Sulfur-Bridged Cationic Diazulenomethenes: Formation of Charge-Segregated Assembly with High Charge-Carrier Mobility.

Sulfur-bridged cationic diazulenomethenes were synthesized and exhibited high stability even under basic conditions due to the delocalization of positive charge over the whole π-conjugated skeleton. As a result of the effective delocalization and the absence of orthogonally oriented bulky substituents, the cationic π-conjugated skeletons formed a π-stacked array with short interfacial distances. A derivative with SbF6- as a counter anion formed a charge-segregated assembly in the crystalline state, rather than the generally favored charge-by-charge arrangement of oppositely charged species based on electrostatic interactions. Theoretical calculations suggested that the destabilization caused by electrostatic repulsion between two positively charged π-conjugated skeletons is compensated by the dispersion forces. In addition, the counter anion SbF6- played a role in regulating the molecular alignment through F⋯H-C and F-S interactions, which resulted in the charge-segregated alignment of the cationic π-skeletons. This characteristic assembled structure gave rise to a high charge-carrier mobility of 1.7 cm2 V-1 s-1 as determined using flash-photolysis time-resolved microwave conductivity.

Tensile Strength of Nerve Bridging Models Using Collagen Nerve Conduits.

BACKGROUND: In the treatment of peripheral nerve injuries with nerve defects, second-generation collagen-based conduits, such as Renerve® (Nipro, Osaka, Japan), have shown the potential for promoting nerve regeneration. However, there is concern related to the weak material properties. No previous studies have addressed the strength of the bridging model using collagen conduits. This study aimed to investigate the tensile strength and failure patterns in nerve defect models bridged with Renerve® conduits through biomechanical research. METHODS: Using fresh chicken sciatic nerves, we examined the maximum failure load of four groups: bridging models using Renerve® with one suture (group A), with two sutures (group B), with three sutures (group C), and end-to-end neurorrhaphy models with two sutures (group N). Each group had eight specimens. We also evaluated failure patterns of the specimens. RESULTS: Group N showed a significantly higher maximum failure load (0.96 ± 0.13 N) than groups A (0.23 ± 0.06 N, p < 0.0001), B (0.29 ± 0.05 N, p < 0.0001), and C (0.40 ± 0.10 N, p < 0.0001). Regarding failure patterns, all specimens in group A showed nerve end dislocation from the conduit. Two specimens in group B and three specimens in group C failed due to circumferential cracks in the conduit. Six specimens in group B and five specimens in group C exhibited cutting out of sutures from the conduit. CONCLUSION: This study suggests that the number of sutures in synthetic collagen nerve conduits has little effect on the maximum failure load. To take advantage of its biomaterial benefits, a period of postoperative range of motion restriction may be required.

Evaluation of the effect of granule size of raw tableting materials on critical quality attributes of tablets during the continuous tablet manufacturing process using near-infrared spectroscopy.

OBJECTIVE: The effects of granule size of raw materials on tablet hardness (TH) and weight (TW) in the continuous tablet manufacturing process (CTMP) were investigated using near-infrared spectroscopy (NIRS). METHODS: Granule materials of different sizes were prepared by extrusion granulation from a standard granule formula powder containing lactose/starch and 4.5% acetaminophen. Large-, small-, and medium-sized granules were sequentially filled in a hopper, and tablets were produced continuously using a single-shot tableting machine. After arranging approximately 500 tablets in order, the tablets were subjected to NIRS. A total of 450 NIRS datasets were divided into three groups of 150 each (calibration, validation 1, and validation 2 datasets). RESULTS: The best fitted calibration models for predicting TH and TW were obtained, with sufficient accuracy, based on NIRS using the partial least squares regression, and comprised both physical and chemical information. The regression and loading vectors of the calibration models suggested that the models used to predict TH and TW involve physical information based on geometrical factors of the tablet and chemical information related to binder-related intermolecular interactions. CONCLUSIONS: The changes in the predicted value profiles of TH and TW using NIRS reflected the changes in the measured values depending on the raw granule size during CTMP.

