Tooth morphology fusion technique is more accurate than conventional technique in transferring morphology of provisional to definitive screw-retained, implant-supported crown: A preliminary intervention study.

PURPOSE: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown. METHODS: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test. RESULTS: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05). CONCLUSIONS: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis.

Fixed Partial Denture Designed by Combining the Whole 3D Digital Surface Morphology of the Provisional Restoration and Abutment Teeth Surfaces.

We introduce a new digital workflow to fabricate a fixed partial denture (FPD) utilizing the three-dimensional surface morphology of provisional restoration (PR) and abutment teeth. Scanned images of the full maxilla with abutment teeth, full maxilla with PR, and PR alone were superimposed. The surfaces of the final FPD were designed based on the entire morphology of the PR and abutment teeth surfaces. The inner and outer surfaces converged at the margin lines of the abutment teeth. Fine modifications to the final FPD design were performed manually, and the final FPD was fabricated and successfully installed in the patient.

Outcomes of treatment for localized prostate cancer in a single institution: comparison of radical prostatectomy and radiation therapy by propensity score matching analysis.

OBJECTIVES: To compare the outcomes of radical prostatectomy (RP), intensity-modulated radiation therapy (IMRT), and low-dose-rate brachytherapy (BT) using propensity score matching analysis in patients with clinically localized prostate cancer. METHODS: A group of 2273 patients with clinically localized prostate cancer between January 2004 and December 2015 at the Yokohama City University hospital were identified. The records of 1817 of these patients, who were followed up for a minimum of 2 years, were reviewed; 462 were treated with RP, 319 with IMRT, and 1036 with BT. The patients were categorized according to the National Comprehensive Cancer Network risk classification criteria, and biochemical outcomes and overall survival rates were examined. Biochemical failure for RP was defined as prostate-specific antigen (PSA) levels > 0.2 ng/ml, and for IMRT and BT as nadir PSA level + 2 ng/ml. Propensity scores were calculated using multivariable logistic regression based on covariates, including the patient's age, preoperative PSA, Gleason score, number of positive cores, and clinical T stage. RESULTS: Median follow-up was 77 months for the RP, 54 months for IMRT, and 66 months for BT patients. After the propensity scores were adjusted, a total of 372 (186 each) and 598 (299 each) patients were categorized into RP vs IMRT and RP vs BT groups, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival rate between these groups (RP vs IMRT: p = 0.220; RP vs BT: p = 0.429). IMRT was associated with improved biochemical failure-free survival compared to RP in all risk groups (high-risk: p < 0.001; intermediate-risk: p = 0.009; low-risk: p = 0.001), whereas significant differences were observed only in the intermediate-risk group (p = 0.003) within the RP vs BT group. CONCLUSION: The results of our propensity score analysis of mid-term localized prostate cancer treatment outcomes demonstrated no significant differences in the overall survival rate. Despite the difference in biochemical failure definition between surgery and radiotherapeutic approaches, the results of this study demonstrate improved biochemical control favoring IMRT and BT as compared to RP.

Successful Resection of Cisplatin-Resistant Renal Pelvic Cancer after the Administration of Pembrolizumab as Second-Line Therapy.

Pembrolizumab has been used as a second-line systemic therapy for urothelial carcinoma. We herein report a case of cisplatin-resistant renal-pelvic urothelial carcinoma that was successfully resected after pembrolizumab treatment. A 74-year-old woman was referred to our hospital for further examination for gross hematuria and a renal-pelvis tumor. Retrograde pyelography showed a defect lesion in her renal pelvis and urinary cytology of the renal pelvis showed class V. Because staging CT could not deny lung metastasis, we planned to perform nephro-ureterectomy after evaluating the response to neoadjuvant chemotherapy. After three courses of gemcitabine and cisplatin chemotherapy, the original site showed progression; thus, nephro-ureterectomy was cancelled. We introduced pembrolizumab as a second-line therapy. After four courses of pembrolizumab treatment, the size of the original lesion was significantly decreased. During these therapies the lung tumor size was unchanged; thus, we determined that the lung tumor was not metastatic and performed nephro-ureterectomy. A pathological examination demonstrated that the tumor was completely resected with a negative surgical margin. We described the first case in which cisplatin-resistant renal pelvic tumor was successfully resected after pembrolizumab treatment.

Androgen receptor mRNA expression is a predictor for recurrence-free survival in non-muscle invasive bladder cancer.

