ABSTRACT
A 63-year-old man presented with right scrotal swelling. A physical examination revealed a painless, palpable mass in the right scrotum. The mass was well defined and lobulated. Subsequently, a diagnosis of right epididymal tumor was made, and right high orchiectomy was performed. Hematoxylin-eosin and immunostaining revealed leiomyosarcoma of the epididymis. When a diagnosis of epididymal malignant tumor is made, the standard treatment is radical orchiectomy.
Subject(s)
Genital Neoplasms, Male , Leiomyosarcoma , Male , Humans , Middle Aged , Epididymis/diagnostic imaging , Epididymis/surgery , Epididymis/pathology , Leiomyosarcoma/diagnostic imaging , Leiomyosarcoma/surgery , Genital Neoplasms, Male/diagnostic imaging , Genital Neoplasms, Male/surgery , Orchiectomy , PelvisABSTRACT
Photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is expected to be useful in preventing oversight of non-muscle-invasive bladder cancer (NMIBC) and in reducing the intravesical recurrence rate after transurethral resection of bladder tumor (TURBT). We report our initial experience with28 cases of PDD-assisted TURBT (122 samples) performed at our hospital from February 2018 to April 2019. The median age of the patients was 74.5 years, and 18 of the 28 were primary cases. Each patient underwent TURBT with oral administration of 5-ALA 20 mg/kg 3 hours before endoscopic examination. The sensitivity was 89.8% when both white light and blue light were used, which was superior to the sensitivity of 67.8% when using only white light (pï¼0.01, McNemar's test). Among the first several cases, we experienced high false positivity, which suggested that some experience may be required to discriminate tumors from inflammatory lesions. In fact, the specificity and the positive likelihood ratio improved with experience. No grade 2 or higher adverse events were observed among our cases. The median follow-up period was 738 days, and 9 of 28 patients (32. 1%) had recurrence within the follow-up period. In conclusion, our initial experience with PDD-assisted TURBT demonstrated its excellent diagnostic sensitivity and safety, as previously reported.
Subject(s)
Urinary Bladder Neoplasms , Aged , Aminolevulinic Acid , Cystectomy , Cystoscopy , Humans , Neoplasm Invasiveness , Neoplasm Recurrence, Local/diagnosis , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/surgeryABSTRACT
The normal prostate epithelial structure is maintained by homeostatic interactions with smooth muscle cells. However, structural alterations of the stroma are commonly observed in prostatic proliferative diseases, leading to the abnormalities of prostate epithelial structure. A decrease in the androgen level experimentally induces stromal remodeling, i.e., replacement of smooth muscle cells with fibroblasts or myofibroblasts. In this study, we investigated the effects of castration-induced stromal remodeling and subsequent aberrant activation of epithelial-stromal interactions on the reconstituted human prostate-like epithelial structure. We performed in vivo experiments using the human prostate epithelial cell line BPH-1 and fetal rat urogenital sinus mesenchyme to generate heterotypic tissue recombinants that form human prostate-like epithelial structure (i.e., solid- and canalized-epithelial cords). Host mice were castrated at 12 weeks post transplantation (castration) and implanted with a dihydrotestosterone pellet at 14 days post castration (androgen replacement treatment; ART). In the castration group, the percentages of fibrotic area and disrupted prostate epithelial structure without the basement membrane (BM) increased proportionally in a time-dependent manner, but were suppressed by ART. In the castration group, tenascin-C (TNC)-positive fibroblasts were abundant in the stroma surrounding disrupted prostate epithelial structure without the BM. TGF-ß1 secretion from BPH-1 cells was increased by co-culturing with human primary cultured prostate fibroblasts. TNC mRNA expression was increased in fibroblasts co-culturing with BPH-1 cells and was suppressed by treatment with a TGF-ß RI kinase inhibitor. Moreover, in the castration group, the percentage of p-Smad2-positive cells was significantly higher in the stroma surrounding disrupted prostate epithelial structure without the BM. Our results demonstrate that castration-induced stromal remodeling disrupted the reconstituted human prostate-like epithelial structure and induced the appearance of TNC-positive fibroblasts accompanied by activation of TGF-ß signaling. The alteration of prostate stromal structure may be responsible for loss of the BM and epithelial cell polarity.
