[Complete resection for giant thymic carcinoma after simultaneous combination chemotherapy].

A 19-year-old man visited our hospital complaining of dyspnea. Chest X-ray and computed tomography (CT) showed a huge mass in the right anterior mediastinum. We diagnosed this as invasive thymoma by microscopic examination of specimens obtained by echo-guided needle biopsy. The patient underwent 6 courses chemotherapy [1st course : carboplatin (CBDCA) + doxorubicin hydrochloride (DXR) + vincristine sulfate (VCR) + cyclophosphamide (CPA), 2nd, 3rd-6th course : cisplatin (CDDP) + ADM + VCR + CPA]. At achievement of partial response (the reduction rate of the tumor size : 91.4%), the tumor was completely resected. The pathological examination of the resected specimens yielded a diagnosis of large cell carcinoma. Preoperative chemotherapy with ADOC regimen may be effective in advanced thymic carcinoma.

[Thoracoscopic repair of diaphragmatic thinning for pleuroperitoneal communication; report of a case].

A 53-year-old man presented with massive right hydrothorax just after introduction of continuous ambulatory peritoneal dialysis (CAPD). Because the glucose concentration of pleural fluid was markedly high compared with that of serum, we diagnosed pleuroperitoneal communication. Thoracoscopic surgery was performed and thinning of the diaphragm was found. We sutured the diaphragm to repair the thin portion and performed pleurodesis with 50% glucose solution. He restarted CAPD 1 month post-operatively and continued at home without pleural effusion. Eight months post-operatively, he experienced dyspnea again and chest X-ray showed right hydrothorax. Although the cause of recurrent hydrothorax is unknown, it may be that not only surgical repair but also more intense pleurodesis is needed.

Vascular endothelial growth factor mRNA synthesis by peripheral blood mononuclear cells in patients with acute myocardial infarction.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.

Uterine adenomatoid tumors confirmed by immunohistochemical staining.

We present a 39-year-old nulliparous woman who consulted our clinic for an 8-year history of infertility with no notable symptoms. There apparent uterine leiomyomas were found incidentally on clinical examination and imaging. The surgically enucleated specimens were white in color with variable consistency poorly defined margins. The tissues stained positive for cytokeratin but were negative for CD34 antibodies, indicating a mesothelial origin. Staining for vimentin and HBME1 was also strongly positive, supporting a mesothelial origin of the tumors. The patient became pregnant 6 months after surgery. A healthy male infant was delivered at term. Immunohistochemical staining establish the diagnosis of benign adenomatoid tumors derived from mesothelial tissue.

Influence of midluteal serum prolactin on outcome of pregnancy after IVF-ET: a preliminary study.

PURPOSE: To investigate the relationship between serum prolactin levels in the midluteal phase and the prognosis of pregnancy after IVF-ET. DESIGN: Prospective study; SETTING: Shimane Medical University Hospital; PATIENTS: 29 patients completing their 34th IVF cycle; and MAIN OUTCOME MEASURES: Serum levels of prolactin, estradiol-17 beta, and progesterone in the midluteal phase. RESULTS: Midluteal prolactin levels were significantly lower in patients with early pregnancy loss than in the successful pregnancy group. The mean progesterone/prolactin ratio and the estradiol-17 beta/prolactin ratio were highest in patients with early pregnancy loss and were lowest in patients with successful pregnancies. CONCLUSIONS: Findings of this study suggest that measurement of the serum prolactin concentration in the midluteal phase is useful for predicting the outcome of IVF-ET.

Benign or malignant ovarian neoplasms and ovarian endometriomas.

