Trend in unequal geographical distribution of dentists by age and gender in Japan from 1996-2014.

OBJECTIVES: To evaluate the relationship between dentists' demographic changes and their uneven geographical distribution. METHODS: Secondary analysis of nationwide government surveys, to assess trends in the geographical distribution of dentists by gender and age from 1996 to 2014 in Japan. RESULTS: The Gini-coefficient for the number of dentists per population from 47 prefectures decreased from 0.084 in 1996 to 0.069 in 2014. The coefficients for female (0.124-0.144) were higher than for male dentists (0.058-0.081). Coefficients for dentists aged 60 and older were lower than those for dentists younger than 40 in 2014 (male: 0.060 vs. 0.112; female: 0.107 vs. 0.169). CONCLUSION: The geographical maldistribution of dentists in Japan has improved. Demographic changes among dentists, including the increasing number of female dentists, could moderate this improvement.

Detection of Slackia exigua, Mogibacterium timidum and Eubacterium saphenum from pulpal and periradicular samples using the Polymerase Chain Reaction (PCR) method.

AIM: The purpose of this study was to detect Slackia exigua from root canal samples using a sensitive PCR amplification method. Mogibacterium timidum and Eubacterium saphenum were also included because of their culture-difficult properties. METHODOLOGY: The species-specific PCR primers were prepared according to 16S rDNA sequence analysis data, and confirmed to be effective for PCR amplification as species-specific, respectively. A total of 36 clinical samples were obtained during the first visit of root canal treatment. RESULTS: The sensitivity of detection was a minimum of 10 organisms for S. exigua and five organisms for M. timidum and E. saphenum, respectively. In seven cases of pulpitis, Sexigua was detected in two cases (29%), and M. timidum in two cases (29%), but E. saphenum was not detected. In 17 cases of root canal treatment, S. exigua was detected in seven cases (41%), M. timidum in 12 cases (71%) and E. saphenum in four cases (24%). In 12 cases of root canal retreatment, S. exigua was detected in three cases (25%), M. timidum in three cases (25%) and E. saphenum in two cases (17%). CONCLUSIONS: S. exigua, M. timidum and E. saphenum were present in root canal systems, and may be associated with pulpal and periradicular pathosis.

Multivariate analysis of prognostic determinants after surgery for renal cell carcinoma at Himeji National Hospital.

A clinico-pathological study was performed retrospectively on 62 patients who underwent surgery for renal cell carcinoma between January 1992 and October 1998 at Himeji National Hospital to clarify the prognostic determinants for survival. The median follow-up period was 32 months and the cause-specific survival rates at 1, 3 and 5 years were 86.7, 81.3, 81.3%, respectively. Of the 62 patients, 11 (17.7%) patients died of renal cell carcinoma and 2 (3.2%) patients died of unrelated causes. Of the variables related to survival, presenting symptoms, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALP), tumor size, pathological tumor grade, infiltration pattern, pathological tumor stage, N classification and M classification were significant risk factors for survival by univariate analysis. However, ALP, N classification and M classification were significant for survival as determined by the step-wise procedure and M classification was the most significant factor according to Cox's proportional hazard model analysis.

Geriatric ureteropelvic junction obstruction: the possible role of an arteriosclerotic lower pole branch of renal artery: report of two cases.

An 83-year-old woman presented with left flank pain and high grade fever. After left ureteral catheterization and intensive chemotherapy with hemoperfusion, surgical exploration revealed the lower pole branches of the renal vessels were obstructing the ureteropelvic junction (UPJ), and dissection of the vessels released the obstruction. An 82-year-old man presented with right flank pain. Angiography demonstrated UPJ obstruction caused by the lower pole branch of the renal artery. Arterial dissection with dismembered pyeloplasty resulted in improvement of obstruction. In both cases, the patients had a long history of hypertension with mild to severe arteriosclerosis. Arteriosclerosis associated with fixation of the UPJ, may be one of the important factors leading to progressive hydronephrosis in geriatric patients.

Description of Mogibacterium pumilum gen. nov., sp. nov. and Mogibacterium vescum gen. nov., sp. nov., and reclassification of Eubacterium timidum (Holdeman et al. 1980) as Mogibacterium timidum gen. nov., comb. nov.