Subject(s)
Orchiectomy , Prostate , Stromal Cells , Animals , Cell Line , Dihydrotestosterone/pharmacology , Epithelium/drug effects , Fibroblasts/cytology , Fibroblasts/drug effects , Humans , Male , Mice , Mice, SCID , Prostate/cytology , Prostate/drug effects , Prostate/physiology , Rats , Stromal Cells/cytology , Stromal Cells/physiology , Tenascin/genetics , Tenascin/metabolismABSTRACT
Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.
Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines/immunology , Membrane Proteins/immunology , Neoplasms/immunology , Nod2 Signaling Adaptor Protein/immunology , Toll-Like Receptor 9/immunology , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Neoplasm/blood , Antibodies, Neoplasm/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cancer Vaccines/administration & dosage , Cell Line, Tumor , Female , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Male , Mice, Inbred BALB C , Middle Aged , Neoplasms/pathology , Neoplasms/therapy , Nod2 Signaling Adaptor Protein/metabolism , Toll-Like Receptor 9/metabolism , Vaccination/methodsABSTRACT
BACKGROUND: Epidemiological studies have shown an association between obesity and prostate cancer (PCa) aggressiveness. However, little is known about periprostatic fat (PPF) and its relationship with overall fat deposition in PCa. PPF is thought to contribute to PCa growth and migration via secreted factors and induction of chronic inflammation. We investigated if pre-treatment PPF thickness correlates with overall survival (OS). METHODS: We reviewed 85 hormone-naïve men with advanced PCa who had received androgen deprivation therapy (ADT). PPF thickness was measured by magnetic resonance imaging (MRI) and compared with subcutaneous fat (SCF) thickness as an internal control. Visceral fat (VF) area measured by computed tomography served as an additional control. We evaluated the relationship between laboratory data, pathology results, and obesity parameters and OS. RESULTS: Median follow-up was 50.6 months. Thirty-six patients died during follow-up. Univariate analysis revealed that nadir PSA titer, Gleason score, N stage, M stage, extent of disease by bone scan grade, hemoglobin, lactate dehydrogenase, alkaline phosphatase, and PPF/SCF ratio were associated with OS. Multivariate analysis revealed that nadir PSA titer, N stage, and PPF/SCF ratio were independent prognostic factors for survival. The 5-year OS in the patients with higher PPF/SCF ratio (≥ 1) and lower PPF/SCF ratio (< 1) was 49.5% and 66.5%, respectively (P = 0.039). CONCLUSIONS: Pre-treatment ratio of PPF-to-SCF thickness on MRI is an independent predictor of survival in hormone-naïve men with advanced PCa. This could be useful for predicting which patients are more likely to develop castration-resistant PCa.
Subject(s)
Intra-Abdominal Fat/diagnostic imaging , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/mortality , Subcutaneous Fat/diagnostic imaging , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasm Grading , Orchiectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Tomography, X-Ray ComputedABSTRACT
Patients with bronchial foreign bodies often present with subjective symptoms, mainly cough, and removing the foreign bodies is difficult. Bronchial foreign bodies are mostly located in the right lower bronchus, and rarely in the right middle bronchus. An 85-year-old man had no subjective symptoms. He aspirated an artificial tooth during dental treatment the day before visiting our clinic, and consulted his home doctor. He was admitted to our hospital because a chest radiograph indicated the presence of a foreign body in the right middle and lower lung field. Chest computed tomography showed that the bronchial foreign body was located in the right middle bronchus, and it was accompanied by an artifact in the circumference of the lesion, and it seemed to be the metal piece of an artificial tooth. Three-dimensional CT showed the root of the artificial tooth located in center side of the right middle bronchus, and, considering the invasiveness, we decided to remove the tooth by flexible bronchoscopy. The bronchoscopy revealed a metal piece occluding the right middle bronchus without granulation, and we could remove the tooth immediately by grasping the root of the tooth with alligator forceps. We experienced a case of a foreign body located in the right middle bronchus without respiratory symptoms. It is important to carry out image examinations, because elderly patients may not exhibit respiratory symptoms.
