Tumor-neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression.

The immune landscape of bladder cancer progression is not fully understood, and effective therapies are lacking in advanced bladder cancer. Here, we visualized that bladder cancer cells recruited neutrophils by secreting interleukin-8 (IL-8); in turn, neutrophils played dual functions in bladder cancer, including hepatocyte growth factor (HGF) release and CCL3highPD-L1high super-immunosuppressive subset formation. Mechanistically, c-Fos was identified as the mediator of HGF up-regulating IL-8 transcription in bladder cancer cells, which was central to the positive feedback of neutrophil recruitment. Clinically, compared with serum IL-8, urine IL-8 was a better biomarker for bladder cancer prognosis and clinical benefit of immune checkpoint blockade (ICB). Additionally, targeting neutrophils or hepatocyte growth factor receptor (MET) signaling combined with ICB inhibited bladder cancer progression and boosted the antitumor effect of CD8+ T cells in mice. These findings reveal the mechanism by which tumor-neutrophil cross talk orchestrates the bladder cancer microenvironment and provide combination strategies, which may have broad impacts on patients suffering from malignancies enriched with neutrophils.

Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.

BACKGROUND: CDC6 is an oncogenic protein whose expression level fluctuates during the cell cycle. Although several E3 ubiquitin ligases responsible for the ubiquitin-mediated proteolysis of CDC6 have been identified, the deubiquitination pathway for CDC6 has not been investigated. METHODS: The proteome-wide deubiquitinase (DUB) screening was used to identify the potential regulator of CDC6. Immunofluorescence, protein half-life and deubiquitination assays were performed to determine the protein stability of CDC6. Gain- and loss-of-function experiments were implemented to analyse the impacts of OUTD6A-CDC6 axis on tumour growth and chemosensitivity in vitro. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced conditional Otud6a knockout (CKO) mouse model and tumour xenograft model were performed to analyse the role of OTUD6A-CDC6 axis in vivo. Tissue specimens were used to determine the association between OTUD6A and CDC6. RESULTS: OTUD6A interacts with, depolyubiquitinates and stabilizes CDC6 by removing K6-, K33-, and K48-linked polyubiquitination. Moreover, OTUD6A promotes cell proliferation and decreases sensitivity to chemotherapy by upregulating CDC6. CKO mice are less prone to BCa tumorigenesis induced by BBN, and knockdown of OTUD6A inhibits tumour progression in vivo. Furthermore, OTUD6A protein level has a positive correlation with CDC6 protein level, and high protein levels of OTUD6A and CDC6 are associated with poor prognosis in patients with bladder cancer. CONCLUSIONS: We reveal an important yet missing piece of novel DUB governing CDC6 stability. In addition, our findings propose a model for the OTUD6A-CDC6 axis that provides novel insights into cell cycle and chemosensitivity regulation, which may become a potential biomarker and promising drug target for cancer treatment.

The changes of intestinal microbiota and metabolomics during the inhibition of bladder cancer by liquiritigenin.

Liquiritigenin is a natural medicine. However, its inhibitory effect and its potential mechanism on bladder cancer (BCa) remain to be explored. It was found that it could be visualized that the transplanted tumours in the low-dose liquiritigenin -treated group and the high-dose liquiritigenin -treated group were smaller than those in the model group. Liquiritigenin treatment led to alterations in Lachnoclostridium, Escherichia-Shigella, Alistipes and Akkermansia. Non-targeted metabolomics analysis showed that a total of multiple differential metabolites were identified between the model group and the high-dose liquiritigenin-treated group. This provides a new direction and rationale for the antitumour effects of liquiritigenin.

Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer.

