Cost-Effectiveness of Teduglutide for Pediatric Patients with Short Bowel Syndrome in Japan, Including Caregiver Burden.

INTRODUCTION: Short bowel syndrome (SBS) is associated with a significant mental and physical burden for patients and caregivers. Standard of care (SOC) for SBS includes parenteral support (PS) to optimize intestinal function. Teduglutide, a recombinant human glucagon-like peptide 2 analogue, reduces the need for PS in patients with SBS. In this study, we assessed the cost-effectiveness of teduglutide in pediatric patients with SBS from multiple perspectives, considering the caregiver's burden. METHODS: A Markov model was used to evaluate cost (Japanese yen, JPY) and effectiveness (quality-adjusted life years, QALYs) of teduglutide compared with SOC for pediatric patients with SBS in Japan. We conducted a base-case analysis and selected sensitivity and scenario analyses from three perspectives: (1) the public healthcare payer, (2) the public healthcare and long-term care payer, and (3) society. RESULTS: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) was 9,533,412 JPY per QALY from the public healthcare payer perspective, 6,335,980 JPY per QALY from the public healthcare and long-term care payer perspective, and 3,510,371 JPY per QALY from the societal perspective. The probability that cost-effectiveness of teduglutide is favorable from a societal perspective was 59.3%. In all scenario analyses, consistent with the base-case analysis, ICERs for teduglutide compared with SOC were different depending on whether caregiver utility and productivity loss were considered. CONCLUSIONS: Incorporating the caregiver's burden in the cost-effectiveness analysis of teduglutide for pediatric patients with SBS provided a more comprehensive assessment of the value of teduglutide for patients, their families, and society. This approach enhances our understanding of the overall value of a treatment, especially for diseases with significant caregiver burden.

Cost-effectiveness analysis of NVX-CoV2373 COVID-19 vaccination for elderly people in Japan.

Background: NVX-CoV2373 is one of the vaccines marketed for COVID-19 prevention in Japan. Information on its cost-effectiveness is important for making well-informed decisions on the future of Japan's COVID-19 vaccination programme from the public healthcare payer's perspective. The aim of this study was to evaluate the cost-effectiveness of NVX-CoV2373 vaccination in the elderly Japanese population. Methods: Two analysis populations that included elderly Japanese individuals (aged ≥ 65 years) were defined in this study: those who had not received a COVID-19 vaccine or had not completed a primary vaccination series (i.e., first two vaccinations) with an approved COVID-19 vaccine (analysis population 1), and those who had received two primary vaccinations with an approved COVID-19 vaccine (analysis population 2). A literature-informed Markov model for each analysis population was developed to evaluate the cost-effectiveness of vaccination with NVX-CoV2373 against no vaccination with NVX-CoV2373 from the public healthcare payer's perspective as a base-case analysis and from the societal perspective as a scenario analysis. Vaccine efficacy was estimated from a phase 3 study of NVX-CoV2373 (EudraCT number: 2020-004123-16). Cost-effectiveness was assessed using a willingness-to-pay threshold of Japanese yen (JPY) 5 million per quality-adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses were also performed. Results: For analysis population 1, NVX-CoV2373 primary and booster vaccinations would reduce costs by JPY 37,647 and prolong QALYs by 0.01601. Therefore, NVX-CoV2373 primary and booster vaccinations were considered to be dominant over no vaccination. For analysis population 2, an NVX-CoV2373 booster vaccination would increase costs by JPY 5010 and prolong QALYs by 0.00550, with the incremental cost-effectiveness ratio of JPY 910,566 per QALY gained. Conclusions: Our analyses suggest that a vaccination strategy with NVX-CoV2373 is cost-effective in the elderly population (aged ≥ 65 years) of Japan.

Cost-effectiveness analysis of cabozantinib compared with everolimus, axitinib, and nivolumab in subsequent line advanced renal cell carcinoma in Japan.