A new genus, Mogibacterium, is proposed for anaerobic, non-spore-forming, Gram-positive, rod-shaped bacteria which have been isolated from the periodontal pockets of adult human patients with periodontal disease and infected root canals. The novel isolates, strains D2-18T, BA11a-f and D5-2T, were inert in most of the conventional biochemical tests and phenotypically resemble asaccharolytic Eubacterium species. The protein profiles of whole cells on SDS-PAGE gels and Western immunoblotting reaction analysis distinguished these organisms from type strains belonging to the previously described Eubacterium species. The G + C content of the DNA is 45-46 mol% for Mogibacterium pumilum and 46 mol% for Mogibacterium vescum. The levels of DNA-DNA relatedness of these new species to other Eubacterium species, including Eubacterium limosum, Eubacterium brachy, Eubacterium lentum, Eubacterium nodatum, Eubacterium saphenum, and the more recently proposed Eubacterium minutum and Eubacterium exiguum (reclassified as Slackia exigua), are less than 2%. The DNA-DNA hybridization value between M. pumilum and M. vescum was 30%. Eubacterium timidum exhibited DNA homologies with Mogibacterium species which were low (17 and 18%) but clearly higher than with all the other Eubacterium species. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the closest phylogenetic neighbour of Mogibacterium species was E. timidum, and that these three species represent a novel lineage distinct from the previously described genera of Gram-positive, rod-shaped bacteria. On the basis of phenotypic characteristics and 16S rRNA gene sequence comparisons, it is also proposed that E. timidum is transferred to the genus Mogibacterium gen. nov. as Mogibacterium timidum gen. nov., comb. nov. (type strain ATCC 33093T).

[Endoscopical reconstruction of traumatic urethral disruption with ureteral resectoscope: a case report].

A 19-year-old man sustained a fracture of the left ischial rami and disruption of the membranous urethra when a car hit him against a wall. A suprapubic tube was placed and was used for reconstruction of the disrupted urethra 3 months later. Eighty days after the injury, an 11.5 F ureteral resectoscope was inserted through the open cystostomy tract. Simultaneously, a 11 F pediatric cystoscope was inserted via urethra. Using the "cut to the light" procedure, the scar tissue was incised with sharp strokes of the ureteral resectoscope revealing the distal urethral lumen. Sequentially, urethral dilatation to 24 F was performed over a 0.038 Teflon-coated guide wire following insertion of a 24 F urethral catheter. The urethral catheter was removed 22 days after the operation. Direct vision urethroscopy was performed at 1- to 2-week intervals for 3 months. At present 13 months after the operation, he performs 18 F urethral self-dilation and has been free of voiding complaints. The ureteral resectoscope is useful for endoscopical reconstruction of urethral disruption.

[Intravesical bacillus Calmette-Guerin instillation for patients over 80 years old].

To study the efficacy and the safety of intravesical bacillus Calmette-Guerin (BCG) therapy for very elderly patients with superficial bladder cancer, we retrospectively compared patients over 80 years old who had received BCG therapy at our department between 1991 and 1996 (Group A; 10 patients 11 courses), with those below 80 years old (Group B, 17 patients 18 courses). In these patients, skin test reactivity to purified protein derivative showed a significant negative correlation with age (p = 0.016). No irreversible complications were observed in any patient. Persistence of acid-fast bacilli for more than one month after the termination of the course was observed in two patients in group A, and one in group B. A comparison of the cases undergoing eradicational BCG therapy in the two groups, grade 2 transitional cell carcinoma (TCC) was significantly more predominant than grade 3 TCC in group A (p = 0.004). (None of the tumors in group A were of grade 3) The disease-free rate was significantly lower in group A (p < 0.05), but 5 of the 10 patients in this group were finally disease-free. From these results, we conclude that intravesical BCG instillation therapy can be performed in patients over 80 years old, although a relatively lower disease-free rate is expected and special attention should be taken with regard to persistent BCG infection. The lower disease-free rate could be attributable to either diminished cellular immunity or a difference in tumor grade, although a definite conclusion could not be obtained here.

[Combination therapy of daily intramuscular injection of interferon-alpha and oral administration of fluorouracil for advanced renal cell carcinoma].

