Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease characterized by progressive cartilage degeneration, abnormal bone remodeling, and chronic pain. In this study, we aimed to investigate effective therapies to reverse or suppress TMJOA progression. DESIGN: To this end, we performed intravenous administration of serum free conditioned media from human exfoliated deciduous teeth stem cells (SHED-CM) into a mechanical-stress induced murine TMJOA model. RESULTS: SHED-CM administration markedly suppressed temporal muscle inflammation, and improved bone integrity and surface smoothness of the destroyed condylar cartilage. Moreover, SHED-CM treatment decreased the number of IL-1ß, iNOS, and MMP-13 expressing chondrocytes, whereas it specifically increased PCNA-positive cells in the multipotent polymorphic cell layer. Notably, the numbers of TdT-mediated dUTP nick end labeling (TUNEL)-positive apoptotic chondrocytes in the SHED-CM treated condyles were significantly lower than in those treated with DMEM, whereas the proteoglycan positive area was restored to a level similar to that of the sham treated group, demonstrating that SHED-CM treatment regenerated the mechanical-stress injured condylar cartilage and subchondral bone. Secretome analysis revealed that SHED-CM contained multiple therapeutic factors that act in osteochondral regeneration. CONCLUSIONS: Our data demonstrated that SHED-CM treatment promoted the regeneration and repair of mechanical-stress induced mouse TMJOA. Our observations suggest that SHED-CM has potential to be a potent tissue-regenerating therapeutic agent for patients with severe TMJOA.

Extracellular Vesicles of Stem Cells to Prevent BRONJ.

Extracellular vesicles (EVs), several tens to hundreds of nanometers in size, are vesicles secreted by cells for intercellular communication. EVs released from mesenchymal stem cells (MSC-EVs) have the potential to treat multiple diseases. This study aimed to determine the effects of MSC-EVs on bisphosphonate-related osteonecrosis of the jaw (BRONJ), whose pathogenesis and treatment are not yet established. To this end, zoledronic acid (ZOL) was administered to bone marrow cells and fibroblasts in vitro. In vivo, a BRONJ model was produced by administering ZOL to rats and extracting teeth. Each MSC-EV-treated and nontreated group was compared histologically and molecularly. In vitro, the nontreated group showed an increased number of ß-galactosidase-positive cells and expression of senescence-associated genes p21, pRB and senescence-related inflammatory cytokines. Conversely, MSC-EV administration decreased the number of senescent cells and expression levels of p21, pRB and inflammatory cytokines. In vivo, in the nontreated group, the socket was partially uncovered by the oral epithelium, leaving an exposed bone. Conversely, in the MSC-EV-treated group, the socket was healed. Besides, in the nontreated group, ß-galactosidase-positive cells existed in the socket and colocalized with the CD90 and periostin-positive cells. However, there were few ß-galactosidase-positive cells in the MSC-EV-treated group. Furthermore, gene expression of stem cell markers Bmi1 and Hmga2 and the vascular endothelial marker VEGF was significantly increased in the MSC-EV-treated group, compared with that in the nontreated group. These results indicate that MSC-EVs prevent ZOL-induced senescence in stem cells, osteoblasts, and fibroblasts and reduce inflammatory cytokines. Furthermore, administration of MSC-EVs prevented senescence of cells involved in wound healing and the spread of chronic inflammation around senescent cells, thereby promoting angiogenesis and bone regeneration and preventing BRONJ.

Testicular sperm extraction and ICSI in patients with post-chemotherapy non-obstructive azoospermia.

146 MD-TESE procedures were performed in 74 patients presenting with non-obstructive azoospermia (NOA). Five of the 74 patients displayed a history of chemotherapy. Etiology of chemotherapies included testicular cancer, osteosarcoma, Ewing sarcoma, and malignant lymphoma of the stomach. Post-chemotherapy duration was 2.5-18 years. All patients underwent MD-TESE using local anesthesia with spermatic block and sedation. Extracted sperm was cryopreserved for ICSI. Histopathologic examination revealed Sertoli cell-only syndrome in all five patients; however, sperm were retrieved in 3 subjects. Post-chemotherapy MD-TESE and ICSI can be applied successfully in some patients with NOA. However, freezing semen prior to chemotherapy is recommended.

Alveolar cleft osteoplasty using tissue-engineered osteogenic material.

