Transvaginal Polytetrafluoroethylene Mesh Surgery for Pelvic Organ Prolapse: One-Year Safety and Efficacy Results.

OBJECTIVE: To evaluate the efficacy and safety of the polytetrafluoroethylene (PTFE) mesh by comparing conventionally used polypropylene (PP) mesh in tension-free vaginal mesh (TVM) surgery for pelvic organ prolapse (POP). METHODS: We conducted an observational cohort study of patients who underwent TVM using a PTFE or PP mesh. PTFE was used from June 2019 to May 2021, and PP mesh from January 2018 to May 2019. Outcomes included POP recurrence, perioperative complications, and patient satisfaction. Restricted mean survival time was used to analyze POP recurrence, comparing the time to recurrence between the two groups at 1year after TVM. RESULTS: Of 171 patients, 104 underwent PP mesh placement (PP group) and 67 underwent PTFE mesh placement (PTFE group). POP recurrence was observed in 10 and nine patients in the PP and PTFE groups, respectively. The mean time until the recurrence in the PTFE group was significantly shorter than that in the PP group (restricted mean survival time difference: -20.3days; 95% CI, -40.1 to -0.5; P = .044). Subgroup analysis revealed the meantime until recurrence was significantly shorter in the PTFE group for postoperative periods 3months or less, ages >70years, and POP stage ≥3. There were no intervention cases in either group and no significant differences in the perioperative complications. Patient satisfaction was greater in the PTFE group after 3months postoperatively. CONCLUSION: TVM surgery with a PTFE mesh is more prone to recurrence than that with a PP mesh, but with higher patient satisfaction. Within 3months of surgery, elderly patients and those with advanced-stage POP require care to prevent recurrence.

[A Case of IgG4-Related Disease Arising in Female Periurethra].

A 67-year-old female, with a past medical history of IgG4-related Mikulicz disease, was referred to our department for a periurethral mass revealed by contrast-enhanced computed tomography. She presented with weak urine flow a half year before the first consultation. Magnetic resonance imaging (MRI) revealed a periurethral mass, 39×39×29 mm, extending from the bladder neck to the urethral meatus. Serum IgG4 level was elevated to 580 mg/dl. Histological examination by the transvasinal biopsy revealed a lymphocytic infiltrate with IgG4-positive plasmacytoid predominance, leading to the diagnosis of IgG4-related disease arising in the periurethra. She was treated with prednisolone for 4 months, and urinary disturbance disappeared. MRI showed that the periurethral mass decreased in size.

[A Case of Ipsilateral Multifocal Renal Cell Carcinoma Treated with Robot-Assisted Partial Nephrectomy].

A 55-year-old male was referred to our hospital for left lower back pain. Computer tomography suggested a left ureteral stone and two left renal tumors at ventral and lateral sites. The ventral tumor measured 7 mm, and it showed intense early enhancement. On the other hand, the lateral tumor measured 22 mm, and it was enhanced weakly. We performed a single-stage robot-assisted partial nephrectomy, because he had chronic renal insufficiency and the two tumors appeared to be different types of renal cell carcinoma. Pathological examination revealed the ventral tumor was clear cell renal cell carcinoma, while the lateral tumor was papillary renal cell carcinoma. He is free of recurrence 1 year and 2 months after operation.

[A Case of Retroperitoneal Primary Castleman's Disease which was Difficult to Differentiate from Liposarcoma].

A 38-year-old man had a right lower retroperitoneal mass found by abdominal echography in a medical examination, and he consulted the internal medicine of Sumitomo Hospital. On the suspicion of malignant lymphoma, he received a laparotomy with biopsy. Pathological examination revealed that the tumor was either benign lymphadenopathy or low-grade malignant lymphoma, and he was follow-up. Two years later, he was introduced to our department because the follow-up computed tomography revealed signs of a tumor and a mass of adjunctive adipose tissue that increased markedly. Thus, we suspected that the tumor was liposarcoma before the operation, and performed retroperitoneal tumor resection. However, we found that the tumor was pathologically a hyaline vascular type of Castleman's disease and the pathological examination showed no malignant cells in the peritumoral adipose tissue. Since Castleman's disease lacks the characteristic symptoms or image findings, the preoperative diagnosis is generally difficult. Cases with growth of the peritumoral adipose tissue are rare, and the differentiation from the liposarcoma is usually difficult. We discussed how to perform the differential diagnosis of Castleman's disease, and especially about the differential diagnosis of liposarcoma.