BACKGROUND: To achieve optimum drug delivery of Interferon-alpha in treatment of renal cell carcinoma, a regimen consisting of its daily intramuscular administration, in combination with oral fluorouracil, was designed and carried out. Its efficacy is examined retrospectively. METHODS: In our department 7 patients with disseminated renal cell carcinoma were treated with daily intramuscular injection of interferon-alpha (3 x 10(6) IU) and daily oral administration of fluorouracil. All patient was nehprectomized before initiation of the regimen. RESULTS: Two patients achieved complete, and three patients achieved partial response radiographically (Overall response rate 71%). Metastatic sites of responders were lung (4) and pleura (2). The time required until response was 3.9 (median 5.4) months. In two responders, new lesions appeared in other organs despite durable response in initial pulmonary metastatic sites. There were two no-responders, one patient is alive with stable disease and the other patient died for progression of the disease. In all, two patients died of disease, one died for other cause, one surviving without evidence of disease, and three are surviving with disease. No significant side effect was noted in these seven patients. CONCLUSIONS: This regimen can be carried out on outpatient basis and considerable response can be expected for pulmonary and pleural lesions.

Absence of p53 overexpression and favorable response to cisplatin-based neoadjuvant chemotherapy in urothelial carcinomas.

It has been controversial whether cancer cells harboring loss or inactivation of the tumor suppressor p53 are resistant or sensitive to DNA-damaging agents including cisplatin and doxorubicin. Overexpression of mdm2 oncoprotein, a negative regulator of p53, is assumed to be an alternative to p53 dysfunction. Archival urothelial carcinoma specimens obtained from 60 patients prior to cisplatin-based chemotherapy were immunohistochemically studied for overexpression of p53 and mdm2. Thirty-two patients (group I) were treated with chemotherapy in the neoadjuvant setting, while 28 patients (group II) underwent chemotherapy for distant metastases or inoperable locoregional tumors. In group I, the responsiveness was correlated with staining status of p53 (P=0.0225) and the combination of p53 and mdm2 (P=0.0497). Negative staining of p53 and negative for both p53 and mdm2 could have predicted favorable response to chemotherapy in 16 of 18 (88.9%) and in 12 of 13 (92.3%) tumors, respectively. On the other hand, p53-positive and p53 and/or mdm2-positive staining could have predicted poor response only in 7 of 14 (50.0%) and 8 of 19 (42.1%) tumors, respectively. Disease-specific survival of the p53-negative group was significantly superior to that of the p53-positive group (P=0.0086). Difference in survival did not become more significant when overexpression of mdm2 was taken into consideration (P=0.0456). In contrast, in group II, there was no correlation of responsiveness to chemotherapy or survival with p53- or p53/mdm2-staining status. The patients with urothelial carcinomas negative for overexpression of p53 will benefit from neoadjuvant chemotherapy. From clinical viewpoint, however, p53 status alone or the combination of p53 and mdm2 status is not enough to identify those patients who will not benefit from the treatment.

[Renal artery embolism treated by selective intra-arterial infusion of tissue plasminogen activator: report of 2 cases].

Two cases of renal artery embolism treated by selective intra-arterial infusion of tissue plasminogen activator (t-PA) are reported. A 74-year-old woman with atrial fibrillation presented with left flank pain of 54-hour duration. Selective renal angiography revealed embolic obstruction of multiple segmental arteries in the left kidney. She was treated by one-shot intra-arterial t-PA infusion (8,000,000 units) and intravenous heparinization (25,000 units/3 days). Although fibrinolysis was successful except for most distal arterial branches, complete recovery of renal function was not obtained. A 66-year-old man presented with complete obstruction of left main renal artery. He had hyperthyroidism and atrial fibrillation. At 75 hours after onset of left flank pain, he was treated by one-shot intra-arterial t-PA infusion (18,000,000 units) and intravenous heparinization (4,000 units/24 hours). His renal function was recovered completely. Selective intraarterial t-PA infusion is considered an effective treatment for renal artery embolism.

[A case of uretero-aortic fistula].

We report a case of uretero-aortic fistula. A 69-year-old man with rectal cancer underwent a pelvic exenteration and a double--barreled cutaneous ureterostomy in the right lower abdomen. Stomal stenosis necessitated continuous indwelling of double J stents in the two ureters. Two years postoperatively, massive bleeding occurred during exchange of double J catheters. Occlusive ureterogram demonstrated a uretero-aortic fistula at the crosspoint between the left ureter and the aorta. The surgical repair consisted of closure of the aortic fistula, ligation of the left ureter proximal to the fistula and percutaneous left nephrostomy.

