Case report of primary carcinoma in situ in upper urinary tract and review of the Japanese literature

A case of carcinoma in situ (CIS) in the right renal pelvis in a 71-year-old women is reported. The patient was admitted because of macroscopic hematuria. Drip infusion pyelography showed a filling defect (coagulum) in the right renal pelvis. Other abnormal findings were not made. Malignancy was suspected by cytology examination in both voiding urine and that obtained by catheter from the right pelvis. A right total nephroureterectomy was performed. Macroscopic abnormal findings were only of the coagulum in the renal pelvis. Pathologic examination showed CIS in the renal pelvis. We studied the features, pattern of recurrence, and prognosis of 19 cases of primary CIS in the upper urinary tract in the Japanese literature. A slight higher frequency was reported for women than for men. When the CIS was in the ureter, abnormal roentgenological findings, such as stenosis, filling defects, or a dilated ureter, were common (77%), contrary to expectation. But when the CIS was in the pelvis, such findings were rare. Urine cytology examination was positive in 95% of the patients. In four of the 19 patients, a recurrence was found. In all four patients, the first recurrence was in the bladder within 2 years of surgery. The kind of recurrent bladder tumors varied with the patients. The prognosis with recurrence was poor. If signs of recurrence were not recognized within 2 years of surgery, the prognosis was good.     

Nonfunctioning adrenocortical adenoma: a report of two cases

Two cases of nonfunctioning adrenocortical adenoma are herein reported. The adrenal tumor was found incidentally by computed tomography in both patients. Preoperative evaluation revealed that both patients had neither abnormal values in a variety of adrenal function studies nor any recognizable clinical signs associated with adrenal tumor. Following a definitive diagnosis of nonfunctioning adrenal tumors, surgical extirpation was performed in both cases. Histopathological finding was adrenocortical adenoma. Nonfunctioning adrenocortical tumor will be found more frequently with the increasing use of computed tomography in ordinary clinical practice. The management of nonfunctioning adrenocortical tumor is briefly discussed.     

Serum levels of interleukin‐1α in patients with systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune systemic connective tissue disorder characterized by sclerotic change of the skin and multiple internal organs. Although the pathogenesis of this disorder is still unknown, overproduction of extracellular matrix proteins, including collagens and fibronectin, and aberrant immune activation may be involved in the mechanism. Interleukin (IL)‐1 is one of the key regulators of inflammatory response. IL‐1 is also involved in regulating connective tissue remodeling and cellular differentiation of epithelial and ectodermal cells. There are three major members of the IL‐1 family: IL‐1α, IL‐1β and IL‐1 receptor antagonist. IL‐1α was first described as a factor derived from keratinocytes that stimulates thymocyte proliferation. IL‐1α plays a crucial role in procollagen production by fibroblasts derived from patients with SSc. The present study was undertaken to investigate the serum levels of IL‐1α in patients with SSc. Serum samples were obtained from 66 Japanese patients with SSc and 19 healthy controls. Levels of serum IL‐1α were measured with a specific enzyme‐linked immunoassay kit. Mean serum levels were significantly higher in SSc patients than in those healthy control subjects. Moreover, contracture of phalanges was found at a significantly lower prevalence in SSc patients with elevated serum IL‐1α levels than those with normal levels. These results suggest that IL‐1α may play a role in the pathogenesis of SSc.     

Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.     

A case of bilateral testicular tumor

A case of bilateral germ cell tumor of the testis is reported. In 1988, a 36-year-old male presented with painless swelling of left scrotal contents. Right orchiectomy and retroperitoneal lymph node dissection for embryonal carcinoma had been performed 5 years earlier. Left orchiectomy was performed and its histological finding was seminoma and embryonal carcinoma. Evaluations including CT scan and Ga scintigraphy revealed no metastasis. Postoperatively, the patient was treated with PVB therapy. Previous reports of bilateral germ cell testicular tumor were reviewed, and the age distribution, interval, and histological classification of these cases are discussed.     

