Prognostic factors for survival in cervical cancer patients with bone metastasis.

PURPOSE: To investigate the prognostic factors for survival in uterine cervical cancer patients who developed bone metastasis. MATERIALS AND METHODS: Cervical cancer patients with bone metastasis who were treated at the present institute from April 1996 to September 2010 were identified from the authors' institutional tumor registries. Primary disease, follow-up, and recurrence data were collected and retrospectively reviewed. Univariate and multivariate analyses of prognostic factors for survival were performed. RESULTS: A total of 37 patients that developed cervical cancer bone metastasis were included in the authors' database. The median survival time after recurrence was 12 months. Univariate analysis revealed that patients with a disease-free interval (DFI) of ten months or less achieved significantly shorter survival after bone metastasis detection than those with a DFI of 11 months or more (median: 8.5 months versus 17 months, p < 0.0001). Multivariate analysis also showed that DFI of ten months or less was a significant predictor of short survival (p = 0.0018). CONCLUSIONS: The DFI was found to be independent prognostic factors for survival in cervical cancer patients who developed bone metastasis.

Motor and cognitive function analysis for home discharge using the Functional Independence Measure in patients undergoing cardiac rehabilitation at a long-term acute-care hospital.

BACKGROUND: Although numerous studies on Functional Independence Measure (FIM) analysis in stroke, orthopedic disease, and spinal cord injury patients have been conducted, it has rarely been done in patients undergoing cardiac rehabilitation (CR). AIM: To verify whether the Functional Independence Measure (FIM) score, and its subscale motor FIM and cognitive FIM, during inpatient CR can be a predictor of a patient's readiness for home discharge by establishing an FIM cutoff value. DESIGN: A retrospective, observational cohort study SETTING: This study was conducted at a long-term acute-care hospital. POPULATION: Participants were in-hospital patients undergoing CR (N.=949). METHODS: Measurements included motor FIM, cognitive FIM, CR period, FIM gain per week, and discharge disposition. The strongest predictor for home discharge was analyzed by using multiple logistic regression analysis, and the cutoff value of the FIM score for home discharge was determined by using receiver operating characteristic (ROC) curves. RESULTS: Discharge to home was possible in 723 patients (76.2%), whereas 226 patients (23.8%) had other outcomes. In univariate analysis, a motor FIM gain per week of five points was achieved in the home discharge group. Multiple logistic regression analysis revealed that Body Mass Index, number of comorbidities, motor FIM at discharge, cognitive FIM gain, and CR period were predictive factors with 89.6% predictive ability. ROC curve analysis showed that the cutoff value was a discharge motor FIM score of 63/64 points with 0.912 areas under the curve. CONCLUSION: Discharge motor FIM and cognitive FIM gain were predictive factors for home discharge. A motor FIM gain per week of five points and discharge motor FIM score of 64 points at the end of inpatient CR may be important predictors of a patient's readiness for discharge to home. CLINICAL REHABILITATION IMPACT: The findings of this study indicate an alternative goal to the activities of daily living in inpatients with cardiovascular disease.

Condyloma acuminata induces focal intense FDG uptake mimicking vaginal stump recurrence from uterine cervical cancer: a case report.

The 2-deoxy-2-[18F] fluoro-D-glucose position emission tomography/computed tomography (FDG PET/CT) findings of condyloma acuminata in a patient with FIGO Stage IB1 cervical cancer who had previously been treated with radical hysterectomy, pelvic chemoradiotherapy, and consolidation chemotherapy is described in this article. This case highlights the importance of considering condyloma acuminata during the differential diagnosis of abnormal vaginal FDG uptake in patients who have been treated for gynecological cancer.

Utility of risk-weighted surgical-pathological factors in early-stage cervical cancer.