AIMS: The treatment landscape of renal cell carcinoma has changed with the introduction of targeted therapies. While the clinical benefit of cabozantinib is well-established for Japanese patients who have received prior treatment, the economic benefit remains unclear. The objective of this study was to assess the cost-effectiveness of cabozantinib compared with everolimus, axitinib, and nivolumab in patients with advanced renal cell carcinoma who have failed at least one prior therapy in Japan. METHODS: A cost-effectiveness model was developed using a partitioned survival approach and a public healthcare payer's perspective. Over a lifetime horizon, clinical and economic implications were estimated according to a three-health-state structure: progression-free, post-progression, and death. Key clinical inputs and utilities were derived from the METEOR trial, and a de novo network meta-analysis and cost data were obtained from publicly available Japanese data sources. Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were estimated. Costs and health benefits were discounted annually at 2%. RESULTS: Cabozantinib was more costly and effective compared with everolimus and axitinib, with deterministic incremental cost-effectiveness ratios of ¥5,375,559 and ¥2,223,138, respectively. Compared to nivolumab, cabozantinib was predicted to be less costly and more effective. Sensitivity and scenario analyses demonstrated that the key drivers of cost-effectiveness results were the estimation of overall survival and treatment duration, relative efficacy, drug costs, and subsequent treatment costs. LIMITATIONS: METEOR was an international trial but did not enroll any patients from Japan. Efficacy and safety data from METEOR were used as a proxy for the Japanese population following validation by clinical experts, and alternative assumptions specific to clinical practice in Japan were evaluated in scenario analyses. CONCLUSIONS: In Japan, cabozantinib is a cost-effective alternative to everolimus, axitinib, and nivolumab for the treatment of patients with advanced renal cell carcinoma who have received at least one prior line of therapy.

Value elements and methods of value-based pricing for drugs in Japan: a systematic review.

INTRODUCTION: Value-based pricing (VBP) can be a promising tool for optimizing drug prices. However, there is no consensus on the specific value elements and pricing method that should be used for VBP. AREAS COVERED: We performed a systematic review and narrative synthesis to investigate the value elements and pricing method for VBP. The main inclusion criterion was that value elements, VBP method, and estimated prices for actual drugs were reported. We performed a search in MEDLINE and ICHUSHI Web. Eight articles met the selection criteria. Four studies adopted the cost-effectiveness analysis (CEA) approach and the others used different approaches. The CEA approach included the value elements of productivity, value of hope, real option value, disease severity, insurance value in addition to costs and quality-adjusted life years. The other approaches used efficacy, toxicity, novelty, rarity, research and development costs, prognosis, population health burden, unmet needs, and effectiveness. Each study used individual methods to quantify these broader value elements. EXPERT OPINION: Both conventional and broader value elements are used for VBP. To allow VBP to be widely applied to various diseases, a simple, versatile method is preferable. Further research is needed to establish VBP method which enables to incorporate broader values.

Health-related quality of life in health states corresponding to different stages of perianal fistula associated with Crohn's disease: a quantitative evaluation of patients and non-patients in Japan.

Background: Perianal fistula (PF), a complication of Crohn's disease (CD), affects health-related quality of life (QOL). Objective: To elucidate QOL of health states corresponding to different stages of PF associated with CD in Japan. Method: This cross-sectional, observational, web-based questionnaire survey assessed eight different health states in patients with CD and PF and individuals without CD (non-patients) from the Medilead Healthcare Panel (MHP) and determined the utility values (QOL scores) in each health state by the time trade-off method. In patients, we determined also the utility value of the current health state associated with CD and the PF. The analysis excluded respondents with logical inconsistencies. Results: The analysis included 82 patients and 576 non-patients with the same sex and age distribution as the Japanese population. In both groups, mean utility values were higher in remission (patients, 0.78; non-patients, 0.51) than in non-remission states, with lowest values for poor prognosis after proctectomy (patients, 0.13; non-patients, -0.10) and highest values for the state with mild symptoms (patients, 0.60; non-patients, 0.30). In patients, the mean utility value of the current health state was 0.71. Conclusion: QOL decreases with increasing severity of PF and is lower for good prognosis after proctostomy than for remission.

Association between High Platelet Reactivity Following Dual Antiplatelet Therapy and Ischemic Events in Japanese Patients with Coronary Artery Disease Undergoing Stent Implantation.