A physiological role of interferon (IFN)-beta derived from tumor: tumor growth of a mouse bladder carcinoma line MBT-2 is partially suppressed by autocrine IFN-beta.

Although some tumor cells endogenously produce a wide variety of cytokines, their physiological roles remain to be fully understood. In this study, we found that mouse subcutaneous tumor induced by inoculation of bladder tumor MBT-2 cells into syngeneic mice secreted a significant amount of interferon (IFN), whereas the cells exhibited no IFN production in in vitro cell culture. Typing experiment using IFN-specific neutralizing antibodies showed that the tumor-derived IFN was exclusively beta type. Since the MBT-2 tumor tissues were homogenous and not infiltrated by immune cells, MBT-2 cells themselves were considered to be IFN-beta producers. By intraperitoneal injection of neutralizing anti-IFN-beta antibodies into MBT-2 cell-inoculated mice, the tumor growth was substantially precipitated and survival days of the tumor-bearing mice were shortened. As the in vitro cell growth of MBT-2 cells was dose-dependently inhibited by IFN-beta, it was suggested that apparent immunogenicity of MBT-2 tumor is partially mediated by tumor suppression by autocrine IFN-beta.

[Gene therapy by in vivo interferon-gamma gene transfer to murine bladder tumor].

For the clinical application of the cytokine gene therapy, the antitumor effects of systemic administration of Interferon-gamma (IFN-gamma) and those of in vivo direct IFN-gamma gene transfer to the tumors of mouse bladder carcinoma (MBT2) were compared. After the subcutaneous inoculation of MBT2 cells into mice, 10(2), 10(3) or 10(4) units of IFN-gamma were injected intraperitoneally (i.p.) or subcutaneously (s.c.). Neither i.p. nor s.c. injection of IFN-gamma resulted in tumor suppression or prolonged the survival time of tumor-bearing mice. The effect of in vivo direct IFN-gamma gene transfer by a retrovirus vector to MBT2 tumors was also evaluated. After the subcutaneous inoculation of MBT2 cells into mice, a virus culture supernatant containing IFN-gamma gene was injected into the same tumor site once a day for 3 days. In 50% of the mice in the treatment groups with IFN-gamma gene induction, no tumor formation was observed. Tumor-free survival and actuarial survival in the treatment groups were significantly longer than those in the control group. These results showed the possibility of in vivo direct IFN-gamma gene transfer into tumors and were encouraging for the execution of tumor cell-targeted IFN-gamma gene therapy against human bladder cancer.

Nuclear morphometry for improved prediction of the prognosis of human bladder carcinoma.

BACKGROUND: Histologic grade and clinical stage generally are used for estimating the prognosis of bladder carcinoma. However, both methods have been reported to have a rather low reproducibility and to be unsatisfactory for predicting the recurrence and progression of superficial bladder carcinoma. Recently, nuclear morphometry was used to quantitate the malignant potential of cancer cells in a more objective and reproducible manner. The authors quantitatively analyzed the malignant potential of bladder carcinoma at initial presentation using a combination of several nuclear morphometric variables. METHODS: The subjects were 156 patients with previously untreated bladder carcinoma. Three morphometric variables were measured in each subject: the mean nuclear volume (MNV), the nuclear roundness factor (NRF), and the variation of nuclear area (VNA). RESULTS: Univariate analysis showed that MNV and NRF were significant prognostic indicators for survival (MNV, P < 0.0001; NRF, P = 0.008). In addition, MNV was a prognostic indicator for tumor recurrence (P = 0.001), whereas MNV and NRF were prognostic indicators for invasive progression (MNV, P = 0.02; NRF, P = 0.009). For accurate prediction of the prognosis of patients with bladder carcinoma, a prognostic score, a recurrence score, and a progression score were designed using the coefficients of MNV and NRF in a proportional hazards model. The prognostic score clearly divided the patients into two different groups with 5-year survival rates of 88% and 64% (P = 0.0002). In addition, patients with superficial bladder carcinoma and a low recurrence score had a significantly higher 5-year recurrence free rate than those with a high recurrence score (40% vs. 23%, P = 0.0004), and the 5-year progression free rate of patients with a low progression score was significantly higher than that of those with a high progression score (98% vs. 73%, P = 0.0006). CONCLUSIONS: These findings suggest that nuclear morphometry is a reliable technique with which to identify prognostic indicators for human bladder carcinoma. A combination of several nuclear morphometric variables provides a more accurate indication of prognosis than any single parameter.