Charge-Segregated Stacking Structure with Anisotropic Electric Conductivity in NIR-Absorbing and Emitting Positively Charged π-Electronic Systems.

Squarylium-based π-electronic cation with an augmented dipole was synthesized by methylation of zwitterionic squarylium. The cation formed various ion pairs in combination with anions, and the ion pairs exhibited distinct photophysical properties in the dispersed state, ascribed to the formation of J- and H-aggregates. The ion pairs provided solid-state assemblies based on cation stacking. It is noteworthy that complete segregation of cations and anions was observed in a pseudo-polymorph of the ion pair with pentacyanocyclopentadienide as a π-electronic anion. In the crystalline state, the ion pairs exhibited photophysical properties and electric conductivity derived from cation stacking. In particular, the charge-segregated ion-pairing assembly induces an electric conductive pathway along the stacking axis. The charge-segregated mode and fascinating properties were derived from the reduced electrostatic repulsion between adjacent π-electronic cations via dipole-dipole interactions.

Formation of Indomethacin-Saccharin Cocrystals during Wet Granulation: Role of Polymeric Excipients.

Formulation of a cocrystal into a solid pharmaceutical dosage form entails numerous processing steps during which there is risk of dissociation. In an effort to reduce the number of unit operations, we have attempted the in situ formation of an indomethacin-saccharin (INDSAC) cocrystal during high-shear wet granulation (HSWG). HSWG of IND (poorly water-soluble drug) and SAC (coformer), with polymers (granulating agents), was carried out using ethanol as the granulation liquid and yielded INDSAC cocrystal granules. Therefore, cocrystal formation and granulation were simultaneously accomplished. Our objectives were to (i) evaluate the influence of polymers on cocrystal formation kinetics during wet granulation and (ii) mechanistically understand the role of polymers in facilitating the cocrystal formation. Polyvinylpyrrolidone (PVP), hydroxypropyl cellulose (HPC), and polyethylene oxide (PEO) were chosen to investigate the influence of soluble polymers. The cocrystal formation kinetics was influenced by the polymer (PVP < HPC < PEO) and its concentration. The interaction of the polymer with cocrystal components inhibited the cocrystal formation. Complete cocrystal formation was observed in the presence of PEO, a polymer which does not interact with IND and SAC.

A novel risk score on admission for predicting death or need for surgery in patients with acute type A intramural hematoma receiving medical therapy.

There has been continuing discussion regarding the treatment strategy for acute type A intramural hematoma (IMH). Most patients are treated conservatively in Japan; hence, predicting fatal events and stratifying risks based on results normally obtained on hospital arrival are important. We aimed to examine the incidences and risk factors of death or need for surgery for acute type A IMH in patients receiving medical treatment and to identify high-risk patients using clinical findings on hospital arrival. From 2011 to 2016, 57 consecutive patients (mean age 72.5 years; male 36.8%) diagnosed with acute type A IMH who were receiving treatment at Shizuoka City Shizuoka Hospital were retrospectively included. Primary endpoint was a composite of cardiovascular death and operation within 1 year after onset. To evaluate sensitivity and specificity of the risk factors and risk score, we estimated the area under the receiver operating characteristic (ROC) curve. Mean follow-up duration was 621 days. Mean systolic blood pressure (SBP) was 129 mmHg. Computed tomography (CT) on arrival showed a mean ascending aorta diameter of 46 mm. Ulcer-like projection (ULP) in the ascending aorta and pericardial effusion (PE) were seen in 33% and 42% of cases, respectively. Twenty-eight patients (49.1%) reached the primary endpoint (cardiovascular death, 7 cases [12.3%]; operation, 21 cases [36.8%]). In univariate analysis of admission values, the primary endpoint group had significantly lower SBP (113.0 ± 28.5 vs 144.3 ± 33.5 mmHg), higher ascending aorta diameter (49.5 ± 8.1 vs 43.6 ± 5.9 mm), and higher frequency of ULP (53.8% vs 13.8%) and PE (58.6% vs 25.0%) than the event-free group. Multivariate analysis showed that ULP on admission CT was a significant predictor of the primary endpoint. The risk score was considered using these risk factors. On admission, the primary endpoint could be predicted with 89.7% sensitivity and 75% specificity (area under the ROC curve 0.823) if the patient had ULP and/or > 2 of the following factors: SBP < 120 mmHg, ascending aorta diameter > 45 mm, and PE. SBP and CT findings on arrival were significantly associated with cardiovascular death and the need for surgery in patients with acute type A IMH receiving initial medical therapy. The novel risk score was useful for predicting cardiovascular death and surgery.