BACKGROUND: Surgical-pathological risk factors were evaluated by weighting the magnitude of significance of multiple risk factors correlating to survival and treatment response in cervical cancer. METHODS: Multivariate analysis was performed for survival outcomes entering seven pathological factors obtained from 540 radical hysterectomy specimens in stage IA2-IIB cervical cancer cases. Hazard ratio (HR) in each risk factor was determined, and the sum of HR scores for the corresponding risk factors was determined per case. Survival curves and postoperative treatment response (concurrent chemoradiotherapy (CCRT) vs radiotherapy alone) were evaluated based on the extent of HR-weighted scores. RESULTS: Hazard ratios for risk factors relating to disease-free survival (DFS) was: lympho-vascular space invasion 3.95, nodal metastasis 3.88, adenocarcinoma 3.40, large tumour 2.36, positive margin 1.99, deep stromal invasion 1.29, and parametria invasion 1.21. The HR-weighted scoring method showed a high predictive value for recurrence (area-under-curve 0.836, P<0.001). Hazard ratio-weighted scores were negatively correlated to DFS, and the cases with score 12.5 showed 5-year DFS rate of 23.8%. Tumours with larger score offset the benefits of CCRT over radiotherapy alone for postoperative adjuvant treatment (P<0.001). CONCLUSION: Surgical-pathological risk factors provide valuable information for survival and management of early-stage cervical cancer when number and significance of risks are weighted.

Estradiol and raloxifene induce the proliferation of osteoblasts through G-protein-coupled receptor GPR30.

BACKGROUND: Although G-protein-coupled receptor, GPR30, has been considered as a G-protein-coupled estrogen receptor, conflicting results have been reported and the function of GPR30 in bone remains unresolved. The aim of this study was to clarify the functional role of GPR30 in osteoblasts using its derived cell line. METHODS AND RESULTS: Immunohistochemical study revealed that GPR30 is expressed in human osteoblasts. Human fetal osteoblast cell lines, hFOB cells, which express GPR30 but lack estrogen receptor, were used for the in vitro experiments. Estradiol or raloxifene induced the proliferation of hFOB cells, which was accompanied by the activation of mitogen-activated protein (MAP) kinase. Those proliferative effects were completely abrogated by the transfection of GPR30 small interfering RNA, while the transfection alone did not affect the cell viability. CONCLUSION: GPR30 is required for the proliferation of hFOB cells induced by estradiol or raloxifene. This proliferative effect was at least partly mediated via MAP kinase activation. These findings revealed a novel function of GPR30 in osteoblasts and might lead to a better understanding of how estrogen and selective estrogen receptor modulators show their osteoprotective effects.

Calcaneal metastasis in uterine cervical cancer: a case report and a review of the literature.

A 64-year-old woman with FIGO Stage IB2 cervical cancer was treated with radical surgery. Six months after her initial surgery, the patient developed calcaneal metastasis. Significant relief in bone pain was achieved with palliative radiotherapy followed by platinum-based combination chemotherapy, and the patient is currently alive with disease at eight months after the development of recurrence. Bone metastasis from uterine cervical cancer is uncommon, especially in the distal appendicular skeleton. Currently, and to the best of the authors' knowledge, calcaneal metastasis derived from cervical cancer has never been reported in English literature. As the prognosis of patients with bone metastasis is dismal and most patients die within a year, treatment should be directed towards improving the patient's quality of life and palliating their symptoms.

G-CSF induces focal intense bone marrow FDG uptake mimicking multiple bone metastases from uterine cervical cancer: a case report and review of the literature.

We describe a case of FIGO Stage IB2 uterine cervical cancer which showed focal intense bone marrow FDG uptake mimicking bone metastases after the administration of G-CSF This case highlights the importance of avoiding the administration of G-CSF prior to PET imaging.

A retrospective analysis of endometrial carcinoma cases surgically treated with or without para-aortic lymph node dissection followed by adjuvant chemotherapy.

PURPOSE: To analyze the efficacies of para-aortic node (PAN) dissection for patients undergoing surgery and adjuvant chemotherapy for endometrial carcinomas. METHODS: At the Osaka University Hospital and the Kaizuka City Hospital in Osaka, Japan, either pelvic lymph nodes (PLN) plus para-aortic lymph nodes (PAN) or PLN-only dissections were performed for endometrial carcinomas. An adjuvant chemotherapy using paclitaxel, epirubicin, and carboplatin was conducted for all such patients. A retrospective comparison of the efficacy of PAN dissection was conducted. RESULTS: Disease-free and overall survivals and frequency of PAN involvement at the first recurrence did not exhibit a statistically significant difference between the PLN-only group and the PLN + PAN group. Operation time was significantly longer in the PLN + PAN group than the PLN-only group, and the total blood loss was also significantly greater in the PLN+PAN group. CONCLUSION: PAN dissection may be omitted, without adverse effect on prognosis, for endometrial carcinoma patients with recurrence risks who undergo adjuvant chemotherapy using platinum, anthracycline and taxane derivatives.

Activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth: a case report and a review of the literature.

A 47-year-old woman was diagnosed with extragenital mullerian adenosarcoma with sarcomatous overgrowth. One month after her initial surgery, the patient developed pelvic recurrence, which was completely excised by surgery. However, one month later, the patient developed further recurrences in her pelvis and upper abdomen. A clinical complete response was achieved with three cycles of liposomal doxorubicin and is currently clinically free of disease. So far, including the present case, 23 cases of extragenital mulleian adenosarcoma have been reported in the English literature. Because of the rarity of the reported cases, there are no treatment guidelines based on a good level of evidence. In the current report, through a literature review, we provide information on the activity of pegylated liposomal doxorubicin for extragenital mullerian adenosarcoma with sarcomatous overgrowth.

Targeting mTOR signaling pathway in ovarian cancer.

The mammalian target of rapamycin (mTOR) is frequently activated in epithelial ovarian cancer, and is regarded as an attractive therapeutic target for therapy. Preclinical investigations using rapamycin and its analogs have demonstrated significant growthinhibitory effects on the growth of ovarian cancer both in the setting of monotherapy and in combination with cytotoxic agents. Based on promising preclinical data, mTOR inhibitors are currently being evaluated in several phase I/II trials in patients with ovarian cancer. In an effort to overcome resistance to rapamycin and its analogs, the novel ATP-competitive mTOR inhibitors have recently been developed. In this report, we review the scientific rationale and evidence for the potential clinical benefits provided by mTOR inhibitor therapy for patients with epithelial ovarian cancer.

Both estrogen and raloxifene cause G1 arrest of vascular smooth muscle cells.

The proliferation of vascular smooth muscle cells (VSMC) is a crucial pathophysiological process in the development of atherosclerosis. Although estrogen is known to inhibit the proliferation of VSMC, the mechanism responsible for this effect remains to be elucidated. In addition, the effect of raloxifene on VSMC remains unknown. We have shown here that 17beta-estradiol (E(2)) and raloxifene significantly inhibited the platelet-derived growth factor (PDGF)-stimulated proliferation of cultured human VSMC. Flow cytometry demonstrated that PDGF-stimulated S-phase progression of the cell cycle in VSMC was also suppressed by E(2) or raloxifene. We found that PDGF-induced phosphorylation of retinoblastoma protein (pRb), whose hyperphosphorylation is a hallmark of the G1-S transition in the cell cycle, was significantly inhibited by E(2) and raloxifene. These effects were associated with a decrease in cyclin D1 expression, without a change in cyclin-dependent kinase 4 or cyclin-dependent kinase inhibitor, p27(kip1) expression. ICI 182,780 abolished the inhibitory effects of E(2) and raloxifene on PDGF-induced pRb phosphorylation. Next, we examined which estrogen receptor (ER) is necessary for these effects of E(2) and raloxifene. Since VSMC express both ERalpha and ERbeta, A10, a rat aortic smooth muscle cell line that expresses ERbeta but not ERalpha, was used. The dose-dependent stimulation of A10 cell proliferation by PDGF was not inhibited by E(2) or raloxifene in contrast to the results obtained in VSMC. Moreover, E(2) and raloxifene significantly inhibited the PDGF-induced cyclin D1 promoter activity in A10 cells transfected with cDNA for ERalpha but not in the parental cells. These results suggested that E(2) and raloxifene exert an antiproliferative effect in VSMC treated with PDGF, at least in part through inhibition of pRb phosphorylation, and that the inhibitory effects of E(2) and raloxifene may be mainly mediated by ERalpha.

Induction of endothelial nitric-oxide synthase phosphorylation by the raloxifene analog LY117018 is differentially mediated by Akt and extracellular signal-regulated protein kinase in vascular endothelial cells.

