Delayed publication of clinical trials in gynecologic oncology.

OBJECTIVES: Delays in clinical trial publication can hinder timely implementation of evidence-based practices. We sought to determine publication rates and time to publication for clinical trials addressing gynecologic malignancies. METHODS: All clinical trials addressing gynecologic cancers in the ClinicalTrials.gov registry with a primary completion date between 1/1/2018 and 1/1/2020 were identified. The primary outcome was publication rate. All included studies had been completed for at least 3 years. Secondary outcomes were time to publication and associations between publication rate and sponsor, cancer type, and the number and location of primary study sites. RESULTS: Of the 290 trials included, 161 (55.5%) had a peer-reviewed publication for the primary outcome within at least 3 years after completion. Of these, 123 had positive results (76.4%) and 38 were negative (23.6%). The average duration from primary completion to manuscript publication was 23.6 months (SD 13.9; median 21.4, IQR 15.1-32.4). Only 73 had results posted on the ClinicalTrials.gov registry (25.2%). Studies with positive findings had a significantly faster time to publication than those with negative results (22.0 mo vs 29.0 mo, p = 0.009). There was no significant difference between publication rate and funding source, cancer type, or location and number of primary sites. CONCLUSIONS: Timely publication of clinical trials addressing gynecologic cancers remains an issue. Studies with positive findings were published faster than those with negative results, but the average publication time was still almost 2 years from trial completion. Further efforts should be made to identify and address barriers to clinical trial publication.

Two galactinol synthases contribute to the drought response of Camellia sinensis.

MAIN CONCLUSION: CsGolS2-1 and CsGolS2-2 are involved in the transcriptional mechanism and play an important role in the drought response of tea plants. GolS is critical for the biosynthesis of galactinol and has been suggested to contribute to drought tolerance in various plants. However, whether GolS plays a role in drought response and the underlying transcriptional mechanism of GolS genes in response to drought stress in tea plants is still unclear. In this study, we found that drought stress promotes the accumulation of galactinol in tea leaves and that the expression of CsGolS2-1 and CsGolS2-2, which encode proteins capable of catalyzing galactinol biosynthesis, is continuously and dramatically induced by drought stress. Moreover, transgenic Arabidopsis plants expressing CsGolS2-1 and CsGolS2-2 were more drought-tolerant than WT plants, as evidenced by increased cell membrane stability. In addition, the drought-responsive transcription factor CsWRKY2 has been shown to positively regulate the expression of CsGolS2-1 and CsGolS2-2 by directly binding to their promoters. Furthermore, CsVQ9 was found to interact with CsWRKY2 and promote its transcriptional function to activate CsGolS2-1 and CsGolS2-2 expression. Taken together, our findings provide insights not only into the positive role played by CsGolS2-1 and CsGolS2-2 in the drought response of tea plants but also into the transcriptional mechanisms involved.

Contemporary primary treatment of women with stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC): Determinants of relapse and disease-free survival.

OBJECTIVE: The purpose of the present study is to describe a cohort who received contemporary primary treatment for stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC), including patient characteristics and determinants of relapse and disease-free survival. METHODS: The study included 99 patients: 1) with pathologically confirmed stage II-IV LGSOC of the ovary or peritoneum, 2) who underwent primary treatment consisting of cytoreductive surgery and either a) platinum/taxane chemotherapy followed by aromatase inhibitor maintenance therapy or b) aromatase inhibitor monotherapy, and 3) for whom there was availability of clinical data. Descriptive statistics were used to characterize clinicodemographic features. Subgroups were compared for PFS and OS. Multivariable Cox regression analyses were performed. RESULTS: Median PFS for the entire cohort was 56.8 months (95% CI, 41.3-NE), and median OS was 130.7 months (95% CI, 115.0-146.4). Forty-nine of 99 (49.5%) patients have relapsed to date. For these 49 patients, median time from diagnosis to relapse was 29.6 months (95% CI, 24.6-33.1) (range, 5.4-69.1 months). Only 1/49 (2%) patients who relapsed did so >5 years from diagnosis. Fifty (50.0%) patients have not experienced disease progression or relapse. Median follow-up time for these 50 patients is 86.2 months (range, 25.3-169.0). Thirty-three of the 50 (66.0%) have been followed for >5 years from diagnosis. On regression analyses, factors associated with improved patient outcomes-either PFS, OS, or both-included no gross residual disease, normal serum CA 125 at diagnosis, primary peritoneal site, and presence of extensive psammomatous calcifications. CONCLUSIONS: This is the first report to describe the clinicopathologic features and outcomes of women with stage II-IV LGSOC who received contemporary primary therapy.