BACKGROUND: Prostate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prostate cancer remain ambiguous. METHODS: The tumor immune contexture score (TICS) involving eight immune contexture-related signatures was developed using seven cohorts of 1120 patients treated with radical prostatectomy (training: GSE46602, GSE54460, GSE70769, and GSE94767; validation: GSE70768, DKFZ2018, and TCGA). The association between the TICS and treatment efficacy was investigated in GSE111177 (androgen deprivation therapy [ADT]) and EGAS00001004050 (ipilimumab). RESULTS: A high TICS was associated with prolonged BCRFS after radical prostatectomy in the training (HR = 0.32, 95% CI 0.24-0.45, P < 0.001) and the validation cohorts (HR = 0.45, 95% CI 0.32-0.62, P < 0.001). The TICS showed stable prognostic power independent of tumor stage, surgical margin, pre-treatment prostatic specific antigen (PSA), and Gleason score (multivariable HR = 0.50, 95% CI 0.39-0.63, P < 0.001). Adding the TICS into the prognostic model constructed using clinicopathological features significantly improved its 1/2/3/4/5-year area under curve (P < 0.05). A low TICS was associated with high homologous recombination deficiency scores, abnormally activated pathways concerning DNA replication, cell cycle, steroid hormone biosynthesis, and drug metabolism, and fewer tumor-infiltrating immune cells (P < 0.05). The patients with a high TICS had favorable BCRFS with ADT (HR = 0.25, 95% CI 0.06-0.99, P = 0.034) or ipilimumab monotherapy (HR = 0.23, 95% CI 0.06-0.81, P = 0.012). CONCLUSIONS: Our study delineates the associations of tumor immune contexture with molecular features, recurrence after radical prostatectomy, and the efficacy of ADT and immunotherapy. The TICS may improve the existing risk stratification systems and serve as a patient-selection tool for ADT and immunotherapy in prostate cancer.

Pan-cancer analysis and experimental validation of DTL as a potential diagnosis, prognosis and immunotherapy biomarker.

BACKGROUND: DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far. METHODS: Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation. RESULTS: DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer. CONCLUSIONS: Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers.

siRNA-based approaches for castration-resistant prostate cancer therapy targeting the androgen receptor signaling pathway.

Androgen deprivation therapy is a common treatment method for metastatic prostate cancer through lowering androgen levels; however, this therapy frequently leads to the development of castration-resistant prostate cancer (CRPC). This is attributed to the activation of the androgen receptor (AR) signaling pathway. Current treatments targeting AR are often ineffective mostly due to AR gene overexpression and mutations, as well as the presence of splice variants that accelerate CRPC progression. Thus there is a critical need for more specific medication to treat CRPC. Small interfering RNAs have shown great potential as a targeted therapy. This review discusses prostate cancer progression and the role of AR signaling in CRPC, and proposes siRNA-based targeted therapy as a promising strategy for CRPC.

Initial experience with 161 extraperitoneal laparoscopic radical cystectomy procedures: Comparison with transabdominal laparoscopic radical cystectomy.

OBJECTIVES: There is substantial concern about traditional transperitoneal laparoscopic radical cystectomy (TLRC) due to multiple postoperative complications. In contrast, extraperitoneal laparoscopic radical cystectomy (ELRC) appears to cause a lower rate of morbidity. The present study aimed to compare the efficacy of ELRC and TLRC for bladder cancer (BCa). METHODS: The clinical data of patients undergoing laparoscopic radical cystectomy for BCa from April 2018 to October 2021 were retrospectively analyzed, as ELRC and TLRC groups. The postoperative follow-up data of 275 patients were collected and the incidence of postoperative complications and other perioperative outcomes were compared between the two groups. RESULTS: Surgery was successfully completed in all patients without conversion to open surgery. There was no significant difference in the duration of cystectomy surgery (67.32 ± 23.53 vs 72.17 ± 25.72 min, p = 0.106), intraoperative blood loss (178.06 ± 110.4 vs. 174.56 ± 127.40 ml, p = 0.413), or the number of lymph node dissection (15.1 ± 5.7 vs. 14.5 ± 5.1, p = 0.380) between the two groups. The length of stay (11.6 ± 3.8 vs 14.7 ± 5.6 d, p < 0.001), time to resume food intake after surgery (2.3 ± 0.9 vs 3.0 ± 1.3 d, p < 0.001), and the incidence of ileus (p < 0.001) in the ELRC group were significantly lower than in the TLRC group. CONCLUSIONS: ELRC is a safe procedure that can reduce the incidence of postoperative complications, shorten postoperative hospital stay, reduce the duration of recovery of patients, and, therefore, should be promoted.

Surgical Maneuver and Tactics of Using the Inferior Phrenic Vein as a Landmark in Retroperitoneal Laparoscopic Left Adrenalectomy.

