Thrombocytopenia Following Perceval Sutureless Aortic Valve Replacement in Asian Patients.

BACKGROUND: This study analyzed the safety and performance of the Perceval valve for aortic valve replacement (AVR) in patients at 1 year after undergoing aortic stenosis (AS) treatment, and its effect on significant declines in the platelet count during the immediate postoperative period.Methods and Results: Data were collected retrospectively for the initial 121 patients (median age 77 years; 47.1% females) who underwent Perceval sutureless AVR between May 2019 and July 2022. Implantation was successful in all (100%), with median cross-clamp and CPB times of 59 and 100 min, respectively. Postoperative thrombocytopenia (platelet count <50×103/µL) was noted in 80 (66.1%) patients. Multivariate analysis showed advanced age (>80 years), preoperative low platelet count (<200×103/µL), and a sternotomy approach as significant risk factors for postoperative thrombocytopenia. One (0.8%) patient died within 30 days after the procedure. The 2-year site-reported event rate was 14% (n=17) for all-cause mortality, 0.8% (n=1) for cardiac mortality, 4.1% (n=5) for stroke, and 1.7% (n=2) for endocarditis and valve-related reoperation; there were no instances of paravalvular leakage or structural valve deterioration. CONCLUSIONS: Thrombocytopenia was common after Perceval sutureless AVR, although its impact was not significant. Although Perceval sutureless AVR was found to be a safe and effective option, preoperative assessment of potential bleeding should be performed and the Perceval valve should not be used for patients with a high bleeding risk.

Intracellular Major Histocompatibility Complex Class II and C-X-C Motif Chemokine Ligand 10-Expressing Neutrophils Indicate the State of Anti-Tumor Activity Induced by Bacillus Calmette-Guérin.

(1) Background: Inflammatory responses induce the formation of both anti-tumor and pro-tumor neutrophils known as myeloid-derived suppressor cells (MDSCs). Intermittent intravesical infusion of Bacillus Calmette-Guérin (BCG) is an established cancer immunotherapy for non-muscle-invasive bladder cancer (NMIBC). However, the types of neutrophils induced via the inflammatory response to both tumor-bearing and BCG remain unclear. (2) Methods: We therefore analyzed neutrophil dynamics in the peripheral blood and urine of patients with NMIBC who received BCG therapy. Further, we analyzed the effects of BCG in a mouse intraperitoneal tumor model. (3) Results: BCG therapy induced the formation of CXCL10 and MHC class II-positive neutrophils in the urine of patients with NMIBC but did not induce MDSC formation. CXCL10- and MHC class II-expressing neutrophils were detected in peritoneal exudate cells formed after BCG administration. Partial neutrophil depletion using an anti-Ly6G antibody suppressed the upregulation of CXCL10 and MHC class II in neutrophils and reversed the anti-tumor activity of BCG in mouse models. (4) Conclusions: These results indicated that intracellular MHC class II- and CXCL10-expressing neutrophils indicate the state of anti-tumor activity induced via BCG. The status of neutrophils in mixed inflammation of immunosuppressive and anti-tumor responses may therefore be useful for evaluating immunological systemic conditions.

Initial Myeloid Cell Status Is Associated with Clinical Outcomes of Renal Cell Carcinoma.

The therapeutic outcome of immune checkpoint inhibition (ICI) can be improved through combination treatments with ICI therapy. Myeloid-derived suppressor cells (MDSCs) strongly suppress tumor immunity. MDSCs are a heterogeneous cell population, originating from the unusual differentiation of neutrophils/monocytes induced by environmental factors such as inflammation. The myeloid cell population consists of an indistinguishable mixture of various types of MDSCs and activated neutrophils/monocytes. In this study, we investigated whether the clinical outcomes of ICI therapy could be predicted by estimating the status of the myeloid cells, including MDSCs. Several MDSC indexes, such as glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80), CD16, and latency-associated peptide-1 (LAP-1; transforming growth factor-ß1 precursor), were analyzed via flow cytometry using peripheral blood derived from patients with advanced renal cell carcinoma (n = 51) immediately before and during the therapy. Elevated CD16 and LAP-1 expressions after the first treatment were associated with a poor response to ICI therapy. Immediately before ICI therapy, GPI-80 expression in neutrophils was significantly higher in patients with a complete response than in those with disease progression. This is the first study to demonstrate a relationship between the status of the myeloid cells during the initial phase of ICI therapy and clinical outcomes.

An elderly case of aortic stenosis associated with double-chambered right ventricle.