[A Case of Androgen Insensivity Syndrome with a Seminoma in the Abdominal Undescended Testis].

A 48-year-old female was referred to our hospital for further urological examination of primary amenorrhea. She had been suffering from amenorrhea since 12 years old. Although she had normal female external genitalia, she had a blind-ended vagina with complete absence of the uterus.Laboratory tests showed high testosterone level and the 46 XY karyotype. Thus, our diagnosis was androgen insensivity syndrome. Magnetic resonance imaging showed bilateral intra-abdominal testes. We performed laparoscopic bilateral gonadalectomy. Pathological diagnosis was seminoma in the right gonad. She is free of recurrence 6 months after operation.

Inhibition of ß2-microglobulin/hemochromatosis enhances radiation sensitivity by induction of iron overload in prostate cancer cells.

BACKGROUND: Bone metastasis is the most lethal form of several cancers. The ß2-microglobulin (ß2-M)/hemochromatosis (HFE) complex plays an important role in cancer development and bone metastasis. We demonstrated previously that overexpression of ß2-M in prostate, breast, lung and renal cancer leads to increased bone metastasis in mouse models. Therefore, we hypothesized that ß2-M is a rational target to treat prostate cancer bone metastasis. RESULTS: In this study, we demonstrate the role of ß2-M and its binding partner, HFE, in modulating radiation sensitivity and chemo-sensitivity of prostate cancer. By genetic deletion of ß2-M or HFE or using an anti-ß2-M antibody (Ab), we demonstrate that prostate cancer cells are sensitive to radiation in vitro and in vivo. Inhibition of ß2-M or HFE sensitized prostate cancer cells to radiation by increasing iron and reactive oxygen species and decreasing DNA repair and stress response proteins. Using xenograft mouse model, we demonstrate that anti-ß2-M Ab sensitizes prostate cancer cells to radiation treatment. Additionally, anti-ß2-M Ab was able to prevent tumor growth in an immunocompetent spontaneous prostate cancer mouse model. Since bone metastasis is lethal, we used a bone xenograft model to test the ability of anti-ß2-M Ab and radiation to block tumor growth in the bone. Combination treatment significantly prevented tumor growth in the bone xenograft model by inhibiting ß2-M and inducing iron overload. In addition to radiation sensitive effects, inhibition of ß2-M sensitized prostate cancer cells to chemotherapeutic agents. CONCLUSION: Since prostate cancer bone metastatic patients have high ß2-M in the tumor tissue and in the secreted form, targeting ß2-M with anti-ß2-M Ab is a promising therapeutic agent. Additionally, inhibition of ß2-M sensitizes cancer cells to clinically used therapies such as radiation by inducing iron overload and decreasing DNA repair enzymes.

Serum heat shock protein 47 levels are elevated in acute exacerbation of idiopathic pulmonary fibrosis.

Little is known about the pathophysiology of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is essential for biosynthesis and secretion of collagen molecules. Previous studies in experimental animal fibrosis models have shown that downregulation of HSP47 expression reduces collagen production and diminishes fibrosis progression. In this study, serum HSP47 levels were evaluated to elucidate pathogenic differences involving HSP47 between AE-IPF and stable (S)-IPF. Subjects comprised 20 AE-IPF and 33 S-IPF patients. Serum levels of HSP47, Krebs von den Lungen-6 (KL-6), surfactant protein (SP)-A, SP-D, and lactate dehydrogenase (LDH) were measured. Immunohistochemical analysis of lung HSP47 expression was determined in biopsy and autopsy tissues diagnosed as diffuse alveolar damage (DAD) and usual interstitial pneumonia (UIP). Serum levels of HSP47 were significantly higher in AE-IPF than in S-IPF patients, whereas serum levels of KL-6, SP-A, and SP-D did not differ significantly. Receiver operating characteristic curves revealed that HSP47 was superior for discriminating AE-IPF and S-IPF. The cutoff for HSP47 resulting in the highest diagnostic accuracy was 559.4 pg/mL; sensitivity, specificity, and diagnostic accuracy were 100.0%, 93.9%, and 96.2%, respectively. Immunohistochemical analysis revealed that pulmonary HSP47 expression was greater in DAD than UIP tissues. Serum HSP47 was significantly higher in AE-IPF than in S-IPF patients, suggesting that underlying fibrogenic mechanisms involving HSP47 differ in the two conditions.

Water avoidance stress induces frequency through cyclooxygenase-2 expression: a bladder rat model.