Subject(s)
Bronchi/surgery , Bronchoscopy/methods , Foreign Bodies/etiology , Foreign Bodies/surgery , Tooth, Artificial/adverse effects , Aged, 80 and over , Asymptomatic Diseases , Bronchi/diagnostic imaging , Foreign Bodies/diagnostic imaging , Humans , Imaging, Three-Dimensional , Male , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
We report a 79-year-old woman, who had undergone surgery for papillary thyroid carcinoma 18 years previously and lung adenocarcinoma 15 years previously. She didn't receive any follow-up because she had no recurrence for 5 years in both diseases. She visited a local doctor with precordial pain and thorax discomfort as her chief complaints, where chest computed tomography indicated a 14 mm-sized nodule in the right lower lobe and 5-7 mm-sized small nodules in both lungs. Using endobronchial ultrasonography with a guide sheath (EBUS-GS) for the diagnosis in our department, the lesions were confirmed by ultrasonography, and a transbronchial biopsy was carried out under fluoroscopy. Pathologically, a sufficient amount of tumor cells were collected, and the findings of adenocarcinoma were obtained. Her condition was diagnosed as recurrent pulmonary metastases of thyroid papillary carcinoma because of the atypical columnar epithelial cells with nuclear variants and the papillary proliferation of intranuclear inclusion, and because of the positive findings in immunohistochemical staining for thyroglobulin. Since papillary thyroid carcinoma is positive for thyroid transcription factor-1 (TTF-1), which is widely used as a marker of lung adenocarcinoma, it cannot be used to differentiate between the two. It is often difficult to diagnose papillary thyroid carcinoma by bronchoscopy, because its progress is slow and the origin of the metastatic lung tumor is not in the bronchus, unlike primary lung cancer. However, a devised transbronchial biopsy procedure for slowly progressive metastatic lung tumors such as papillary thyroid carcinoma is considered to be a useful technique for diagnosis.
Subject(s)
Bronchi/pathology , Image-Guided Biopsy/methods , Lung Neoplasms/diagnosis , Lung Neoplasms/secondary , Thyroid Cancer, Papillary/diagnosis , Thyroid Cancer, Papillary/secondary , Thyroid Neoplasms/pathology , Aged , Endosonography/methods , Female , Fluoroscopy/methods , Humans , Lung Neoplasms/pathology , Neoplasm Recurrence, Local , Thyroid Cancer, Papillary/pathology , Time Factors , Tomography, X-Ray ComputedABSTRACT
A 37-year-old Japanese man presented with a bulla with niveau-like opacity in the right upper lung on chest radiography. Air-fluid level gradually increased despite broad-spectrum antibiotic therapy. Right upper lobectomy was performed, and epithelioid granuloma with mycobacteria was histopathologically observed. Bacterial culture of the fluid was negative, but mycobacterial culture was positive for Mycobacterium avium; therefore, the patient was diagnosed with pulmonary infected bulla caused by Mycobacterium avium. He was further treated with antimycobacterial agents after resection of the infected bulla. To our knowledge, this is the first report of pulmonary infected bulla caused by only Mycobacterium avium in the English literature.
Subject(s)
Blister/microbiology , Lung Diseases/microbiology , Mycobacterium avium-intracellulare Infection , Adult , Anti-Bacterial Agents , Blister/therapy , Humans , Lung Diseases/therapy , Male , PneumonectomyABSTRACT
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been reported to be useful not only for the diagnosis of lymph node metastasis of lung cancer but also for benign diseases. We retrospectively analyzed the results of patients with tuberculous lymphadenitis (TL) who had undergone EBUS-TBNA between November 2010 and January 2016. EBUS-TBNA was performed in 427 cases during that period. Six cases were finally diagnosed as TL. The punctured lymph node was 8 lesions. Pathological findings consistent with TL were obtained in all 6 cases (100%), and the tissue specimens were positive in Ziehl-Neelsen staining in 3 of the 6 cases (50%). In all 6 cases, the acid-fast bacteria (AFB) smear test of the needle rinse fluid was negative, 2 cases were positive for AFB culture (33.3%), and 2 cases were positive for Mycobacterium tuberculosis (MTB)-PCR test (33.3%). In this study, the positive rate of mycobacterial culture and the MTB-PCR test of the needle rinse fluid was low, though the concordance rate of pathological findings with TL was high (100%). The results suggest that EBUS-TBNA should be carefully evaluated in patients with TL, considering the low positive rate of mycobacterial culture and MTB-PCR test in the needle rinse fluid.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Tuberculosis, Lymph Node/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Tuberculosis, Lymph Node/diagnostic imagingABSTRACT
A 21-year-old man with chief complaints of left hypochondriac and chest pain was shown to have multiple masses in the lung, a pleural effusion in the right cavum thoracis, a mediastinal mass, and lymphadenopathy detected by computed tomographic scan. He was diagnosed with an extragonadal germ cell tumor based on pathologic findings from lung biopsies and elevation of the serum total human chorionic gonadotropin. He underwent a reduced chemotherapy regimen consisting of bleomycin, cisplatin, and etoposide (reduced BEP) to lower the risk of acute respiratory distress syndrome (ARDS), a manifestation of choriocarcinoma syndrome, which occurs at induction chemotherapy with the full-dose BEP regimen. Choriocarcinoma syndrome did not develop during chemotherapy, and he has been disease-free since salvage chemotherapy and subsequent retroperitoneal lymph node dissection.