AIM: Although high on-treatment platelet reactivity (HTPR) with dual antiplatelet therapy (DAPT) correlates with long-term adverse outcomes in patients undergoing percutaneous coronary intervention, the correlation in Japanese patients remains unclear. Therefore, we examined the relationship between platelet reactivity during DAPT with aspirin and clopidogrel and 1-year clinical outcomes following successful coronary stent implantation. METHODS: A prospective, multicenter registry study (j-CHIPS) was conducted in patients undergoing coronary stenting and receiving aspirin and clopidogrel at 16 hospitals in Japan. A VerifyNow point-of-care assay was used to assess platelet reactivity, and a cutoff value to define HTPR was established. RESULTS: Between February 2011 and May 2013, 1047 patients were prospectively enrolled, of which 854 patients with platelet function evaluation at 12-24 h after PCI were included in the final analysis. After 1 year of follow-up, the incidence of the primary endpoint (a composite of all-cause mortality, myocardial infarction, stent thrombosis, and ischemic stroke) was significantly higher in patients with HTPR than in those without (5.9% vs. 1.5%, p=0.008), and HTPR showed a modest ability to discriminate between patients who did and did not experience major adverse cardiac and cerebrovascular events (area under the curve, 0.60; 95% confidence interval, 0.511-0.688, p=0.039). HTPR status did not identify patients at risk for major or minor bleeding events. CONCLUSION: HTPR was significantly associated with adverse ischemic outcomes at 1 year after PCI in Japanese patients receiving maintenance DAPT, indicating its potential as a prognostic indicator of clinical outcomes in this high-risk patient population.

Efficacy and safety of adjunctive rasagiline in Japanese Parkinson's disease patients with wearing-off phenomena: A phase 2/3, randomized, double-blind, placebo-controlled, multicenter study.

INTRODUCTION: Rasagiline, a selective, irreversible monoamine oxidase-B inhibitor, is in development in Japan as adjunctive therapy to levodopa. This Phase 2/3 trial evaluated the efficacy and safety of adjunctive rasagiline in Japanese patients with Parkinson's disease (PD) and wearing-off phenomena. METHODS: Patients aged 30-79 years with diagnosed PD and stable levodopa use were randomized 1:1:1 to rasagiline (0.5/1 mg/day) or placebo for 26 weeks. The primary endpoint was change from baseline in mean daily OFF-time during the treatment period. RESULTS: In total, 141, 134, and 129 patients were randomized to placebo, rasagiline 0.5 mg, or rasagiline 1 mg, respectively. Baseline characteristics were well balanced. Least squares (LS) mean differences vs. placebo for change from baseline in mean daily OFF-time were -0.84 h (rasagiline 1 mg/day) and -0.60 h (rasagiline 0.5 mg/day); both differences were statistically significant. LS mean differences vs. placebo for change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II and Part III total scores (in ON-state) and Parkinson's Disease Questionnaire-39 Summary Index Score were: -1.27, -1.74, and -2.51 (0.5 mg/day) and -1.27, -2.14, and -3.84 (1 mg/day); all statistically significant. Treatment-emergent adverse events (TEAEs) occurred in 50.4/69.9/73.6% of the placebo, 0.5 mg/day, and 1 mg/day groups, respectively (most common TEAEs were nasopharyngitis [9.2/18.0/14.7%] and dyskinesia [7.1/8.3/16.3%]). CONCLUSIONS: As an adjunct to levodopa, rasagiline reduced OFF-time and improved PD symptoms/signs (MDS-UPDRS scores) and quality of life in Japanese patients with PD and wearing-off phenomena. No important safety concerns were raised.

Effect of ARID1A/BAF250a expression on carcinogenesis and clinicopathological factors in pure-type clear cell adenocarcinoma of the ovary.

Frequent mutation of the ARID1A gene has been recently identified in ovarian clear-cell adenocarcinoma (CCA); however, the clinical significance of BAF250a expression encoded by the ARID1A gene remains to be determined. The aim of the present study was to assess whether BAF250a expression had an impact on the clinical features of CCA. A total of 97 cases of CCA treated at a single institution were enrolled in the present study. The tissue samples were evaluated by immunohistochemical staining. BAF250a-deficient expression was observed in 30% (29/97) of all CCA cases. Of this, 19% of non-atypical endometriosis, 26% of atypical endometriosis, 39% of endometriosis-related CCA, 5% of benign clear-cell adenofibroma (CCAF), 5% of borderline CCAF and 10% of CCAF-related CCA. BAF250a-deficient expression was significantly more frequent in endometriosis-related CCA compared with that in CCAF-related CCA (P=0.02). No significant difference was observed in the response rate of primary chemotherapy according to BAF250a expression status (P=0.48). Additionally, BAF250a expression status was not significantly correlated with progression-free and overall survival in patients with CCA. Although loss of BAF250a expression was associated with early tumorigenesis in endometriosis-related CCA, this alteration was not significantly correlated with chemosensitivity and prognoses of CCA. Further biomarker analyses, including BAF250a expression, are required to improve the prognoses of CCA.