The use of tissue-engineered osteogenic material comprising platelet-rich plasma and autologous mesenchymal stem cells isolated, expanded and induced to osteogenic potential in bone augmentation procedures as a replacement for autologous bone grafts, offers predictable results with minimal donor-site morbidity. This material was applied for an alveolar cleft osteoplasty of a 9-year-old female patient. Serial computed tomograms showed the regenerated bone extending from the cleft walls after 3 months and bridging the cleft after 6 months, with 79.1% of the grafted region after 9 months at the time when the canine and lateral incisor in the affected side erupted in the reconstructed alveolar ridge.

Probability of sperm recovery in non-obstructive azoospermic patients presenting with testes volume less than 10 ml/FSH level exceeding 20 mIU/ml.

We evaluated the sperm recovery rate in non-obstructive azoospermia (NOA) patients presenting with bilateral testicular atrophy characterized by testes volume of less than 10ml and FSH levels exceeding 20 mIU/ml (group NOA-1), and compared the results to those NOA cases displaying unilateral testis volume exceeding 10 ml or FSH levels less than 20 mIU/ml (group NOA-2). Sperm retrieval was conducted in 261 azoospermic patients from April 1995 to December 2002. Forty-six NOA-1 and 37 NOA-2 individuals underwent microdissection TESE or 3-4 standard biopsies. Sperm recovery was achieved in 11 (24%) and 12 (32%) cases in NOA-1 and NOA-2, respectively. All couples received ICSI. Four clinical pregnancies (36.3%) in NOA-1 and two (17%) in NOA-2 resulted. Five subsequent healthy deliveries were obtained. NOA patients presenting with bilateral severe atrophic testes volume and obviously elevated FSH levels exhibited approximately 24% probability of sperm recovery. On the other hand, NOA characterized by testicular atrophy or elevated FSH levels displayed probability of approximately 32%. Differences in sperm recovery were not evident between NOA-1 and NOA-2. No successful pre-operative predictors of sperm recovery were identified.

Body posture during sleep and disc displacement in the temporomandibular joint: a pilot study.

Many possible factors associated with internal derangement of the temporomandibular joint (TMJ) have been discussed, but the causal factors remain unproven. The present study aimed to investigate habitual body posture during sleep (HBP) of patients with anterior disc displacement (ADD) in the TMJ. The sample comprised 87 patients (12 males, 75 females) aged 13-68 years (mean 25 years) and diagnosed by magnetic resonance imaging as having unilateral or bilateral ADD in the TMJ. The HBPs were classified into five categories: supine, prone, right lateral, left lateral, and no-dominant positions. Of the 50 patients with the unilateral ADD, 33 (66%) had the ipsilateral HBP to the affected joint while none (0%) had the contralateral HBP. This contrast showed that the HBP was a possible contributing factor to the ADD. It was suggested that HBP allows the ipsilateral condyle to displace posteriorly and this posterior position causes relative ADD.

Treatment of oligoasthenozoospermia with tranilast, a mast cell blocker, after long-term administration.

The authors retrospectively examined whether long-term administration of tranilast improves semen parameters in severe oligoasthenozoospermia. Fifty-two patients presenting with sperm concentration of less than 10 x 10(6) sperm/mL were enrolled. Subjects were partitioned into 3 groups as follows: patients displaying an atrophic testis with elevated (FSH) (group 1), patients exhibiting normal testicular volume with elevated FSH (group 2), and patients with normal testicular volume and normal FSH levels (group 3). Tranilast (300mg/day) was administered until pregnancy was achieved or for a period of up to 12 months. Sperm concentration was significantly increased at 3 months in 16 subjects (44%) in groups 1 and 3. In group 2, sperm concentration was increased at 12 months (5 of 16 subjects; 31%). Total sperm count was obviously elevated at 3 months in groups 1 and 2, and at 6 months in group 3. Six pregnancies were achieved via natural intercourse. Tranilast, a mast cell blocker, demonstrates a certain clinical benefit in terms of improvement of semen parameters involving severe oligoasthenozoospermia, but it does not appear to afford clinical benefit in long-term administration.

Leukocyte apheresis using a centrifugal cell separator in refractory ulcerative colitis: a multicenter open label trial.

