Advantages of retrograde intrarenal incision versus laparoscopic surgery in management of pararenal cysts: a single-center experience.

PURPOSE: Renal cysts are typically a benign condition, and parapelvic cysts are a type of renal cyst that occur adjacent to the renal pelvis or renal sinus. Parapelvic cysts can increase the risk for injury to adjacent organs or urine leakage during laparoscopic surgery. Flexible ureteroscopes with laser assistance were used to make internal incisions in cysts. Perioperative outcomes of this method were compared with those of laparoscopic surgery. METHODS: Eight-three patients, who underwent surgical treatment for renal cysts at the authors' medical center between January 2019 and June 2022, were evaluated. Two patients were excluded because they originally opted for RIRS but subsequently converted to laparoscopic surgery. Patients were divided into 2 groups based on surgery type: laparoscopic; and RIRS for internal incision. Outcomes in both groups were analyzed. RESULTS: Of the 81 patients analyzed, 60 [74% (group 1)] underwent laparoscopic surgery and 21 [26% (group 2)] underwent RIRS for internal incision. The median operative durations for groups 1 and 2 were 87 and 56 min, respectively (p < 0.001). Relative to RIRS, laparoscopic surgery resulted in greater postoperative painkiller use (laparoscopic surgery versus [vs.] RIRS, 43% vs. 19%; p = 0.047). The median length of hospital stay was 2 and 1 days, respectively (p < 0.001). CONCLUSIONS: RIRS demonstrated several advantages over laparoscopic surgery for the internal incision of parapelvic cysts, including shorter operative duration, shorter hospital stay, and less postoperative pain control. These findings may guide the selection of appropriate surgical approaches for patients with renal cysts.

Development of Combretastatin A-4 Analogues as Potential Anticancer Agents with Improved Aqueous Solubility.

Combretastatin A-4 (CA-4) is a potent tubulin polymerisation inhibitor. However, the clinical application of CA-4 is limited owing to its low aqueous solubility and the easy conversion of the olefin double bond from the more active cis- to the less active trans-configuration. Several structural modifications were investigated to improve the solubility of CA-4 derivatives. Among the compounds we synthesized, the kinetic solubility assay revealed that the solubility of compounds containing a piperazine ring increased the most, and the solubility of compounds 12a1, 12a2, 15 and 18 was increased 230-2494 times compared with that of the control compound (Z)-3-(4-aminophenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (9a). In addition, these synthesised stilbene nitriles had high anticancer cell (AGS, BEL-7402, MCF-7, and HCT-116) selectivity over L-02 and MCF-10A normal cells while maintaining micromolar activity against cancer cells. The most cytotoxic compound is 9a, and the IC50 value is 20 nM against HCT-116 cancer cells. Preliminary studies indicated that compound 12a1 had excellent plasma stability and moderate binding to rat plasma proteins, suggesting it is a promising lead compound for the development of an anticancer agent.

Predictive Value of Flank Pain and Gross Hematuria on Long-Term Survival in Patients With Upper Tract Urothelial Carcinoma Treated by Radical Nephroureterectomy.

Background: Assessing the prognosis preoperatively in patients with upper tract urothelial carcinoma (UTUC) remains a challenge for urologists. Gross hematuria (GH) and flank pain (FP) are the 2 most common and easily perceived symptoms of UTUC. Therefore, we aimed to investigate the prognostic values of GH and FP in patients with UTUC after undergoing radical nephroureterectomy (RNU). Methods: This article retrospectively analyzed 179 patients with UTUC who underwent RNU and examined the associations between the FP, GH, and long-term survival. After dividing patients into 4 subgroups (presenting as GH without FP, FP without GH, no FP and GH, FP with GH), we focused on the prognostic values of the 4 subgroups using univariate and multivariate analyses. We then proposed a risk stratification model for UTUC based on the independent prognostic factors for cancer-specific survival (CSS) with external validation (146 additional UTUC patients formed the validation cohort). Results: Patients with FP had worse oncological outcomes than those without FP (P < .05). After dividing the 179 patients into 4 subgroups, the "FP without GH" subgroup suffered the worst oncological outcomes (P < .001). The Cox multivariate regression analysis showed that "FP without GH" (P < .001), tumor multifocality (P = .005), and pathological stage (P = .004) were independent prognostic factors for CSS. Good performance of the risk stratification model was achieved in both the training and external validation cohorts. Conclusion: The presence of "flank pain without gross hematuria" was one of the independent risk factors of CSS and OS besides the pathological stage and tumor multifocality. To our knowledge, this is the first study that adding complaint to risk stratification model in UTUC.

Spontaneous expulsion of a duodenal lipoma after endoscopic biopsy: A case report.