Is Modified Radical Hysterectomy Needed for Patients with Clinical Stage I/II Endometrial Cancers? A Historical Control Study.

OBJECTIVE: The aim of the present study was to assess whether hysterectomy with wider resection could improve survival by preventing local recurrence. METHODS: Medical charts of the patients with clinical stage I/II endometrial cancers treated at our hospital between 1990 and 2009 were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse effects according to the type of hysterectomy. RESULTS: A total of 247 patients were identified: 46 patients treated with total abdominal hysterectomy (TAH group) and 201 patients with modified radical hysterectomy (mRH group). No significant differences were observed in OS (p = 0.52) and PFS (p = 0.67) between the two groups. Also, there was no significant difference in the distribution of recurrent sites between the two groups. The patients treated with mRH had a longer operation time and more frequently developed severe adverse events, such as blood loss and lymphedema. CONCLUSION: In our cohorts, there were no significant differences in both PFS and OS according to surgical procedures, and the mRH group more frequently developed severe adverse events. Overall, clinical benefit was not obtained by mRH in patients with clinical stage I/II endometrial carcinomas.

A case of successful percutaneous transluminal septal myocardial ablation for heart failure due to severe left ventricular outflow obstruction with Mönckeberg's arteriosclerosis, manifested after aortic valvular replacement.

Although percutaneous transluminal septal myocardial ablation (PTSMA) has been the established treatment of symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM), the efficacy for specific HOCM is not elucidated. We report a successful case of PTSMA for heart failure with severe left ventricular outflow tract (LVOT) obstruction due to sigmoid-shaped interventricular septum and diffuse left ventricular hypertrophy with Mönckeberg's arteriosclerosis and aortic valvular stenosis. While the PTSMA relieved LVOT obstruction and symptoms in the acute phase, the modest recurrence was confirmed 6 months later, which is rare in the case of idiopathic HOCM. The possible mechanisms of LVOT obstruction and recurrence are discussed.

DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers.

OBJECTIVE: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study. METHODS: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively. RESULTS: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers. CONCLUSION: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.

A case with fistula formation between a perinephric retroperitoneal abscess, a ureter and a descending colon: Successful outcome after conservative management.

A 72-year-old man diagnosed with hydronephrosis and perinephric abscess because of an impacted urinary stone in the left uretero-pelvic junction was admitted to hospital with high-grade fever. The insertion of a percutaneous drain improved his general condition. Then, imaging from the percutaneous drainage tube revealed a fistula formation between the cavity of the perinephric retroperitoneal abscess, the descending colon, and the left renal pelvis. The patient received conservative management, including insertion of a percutaneous drain, discontinuation of oral intake and antimicrobial chemotherapy. Three days after the percutaneous drainage and discontinuation of oral intake, imaging revealed no apparent fistula. Fistula formation between a perinephric abscess and the descending colon is very rare; this is the first case of a long-term favourable outcome by conservative management.

Clear cell histology as a poor prognostic factor for advanced epithelial ovarian cancer: a single institutional case series through central pathologic review.

OBJECTIVE: Compared with serous adenocarcinoma (SAC), clear cell carcinoma (CCC) often shows chemo-resistance, which would potentially lead to a poor prognosis. On the other hand, there have been arguments over prognoses of CCC and SAC disease. In the present study, multivariate analysis to compare prognosis of CCC patients with that of SAC was aimed for the patients selected from central pathologic review. METHODS: Between 1984 and 2009, a total of 500 ovarian cancer patients were treated at our university hospital. Among them, 111 patients with CCC and 199 patients with SAC were identified through central pathological review. Overall survival and progression-free survival were compared using Kaplan-Meier method, and prognostic factors were investigated by multiple regression analyses. RESULTS: Median age was 52 years for CCC and 55 years for SAC (p=0.03). The ratio of stage I patients were significantly higher in CCC compared with SAC (55% vs. 13%, p<0.01). Among evaluable cases, response rate was significantly lower in CCC than that in SAC (32% vs. 78%, p<0.01). No significant differences of progression-free survival and overall survival were observed in stage I patients; however, prognoses of CCC were significantly poorer than those of SAC in advanced-stage disease. In stage II-IV patients, not only residual tumors and clinical stages, but also clear cell histology were identified as predictors for poor prognosis. CONCLUSION: Clear cell histology was identified as a prognostic factor for advanced-stage ovarian cancers. Histologic subtypes should be considered in further clinical studies, especially for advanced epithelial ovarian cancers.