Comparison of vacuum suction ureteroscopic laser lithotripsy and traditional ureteroscopic laser lithotripsy for impacted upper ureteral stones.

PURPOSE: To compare a novel vacuum suction ureteroscopic laser lithotripsy (VS-URS) with traditional ureteroscopic laser lithotripsy (T-URS) for impacted upper ureteral stones and to better define the potential benefits of VS-URS. METHODS: Between May 2019 and March 2021, 158 patients with impacted upper ureteral stones underwent ureteroscopic holmium-YAG laser lithotripsy. Of these, 76 underwent VS-URS and 82 underwent T-URS. In VS-URS procedures, the vacuum suction device is composed of a 5F ureteral catheter and a tee joint. The ureteral catheter is linked to the vacuum aspirator by the sidearm of the tee joint, and a 200 µm fiber is inserted through the tee joint and the ureteral catheter into the stone site for lithotripsy. RESULTS: When compared to the T-URS group, the VS-URS group had a shorter mean operation time (38.18 ± 6.37 min vs. 46.65 ± 5.66 min; P = 0.000), lower fever rate (3.9% vs. 14.6%; P < 0.022), less stone retropulsion (5.3% vs. 18.3%; P = 0.012), lower extra management rate (6.58% vs. 21.95%; P = 0.006), and a higher stone-free rate of the first postoperative day (88.2% vs. 72.0%; P = 0.011). There were no significant differences in stone-free rates 1 month after surgery between groups (94.7% vs. 92.7%; P = 0.748). CONCLUSIONS: VS-URS is an effective modality for impacted upper ureteral stones, and has a shorter operating time, lower fever rate, less stone retropulsion, and a higher primary stone-free rate compared with T-URS.

Double-Sheath Vacuum Suction Minimally Invasive Percutaneous Nephrolithotomy for Management of Large Renal Stones.

OBJECTIVES: This study aimed to describe a novel double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (mini-PCNL) to overcome the deficiencies of the conventional procedure. PATIENTS AND METHODS: Between March 2019 and December 2019, 65 patients (37 males and 28 females) with a mean age of 41 years (range 23-69) underwent mini-PCNL with double-sheath vacuum suction. It consisted of an F20 Y-shaped sheath as an outer sheath and an F16 Y-shaped sheath as an inner sheath, in which the inner sheath was longer than the outer sheath. The oblique arm of the outer sheath and the inner sheath was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was introduced for stone fragmentation through the working channel of the mini-nephroscope, which was no longer connected to the perfusion fluid. RESULTS: All procedures were successful. Mean operation time was 50.2 min (range 39-83). Mean hemoglobin decrease was 5.2 g/L (range 1.0-15.5), and no patient needed a blood transfusion. One patient (1.5%) with low fever (<38°C) at day 1 had returned to normal at day 2 without administration of antibiotics. There were no Clavien grade 2-4 complications. Mean postoperative hospital stay was 2.4 days (range 2-6). The initial stone-free rate of PCNL was 81.53% (53 of 65 patients). One month after surgery, the final stone-free rate increased to 90.77% (59/65 patients). CONCLUSIONS: The double-sheath vacuum suction mini-PCNL is a safe and effective modality for large renal stones, which might increase the efficiency of stone extraction with low intrapelvic pressure.