Role of heat shock protein 47, a collagen-binding chaperone, in lacrimal gland pathology in patients with cGVHD

PURPOSE: Uncontrolled fibrosis due to excessive accumulation of extracellular matrix proteins in the lacrimal glands of patients with chronic graft-versus-host disease (cGVHD) is well documented. Heat-shock protein 47 (HSP47) is involved in the molecular maturation of collagen and has been shown to have a fibrogenic role in various fibrotic diseases. In this study, the role of HSP47 in the pathogenesis of lacrimal gland of patients with cGVHD was investigated. METHODS: The expression of HSP47, Ki67 (a proliferation marker), types I and III collagen, and alpha-smooth muscle actin (alpha-SMA) was examined in tissue sections and in primary cultures of fibroblasts obtained from the lacrimal glands of patients with cGVHD (n = 8) and Sj?gren's syndrome (SS; n = 7). RESULTS: Tissue sections of the lacrimal glands of patients with cGVHD showed markedly increased expression of HSP47 in fibroblasts around the medium-sized ducts than did those from patients with SS. The elevated expression of HSP47 in patients with cGVHD was mostly detected in Ki67-positive fibroblasts and was associated with increased accumulation of types I and III collagen in and around the fibrotic areas. Primary fibroblast cultures generated from cGVHD lacrimal gland showed higher HSP47 mRNA expression than did fibroblasts isolated from SS biopsy tissue, as determined by RT-PCR (P < 0.05). In contrast, alpha-SMA was higher in the SS than cGVHD fibroblasts at both mRNA and protein levels, and more lacrimal gland fibroblasts in the SS were positive for alpha-SMA than cGVHD (P < 0.01). CONCLUSIONS: In cGVHD, increased expression of HSP47 may promote excessive collagen assembly in and around the periductal areas where fibroblasts are mostly in an active state. The less alpha-SMA in the cGVHD lacrimal gland fibroblasts suggests a relative lack of myofibroblastic transformation. It is likely that fibroblasts incapable of myofibroblastic transformation are the main source of HSP47 and collagen production, and the resultant effect is the periductal fibrotic changes seen in lacrimal glands of patients with cGVHD.     

Transurethral resection of the prostatic gland (TUR-P) and incidental carcinoma

During the four years between January, 1983 and December, 1986, transurethral resection of the prostatic gland (TUR-P) was performed on 108 patients with benign prostatic hypertrophy at Osaka Municipal Kita Citizen's Hospital. Histopathological examination of the transurethral resection specimens revealed 9 cases (8.3%) of incidental carcinoma. In this study, the average patient age, preoperative prostatic acid phosphatase (PAP) level and weight of resection specimens were compared for all 108 patients. For the 9 patients with incidental carcinoma, the clinical stage, histological grade and therapy were evaluated.     

Effect of activated human mast cells and mast cell-derived mediators on proliferation,type I collagen production and glycosaminoglycans synthesis by human dermal fibroblasts

Although an increased number of mast cells in fibrotic tissues such as scleroderma, keloid or healing wound has been highlighted, it is still unclear whether or not mast cells are fibrogenic. The aim of the present study is to determine whether functionally active human mast cells can provide human dermal fibroblasts directly with fibrogenic properties. In order to examine the effects of IgE-mediated mast cell activation on fibroblast proliferation and synthesis of type I collagen, we utilized an in vitro defined system in which cultured human mast cells were co-cultured with human dermal fibroblasts. We also employed a three-dimensional fibroblast culture system using supplementation of L-ascorbic acid as an assay system to investigate the effects of mast cell-derived mediators on synthesis of glycosaminoglycans by human fibroblast. Fibroblast proliferation was actively stimulated with IgE-activated mast cells. However, this stimulatory effect was canceled in co-cultures with a higher number of IgE-activated mast cells. In the presence of a higher number of activated mast cells, the fibroblast cell layer was destroyed, in contrast to an intact cell layer in the presence of same number of the mast cells without activation. Type I collagen synthesis was unchanged in fibroblasts co-cultured with mast cells. The total amount of main disaccharide units, particularly DELTADi-HA, was increased when fibroblasts were exposed to histamine. Thus, we conclude that other factors, in addition to mast cells, are important in the development of human tissue fibrosis or sclerosis.