Outcomes of palliative bowel surgery for malignant bowel obstruction in patients with gynecological malignancy.

The aim of this study was to evaluate the outcomes of patients with a gynecological malignancy who received palliative care with and without surgical procedures for malignant bowel obstruction (MBO) and to explore prognostic factors to aid the selection of patients who would benefit from palliative surgery. Medical records of patients with MBO due to a gynecological malignancy treated at our institute between 2005 and 2010 were reviewed. Successful palliation following surgery was defined as the ability to tolerate solid food for at least 60 days. Clinical variables were analyzed using Chi-square or Fisher's exact tests. Survival was evaluated using the Kaplan-Meier method and log-rank test. A total of 53 cases were identified; 20 had bowel surgery for MBO as a palliative procedure and 33 did not. Colostomy was performed in 11 (55%) of 20 patients and ileostomy was performed in 7 (35%). The postoperative morbidity was 35% and mortality within 30 days was 5%. Successful palliation following surgery was achieved in 14 (70%) of 20 cases with a median period of 146 days (range, 61-294). Survival following the diagnosis of MBO was longer in cases with surgery than those without (median survival time, 146 versus 69 days; P<0.0001). Although age, presence of ascites, laboratory values and types of prior anticancer therapy were not significantly different, a longer interval from last anticancer therapy to diagnosis of MBO was observed in patients who underwent surgery compared with those who did not (median, 57 versus 30 days; P<0.05), as well as superior performance status. Among the patients with surgery, the interval was also longer in patients with successful palliation compared with those without (median, 83 versus 32 days; P<0.05). The palliative benefit of surgery for MBO in selected patients with gynecological malignancy was observed. The interval from last anticancer therapy to diagnosis of MBO may serve as a prognostic factor when considering surgical intervention.

Comparison of five-year outcome of sirolimus-eluting stent implantation for chronic total occlusions versus for non-chronic total occlusion (from the j-Cypher registry).

The aim of this study was to evaluate the 5-year clinical outcomes of patients who underwent sirolimus-eluting stent implantation for chronic total occlusion (CTO). Among 10,759 patients treated exclusively with sirolimus-eluting stent in the j-Cypher registry, clinical outcomes were compared between 1,210 patients with revascularization for CTO and 9,549 patients with revascularization for non-CTO only. The cumulative 5-year incidence of all-cause death (13.2% vs 14.3%, p = 0.56) and definite stent thrombosis (1.9% vs 1.6%, p = 0.76) was similar between the 2 groups. The adjusted risk for CTO relative to non-CTO for all-cause death and definite stent thrombosis was insignificant (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.81 to 1.16, and HR 0.99, 95% CI 0.6 to 1.65, respectively). The cumulative incidence of target lesion revascularization was significantly higher in the CTO group (20.7% vs 14.8%, p <0.001). The adjusted risk for target lesion revascularization was significant (HR 1.31, 95% CI 1.13 to 1.52, p <0.001). In the subgroup analysis, the risk for CTO for all-cause death tended to be lower in the subgroup of patients with left ventricular ejection fractions ≤40% (HR 0.68, 95% CI 0.45 to 1.01, p = 0.053), while the risk was significantly higher in the subgroup of patients with end-stage renal disease without hemodialysis (HR 1.66, 95% CI 1.02 to 2.70, p = 0.04). In conclusion, sirolimus-eluting stent implantation for CTO appears to be as safe as that for non-CTO for up to 5 years, except for the modestly elevated risk for target lesion revascularization and the higher risk for all-cause death in patients with end-stage renal disease without hemodialysis.

Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible factor-1α, and glucose transporter 1 in the development of ovarian clear-cell adenocarcinoma.

