endoscopic submucosal dissection (ESD) and laparoscopy-assisted radical gastrectomy (LARG) in the treatment of early gastric carcinoma (EGC) with different risks of lymph node metastasis. METHODS: The clinical data of 194 EGC patients who underwent ESD (ESD group, n=58) or LARG (LARG group, n=136) in our hospital from January 2014 to January 2016 were collected. The baseline data, pathological features of tumor, perioperative indexes and long- and short-term complications were compared between the two groups, the overall survival (OS) rate of patients was recorded through follow-up, and the tumor-free survival (TFS) rate was compared after ESD and LARG for EGC with different risks of lymph node metastasis. RESULTS: The general clinical features were comparable between the two groups of patients, and there was no perioperative death. The pathological features of the tumor had no statistically significant differences between the two groups (p>0.05). The operation time in ESD group (73.57±21.30 min) was significantly shorter than that in LARG group (159.22±39.40 min) (p<0.001), and the time of first ambulation after operation in ESD group (1.6±0.8 d) was also overtly shorter than that in LARG group (3.5±1.7 d) (p<0.001). Postoperatively, no drainage tube was placed in the ESD group, while it was placed for 5.7±2.4 days on average in the LARG group. The time of first flatus after operation, time of first liquid diet after operation, and total hospitalization time in the ESD group were significantly compared with the LARG group (p<0.001). The incidence rate of short-term complications after surgery was 10.3% and 7.4% in the two groups, (p=0.570), while long-term complications were 17.6% (9/51) and 20.9% (24/115) in the two groups (p=0.631). The in situ tumor recurrence by the end of follow-up was 3.92% (2/51) and 0.87% (1/115) in the two groups, while the ectopic recurrence rate was 5.89% (3/51) and 0.87% (1/115) (p=0.173, p=0.087). OS survival was 96.1% (49/51) and 97.4% (112/115) in the two groups (p=0.751). The postoperative TFS of EGC patients with a low risk of lymph node metastasis was 93.8% (30/32) and 98.6% (70/71) in the two groups, again without significant difference (p=0.197). The postoperative TFS of EGC patients with a high risk of lymph node metastasis was 84.2% (16/19) and 97.7% (43/44) in the two groups, with statistically significant difference (log-rank, p=0.034). CONCLUSIONS: ESD is characterized by small trauma, rapid postoperative recovery, postoperative recurrence and survival comparable to those after surgical operation and high safety for EGC with a low risk of lymph node metastasis. LARG can reduce the postoperative recurrence rate of EGC in patients with high risk of lymph node metastasis.

ANTICANCER ACTIVITY OF 5, 7-DIMETHOXYFLAVONE AGAINST LIVER CANCER CELL LINE HEPG2 INVOLVES APOPTOSIS, ROS GENERATION AND CELL CYCLE ARREST.

BACKGROUND: Flavonoids are considered potential anticancer agents owing to their properties to interact with a diversity of cellular entities. Among flavonoids, methylated flavones are more efficient anticancer agents due to their higher stability in vivo. The purpose of the present study was, therefore, to evaluate the anticancer effect of methylated natural flavonoid 5, 7-dimethoxyflavone (5, 7-DMF). MATERIALS AND METHODS: MTT assay was used to determine the anticancer activity and IC50 of 5, -DMF). Cell viability, cell cycle distribution, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were carried out by flow cytometry. Apoptosis was studied by DAPI staining. RESULTS: MTT assay revealed that the molecule reduced the cell viability of HepG2 cancer cells. The IC50 of 5, 7-DMF was found to be 25 µM. Our result indicated that 5, 7-DMF triggered production of ROS and significantly reduced ΔΨm . It also leads to arrest of HepG2 cells in Sub-G1 stage of cell cycle, and ultimately induced apoptosis in a concentration-dependent manner, as indicated by DAPI staging. Additionally, 5, 7-DMF also reduced the colony forming potential of the HepG2 cells concentration dependently. CONCLUSION: Taken together, we conclude that 5, 7-DMF induces cell death via ROS generation, cell cycle arrest and apoptosis, and, therefore, may prove beneficial in the treatment of liver cancer.

Simultaneous metastases of clear cell renal cell carcinoma to the urinary bladder and left retroperitoneal space: A case report and review of the literature.

The present study describes an extremely rare case of simultaneous metastases of clear cell renal cell carcinoma (ccRCC) to the urinary bladder and left retroperitoneal space, occurring subsequent to an open radical nephrectomy. A review of the literature is also considered. A 70-year-old man presenting with diabetes mellitus and hypertension was referred to West China Hospital (Chengdu, China) with constant left flank pain that had been apparent for 2 months. Ultrasonography identified a heterogeneous tumor with a solid component measuring 4.4×3.4×5.0 cm, and computed tomography (CT) revealed a circumscribed and contrast-enhanced tumor in the left kidney. Subsequent pathological analysis of the specimen, obtained from an open radical nephrectomy, confirmed the presence of ccRCC. At 1 month after the radical nephrectomy, an abdominopelvic CT scan identified tumors located on the posterior bladder wall and also in the left retroperitoneal space, forming due to hematuria and acute urinary clot retention. There was no evidence of metastasis to the lungs, bones or other organs. A transurethral resection of the bladder tumor was performed and pathological analysis of the bladder specimen demonstrated metastatic ccRCC. Extensive hydrothorax and general anasarca presented half a month after the transurethral resection, with the patient subsequently succumbing 15 days later.