STUDY OBJECTIVE: To investigate clinical features and biologic behavior of ovarian cancer that might be closely related to endometrioma and/or endometriosis. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: All 324 women who were operated for endometriomas and/or ovarian tumors 5 cm or greater in diameter between January 1988 and December 1997. INTERVENTION: One hundred twelve women underwent laparoscopic surgery and 212 had laparotomy. MEASUREMENTS AND MAIN RESULTS: All tissues were evaluated histologically. Clinical examinations including ultrasound and serum tumor makers were performed in all patients preoperatively. No malignancies were found at laparoscopic surgery (76 endometriomas, 36 ovarian tumors). The frequency of endometriosis in benign, borderline malignant, and malignant tumors was 9.7%, 12.5%, and 11.4%, respectively. Endometriosis was present most frequently (40%) in women with endometrioid adenocarcinoma. It was present in 81 patients with endometriomas and 25 with ovarian neoplasms. Of these, nine women (8.5%) had malignant tumors, including borderline malignancy. Among patients with malignant tumors, those without endometriosis were significantly older (mean +/- SD age 54.9 +/- 16.2 yrs) than those with endometriosis elsewhere in the pelvis (45.9 +/- 8.9 yrs). CONCLUSION: Endometriosis may be closely related to ovarian tumors such as endometrioid adenocarcinoma. Surgeons should be aware of this possibility, and candidates for laparoscopic surgery should be carefully selected based on preoperative evaluations.

Ischemic preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium.

Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCepsilon was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but was not translocated in the non-IP and the sham groups. VEGF mRNA expression 3 hours after infarction was significantly higher in the IP group than in the non-IP and the sham groups. Capillary density in the infarction was significantly higher, whereas the infarct size was smaller in the IP group than in the non-IP group at 3 days of infarction. Chelerythrine but not bisindolylmaleimide blocked all of the IP effects on the nuclear translocation of PKCepsilon, enhancement of VEGF mRNA expression and angiogenesis, and infarct size limitation. These results show that IP may enhance VEGF gene expression and angiogenesis through nuclear translocation of PKCepsilon in the infarcted myocardium.

Enlarged focal nodular hyperplasia of the liver under the influence of oral contraceptives.

Two cases of focal nodular hyperplasia of the liver in mature women treated with the oral contraceptive are described. Radiological investigations in one case revealed the typical findings of focal nodular hyperplasia with computed tomography and magnetic resonance imaging demonstrating central scar structures while spoke-wheel appearance was evident on arteriography, in the other case however findings were atypical. Routine investigations including liver function tests and alpha-fetoprotein levels were normal while hepatitis B surface antigen and hepatitis C virus antibody were negative. The lesions of these two cases enlarged significantly during the follow-up and they were therefore surgically resected. Pathological features of both resected specimens, such as hepatocellular hyperplasia, bile duct proliferation and vascular abnormalities, were compatible with focal nodular hyperplasia. It has been suggested that tumor growth may be augmented by sex hormone stimulation and therefore estrogen and progesterone receptor expressions in the resected tumors were determined by immunocytochemistry. Interestingly, stainings for both receptors were negative. In case 2, the tumor was enlarging although oral contraceptive use had been discontinued for the past 7 years. These results suggest that there is no direct relationship of focal nodular hyperplasia with oral contraceptives. The role of sex hormones in focal nodular hyperplasia of the liver merits further study.

Esophagogastrostomy reconstruction after limited proximal gastrectomy.

BACKGROUND/AIMS: Recent advances in diagnostic techniques have led to the detection of an increasing number of early gastric cancers in the upper third of the stomach. The objective of this study was to determine the most appropriate surgical treatment for these cancers. METHODOLOGY: The clinicopathologic characteristics of 35 patients with early gastric cancer in the upper third of the stomach who underwent three different types of gastrectomies were reviewed retrospectively from hospital records between January 1992 and August 1999. RESULTS: Patients undergoing limited proximal gastrectomy with esophagogastrostomy reconstruction had shorter operation times and less blood loss than those for patients undergoing total gastrectomy or proximal gastrectomy with jejunal interposition. No lymph node metastasis was identified in any of these patients. Heartburn due to reflux esophagitis was seen in a few patients of each group, but they were successfully treated by antacids. The extreme reduction in food intake volume was more frequently experienced in patients with total gastrectomy than those with both proximal gastrectomies. When mortality due to other disease was excluded, all patients survived without recurrence. CONCLUSIONS: A limited proximal gastrectomy with esophagogastrostomy reconstruction decreased surgical risk and realized preservation of maximal function.

A case of a pregnant woman with luteal insufficiency and a mutation in the beta-subunit of luteinizing hormone.