Application of spray freeze drying to theophylline-oxalic acid cocrystal engineering for inhaled dry powder technology.

Spray freeze drying (SFD) produces suitable particles for the pharmaceutical formulation of dry powders used in dry powder inhalers (DPIs). However, SFD particles have large specific surface area and are partially made up of amorphous solids; this state is hygroscopic and would lead to changes in physicochemical properties by humidity when the particles are stored over the long-term or under high humidity conditions such as in the lungs. This study focused on the application of SFD with a cocrystal technique which can add humidity resistance to the active pharmaceutical ingredients (APIs), and the investigation of the physicochemical properties under high humidity conditions. Cocrystal samples containing theophylline anhydrate (THA) and oxalic acid (OXA) in a molar ratio of 2:1 were prepared by SFD. The crystalline structure, thermal behavior, solid-state, hygroscopicity, stability, and aerodynamic properties were evaluated. Simultaneous in situ measurement by near-infrared and Raman (NIR-Raman) spectroscopy was performed to analyze the humidification process. The SFD sample had a porous particle and an optimal aerodynamic particle size (3.03 µm) although the geometric particle diameter was 7.20 µm. In addition, the sample formed the THAOXA cocrystal with partial coamorphous. The hydration capacity and pseudopolymorphic transformation rate of the SFD sample were much lower than those of THA under conditions of 96.4% relative humidity and 40.0°C temperature because of the cocrystal formation. The reasons were discussed based on the crystalline structure and energy. The SFD technology for cocrystallization would enable the pharmaceutical preparation of DPI products under environmentally friendly conditions.

Gastrointestinal cancer and bilateral hydronephrosis resulted in a high risk of ureteral stent failure.

BACKGROUND: Urologists frequently encounter malignant ureteral obstruction (MUO) caused by advanced urological or non-urological malignant disease, but the treatment policy is unclear. The present study examined the risk factors for predicting ureteral stent failure in patients with MUO after ureteral stent insertion and the change in the renal function after retrograde ureteral stent insertion in cases of bilateral hydronephrosis. METHODS: A total of 39 patients who required ureteral stent placement for MUO at Yokohama City University Medical Center (Yokohama, Japan) between February 2007 and May 2016 were included in this study. The age, gender, type of cancer, hydronephrosis side, pre-stenting estimated glomerular filtration rate (eGFR), and eGFR increase were assessed as predictive factors for stent failure. Among these 39 patients, 25 showed bilateral hydronephrosis. Thirteen of these patients had bilateral ureteral stents placed, and the remaining 12 had a unilateral ureteral stent placed. The renal function and overall survival (OS) were analyzed between these two groups. RESULTS: Among all 39 patients, 9 (23.1%) had stent failure. A univariate analysis revealed that causative disease (gastrointestinal cancer vs. others; p = 0.045) and laterality of hydronephrosis (bilateral vs. unilateral; p = 0.05) were associated with stent failure. A multivariate analysis revealed that only age (hazard ratio, 0.938; 95% confidence interval, 0.883-0.996; p = 0.038) was associated with stent failure. A Kaplan-Meier analysis and log-rank test indicated that having a unilateral ureteral stent placed was not correlated with a lower OS rate than having bilateral ureteral stents placed (p = 0.563). Among patients with bilateral hydronephrosis, the increase in the eGFR of those who had bilateral ureteral stents placed was not significantly different from that of those who had a unilateral ureteral stent placed (p = 0.152). CONCLUSIONS: We revealed that age > 60 years was helpful for predicting stent failure. MUO due to gastrointestinal cancer and bilateral hydronephrosis may be predictive of stent failure. These factors may help urologists decide the optimal time to perform early percutaneous nephrostomy. These findings suggest that patients with bilateral hydronephrosis do not necessarily need to have a ureteral stent placed into both sides of the hydronephrosis.

