Evaluation of the Effectiveness of Additional Risk Minimization Measures for Ixazomib Citrate for Relapsed/Refractory Multiple Myeloma in Japan: A Web-Based Survey Among Pharmacists.

BACKGROUND: Ixazomib citrate (IXA) in combination with lenalidomide and dexamethasone (IRD therapy) has been approved for the treatment of relapsed or refractory multiple myeloma. In Japan, as these three drugs have different dosing schedules, dosing instructions for patients have been prepared and distributed to patients via healthcare professionals to promote an understanding of the appropriate dosing regimen, as an additional risk minimization measure (aRMM). OBJECTIVES: This survey aimed to investigate whether the aRMM material is being utilized for the adequate use of IXA. METHODS: A web-based questionnaire survey was conducted among in-hospital pharmacists in Japan who instructed patients on IXA dosing for IRD therapy. The primary endpoint was the proportion of pharmacists who provided patients with the contents of the aRMM material (i.e., how to take IXA). The secondary endpoints were the proportion of pharmacists who had obtained the aRMM material and the proportion of pharmacists who understood the importance of explaining how to take IXA to patients. RESULTS: Of the 330 pharmacists who completed the questionnaire, 93.0% answered that they had explained how to take IXA to patients. Of those who answered that they had explained how to take IXA, 33.2% responded that they had experience in using the aRMM material. In addition, 37.6% of the pharmacists answered that they had obtained the aRMM material. Moreover, 95.8% stated that they knew how to take IXA, and 90.3, 9.1, 0.3, and 0.3% of pharmacists answered that the importance of explaining how to take IXA was "very important," "probably important," "less important" and "not important," respectively. CONCLUSIONS: How to take IXA was explained to patients by pharmacists and the aRMM material was utilized at the time of the explanation, indicating that the aRMM material contributes to the promotion of the appropriate use of IXA.

Analgesic Effect of the Kampo Formula Yokukansan via the Suppression of Substance P in an Experimental Rat Model of Hunner-Type Interstitial Cystitis.

INTRODUCTION: Yokukansan (YKS), a Kampo formula used in traditional Japanese medicine, has an analgesic effect, and is used for various pain disorders. This study investigated its analgesic effects on Hunner-type interstitial cystitis (HIC) and its mechanism of action in animal models.   Methods: Rats with toll-like receptor-7 agonist (loxoribine)-induced HIC were used. Eight-week-old female Wistar rats were divided into three groups: control, HIC, and HIC-administered YKS (YKS + HIC). Bladder pain was assessed based on escape behavior using the von Frey test. Three days after HIC induction, the bladder and spinal cord were excised, and the expression of substance P (SP) was examined.   Results: The pain threshold decreased significantly in the HIC group compared to that in the control group, but this decrease was suppressed by further YKS administration. The expression of SP in the bladder wall and spinal cord increased significantly in the HIC group compared to that in the control group; however, this increase was suppressed by YKS administration. CONCLUSION: SP is involved in the onset of bladder pain via neurokinin 1 receptors in bladder tissue. YKS may be useful for managing HIC-induced pain, and the suppression of SP secretion is one of its mechanisms of action.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios alone or combined with prostate-specific antigen for the diagnosis of prostate cancer and clinically significant prostate cancer.

Objective: We evaluated whether the blood parameters before prostate biopsy can diagnose prostate cancer (PCa) and clinically significant PCa (Gleason score [GS] ≥7) in our hospital. Methods: This study included patients with increased prostate-specific antigen (PSA) up to 20 ng/mL. The associations of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) alone or with PSA with PCa and clinically significant PCa were analyzed. Results: We included 365 patients, of whom 52.9% (193) had PCa including 66.8% (129) with GS of ≥7. PSA density (PSAD) and PSA had better the area under the curve (AUC) of 0.722 and 0.585, respectively with p=0.001 for detecting PCa compared with other blood parameters. PSA combined with PLR (PsPLR) and PSA with NLR (PsNLR) had better AUC of 0.608 and 0.610, respectively with p<0.05, for diagnosing GS≥7 population, compared with PSA, free/total PSA, NLR, PLR, and PsNPLR (PSA combined with NLR and PLR). NLR and PLR did not predict PCa on multivariate analysis. For GS≥7 cancer detection, in the multivariate analysis, separate models with PSA and NLR (Model 1: PsNLR+baseline parameters) or PSA and PLR (Moder 2: PsPLR+baseline parameters) were made. Baseline parameters comprised age, digital rectal exam-positive lesions, PSA density, free/total PSA, and magnetic resonance imaging. Model 2 containing PsPLR was statistically significant (odds ratio: 2.862, 95% confidence interval: 1.174-6.975, p=0.021) in finding aggressive PCa. The predictive accuracy of Model 2 was increased (AUC: 0.734, p<0.001) than that when only baseline parameters were used (AUC: 0.693, p<0.001). Conclusion: NLR or PLR, either alone or combined with PSA, did not detect PCa. However, the combined use of PSA with PLR could find the differences between clinically significant and insignificant PCa in our retrospective study limited by the small number of samples.

