Red cell distribution width predicts time to recurrence in patients with primary non-muscle-invasive bladder cancer and improves the accuracy of the EORTC scoring system.

PURPOSE: To investigate the clinical prognostic value of red cell distribution width (RDW) in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively evaluated 582 consecutive patients with primary NMIBC. The efficacy of preoperative RDW at predicting treatment outcome was assessed. A cut-off point for predicting recurrence was also identified. Uni- and multivariable analyses of time to recurrence (TTR) and progression were conducted. Harrell's concordance index (c-index) was used to evaluate the additive value of RDW to the European Organization of Research and Treatment of Cancer (EORTC) risk scoring model for recurrence. RESULTS: According to the receiver operating characteristic curve of RDW for recurrence, a RDW ≥ 14.5% was classified as high. In the multivariable analysis, a high RDW could independently predict shorter TTR (subdistribution hazard ratio [SHR]: 2.65, 95% confidence interval [CI]: 1.83-3.84, P < 0.001), irrespective of tumor characteristics. No significant relationship was observed between RDW and time to progression (SHR: 1.75, 95% CI: 0.76-4.08, P = 0.19). Adding binary-coded RDW to the EORTC risk scoring model significantly improved its discriminatory performance in assessing recurrence risk (c-index: 0.62, improvement: 0.052, P < 0.001). High RDW was associated with shorter TTR in patients treated with bacillus Calmette-Guerin in the multivariable analysis (SHR: 2.0, 95% CI: 1.01-3.98, P = 0.047). CONCLUSIONS: RDW was an independent, significant prognostic factor of TTR in patients with primary NMIBC. Adding RDW to the EORTC risk model significantly improved the model's predictability for tumor recurrence.

Effectiveness of Intravesical Doxorubicin Immediately Following Resection of Primary Non-muscle-invasive Bladder Cancer: A Propensity Score-matched Analysis.

BACKGROUND: The purpose of this study was to investigate whether adding single immediate postoperative intravesical instillation of doxorubicin (SID) to transurethral resection of bladder tumor (TURBT) significantly reduced the risk of recurrence in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively analyzed the records of 720 patients diagnosed with primary NMIBC between 2002 through 2018 at the Kameda Medical Center. The primary outcome measure was time to recurrence. Time to progression was also compared. The cohort of SID and the cohort of TURBT alone were matched one-to-one by propensity scores. Matching was done by patient age, gender, and factors of the European Organization of Research and Treatment of Cancer recurrence risk table. The associations of adding SID and clinical outcomes were assessed with uni- and multivariate competing-risk regression models. RESULTS: After matching, a total of 364 patients, including 182 receiving SID and 182 receiving TURBT alone, were analyzed. No statistically significant differences existed among the measured baseline characteristics in propensity score-matched cohorts. In the multivariate analysis, there was a significantly longer time to recurrence in patients receiving SID (subdistribution hazard ratio, 0.68; 95% confidence interval, 0.49-0.95; P = .024) in propensity score-matched cohorts. There was no significant difference in time to progression (subdistribution hazard ratio, 0.61; 95% confidence interval, 0.11-3.49; P = .58) in univariate analysis. CONCLUSIONS: Our results demonstrated that SID significantly reduced the recurrence risk of primary NMIBC. Doxorubicin could be an inexpensive alternative to other evidenced-based chemotherapeutic agents for single immediate intravesical chemotherapy.

Two-step technique of early adrenal artery ligation in open adrenalectomy of giant right adrenal pheochromocytomas: Three case reports.

INTRODUCTION: Surgical manipulation of a pheochromocytoma carries the risk of releasing catecholamines into bloodstream leading to severe intraoperative hypertension. CASE PRESENTATION: We present three patients with right adrenal pheochromocytoma over 10 cm diameter: a 40-year-old woman, 63-year-old man, and 66-year-old woman. They were diagnosed by 123I-MIBG scintigraphy and received preoperative antihypertensive treatment with 16 mg/day of doxazosin. Open adrenalectomy was performed with early right adrenal artery ligation between the inferior vena cava and ventral aorta (Step 1) as well as between the tumor and upper pole of the right kidney (Step 2). There was no severe intraoperative hypertension, and no recurrence was observed over 33 months, postoperatively. CONCLUSION: Early adrenal artery ligation may stop tumor blood supply and significantly reduce the catecholamine release. Our technique was thought to be safe and useful for preventing severe intraoperative hypertension in giant right adrenal pheochromocytoma.