BACKGROUND: Non-muscular invasive bladder cancer (NMIBC) has a high risk of recurrence. As androgen receptor (AR) reportedly affects bladder cancer, we assessed the correlation between NMIBC recurrence and tumor AR expression in Japanese patients. METHODS: We retrospectively reviewed 53 specimens of non-metastatic NMIBC, with recurrence-free survival (RFS) as the primary endpoint. We used real-time quantitative polymerase chain reaction to quantify AR mRNA expression. Kaplan-Meier product-limit estimators were used to assess RFS distribution, log-rank tests to analyze differences in RFS between high- and low-risk groups; and multivariate analyses of AR mRNA expression and other clinicopathological factors to predict independent factors for RFS. RESULTS: The high AR mRNA-expressing group (n = 43) tended to have a longer median RFS (not reached) than did the low-AR group (n = 10; 9.04 months; P = 0.112). Multivariate analysis showed female sex (hazard ratio [HR]: 7.360, 95% CI: 1.649-32.856, P = 0.009), tumor size ≥3 cm (HR: 23.697, 95% CI: 4.383-128.117, P < 0.001) and low AR mRNA expression (HR: 0.202, 95% CI: 0.048-0.841, P = 0.028) to be independent predictors of shorter RFS. CONCLUSION: Our study showed that low AR mRNA expression level is an independent risk factor for RFS in Japanese patients with NMIBC. Further studies are necessary but AR expression might be a new indicator of recurrence of NMIBC.

Early assessment with 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab.

BACKGROUND: We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab. METHODS: Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not). RESULTS: There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373-124.716). CONCLUSION: Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012.

Clear cell adenocarcinoma of the prostatic urethra: A case report.

INTRODUCTION: Clear cell adenocarcinoma of the prostatic urethra in men is an extremely rare disease, with only eight case reports published. CASE PRESENTATION: A 56-year-old man visited our hospital for gross hematuria. Urinary cytology detected class V, cystoscopy showed no abnormal findings, and contrast-enhanced computed tomography also showed no abnormal findings in his upper urinary tract except for a low-enhancement lesion on his left prostate lobe. Magnetic resonance imaging revealed a cystic lesion surrounding the prostate that was suspected of being urethral or prostate cancer, so transurethral resection was performed. A papillary tumor was detected at the prostatic urethra, and after resecting this tumor, a cavity showing multiple tumors was observed. The final pathological diagnosis was clear cell adenocarcinoma. Laparoscopic radical cystectomy and urethrectomy were thus performed. The pathological diagnosis was the same as at the primary tumor site. CONCLUSION: We herein report a case of clear cell adenocarcinoma of the prostatic urethra.

Successful treatment with sorafenib for sunitinib-refractory metastatic papillary renal cell carcinoma: Potential impact of Raf overexpression on predicting the efficacy of sorafenib.

INTRODUCTION: The prognosis of type 2 papillary renal cell carcinoma is often poor. We herein report a case of papillary renal cell carcinoma with liver metastasis that was successfully treated with sorafenib as a second-line therapy. CASE PRESENTATION: An 82-year-old man who had undergone radical nephrectomy 5 years previously experienced biopsy-proven liver metastasis. He received sunitinib as a first-line treatment; the dose was initially 12.5 mg/day and was escalated to 25 mg/day, but it was discontinued due to several adverse events. We then switched to sorafenib as a second-line treatment, which resulted in a partial response (51% reduction in tumor size); the patient showed no recurrence 5 months after the initiation of sorafenib treatment. An immunohistochemical analysis revealed the overexpression of Raf in both the primary and metastatic tumors. CONCLUSION: As sorafenib blocks Raf signaling, the expression of Raf may serve as a useful predictor of the efficacy of sorafenib.

High orchiectomy and ipsilateral testicular sperm extraction in a man with a testicular tumor and Klinefelter syndrome: A case report.

INTRODUCTION: Testicular epidermal cysts in Klinefelter syndrome are very rare. We report a case of Klinefelter syndrome associated with a testicular epidermal cyst. To our knowledge, this is the first report showing successful spermatozoa retrieval from the affected testis. CASE PRESENTATION: A 25-year-old married man was referred to our hospital with right scrotal induration, which was in lower pole of the right testis. Testicular cancer tumor markers were normal; endocrinological findings indicated hypergonadotropic hypogonadism. Semen analyses revealed azoospermia. Preoperative chromosome test result: 47, XXY karyotype; ultrasonography report: 1.9-cm internal heterogeneous echoic mass in the right testis (malignancy not discarded). Because the patient hoped for children, he underwent high orchiectomy with ipsilateral testicular sperm extraction (200 spermatozoa from normal testicular tissue) for future fertilization procedures. Tumor pathology was an epidermal cyst. CONCLUSION: While performing orchiectomy for testicular tumors, sperm retrieval should be attempted from normal tissues in patients planning for children.