M2a macrophage can rescue proliferation and gene expression of benign prostate hyperplasia epithelial and stroma cells from insulin-like growth factor 1 knockdown.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease in elderly men and is often accompanied by chronic inflammation. Macrophages (several subtypes) are the main inflammatory cells that infiltrate the hyperplastic prostate and are found to secrete cytokines and growth factors. The current study aims to explore the effect of M2a macrophages on the development of BPH via insulin-like growth factor 1 (IGF-1). METHODS: Human prostate tissues, prostate, and monocyte cell lines (WPMY-1, BPH-1, and THP-1) were used. THP-1 was polarized into several subtypes with cytokines. The expression and localization of IGF-1 and M2 macrophages were determined via immunofluorescent staining, quantitative real-time polymerase chain reaction, and Western blot analysis. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays were used to investigate the effects of different subtypes of macrophages on prostate cells. IGF-1 in WPMY-1 and BPH-1 cells was silenced and cocultured with or without M2a macrophages. Cell proliferation, apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), and fibrosis processes were examined. RESULTS: The polarized subtypes of macrophages were verified by amplifying their specific markers. M2a macrophages enhanced prostate cell proliferation more significantly and CD206 was more expressed in hyperplastic prostate. IGF-1 was localized in both epithelial and stromal components of prostate and upregulated in BPH tissues. M2a macrophages expressed more IGF-1 than other subtypes. Knockdown of IGF-1 in WPMY-1 and BPH-1 cells attenuated cell proliferation, promoted cell apoptosis, retarded cell cycle at the G0/G1 phase, and suppressed the EMT process in BPH-1 cells as well as the fibrotic process in WPMY-1 cells, which was reversible when cocultured with M2a macrophages. CONCLUSION: These data demonstrated that knockdown of IGF-1 expression in cultured BPH epithelial and stromal cells reduces proliferation and increases apoptosis. These effects are reversed by coculture with M2a macrophages.

Double-sheath vacuum suction versus vacuum-assisted sheath minimally invasive percutaneous nephrolithotomy for management of large renal stones: single-center experience.

PURPOSE: To compare double-sheath vacuum suction minimally invasive percutaneous nephrolithotomy (DS-mini-PCNL) with vacuum-assisted mini-PCNL (VS-mini-PCNL) and to better define the potential benefits of DS-mini-PCNL. METHODS: Between July 2019 and May 2020, 117 patients with large radiopaque renal stones underwent mini-PCNL. Of these, 63 underwent DS-mini-PCNL and 54 underwent VS-mini-PCNL. For VS-mini-PCNL, a F20 Y-shaped sheath was used and the oblique arm of the sheath was connected to the vacuum suction. For DS-mini-PCNL, the oblique arm of a F20 Y-shaped sheath (the outer sheath) and a F16 Y-shaped sheath (the inner sheath) was connected to the perfusion inflow and the vacuum suction, respectively. A 550-µm holmium-YAG laser was used for stone fragmentation. RESULTS: Compared with VS-mini-PCNL group, DS-mini-PCNL group had significantly shorter operative time (35.78 ± 7.77 min vs. 44.56 ± 13.19 min; P = 0.000) and significantly lower fever rate (1.6% vs. 11.1%; P = 0.048). It was not significantly different between the two groups despite the higher initial stone-free rate seen for DS-mini-PCNL group relative to VS-mini-PCNL group (87.7% vs. 81.5%, P = 0.346). Auxiliary procedure rates were 4.8% (three patients) in DS-mini-PCNL group and 16.7% (nine patients) in VS-mini-PCNL group, with a significant difference (P = 0.034). The difference in the final stone-free rate between the two groups was rendered insignificant (93.8% vs. 89.1%, P = 0.510). CONCLUSIONS: DS-mini-PCNL is a safe and effective modality for large renal stones, which could increase the efficiency of stone extraction and decrease infectious complications compared with VS-mini-PCNL.

Comparing Laparotomy with Robot-assisted Interval Debulking Surgery for Patients with Advanced Epithelial Ovarian Cancer Receiving Neoadjuvant Chemotherapy.