Laparoscopic pelvic organ prolapse repair by mesh interposition following radical cystectomy.

INTRODUCTION: The present study aims to introduce laparoscopic treatment by the interposition of polypropylene mesh for a pelvic organ prolapse in females following radical cystectomy for treating muscle-invasive bladder carcinoma. CASE PRESENTATION: The patients included two women aged 77 and 79 years with symptomatic enterocele following radical cystectomy and ileal conduit urinary diversion. We performed laparoscopic sacrospinous colpopexy using polypropylene and polypropylene/ePTFE composite meshes. CONCLUSION: No recurrent prolapse occurred during 26 and 14 months of follow-up after the operation. No severe perioperative complications were noted. This is a first report on cases of laparoscopic sacrospinous colpopexy for post-cystectomy pelvic organ prolapse. Our procedure could be safely performed in two patients with post-cystectomy pelvic organ prolapse.

Region-specific alteration of histone modification by LSD1 inhibitor conjugated with pyrrole-imidazole polyamide.

Epigenome regulates gene expression to determine cell fate, and accumulation of epigenomic aberrations leads to diseases, including cancer. NCD38 inhibits lysine-specific demethylase-1 (LSD1), a histone demethylase targeting H3K4me1 and H3K4me2, but not H3K4me3. In this study, we conjugated NCD38 with a potent small molecule called pyrrole (Py) imidazole (Im) polyamide, to analyze whether targets of the inhibitor could be regulated in a sequence-specific manner. We synthesized two conjugates using ß-Ala (ß) as a linker, i.e., NCD38-ß-ß-Py-Py-Py-Py (NCD38-ß2P4) recognizing WWWWWW sequence, and NCD38-ß-ß-Py-Im-Py-Py (NCD38-ß2PIPP) recognizing WWCGWW sequence. When RKO cells were treated with NCD38, H3K4me2 levels increased in 103 regions with significant activation of nearby genes (P = 0.03), whereas H3K4me3 levels were not obviously increased. H3K27ac levels were also increased in 458 regions with significant activation of nearby genes (P = 3 × 10-10), and these activated regions frequently included GC-rich sequences, but less frequently included AT-rich sequences (P < 1 × 10-15) or WWCGWW sequences (P = 2 × 10-13). When treated with NCD38-ß2P4, 234 regions showed increased H3K27ac levels with significant activation of nearby genes (P = 2 × 10-11), including significantly fewer GC-rich sequences (P < 1 × 10-15) and significantly more AT-rich sequences (P < 1 × 10-15) compared with NCD38 treatment. When treated with NCD38-ß2PIPP, 82 regions showed increased H3K27ac levels, including significantly fewer GC-rich sequences (P = 1 × 10-11) and fewer AT-rich sequences (P = 0.005), but significantly more WWCGWW sequences (P = 0.0001) compared with NCD38 treatment. These indicated that target regions of epigenomic inhibitors could be modified in a sequence-specific manner and that conjugation of Py-Im polyamides may be useful for this purpose.

Synthesis of pyrrole-imidazole polyamide oligomers based on a copper-catalyzed cross-coupling strategy.

Pyrrole-imidazole (Py-Im) polyamides are useful tools for chemical biology and medicinal chemistry studies due to their unique binding properties to the minor groove of DNA. We developed a novel method of synthesizing Py-Im polyamide oligomers based on a Cu-catalyzed cross-coupling strategy. All four patterns of dimer fragments could be synthesized using a Cu-catalyzed Ullmann-type cross-coupling with easily prepared monomer units. Moreover, we demonstrated that pyrrole dimer, trimer, and tetramer building blocks for Py-Im polyamide synthesis were accessible by combining site selective iodination of the pyrrole/pyrrole coupling adduct.

[ANEURYSMAL TYPE RENAL ARTERIOVENOUS FISTULA WITH GIANT VENOUS ANEURYSM, MIMICKING RENAL CELL CARCINOMA: A CASE REPORT].