Spontaneous adrenal hemorrhage with dehydroepiandrosterone-sulfate elevation in a patient with suspected adrenal cortical carcinoma.

INTRODUCTION: Spontaneous adrenal hemorrhage is a relatively rare disease that is sometimes difficult to differentiate from adrenal cortical carcinoma. We herein report a case of spontaneous adrenal hemorrhage with dehydroepiandrosterone-sulfate elevation. CASE PRESENTATION: The patient was a 78-year-old man with an adrenal tumor that had increased in size to 42 mm. With the exception of an elevated dehydroepiandrosterone-sulfate level (2281 ng/mL), the results of a hormone analysis were almost normal. Laparoscopic adrenal tumor resection was performed. The pathological diagnosis was adrenal hematoma. CONCLUSION: We reported a case of spontaneous adrenal hemorrhage in a patient with dehydroepiandrosterone-sulfate elevation.

Functional paraganglioma of the bladder: Both radiographic-negative and laboratory-negative case.

INTRODUCTION: Paraganglioma has been determined to be an extra-adrenal pheochromocytoma. Paraganglioma of the bladder is a rare entity, accounting for 0.06% of all bladder tumors. CASE PRESENTATION: A 58-year-old woman had been annually followed up since being diagnosed with rectal cancer 5 years ago. In January 2018, follow-up computed tomography detected a bladder tumor, and she was referred to our department for a further examination. Cystoscopy revealed a submucosal tumor on her right bladder wall. We performed transurethral resection of the bladder tumor. When we first marked the tumor margin, the systolic blood pressure increased, so we abandoned resection. We performed meta-iodobenzylguanidine scintigraphy and acid urinary collection, neither of which revealed any abnormal findings. We therefore performed open partial cystectomy based on a clinical diagnosis of paraganglioma of the bladder. The pathological findings revealed paraganglioma of the bladder. CONCLUSION: We herein report a case of paraganglioma of the bladder.

Digital transfer of the subgingival contour and emergence profile of the provisional restoration to the final bone-anchored fixed restoration.

PURPOSE: This report was written to introduce an attempt at clinical application of our newly developed digital workflow to reproduce the morphology of the subgingival contour and the emergence profile of the provisional restoration within the final bone-anchored fixed restoration, using a bounded unilateral edentulous case. METHODS: This digital workflow involves superimposition of the composite images of two specific types of working casts onto the working cast for the provisional restoration namely, a split cast screwed with a titanium base and a split cast screwed with a provisional restoration and integrating these with the whole intraoral surface image, in which the provisional restoration was present. The final restoration fabricated using this technique could be installed without any clinical problems. The results of in silico analysis revealed that the cubic volume ratio of the total discrepancy between the provisional and the final restorations was only 2.4%. Further, sufficient oral hygiene was maintained and the patient was satisfied with the outcome of the treatment. CONCLUSIONS: This technical report suggests that our newly developed digital workflow provided clinical applicability and may enable accurate transfer of the morphology of the subgingival contour and emergence profile of the provisional to the final bone-anchored fixed restoration.

PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer.

BACKGROUND: Bladder cancers have been characterized as a tumor group in which the immunological response is relatively well preserved. Programmed death ligand 1 (PD-L1, B7-H1, CD274) has been shown to be expressed in several malignancies, including bladder cancer. However, the clinicopathological impact of this biomarker has not yet been established. In the present study, a quantitative real-time polymerase chain reaction (qPCR) was performed using paired normal and cancerous bladder cancer tissue to investigate PD-1/PD-L1 gene expression. METHODS: We examined the mRNA expression of PD-1/PD-L1 by a qPCR using 58 pairs of normal and cancerous human bladder tissue specimens. We also examined the correlation with the expressions of the STAT1 and NFAT genes, which are thought to be upstream and downstream of the PD-L1 pathway, respectively. RESULTS: There were no significant differences between normal and cancerous tissue in the expression of the PD-1 and PD-L1 genes (p = 0.724 and p = 0.102, respectively). However, PD-1 and PD-L1 were both more highly expressed in high-grade bladder cancer than in low-grade bladder cancer (p < 0.050 and p < 0.010). PD-L1 was positively correlated with the expressions of both the STAT1 (r = 0.681, p < 0.001) and the NFATc1 genes (r = 0.444. p < 0.001). CONCLUSIONS: PD-1 and PD-L1 might be a new biomarker that correlates with the pathological grade of bladder cancer. PD-L1 might function as a mediator of stage progression in bladder cancer and STAT1-NFAT pathway might associate this function.