Double-chambered right ventricle (DCRV) caused by right ventricular outflow tract obstruction, is a developmental cardiac anomaly in which the anomalous muscle bundles divide the right ventricular cavity into two chambers. Few cases with DCRV coexisting with severe aortic stenosis (AS) have been reported. Moreover, adult cases are extremely uncommon.We report an elderly case of a heavy DCRV with severe AS detected by transthoracic echocardiography and catheterization study. An 85-year-old woman with dyspnea on effort and right-sided heart failure was diagnosed with DCRV and severe AS by echocardiography. She underwent a resection of the anomalous muscle of the right ventricle and aortic valve replacement. Her symptoms disappeared postoperatively and was discharged home. At 2 years postoperatively, she was generally well without recurrence of DCRV. In conclusion, the case of DCRV with AS is rare and surgery is useful to relieve the heart failure symptoms and improve the prognosis of both young and adult patients. Learning objective: Double-chambered right ventricle (DCRV) is uncommon in the older population; however, clinicians should consider DCRV in patients with right-sided heart failure as a differential diagnosis. The case of DCRV with aortic stenosis is rare, surgical treatment is particularly useful for these patients to relieve the heart failure symptoms and improve the prognosis in young and adult cases.

Association between Hyposensitivity of C-fiber Afferents at The Proximal Urethra and Storage/voiding Dysfunction in Female Patients with Detrusor Overactivity.

PURPOSE: We examined the associations between urethral sensation and storage/voiding function in female patients with detrusor overactivity (DO) by measuring urethral current perception threshold (CPT). MATERIALS AND METHODS: We retrospectively investigated the medical records of 27 consecutive patients with lower urinary tract symptoms who underwent cystometry, uroflowmetry (UFM), and urethral CPT tests from 2000 to 2015. Patients were classified into 2 groups: with/without DO. Seven DO-negative cases were selected as normal controls on cystometrogram (CMG) matching the inclusion criteria: bladder compliance ?12.5 mL/cmH2O, volume <275 mL at first sensation, and no comorbidities possibly influencing micturition. Finally, 17 patients were included. Urethral CPT was evaluated with intraurethral square-wave impulses at 3 Hz to stimulate C-fibers. Urethral loss coefficient (LC), reflecting urethral resistance during voiding, was calculated by curve-fitting a mathematical model to a UFM waveform. RESULTS: Urge incontinence (UI) was observed in 7 DO-positive patients, but not in those with normal CMG. Urethral CPT and LC were significantly higher in patients with DO than in those with normal CMG. Median urethral CPT significantly increased in patients with both DO and UI than in those without these symptoms (p<0.005). CPT values were correlated with the volume at first sensation (?=0.53, p<0.05) and LC (?=0.59, p<0.05). LC was not calculated in 3 cases due to poor curve-fitting. CONCLUSIONS: In females, urethral C-fiber afferents may become hyposensitive as the detrusor becomes overactive with UI in the storage phase. During voiding, C-fiber hyposensitivity may relate to increased functional resistance of the urethra to urine outflow.

New prognostic model for synchronous metastatic renal cell carcinoma.

OBJECTIVES: To create a new model for the prediction of overall survival in synchronous metastatic renal cell carcinoma. METHODS: Medical records of 158 patients with metastatic renal cell carcinoma diagnosed at the Yamagata University Hospital from August 2007 to February 2018 were reviewed. Among them, 77 with synchronous metastatic renal cell carcinoma were retrospectively analyzed using the univariate and multivariate analyses. A new prognostic model was constructed, followed by a bootstrap validation to estimate the model fitting. In addition, these prognostic factors were estimated in 67 metachronous metastatic renal cell carcinoma patients. RESULTS: Five independent prognostic factors were identified in synchronous metastatic renal cell carcinoma: cT3/4, cN1, high corrected calcium, >3.6 neutrophil-to-lymphocyte ratio and central nerve system metastasis. The number (%) and overall survival (95% confidence interval) in the favorable- (0 or 1 risk factor), intermediate- (2 risk factors) and poor-risk (≥3 risk factors) groups were 29 (45.3%) and 67.4 (31.8-NA), 21 (32.8%) and 16.8 (10.0-27.6), and 14 (21.9%) and 9.1 (7.3-13.7) months, respectively. The C-index was 0.72. Patients in the favorable-risk group had better overall survival with nephrectomy than without nephrectomy (hazard ratio 0.29, 95% confidence interval 0.09-0.91 with nephrectomy). In metachronous metastatic renal cell carcinoma, these prognostic factors showed no statistical differences in the overall survival. CONCLUSIONS: Prognostic factors are completely different between synchronous and metachronous metastatic renal cell carcinoma. The new model for synchronous metastatic renal cell carcinoma can predict a good candidate for cytoreductive nephrectomy.

Effect of third- and fourth-line systemic therapies for metastatic renal cell carcinoma.