Predictive Evaluation of Pharmaceutical Properties of Ulinastatin-Containing Vaginal Suppositories as a Hospital Preparation by Near-Infrared Spectroscopy.

A vaginal suppository containing ulinastatin (UTI) was developed as a hospital pharmacy product from UTI injection solution and Witepsol® S-55. After mixing at 50°C for 0-8 h, UTI suppositories were prepared, which had good UTI content uniformity. Because 2% surfactant was contained in S-55, the UTI injection solution formed a water-in-oil type emulsion as a suppository base. The measured residual moisture content (loss on drying (LOD)) in the prepared vaginal suppositories decreased as the mixing time increased, but their hardness (hardness test (HT)) increased. Near (N) IR spectra of UTI suppositories were measured after mixing for 0-8 h. The best calibration models to predict the HT and LOD of the suppositories were determined based on the NIR spectra by the leave-one-out method in a partial least-squares regression analysis (PLS). The validation result indicated that PLS models for HT and LOD were obtained based on the spectra treated by a combination of smoothing and normalized, respectively, and the model consisted of three latent variables. The plots between the predicted and measured pharmaceutical properties (HT and LOD) based on the calibration data were superimposed with those of the external validation data. The developed NIR spectroscopy method was applied to the preparation process monitoring for UTI vaginal suppositories. In the prepared vaginal suppositories, the predicted LOD decreased as the mixing time increased, and the measured LOD values superimposed well with the predicted values. In contrast, the predicted HT increased as the mixing time increased, and the measured values superimposed with the predicted values.

Application of near-infrared spectroscopy to optimize dissolution profiles of tablets according to the granulation mechanism.

We developed a method for the optimization of dissolution properties of solid oral dosage forms manufacturing using high shear wet granulation (HSWG) by using near-infrared spectroscopy (NIRS) with chemometrics in small-scale experiments. The changes in rheology and NIR spectra of the granules were monitored to verify the granulation mechanism and determine the suitable water amount for model formulation during the HSWG. Tablets were manufactured by altering the added water amount to investigate the impact of the granulation mechanism on drug product qualities. Model formulation granules were prepared with 10-20% w/w water in a funicular state, corresponding to the plateau region in score plots obtained by principal component analysis (PCA). The dissolution rate of model formulation tablets manufactured with more than 20% w/w of water was significantly delayed while tablets manufactured with 15% w/w water showed 100% dissolution at 15 min. NIRS and PCA are applicable to the optimization of dissolution properties via the process understanding of HSWG at the early formulation development stage and could facilitate drug development.

In-Line Monitoring of a High-Shear Granulation Process Using the Baseline Shift of Near Infrared Spectra.

Although near infrared (NIR) spectra are primarily influenced by undesired variations, i.e., baseline shifts and non-linearity, and many applications of NIR spectroscopy to the real-time monitoring of wet granulation processes have been reported, the granulation mechanisms behind these variations have not been fully discussed. These variations of NIR spectra can be canceled out using appropriate pre-processing techniques prior to spectral analysis. The present study assessed the feasibility of directly using baseline shifts in NIR spectra to monitor granulation processes, because such shifts can reflect changes in the physical properties of the granular material, including particle size, shape, density, and refractive index. Specifically, OPUSGRAN®, a novel granulation technology, was investigated by in-line NIR monitoring. NIR spectra were collected using a NIR diffuse reflectance fiber optic probe immersed in a high-shear granulator while simultaneously examining the morphology, particle size, density, strength, and Raman images of the mixture during granulation. The NIR baseline shift pattern was found to be characteristic of the OPUSGRAN® technology and was attributed to variations in the light transmittance, reflection, and scattering resulting from changes in the physicochemical properties of the samples during granulation. The baseline shift also exhibited an inflection point around the completion of granulation, and therefore may be used to determine the endpoint of the process. These results suggest that a specific pattern of NIR baseline shifts are associated with the unique OPUSGRAN® granulation mechanism and can be applied to monitor the manufacturing process and determine the endpoint.

