Photoredox-Catalyzed Divergent Radical Cascade Annulations of 1,6-Enynes via Pyridine N-Oxide-Promoted Vinyl Radical Generation.

The divergent organophotoredox-catalyzed radical cascade annulation reactions of 1,6-enynes were developed. A series of cyclopropane-fused hetero- and carbo-bicyclic, tricyclic, and spiro-tetracyclic compounds were facilely synthesized from a broad scope of 1,6-enynes and 2,6-lutidine N-oxide under mild and metal-free conditions with blue light-emitting diode light irradiation. The cascade annulation reaction occurs with the intermediacy of a ß-oxyvinyl radical, which is produced from photocatalytically generated pyridine N-oxy radical addition to the carbon-carbon triple bond.

Negative Pressure Wound Therapy for Patients With Complicated Mucocutaneous Separation Following Ileal Conduit Urinary Diversion: A Case Series.

BACKGROUND: Mucocutaneous separation (MCS) is one of the early stomal complications of ileal conduit diversion after radical cystectomy. It can result in abdominal infection and sepsis, prolonging patient recovery. Negative pressure wound therapy (NPWT) has been widely used for abdominal wounds after orthopedic and burn surgery. This case series describes its use in complicated MCS and ostomy retraction after ileal conduit diversion. CASES: We describe a case series of 3 patients with moderate to severe MCS with and without infection after robot-assisted radical cystectomy with ileal conduit diversion. Our patients were treated with NPWT to avoid infection and create a satisfactory environment for healing MCS. After 2 to 4 weeks of NPWT, all 3 patients had normal micturition function with no additional peristomal wounds or complications. CONCLUSION: Negative pressure wound therapy may be used in the management of complicated MCS after ileal conduit diversion.

Tumor-intrinsic RGS1 potentiates checkpoint blockade response via ATF3-IFNGR1 axis.

Background: Non-responsiveness is a major barrier in current cancer immune checkpoint blockade therapies, and the mechanism has not been elucidated yet. Therefore, it is necessary to discover the mechanism and biomarkers of tumor immunotherapeutic resistance. Methods: Bioinformatics analysis was performed based on CD8+ T cell infiltration in multiple tumor databases to screen out genes related to anti-tumor immunity. Associations between Regulator of G-protein signaling 1 (RGS1) and IFNγ-STAT1 signaling, and MHCI antigen presentation pathway were examined by RT-qPCR, western blotting, and flow cytometry. The modulatory mechanisms of RGS1 were investigated via CHIP-qPCR and dual-luciferase assay. The clinical and therapeutic implications of RGS1 were comprehensively investigated using tumor cell lines, mouse models, and clinical samples receiving immunotherapy. Results: RGS1 was identified as the highest gene positively correlated with immunogenicity among RGS family. Inhibition of RGS1 in neoplastic cells dampened anti-tumor immune response and elicited resistance to immunotherapy in both renal and lung murine subcutaneous tumors. Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Clinically, lower expression level of RGS1 was associated with resistance of PD1 inhibition therapy and shortened progression-free survival among 21 NSCLC patients receiving immunotherapy. Conclusions: Together, these findings uncover a novel mechanism that elicits immunotherapy resistance and highlight the function of tumor-intrinsic RGS1, which brings new insights for future strategies to sensitize anti-PD1 immunotherapy.

Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.

Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis.

circDHTKD1 promotes lymphatic metastasis of bladder cancer by upregulating CXCL5.

Lymph node (LN) metastasis is associated with unfavorable prognosis of bladder cancer (BCa). Although lymphangiogenesis is functionally important in LN metastasis of tumors, the potential mechanism in BCa remains unclear. Here, we clarified a regulatory mechanism of circRNA-mediated lymphangiogenesis and LN metastasis in BCa based on next-generation sequencing data. We revealed that circDHTKD1 was positively associated with LN metastasis and significantly upregulated in BCa. By analyzing the co-expression patterns of circDHTKD1 and differentially expressed mRNAs, we identified that circDHTKD1 facilitated lymphangiogenesis by upregulating CXCL5. Mechanistically, circDHTKD1 directly interacted with miR-149-5p, and antagonized the repression of miR-149-5p on CXCL5. Furthermore, circDHTKD1-induced CXCL5 expression recruited and activated neutrophils, which participated in lymphangiogenesis by secreting VEGF-C. Our study supports circDHTKD1 as a promising diagnostic and therapeutic target for LN metastasis in BCa.