Subject(s)
Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin , Cisplatin/therapeutic use , Etoposide/therapeutic use , Humans , Induction Chemotherapy , Male , Neoplasms, Germ Cell and Embryonal/drug therapy , Testicular Neoplasms/drug therapy , Young AdultABSTRACT
A 67-year-old female presented for evaluation of a left inguinal mass. Contrast-enhanced computed tomography revealed a tumor surrounding the urethra. Magnetic resonance imaging showed that the tumor had invaded the bladder neck on the anterior aspect of the urethra. The serum carbohydrate antigen 19-9 level was elevated. The clinical diagnosis was a primary adenocarcinoma of the female urethra (cT4N2M0). The initial treatment consisted of gemcitabine plus cisplatin (GC) and oral fluoropyrimidine (S-1). A total cysto-urethrectomy with anterior vaginal wall resection, pelvic and inguinal lymphadenectomy, and urinary diversion with ileal conduit formation were performed. The final diagnosis was urethral adenocarcinoma (ypT4ypN2, stage IV). Twelve months post-operatively, there was no evidence of recurrence or distant metastases.
Subject(s)
Adenocarcinoma , Urethral Neoplasms , Urinary Bladder Neoplasms , Aged , Cisplatin , Deoxycytidine/analogs & derivatives , Female , Humans , Male , Neoplasm Recurrence, Local , Urethra , GemcitabineABSTRACT
Carotenoids-natural fat-soluble pigments-have attracted considerable attention because of their potential to prevent of various diseases, such as cancer and arteriosclerosis, and their strong antioxidant capacity. They have many geometric isomers due to the presence of numerous conjugated double bonds in the molecule. However, in plants, most carotenoids are present in the all-E-configuration. (all-E)-Carotenoids are characterized by high crystallinity as well as low solubility in safe and sustainable solvents, such as ethanol and supercritical CO2 (SC-CO2). Thus, these properties result in the decreased efficiency of carotenoid processing, such as extraction and emulsification, using such sustainable solvents. On the other hand, Z-isomerization of carotenoids induces alteration in physicochemical properties, i.e., the solubility of carotenoids dramatically improves and they change from a "crystalline state" to an "oily (amorphous) state". For example, the solubility in ethanol of lycopene Z-isomers is more than 4000 times higher than the all-E-isomer. Recently, improvement of carotenoid processing efficiency utilizing these changes has attracted attention. Namely, it is possible to markedly improve carotenoid processing using safe and sustainable solvents, which had previously been difficult to put into practical use due to the low efficiency. The objective of this paper is to review the effect of Z-isomerization on the physicochemical properties of carotenoids and its application to carotenoid processing, such as extraction, micronization, and emulsification, using sustainable solvents. Moreover, aspects of Z-isomerization methods for carotenoids and functional difference, such as bioavailability and antioxidant capacity, between isomers are also included in this review.