Identification and control of the central adrenal vein (CAV) are key steps in laparoscopic adrenalectomy. However, the retroperitoneal laparoscopic left adrenalectomy (RLLA) lacks identifiable anatomical landmarks and does not have advantage of quickly exposing CAV. Here, we developed surgical maneuver and tactics of using the inferior phrenic vein (IPV) as a landmark in RLLA. During operations, we searched for the IPV between superior margin of renal artery and anterior aspect of psoas major muscle, and then the left IPV was followed and applied as an anatomical landmark to identify the CAV. Moreover, our study showed that variations in the left adrenal venous anatomy occurred in cases with pheochromocytomas. The application of left IPV as a landmark to search for CAV has important clinical significance in RLLA.

Efficacy and safety of surgery in renal carcinoma patients 75 years and older: a retrospective analysis.

OBJECTIVE: To investigate the efficacy and complications of surgical treatment in patients with renal cell carcinoma aged ≥ 75 years. METHODS: From January 2009 to May 2019, we assessed 166 patients aged 75 years and older, who either had radical nephrectomy (RN) or partial nephrectomy (PN) as treatments for diagnosed renal cell carcinoma. Patients were divided into one group of patients aged 75-79 years and the second group of patients ≥ 80 years. The complications and survival were compared between the two groups. RESULTS: All 166 patients were successfully operated on. Differences between the two groups were statistically significant in intraoperative and postoperative complications and Clavien-Dindo score of ≥ 1 (P = 0.02, P < 0.001, P = 0.001). Univariate analysis revealed no significant correlation between a Clavien-Dindo score ≥ 1 versus gender, body mass index (BMI), lack of symptoms, KPS, baseline GFR, postoperative GFR, tumor size, tumor location, surgical method, and transfusion or no transfusion (ALL P > 0.05). Multifactor analysis showed that age ≥ 80 years, partial nephrectomy, and operation time were independent predictors of a Clavien-Dindo score ≥ 1. No significant difference was found in OS between the two groups, (P < 0.0001), and no significant difference in CSS (P = 0.056). There was no significant difference in OS and CSS between the RN and PN groups (P = 0.143, P = 0.281, respectively). CONCLUSIONS: According to our findings, the overall safety of surgical therapy for elderly patients with renal cell carcinoma is adequate. PN should be carefully examined, especially over the age of 80. To select suitable patients based on an assessment of the tumor's complexity and patients' physical condition, such as age, underlying diseases and other conditions, technical feasibility, balance of benefits and a case-by-case.

The potential biological effects of quercetin based on pharmacokinetics and multi-targeted mechanism in vivo.

Quercetin is a plant-derived polyphenol flavonoid that has been proven to be effective for many diseases. However, the mechanism and in vivo metabolism of quercetin remains to be clarified. It achieves a wide range of biological effects through various metabolites, gut microbiota and its metabolites, systemic mediators produced by inflammation and oxidation, as well as by multiple mechanisms. The all-round disease treatment of quercetin is achieved through the organic combination of multiple channels. Therefore, this article clarifies the metabolic process of quercetin in the body, and explores the new pattern of action of quercetin in the treatment of diseases.

Biotransformation of Liquiritigenin into Characteristic Metabolites by the Gut Microbiota.

The bioavailability of flavonoids is generally low after oral administration. The metabolic transformation of flavonoids by the gut microbiota may be one of the main reasons for this, although these metabolites have potential pharmacological activities. Liquiritigenin is an important dihydroflavonoid compound found in Glycyrrhiza uralensis that has a wide range of pharmacological properties, such as antitumor, antiulcer, anti-inflammatory, and anti-AIDS effects, but its mechanism of action remains unclear. This study explored the metabolites of liquiritigenin by examining gut microbiota metabolism and hepatic metabolism in vitro. Using LC-MS/MS and LC/MSn-IT-TOF techniques, three possible metabolites of liquiritigenin metabolized by the gut microbiota were identified: phloretic acid (M3), resorcinol (M4), and M5. M5 is speculated to be davidigenin, which has antitumor activity. By comparing these two metabolic pathways of liquiritigenin (the gut microbiota and liver microsomes), this study revealed that there are three main metabolites of liquiritigenin generated by intestinal bacteria, which provides a theoretical basis for the study of pharmacologically active substances in vivo.