Recently, successful results of ulcerative colitis (UC) treatments with leukocyte apheresis have been reported by several institutes. To certify the efficacy of leukocyte apheresis in refractory UC patients, a multicenter open label trial was conducted, and results were analyzed. Fifty patients diagnosed with active steroid-resistant UC were enrolled in this study from 14 medical centers. Using a centrifugal cell separator (Component Collection System, Haemonetics), leukocyte apheresis was performed once a week for 5 weeks. General conditions and abdominal symptoms were recorded daily, and laboratory tests were followed weekly. Changes of colonoscopic and histological manifestations of luminal activity through the study period were evaluated. At the end of the study period, stool frequency was decreased to less than 4 times a day in 68.4% (26 of 38) and serum C-reactive protein (CRP) concentration was normalized in 56.7% (17 of 30) of the patients. Colonoscopic remission was achieved in 57.7% (26 of 45), and histological improvement was noted in 54.1% (20 of 37) of the patients tested. Improved disease activity was demonstrated in 74% (37 of 50) of the patients by general assessment criteria. Analysis of the trial data confirmed the valid clinical efficacy of leukocyte apheresis by centrifugal cell separator in refractory UC patients.

The treatment with tranilast, a mast cell blocker, for idiopathic oligozoospermia.

Although many drug treatments have been reported to theoretically improve semen parameters in male infertility, a standard method has not been established. The authors examined whether tranilast, a mast cell blocker, improves fertility and/or semen parameters in severe oligozoospermia. Seventeen patients with a sperm density of less than 10 x 10(6) sperm/mL and their fertile partners were enrolled in this study. Patients were prescribed tranilast 300 mg/day for at least 12 weeks. Semen and blood samples were collected before and after the prescription of tranilast for 12 weeks. Semen parameters, serum gonadotropins, luteinizing hormone, follicle-stimulating hormone, serum testosterone, and testicular size were evaluated. One patient complained of mild drowsiness during treatment. The sperm count was significantly increased after administration of tranilast in 7 patients (41.1%), although sperm motility was not altered. Semen volume and normal morphology were also unaltered. Three pregnancies were achieved. Endocrine profile and testicular size were unchanged. Tranilast, a mast cell blocker, is clinically useful for the treatment of severe idiopathic oligozoospermic men.

Holmium:YAG laser endoureterotomy in the treatment of ureteroenteric stricture following Indiana urinary diversion.

A 57-year-old man who had received radical urethrocystectomy and Indiana urinary diversion 6 months earlier was treated for ureteroenteric anastomosis stricture (left side) using a Holmium:YAG laser via antegrade approach. The availability of small (6.9 Fr) flexible ureteroscope, as well as the use of the Holmium:YAG laser has facilitated the ability to precisely incise the stricture under direct endoscopic visualization. The technique is described for laser endoureterotomy in a patient with ureteroenteric stricture following Indiana urinary diversion.

CA19-9-producing transitional cell carcinoma of the renal pelvis: a case report.

We report a case of CA19-9-producing transitional cell carcinoma of the renal pelvis. A 59-year-old male patient with left hydronephrosis was referred to us from a local physician. Retrograde pyelogram revealed irregular filling defects involving calices, pelvis and proximal ureter. The serum CA19-9 level was elevated. Under the diagnosis of renal pelvic tumor, we performed radical left nephroureterectomy. The tumor was histologically diagnosed as transitional cell carcinoma. The tumor cells showed positive immunostaining for CA19-9. The serum CA19-9 level was normalized after the operation. To our knowledge, this is the 28th case of a CA19-9-producing tumor in the Japanese literature.

Endoscopic ureteral incision using the holmium:YAG laser.

BACKGROUND: We reviewed the results of endoscopic ureteral incision for benign ureteral stricture, ureteropelvic junction obstruction and ureteroenteroanastomotic stricture using the holmium laser. METHODS: We carried out endoscopic ureteral incision using the holmium laser through an 8-Fr semirigid or 6.9-Fr flexible ureteroscope on 17 ureters in 15 patients. Balloon dilatation was not necessary before insertion of the ureteroscope. The stricture was incised with the holmium laser using a 200-365 microm fiber through the working channel of the ureteroscope. After completion of the incision, a 12-Fr double-J catheter was left for 6 weeks. Thereafter patients were followed by renal scan and/or ultrasound and excretory urography at 3-6 month intervals. RESULTS: The mean operative time was 65 min (18-135 min). The stricture resolved completely in 86.7% of cases at an average follow up of 20.5 months (11-32 months). CONCLUSIONS: The holmium laser endoscopic ureteral incision was associated with a good outcome in our series. We recommend this procedure to be employed initially because it is less invasive and has a favorable outcome.