Subject(s)
Carotenoids/chemistry , Solvents/chemistry , Chemical Phenomena , Emulsions , Isomerism , Molecular Structure , SolubilityABSTRACT
BACKGROUND: The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because of its association with the cells' progression to castration-resistant prostate cancer (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate the androgen receptor (AR). For example, IL-6 is a multifunctional cytokine that is involved in the malignancy of PCa cells through AR activation. In the present study, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines to investigate the relationship between the responsiveness of PCa cells to IL-6 treatment and the cellular AR signaling pathway. METHODS: The androgen-low-sensitive F10 and E9 cells were obtained from LNCaP cells by limiting dilution method in regular culture condition. In contrast, the androgen-insensitive AIDL cells were established from LNCaP cells by continuous passaging in hormone-depleted condition. Original carcinoma-associated fibroblasts (CAFs) PCaSC-8 and PCaSC-9 cells were isolated from needle biopsy samples of PCa patients. RESULTS: In fibroblasts derived from PCa patients, IL-6 secretion was generally higher than that observed with normal fibroblasts. In contrast, IL-6 secretion was not detected in LNCaP and its sublines. The soluble IL-6 receptor was detected in PCa cells but not in fibroblasts. IL-6 treatment suppressed cell growth of LNCaP, F10, and E9 cells but not AIDL cells and it was accompanied with neuroendocrine-like differentiation. Induction of PSA secretion was observed in IL-6-treated LNCaP and F10 cells. VEGF secretion was strongly induced in IL-6-treated LNCaP and AIDL cells. IL-6-induced VEGF secretion was significantly suppressed by a PI3K inhibitor (LY294002) and it was accompanied by inhibited phosphorylation of Akt. CONCLUSIONS: Our results suggest that IL-6 might induce VEGF secretion from PCa cells in a manner independent of AR activation. To prevent IL-6-induced VEGF secretion, inhibition of the PI3K/AKT signaling pathway could be an important pharmacological goal regardless of ADT.
Subject(s)
Interleukin-6/pharmacology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Receptors, Androgen/metabolism , Vascular Endothelial Growth Factor A/metabolism , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Cell Line, Tumor , Humans , Interleukin-6/metabolism , Male , Prostatic Neoplasms/pathology , Signal Transduction/drug effectsABSTRACT
The effect of Z-isomerization of (all-E)-lycopene on its solubility in organic solvents and physical properties was investigated. Lycopene samples containing different Z-isomer contents (23.8%, 46.9%, and 75.6% of total lycopene) were prepared from high-purity (all-E)-lycopene by thermal Z-isomerization in dichloromethane (CH2Cl2). As the Z-isomer content increased, the relative solubility of lycopene significantly improved. Although (all-E)-lycopene barely dissolved in ethanol (0.6 mg/L), the solubilities of lycopene containing 23.8%, 46.9%, and 75.6% Z-isomers were 484.5, 914.7, and 2401.7 mg/L, respectively. Furthermore, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), and scanning electron microscopy (SEM) analyses clearly indicated that (all-E)-lycopene was present in the crystal state, while Z-isomers of lycopene were present in amorphous states. A number of studies have suggested that Z-isomers of lycopene are better absorbed in the human body than the all-E-isomer. This may be due to the change in solubility and physical properties of lycopene by the Z-isomerization.