68Ga-PSMA-11 PET/CT Parameter Correlates with Pathological VEGFR-2/PDGFR-ß Expression in Renal Cell Carcinoma Patients.

BACKGROUND: Response prediction is necessary for renal cell carcinoma (RCC) tumors. We aim to evaluate parameters derived from 68 Ga-PSMA-11 PET/CT images for prediction of pathological VEGFR-2/PDGFR-ß expression of primary RCC tumors. METHODS: Forty-eight RCC patients were retrospectively enrolled with preoperative 68 Ga-PSMA-11 PET/CT scan and surgical specimen. Radiological parameters including tumor diameter, mean CT value, and maximal standard uptake value (SUVmax) were derived from PET/CT images and pathological VEGFR-2/PDGFR-ß/PSMA expression were identified with immunohistochemistry. Mann-Whitney U test was performed for continuous variables and the chi-square test for categorical variables. ROC was used for determining the effectiveness of preoperative parameters in differentiating VEGFR-2/PDGFR-ß expression. Univariate and multivariate logistic regression analyses were performed for significant parameters to predict VEGFR-2 & PDGFR-ß co-expression. RESULTS: Of the 48 tumors, 25 (52.1%) harbored positive VEGFR-2 expression, 28 (58.3%) harbored positive PDGFR-ß expression, and 24 (50%) were both VEGFR-2 positive and PDGFR-ß positive. SUVmax significantly differed by subgroups of VEGFR-2/PDGFR-ß expression (both P < 0.001). SUVmax demonstrated superior performance for differentiating VEGFR-2 & PDGFR-ß co-expression (positive vs. negative), with area under the curve 0.87 (95% CI 0.78-0.96, P < 0.001), sensitivity 93% and specificity 78%. Moreover, SUVmax was identified as the significant predictor for VEGFR-2 & PDGFR-ß co-expression (odds ratio 4.01, 95% CI 1.99-8.08, P < 0.001). Concordant with radiological findings with 68 Ga-PSMA-11 PET/CT, pathological PSMA staining intensity was significantly higher in both VEGFR-2-positive tumor and PDGFR-ß-positive tumor (P = 0.009 and P < 0.001, respectively). CONCLUSION: 68 Ga-PSMA-11 PET/CT could effectively identify pathological VEGFR-2/PDGFR-ß expression of primary RCC tumors, which may help with selection of mRCC patients suitable for TKIs treatment.

[Trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy for large-volume benign prostate hyperplasia].

