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.

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.

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.

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.

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.

Potential survival benefit of secondary cytoreductive surgery for recurrent epithelial ovarian, tubal, and peritoneal cancers.

OBJECTIVE: Although treatment for recurrent epithelial ovarian, tubal, and peritoneal cancers is usually not curative and intends to be palliative, a certain significance of secondary cytoreductive surgery (SCS) for recurrent tumor has been reported; still, there are limitations in this strategy including difficulty in predicting successful complete resection and selecting good candidates. The purpose of this study was to explore the potential survival benefit of SCS in patients with recurrent epithelial ovarian, tubal, and peritoneal cancers. METHODS: Among all patients who underwent primary therapy for epithelial ovarian, tubal, and peritoneal cancers between 1994 and 2006 at our institute, medical records of patients who were submitted to SCS for recurrence following complete remission after primary therapy were retrospectively investigated. Kaplan-Meier method and log-rank test were used for survival analysis, and Cox proportional hazard regression model was used for quantifying the relations between survival and covariates. RESULTS: Thirty-four patients met the inclusion criteria. Complete resection of all visible tumors at SCS was achieved in 24 of patients (75%). Median postrecurrence survival was 60 months. On univariate analysis, solitary recurrence, disease-free interval, CA125 value at recurrence, and complete resection were significant prognostic factors on postrecurrence survival; whereas on multivariate analysis, CA125 value at recurrence and complete resection were independent prognostic factors. In addition, a comparison according to the initial method that detected recurrence revealed that patients whose recurrence was detected with CA125 elevations had significantly worse postrecurrence survival than those detected with routine examinations including image scans (P = 0.021). CONCLUSIONS: In the present study, the impact of SCS on the significant survival benefit was identified for patients with low CA125 value at recurrence as well as with complete resection. Although further analyses are needed, patients whose recurrence was diagnosed by routine examinations without CA125 elevation might be better candidates for SCS.

[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.

[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.

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.

Clinical significance of UDP-glucuronosyltransferase 1A1*6 for toxicities of combination chemotherapy with irinotecan and cisplatin in gynecologic cancers: a prospective multi-institutional study.

BACKGROUND: To investigate the effects of UDP-glucuronosyltransferase 1A1 (UGT1A1) *28, *6 and *27 in patients with gynecologic cancer who received chemotherapy with irinotecan and cisplatin. METHODS: Patients eligible for this study had cervical or ovarian cancer treated with chemotherapy; a course of the regimen consisted of 60 mg/m(2) of irinotecan on days 1, 8 and 15, and 60 mg/m(2) of cisplatin on day 1 every 4 weeks. UGT1A1 polymorphisms and toxicities were analyzed. RESULTS: From March 2007 to December 2007, 30 Japanese patients were enrolled; 24 ovarian carcinoma patients and 6 cervical cancer patients. The following genotypes of UGT1A1 were found: wild type in 17 patients (57%), *28 in 4 patients (13%), *6 in 8 patients (27%), *28*6 in 1 case (3%) and no case of *27 (0%). Grade 3/4 neutropenia, thrombocytopenia and diarrhea were significantly more frequent in *6 patients compared with wild-type patients. Also, in *6 patients irinotecan administration on days 8 or 15 was significantly more often omitted due to toxicities. In patients with *28 or *28*6, side effects were similar to those in patients with *6. CONCLUSION: In addition to UGT1A1*28, UGT1A1*6 might also be a key candidate to determine the dose of combination chemotherapy with irinotecan and cisplatin.

Complete remission of metastatic and relapsed uterine cervical cancers using weekly administration of bevacizumab and paclitaxel/carboplatin.

BACKGROUND: Palliative therapy is usually employed for the treatment of metastatic or relapsed cervical cancer. Many agents including cisplatin have been used for fighting the tumor; however, the gold standard therapy has not yet been confirmed. CASE REPORT: Two cases of recurrent metastatic or refractory cervical cancer successfully treated with weekly administration of bevacizumab (2 mg/kg), paclitaxel (80 mg/m(2)), and carboplatin (area under the curve (AUC) = 2.0) are presented. 1 course of the therapy consisted of weekly paclitaxel/carboplatin on days 1, 8, and 15 and weekly bevacizumab on days 1, 8, 15, and 21, q28 days. Complete remission was observed after 3-4 courses of the therapy. Hematologic and non-hematologic toxicities higher than grade 3 were not observed during the chemotherapy. In both cases, there was no evidence of disease more than 10 months after the therapy. CONCLUSIONS: Weekly administration of bevacizumab and paclitaxel/carboplatin has potential activity in recurrent, metastatic, and refractory cervical carcinomas. These findings warrant further trials in such clinical settings.

Survival analysis of ovarian clear cell carcinoma confined to the ovary with or without comprehensive surgical staging.

Pure-type clear cell carcinoma (CCC) has been recognized as a distinct subtype of ovarian cancer, showing a resistance to chemotherapy and resulting in poor prognosis. Our aim was to evaluate the effects of complete surgical procedures followed by adjuvant chemotherapy for CCC patients whose tumors were confined to the ovary (pT1M0). During the period of 1987-2005, 56 patients with stage I CCC were identified and two cases were excluded due to retroperitoneal lymph node metastasis. A total of 54 patients were enrolled in the study and divided into two groups: Group A (n=38, 1993-2005) underwent complete surgical staging including pelvic and para-aortic lymphadenectomy. Group B (n=16, 1987-1992) underwent a hysterectomy, bilateral salpingo-oopherectomy, omentectomy without comprehensive lymphadenectomy. Every patient received six courses of adjuvant chemotherapy using a platinum agent. Survival analysis was estimated by the Kaplan-Meier method and prognostic factors were evaluated using a Cox regression model. The clinical characteristics of the two groups were similar, except for the rate of conventional platinum-based chemotherapy (p=0.02). Multiple regression survival analysis revealed that the completion of a comprehensive staging operation was the only independent factor for progression-free survival of stage I CCC patients (p=0.03) and that the chemotherapeutic regimen was not a prognostic factor (p=0.43). The present study indicates that we should accomplish complete surgical staging procedures for CCC confined to the ovary.

[Bowel perforation associated with bevacizumab therapy in recurrent ovarian cancers without bowel obstruction or bowel involvement].

Recent reports showed that bevacizumab, a humanized recombinant antibody binding to vascular endothelial growth factor (VEGF), harbored a significant activity in advanced or recurrent epithelial ovarian cancers. However, life-threatening complications including arterial thrombosis, pulmonary hemorrhage, and gastrointestinal perforation (GIP) are not negligible. A Japanese case of bowel perforation associated with bevacizumab treatment in heavily pretreated ovarian cancers is reported. The case affected with refractory ovarian cancer had no signs of bowel obstruction and bowel thickness which are now recognized as risk factors of GIP associated with bevacizumab. After obtaining a written informed consent, a combination of weekly paclitaxel and weekly bevacizumab was administered as the fourth-line therapy. After nine cycles of the regimen, the case developed GIP, although the recurrent tumor showed a stable disease. After conservative therapy for two months, the patient died. The case was severely pretreated; however, there seemed to be no risk factors for GIP. Therefore, we do recommend that special cautions are required for the bevacizumab- based chemotherapy, especially severely pretreated ovarian cancer patients.

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.

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 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.