Ovarian clear-cell adenocarcinoma (CCA) is known to be a type of cancer in humans with a high frequency of expression of the mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 (HIF-1), and glucose transporter 1 (Glut1). In this study, we aimed to determine how these alterations contribute to tumor development of CCAs. Immunohistochemical expressions of phosphorylated-mTOR (p-mTOR), HIF-1α, and Glut1 were analyzed in 36 CCAs and 60 coexistent putative precursor lesions: 19 nonatypical and 16 atypical endometriotic lesions, and 11 benign and 14 borderline clear-cell adenofibroma (CCAF) components. Twenty-one cases with solitary endometriosis were also examined. The frequencies of immunopositivity for p-mTOR (in cytoplasm or nucleus), HIF-1α (in nucleus), and Glut1 increased in accordance with higher cytological atypia in the putative precursors: 58%, 5%, and 16% in the nonatypical endometriosis; 63%, 37%, and 50% in the atypical endometriosis; 77%, 95%, and 95% in the endometriosis-associated CCAs; 27%, 0%, and 0% in the benign-CCAF components; 64%, 79%, and 43% in the borderline CCAF components; and 71%, 100%, and 93% in the CCAF-associated CCAs, respectively. p-mTOR, HIF-1α (in the nucleus), and Glut1 were positive in 10%, 5%, and 19% of the solitary endometriosis, respectively. In the putative precursor lesions coexisting with CCA, a strong correlation in the expression between p-mTOR and HIF-1α and between HIF-1α and Glut1 was identified. Expressions of p-mTOR, HIF-1α, and Glut1 have already been evident in the putative precursor lesions of CCA, and these alterations cumulatively occur in the development of ovarian CCA.

[The impact of systematic lymphadenectomy for early-stage ovarian carcinomas].

Among the 161 cases of pT1 ovarian cancer treated at our hospital during the last 25 years, the impact of systematic lymphadenectomy was evaluated in 93 cases of the pT1N0M0 group(N0 group), 59 cases of the pT1NxM0(Nx group), and 9 cases of the pT1N1M0(N1 group). Significantly greater relapse-free survival(RFS)and overall survival(OS)were observed in 108 cases of the N0+N1 group compared to the Nx group(p=0. 006, p=0. 02). Multivariate analysis showed that systematic lymphadenectomy was a significant prognostic factor(hazard ratio 0. 473(95%CI, 0. 235-0. 951; p=0. 036). The present study suggested the systematic lymphadenectomy had a significant therapeutic effect on pT1 stage ovarian cancers.

Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers.

OBJECTIVES: Currently, pegylated liposomal doxorubicin (PLD) is regarded as one of the standard treatment options in recurrent ovarian cancers (ROC). Bevacizumab has shown significant antitumor activity for ROC in single-agent or in combination with cytotoxic agents. We have conducted a preliminary study to investigate effects of combination of bevacizumab and PLD for heavily pretreated patients with ROC. METHODS: Thirty patients with ROC were treated with combination therapy with weekly bevacizumab and PLD, 2 mg/kg of continuous weekly bevacizumab and 10 mg/m(2) of PLD (3 weeks on, 1 week off). The treatment was continued until development of disease progression, or unmanageable adverse effects. Response evaluation was based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and Gynecologic Cancer Intergroup (GCIG) CA125 response criteria. Adverse effects were analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. RESULTS: Overall response rate was 33%, and clinical benefit rate (CR+PD+SD) was 73%. Median progression-free survival was 6 months (range: 2-20 months), and a 6-months progression-free survival was 47%. Any hematological toxicities more than grade 3 were not observed. Two cases developed non-hematologic toxicities more than grade 2; a case with grade 3 hand-foot syndrome, another with grade 3 gastrointestinal perforation (GIP). The case with GIP was conservatively treated and recovered after 2 months, and there was no case with treatment-related death. CONCLUSION: The present investigation suggested that combination therapy with bevacizumab and PLD was active and well tolerated for patients with ROC. We recommend the regimen be evaluated in further clinical studies.

[Late thrombosis of sirolimus-eluting stent occurring in the perioperative period].

We report a late thrombosis of sirolimus-eluting stent 6 months after implantation of a drug-eluting stent. A 70-year-old man (52 kg, 148 cm) was diagnosed as acute cauda equina syndrome, and spinal surgery was scheduled. One week before the operation, the patient's aspirin and clopidogrel regimen was replaced with heparin injection, which was then discontinued 8 hours before the operation. The operation was completed uneventfully. The patient complained of severe chest pain 1 hour after the end of operation. Coronary angiography demonstrated stent thrombosis. PCI (removal of the thrombosis and plain old balloon angioplasty) was performed, and incomplete stent apposition was diagnosed with coronary angiography.