OBJECTIVE: To report the safety and efficacy of trans-Douglas Retzius' space-sparing robot-assisted simple prostatectomy (RSS-RASP) in the treatment of large-volume BPH. METHODS: This retrospective study included 24 cases of large-volume (>80 ml) BPH treated by trans-Douglas RSS-RASP from August 2019 to June 2021. The patients ranged in age from 55 to 80 (mean 68.5) years, with an average body mass index of 25.1 (20.5－34.9) kg/m2 , median prostate volume of 132.4 (85.6－235.7) ml, and preoperative tPSA of 10.8 (0.5－37.9) ng/ml, IPSS of 25 (3－35) and quality of life (QOL) score of 5 (3－8). Before surgery, 12 of the patients received catheterization for urinary retention, 1 underwent cystostomy, 2 were complicated with hydronephrosis, 1 had stones and diverticulum in the bladder, and 14 were excluded from the cases of PCa by prostatic biopsy. The operation time, intraoperative blood loss, hemoglobin level on the first day after surgery, blood transfusion, and intra- and postoperative complications were recorded. The patients were followed up for 3 to 21 months postoperatively. Comparisons were made before and after operation in the IPSS, maximum urinary flow rate (Qmax), postvoid residual volume (PVR), QOL score, IIEF score and Male Sexual Health Questionnaire (MSHQ) score. RESULTS: Trans-Douglas RSS-RASP was successfully completed in all the 24 cases, with a mean operation time of 175 (100－285) min, intraoperative blood loss of 200 (50－800) ml, hemoglobin decrease of 25 (4－57) g/L on the first day after surgery, postoperative drainage tube indwelling of 3 (2－7) d, and urinary catheterization of 12 (4－18) d. Six (25%) of the patients received intraoperative blood transfusion, 1 underwent transurethral electrocoagulation hemostasis 1 month after surgery because of postoperative bleeding, and 1 received transurethral resection of the cicatrical adhesive tissue of the bladder neck 12 months after surgery. No other complications occurred postoperatively. The IPSS (3 ［1－7］), Qmax (19.6 ［9.9－32.1］ ml/s), PVR (0 ［0－34.9］ ml) and QOL score (2 ［0－3］) of the patients were significantly improved after surgery (P < 0.05), but no statistically significant differences were observed in the IIEF (20 ［19－24］) and MSHQ scores (14 ［13－14］) as compared with the baseline (P > 0.05). CONCLUSION: Trans-Douglas RSS-RASP is a safe and effective minimally invasive method for the treatment of large-volume (>80 ml) BPH, which can improve the urinary function of the patient after operation.

Photoinduced oxidative cyclopropanation of ene-ynamides: synthesis of 3-aza[n.1.0]bicycles via vinyl radicals.

The first photoinduced synthesis of polyfunctionalized 3-aza[n.1.0]bicycles from readily available ene-ynamides and 2,6-lutidine N-oxide using an organic acridinium photocatalyst is reported. Applying a photocatalytic strategy to the reactive distonic cation vinyl radical intermediate from ynamide, a series of bio-valuable 3-azabicycles, including diverse 3-azabicyclio[4.1.0]heptanes and 3-azabicyclo[5.1.0]octanes that are challenging to accomplish using traditional methods, have been successfully synthesized in good to high yields under mild and metal-free conditions. Mechanistic studies are consistent with the photocatalyzed single-electron oxidation of ene-ynamide and the intermediacy of a putative cationic vinyl radical in this transformation. Importantly, this strategy provides new access to the development of photocatalytic vinyl radical cascades for the synthesis of structurally sophisticated substrates.

Robot-Assisted versus Conventional Open Kidney Transplantation: A Meta-Analysis.

BACKGROUND: Perioperative and follow-up outcomes for patients that received robot-assisted kidney transplant (RAKT), compared to patients that received conventional open kidney transplant (OKT), remain unknown. We performed a meta-analysis of controlled studies to compare the safety and efficacy of RAKT versus OKT. METHODS: Systematic searching of PubMed, Embase, and Cochrane Library databases was performed to identify relevant randomized or nonrandomized controlled studies. Perioperative, in-hospital, and follow-up outcomes were summarized. A random-effect model incorporating the potential heterogeneity was used to synthesize the results. RESULTS: Six nonrandomized controlled studies including 263 patients with RAKT and 804 patients with OKT were included. Pooled results showed that compared to those that received OKT, patients that received RAKT had significant higher rewarming time (mean difference (MD): 20.8 min, p < 0.001) and total ischemia time (MD: 17.8 min, p = 0.008) but a lower incidence of surgical site infection (SSI, risk ratio (RR): 0.22, p = 0.03). The incidence of delayed graft function was comparable between groups (RR: 1.10, p = 0.82), and the length of hospital stay was similar (MD: -2.03 days, p = 0.21). During a follow-up of 31 months, patients that received RAKT and OKT had similar serum creatinine levels (MD: 10.12 mmol/L, p = 0.42) and similar incidences of graft rejection (RR: 1.16, p = 0.53), graft failure (RR: 0.94, p = 0.79), and all-cause mortality (RR: 1.16, p = 0.77). CONCLUSION: Current evidence from nonrandomized studies suggests that RAKT is associated with a lower risk of SSI and similar midterm functional and clinical efficacy compared to OKT. Randomized studies are needed to validate these findings.