The neutrophil-to-lymphocyte ratio (NLR) predicts adrenocortical carcinoma and is correlated with the prognosis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is reported as a biomarker for some solid malignant diseases. Thus far, however, no reports of the relationship between the NLR and adrenal tumors have been published. We analyzed the utility of the preoperative NLR as a biomarker for predicting the prognosis or diagnosis of malignant disease. METHODS: A total of 59 patients with adrenal tumors (13 cases of malignant disease and 46 with benign disease) were analyzed in this study from February 2004 to June 2015 at our institute. The NLR was obtained just before adrenalectomy. The diagnosis of adrenal tumor was confirmed by a pathological examination of surgical specimens. RESULTS: The NLR in malignant adrenal tumor specimens was significantly higher than in non-malignant specimens (p = 0.028). Adrenocortical carcinoma (ACC) showed the highest NLR among all adrenal tumors. In ACC, the higher NLR group (NLR ≥ 5) showed a significantly poorer overall survival than the lower NLR group (NLR < 5) (p = 0.032). CONCLUSIONS: In adrenal tumors, a higher NLR indicates a higher incidence of malignancy. The NLR might be a new biomarker for predicting the prognosis of adrenal tumor patients.

A low psoas muscle volume correlates with a longer hospitalization after radical cystectomy.

BACKGROUND: Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. METHODS: A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. RESULTS: The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p < 0.001). Based on the differences in gender, we analyzed 63 male patients for a further analysis. In male patients, those hospitalized longer showed a significantly smaller PMI than those normally discharged (377 ± 93.1 vs. 425 ± 83.4; p = 0.04). Similarly, male patients with a small PMI (<400) had a significantly worse overall survival (p = 0.02) than those with a large PMI (≥400). CONCLUSIONS: The presence of sarcopenia was found to be associated with significantly longer hospitalization after radical cystectomy in male patients. Furthermore, in men, a PMI <400 may suggest a significantly worse prognosis.

Prediction of Time to Castration-Resistant Prostate Cancer Using Bone Scan Index in Men with Metastatic Hormone-Sensitive Prostate Cancer.

INTRODUCTION: We evaluated bone scan index (BSI) as a predictive biomarker for time to castration-resistant prostate cancer (CRPC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS: We identified 85 consecutive mHSPC patients treated with first-line androgen deprivation therapy. We analyzed the correlations between time to CRPC and clinicopathological characteristics, including age, prostate-specific antigen (PSA) level, Gleason score, clinical TNM stage, hemoglobin, lactate dehydrogenase, C-reactive protein, and BSI. RESULTS: The median BSI was 2.7%. Progression to CRPC occurred in 55 (64.7%) patients and the median time to CRPC was 12.9 months. In multivariate analysis, 3 significant risk factors for time to CRPC were identified: age (>73 vs. ≤73 years; hazard ratio [HR] 0.53), p = 0.038, PSA level (>270 vs. ≤270 ng/mL; HR 0.53, p = 0.038), and BSI (>2.7 vs. ≤2.7%; HR 2.97, p < 0.001). CONCLUSION: Age, PSA level, and BSI were found to be significant predictive factors for time to CRPC in patients with mHSPC.

[Pulmonary Mycobacterium Avium-Complex (MAC) Disease Differentially Diagnosed from Metastasis of Testicular Cancer : A Case Report].

A 45 year-old-man was admitted to our hospital because of discomfort in his left scrotum. He had a left testicular tumor. We performed high orchiectomy and pathological findings revealed testicular cancer. He was treated with bleomycin, etoposide and cisplatin. Computed tomography showed a new mass in the left lung after 3 cycles of the chemotherapy. Because of its rapid growth, the tumor was thought to be a metastasis lesion of testicular cancer or pulmonary infection. Transbronchial lung biopsy showed an invasion of multinucleated giant cells and granuloma. The culture and polymerase chain reaction of the bronchial sputum were positive for myobacterium avium-complex (MAC). From these findings, the left lung tumor was diagnosed as pulmonary MAC disease. He received partial resection of the left lung and the lesion was diagnosed as granuloma. There was no recurrence of testicular cancer or pulmonary disease after the surgery.

