The treatment of refractory atlanto-axial rotatory fixation using a halo vest: results of a case series involving seven children.

We reviewed seven children with torticollis due to refractory atlanto-axial rotatory fixation who were treated in a halo vest. Pre-operative three-dimensional CT and sagittal CT imaging showed deformity of the superior articular process of C2 in all patients. The mean duration of halo vest treatment was 67 days (46 to 91). The mean follow-up was 34 months (8 to 73); at the latest review six patients demonstrated remodelling of the deformed articular process. The other child, who had a more severe deformity, required C1-2 fusion. We suggest that patients with atlanto-axial rotatory fixation who do not respond to conservative treatment and who have deformity of the superior articular process of C2 should undergo manipulative reduction and halo-vest fixation for two to three months to induce remodelling of the deformed superior articular process before C1-2 fusion is considered.

The usefulness of serum amyloid A as a postoperative inflammatory marker after posterior lumbar interbody fusion.

The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) mug/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker.

A prostaglandin D2 receptor antagonist modifies experimental asthma in sheep.

BACKGROUND: Prostaglandin (PG) D(2) is the major cylooxygenase metabolite released by mast cells upon allergen stimulation, and elicits responses through either the prostanoid DP1 receptor and/or the chemoattractant receptor homologous molecule expressed on T-helper type 2 (Th2) cells (CRTH2/DP2). Experimental evidence suggests that stimulation of one or both these receptors contributes to asthma pathophysiology. OBJECTIVE: The aim of this study was to test the hypothesis that the prostanoid DP1 receptor contributes to asthma pathophysiology by determining the efficacy of an orally active antagonist for this receptor, S-5751, on allergen-induced bronchoconstriction, airway hyperresponsiveness (AHR) and cellular inflammation in the sheep model of asthma. METHODS: PGD(2)-induced cyclic adenosine monophosphate (cAMP) production in platelet-rich plasma was used to establish the in vitro efficacy of S-5751. In vivo, sheep naturally allergic to Ascaris suum were challenged with an aerosolized antigen with and without S-5751 treatment (given 4 days before and for 6 days after the challenge). RESULTS: S-5751 inhibited PGD(2)-induced cAMP production in platelet-rich plasma with an IC(50) value of 0.12 microm. S-5751 at 30 mg/kg, but not at 3 mg/kg, reduced the early bronchoconstriction and inhibited the late bronchoconstriction. AHR and inflammatory cell infiltration in bronchoalveolar lavage fluid at days 1 and 7 were also inhibited with the 30 mg/kg dose. The responses observed with S-5751 at 30 mg/kg were comparable with those with montelukast treatment (0.15 mg/kg, twice a day, intravenous); however, S-5751 did not block inhaled leukotrieneD(4)-induced broncoconstriction. CONCLUSION: Prostanoid DP1 receptor inhibition may represent an alternative target for asthma therapy.

Association study of vascular endothelial growth factor gene polymorphisms in endometrial carcinomas in a Japanese population.

OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays a critical role in angiogenesis of endometrial carcinomas. Several studies have demonstrated positive associations between VEGF gene polymorphisms and several carcinomas. In this study we investigated whether VEGF gene polymorphisms are associated with endometrial carcinomas in a Japanese population. METHODS: The allele frequencies and genotype distributions of VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were examined in 105 endometrial carcinomas and 179 controls using PCR-RFLP analysis. An association of these polymorphisms with three-year disease-free survival was evaluated using the Kaplan-Meier method. RESULTS: No significant differences in the allele frequencies and genotype distributions of VEGF -460 C/T (p = 0.54, 0.90), +405 G/C (p = 0.31, 0.17), and +936 C/T polymorphisms (p = 0.46, 0.24) were observed between endometrial carcinoma patients and controls. There were no significant differences in the frequencies of haplotype -460 T/+405 C between patients and controls. Futhermore, VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms were not associated with three-year disease-free survival of endometrial carcinoma patients. CONCLUSIONS: Although limited by sample size, our study did not demonstrated any evidence that VEGF -460 C/T, +405 G/C, and +936 C/T polymorphisms are associated with an increased risk of endometrial carcinomas in Japanese women.

Association study between catechol-O-methyltransferase polymorphisms and uterine leiomyomas in a Japanese population.