Bis(imino)pyridine iron complexes for catalytic carbene transfer reactions.

The bis(imino)pyridine iron complex, for the first time, is developed as an effective metal carbene catalyst for carbene transfer reactions of donor-acceptor diazo compounds. Its broad catalytic capability is demonstrated by a range of metal carbene reactions, from cyclopropanation, cyclopropenation, epoxidation, and Doyle-Kirmse reaction to O-H insertion, N-H insertion, and C-H insertion reactions. The asymmetric cyclopropanation of styrene and methyl phenyldiazoacetate was successfully achieved by the new chiral bis(imino)pyridine iron catalyst, which delivers a new gateway for the development of chiral iron catalysis for metal carbene reactions.

Chiral donor-acceptor azetines as powerful reactants for synthesis of amino acid derivatives.

Coupling reactions of amines and alcohols are of central importance for applications in chemistry and biology. These transformations typically involve the use of a reagent, activated as an electrophile, onto which nucleophile coupling results in the formation of a carbon-nitrogen or a carbon-oxygen bond. Several promising reagents and procedures have been developed to achieve these bond forming processes in high yields with excellent stereocontrol, but few offer direct coupling without the intervention of a catalyst. Herein, we report the synthesis of chiral donor-acceptor azetines by highly enantioselective [3 + 1]-cycloaddition of enoldiazoacetates with aza-ylides and their selective coupling with nitrogen and oxygen nucleophiles via 3-azetidinones to form amino acid derivatives, including those of peptides and natural products. The overall process is general for a broad spectrum of nucleophiles, has a high degree of electronic and steric selectivity, and retains the enantiopurity of the original azetine.

Synthesis of Chiral Tetrasubstituted Azetidines from Donor-Acceptor Azetines via Asymmetric Copper(I)-Catalyzed Imido-Ylide [3+1]-Cycloaddition with Metallo-Enolcarbenes.

The all-cis stereoisomers of tetrasubstituted azetidine-2-carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl-protected Z-γ-substituted enoldiazoacetates and imido-sulfur ylides by asymmetric [3+1]-cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p-methoxybenzyl azetine-2-carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.

ortho-Alkylation of Pyridine N-Oxides with Alkynes by Photocatalysis: Pyridine N-Oxide as a Redox Auxiliary.

A photocatalyzed ortho-alkylation of pyridine N-oxide with ynamides and arylacetylenes has been developed, which yields a series of α-(2-pyridinyl) benzyl amides/ketones. Mechanistic studies, including electrochemical studies, radical-trapping experiments, and Stern-Volmer fluorescence quenching studies demonstrate that pyridine N-oxide serves as both a redox auxiliary and radical acceptor to achieve the mild photocatalytic single-electron oxidation of carbon-carbon triple bonds with the generation of a cationic vinyl radical intermediate.

[Combination of serum PSA assay, multi-parametric MRI and targeted prostate biopsy for prostate cancer screening in Nanjing].

OBJECTIVE: To investigate the exact prevalence of PCa among males in Nanjing and search for a mode of PCa screening suitable for the specific conditions. METHODS: From January to December 2018, we collected serum samples and clinical information from 6 903 men aged ≥50 years taking physical examination in 16 community health service centers in Nanjing. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 µg/L, transperineal systematic biopsy and MRI/ultrasound fusion targeted prostate biopsy for those who scored ≥3 points on the Prostate Imaging-Reporting and Data System Version 2 (PI-RADS v2), transperineal systematic biopsy only for those with a PI-RADS v2 score of <3 and serum PSA ≥10 µg/L, and follow-up examinations every 6 months for those with a PI-RADS v2 score of <3 and serum PSA <4 µg/L. RESULTS: Among the 6 903 male subjects, 835 (12.1%) were found with serum PSA≥4 µg/L; 229 (77.4%) of the 296 men that received mpMRI scored ≥3 points on PI-RADS v2; and 79 (53.4%) of the 148 males that underwent prostate biopsy were diagnosed with PCa, with a total detection rate of 1.14% in all the subjects. Of the 77 patients with complete pathological data, 73 (94.8%) were found with clinically significant PCa, 30 (39.0%) with localized, 41 (53.2%) with locally advanced and 6 (7.8%) with metastatic malignancy, 6 (7.8%) in stage Ⅰ, 21 (27.3%) in stage Ⅱ, 34 (44.2%) in stage Ⅲ and 16 (20.8%) in stage Ⅳ. There were 47 (66.2%) high-risk, 18 (25.4%) moderate-risk and 6 (8.5%) low-risk cases among those with localized or locally advanced PCa. CONCLUSIONS: The prevalence of PCa in Nanjing deserves considerable attention, and PCa screening is highly necessary in the high-risk population, for which the combination of serum PSA assay, mpMRI and targeted prostate biopsy may be an ideal method.