Data on the outcomes of third- or fourth-line therapy for metastatic renal cell carcinoma (mRCC) are limited. The aim of our study was to evaluate the efficacy of therapy beyond the second line. We retrospectively analysed data of mRCC patients who underwent systemic therapy at Yamagata University Hospital. The best objective response (BOR), response rate (RR), and progression-free survival (PFS) were assessed for each line of treatment. To investigate the correlation between overall survival (OS) and the number of treatment lines during a patient's lifetime, the median OS was assessed using univariate and multivariate analyses. In the first-, second-, and third-line therapies, approximately 20% of patients had long PFS of >15 months. In targeted treatments beyond the third line, only one treatment suppressed disease progression for >10 months. Among patients who died during the follow-up period, those treated with triple and quadruple lines had similar OS (42.5 months vs. 48.4 months, respectively). Multivariate analysis showed that patients with triple or more lines of therapy had better OS; however, quadruple or more lines of therapy was not an independent prognostic factor. We concluded that third-line systemic therapy could improve OS; however, fourth-line therapy could not.

Impact of eIF4E phosphorylation at Ser209 via MNK2a on tumour recurrence after curative surgery in localized clear cell renal cell carcinoma.

Background: We investigated the roles of eIF4E phosphorylation (Ser209) in tumour recurrence after curative nephrectomy for localized clear cell renal cell carcinoma (ccRCC). Methods: Expression of eIF4E, p eIF4E and MNKs (MAPK interacting kinases), was evaluated in surgical specimens obtained from consecutive non metastatic ccRCC patients (n = 290) by immunohistochemistry (IHC), immunoblotting, and qRT PCR at the protein and mRNA levels. In human RCC cell lines, the effects of eIF4E phosphorylation were examined using immunoblotting, proliferation, migration and invasion assays with pharmacological inhibitors (CGP57380 or ETP45835) and specific small interfering (si) RNAs against MNK1/2(a/b). Results: In postoperative follow-up (median, 7.9 y), 40 patients experienced metastatic recurrence. In multivariate Cox analyses, higher IHC expression of p eIF4E in ccRCC significantly predicted a longer recurrence-free interval. eIF4E is phosphorylated mainly by MNK2a in tumour specimens and cell lines. In 786-O and A-498 cell lines, pharmacological inhibition of MNKs decreased p-eIF4E and increased vimentin and N cadherin but did not influence proliferation. Similarly, MNK2 or MNK2a inhibition with siRNA reduced p-eIF4E and enhanced vimentin translation, cell migration and invasion in the cell lines. Conclusions: MNK2a-induced eIF4E phosphorylation may suppress metastatic recurrence of ccRCC, partially due to vimentin downregulation at the translational level, consequently leading to inhibition of epithelial-mesenchymal transition.

Successful Treatment with Paclitaxel, Carboplatin, and Gemcitabine as Second-line Chemotherapy for Recurrent Urothelial Carcinoma of the Bladder with Glandular Differentiation After Radical Cystectomy: A Case Report.

Urothelial carcinoma of the bladder (UCB) with glandular differentiation is a histological variant (HV) that is more likely to have positive extravesical tumors or nodes than those in pure UCB. Cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) is more effective for pure UCB; however, few reports are available on second-line chemotherapy for recurrence of UCB with HV. Here we report a 65-year-old Japanese male diagnosed with local recurrence UCB with HV after NAC + RC who safely achieved complete response with paclitaxel, carboplatin, and gemcitabine combination chemotherapy.

[CEREBRAL VENOUS SINUS THROMBOSIS IN PATIENTS WITH METASTATIC TESTICULAR CANCER DURING CHEMOTHERAPY: REPORTS OF TWO CASES].

Cerebral venous sinus thrombosis (CVT) is rare but sometimes develops in association with malignant neoplasm. We report two cases of CVT that occurred during cisplatin-based chemotherapy for testicular cancer. A 46-year-old man with stage IIA non-seminomatous germ cell tumour was treated with conventional doses of etoposide and cisplatin (EP). On day 11 of the third treatment course, he developed a systemic seizure. Brain computed tomography (CT) and magnetic resonance (MR) imaging could not detect the cause. Enhanced chest-pelvic CT revealed pelvic thrombosis. Administration of phenytoin for epilepsy of unknown cause and heparin for thrombosis was started. He had completed 4 courses of EP therapy without seizure recurrence. After re-evaluating the brain CT images retrospectively, we found high density of superior sagittal sinus (SSS) and strongly suspected CVT. Another patient was a 47-year-old man with stage IIIB seminomatous germ cell tumour treated with bleomycin, etoposide, and cisplatin (BEP) therapy. On day 11 of the second treatment course, he developed a systemic seizure. Brain CT revealed subarachnoid haemorrhage localised in the right parietal lobe. CT venography revealed a filling defect in the superior sagittal sinus (SSS). MR venography revealed a SSS stenosis. We diagnosed the cause of the seizure as CVT and started administration of anticoagulant therapy. After the thrombus had diminished, chemotherapy was restarted and another 2 courses of BEP therapy was completed.