PURPOSE: To investigate a possible association between uterine leiomyomas and catechol-O-methyltransferase (COMT) polymorphisms in a Japanese population. METHODS: We compared the allele frequencies and genotype distributions of the exon 4 NlaIII restriction site polymorphism (RSP), the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP in the COMT gene in 250 leiomyoma cases and 182 controls using polymerase chain reaction-restriction fragment-length polymorphism analysis. RESULTS: No significant differences in allele frequencies and genotype distributions of the exon 4 NlaIII RSP, the P2 promoter HindIII RSP at -1217, and the exon 6 BglI RSP were found between uterine leiomyoma cases and controls. Moreover, no associations were noted between these three polymorphisms in COMT genes and leiomyoma size or a family history of uterine leiomyomas. CONCLUSION: COMT gene polymorphisms are unlikely to be associated with an increased risk of uterine leiomyomas in a Japanese population.

A case of postirradiation vaginal angiosarcoma treated with recombinant interleukin-2 therapy.

Angiosarcoma of the vagina is an extremely rare neoplasm and is characterized by frequent recurrence and early metastatic spread. Although previous reports emphasized the poor prognosis of this disease, effective treatment strategies have not been adequately stated. We report a case of angiosarcoma of the vagina, in which the diagnosis was made 9 years after intrapelvic irradiation, and recombinant interleukin-2 (rIL-2) therapy could be effective to suppress the development of distant metastasis. We recommend rIL-2 therapy in combination with irradiation as a palliative therapeutic option for vaginal angiosarcoma when the tumor is inoperable or the patient refuses to undergo surgery. Although vaginal angiosarcoma is an extremely rare condition, its possibility should be borne in mind when finding a vaginal mass in a previously irradiated patient.

Adenofibromasarcoma originating from a mural nodule of ovarian serous cystadenoma.

A 83-year-old woman received bilateral salpingo-oophorectomy and hysterectomy due to a provisional diagnosis of ovarian cystic tumor. The tumor had a unilocular cystic cavity demonstrating serous cystadenoma and a solid mural nodule representing a biphasic pattern with mesenchymal and glandular components. The glandular elements were composed of benign serous cells, whereas the mesenchymal components consisted of an admixture of fibromatous stromal cells without atypia and sarcomatous overgrowth. The area of transition from a fibromatous component to sarcomatous overgrowth was identified. After a 2-year follow-up, there were no signs of tumor recurrence or systemic disease. To the authors' knowledge, this is the first reported case of adenofibrosarcoma originating from a mural nodule of ovarian serous cystadenoma.

Pregnancy complicated with pulmonary lymphangioleiomyomatosis: case report.

A case of a 30-year-old primiparous woman with pulmonary lymphangioleiomyomatosis is described. The patient had experienced six episodes of spontaneous pneumothorax at the age of 27 years and had been diagnosed as having pulmonary lymphangioleiomyomatosis based on histological findings of specimens obtained by transbronchial biopsy. She had undertaken open lung surgery and thoracoscopy. Thereafter, she became pregnant spontaneously. Her antenatal course was uneventful with no exacerbation of respiratory status. At 38 weeks of gestation, she underwent a selective cesarean section and myomectomy under combined spinal and epidural anesthesia. Her postoperative course was uneventful. No remarkable changes in computed tomographic findings of the lung were noted on the 20th day of postoperation compared with those before pregnancy. She has been followed-up in the pulmonary outpatient clinic with no deterioration of the disease.

A case of multiple ovarian cysts in a prepubertal girl with severe hypothyroidism due to autoimmune thyroiditis.

Some children with profound and long-standing hypothyroidism present with signs of paradoxical sexual maturation. In females, it is characterized by breast development, vaginal bleeding, lack of pubic hair, and delayed bone age. A case of multiple ovarian cysts in a prepubertal girl with severe hypothyroidism due to autoimmune thyroiditis is reported. A 7-year, 8-month-old girl presented with precocious puberty and vaginal bleeding. A pelvic ultrasound revealed markedly enlarged ovaries with numerous cysts which disappeared dramatically after thyroid replacement. When large multiple ovarian cysts with vaginal bleeding are found in a prepubertal girl who has a retarded bone age, the possibility of associated hypothyroidism should be considered. Health care providers should keep this in mind because this constellation of symptoms can be completely reversed with the initiation of thyroid replacement.

Simultaneous immunohistochemical localization of beta-catenin and cyclin D1 in differentiated but not in undifferentiated human endometrial carcinoma.