Subject(s)
Carotenoids/chemistry , Plant Extracts/chemistry , Solanum lycopersicum/chemistry , Carotenoids/isolation & purification , Kinetics , Lycopene , Methylene Chloride/chemistry , Solubility , Solvents/chemistry , Stereoisomerism , TemperatureABSTRACT
Japanese Urological Association reported that 3,648 patients of renal cell carcinoma were diagnosed in 2007 from 340 institutions and 70 years old or more accounted for 35.5% of pa- tients and 8.3% were more than 80 years old. If the elderly patients are frail and have severe comorbidity, surveillance might be taken for small renal cancer. However, relatively large tu- mor or rapid tumor growth rate lead to disease progression. Because percutaneous ablation to renal cell carcinoma is less invasive treatment than surgery and is superior in quality of life maintenance, it will be suitable treatment for small renal carcinoma of elderly patients. We showed results of the radiofrequency ablation of renal cell carcinoma of elderly patients 80 years or older. Among 17 patients, four patients were dead of other causes and the death due to renal carcinoma was absent. Only one patient had local tumor progression and needed re- ablation. Renal function preservation after treatment was good.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Aged , HumansABSTRACT
In patients with prostate cancer (PCa), serum prostate-specific antigen (PSA) is a useful marker for evaluating the effects of androgen deprivation therapy (ADT). Intuitively, most urologists expect that a more rapid PSA decline in response to ADT would be positively associated with extended survival. Recently, we have reported that prolonged gradual serum PSA decline after ADT is strongly associated with favorable prognosis in PCa patients, however, the mechanism remains unknown. We investigated the role of fibroblasts in serum PSA decline after ADT. We performed in vitro experiments using androgen-sensitive, androgen receptor (AR)-positive prostate epithelial cell lines (LNCaP, 22Rv1, and RWPE-1 cells), commercially available prostate stromal cells (PrSC), and primary cultures of prostate fibroblasts (pcPrFs). In LNCaP and 22Rv1 cells, PSA production was increased by co-culture with fibroblasts under androgen-deprived conditions. In an in vivo model using LNCaP cells, serum PSA declined rapidly after ADT becoming undetectable within 14 days in mice inoculated with LNCaP cells alone. In contrast, when LNCaP cells were co-inoculated with fibroblasts, serum PSA levels were still high on 14 days post ADT and did not drop to undetectable levels until 21 days post ADT. Tumor volumes and Ki67 labeling indices were not altered between days 14 and 21 post ADT in mice inoculated with LNCaP cells; however, those in mice inoculated with LNCaP cells plus fibroblasts decreased gradually. PSA protein was detected in all tumors on 21 days post ADT by immunohistochemical staining. Microvessel densities were higher on 14 days post ADT for tumors from mice inoculated with LNCaP cells plus fibroblasts as compared with LNCaP cells alone. In summary, co-inoculation of fibroblasts with LNCaP cells prolonged serum PSA decline after ADT and enhanced the efficacy of ADT. Prolonged serum PSA decline may indicate the presence of protective fibroblasts that preserve the AR dependence of PCa cells, improving treatment efficacy.
Subject(s)
Androgen Antagonists/therapeutic use , Fibroblasts/physiology , Prostate-Specific Antigen/blood , Prostatic Neoplasms/drug therapy , Animals , Cell Line, Tumor , Humans , Male , Mice , Mice, Inbred BALB C , Neovascularization, Pathologic/etiology , Prostatic Neoplasms/blood , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/pathologyABSTRACT
OBJECTIVE: Active surveillance has emerged as an alternative to immediate treatment in men with favorable-risk prostate cancer; however, consensus about defining the appropriate candidates is still lacking. To examine the factors predicting unfavorable pathology among active surveillance candidates, we assessed low-risk radical prostatectomy specimens. METHODS: This retrospective study included 1753 men who had undergone radical prostatectomy at six independent institutions in Japan from 2005 to 2011. Patients who met the active surveillance criteria were categorized depending on the pathological features of the radical prostatectomy specimens. 'Reclassification' was defined as upstaging (≥pT3) or upgrading (radical prostatectomy Gleason score ≥7), and 'adverse pathology' was defined as pathological stage ≥pT3 or radical prostatectomy Gleason score ≥4 + 3. Multivariate analysis was used to analyze the preoperative factors for reclassification and adverse pathology. The rates of reclassification and adverse pathology were evaluated by classifying patients according to biopsy core numbers. RESULTS: The active surveillance criteria were met by 284 cases. Reclassification was identified in 154 (54.2%) cases, while adverse pathology in 60 (21.1%) cases. Prostate-specific antigen density and percentage of positive cores were independently associated with reclassification and adverse pathology. The rates of reclassification and adverse pathology were significantly higher among patients with <10 biopsy cores than among others. Thus, focusing on 149 patients with ≥10 biopsy cores, prostate-specific antigen density was the only independent predictor of unfavorable pathological features. The receiver operating characteristic curve analysis determines an optimal cut-off value of prostate-specific antigen density as 0.15 ng/ml2. CONCLUSIONS: Prostate-specific antigen density is the most important predictor of unfavorable pathological features in active surveillance candidates.