We report a case of a pregnant woman with luteal insufficiency and infertility associated with a variant luteinizing hormone (LH) beta-subunit and normal follicle-stimulating hormone (FSH) concentration. A 29-year-old woman presented to our hospital with infertility. Given the presence of low mid-luteal serum progesterone concentration and out-of-phase endometrial biopsy, luteal insufficiency was suspected. Several forms of treatment (clomiphene citrate therapy and human menopausal gonadotrophin therapy) were administered, but did not improve the patient's luteal insufficiency. However, administration of hCG during the luteal phase could distinctly improve the luteal insufficiency. She became pregnant after luteal support with progesterone. Sequence analysis of the patient's LH beta-subunit gene indicated heterozygosity for the point mutations Trp8 to Arg8 and Ile15 to Thr15 in the coding sequence. LH hypersecretion resembling that seen in polycystic ovary syndrome was observed. Serum concentrations of variant LH showed a more rapid increase in response to gonadotrophin-releasing hormone and reached a higher apparent value than did those of normal LH. Therefore, abnormal bioactivity and mistimed secretion of variant LH at mid-cycle may have a deleterious effect on the completion of oocyte maturation, ovulation, and subsequent corpus luteum function.

Molecular detection of disseminated cancer cells in the peripheral blood and expression of sialylated antigens in colon cancers.

BACKGROUND AND OBJECTIVES: To improve the survival rate of patients with colon cancer, liver metastases must be eradicated in a clinically occult state. This study was designed to find a predictor for potential liver metastases or micrometastases in colon cancer. METHODS: Peripheral blood samples and tumor specimens were obtained from 36 patients with colon cancers. The blood samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, and the expression of sialylated carbohydrates was also investigated in the tumors immunohistochemically. RESULTS: A carcinoembryonic antigen (CEA)-specific signal in the blood was detected in 9 of 12 (75%) patients with liver metastasis and in 8 of 24 (33%) patients without liver metastasis, respectively (P < 0.05). The positive rates of sialyl Lewis A (sLeA) and sialyl Lewis X (sLeX) were 36.3% and 40% in tumors without liver metastasis vs. 58.3% and 100% with liver metastasis, respectively. Within a year after surgery, liver metastases became clinically evident in three of the four patients without liver metastasis who showed a CEA-positive signal in their blood preoperatively and who had tumors with a strong expression of sLeX. CONCLUSIONS: A combination of both markers may provide prognostic information for liver metastases in colon cancer.

Pituitary response to luteinizing hormone-releasing hormone in women with variant luteinizing hormone.

OBJECTIVE: To assess the LH response of the pituitary gland to GnRH stimulation in healthy women with a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15). DESIGN: Clinical study. PATIENTS: We studied 40 healthy non-pregnant Japanese women of known zygosity for the LH beta-subunit gene (3 homozygotes for the mutant gene, 17 heterozygotes, and 20 homozygotes for the wild type). All women had normal ovulatory cycles. MEASUREMENTS: Serum LH status was determined by comparing LH immunoassays results using a monoclonal antibody recognizing only wild-type LH with those from a polyclonal antibody assay recognizing both variant and wild-type LH. The ratio of monoclonal to polyclonal immunoassay results determined the serum LH status. LH secretion in response to a GnRH stimulation test was measured. RESULTS: All women with the wild-type LH showed a normal response of LH to GnRH according to both assays. Over the time course of the response, the ratios in women with wild-type LH showed no remarkable changes. The response curves in women heterozygous for the mutant peaked 15-30min after GnRH injection; their response patterns included a statistically significant decrease in the rates of response at 15min after injection. CONCLUSIONS: There are the differences in circulatory kinetics between the two LH forms and in regulation of the two types of LHbeta genes. The maximal response of the variant LH to pituitary stimulation with GnRH appears to be greater than that of wild-type LH.

Benign teratoma in an 85-year-old woman.

BACKGROUND: In women over the age of 50, a mature cystic teratoma is reportedly likely to change into a malignant form. A mature cystic teratoma that remained in a benign form in a very old woman is a rare event. We report a case of a benign cystic teratoma, which is the oldest in Japan. CASE: An 85-year-old Japanese woman with a pelvic mass measuring 8.90x5.81 cm by ultrasonography was referred to our Department for detailed. Transvaginal ultrasonography, magnetic resonance imaging, and serum concentrations of tumor markers led to a diagnosis of a mature cystic teratoma. Histological findings postoperatively confirmed the presence of a mature cystic teratoma. CONCLUSIONS: This case report describes a mature cystic teratoma which is the second oldest case reported in the world. We reconfirmed that a mature cystic teratoma in elderly women is not frequent, but does occur.