OBJECTIVES: Water avoidance stress is a potent psychological stressor and it is associated with visceral hyperalgesia, which shows degeneration of the urothelial layer mimicking interstitial cystitis. Cyclooxygenase-2 inhibitors have been recognized to ameliorate frequency both in clinical and experimental settings. We investigated the voiding pattern and cyclooxygenase-2 expression in a rat bladder model of water avoidance stress. METHODS: After being subjected to water avoidance stress or a sham procedure, rats underwent metabolic cage analysis and cystometrography. Real time reverse transcription polymerase chain reaction was carried out to examine cyclooxygenase-2 messenger ribonucleic acid in bladders of rats. Protein expression of cyclooxygenase-2 was analyzed with immunohistochemistry and western blotting. Furthermore, the effects of the cyclooxygenase-2 inhibitor, etodolac, were investigated by carrying out cystometrography, immunohistochemistry and western blotting. RESULTS: Metabolic cage analysis and cystometrography showed significantly shorter intervals and less volume of voiding in water avoidance stress rats. Significantly higher expression of cyclooxygenase-2 messenger ribonucleic acid was verified by reverse transcription polymerase chain reaction. Immunohistochemistry and western blotting showed significantly higher cyclooxygenase-2 protein levels in water avoidance stress bladders. Furthermore, immunohistochemistry showed high cyclooxygenase-2 expression exclusively in smooth muscle cells. All water avoidance stress-induced changes were reduced by cyclooxygenase-2 inhibitor pretreatment. CONCLUSIONS: Chronic stress might cause frequency through cyclooxygenase-2 gene upregulation in bladder smooth muscle cells. Further study of cyclooxygenase-2 in the water avoidance stress bladder might provide novel therapeutic modalities for interstitial cystitis.

Tumor-stroma co-evolution in prostate cancer progression and metastasis.

Cancer development is complex and involves several layers of interactions and pleotropic signaling mechanisms leading to progression. Cancer cells associate with resident stromal fibroblasts, smooth muscle cells, macrophages, endothelium, neurons and migrating cells at metastatic sites and phenotypically and genotypically activate them. These become an integral part of the cancer cell community through activated cell signaling mechanisms. During this process, the cancer cells and cells in the cancer microenvironment "co-evolve" in part due to oxidative stress, and acquire the ability to mimic other cell types (which can be termed osteomimicry, vasculomimicry, neuromimicry and stem cell mimicry), and undergo transition from epithelium to mesenchyme with definitive morphologic and behavioral modifications. In our laboratory, we demonstrated that prostate cancer cells co-evolve in their genotypic and phenotypic characters with stroma and acquire osteomimetic properties allowing them to proliferate and survive in the skeleton as bone metastasis. Several signaling interactions in the bone microenvironment, mediated by reactive oxygen species, soluble and membrane bound factors, such as superoxide, beta2-microglobulin and RANKL have been described. Targeting the signaling pathways in the cancer-associated stromal microenvironment in combination with known conventional therapeutic modalities could have a synergistic effect on cancer treatment. Since cancer cells are constantly interacting and acquiring adaptive and survival changes primarily directed by their microenvironment, it is imperative to delineate these interactions and co-target both cancer and stroma to improve the treatment and overall survival of cancer patients.

[A case of metachronous testicular tumor developing seven years after complete remission of retroperitoneal extragonadal germ cell tumor].

A 26-year-old man was admitted to our hospital with a chief complaint of left cervical lymphadenopathy. He was diagnosed as having seminoma by needle biopsy. Computed tomography revealed an aorto-caval retroperitoneal tumor. Levels of lactic deydrogenase, human beta-chorionic gonadotropin, alpha-fetoprotein were not elevated. No abnormal findings were present on palpation and ultrasonography of the testes. The patient was diagnosed as having a retroperitoneal extragonadal germ cell tumor (EGCT). Three courses of chemotherapy (bleomycin, etoposide and cisplatin) and another course of chemotherapy (etoposide, ifosfamide and cisplatin) were performed. Complete remission was achieved. Seven years later, the patient noticed an enlargement of his right scrotal contents. Neither distant metastasis nor lymph node metastasis was detected by computed tomography. Right radical orchiectomy was performed and histology revealed seminoma with yolk sac tumor components. No recurrence has been seen after 10 months.

[Idiopathic elephantiasis of the penis: a case report].