Biomolecular Fluorescence Complementation Profiling and Artificial Intelligence Structure Prediction of the Kaposi's Sarcoma-Associated Herpesvirus ORF18 and ORF30 Interaction.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. During KSHV lytic infection, lytic-related genes, categorized as immediate-early, early, and late genes, are expressed in a temporal manner. The transcription of late genes requires the virus-specific pre-initiation complex (vPIC), which consists of viral transcription factors. However, the protein-protein interactions of the vPIC factors have not been completely elucidated. KSHV ORF18 is one of the vPIC factors, and its interaction with other viral proteins has not been sufficiently revealed. In order to clarify these issues, we analyzed the interaction between ORF18 and another vPIC factor, ORF30, in living cells using the bimolecular fluorescence complementation (BiFC) assay. We identified four amino-acid residues (Leu29, Glu36, His41, and Trp170) of ORF18 that were responsible for its interaction with ORF30. Pull-down assays also showed that these four residues were required for the ORF18-ORF30 interaction. The artificial intelligence (AI) system AlphaFold2 predicted that the identified four residues are localized on the surface of ORF18 and are in proximity to each other. Thus, our AI-predicted model supports the importance of the four residues for binding ORF18 to ORF30. These results indicated that wet experiments in combination with AI may enhance the structural characterization of vPIC protein-protein interactions.

Prevention of non-infectious pulmonary complications after intra-bone marrow stem cell transplantation in mice.

Non-infectious pulmonary complications including idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans syndrome (BOS), which are clinical and diagnostic manifestations of lung chronic graft-versus-host disease (GVHD), cause significant mortality after allogeneic stem cell transplantation (SCT). Increasing evidence suggests that alloantigen reactions in lung tissue play a central role in the pathogenesis of IPS and BOS; however, the mechanism is not fully understood. Several clinical and experimental studies have reported that intra-bone marrow (IBM)-SCT provides high rates of engraftment and is associated with a low incidence of acute GVHD. In the present study, allogeneic SCT was conducted in mouse models of IPS and BOS, to compare intravenous (IV)-SCT with IBM-SCT. Allogeneic IBM-SCT improved the clinical and pathological outcomes of pulmonary complications compared to those of IV-SCT. The mechanisms underlying the reductions in pulmonary complications in IBM-SCT mice were explored. The infiltrating lung cells were mainly CD11b+ myeloid and CD3+ T cells, in the same proportions as in transplanted donor cells. In an in vivo bioluminescence imaging, a higher proportion of injected donor cells was detected in the lung during the early phase (1 h after IV-SCT) than after IBM-SCT (16.7 ± 1.1 vs. 3.1 ± 0.7 × 105 photons/s/animal, IV-SCT vs. IBM-SCT, P = 1.90 × 10-10). In the late phase (5 days) after SCT, there were also significantly more donor cells in the lung after IV-SCT than after IBM-SCT or allogeneic-SCT (508.5 ± 66.1 vs. 160.1 ± 61.9 × 106 photons/s/animal, IV-SCT vs. IBM-SCT, P = 0.001), suggesting that the allogeneic reaction induces sustained donor cell infiltration in the lung during the late phase. These results demonstrated that IBM-SCT is capable of reducing injected donor cells in the lung; IBM-SCT decreases donor cell infiltration. IBM-SCT therefore represents a promising transplantation strategy for reducing pulmonary complications, by suppressing the first step in the pathophysiology of chronic GVHD.

The Japanese Herbal Medicine Yokukansan Exerted Antioxidant and Analgesic Effects in an Experimental Rat Model of Hunner-Type Interstitial Cystitis.

