Keiichiro Uemura

A useful treatment for patients with advanced mixed-type small cell neuroendocrine carcinoma of the prostate: A case report.

Treating extended prostatic small cell neuroendocrine carcinoma (PSCNC) is extremely difficult and no standard treatment has yet been established. We experienced a case of advanced mixed-type PSCNC in which the patient achieved long-term survival and local control following combined therapy. Locally advanced PSCNC causing lower urinary obstruction was detected during androgen-ablation therapy for stage D2 mixed adenocarcinoma PSCNC. The patient was treated with intra-arterial infusion chemotherapy using a reservoir system and external-beam radiotherapy (EBRT) to the whole pelvis and local tumor. After chemoradiotherapy, the patient’s lower urinary obstruction was reduced and did not return during the remaining 40 months of the patient’s life. The patient survived for 70 months following the start of the androgen-ablation therapy. The present study reports a useful treatment for advanced mixed-type PSCNC, androgen-ablation therapy and chemoradiotherapy. The present results also suggest that the prognostic factors for advanced mixed-type PSCNC are the sensitivity of the conventional adenocarcinoma to androgen-ablation therapy, degree of metastasis and extent of the small cell neuroendocrine carcinoma component.

Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution

Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

Anchoring structure of the calvarial periosteum revealed by focused ion beam/scanning electron microscope tomography

An important consideration in regeneration therapy is the fact that the tissue surrounding an organ supports its function. Understanding the structure of the periosteum can contribute to more effective bone regeneration therapy. As a cellular source, the periosteum also assists bone growth and fracture healing; this further necessitates its direct contact with the bone. However, its anchoring strength appears to be inexplicably stronger than expected. In this study, we used focused ion beam/scanning electron microscope tomography to investigate ultrathin serial sections as well as the three dimensional ultrastructure of the periosteum to clarify the architecture of its anchoring strength, as such assessments are challenging using conventional methods. We discovered perforating fibres that arise from the bone surface at 30 degree angles. Additionally, the fibres across the osteoblast layer were frequently interconnected to form a net-like structure. Fibroblast processes were observed extending into the perforating fibres; their morphologies were distinct from those of typical fibroblasts. Thus, our study revealed novel ultrastructures of the periosteum that support anchorage and serve as a cellular source as well as a mechanical stress transmitter.

Improvement in urinary retention due to recurrent anastomotic prostate cancer treated with various therapies by intra-arterial infusion of cisplatin and ifosfamide

Although many treatments have been applied to treat hormone-refractory prostate cancer (HRPC), therapeutic outcome is not altogether satisfactory. In the case of locally recurring HRPC, uncontrolled gross hematuria, dysuria, and scalding are often experienced. We report a patient who improved following intra-arterial infusion of cisplatin (CDDP) and ifosfamide (IFM) to treat urinary retention caused by locally recurring HRPC. After chemotherapy, cancer volume was remarkably reduced and symptoms improved.

Subcutaneous transplantation promotes organ formation of the fetal rat urogenital sinus.

The aim of this study is to develop a novel experimental model of the subcutaneous transplantation of fetal urogenital sinus (UGS) into normal and castrated adult male rats for the pathophysiological investigation of the normal and developing prostate. Fetal UGS obtained from 20-day-old male rat embryos was subcutaneously transplanted into 7-week-old normal and castrated male rats. We observed the growth pattern, histopathological characteristics and immunohistochemical localization of cytokeratin 5 (CK 5), cytokeratin 8 (CK 8) and androgen receptor (AR) in the transplanted tissues. Almost all of the transplanted UGS organs gradually increased in weight over time in the non-castrated recipient animals, and the histopathological observations and immunohistochemical analysis of CK 5 and CK 8 revealed that the morphological changes in the tissues were in accordance with the features of normal prostate development. The histological characteristics included glandular epithelial dominant and stromal dominant area, with an increase in the glandular epithelial dominant areas over time and resemblance among a portion of the transplanted tissues within a certain period during the developmental course to the histopathology of human benign prostatic hyperplasia (BPH). The effects of androgens and resemblance in the immunohistochemical localization pattern changes in AR to that observed in the normal differentiating rat prostate were also noted. We conclude that the subcutaneous space provides an adequate microenvironment for UGS growth.

Solitary fibrous tumor of the greater omentum in an inguinal hernia sac

A 40-year-old man visited our hospital in December 2008 complaining of a painless mass in the left inguinoscrotal area. The surface of the mass, expected to be a tumor, was smooth and mobile. Ultrasonography showed the tumor was separated from the same-side testis, and extended to the spermatic cord. Computed tomography (CT) revealed that the heterogeneous tumor extended to the spermatic cord, and that the left inguinal canal was dilated. We diagnosed him with a left spermatic cord tumor, and left ascensus orchiectomy was performed on February 5th, 2009. With regard to the operative findings, the tumor was located in the inguinal hernia sac and extended to the greater omentum, and was separated from the spermatic cord. Immunohistochemical examination showed positive reactivity for CD99 and vimentin; however, desmin, S100, and bcl-2 were negative. CD34 was positive only in a few tumor cells around the blood vessel. The final diagnosis was solitary fibrous tumor (SFT), although it was not a representative type, originating from the greater omentum, existing in an inguinal hernia sac. This is the first such case to be reported anywhere in the world. So, we describe this rare case.

AGEs–RAGE overexpression in a patient with smoking-related idiopathic nodular glomerulosclerosis

We report a case of smoking-related idiopathic nodular glomerulosclerosis (ING) with overexpression of glomerular advanced glycation end products (AGEs) and their receptor (RAGE). A 59-year-old Japanese man with nephrotic syndrome, who had a smoking history of one pack of cigarettes per day for approximately 40 years, presented with a 3-year history of urinalysis abnormalities without clinical evidence of diabetic mellitus. The patient’s leg edema progressively worsened over the previous 2 years, and he was admitted to our hospital. Renal biopsy showed mesangial expansion with diabetic Kimmelstiel–Wilson-like nodular lesions, glomerular basement thickening, and arteriosclerosis. No electron-dense deposits, fibrils, or microtubule deposits were seen in the glomeruli on electron microscopy. Skin AGE level measured using AGE reader was higher in this case than the average level in age-matched Caucasians. In addition, immunohistochemical analysis revealed that N-carboxymethyl lysine, one of the major AGEs, and RAGE were overexpressed and podocin expression was decreased in the peripheral area of the glomerular nodular lesions. These observations suggest that AGEs–RAGE system may be activated in smoking-related ING, possibly leading to the progression of renal dysfunction.

Efficacy of Axitinib as Second-line Treatment in Locally Advanced and Metastatic Renal Cell Carcinoma

Aim: To investigate prognostic factors for patients with advanced renal cell carcinoma (RCC) treated with axitinib as second-line therapy. Patients and Methods: This study included 35 patients with RCC who received axitinib as second-line therapy after the failure of first-line tyrosine kinases inhibitor from November 2012 to March 2017. Results: In univariate analyses, the following factors were associated with poor prognosis: bone and extrapulmonary metastasis for progression-free survival; and prior nephrectomy, Memorial Sloan Kettering Cancer Center risk classification, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification of poor, extrapulmonary metastasis and early tumor response for overall survival. Multivariate analyses identified the following factors as independent poor prognostic effects: extrapulmonary metastasis for progression-free survival, and no prior nephrectomy, IMDC risk classification of poor and extrapulmonary metastasis for overall survival. Conclusion: Axitinib as second-line treatment is effective for patients with pulmonary metastasis alone of RCC, but not for those with extrapulmonary metastasis.