Oxidative stress marker 8-hydroxyguanosine is more highly expressed in prostate cancer than in benign prostatic hyperplasia.

Oxidative stress is a primary cause of vascular endothelial damage. In the prostate, ischemia increases the levels of reactive oxygen species, growth factors and cytokines, and induces the development of angiogenesis, which results in cancer progression. The expression levels of an oxidative stress marker, 8-hydroxyguanosine (8-OHdG), were compared between prostate cancer and non-neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were significantly higher than those in benign prostatic hyperplasia (71.4% moderate and 28.6% strong; (p<0.01). Notably, 8-OHdG is expressed more highly in prostate cancer tissues in comparison to benign prostate tissues.

BHD-associated kidney cancer exhibits unique molecular characteristics and a wide variety of variants in chromatin remodeling genes.

Birt-Hogg-Dubé (BHD) syndrome is a hereditary kidney cancer syndrome, which predisposes patients to develop kidney cancer, cutaneous fibrofolliculomas and pulmonary cysts. The responsible gene FLCN is a tumor suppressor for kidney cancer, which plays an important role in energy homeostasis through the regulation of mitochondrial oxidative metabolism. However, the process by which FLCN-deficiency leads to renal tumorigenesis is unclear. In order to clarify molecular pathogenesis of BHD-associated kidney cancer, we conducted whole-exome sequencing analysis using next-generation sequencing technology as well as metabolite analysis using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Whole-exome sequencing analysis of BHD-associated kidney cancer revealed that copy number variations of BHD-associated kidney cancer are considerably different from those already reported in sporadic cases. In somatic variant analysis, very few variants were commonly observed in BHD-associated kidney cancer; however, variants in chromatin remodeling genes were frequently observed in BHD-associated kidney cancer (17/29 tumors, 59%). Metabolite analysis of BHD-associated kidney cancer revealed metabolic reprogramming toward upregulated redox regulation which may neutralize reactive oxygen species potentially produced from mitochondria with increased respiratory capacity under FLCN-deficiency. BHD-associated kidney cancer displays unique molecular characteristics that are completely different from sporadic kidney cancer, providing mechanistic insight into tumorigenesis under FLCN-deficiency as well as a foundation for development of novel therapeutics for kidney cancer.

[A Case of Renal Cell Carcinoma Growing into the Renal Pelvis with a Fibrin Cap in the Ureter and Bladder].

We present a case of renal cell carcinoma growing into the renal pelvis with a fibrin cap in the ureter and bladder. A 66-year-old man presented to our hospital with anemia and gross hematuria. Computed tomography showed a large left renal tumor and space-occupying lesions in the left renal pelvis and ureter. Cystoscopy showed a 2 cm-restiform mass protruding from the left ureteral orifice. We performed open left nephroureterectomy, and there was a 3 cm white mass with a smooth surface in the bladder. Pathological examination of the resected mass revealed clear cell carcinoma with urinary collecting system invasion and fibrin cap in the ureter and bladder. As a result, it would have been difficult to make the diagnossis of renal cell carcinoma preoperatively if we had performed biopsy of the mass in the bladder or ureter. The patient was diagnosed as having lung metastases 5 months after surgery. Urinary collecting system invasion has been considered an independent prognostic factor in pT3 renal cell carcinoma.

Fluorescent Light-Guided Cystoscopy with 5-ALA Aids in Accurate Surgical Margin Detection for TURBO: A Case Report.

Recent studies have revealed that transurethral resection in one piece (TURBO) has several benefits over standard transurethral resection of bladder tumor (TUR-Bt), including a higher rate of containing the bladder muscle tissue and single-block resection. Five-aminolevulinic acid (5-ALA) was approved for the detection of bladder tumor treated with TUR-Bt. A 71-year-old male patient who received right nephroureterectomy developed bladder tumor recurrence on routine cystoscopy follow-up. We planned TURBO using fluorescent light-guided cystoscopy with 5-ALA. We herein report a case of bladder tumor successfully treated with TURBO using fluorescent light-guided cystoscopy with 5-ALA to detect the tumor surgical margin.