We report a case of idiopathic elephantiasis of penis. A 41-year-old man was refered to our hospital with a painful penile swelling and severe miction pain. He had no particular past or familial history, and had never been to tropical or semitropical region. Physical examination showed a prominent swelling and flection of his penis. Magnetic resonance imaging revealed a significant thickening of the penile skin and subcutaneous tissue. Due to the difficulty of voiding, an urethral catheter was placed. The penile skin biopsy showed no malignancy. Under the diagnosis of penile elephantiasis, the resection of abnormal penile skin and penile plasty with the split skin graft from his thigh was performed. Histopathological findings showed nonspecific inflammation. The skin graft was successfully adapted. He could urinate smoothly without pain after the urethral catheter was removed. There has been no recurrence 6 months after the operation. He recovered normal micturition and sexual function.

Relationship between substances in seminal plasma and Acrobeads Test results.

OBJECTIVE: To asses the effects of seminal plasma on sperm function. DESIGN: Retrospective case-control study. SETTING: University hospital. PATIENT(S): One hundred fourteen infertile men. INTERVENTION(S): Acrobeads Test scores (0-4) and measurement of interleukin (IL)-6, soluble IL-6 receptor, epidermal growth factor, insulin-like growth factor-I (IGF-I), transforming growth factor-beta I, superoxide dismutase, calcitonin, and macrophage migration inhibitory factor (MIF) levels in seminal plasma. MAIN OUTCOME MEASURE(S): Kruskal-Wallis test to compare the concentrations of substances as a nonparametric test for differences among Acrobeads Test scores and a multivariable logistic regression model to find independent risk factors associated with abnormal Acrobeads Test results. RESULT(S): The Acrobeads Test score was 0 for 7 samples, 1 for 20 samples, 2 for 18 samples, 3 for 28 samples, and 4 for 41 samples. Age, abstinence period, and semen parameters, except for sperm motility and percentage of sperm with abnormal morphology, had no effect on the Acrobeads Test results. Concentrations of IGF-I and MIF were significantly higher in patients with abnormal Acrobeads Test results. Multivariate analysis indicated that MIF and IGF-I were significantly associated with abnormal Acrobeads Test results (scores 0 to 1). CONCLUSION(S): Although further studies are needed, IGF-I and MIF in seminal plasma may have negative effects on sperm function.

High serum concentrations of autoantibodies to HSP47 in nonspecific interstitial pneumonia compared with idiopathic pulmonary fibrosis.

BACKGROUND: The pathological diagnosis of idiopathic interstitial pneumonias (IIP) by surgical lung biopsy is important for clinical decision-making. However, there is a need to use less invasive biomarkers to differentiate nonspecific interstitial pneumonia (NSIP) from other IIP such as usual interstitial pneumonia (UIP). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen. HSP47 is increased in various fibrotic diseases. We investigated the autoantibodies to HSP47 in IIPs. METHODS: We measured the serum levels of the autoantibodies to HSP47 in 38 patients with various forms of IIP [16 with idiopathic pulmonary fibrosis (IPF), 15 with idiopathic NSIP, 7 with cryptogenic organizing pneumonia (COP)] and 18 healthy volunteers. RESULTS: The serum levels of autoantibodies to HSP47 in patients with idiopathic NSIP were significantly higher than in patients with IPF (P < 0.01), COP (P < 0.05), and healthy volunteers (P < 0.05). In addition, those in fibrosing NSIP were significantly higher than those of cellular and fibrosing NSIP (p < 0.05). CONCLUSION: We found high levels of anti-HSP47 autoantibody titers in sera of patients with idiopathic fibrosing NSIP compared with other IIPs and healthy volunteers.

Early efficacy of silodosin in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVES: To evaluate the early efficacy of the alpha(1A)-adrenoceptor selective drug, silodosin, for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia. METHODS: A total of 68 patients with an International Prostate Symptom Score (IPSS) of >==8 and a Quality of Life (QOL) index of >==2 were included. Changes in the IPSS and QOL index were evaluated before and after 1, 2, 3, 4, 5, 6, 7, 14, and 28 days of twice daily oral administration of 4 mg silodosin. Next, changes in IPSS subscores as well as voiding, storage, and post micturition symptoms were assessed. Changes in total IPSS based on symptom severity were also determined. RESULTS: Total IPSS and QOL index improved significantly from 19.38 +/- 7.46, 4.68 +/- 1.07 at baseline to 15.81 +/- 7.40, 4.22 +/- 1.30 at day 1. The subscores of voiding, storage, and post micturition symptoms were significantly decreased from 8.93 +/- 3.95, 7.97 +/- 3.88, and 2.49 +/- 1.70 at baseline to 7.28 +/- 4.09, 6.52 +/- 3.47, and 2.02 +/- 1.56 at day 1, respectively. This trend continued throughout the study. Regardless of severity, total IPSS were significantly decreased at day 1 and maintained throughout the study. CONCLUSIONS: Silodosin may be considered a promising treatment for benign prostatic hyperplasia/lower urinary tract symptom patients.