Adrenomedullin gene transcription is decreased in peripheral blood mononuclear cells of patients with IgA nephropathy.

We measured mRNA levels of adrenomedullin (AM), C-type natriuretic peptide (CNP), vascular endothelial growth factor (VEGF), interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) in peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy. To evaluate these mRNA levels, we employed a real-time quantitative PCR method which was performed using a hybridization probe labeled with two fluorescence dyes. This strategy was found to afford the standard curves with a high correlation, suggesting that this method is useful for evaluations of mRNA levels. By this method, levels of AM, CNP, VEGF, IL-1beta and IL-6 mRNA in PBMC of 49 IgA nephropathy patients and 35 healthy volunteers were evaluated. Among the mRNAs examined, AM mRNA levels were significantly lower in severe-grade than in mild-grade IgA nephropathy patients. Furthermore, AM mRNA levels correlated with CNP mRNA levels in PBMC of patients with IgA nephropathy, and each peptide generated from these mRNAs has antiproliferative effects on mesangial cells. These data indicate that gene expression of AM in PBMC is regulated according to the pathophysiological states of IgA nephropathy and that decreased AM production may contribute to the progression of IgA nephropathy.

Safety and efficacy of oestriol for symptoms of natural or surgically induced menopause.

To assess the safety and efficacy of oestriol in relieving post-menopausal symptoms 53 post-menopausal Japanese women with climacteric symptoms, 27 with natural menopause (group I) and 26 with surgically induced menopause (group II), received oral oestriol, 2 mg daily for 12 months. Clinical parameters including Kupperman index (KI) and the degree of satisfaction with symptomatic relief; serum concentrations of oestradiol, FSH and LH; serum lipids; blood pressure; bone mineral density, serum calcium (Ca), alkaline phosphatase (ALP), and urinary Ca were compared between the two groups. Oestriol improved KI in groups I and II by 49 and 80% respectively. Satisfaction with treatment was 85% in group I and 93% in group II. For both parameters, values were significantly different between groups I and II (P < 0.05 for both). Serum concentrations of oestradiol, FSH and LH changed in group I versus group II 6 months after initiation. A significant decrease in serum ALP and Ca/Cr was observed in group I at 6 months. Except for serum triglycerides, oestriol had no significant effect on lipids. Systolic and diastolic blood pressures were significantly decreased in group I at 3 months versus baseline. Slight vaginal bleeding occurred in 14.3% of group I. Histological evaluation of the endometrium in all women of group I and ultrasound assessment of the breasts following 12 months of oestriol treatment found normal results in all women. Therefore, oestriol appeared to be safe and effective in relieving symptoms of menopausal women. The beneficial biochemical effects of oestriol were marked in the natural menopause. Overall, oestriol may serve as a good choice for hormone replacement therapy to protect against other climacteric symptoms in post-menopausal women who do not need medication for osteoporosis or coronary artery disease.

Efficacy and safety of oral estriol for managing postmenopausal symptoms.

OBJECTIVE: to assess the therapeutic efficacy and safety of oral estriol for the treatment of climacteric symptoms in postmenopausal women. METHODS: 68 postmenopausal women with climacteric symptoms received oral estriol, 2 mg/day, daily for 12 months. We evaluated the degree of climacteric complaints with estriol therapy; serum levels of gonadotropins, estradiol (E2) and lipids; biochemical markers of bone metabolism; blood pressure; and side effects both at baseline and during treatment. Climacteric symptoms were assessed according to the menopausal index (MI), a version of the Kupperman index that had been modified for Japanese women. RESULTS: oral estriol therapy significantly reduced total MI scores. The greatest relief was noted for hot flushes, night sweats, and insomnia. Estriol treatment significantly lowered serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations but did not affect any of the other parameters (lipids, bone, liver and blood pressure) during the study period. Slightly vaginal bleeding occurred in 14.3% of those who underwent natural menopausal women. Histologic evaluation of the endometrium and ultrasound assessment of the breasts following 12 months of estriol treatment found normal results in all women. CONCLUSION: Estriol is a safe and effective alternative for relieving climacteric symptoms in postmenopausal Japanese women.