Prognostic value of a computer-aided diagnosis system involving bone scans among men treated with docetaxel for metastatic castration-resistant prostate cancer.

BACKGROUND: The bone scan index (BSI), which is obtained using a computer-aided bone scan evaluation system, is anticipated to become an objective and quantitative clinical tool for evaluating bone metastases in prostate cancer. Here, we assessed the usefulness of the BSI as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated using docetaxel. METHODS: We analyzed 41 patients who received docetaxel for mCRPC. The Bonenavi system was used as the calculation program for the BSI. The utility of the BSI as a predictor of overall survival (OS) after docetaxel was evaluated. The Cox proportional hazards model was used to investigate the association between clinical variables obtained at docetaxel treatment, namely PSA, patient age, liver metastasis, local therapy, hemoglobin (Hb), lactase dehydrogenase (LDH), albumin (Alb), PSA doubling time, and BSI and OS. RESULTS: The median OS after docetaxel therapy was 17.7 months. Death occurred in 22 (53.7%) patients; all deaths were caused by prostate cancer. In multivariate analysis, three factors were identified as significant independent prognostic biomarkers for OS after docetaxel; these were liver metastases (yes vs no; HR, 3.681; p = 0.026), Alb (<3.9 vs ≥ 3.9; HR, 3.776; p = 0.020), and BSI (>1% vs ≤ 1%; HR, 3.356; p = 0.037). We evaluated the discriminatory ability of our models including or excluding the BSI by quantifying the c-index. The BSI improved the c-index from 0.758 to 0.769 for OS after docetaxel. CRPC patients with a BSI >1 had a significantly shorter OS than patients with a BSI ≤ 1 (p = 0.029). CONCLUSIONS: The BSI, liver metastases and Alb were independent prognostic factors for OS after docetaxel. The BSI might be a useful tool for risk stratification of mCRPC patients undergoing docetaxel treatment.

Prognostic value of the bone scan index using a computer-aided diagnosis system for bone scans in hormone-naive prostate cancer patients with bone metastases.

BACKGROUND: The bone scan index (BSI) using a computer-aided diagnosis system for bone scans is expected to be an objective and quantitative clinical tool for evaluating bone metastatic prostate cancer. This study aimed to evaluate the pretreatment BSI as a prognostic factor in hormone-naive prostate cancer patients with bone metastases. METHODS: The study included 60 patients with hormone-naive, bone metastatic prostate cancer that was initially treated with combined androgen blockade therapy. The BONENAVI system was used for calculating the BSI. We evaluated the correlation between overall survival (OS) and pretreatment clinicopathological characteristics, including patients' age, initial prostate-specific antigen (PSA) value, Gleason scores, clinical TNM stage, and the BSI. Cox proportional hazards regression models were used for statistical analysis. RESULTS: The median follow-up duration was 21.4 months. Clinical or PSA progression occurred in 37 (61.7%) patients and 18 (30.0%) received docetaxel. Death occurred in 16 (26.7%) patients. Of these deaths, 15 (25.0%) were due to prostate cancer. The median OS was not reached. In multivariate analysis, age and the BSI were independent prognostic factors for OS. We evaluated the discriminatory ability of our models, including or excluding BSI by quantifying the C-index. The BSI improved the C-index from 0.751 to 0.801 for OS. Median OS was not reached in patients with a BSI ≤ 1.9 and median OS was 34.8 months in patients with a BSI >1.9 (p = 0.039). CONCLUSIONS: The pretreatment BSI and patients' age are independent prognostic factors for patients with hormone-naive, bone metastatic prostate cancer.