Copper-Catalyzed Formal [4+2] Cycloaddition of Enoldiazoimides with Sulfur Ylides.

Enoldiazoimides, a new subclass of enoldiazo compounds, generate enol-substituted carbonyl ylides whose reactions with sulfur ylides enable an unprecedented formal [4+2] cycloaddition. The resulting multifunctionalized indolizidinones, which incorporate sulfur, are formed in good yields under mild reaction conditions. The uniqueness of this transformation stems from the role of the silyl-protected enol, since the corresponding acetyldiazoimide failed to provide any cross-products in metal-catalyzed reactions with sulfur ylides. This copper-catalyzed cycloaddition is initiated with the generation of enol-substituted carbonyl ylides and sulfur ylides from enoldiazoimides and sulfonium salts, respectively, and proceeds through stepwise six-membered ring formation, C-O and C-S bond cleavage, and silyl and acetyl group migration.

Nanocapsules of Magnetic Au Self-Assembly for DNA Migration and Secondary Self-Assembly.

To endow valuable responsiveness to self-assemblies of Au nanoparticles (Au NPs), the magnetic Au nanoparticles (Au NPs)/C16H33(CH3)3N+[CeCl3Br]- (CTACe) mixtures were first prepared by using an emulsion self-assembly of a magnetic surfactant, C16H33(CH3)3N+[CeCl3Br]-. A versatile morphology of self-assemblies of Au NPs could be controlled by the counterions in surfactants including [CeCl3Br]-, [FeCl3Br]-, and Br- as well as solvent. In particular, the magnetic counterion, [CeCl3Br]-, can induce self-growth of Au NPs in an emulsion self-assembly process due to the oxidability of [CeCl3Br]-. It enhances the rigidity of Au NPs/CTACe scaffolds template compared with Au NPs/hexadecyltrimethylammonium bromide. [CeCl3Br]- engaged Au NPs/CTACe with fascinating capability of conglutination and targeted migration of DNA (150 µmol/L) under a magnet field. The conglutination capability of the DNA molecules can increase to 39.8% by adopting the magnetic strategy when using Au NPs/CTACe as a magnetic booster. Au NPs/CTACe mixtures can ideally self-assemble to be scaffolds, providing abundant conjugation sites of surface charges. Magnetic Au NPs/CTACe can serve as a template scaffold to secondary self-assemble with DNA (40 mmol/L) outside, producing smooth-faced and hollow DNA nanocapsules. We believe that the creative Au NPs/CTACe/DNA nanocapsules will extend the biological application field of Au NPs assemblies.

miR34a/GOLPH3 Axis abrogates Urothelial Bladder Cancer Chemoresistance via Reduced Cancer Stemness.