Effect of human leukemia cells in testicular tissues grafted into immunodeficient mice.

OBJECTIVES: To preserve the fertility of prepubertal boys with childhood cancer, it has been proposed that testicular tissues could be harvested before treatment and then immature germ cells matured by xenografting under the skin of immunodeficient mice. However, malignant cells present in the testicular tissue may disturb spermatogenesis in the xenografts. Here we examined the effect of human leukemia cells on ectopic xenografts in immunodeficient mice. METHODS: First, in order to evaluate the tumor forming ability of Human leukemia cells (Jurkat cells), different amounts of these cells were injected into nude mice and analyzed 8 weeks later. Testicular tissues from 5-week-old donor SCID mice injected with Jurkat cells were xenografted under the skin of recipient nude mice. After 8 weeks, xenografts were histologically evaluated and expression of testicular markers in xenografts was assessed. RESULTS: More than 1 x 10(6) Jurkat cells were necessary to develop a tumor under the skin of nude mice. Eight weeks after xenografting, 5 of 20 xenografts (25%) developed tumors. Spermatogenesis was not detected in any xenografts. Testicular cells were not detected in the tumor by the reverse transcription-polymerase chain reaction technique. CONCLUSIONS: Human leukemia cells infiltrating testicular tissue may disturb spermatogenesis in xenografts. Xenografting cannot be considered a reliable method for the detection of human leukemic cells in testicular tissues before auto-transplantation. Other measures should be developed to preserve the fertility of prepubertal boys with leukemia.

[A case report of prostatic stromal tumor of uncertain malignant potential (STUMP)].

Sarcomas and related proliferative lesions of specialized stroma of prostate are rare. Lesions have been classified into prostatic stromal tumor of uncertain malignant potential (STUMP) and prostatic stromal sarcoma (SS) based on the degree of stromal cellularity, presence of mitotic figures, necrosis, and stromal overgrowth. STUMPs are considered neoplastic, based on the observations that they may diffusely infiltrate the prostate gland and extend into adjacent tissues, and often recur. Although most cases of STUMP do not behave in an aggressive fashion, occasional cases have been documented to recur rapidly after resection and a minority have progressed to stromal sarcoma. Here we describe a case of STUMP. A 42-year-old male was seen at a hospital with the chief complaint of elevated levels of prostate specific antigen. Since digital examination revealed abnormal findings in the prostate, then he was referred to our hospital. We diagnosed STUMP by ultra-sound-guided needle biopsy of the prostate. Then we performed radical prostatectomy. Finally we made the pathological diagnosis of prostatic STUMP. Ten months later, there was no sign of metastasis or recurrence.

[Myxofibrosarcoma of the spermatic cord: a case report].

A 77-year-old man visited our department with a painless mass in the left scrotum. He underwent left high orchiectomy with clinical diagnosis of testicular tumor. The tumor penetrated deeply into the internal inguinal ring. The tumor was resected as proximally as possible with positive surgical margin at the internal ring. Macroscopically, the left testis was intact in the resected specimen. Microscopic examination revealed that the tumor was consisted of myxoid stroma with spindle cells, and there was a large variation in histological findings. Immunohistchemical staining was positive with vimentin, and negative with alphaSMA, S-100, Myo D1, EMA, keratin, HMB45, and LCA. Accordingly, the tumor was diagnosed as myxofibrosarcoma, high-grade, of the spermatic cord. Postoperative CT scanning revealed multiple retroperitoneal lymph node metastases. He underwent radiation therapy, but soon developed lung metastases and pleural dissemination, and died 2 months after the operation. Myxofibrosarcoma, which had been called myxoid MFH is one of the most common soft tissue sarcomas. Myxofibrosarcoma or myxoid MFH of the spermatic cord is a rare disease. To our knowledge, only 7 cases have been reported in Japan to date.

Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway in human corpus cavernosal smooth muscle cells.