A new and practical surgical technique of transvaginal natural orifice specimen extraction surgery (NOSES) in laparoscopic nephroureterectomy-an initial clinical experience.

OBJECTIVE: To explore the safety, feasibility and clinical effect of transvaginal natural orifice specimen extraction surgery (NOSES) in 3D laparoscopic nephroureterectomy (LNU) for upper tract urothelial carcinoma (UTUC). METHODS: A retrospective analysis was made of 16 female patients who underwent 3D LNU and NOSES in the Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences from June 2019 to December 2020. The basic clinical data, perioperative related data, perioperative complications, visual analogue pain score (VAS), postoperative scar assessment questionnaire (PSAQ) at 3 months, female pelvic floor dysfunction questionnaire (PFDI-20) and female sexual function index questionnaire (FSFI) at preoperative and postoperative 3 months were analyzed and evaluated. RESULTS: The surgery was successfully completed in all 16 patients, and none of them was converted to open surgery. No postoperative complications, such as abdominal incision-related infection. No cases of local recurrence and distant metastasis were observed during follow-up of 3 to 21 months. The VAS scores at 24 h and 48 h after operation were 2.9 ± 0.7, 1.3 ± 0.6, respectively. PSAQ scores at 3 months after operation were 34.3 ± 3.3. PFDI-20 scores of women preoperative and postoperative 3 months were 6.25 ± 1.75, 6.3 ± 1.8, respectively, and the difference was not statistically significant (p = 0.924). There was no significant difference in FSFI scores between preoperative and postoperative 3 months (p = 0.892). CONCLUSION: Transvaginal NOSES in 3D LNU for UTUC is safe, feasible and practical. The successful development of this technique has laid a solid foundation for further clinical application and promotion.

Transvaginal natural orifice specimen extraction surgery (NOSES) in 3D laparoscopic partial or radical nephrectomy: a preliminary study.

BACKGROUND: With the development of minimally invasive technology, more and more people pay attention to aesthetics of the wound after operation. This study is aim to introduce a new surgical technique of transvaginal natural orifice specimen extraction surgery (NOSES) in 3D laparoscopic partial or radical nephrectomy and evaluate the safety, feasibility and clinical effect. METHODS: Eleven patients who underwent 3D laparoscopic partial nephrectomy (n = 7) or radical nephrectomy (n = 4) and NOSES were included in this study. The surgical procedures and techniques, especially the NOSES operation, are reported in detail. In addition, the basic clinical data, perioperative related data, perioperative complications were analyzed. RESULTS: All 11 patients were performed successfully without conversion to open surgery. The mean total operative time was 133 (84, 150) min. NOSES time was 15 (13, 16) min, and the postoperative hospital stay was 5 (5, 5) d. The mean visual analogue score (VAS) was 3 (2, 4) point and 1 (0, 1) point at 24 h and 48 h after operation, respectively. No patient had recurrence, metastasis and death during the follow-up period of 3 to 17 months. The median Vancouver Scar Scale (VSS) was 1 (1, 1) point. The mean of Female Sexual Function Index (FSFI) was 21.60 (20.20, 21.60), 21.80 (19.80, 21.80) respectively between preoperative and postoperative 3 months, which has no statistical difference (P = 0.179). There was no statistical difference in the Pelvic Floor Distress Inventory-short form 20 (PFDI-20) score between preoperative and postoperative 3 months (P = 0.142). CONCLUSIONS: Transvaginal NOSES is safe and feasible in 3D laparoscopic partial or radical nephrectomy. Furthermore, it results in low incision-related pain without affecting the pelvic floor and sexual function.

Feasibility of single position laparoscopic radical nephrectomy and tumor thrombectomy for left renal cell carcinoma with high-risk Mayo grade 0 and 1 tumor thrombus.