PURPOSE: Beta-catenin plays dual important roles in epithelial cell-cell adhesion in cytoplasm as well as in the nuclear T-cell factor (TCF)/lymphoid enhancing factor-1 (LEF-1) signaling pathway. Abnormal nuclear accumulation of beta-catenin promotes colorectal carcinogenesis by triggering the expression of cyclin D1 gene through the TCF/LEF-1 pathway. The purpose of this study was to investigate the possible involvement of the TCF/LEF-1 pathway in endometrial carcinogenesis. METHODS: Immunohistochemical localization of beta-catenin and cyclin D1 in normal endometrium, hyperplastic endometrium and endometrial carcinoma were assessed on serial tissue sections. RESULTS: Nuclear accumulation of beta-catenin was observed in endometrial carcinomas compared with normal endometria. Cyclin D1-positive endometrial cancer cases were beta-catenin-positive in the nuclei, especially in 70% (7/10) of G1 and 55.6% (5/9) of G2 differentiated endometrial carcinomas, but never in G3 undifferentiated ones. CONCLUSIONS: These results imply that the simultaneous nuclear accumulation of beta-catenin and cyclin D1--suggesting the activation of the TCF/LEF-1 pathway--may be a potential marker for the progression of Type 1 endometrial carcinogenesis.

The CA125 regression rate to predict overall survival differ between paclitaxel-containing regimen and nonpaclitaxel regimen in patients with advanced ovarian cancer.

In this study, we compare the time to normalization of CA125 after cytoreductive surgery between a paclitaxel-containing regimen and a non-paclitaxel regimen. This study demonstrates that CA125 regression in a paclitaxel-containing regimen was slower than that in a non-paclitaxel regimen. When we determine the CA125 regression rate to predict overall survival in ovarian cancer, we should take into account the kind of chemotherapy regimen, especially the use of paclitaxel.

Granulomatous chemical peritonitis on the ileocecum after laparoscopic surgery of an ovarian mature cystic teratoma: case report.

The possibility of granulomatous peritonitis should be considered when laparoscopy is necessary in patients with ovarian mature cystic teratoma.

Treatment of hepatocellular carcinoma and the exacerbation of liver function.

We performed interventional treatments on 50 patients with hepatocellular carcinoma (HCC) and analyzed the relationship between these treatments and the exacerbation of liver function after treatment. The different treatments included transcatheter arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), selective segmental sclerotherapy (SSS), combined TAE and PEIT, or transcatheter arterial chemo-injection (TAI). Thirteen patients showed an exacerbation of liver function after treatment. The laboratory data on admission, showed the lower levels of serum albumin and cholinesterase in this group. In comparison to patients who did not show any exacerbation of liver function, these 13 patients had undergone combined TAE and PEIT. An analysis of cases after TAE and PEIT treatment revealed that the time from TAE to PEIT was shorter in the exacerbation group than in the non-exacerbation group, however, there was no significant difference in the amount of injected ethanol between the two groups. It is assumed that the values of albumin and cholinesterase before treatment, or the period from TAE to PEIT are related to liver failure after treatment. Combining TAE and PEIT treatment may be effective for HCC, however, we should pay special attention to liver failure after treatment.

Impact of hepatitis B and C virus infection on the clinical prognosis of alcoholic liver cirrhosis.

To elucidate the rates of appearance of hepatocellular carcinoma (HCC) and the prognosis of alcoholic liver cirrhosis upon infection with hepatitis virus, we retrospectively studied 190 consecutive patients. The patients were divided into three groups based on whether they were exposed either to hepatitis B virus (HBV), hepatitis C virus (HCV) or not. The cumulative survival rate of the alcoholic liver cirrhosis patients with hepatitis B surface antigen (HBsAg) was significantly lower than that in those with hepatitis C antibody (anti-HCV). Most alcoholic liver cirrhosis patients without hepatitis virus infection died of liver failure, gastrointestinal (G1) bleeding, or other diseases. However, alcoholic liver cirrhosis patients with anti-HCV tended to die of HCC. The cumulative HCC appearance rate in alcoholic liver cirrhosis patients without HBsAg or anti-HCV was 7% at the end of the fifth year after the diagnosis of cirrhosis and 15% at the end of the tenth year. However; the HCC appearance rate was about 20% at the end of the fifth year after the diagnosis of cirrhosis and about 50% at the end of the tenth year in both alcohol drinkers with HBsAg or anti-HCV. These data suggest that hepatitis virus infection may modify the prognosis for alcoholic liver cirrhosis patients, especially in the development of carcinogenesis.

Comparison of screening methods for hepatocellular carcinomas in patients with cirrhosis.