Raloxifene is a tissue-selective estrogen receptor modulator. The effect of estrogen on cardiovascular disease is mainly dependent on direct actions on the vascular wall involving activation of endothelial nitric oxide synthase (eNOS) via Akt and extracellular signal-regulated protein kinase (ERK) cascades. Although raloxifene is also known to activate eNOS in the vascular endothelium, the molecular mechanism responsible for this effect remains to be elucidated. In studies of both human umbilical vein endothelial cells and simian virus 40-transformed rat lung vascular endothelial cells (TRLECs), the raloxifene analog LY117018 caused acute phosphorylation of eNOS that was unaffected by actinomycin D and was blocked by the pure estrogen receptor antagonist ICI182,780. Activation of Akt by raloxifene reached a plateau at 15-30 min and declined thereafter, a similar time frame to that of Akt activation by 17beta-estradiol. On the other hand, both activation and phosphorylation of ERK by raloxifene showed a biphasic pattern (peaks at 5 min and 1 h), whereas ERK activation and phosphorylation by 17beta-estradiol reached a plateau at 5 min and declined thereafter. A MEK inhibitor, PD98059, had no effect on the raloxifene-induced Akt activity, suggesting an absence of cross-talk between the ERK and Akt cascades. Either exogenous expression of a dominant-negative Akt or pretreatment of TRLECs with PD98059 decreased the raloxifene-induced eNOS phosphorylation. Moreover, raloxifene stimulated the activation of Akt, ERK, and eNOS in Chinese hamster ovary cells expressing estrogen receptor alpha but not Chinese hamster ovary cells expressing estrogen receptor beta. Our findings suggest that raloxifene-induced eNOS phosphorylation is mediated by estrogen receptor alpha via a nongenomic mechanism and is differentially mediated by Akt- and ERK-dependent cascades.

Successful double autografts for patients with relapsed clear cell sarcoma of the kidney.

Although the prognosis of clear cell sarcoma of the kidney (CCSK) has improved, when metastases occur the probability of cure is very low. We have treated two pediatric patients with relapsed CCSK, one with multiple bone metastases and another with brain metastases. After one or two courses of re-induction chemotherapy and radiation therapy to the sites of metastasis, they received double high-dose chemotherapy with autologous bone marrow rescue. Conditioning regimens were ifosphamide plus melphalan for the first autograft and busulfan plus thiotepa for the second. Hematological recovery was prompt, and no severe complications were observed. They are doing well without evidence of recurrence at 19 and 49 months after the second autograft, respectively.

Staged surgery for a large cerebral arteriovenous malformation to prevent the overload phenomenon.

Intracerebral hemorrhage and/or edema is a sequel following removal of a large nidus. We call the vascular load an 'overload phenomenon'. To prevent it by stepwise reduction of the nidus size, staged surgery is recommended for a large AVM (nidus size of more than 5 cm). With the recent advancement of the intravascular technique, preoperative embolization is also a good option to reduce the nidus size resulting in a prevention of the overload phenomenon and a reduction in intraoperative bleeding. The overload phenomenon is visualized on the immediate postoperative angiogram as 'modja-modja' (stagnating and shaggy) vessels around the removed nidus, which disappear in a month. We present a case in which those vessels were identified. Maintaining the postoperative blood pressure at 80 to 100 mmHg is also essential for preventing the overload phenomenon prior to staged surgery and/or preoperative embolization.

Anterior decompression and fusion using bone grafts obtained from cervical vertebral bodies for ossification of the posterior longitudinal ligament of the cervical spine: technical note.

OBJECTIVE: To describe a surgical technique of anterior decompression and fusion using bone grafts obtained from cervical vertebral bodies with ossification of the posterior longitudinal ligament of the cervical spine. This technique seeks to avoid complications associated with an anterior approach of decompression and bone fusion, which widely uses autogenous bone from the iliac crest. METHODS: Forty patients with cervical myelopathy were studied. The ossified ligament was localized to one, two, three, four, five, six, and seven vertebral bodies in 10, 18, 5, 4, 1, 1, and 1 patients, respectively. The ossified area of all posterior longitudinal ligament was completely removed using microsurgical techniques, and 11 patients were operated on at one level, 21 at two levels, and 8 at three levels. RESULTS: The symptoms of all patients improved after the operation. Postoperative x-ray films showed solid bone fusion in all patients at a mean follow-up time of 3 years (range, 1-5.25 yr). Anterior angulation was found in one of eight patients (13%) who underwent three-level fusion. CONCLUSION: Two major advantages were as follows: 1) no complications related to the iliac donor site occurred, and 2) early mobilization of patients was possible with a soft cervical collar. Anterior decompression and fusion should be used for cases with ossification of up to three consecutive vertebrae needing either one- or two-level fusions.