STUDY OBJECTIVE: Compare survival of patients with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with either robot-assisted (R-IDS) or open (O-IDS) approach. Second, we assessed the impact of adjuvant and neoadjuvant chemotherapy (NACT) cycles as independent variables associated with survival in this patient population. DESIGN: Retrospective cohort study. SETTING: Single tertiary care center. PATIENTS: Total of 93 patients diagnosed with advanced EOC who underwent NACT before primary debulking surgery after consultation with a gynecologic oncologist. INTERVENTIONS: All patients underwent IDS after completion of NACT with either R-IDS or O-IDS between 2011 and 2018 at a single tertiary care center. Exclusion criteria included receiving fewer than 3 or more than 6 cycles of NACT or having concurrent diagnoses of other malignancies during the treatment period. MEASUREMENTS AND MAIN RESULTS: A total of 93 patients were identified (n = 43 R-IDS; n = 50 O-IDS). Median age (63.0 vs 66.2 years) did not differ between the 2 groups (p = .1). Of the total patients, 91% were optimally cytoreduced (57% R0 and 34% R1), and R0 rate was not influenced by surgical modality (52% O-IDS vs 63% R-IDS, p = .4). Progression-free survival (PFS) and overall survival (OS) did not differ between patients undergoing O-IDS and those undergoing R-IDS (PFS 15.4 vs 16.7 months, p = .7; OS 38.2 vs 35.6 months, p = .7). Cytoreduction to R0 improved both PFS and OS independent of surgical approach. Subgroup analysis showed that, specifically in patients undergoing R-IDS, receiving >6 total cycles of chemotherapy was independently associated with both decreased PFS (hazard ratio 3.85; 95% confidence interval, 1.52-9.73) and OS (hazard ratio 3.97; 95% confidence interval, 1.08-14.59). When analyzed separately, neither NACT nor adjuvant cycle numbers had any effect on survival. CONCLUSION: In this retrospective study of patients with advanced EOC undergoing IDS after NACT, the use of robot-assisted surgery did not affect debulking success or oncologic survival indices. Receiving >6 total cycles of chemotherapy before IDS was associated with a decrease in both PFS and OS in patients undergoing R-IDS in this cohort and warrants further investigation.

Experience in identifying the variant adrenal venous anatomy during modified retroperitoneoscopic adrenalectomy.

BACKGROUND: Adrenal vein plays an important role in performing laparoscopic adrenalectomy successfully. However, it often presents with a multitude of venous anatomical variants. Hence, having a thorough knowledge on the variant types is crucial to reduce operative complications. This study aims to present our experience in identifying adrenal vein variation in adrenalectomy through modified retroperitoneal approach. PATIENTS AND METHODS: A total of 187 patients underwent modified retroperitoneoscopic adrenalectomy between July 2017 and February 2019. Perioperative data and adrenal vein variants were recorded and analysed. RESULTS: Variant adrenal veins were encountered in seven patients. On the right side, two cases were drained by two adrenal veins; one case had a common trunk of adrenal vein and an accessory hepatic vein and one case had an adrenal vein joined with the opening of the right renal vein. On the left side, two cases of anatomic variations were described as follows: one vein converged with the left inferior phrenic vein and joined with the left renal vein, whereas the other vein directly joined with the left renal vein. One case had two adrenal veins that joined with the left renal vein. CONCLUSIONS: Accurate identification and proper handling of the anatomical variation in the drainage of adrenal vein are crucial to safe LA. It is helpful to anticipate and avoid bleeding, especially in large adrenal tumours.

Lin28a Regulates Pathological Cardiac Hypertrophic Growth Through Pck2-Mediated Enhancement of Anabolic Synthesis.

BACKGROUND: Hypertrophic response to pathological stimuli is a complex biological process that involves transcriptional and epigenetic regulation of the cardiac transcriptome. Although previous studies have implicated transcriptional factors and signaling molecules in pathological hypertrophy, the role of RNA-binding protein in this process has received little attention. METHODS: Here we used transverse aortic constriction and in vitro cardiac hypertrophy models to characterize the role of an evolutionary conserved RNA-binding protein Lin28a in pathological cardiac hypertrophy. Next-generation sequencing, RNA immunoprecipitation, and gene expression analyses were applied to identify the downstream targets of Lin28a. Epistatic analysis, metabolic assays, and flux analysis were further used to characterize the effects of Lin28a and its downstream mediator in cardiomyocyte hypertrophic growth and metabolic remodeling. RESULTS: Cardiac-specific deletion of Lin28a attenuated pressure overload-induced hypertrophic growth, cardiac dysfunction, and alterations in cardiac transcriptome. Mechanistically, Lin28a directly bound to mitochondrial phosphoenolpyruvate carboxykinase 2 ( Pck2) mRNA and increased its transcript level. Increasing Pck2 was sufficient to promote hypertrophic growth similar to that caused by increasing Lin28a, whereas knocking down Pck2 attenuated norepinephrine-induced cardiac hypertrophy. Epistatic analysis demonstrated that Pck2 mediated, at least in part, the role of Lin28a in cardiac hypertrophic growth. Furthermore, metabolomic analyses highlighted the role for Lin28a and Pck2 in promoting cardiac biosynthesis required for cell growth. CONCLUSIONS: Our study demonstrates that Lin28a promotes pathological cardiac hypertrophy and glycolytic reprograming, at least in part, by binding to and stabilizing Pck2 mRNA.