BACKGROUND: To explore the feasibility of single-position laparoscopic radical nephrectomy (LRN) and tumor thrombectomy for left renal cell carcinoma with high-risk Mayo 0 and 1 tumor thrombus (TT). METHODS: All patients with left renal cell carcinoma and venous TT (high-risk Mayo grade 0 and 1) who were performed single-position LRN and tumor thrombectomy were involved. After the renal artery was controlled by Hem-o-lok, the left renal vein was dissected through descending colon mesentery. The left renal vein was divided by EndoGIA for high-risk Mayo grade 0 TT. For Mayo grade 1 TT, part of the inferior vena cava was blocked by a bulldog clamp after milking the TT into the left renal vein and the inferior vena cava was sutured after complete excision of the TT. RESULTS: 3 patients were involved and operations were performed successfully without conversion to open surgery. The mean operation time was 136 min and the mean estimated blood loss was 60 mL. No postoperative complications occurred. CONCLUSIONS: It is feasible to control left renal vein and partial inferior vena cava through descending colon mesentery in a single position during LRN and tumor thrombectomy for the treatment of high-risk Mayo grade 0 and 1 TT.

[Lycopene combined with quercetin and curcumin for chronic prostatitis/chronic pelvic pain syndrome in rats: Effect and mechanism].

OBJECTIVE: To study the therapeutic effect of lycopene combined with quercetin and curcumin on chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) in rats and its underlying mechanism. METHODS: Thirty-three 6-week-old SD male rats were randomly divided into six groups: normal control (n = 3), CP/CPPS model control (n = 6), quercetin (n= 6), curcumin (n = 6), lycopene (n = 6) and combination therapy (n = 6). CP/CPPS was induced by injection of complete Freund's adjuvant into the ventral lobe of the prostate in the latter five groups of rats. After modeling, the rats in the normal and CP/CPPS model control groups were given corn oil by gavage, and those in the latter four groups treated intragastrically with quercetin at 50 mg/kg/d, curcumin at 50 mg/kg/d, lycopene at 10 mg/kg/d, and quercetin + curcumin + lycopene, respectively, once daily for a course of 4 weeks. Then, cardiac blood and prostate tissue samples were collected from the rats for measurement of related indexes. RESULTS: Histopathological changes in the model rats were basically consistent with the characteristics of CP/CPPS. The expressions of the inflammatory factors IL-1ß, IL-2, IL-6, TNFα, MCP1 and MIP-1α in the prostate tissue were all dramatically decreased in the quercetin, curcumin, lycopene and combination therapy groups compared with those in the normal controls (P < 0.01), even lower in the combination therapy group than in the quercetin, curcumin and lycopene groups (P < 0.05). The activities of the oxides CAT, GSH-PX and T-SOD were significantly increased and that of MDA decreased in the four treatment groups (P < 0.05), even more significantly in the combination therapy group than in the other three (P < 0.01). The phosphorylation of MAPKs was inhibited, the activation of NF-kB blocked and the transcriptional activity of Nrf2 enhanced in the four treatment groups (P < 0.05), even more significantly in the combination therapy group (P < 0.01). Conclusions: Lycopene combined with quercetin and curcumin is more effective than any of the three drugs used alone in the treatment of CP/CPPS, which may be associated with its alleviation of inflammatory response and oxidative stress by interaction between the NF-κB, MAPKs and Nrf2 signaling pathways.?

New therapy with XLQ® to suppress chronic prostatitis through its anti-inflammatory and antioxidative activities.

Chronic prostatitis is a common urological disease. The etiology of this disease and effective therapy for its treatment are yet to be elucidated. We investigated the functions of XLQ® in chronic nonbacterial prostatitis using a complete Freund's adjuvant-induced rat model. Prostates and blood samples were collected for further evaluation after oral gavage with XLQ ® or a vehicle for 4 weeks. The results showed that XLQ ® significantly decreased the prostate index, ameliorated the histopathologic changes, and reduced CD3+ and CD45+ cell infiltration in the prostate stroma. Further study showed that XLQ ® suppressed the expression of proinflammatory cytokines, such as interleukin (IL)-1ß, IL-2, IL-6, IL-17A, monocyte chemoattractant protein-1, and tumor necrosis factor-α. XLQ ® showed a strong antioxidant capacity by enhancing the activities of antioxidative enzymes (e.g., total superoxide dismutase, catalase, and glutathione peroxidase) and decreasing the level of lipid peroxidation products (malondialdehyde). Moreover, XLQ ® can suppress the activation of nuclear factor-κB and P38-mitogen-activated protein kinase signaling pathways. In summary, XLQ ® has affirmative effects on chronic prostatitis, which could be attributed to its anti-inflammatory and antioxidative capacities. On the basis of these results, XLQ ® can be developed as an effective and safe therapy for chronic prostatitis.