[Two cases of ossified spinal meningioma].

It is generally known that meningioma has histological pleomorphism and ossification is one of them. In the cases of spinal meningioma, osteoblastic type is rare. We encountered two different types of ossified spinal meningioma. Two cases of ossified spinal meningioma are reported in this paper. One case is that of a 45-year-old male who had a sudden transient tetraparesis with a tumor located in the upper cervical spinal column. The tetraparesis was caused by the patient's head having been hit. Another case is a 74-year-old female, who had progressive paraparesis and hypesthesia in her lower extremities, with a tumor located in the 9th thoracic spinal column. The MRI findings in these cases suggested that an ossified area was included in the tumor. We performed surgical therapy in both cases, and an operative finding was that these tumors had a very hard component. Histopathological diagnosis in both cases was meningioma. The former included isolated matured bone tissue with fat marrow mixed with the tumor tissue, and the latter included scattered matured lamellar bone tissue. These tumors are considered to be osteoblastic in type.

Intra-operative monitoring by facial electromyographic responses during microvascular decompressive surgery for hemifacial spasm.

The facial electromyographic response was monitored intraoperatively in 40 patients with hemifacial spasm who were operated on by microvascular decompression of the facial nerve. All 40 patients showed an abnormal facial electromyographic response (lateral spread response) with a latency of about 10 msec after stimulation. The abnormal response resolved before decompression in 22, resolved immediately with decompression in 16, and failed to resolve in two. Of the 38 patients in whom the abnormal response disappeared during surgery, 36 were postoperatively free from hemifacial spasm and two had mild hemifacial spasm. The two patients in whom the lateral spread response did not disappear during surgery showed persistent hemifacial spasm. In conclusion. Disappearance of the lateral spread response during surgery correlated with the absence of hemifacial spasm in the early postoperative period. The prognosis of hemifacial spasm was good in cases in whom the lateral spread response disappeared. Therefore, the authors think that intra-operative facial electromyography is very useful in assessing the efficacy of microvascular decompression and in predicting the prognosis of hemifacial spasm.

A3-A3 side-to-side anastomosis in the anterior communicating artery aneurysm surgery: report of four cases.

BACKGROUND: Giant or large aneurysms prevent direct clipping without compromise of the parent vessels, and any countermeasures should be attempted. METHODS: We describe an A3-A3 side-to-side anastomosis as a method of revascularization of the pericallosal artery in surgery of an aneurysm of the anterior communicating artery (ACoA) in four patients. RESULTS: In two patients with the pericallosal artery narrowed or occluded by the clipping or trapping procedure, and in two other patients with giant aneurysms clipped with prolonged duration of temporary occlusion of the parent vessels, no serious neurologic changes were observed after surgery. CONCLUSIONS: We believe that an A3-A3 side-to-side anastomosis is effective in preventing ischemic complications in the territory of the pericallosal artery.

[Surgical treatment for ossification of the posterior longitudinal ligament of the cervical spine].

The surgical results in 37 patients with cervical myelopathy due to ossification of the posterior longitudinal ligament of the cervical spine were described. This series consisted of 32 patients who underwent anterior decompression with anterior cervical fusion using bone grafts obtained from cervical vertebral bodies, and 5 patients who underwent expansive laminoplasty or laminectomy as a method of posterior decompression. 6 out of 32 patients with anterior cervical fusion were operated on at one level, 18 at two levels and 8 at three levels. The patients were out of bed within two days and treated using a soft collar for 3 months. In all patients, the symptoms improved postoperatively. Postoperative X-ray films showed solid bone fusion in all patients with anterior cervical fusion at a mean follow up time of one year and nine months (range 6 months to 3 years 6 months). Anterior angulation was found in one (3%) out of 32 patients who underwent anterior cervical fusion. Concerning the method of operation, the authors think that anterior decompression is to be recommended for cases with ossification within three consecutive vertebrae and posterior decompression should be applied to cases in which anterior decompression is very difficult. If necessary, a two-stage combined decompression is recommended.

A giant mesenteric aneurysm and sudden death.

In sudden death cases, aortic or cerebral artery aneurysms are not infrequent, but a mesenteric artery branch aneurysm has not previously been reported. In the present paper, we describe a case of sudden death from the rupture of a giant mesenteric aneurysm.