Clinical study of transitional cell carcinoma of the prostate associated with bladder transitional cell carcinoma.

BACKGROUND: Transitional cell carcinoma of the prostate in patients with bladder cancer appears to influence the prognosis and affects the decision about therapeutic modality. Therefore, it is important to characterize transitional cell carcinoma associated with bladder cancer. METHODS: From April 1980 to December 1998, 81 male patients underwent total cystoprostatectomies for transitional cell carcinoma of the bladder. The 81 cystoprostatectomy specimens were examined to clarify the characteristics of prostatic involvement by transitional cell carcinoma. The extent, origin, mode of spread and risk factor of prostatic involvement as well as the prognosis were investigated. In 13 of 15 patients with prostatic involvement the prostate was examined by sequential step sections. RESULTS: Prostatic involvement was observed in 15 of 81 patients (18.5%). Prostatic urethral involvement, invasion to prostatic duct/acinus, prostatic stromal invasion and extraprostatic extension and/or seminal vesicle involvement were recognized in 12 (80%), 14 (93.3%), six (40%), and five (33.3%) of the 15 patients, respectively. Twelve of the 15 patients (80%) with prostatic involvement had papillary or non-papillary tumors (i.e. carcinoma in situ) both in the prostatic urethra and prostatic duct. In 10 of these 12 patients (88.3%), there was contiguity between prostatic urethral and ductal tumors. Seven of the 23 patients (30.4%) with carcinoma in situ of the bladder showed prostatic involvement, which increased to 50% in the presence of carcinoma in situ of the trigone or bladder neck. CONCLUSIONS: Eighty per cent of the patients with prostatic involvement showed papillary or non-papillary tumors both in the prostatic urethra and prostatic duct. There was a high level of contiguity between both tumors. Patients with carcinoma in situ of the trigone or bladder neck revealed significantly higher incidence of prostatic involvement.

Holmium laser incision technique for ureteral stricture using a small-caliber ureteroscope.

BACKGROUND AND OBJECTIVES: The holmium laser has a short absorption depth in tissue and possesses excellent properties both in ablation and hemostasis. We have performed endoscopic incision for ureteral stricture using the holmium laser through a small-caliber ureteroscope. METHODS: This method was used on five patients and seven ureters. The etiology of the stricture was stone scar in two patients, ureteroenteroanastomosis of Indiana urinary pouch in two, and primary in one. We used an 8F semi-rigid or 6.9F flexible ureteroscope. No prior procedures, such as balloon dilation, were necessary in any of the cases. The stricture was incised with the holmium laser using a 365-microm fiber through the working channel of the ureteroscope. The holmium laser operated at a wavelength of 2100 nm, with an output of 1.0 J/pulse at a rate of 10 Hz. After completion of the incision, a 12F Double-J catheter was left in for six weeks. RESULTS: The mean operative time was 89 minutes. The stricture resolved completely in all cases at an average follow-up of 8.6 months. CONCLUSIONS: The holmium laser incision for ureteral stricture using a small-caliber ureteroscope is an easy-to-perform, safe and effective procedure.

Microsurgical vasoepididymostomy with sperm cryopreservation for future assisted reproduction.

BACKGROUND: Although obstructive azoospermia is treatable with microscopic seminal reconstruction, the number of patients who choose to undergo vasoepididymostomy is limited because of recent advances in assisted reproductive technology (ART). We attempted to define the outcome of surgical reconstruction in patients with suspected epididymal obstruction and no previous history of vasectomy. METHODS: We described 40 eligible end-to-side vasoepididymostomy procedures performed on 24 azoospermic patients who had either bilateral or unilateral epididymal obstruction. RESULTS: The overall patency rate following surgery was 54% (13/24) and for four patients (17%), natural intercourse resulted in pregnancy. Two pregnancies were initiated with intracytoplasmic sperm injections using frozen sperm collected during vasoepididymostomy. CONCLUSIONS: In the era of modern ART, microsurgical vasoepididymostomy with cryopreservation of sperm collected during the operation is recommended for patients with epididymal obstructions.

Clinical study on recurrence in bladder cancer patients undergoing total cystectomy--statistical analysis of factors related to recurrence.