Background and Objectives: The Japanese herbal medicine Yokukansan (YKS) has analgesic properties and is used for various pain disorders. The purpose of the present study was to investigate the effects of YKS in Hunner-type interstitial cystitis (HIC) using an experimental rat model of HIC and to explore its antioxidant activity and role as the underlying mechanism of action. Materials and Methods: The antioxidant capacity of YKS was evaluated by determining its hydroxyl radical (·OH) scavenging capacity using electron spin resonance (ESR). Next, the effects of YKS administration were explored using a toll-like receptor-7 agonist-induced rat model of HIC. The von Frey test was performed to assess bladder pain. Three days after HIC induction, the bladder was removed, and the expression of oxidative stress parameters in the bladder wall was investigated (reactive oxygen metabolites (ROMs), ·OH, and 8-hydroxy-2'-deoxyguanosine (8-OhdG)). Results: YKS had a ·OH scavenging capacity according to the ESR study. In the von Frey test, a significant decrease in the withdrawal threshold was observed in the HIC group compared with the control group; however, the decrease was ameliorated by the administration of YKS. Oxidative stress parameters showed increasing tendencies (ROMs test and 8-OHdG) or a significant increase (·OH) in the HIC group compared with the control group; however, the increase was significantly suppressed by the administration of YKS. Conclusions: These findings suggest that YKS is effective against HIC and that its antioxidant activity is involved in the mechanism of action.

A case of complete response following the administration of pembrolizumab and metastasectomy for lung and bone metastases of bladder cancer.

INTRODUCTION: Patients with metastatic urothelial carcinoma have poor prognosis and limited treatment options. CASE PRESENTATION: The patient was a 60-year-old male with bladder cancer and multiple lung metastases. He underwent three courses of gemcitabine and cisplatin chemotherapy, despite left femoral bone metastases. Tumor resection and bone replacement surgery was performed. Following the administration of four courses of pembrolizumab, lung metastasis completely resolved. However, after nine courses, right femoral neck bone metastasis was observed; therefore, tumor resection and bone replacement surgery were repeated. Pathologically, PD-L1 expression was low in lung biopsy tissue and bone metastases. Pembrolizumab treatment continued for up to 20 courses; cancer recurrence and adverse events were not observed upon follow-up examination after 1 year. CONCLUSION: Patients responding well to systemic therapy may have resectable metastatic sites, and long-term survival might be achieved with adjunctive metastasectomy. The effect of pembrolizumab was not associated with positive PD-L1 expression.

MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model.

Costello syndrome (CS) is a congenital disorder caused by heterozygous activating germline HRAS mutations in the canonical Ras/mitogen-activated protein kinase (Ras/MAPK) pathway. CS is one of the RASopathies, a large group of syndromes caused by mutations within various components of the Ras/MAPK pathway. An important part of the phenotype that greatly impacts quality of life is hypotonia. To gain a better understanding of the mechanisms underlying hypotonia in CS, a mouse model with an activating HrasG12V allele was utilized. We identified a skeletal myopathy that was due, in part, to inhibition of embryonic myogenesis and myofiber formation, resulting in a reduction in myofiber size and number that led to reduced muscle mass and strength. In addition to hyperactivation of the Ras/MAPK and PI3K/AKT pathways, there was a significant reduction in p38 signaling, as well as global transcriptional alterations consistent with the myopathic phenotype. Inhibition of Ras/MAPK pathway signaling using a MEK inhibitor rescued the HrasG12V myopathy phenotype both in vitro and in vivo, demonstrating that increased MAPK signaling is the main cause of the muscle phenotype in CS.

Hard bilateral syphilitic testes with vasculitis: a case report and literature review.

BACKGROUND: We report the case of a patient with syphilitic testicular gumma and vasculitis with adrenal failure due to chronic steroid use. CASE PRESENTATION: A 63-year-old male presented with hard right eye swelling and very firm bilateral testes on palpation, which he had for 2 years. Testicular tumor markers were negative; syphilis test was positive. Radiological examination suggested aortitis and bilateral testicular malignancy. The patient received ampicillin for the infection and prednisolone for vasculitis. Left orchidectomy was performed to confirm the presence of testicular tumor; histological examinations revealed granulomatous orchitis. The prednisolone doses were adjusted because of relapses and adverse effects of steroid use. Unfortunately, the patient died in the intensive care unit because of uncontrolled blood pressure and pneumonia. CONCLUSIONS: This is a rare case of syphilis with testicular involvement and vasculitis. This report shows the importance of broadening the differential diagnoses of testicular firmness.