BACKGROUND: Gastrointestinal (GI) lipomas are benign submucosal tumors of mature adipocytes that arise mainly in the colon and stomach, sometimes in the ileum and jejunum, and rarely in the duodenum. Patients with symptomatic lipomas require endoscopic or surgical treatment. Spontaneous expulsion of lipomas after biopsy is a rare condition that has limited case reports. CASE SUMMARY: A 56-year-old man presented to our hospital with intermittent postprandial epigastric fullness. Esophagogastroduodenoscopy (EGD) revealed a 10-mm soft yellowish submucosal lesion with the "pillow sign," located in the second portion of duodenum. Endoscopic ultrasonography (EUS) using a 12-MHz catheter probe showed a hyperechoic, homogenous, and round solid lesion (OLYMPUS EUS EU-ME2, UM-DP12-25R, 12-MHz radial miniprobe, Olympus Corporation, Tokyo, Japan). Deep biopsy was performed using the bite-on-bite technique with forceps. Histological examination was compatible with submucosal lipoma. The lesion spontaneously expelled 12 d after the biopsy. Follow-up EUS performed after 2 mo confirmed this condition. CONCLUSION: Deep biopsy could lead to spontaneous GI lipoma expulsion. This might be the first step in lipoma diagnosis and treatment.

Comparison of mini endoscopic combined intrarenal surgery and multitract minimally invasive percutaneous nephrolithotomy specifically for kidney staghorn stones: a single-centre experience.

BACKGROUND: Staghorn stones require surgical treatment to prevent serious complications. Multitract percutaneous nephrolithotomy (PNL) causes great renal parenchymal injury and blood loss. One-stage endoscopic combined intrarenal surgery (ECIRS) entails the combined use of antegrade nephroscope and retrograde flexible ureteroscope to clear the staghorn stone, which may overcome the limitations of multitract PNL. We aimed to compare the perioperative outcomes of mini ECIRS and multitract minimally invasive PNL in staghorn stone management. METHODS: This was a retrospective single-center study of patients with staghorn stones who underwent ECIRS (n = 17) or multitract minimally invasive PNL (n = 17) between January 2018 and September 2021. RESULTS: There was a significant between-group difference with respect to Guy's stone score. Stone size, stone burden (ECIRS group, 21.41 cm3; multitract minimally invasive PNL group, 20.88 cm3 [P = 0.94]), and degree of hydronephrosis were comparable in the two groups. There was no significant between-group difference with respect to one-step or final stone-free rates. The mean operative time was also not significantly different between the groups (ECIRS group, 140 min; multitract minimally invasive PNL group, 183 min [P = 0.63]). ECIRS was associated with significantly lesser postoperative pain (visual analog scale; ECIRS group: 0; multitract minimally invasive PNL group: 2.7 [P < 0.001]). Hemoglobin loss, postoperative blood transfusion rate, complications, and length of hospital stay were comparable in the two groups. CONCLUSION: Both mini ECIRS and multitract minimally invasive PNL were effective and safe for the management of renal staghorn stones with comparable operation time and stone-free rate, and complications. ECIRS was associated with less severe postoperative pain.

Exosome-Mediated miR-4792 Transfer Promotes Bladder Cancer Cell Proliferation via Enhanced FOXC1/c-Myc Signaling and Warburg Effect.

Bladder cancer is the second-most common malignancy in the urogenital system and the most common in men. However, our understanding of the driving mechanisms of bladder cancer remains incomplete. The forkhead box (FOX) family of transcription factors is implicated in urogenital development and bladder malignancies. Many exosomal microRNAs have been identified as regulators and mediators of the expression of FOX, including the expression of FOXC1. miR-4792 has been known as a tumor miRNA suppressor. However, the function of miR-4792/FOXC1 signaling in bladder cancer development remains unknown. Here, we studied the role of miR-4792/FOXC1 signaling in bladder cancer by using multiple bladder cancer cell lines and bladder cancer mouse models through in vitro and in vivo approaches. We showed that FOXC1 is highly expressed in multiple bladder cancer cell lines and bladder tumor tissues. The knockdown of FOXC1 expression in bladder cancer cell lines decreases c-Myc expression levels, retards cell growth, and reduces aerobic glycolysis (also known as the Warburg effect) and lactic acid content. By contrast, the overexpression of FOXC1 elicits the opposite effects. FOXC1-downregulated bladder cancer cells form significantly smaller tumors in vivo. The inhibition of c-Myc reverses the effects of FOXC1 overexpression and leads to reduced cell proliferation, aerobic glycolysis, and lactic acid content. miR-4792 expression is downregulated in bladder tumor tissues. miR-4792 exposure to bladder cancer cells reduces the expression levels of FOXC1 and c-Myc, slows down cell growth, and decreases aerobic glycolysis and lactic acid content. However, the enhanced miR-4792 expression elicits opposite effects. These findings provided the first evidence that the exosome-mediated delivery of miR-4792 could play an important role in bladder cancer development through the downregulation of FOXC1 and c-Myc, which further inhibited aerobic glycolysis and lactic acid content.

Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway.

Microtubule actin cross-linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3-E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast-specific Osterix (Osx) promoter-driven Macf1 conditional knockout mice (Macf1f/f Osx-Cre). The Macf1f/f Osx-Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1f/f Osx-Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1f/f Osx-Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1f/f Osx-Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease.