Continent urinary reservoir using sigmoid colon and appendix after pelvic exenteration for bulky leiomyosarcoma: a case report.

We report on a man with bulky leiomyosarcoma occupying the entire pelvic cavity that was treated by pelvic exenteration. A urinary reservoir was constructed using a detubularized segment of sigmoid colon. The appendix was tunneled into the taenia to form a continent catheterizable stoma using the Mitrofanoff principle. Descending colostomy was also created. There is no evidence of recurrence 24 months after treatment and the patient has returned to full physical activity. Continence is complete with a capacity of up to 500 ml. and regular bowel movements. Because of the lack of intestinal anastomosis, this procedure may be recommended as an option for urinary diversion after pelvic exenteration.

A case of metastatic yolk sac tumor of testis in a child.

We report a case of testicular yolk sac tumor in a child aged 3 years and 6 months with multiple bulky metastases to lung and retroperitoneum (stage IIIB2). After three courses of chemotherapy with a PVB regimen (cisplatin, vinblastine and bleomycin), complete and partial responses were obtained for lung and retroperitoneal lymph node metastases, respectively. The patient was followed-up closely. However, on the basis of a re-elevated alpha-fetoprotein (AFP) after 4 months' follow-up, he was treated with three courses of salvage chemotherapy with a modified VAB-6 regimen (cyclophosphamide, etoposide, actinomycin D, bleomycin and cisplatin), followed by retroperitoneal lymph node dissection. Histologically, only necrotic tissue was found. There is no evidence of recurrence 24 months after lymphadenectomy. There is very little information in the literature on the appropriate management of postchemotherapy residual mass in pediatric testicular tumors.

[A case of granulomatous orchitis].

A 69-year-old man complained of a painless left scrotal swelling. The scrotal mass was enlarged to a hen's egg size with a smooth surface. The scrotal ultrasonogram showed diffuse hypoechogenicity. A testicular tumor was suspected and left high orchiectomy was performed. Histopathological diagnosis was granulomatous orchitis.

[Bladder hernia associated with bladder diverticulum in a female].

A 77-year-old woman with a previous history of pelvic fracture had suffered from recurrent cystitis. In the excretory urography, post-void upright film revealed the bladder hernia associated with the bladder diverticulum. Transurethral incision and fulguration of the bladder diverticulum and left inguinal herniography was performed. There has been no recurrence since then.

[Single agent carboplatin therapy for advanced seminoma].

Between May 1990 and August 1992, 5 patients with advanced seminoma were treated with single agent carboplatin at Kyoto University. The mean follow-up period of all patients was 23 months. The clinical stage was IIA: 1, IIB: 1, IIIA: 2, IIIB1: 1. Three to 4 courses of carboplatin at 400 mg/m2, were administered intravenously over 1 hour without hydration every 3 to 4 weeks. One patient achieved complete response (CR). Four patients with a residual mass were observed, in two of them the mass disappeared and they remained free of disease. Two of the 4 patients with a residual mass relapsed 11 and 19 months after the start of treatment, and were successfully salvaged with surgery and adjuvant EP (etoposide and cisplatin) therapy. Subsequently, the overall CR rate was 60% and overall survival rate was 100%. The side effects of carboplatin were compared with those of VAB6 (vinblastine, actinomycin-D, bleomycin, cisplatin and cyclophosphamide), with which another 5 patients were previously treated at our hospital. Leukopenia and alopecia were observed in the VAB6 group with a significant difference (p < 0.05). Severe thrombocytopenia, dyspnea, skin rash, tinnitus and numbness were observed in 4 patients in the VAB6 group. However, no other symptoms but nausea and vomiting were observed in the carboplatin group. It was concluded that single agent carboplatin therapy for advanced seminoma was effective and less toxic, and it would be beneficial for the quality of life of patients, but the residual mass should be treated with surgery, cisplatin-based chemotherapy, or radiotherapy because it possibly has a recurrent potential; otherwise it should be carefully observed.