Human chondrocyte proliferation and matrix synthesis cultured in Atelocollagen gel.

To evaluate the potential of Atelocollagen gel as a carrier for chondrocyte transplantation, histological and biochemical characteristics of the chondrocytes in gel culture were compared with those in conventional monolayer cultures. Articular chondrocytes from 20 patients were isolated by enzyme digestion, embedded in Atelocollagen gel, and cultured for up to 4 weeks. The effects on proliferation, morphological changes, and synthesis of proteoglycans were analyzed by cell counts, light and electron microscopy, and measurement of isomers of chondroitin sulfates. Chondrocytes embedded in the Atelocollagen gel gradually proliferated and produced chondroitin 6-sulfate, maintaining the chondrocyte phenotype for up to 4 weeks. In contrast, although monolayer chondrocytes increased in number, most could be characterized as being fibroblast-like cells with a reduced capability of producing chondroitin 6-sulfate. The results suggest that Atelocollagen gel permitted a gradual proliferation and matrix synthesis of chondrocytes and maintaining its phenotype. Atelocollagen gel represents an important carrier for the clinical application of cultured chondrocyte transplantation for repair of cartilage defects.

Live birth after conservative surgery for severe adenomyosis following magnetic resonance imaging and gonadotropin-releasing hormone agonist therapy.

This is a report of a live birth after conservative surgery for severe adenomyosis following diagnosis by MRI and therapy with GnRH-a. A 33-year-old gravida 1 para 1 woman with a 5-year history of secondary infertility received a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide acetate, for 16 weeks to control symptoms of severe adenomyosis and to treat infertility. However, severe dysmenorrhea recurred after the discontinuation of therapy. Because an elevated serum level of CA-125 and MRI findings suggested that she was experiencing a relapse of adenomyosis, GnRH-a therapy was re-instituted. After 24 weeks of the second therapy, her uterus decreased to normal size and an MRI revealed a localized low-signal-intensity myometrial mass with well-defined borders. We easily resected the localized lesion of adenomyosis using the same technique used to treat uterine leiomyoma. The patient became pregnant after 12 weeks of additional danazol therapy. A healthy male infant was delivered at term by cesarean section.

A case of postmenopausal endometriosis unrelated to neoplasm.

A 55-year-old woman was referred to our hospital for evaluation of a lower abdominal mass. Menopause had occurred at age 52 years. Ultrasonography and magnetic resonance imaging showed a partially solid right ovarian tumor, an appearance suggestive of malignancy. A transabdominal simple hysterectomy and bilateral salpingo-oophorectomy were performed. Pathologic examination revealed an endometrial cyst of the right ovary, a uterine leiomyoma, and adenomyosis.

Estradiol-17beta measurement in women receiving conjugated estrogens. Dissociation between two commercial methods.

To investigate problems associated with measurement of estradiol-17beta (E2) in hormone replacement therapy (HRT), two commercial immunometric methods (Coat-A-Count E2 and Immulyze E2) were used to assay E2 concentrations and the two results were expressed as E2 ratios. Samples were obtained from 97 Japanese women receiving HRT and 168 unmedicated women. The largest differences between methods (P < 0.001) occurred in patients receiving oral conjugated estrogen (CE), while the best concordance was found in unmedicated women; like these controls, patients receiving oral estriol or transdermal E2 showed no significant difference between methods. Defining an E2 ratio > or = 2.0 as an abnormal discordance, the mean E2 ratio and the frequency of abnormal discordance in the CE group were 2.15 +/- 1.18 and 43.6%, respectively. No abnormal discordance for E2 occurred in other groups. In serial serum samples from the control group, no significant difference was seen between the mean E2 ratio at first measurement and those at a subsequent measurement. Similarly, no significant difference in the ratio was seen when two serial samples from CE patients were compared. However, E2 ratios after prescription of CE were significantly higher than before treatment in all patients. In conclusion, although measurement of E2 is important in patients receiving HRT, validity of the test methods must be carefully weighed for patients receiving CE.