The effects of microenergy acoustic pulses on animal model of obesity-associated stress urinary incontinence. Part 2: In situ activation of pelvic floor and urethral striated muscle progenitor cells.

AIM: To investigate the possibility and mechanism of microenergy acoustic pulses (MAP) for activating tissue resident stem/progenitor cells within pelvic and urethral muscle and possible mechanism. METHODS: The female Zucker Lean and Zucker Fatty rats were randomly divided into four groups: ZL control, ZLMAP, ZF control, and ZFMAP. MAP was applied at 0.033 mJ/mm2 , 3 Hz for 500 pulses, and the urethra and pelvic floor muscles of each rat was then harvested for cell isolation and flow cytometry assay. Freshly isolated cells were analyzed by flow cytometry for Pax-7, Int-7α, H3P, and EdU expression. Meanwhile, pelvic floor muscle-derived stem cells (MDSCs) were harvested through magnetic-activated cell sorting, MAP was then applied to MDSCs to assess the mechanism of stem cell activation. RESULTS: Obesity reduced EdU-label-retaining cells and satellite cells in both pelvic floor muscle and urethra, while MAP activated those cells and enhanced cell proliferation, which promoted regeneration of striated muscle cells of the pelvic floor and urethral sphincter. Activation of focal adhesion kinase (FAK)/AMP-activated protein kinase (AMPK) /Wnt/ß-catenin signaling pathways by MAP is the potential mechanism. CONCLUSIONS: MAP treatment activated tissue resident stem cells within pelvic floor and urethral muscle in situ via activating FAK-AMPK and Wnt/ß-catenin signaling pathway.

The long-term efficacy of one-shot neoadjuvant intra-arterial chemotherapy combined with radical cystectomy versus radical cystectomy alone for bladder cancer: a propensity-score matching study.

BACKGROUND: Bladder cancer is a complex disease associated with high morbidity and mortality. Management of bladder cancer before radical cystectomy continues to be controversial. We compared the long-term efficacy of one-shot neoadjuvant intra-arterial chemotherapy (IAC) versus no IAC (NIAC) before radical cystectomy (RC) for bladder cancer. METHODS: We performed a retrospective review of patients who underwent either one-shot IAC or NIAC before RC between October 2006 and November 2015. A propensity-score matching (1:3) was performed based on key characters. The Kaplan-Meier method was utilized to estimate survival probabilities, and the log-rank test was used to compare survival outcomes between different groups. A multivariable Cox proportional hazard model was used to estimate survival outcomes. RESULTS: Twenty-six patients were treated using IAC before RC, and 123 NIAC patients also underwent RC. After matching, there was no significant difference between groups in baseline characteristics, perioperative variables, complication outcomes or tumor characteristics. Compared with clinical tumor stages, pathological tumor stages demonstrated a significant decrease (P = 0.002) in the IAC group. There was no significant difference in overall survival (OS, p = 0.354) or cancer-specific survival (CSS, p = 0.439) between the groups. Among all patients, BMI significantly affected OS (p = 0.004), and positive lymph nodes (PLN) significantly affected both OS (p<0.001) and CSS (p = 0.010). CONCLUSIONS: One-shot neoadjuvant IAC before RC shows safety and tolerability and provides a significant advantage in pathological downstaging but not in OS or CSS. Further study of neoadjuvant combination therapeutic strategies with RC is needed.

The methods and techniques of identifying renal pedicle vessels during retroperitoneal laparoscopic radical and partial nephrectomy.