INTRODUCTION: Vascular smooth muscle cells express endothelial nitric oxide synthase (eNOS) and produce nitric oxide (NO). Recently, increased NO production has been reported to induce the synthesis and secretion of vascular endothelial growth factor (VEGF) via the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Expression of eNOS in corpus cavernosal smooth muscle has also been reported. However, it is unclear whether CCSMCs can generate NO. AIM: To elucidate whether CCSMCs can synthesize NO and whether NO synthesis enhances VEGF synthesis via the NO/cGMP pathway. METHODS: Corpus cavernosal cells were cultured and characterized by immunocytochemistry and immunoblotting. CCSMCs were treated with L-arg. CCSMCs were also incubated with L-arg and with vardenafil, an inhibitor of PDE-5. MAIN OUTCOME MEASURES: Release of NO from cells was confirmed by assay of NO metabolites (NOx). Intracellular cGMP concentration and VEGF concentration in the medium were measured. RESULTS: Isolated cells were determined to be CCSMCs. The expression of eNOS by CCSMCs was also identified. NOx and cGMP levels in the L-arg-treated group were significantly greater than those in the control group. VEGF and cGMP levels in the L-arg-treated group were also significantly greater than those in the control group. VEGF and cGMP levels in the L-arg + vardenafil-treated group were significantly greater than those in the L-arg-treated group and the control group. CONCLUSIONS: CCSMCs express eNOS and synthesize NO. NO synthesis leads to enhancement of VEGF synthesis via the NO/cGMP pathway. Combined L-arg and vardenafil treatment, which can enhance VEGF production, may provide a novel therapeutic strategy for the treatment of erectile dysfunction as well as endothelial dysfunction in general.

Androgen decline in patients with nonobstructive azoospemia after microdissection testicular sperm extraction.

OBJECTIVES: Microdissection testicular sperm extraction (TESE) is the ideal procedure for obtaining a high sperm retrieval rate. However, few studies of the postoperative endocrinologic course have been reported. We evaluated the endocrinologic course for 1 year after microdissection TESE and compared the results with the testicular histologic findings. METHODS: A total of 69 patients with nonobstructive azoospermia who had undergone microdissection TESE were included. The overall sperm retrieval rate was 50.7%. The endocrinologic data were evaluated before and 3, 6, and 12 months after surgery. RESULTS: The mean serum total testosterone level in patients with hypospermatogenesis decreased postoperatively and had recovered by 12 months (102%). The mean serum total testosterone level in patients with Klinefelter syndrome also decreased postoperatively but had recovered to only 50% of the baseline value at 12 months after microdissection TESE. At 12 months, the mean serum total testosterone level in patients with maturation arrest was 93.1% of the preoperative level and that in patients with Sertoli cell-only syndrome was 80.6% of the preoperative level. The preoperative serum luteinizing hormone and follicle-stimulating hormone in patients with Klinefelter syndrome was high and remained high after microdissection TESE. The mean serum luteinizing hormone and follicle-stimulating hormone levels in patients with hypospermatogenesis did not change, and those in patients with maturation arrest increased continuously after microdissection TESE. Finally, those in patients with Sertoli cell-only syndrome increased up to 6 months after surgery and decreased after that. CONCLUSIONS: The results of our study indicate that long-term endocrinologic follow-up is necessary after microdissection TESE, particularly for patients with Klinefelter syndrome to detect hypogonadism.

Isolation of germ cells from leukemia and lymphoma cells in a human in vitro model: potential clinical application for restoring human fertility after anticancer therapy.

More than 70% of patients survive childhood cancer, but chemotherapy and radiation therapy may cause irreversible impairment of spermatogenesis. To treat infertility secondary to anticancer treatment for childhood cancer, we have developed a procedure to isolate germ cells from leukemic mice by fluorescence-activated cell sorting with two surface markers, and transplantation of isolated germ cells successfully restored fertility without inducing leukemia. In the present study, we analyzed human germ cells and human malignant cells, including five leukemia cell lines and three lymphoma cell lines, by fluorescence-activated cell sorting with antibodies against MHC class I and CD45. Testicular specimens were obtained from a patient who underwent surgery for testicular rupture. In the high forward scatter and low side scatter region, no malignant cells were found in the MHC class I-negative and CD45-negative fraction (the germ cell fraction), with the exception of K562 cells. A total of 39.2% of the germ cells were found in the germ cell fraction. A total of 1.45% of K562 cells were found in the germ cell fraction. Treatment with IFNgamma induced the expression of MHC class I on K562 cells but not on germ cells and made it possible to isolate germ cells from K562 cells. In conclusion, we isolated human germ cells from malignant cells with two surface markers after treatment with IFNgamma. Immunophenotyping for each patient will be necessary before isolation and induction of surface marker will be clinically applicable.