A 39-year-old man was referred to our clinic for a 7 cm tumor in the right kidney, found by simple CT scan. It was suspected as renal cell carcinoma accompanying tumor emboli in the inferior vena cava by enhanced CT scan. For further evaluation of the tumor emboli, color Doppler ultrasound and enhanced MRI was performed. They showed a large cystic lesion with high velocity turbulent flow and flow voids in T2-weighted imaging, it seemed as giant venous aneurysm of the right renal vein. Subsequently, angiography revealed aneurysmal type renal arteriovenous fistula (AVF), transarterial embolization (TAE) of the arterial feeder with coils was performed on the same day. After 6 months from embolization, there was no recurrences or reinterventions. Color Doppler ultrasound and MRI are beneficial in distinguishing vascular disease from neoplastic disease which may sometimes mimick in other diagnostic imaging studies. In addition TAE seems to be an effective treatment for the AVF.

Synthesis of nitrogen-containing fused-polycyclic compounds from tyramine derivatives using phenol dearomatization and cascade cyclization.

We developed a novel method of synthesizing nitrogen-containing fused-polycyclic compounds using tyramine derivatives as substrates. The method is based on the dearomatization of phenols via an intramolecular ipso-Friedel-Crafts allenylation and sequential bond-forming-cleavage reactions initiated by the construction of an indole skeleton. Structurally diverse fused-heterocycles were produced in reaction sequences requiring only a few steps.

Construction of divergent fused heterocycles via an acid-promoted intramolecular ipso-Friedel-Crafts alkylation of phenol derivatives.

Two different cascade cyclization processes were developed using aryl group-substituted propargyl alcohol derivatives with a p-hydroxybenzylamine unit as common substrates. Using TFA as an acid promoter, an intramolecular ipso-Friedel-Crafts alkylation of phenol derivatives, formation of an iminium cation via a rearomatization-promoted C-C bond cleavage, an aza-Prins reaction, and a 6-membered ring formation proceeded sequentially, producing a variety of fused-tricyclic dihydroquinoline derivatives in 45-99% yield. In addition, a one-pot sequential silver acetate-catalyzed hydroamination/etherification-acid-promoted skeletal rearrangement was examined using the same series of substrates, affording fused-tricyclic indole/benzofuran derivatives in 66-89% yield.

Soft coagulation in partial nephrectomy without renorrhaphy: feasibility of a new technique and early outcomes.

OBJECTIVES: To study the feasibility of a new partial nephrectomy technique using soft coagulation without renorrhaphy. METHODS: Open partial nephrectomy using soft coagulation without renorrhaphy was carried out on 39 consecutive patients with renal tumors. The renal artery was clamped in the initial 23 cases (59%), whereas 16 surgeries (41%) were carried out without clamping. The resected surface of the kidney was coagulated solely by soft coagulation without renorrhaphy. Suturing was used only when the urinary collecting system was opened. The surgical results and perioperative complications were retrospectively evaluated. RESULTS: The mean age of patients was 63.1 years. The mean tumor size was 28.2 mm (range 10-56 mm). The mean RENAL nephrometry score was 8.03 (range 4-10). The mean cold ischemic time (in clamped cases) was 25 min. The mean operative time was 193 min (range 113-310 min), and the mean estimated total blood loss was 172 mL (range 20-530 mL) in all cases. All operations were uneventful, and none required blood transfusion or conversion to nephrectomy. Postoperative complications, such as hemorrhage, urinary fistula formation and requirement of hemodialysis, were not observed. All patients had negative surgical margins, and were free of disease recurrence during the follow-up period (3-49 months). Overall, a remarkable decrease in renal function was not evident at the end of the follow-up period. CONCLUSIONS: This new technique using soft coagulation appears to be safe and feasible for partial nephrectomy.

[Group a streptococcal necrotizing fasciitis of the genital area (Fournier's gangrene): a case report].

A necrotizing fasciitis especially caused by group A streptococcal infection is a life-threatening disease. This infection cause death due to septic shock and multiple organ failure in a short time without the immediate and adequate treatment. Currently a rapid test kit for streptococcal pharyngitis (strep A) is useful for prediction of group A streptococcal infection. We here demonstrate a 61 years old man's case of life-saved necrotizing fasciitis in genital area (Fournier's gangrene) by group A streptococcus infection, and usefulness of this kit for rapid diagnosis, aggressive debridement, and selection of adequate antibiotics.