BACKGROUND: Retroperitoneal laparoscopic radical and partial nephrectomy (RLRN and RLPN) have become the preferred modes of management for renal malignancy. One of the most critical steps in the RLRN and RLPN process is to seek and control the renal pedicle. The current study focuses on introducing methods and techniques that can help quickly and accurately identify the renal pedicle vessels during RLRN and RLPN. METHODS: RLRNs and RLPNs were performed for 292 cases in our hospital from November 2014 to January 2017. Different measures were adopted to seek and manage bilateral renal pedicle vessels. All operation procedures were performed by the following three steps: dissection, opening, and clamping. For the left lateral, after the perirenal fat in the dorsal and lateral side was fully dissected, the kidney was pushed toward the ventral side. The renal artery was visible when opening the dense bulging connective tissue, which was located in the middle of the dorsal interior of the kidney. Then, the renal artery was clamped with a Hem-o-lok or the Bulldog clamp. For the right kidney pedicles, the inferior vena cava was first identified and then dissipated upward. When the inferior vena cava was not visible, it was often the location of the right renal artery. The treatment for the artery was the same as for the left renal artery. Relevant clinical characteristics of patients, such as operative time, intraoperative blood loss, and duration of postoperative drainage, were analyzed retrospectively. The three-step method of identifying renal pedicle vessels during retroperitoneal laparoscopic radical and partial nephrectomy was evaluated. RESULTS: All operations were successfully accomplished with satisfying results, during which the artery could be controlled quickly, and no cases were converted to open surgery due to severe bleeding of renal pedicle vessels. There were no complications involving renal vessels during the entire study. The mean operative times were (81.9 ± 19.71) min and (88.2 ± 21.28) min for RLRN and RLPN, with an average intraoperative blood loss of (91.7 ± 47.10) ml and (62.4 ± 47.45) ml, respectively. The warm ischemia time for RLPN was (19.3 ± 5.6) min. The postoperative drainage-tube was removed within (4.5 ± 1.29) d (RLRN) and (4.6 ± 1.98) d (RLPN); the mean postoperative hospital stay times were (7.0 ± 2.4) d and (5.9 ± 1.98) d, respectively. CONCLUSION: The three-step method of identifying renal pedicle vessels during RLRN and RLPN is direct and feasible, and it may help simplify the operating procedure and improve the safety of the surgery. It may be of great practical application value in the clinical field.

Comparison of intracorporeal and extracorporeal urinary diversions after laparoscopic radical cystectomy in females with bladder cancer.

PURPOSE: To compare the peri-operative outcomes of females undergoing laparoscopic intracorporeal urinary diversions (ICUD) and extracorporeal urinary diversions (ECUD) after laparoscopic radical cystectomies (LRC). PATIENTS AND METHODS: Thirty-eight females who underwent LRCs and urinary diversions from February 2008 to October 2018 were divided into two groups: the ECUD group (19 patients) and the ICUD group (19 patients). We retrospectively analysed the patients in terms of patients' demographics, peri-operative outcomes, and oncological follow-ups. RESULTS: There were significant differences in the mean operative times between ECUDs and ICUDs (364.6 vs. 297.1 min, p = 0.007), transfusion rates (37% vs. 5%, p = 0.042), time to flatus (5 vs. 3 days, p = 0.020), time to ambulation (2 vs. 1 days, p = 0.022), and duration of postoperative hospital stays (22 vs. 13 days, p = 0.002). The mean lymph node yield was 12.9 in the ECUD group and 18.6 in the ICUD group (p = 0.140). Seven out of 19 patients (37%) in the ECUD group and 6 out of 19 patients (32%) in the ICUD group had positive lymph nodes (p > 0.9). Two out of 19 ECUD patients (11%) and 4 of 19 ICUD patients (21%) had positive surgical margins (p = 0.660). Although there were no differences in major complications at 30 days and in all complications at 90 days, the Clavien grade II complications were significantly different at 30 days (ECUD 8, ICUD 2; p = 0.026). The mean follow-up times were 48.7 months (ECUD group) and 26.4 months (ICUD group). There were no statistically significant differences in estimated glomerular filtration rates postoperatively (p = 0.516). Seven patients had disease metastases (ECUD 2 out of 19, ICUD 5 out of 19; p = 0.405) and 5 died (ECUD 3 out of 19, ICUD 2 out of 19; p > 0.9). CONCLUSIONS: ICUDs benefit females by having smaller incisions, faster recoveries, and decreased complication rates.