Numerical Studies on Electrostatic Interaction Forces and the Free Energy between Parallel Colloidal Rods of Finite Size in Skewed Configurations.

Formulas for interaction forces F(s) and the free energy G(s) between two parallel charged prismatic rods of various scaled values of d, ψs, and L in skewed configurations are obtained, where s is the lengthwise positional difference between the front-end faces of the respective rods, and d is the minimal distance between the opposing faces of the rods, ψs is the electric surface potential, L is the length of the rods. To obtain the free-energy function G(s), (i) 3D spatial distributions of the electric potential ψ around two rods were determined by numerically solving the nonlinear Poisson-Boltzmann equation with a finite element method, (ii) with the ψ distributions so determined, the lengthwise interaction electrostatic Maxwell stress tangential to the midplane between the rods was calculated to obtain the (discrete) s dependence of the stress, and (iii) by introducing two different fitting functions, the discrete s dependence was transformed into a continuous force function, F(s), which was then lengthwise integrated to derive G(s). It was found that the curves of G(s) linearly decreased with increasing s between 1 and L + 1 due to a localization of the stress. Although natural, it is of interest that the values of G(0) calculated for rods of various values of d, ψs, and L were in good agreement with those of the interaction free energy obtained in our preceding work by the widthwise integration of repulsive electrostatic forces normal to the midplane between the parallel rods in nonskewed configurations.

Lung adenocarcinoma diagnosed incidentally after renal biopsy for suspected right renal cancer.

We present a case of lung adenocarcinoma metastasizing to the right clear cell renal cell carcinoma diagnosed by computed tomography (CT)-guided renal biopsy and immunohistochemistry. A 72-year-old male patient had right lower abdominal pain for 3 days, followed by right loin pain for 10 days. On CT scan, renal cell cancer was suspected with multiple metastases. Renal cell cancer with metastatic lung adenocarcinoma was diagnosed on CT-guided renal biopsy with positive immunohistochemical markers. The patient, unfortunately, expired after few days of diagnosis. Tumor-to-tumor metastasis is an unusual disease, and its tumors are aggressive. A definite diagnosis of tumor-to-tumor metastasis is a clinical challenge. Immunohistochemistry helped us in the diagnosis without the primary lesion biopsy.

Ras/MAPK dysregulation in development causes a skeletal myopathy in an activating BrafL597V mouse model for cardio-facio-cutaneous syndrome.

BACKGROUND: Cardio-facio-cutaneous (CFC) syndrome is a human multiple congenital anomaly syndrome that is caused by activating heterozygous mutations in either BRAF, MEK1, or MEK2, three protein kinases of the Ras/mitogen-activated protein kinase (MAPK) pathway. CFC belongs to a group of syndromes known as RASopathies. Skeletal muscle hypotonia is a ubiquitous phenotype of RASopathies, especially in CFC syndrome. To better understand the underlying mechanisms for the skeletal myopathy in CFC, a mouse model with an activating BrafL597V allele was utilized. RESULTS: The activating BrafL597V allele resulted in phenotypic alterations in skeletal muscle characterized by a reduction in fiber size which leads to a reduction in muscle size which are functionally weaker. MAPK pathway activation caused inhibition of myofiber differentiation during embryonic myogenesis and global transcriptional dysregulation of developmental pathways. Inhibition in differentiation can be rescued by MEK inhibition. CONCLUSIONS: A skeletal myopathy was identified in the CFC BrafL597V mouse validating the use of models to study the effect of Ras/MAPK dysregulation on skeletal myogenesis. RASopathies present a novel opportunity to identify new paradigms of myogenesis and further our understanding of Ras in development. Rescue of the phenotype by inhibitors may help advance the development of therapeutic options for RASopathy patients.

MRI-guided conservative management of a left segmental testicular infarction.

Segmental testicular infarction is a rare condition. Patients present with clinical features similar to torsion and testicular tumors, with most undergoing surgery. A 55-year-old male patient presented with left scrotal pain. We did a Doppler ultrasonogram and magnetic resonance imaging to diagnose his condition and rule out testicular torsion and tumor. We decided not to operate and asked the patient for follow-up. There was no pain in the left testis, and magnetic resonance imaging showed a reduction in the left testicular lesion after 4 months.