To determine the most suitable screening methods for hepatocellular carcinomas (HCCs), we investigated 45 cases with HCCs. Ultrasonography, computed tomography (CT) scan and measurement of alpha-fetoprotein (AFP) were regularly performed. Thirty-two cases (72%) were detected initially by ultrasonography. Fourteen out of 23 cases (61%) with tumors 20 mm or less in diameter and 11 out of 12 cases (91%) with 21-30 mm tumors were detected initially by.ultrasonography. For the initial detection of tumors sized 20 mm or less, the mean interval of ultrasonography was 3.54 months, unlike the 5.67 months for tumors sized over 21 mm. There was no significant difference between tumor size and measurement interval in AFP levels or CT scan examinations. From these results, we suggest that a suitable screening schedule would be every three months by ultrasonography.

Combining transcatheter arterial chemoembolization with percutaneous ethanol injection therapy for small size hepatocellular carcinoma.

For patients with unresectable small size HCC, percutaneous ethanol injection therapy (PEIT) is used as a non-surgical treatment because it is difficult to achieve complete tumor necrosis by transcatheter arterial chemoembolization (TAE) alone. However, some small HCCs (<21 mm in diameter) are resistant to PEIT with incomplete tumor necrosis, which is associated with insufficient ethanol injection to the tumor. For more effective treatment for HCC, we performed a combination of TAE and PEIT on patients with small size HCC and evaluated the cumulative recurrence and survival rates. The recurrence rate in patients treated with the combination was less than that of TAE or PEIT alone. There were five patients without tumor recurrence during the follow-up period and three out of these underwent the combination treatment. The period of no recurrence was 33.4 months on average. In conclusion, we recommend combination therapy with TAE and PEIT for patients to accomplish more effective treatment of small size HCC.

Cyclooxygenase-2 expression in malignant mesenchymal tumors and related uterine lesions.

The aim of this study was to determine whether the expression of cyclooxygenase-2 (COX-2) in uterine sarcoma cells and carcinosarcoma cells is associated with cell type. Nineteen sections of tissues from uterine sarcomas, carcinosarcomas, and an adenosarcoma, and endometrial stromal sarcomas, were immunohistochemically analyzed for the cellular expression of COX-2. Positive immunostaining for COX-2 was observed in 88.9% (8/9) uterine carcinosarcomas, uterine adenosarcomas but was not observed in uterine sarcomas and the endometrial stromal sarcoma (0/10). But positive immunostaining for COX-2 was observed in some sarcomatoid cells in carcinosarcoma tissue. These findings suggest that some of the sarcoma cells in uterine carcinosarcomas resemble epithelial malignant cells in regard to the increase in COX-2 expression, and support the hypothesis that some uterine carcinosarcomas are combination tumors. This may serve as a basis for new chemoprevention and treatment strategies for uterine carcinosarcomas through the inhibition of COX-2 activity.

Association between overexpression of cyclooxygenase-2 and suppression of apoptosis in advanced cancer of the uterine cervix after cyclic balloon-occluded arterial infusion.

Recent advances in cancer chemotherapy have drawn the attention of investigators to the usefulness of chemotherapy for cancer of the uterine cervix in general, and we ourselves have previously reported satisfactory therapeutic results of cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy (BOAI), which enabled treatment by hysterectomy in patients with advanced cervical cancer. Nevertheless, there have been some patients in whom CDDP therapy by BOAI was ineffective, and hysterectomy was impracticable. In the present study we investigated the expression of cyclooxygenase-2 (COX-2) in these cases in an attempt to identify the cause of the lack of efficacy. The subjects of the study were 38 women with advanced cervical cancer classified as FIGO (International Federation of Gynecology and Obstetrics) stage III or higher who were admitted to the Department of Gynecology of Osaka City University Medical School Hospital between July 1993 and April 2000. All of these patients were treated by BOAI, and expression of COX-2, angiogenic factors, and cancer cell apoptosis, before and after BOAI were examined, and survival rates were compared. The 18 patients in whom BOAI was ineffective showed significantly higher expression of COX-2 after BOAI, and cancer cell apoptosis was inhibited. The 5-year survival rate of these patients was 16.8%, as opposed to 54.1% in the 20 patients in whom BOAI was effective. These results suggest that overexpression of COX-2 inhibits cancer cell apoptosis and adversely influences the prognosis.

Expression of angiogenic factors in extrapelvic endometriosis.

The expression of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were immunohistochemically examined in both pelvic and extrapelvic endometriotic lesions. Different expressions of VEGF and COX-2 were observed in both lesions. VEGF immunoreactivity was distributed mainly in the cytoplasm of the adenocytes in inguinal tumors, but was not seen in ovarian tumors. COX-2 showed the same findings. These results suggest that angiogenesis may be involved in the pathogenesis of extrapelvic endometriosis.