A clinico-pathological study was performed retrospectively for 77 patients undergoing total cystectomy for primary transitional cell carcinoma of the urinary bladder between 1981 and 1995 to clarify the mode of recurrence, the risk factors which may affect recurrence following cystectomy and prognostic factors. Postoperative recurrence was recognized in 27 (35.1%) out of 77 patients and the one-, two- and three-year non-recurrent rates by the Kaplan-Meier method were 75.3, 64.9% and 63.3%, respectively. The duration from cystectomy to recurrence was 1 to 102 months with a mean of 12.1 months, and approximately 92.6% of recurrence occurred within two years. Among 27 patients with recurrence, pelvic recurrence, distant metastasis, both of them and urethral recurrence were recognized in 6 (22.2%), 18 (66.7%), 1 (3.7%) and 2 (7.4%), respectively as the first site of recurrence. The overall one-, three- and five-year cause-specific survival rates of the 77 patients were 84.7, 71.1% and 65.6%, respectively. Of the 27 patients with recurrence, 25 (92.6%) died of bladder cancer. Of the factors related to recurrence or prognosis, pathological stage, lymphatic invasion, venous invasion, type of infiltration and lymph node metastasis but not pathological grade or adjunctive chemotherapy were significant risk factors for recurrence and prognostic factors in univariate analysis. However, lymphatic invasion was the only significant risk factor for recurrence and prognosis in multivariate analysis using Cox's proportional hazard model.

[Clinical study on poor-risk patients with non-seminomatous germ cell tumor].

Between 1988 and 1996, we treated 11 poor-risk patients with non-seminomatous germ cell tumors (NSGCT) at Nagoya University Hospital. "Poor-risk" was defined as i) advanced disease equal to or greater than class 7 of the Indiana University Classification (7 patients), ii) primary mediastinal extragonadal NSGCT (2), iii) tumor markers not normalized by the induction chemotherapy (1) or iv) primary retroperitoneal NSGCT with multiple lung metastases (1). Two patients with mediastinal tumors died during the chemotherapy. The minimal volume of fluid must be administered to patients with giant mediastinal tumors. The tumor marker normalized during the induction chemotherapy in only three patients. Three patients, whose tumor markers elevated during or one month after the induction chemotherapy, eventually died of cancer. The tumor markers in five of the seven patients which had not normalized during the induction chemotherapy, had decreased to the normal range during the salvage chemotherapy and two of the five subsequently achieved the status of "no evidence of disease" (NED). Six patients with and two without normalized tumor markers underwent retroperitoneal lymph nodes dissection and/or resection of residual tumors. Pathological examination of the resected tumors showed necrosis/fibrosis in five patients and two had elevated tumor markers immediately after the surgery and eventually died of the disease. Overall, eight (73%) of 11 poor-risk patients achieved a complete response but only five (45%) eventually achieved a NED status that was maintained (6.6 +/- 3.0 years). Our results were not satisfactory, and we believe that new strategies, such as early high-dose chemotherapy, are required for poor-risk patients, who are not likely to respond well to the induction chemotherapy.

Modified osteosynthesis for condylar neck fractures in atrophic mandibles.

A fixation system combining both plate and lag screw osteosynthesis for condylar neck fractures of the mandible is described. The currently available device is adapted in that the lag screw is inserted in the lateral cortical bone of the condylar segment instead of the cancellous bone alone.

Renal fossa recurrence of a renal cell carcinoma 13 years after nephrectomy: a case report.

Between 1980 and 1995, we performed a nephrectomy with curative intent on 183 patients with renal cell carcinoma at Nagoya University Hospital. Among these patients, 5 (2.7%) developed renal fossa recurrence (median follow-up, 65 months). We report a case of such a recurrence found 13 years after a nephrectomy for renal cell carcinoma (stage pT3a, pN0, M0). A 62-year-old female presented with a nodule on her back. Computed tomography and magnetic resonance imaging revealed a mass in the right back and retroperitoneum, and a biopsy revealed the tumor to be a renal cell carcinoma. Complete resection was performed, followed by administration of alpha-interferon. The patient is doing well 16 months after the operation. The case illustrates that very long-term follow-up after a nephrectomy is mandatory for patients with perinephric invasion of a renal cell carcinoma due to the risk of renal fossa recurrence.