Familial cardio-facio-cutaneous syndrome: Vertical transmission of the BRAF p.G464R pathogenic variant and review of the literature.

Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies and is caused by germline mutations that activate the Ras/mitogen-activated protein kinase (MAPK) pathway. CFC is due to heterozygous germline mutations in protein kinases BRAF, MEK1, or MEK2 and rarely in KRAS, a small GTPase. CFC is a multiple congenital anomaly disorder in which individuals may have craniofacial dysmorphia, heart issues, skin and hair anomalies, and delayed development. Pathogenic variants for CFC syndrome are usually considered de novo because vertical transmission has only been reported with MEK2 and KRAS. The index case was a 3-year-old male with features consistent with the clinical diagnosis of CFC. Sequencing revealed a previously reported heterozygous likely pathogenic variant BRAF p.G464R. Upon detailed family history, the index case's pregnant mother was noted to have similar features to her son. Targeted familial testing of the BRAF pathogenic variant was performed on the mother, confirming her diagnosis. Prenatal genetic testing for the fetus was declined, but postnatal molecular testing of the index case's sister was positive for the familial BRAF p.G464R variant. Functional analysis of the variant demonstrated increased kinase activity. We report the first identified vertically transmitted functional BRAF pathogenic variant. Our findings emphasize the importance of obtaining a comprehensive evaluation of family members and that activating pathogenic variants within the canonical MAPK cascade mediated by BRAF are compatible with human reproduction.

Prostate cancer detection rate and Gleason score in relation to prostate volume as assessed by magnetic resonance imaging cognitive biopsy and standard biopsy.

OBJECTIVE: This study aimed to assess the relationship of the prostate cancer and Gleason scores (GSs) or ISUP Grade system with prostate volume (PV) as assessed by magnetic resonance imaging (MRI) cognitive biopsy and standard biopsy. MATERIAL AND METHODS: Data were collected from 659 patients who underwent MRI cognitive biopsy and standard biopsy from January 2014 to January 2018. The biopsies were performed because of increased prostate-specific antigen (PSA) levels (>4 ng/mL) and/or abnormal digital rectal examination findings. Transrectal ultrasound was used to measure PV. RESULTS: Prostate cancer detection rates in patients with increased PVs of ≤40 cc and >40 cc were 68.8% and 51.6% (p<0.001), respectively. ISUP Grade group ≥2 (Gleason score ≥3+4) detection rates for increased PVs of ≤40 cc and >40 cc were 68% and 73%, and 22.3% and 37.8%, respectively, for those with ISUP Grade group ≥4 (Gleason score ≥8) (p=0.003). Among the patients with PV>40 cc, univariate logistic regression showed a significant relationship between ISUP Grade group ≥2 and PSA, free/total PSA, PSA density, and MRI (p<0.05). On multivariable logistic regression, MRI (p=0.014) and PSA (p=0.039) predicted ISUP Grade group ≥2 in patients with PV>40 cc. CONCLUSION: Although the detection rates of prostate cancer decreased as PV increased, the detection of prostate cancer aggressiveness increased as PV increased. This increase in high ISUP Grade lesions with the rise in PV is due to the use of MRI during prostate biopsy with standard biopsy.

A Novel, Circulating Tumor Cell Enrichment Method Reduces ARv7 False Positivity in Patients with Castration-Resistant Prostate Cancer.

BACKGROUND: The AR-V7 splice variant is a cause of castration-resistant prostate cancer (CRPC). However, testing for the presence of AR-V7 by real-time polymerase chain reaction (RT-PCR) shows AR-V7 positivity in healthy individuals. We hypothesized that the positivity reflects contamination by hematopoietic cells. We tried a novel circulating tumor cell (CTC) enrichment instrument, using Celsee, to clear hematopoietic cells. METHODS: We tested whole blood or Celsee-enriched samples for AR-V7 by RT-PCR, and included samples from 41 CRPC patients undergoing sequential therapy. We evaluated the associations between AR-V7 status and clinical factors. We evaluated factors affecting AR-V7 positivity. RESULTS: AR-V7 positivity was lower in Celsee-enriched than in whole blood specimens. AR-V7 and clinical factors did not predict the therapy effectiveness. We found no significant differences in the effectiveness of enzalutamide/abiraterone (Enz/Abi) upon AR-V7 evaluation. All AR-V7 positive patients had resistance to Enz/Abi. Docetaxel (DTX), cabazitaxel (CBZ), and Radium223 treatment showed no significant difference in the treatment effectiveness, regardless of AR-V7 presence. AR-V7 was more frequently positive than Extent of disease (EOD) 2 in cases with bone metastases. CONCLUSION: Celsee CTC enrichment suppresses AR-V7 false positivity. All AR-V7 positive patients presented resistance to Enz/Abi. DTX, CBZ, and Radium223 were effective and remain treatment options. AR-V7 positivity should progressively appear in patients with advanced bone metastases.