Increased neutrophil-to-lymphocyte ratio is associated with disease-specific mortality in patients with penile cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), a simple marker of the systemic inflammatory response, has been demonstrated to correlate with patient outcomes for various solid malignancies. We investigated the utility of the pretreatment NLR as a prognosticator in patients who presented with penile cancer. METHODS: A total of 41 patients who underwent complete blood count with differential and subsequent radical penectomy from 1988 to 2014 were analyzed. We assessed the correlation between the NLR and the prognosis of penile cancer. RESULTS: The median and mean (± SD) NLRs in 41 penile cancer patients were 3.42 and 5.03 ± 4.99, respectively. Based on the area under receiver operator characteristic curve, the cut-off value of NLR was determined to be 2.82. Patients with a high NLR (≥2.82) showed a significantly poorer cancer-specific survival (p = 0.023) than those with a low NLR. CONCLUSIONS: The pretreatment NLR may function as a biomarker that precisely predicts the prognosis in patients with penile cancer.

Predictors of poor response to secondary alternative antiandrogen therapy with flutamide in metastatic castration-resistant prostate cancer.

OBJECTIVE: In Japan, flutamide had been commonly used as second-line alternative antiandrogen hormonal therapy for metastatic castration-resistant prostate cancer that relapses after initial hormone therapy before new androgen pathway inhibitors became available. In this study, we attempted to identify predictive factors for efficacy of alternative antiandrogen as second-line hormone therapy. METHODS: We identified consecutive 65 patients with metastatic castration-resistant prostate cancer who were treated with alternative antiandrogen as second-line hormonal therapy (bicalutamide to flutamide). All patients were treated with combined androgen blockade initially. We analyzed correlations between progression-free survival of alternative antiandrogen and clinicopathological characteristics, including patients' ages, initial prostate-specific antigen levels, prostate-specific antigen levels at flutamide induction, Gleason scores, T stage, N stage, extent of disease grades on bone scan and previous duration of prostate cancer response to combined androgen blockade. RESULTS: In univariate analysis, T stage, N stage and previous duration of response to combined androgen blockade were correlated with shorter progression-free survival. We found four significant risk factors for shorter progression-free survival in multivariate analysis: initial prostate-specific antigen level, clinical N stage, extent of disease grades and previous duration of response to combined androgen blockade. CONCLUSIONS: Initial prostate-specific antigen, N stage, extent of disease grades on bone scan and previous duration of response to combined androgen blockade were the significant predictors for efficacy of alternative antiandrogen as second-line hormone therapy in patients with metastatic castration-resistant prostate cancer. These findings might support that decision-making of when to start the new androgen receptor pathway inhibitors.

Bioresorbable zinc hydroxyapatite guided bone regeneration membrane for bone regeneration.

OBJECTIVES: The aim of this study was to investigate the bone regenerative properties of a heat treated cross-linked GBR membrane with zinc hydroxyapatite powders in the rat calvarial defect model over a 6-week period. MATERIAL AND METHODS: In vitro physio-chemical characterization involved X-ray diffraction analysis, surface topology by scanning electron microscopy, and zinc release studies in physiological buffers. Bilateral rat calvarial defects were used to compare the Zn-HAp membranes against the commercially available collagen membranes and the unfilled defect group through radiological and histological evaluation. RESULTS: The synthesized Zn-MEM (100 µm thick) showed no zinc ions released in the phosphate buffer solution (PBS) buffer, but zinc was observed under acidic conditions. At 6 weeks, both the micro-CT and histological analyses revealed that the Zn-MEM group yielded significantly greater bone formation with 80 ± 2% of bone filled, as compared with 60 ± 5% in the collagen membrane and 40 ± 2% in the unfilled control group. CONCLUSION: This study demonstrated the use of heat treatment as an alternative method to cross-linking the Zn-MEM to be applied as a GBR membrane. Its synthesis and production are relatively simple to fabricate, and the membrane had rough surface features on one side, which might be beneficial for cellular activities. In a rat calvarial defect model, it was shown that new bone formation was accelerated in comparison with the collagen membrane and the unfilled defect groups. These results would suggest that Zn-MEM has the potential for further development in dental applications.