Neuropeptide FF inhibits LPS-mediated osteoclast differentiation of RAW264.7 cells.

Neuropeptide FF (NPFF) has been implicated in many physiological processes. Previously, we have reported that NPFF modulates the viability and nitric oxide (NO) production of RAW264.7 macrophages. In this study, we investigated the influence of NPFF on lipopolysaccharide (LPS)-mediated osteoclast formation of RAW264.7 cells. Our results suggest that, NPFF dose-dependently (1 nM, 10 nM and 100 nM) inhibited osteoclast formation, TRAP enzyme activity and bone resorption in osteoclasts induced by LPS respectively. Moreover, LPS-provoked NO release was also inhibited by NPFF treatment, indicating a NO-dependent pathway is mainly involved. Furthermore, the alterations of osteoclast marker genes were also assessed including TRAP, Cathepsin K, MMP-9, NFATc1 and Runx2. NPFF downregulated LPS-caused gene augmentations of TRAP, Cathepsin K and MMP-9, whereas showed no influences on NFATc1 and Runx2. In addition, NPFF receptor 2 (NPFFR2) mRNA expression was also augmented in response to NPFF treatment, hinting the involvement of NPFFR2 pathway. It should be mentioned that RF9 (1 µ M), a reported pharmacological inhibitor for NPFF receptors, exerted NPFF-like agonist properties as to attenuate osteoclastogenesis. Collectively, our findings provide new evidence for the in vitro activity of NPFF on osteoclasts, which may be helpful to extend the scope of NPFF functions.

Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella.

The Escherichia coli purine nucleoside phospho-rylase/2-fluoro-2-deoxyadenosine (ePNP/F-dAdo) suicide system has demonstrated a powerful killing and bystander effects on tumor cells. However, several drawbacks to this approach remain to be resolved, such as the side-effects and the low efficiency of ePNP-targeted expression. A human telo-merase reverse transcriptase promoter-driven Semliki Forest virus-based DNA vector (pShT-ePNP) with high expression of the ePNP gene was constructed. Live attenuated Salmonella typhimurium 7207 (SL7207) was used initially as a vehicle to targetly transfer the large alphavirus vector into tumor cells. The in vitro quantitative analysis showed ~2-fold higher green fluorescent protein (GFP) expression for pShT-GFP than for conventional cytomegalovirus (CMV) promoter-mediated eukaryotic expression plasmids such as pIRES-GFP and the targeted expression of the ePNP gene in tumor cells was also detected by RT-PCR. After F-dAdo addition, the enzymatic conversion of F-Ado into 2-fluoroadmine (F-Ade) was tested by HPLC. Cell cytotoxicity assays showed that the significant inhibitory effect of the SL/pShT-ePNP system on tumor cells was dose- and time-dependent. Following oral administration, recombinant bacteria targetly allocated within the solid tumor and the expression of ePNP and GFP genes in vivo were detected by RT-PCR or observed by fluorescence microscopy. SL/pShT-ePNP and F-dAdo were also found to exert powerful therapeutic effects in combination against tumor growth and for prolonging the lifespan of tumor-bearing mice. These findings suggest that the SL/pShT-ePNP system may serve as a powerful strategy for tumor therapy.

[Internal fixation with AO distal humerus plates for the treatment of distal humeral fractures in elderly osteoporotic patients].

OBJECTIVE: To study the clinical effects of AO distal humerus plate (DHP) for the treatment of distal humeral fractures in elderly osteoporotic patients. METHODS: From September 2008 to January 2010, 18 elderly osteoporotic patients with distal humeral fractures were treated with open reduction and internal fixation with DHP. There were 3 males and 15 females, ranging in age from 62 to 83 years (averaged, 71.4 years). According to AO classification, 1 patient was Type A2, 3 patients were Type A3; 2 patients were Type B1, 2 patients were Type B2; 3 patients were Type C1, 4 patients were Type C2, 3 patients were Type C3. The surgical approaches were either bilateral or via olecranon process of ulna. Early mobilization was initiated after surgery. Functional results were evaluated according to the Mayo elbow performance score (MEPS). RESULTS: The average duration of follow-up was 14.6 months (ranged from 11 to 24 months). All the patients had a complete healing of their fractures. There was no infection, hardware failure or loss of reduction after the operations. The average Mayo elbow performance score (MEPS) was (92.2 +/- 9.6) (65 to 100 points), among which the score of pain was (42.5 +/- 5.8) (30 to 45 points), the score of motion range was (19.2 +/- 1.9) (15 to 20 points), the score of stability was (9.2 +/- 1.9) (5 to 10 points), and the score of function was (21.4 +/- 2.9) (15 to 25 points). According to MEPS, 11 patients got excellent results, 5 good and 2 fair. CONCLUSION: Treatment of distal humeral fractures in elderly osteoporotic patients with AO distal humeral plates can obtain immediate stabilization which facilitates early mobilization of the elbow.