Numerical Studies on Electrical Interaction Forces and Free Energy between Colloidal Plates of Finite Size.

By solving the nonlinear Poisson-Boltzmann (PB) equation with a finite element method (FEM), three-dimensional (3D) spatial distributions of the electric potential (ψ, scaled) in electrolyte solutions having two charged parallel finite plates (including cubes and prismatic rods) are determined for various separations (d, scaled by the Debye length, κ-1), surface potentials (ψs), and plate dimensions (length × width × thickness, each scaled by κ-1). The total interaction force between two plates, F, is the sum of the electrostatic double-layer (EDL) repulsion (the osmotic pressure, Fosm) and the Maxwell electrostatic stress (Fes). The EDL repulsion is estimated using the distribution of ψ not only between the facing surfaces of two parallel plates but also around the other extremities of the plates. The Maxwell stress (Fes) is localized near the extremities to act as a repulsive force on the midplane between the two plates. The ratio Fes/F is 0.07-0.5, depending on d, ψs, and dimensions. It is found that, with increasing dimensions, the total F values per unit area calculated for finite plates, F̃, decreasingly approach the exact ones for parallel infinite plates, F̃inf; for example, at d = 1 and ψs = 5, the ratio F̃/F̃inf is 2.83 for plates with dimensions of 1 × 1 × 1 and 1.18 for plates of 10 × 10 × 1. The repulsions arising from the extremities cannot be neglected for plates with dimensions <10 × 10 × 1. Furthermore, the total interaction forces (F) are calculated at a series of discrete d values, respectively, for parallel plates. We introduce a force fitting function, Ff(d), with parameters that can be determined so that Ff(d) fits well to the calculated serial F values. By integrating the Ff(d), we obtain the interaction free energy, G(d), for finite parallel plates that consists of two Γ functions.

Systematic review and two new cases of primary upper urinary tract neuroendocrine carcinomas.

BACKGROUND: Upper urinary tract neuroendocrine carcinoma (UUT-NEC) is extremely rare and has a poor prognosis. Although a few cases of successful treatment have been reported, no treatment has shown established efficacy. PATIENTS AND METHODS: We analyzed 70 UUT-NEC patients, including 68 with small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) reported between 1985 and 2017 and 2 treated at our hospital. RESULTS: Median patient age was 66 years, 58.6% were men, and 60% were of Asian descent. Most UUT-NECs were SCNEC (68; 95.7%), whereas LCNEC was very rare (2; 2.9%). More than half of the patients had accompanying other histological components, the most common being urothelial carcinoma (51.5%), whereas 41.4% had NEC alone. Of the 70 patients, 27 underwent additional therapy (e.g., chemotherapy and radiotherapy) along with surgery. Median survival was 15 months. In univariate analysis, stages T1-2 disease showed better prognosis than stages T3-4 (P < 0.001). Additional treatment (e.g., chemotherapy and radiotherapy) significantly improved prognosis (P = 0.014). Moreover, platinum-based chemotherapy also was associated with improved prognosis (P = 0.017). For platinum-based chemotherapy, multicollinearity with additional treatments was strong, and, thus, these data were not included in the analysis. Multivariate analysis revealed pathological stage (T1-2 vs. T3-4; P = 0.003) and additional treatment (P = 0.028) to be independent predictors of improved prognosis. CONCLUSION: Although UUT-NEC has a poor prognosis, additional treatment along with surgery and therapeutic intervention and stage T1-2 disease are independent factors to improve prognosis.

Oral administration of cernitin pollen extract (Cernilton® ) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study.

OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.