Subject(s)
Prostatic Neoplasms/pathology , Aged , Area Under Curve , Humans , Japan , Logistic Models , Male , Multivariate Analysis , Neoplasm Grading , Prostate-Specific Antigen/analysis , Prostatectomy , Prostatic Neoplasms/classification , Prostatic Neoplasms/surgery , ROC Curve , Retrospective StudiesABSTRACT
PURPOSE: To compare clinical outcomes of radiofrequency (RF) ablation retrospectively with those after radical nephrectomy in patients with stage T1b renal cell carcinoma (RCC). MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, and the requirement to obtain written informed consent was waived. From June 2002 to March 2012, 60 patients (mean age, 65.2 years; age range, 39-86 years) with a single RCC measuring 4.1-7.0 cm (stage T1b) underwent RF ablation (n = 21) or radical nephrectomy (n = 39). Selective renal artery embolization was performed before RF ablation in eight patients. The overall, RCC-related, and disease-free survival rates, the percentage decrease in the glomerular filtration rate (GFR), and safety were compared by using the log-rank (survival), paired and Student t (GFR), and Fisher exact (safety) tests. RESULTS: The overall survival rate was significantly lower in the RF ablation group than in the radical nephrectomy group (48% vs 97% at 10 years, respectively; 95% confidence interval [CI]: 12.4%, 76.7% vs 78.2%, 99.5%; P < .009). The RCC-related survival rate (94% [95% CI: 62.6%, 99.1%] with RF ablation vs 100% with radical nephrectomy at 10 years) and the disease-free survival rate (88% [95% CI: 59.2%, 96.9%] with RF ablation vs 84% [95% CI: 60.6%, 94.3%] with radical nephrectomy at 10 years, P = .99) were comparable between the two groups. No treatment-related deaths occurred. Although major complication rates were similar between the two patient groups (8.0% [two of 25 patients] vs 5.1% [two of 39 patients], P = .61), the percentage decrease in the GFR was significantly lower in the RF ablation group than in the radical nephrectomy group at the last follow-up (12.5% ± 23.4 vs 32.3% ± 20.8, respectively; P < .003). CONCLUSION: RF ablation is a safe procedure for patients at substantial surgical risk for radical nephrectomy, providing comparable RCC-related and disease-free survival and preserving renal function.
Subject(s)
Carcinoma, Renal Cell/surgery , Catheter Ablation , Kidney Neoplasms/surgery , Nephrectomy/methods , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/pathology , Embolization, Therapeutic , Female , Glomerular Filtration Rate , Humans , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
A 51-year-old woman received an ABO blood type-incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium, although there was no 'storiform' fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4-positive plasma cells, most of which expressed kappa-type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4-related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow-up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4-positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL. To our knowledge, this is the first report of IgG4-positive plasma cell-rich tubulointerstitial nephritis mimicking IgG4-related kidney disease after kidney transplantation.
Subject(s)
Immunoglobulin G/immunology , Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/pathology , Nephritis, Interstitial/pathology , Plasma Cells/pathology , Diagnosis, Differential , Female , Humans , Immunoglobulin kappa-Chains/immunology , Lymphoproliferative Disorders/drug therapy , Lymphoproliferative Disorders/immunology , Middle Aged , Nephritis, Interstitial/etiology , Nephritis, Interstitial/immunology , Plasma Cells/immunology , Steroids/therapeutic use , Transplantation, HomologousABSTRACT
Macroalgae are one of potential sources for carotenoids, such as fucoxanthin, which are consumed by humans and animals. This carotenoid has been applied in both the pharmaceutical and food industries. In this study, extraction of fucoxanthin from wet brown seaweed Undaria pinnatifida (water content was 93.2%) was carried out with a simple method using liquefied dimethyl ether (DME) as an extractant in semi-continuous flow-type system. The extraction temperature and absolute pressure were 25 °C and 0.59 MPa, respectively. The liquefied DME was passed through the extractor that filled by U. pinnatifida at different time intervals. The time of experiment was only 43 min. The amount of fucoxanthin could approach to 390 µg/g dry of wet U. pinnatifida when the amount of DME used was 286 g. Compared with ethanol Soxhlet and supercritical CO2 extraction, which includes drying and cell disruption, the result was quite high. Thus, DME extraction process appears to be a good method for fucoxanthin recovery from U. pinnatifida with improved yields.