Duodenal-Jejunal Bypass Surgery Ameliorates Glucose Homeostasis and Reduces Endoplasmic Reticulum Stress in the Liver Tissue in a Diabetic Rat Model.

BACKGROUND: Duodenal-jejunal bypass (DJB) has been shown to be an effective surgical treatment for type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are poorly understood. Recently, accumulating evidences suggest that endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance in T2DM. The present study was designed to investigate the effect of DJB on glucose homeostasis, the ER stress state in the liver tissue, and the involving signaling independently of weight loss. METHODS: Thirty adult male T2DM Sprague-Dawley (SD) rats induced by high-fat diet and low dose of streptozotocin (STZ) were randomly divided into DJB and sham groups. Ten age-matched male SD rats were assigned as the control group. The parameters of body weight and calorie intake were measured at indicated time points. The glucose tolerance and insulin resistance were detected to evaluate the glucose homeostasis. Serum insulin was determined by enzyme-linked immunosorbent assay (ELISA). The markers of ER stress, the activity of c-Jun N-terminal kinase (JNK) and serine phosphorylation of insulin receptor substrate 1 (IRS-1) in the liver tissue, were determined by Western blotting. RESULTS: DJB induced significant improvements in glucose homeostasis and insulin sensitivity, but without weight loss. DJB improved the ER stress state indicated by decreased protein kinase RNA (PKR)-like ER protein kinase (PERK) and inositol-requiring enzyme 1 (IRE-1) phosphorylation in the liver tissue. The JNK activity and serine phosphorylation of IRS-1 in the liver tissue were significantly reduced after DJB. CONCLUSIONS: DJB ameliorates glucose homeostasis. Meanwhile, our study helps to reveal that the reduced hepatic ER stress and the decreased JNK activity may contribute to the improved glucose homeostasis after DJB.

The effect of intravesical chemotherapy in the prevention of intravesical recurrence after nephroureterectomy for upper tract urothelial carcinoma: a meta-analysis.

CONTEXT: The standard management of upper urinary tract urothelial carcinoma (UUT-UC) is nephroureterectomy with bladder cuff excision, but after surgery, approximately 22-47% of patients with UUT-UC develop subsequent bladder tumour recurrence, potentially because of the implantation of cancer cells from the primary tumour. OBJECTIVE: To conduct a meta-analysis to evaluate the effect of prophylactic intravesical chemotherapy in the prevention of bladder recurrence after nephroureterectomy for UUT-UC. DATA ACQUISITION: An electronic database search of Medline, Embase, the Cochrane Library, CancerLit and ClinicalTrials.gov was performed to identify appropriate studies prior to March 2013.All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The main outcome measure for this meta-analysis was the rate of bladder recurrence after nephroureterectomy. The search was not limited by language. The review process followed the guidelines of the Cochrane Collaboration. The analysis was conducted using the Review Manager Version RevMan 5.0 software (The Nordic Cochrane Centre, The Cochrane Collaboration). RESULTS: A total of 592 patients were included in this study, of whom 257 underwent intravesical instillation after nephroureterectomy and 335 underwent nephroureterectomy alone. Our meta-analysis demonstrated that the rate of recurrence after 12 months was significantly lower in the intravesical instillation after nephroureterectomy group than in the nephroureterectomy-alone group [odds ratio (OR): 0.48; 95% confidence interval (CI): 0.28-0.81; P = 0.006]. A significant decrease in bladder recurrence after at least 24  months was also observed in the intravesical instillation after nephroureterectomy group (OR: 0.40; 95% CI: 0.24-0.67; P = 0.0004). A subgroup analysis demonstrated that the pattern of differences was similar to those from the total group analysis. CONCLUSIONS: Prophylactic intravesical chemotherapy was effective for the prevention of bladder recurrence after nephroureterectomy. Therefore, we suggest that prophylactic intravesical chemotherapy should be performed in patients with UUT-UC after nephroureterectomy, but the optimal chemotherapy regimen and the initial time of instillation should be explored in future studies.

Identification of key genes associated with colorectal cancer based on the transcriptional network.

Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism of the cancer is still unclear enough. We aimed to explore the key genes in CRC progression. The gene expression profile (GSE4183) of CRC was obtained from Gene Expression Omnibus database which included 8 normal samples, 15 adenoma samples, 15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8 normal, 15 adenoma, and 15 CRC samples were chosen for our research. The differentially expressed genes (DEGs) in normal vs. adenoma, normal vs. CRC, and adenoma vs. CRC, were identified using the Wilcoxon test method in R respectively. The interactive network of DEGs was constructed to select the significant modules using the Pearson's correlation. Meanwhile, transcriptional network of DEGs was also constructed using the g: Profiler. Totally, 2,741 DEGs in normal vs. adenoma, 1,484 DEGs in normal vs. CRC, and 396 DEGs in adenoma vs. CRC were identified. Moreover, function analysis of DEGs in each group showed FcR-mediated phagocytosis pathway in module 1, cardiac muscle contraction pathway in module 6, and Jak-STAT signaling pathway in module 19 were also enriched. Furthermore, MZF1 and AP2 were the transcription factor in module 6, with the target SP1, while SP1 was also a transcription in module 20. DEGs like NCF1, AKT, SP1, AP2, MZF1, and TPM might be used as specific biomarkers in CRC development. Therapy targeting on the functions of these key genes might provide novel perspective for CRC treatment.