Rationale: Chemoresistance and subsequent recurrence of human urothelial bladder cancer (UBC) is partially driven by a subpopulation of tumor initiating cells, namely cancer stem cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment and following chemoresistance and recurrence remains largely unclear. Methods: Gemcitabine and cisplatin (GC) chemoresistant cell lines (T24 GC 3rd and 5637 GC 3rd cells) and the chemo-sensitive UBC cell lines T24 and 5637 were established in vivo for the investigation of acquired resistance mechanisms. The role of miR34a/GOLPH3 axis in regulating UBC chemoresistance and recurrence was evaluated in cell and animal models. The expression levels of miR34a/GOLPH3 axis and CSCs markers were assayed in specimens of UBC. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. Results: RT-PCR and western blotting confirmed that the expression levels of miR34a were decreased and GOLPH3 were increased in GC chemoresistant UBC cell lines. Downregulation of miR34a resulted in the overexpression of GOLPH3, which is a target gene of miR34a confirmed by luciferase experiment. The ectopic expression of miR34a decreased the stem cell properties of chemoresistant UBC cells and re-sensitized these cells to GC treatment in vitro and in vivo. Moreover, miR34a/GOLPH3 axis has obvious clinical relevance with prognosis and recurrence in human UBC patients with standard GC chemotherapy. Conclusion: Our results suggest that miR34a/GOLPH3 axis exert key role in CSCs involved UBC drug resistance and recurrence and warrant further development as a promising therapeutic approach in treating drug-resistant UBC.

Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer.

BACKGROUND: To evaluate the diagnostic value of 68Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). METHODS: We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D'Amico and without concomitant cancer. Preoperative 68Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. RESULTS: Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12-51.75) and 7.22 (range 5.4-11.2), respectively (P < 0.001). 68Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68Ga-PSMA-11 PET-CT and mpMRI in this study. CONCLUSIONS: Both 68Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.

Transperineal cryotherapy for unresectable muscle invasive bladder cancer: preliminary experience with 7 male patients.

BACKGROUND: Radical cystectomy (RC) with pelvic lymph node dissection (PLND) and urinary diversion (UD) is considered the standard treatment for muscle invasive bladder cancer (MIBC). In a part of patients, RC procedure is aborted due to unresectable disease, other followed treatment like systemic chemotherapy, radiotherapy or cryotherapy may be a better option. The aim of present study was to report the preliminary results of transperineal cryotherapy for unresectable muscle invasive bladder cancer. METHODS: From January 2011 to August 2013, 7 male patients with pT4b unresectable bladder cancer underwent bilateral ureterocutaneostomy. Two performed a pelvic lymph node dissection (PLND). Then primary transperineal cryosurgery for preserved bladder at the guidance of transrectal ultrasound (TRUS) was performed. All patients underwent a dual freeze-thaw cycle using third-generation cryotechnology with ultrathin 17-gauge cryoneedles. Computer tomography (CT) and/or magnetic resonance image (MRI)were performed at 3 month intervals after cryosurgery to determine whether progression or recurrence occurred. RESULTS: All cryosurgery was performed successfully, mean operation time was 76.43 ± 25.12 min (range 50-120 min), mean blood loss was 19.29 ± 15.92 ml (range 5-50 ml). Mean hospital stay was 3.86 ± 1.68 day (range 2-7 days). No operative related deaths occurred. Four patients dead due to the metastasis disease at the follow up time of 8, 15, 18 and 37 months, respectively. Six patients received postoperative therapy, of whom 5 patients were treated with combined chemoradiation, and the other one received chemotherapy alone. The progression free survival (PFS) of the 7 patients was 22.00 ± 14.61 months (range 3-40 months). The one, two and three year overall survival (OS) was 85.7%, 57.1% and 42.9%, respectively. CONCLUSION: Our results suggest that cryosurgery combination with chemoradiotherapy provide a safe and effective alternative method for unresectable pT4b bladder cancer. Longer follow-up is necessary to determine the sustained efficacy.

Catalytic Divergent [3+3]- and [3+2]-Cycloaddition by Discrimination Between Diazo Compounds.

Highly selective divergent cycloaddition reactions of enoldiazo compounds and α-diazocarboximides catalyzed by copper(I) or dirhodium(II) have been developed. With tetrakis(acetonitrile)copper(I) tetrafluoroborate as the catalyst epoxypyrrolo[1,2-a]azepine derivatives were prepared in good yields and excellent diastereoselectivities through the first reported [3+3]-cycloaddition of a carbonyl ylide. Use of Rh2 (pfb)4 or Rh2 (esp)2 directs the reactants to regioselective [3+2]-cycloaddition generating cyclopenta[2,3]pyrrolo[2,1-b]oxazoles with good yields and excellent diastereoselectivities.