Definitive chemoradiotherapy with paclitaxel for locally advanced esophageal squamous cell carcinoma in older patients (PARADISE-1): a phase I trial.

BACKGROUND: In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity. We conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for locally advanced ESCC in older patients. METHODS: Enrollment was conducted at six centers in Japan from April 2016 to September 2019. The participants were aged ≥ 70 years, had locally advanced ESCC, and were intolerant to surgery or unwilling. A fixed 60-Gy radiation dose was administered in 30 fractions. PTX dosing levels started at 30 mg/m2 weekly for 6 weeks. Depending on the number of DLTs, the dose was set to be increased by 10 mg/m2 or switched to biweekly. A geriatric assessment was performed before treatment using the Geriatric-8 screening tool. The primary endpoint was dose-limiting toxicity (DLT). RESULTS: We enrolled 24 patients (6 per group); DLT was observed in one (grade 4 hypokalemia), one (grade 3 aspiration), two (grade 3 radiodermatitis, grade 3 esophageal hemorrhage), and two (grade 3 anorexia, grade 5 pneumonitis) patients in the weekly PTX 30, 40, 50, and 60 mg/m2 groups, respectively. All adverse events, except death in the 60 mg/m2 group, showed reversible improvement, and the safety profile was considered acceptable. The 2-year survival and complete response rates were 40.0% and 54.2%, respectively. There was a significant difference in survival between favorable and unfavorable Geriatric-8 scores. CONCLUSIONS: The recommended PTX dose with concomitant radiation was determined to be 50 mg/m2 weekly. Phase II trials at this dose are underway.

Optimizing Organ-Preservation Strategies Through Chemotherapy-Based Selection in Esophageal Squamous Cell Carcinoma: Results From the CROC Multi-Institutional Phase 2 Clinical Trial.

PURPOSE: This study aimed to assess the viability of definitive chemoradiotherapy (dCRT) as an organ-preservation strategy for remarkable responders who were downstaged to stage IA after receiving induction chemotherapy for resectable esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS: Chemotherapy-naïve patients with resectable ESCC (stage IB-III, Union for International Cancer Control, International Cancer Control seventh edition) were eligible for the study. All patients received 3 cycles of docetaxel, cisplatin, and 5-FU (DCF) therapy (docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5-fluorouracil [5-FU] 750 mg/m2 on days 1-5, repeated every 3 weeks). Remarkable response was defined as a reduction in the tumor to T1, metastatic lymph nodes <1 cm on the short axis, and downstaging to stage IA after 3 cycles of DCF therapy. Remarkable responders then underwent dCRT, which included 2 courses of cisplatin 75 mg/m2 and 5-FU 1000 mg/m2 on days 1 to 4, repeated every 4 weeks, along with 50.4 Gy of concurrent radiation therapy. The primary endpoint was 1-year progression-free survival in remarkable responders following DCF therapy and subsequent dCRT. Secondary endpoints included 3-year overall survival (OS) and esophagectomy-free survival. RESULTS: Of the 92 patients registered, 90 were analyzed. A remarkable response to 3 courses of DCF therapy was observed in 58.4% of patients. Among these responders, 89.8% achieved a complete response after dCRT. During the median follow-up period of 33 months (range, 1-85 months), the 1-year progression-free survival was 89.8% (95% confidence interval [CI], 77.2%-95.6%, primary endpoint), and the 3-year OS was 83.7%. The 3-year OS and esophagectomy-free survival rates in the analysis group were 74.1% and 45.3%, respectively. An 18F-fluorodeoxyglucose-positron emission tomography response after 2 courses of DCF therapy was significantly associated with OS (P = .0049). CONCLUSIONS: In patients with resectable ESCC, dCRT for remarkable responders downstaging to stage IA after induction chemotherapy with 3 courses of DCF therapy is a feasible treatment option and provides an optimizing organ-preservation strategy of chemotherapy-based selection.

Comparison of Effective Imaging Modalities for Detecting Gastric Neoplasms: A Randomized 3-Arm Phase II Trial.

INTRODUCTION: The early detection of gastric neoplasms (GNs) leads to favorable treatment outcomes. The latest endoscopic system, EVIS X1, includes third-generation narrow-band imaging (3G-NBI), texture and color enhancement imaging (TXI), and high-definition white-light imaging (WLI). Therefore, this randomized phase II trial aimed to identify the most promising imaging modality for GN detection using 3G-NBI and TXI. METHODS: Patients with scheduled surveillance endoscopy after a history of esophageal cancer or GN or preoperative endoscopy for known esophageal cancer or GN were randomly assigned to the 3G-NBI, TXI, or WLI groups. Endoscopic observations were performed to detect new GN lesions, and all suspected lesions were biopsied. The primary endpoint was the GN detection rate during primary observation. Secondary endpoints were the rate of missed GNs, early gastric cancer detection rate, and positive predictive value for a GN diagnosis. The decision rule had a higher GN detection rate between 3G-NBI and TXI, outperforming WLI by >1.0%. RESULTS: Finally, 901 patients were enrolled and assigned to the 3G-NBI, TXI, and WLI groups (300, 300, and 301 patients, respectively). GN detection rates in the 3G-NBI, TXI, and WLI groups were 7.3, 5.0, and 5.6%, respectively. The rates of missed GNs were 1.0, 0.7, and 1.0%, the detection rates of early gastric cancer were 5.7, 4.0, and 5.6%, and the positive predictive values for the diagnosis of GN were 36.5, 21.3, and 36.8% in the 3G-NBI, TXI, and WLI groups, respectively. DISCUSSION: Compared with TXI and WLI, 3G-NBI is a more promising modality for GN detection.

Real-world data on the comprehensive genetic profiling test for Japanese patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: comprehensive genomic profiling test has been covered by Japanese health insurance since June 2019. However, no real-world data on the test have been reported with a focus on Japanese patients with prostate cancer. METHODS: we retrospectively reviewed the data of 45 consecutive patients with metastatic castration-resistant prostate cancer, who underwent the comprehensive genomic profiling tests at Kitasato University Hospital between August 2019 and December 2022. Patients' characteristics, prevalence of gene alterations and therapeutic impact of genotype-matched therapy were assessed. RESULTS: genomic data were obtained using a tissue-based test (n = 32) and liquid-based test (n = 13). Actionable genomic alternations were identified in 51.1% of patients, and 22.2% were treated with genotype-matched therapy. The main reason for not receiving genotype-matched therapy was disease progression, accounting for 46.2% (6/13). Kaplan-Meier analysis showed significantly longer overall survival after the comprehensive genomic profiling tests in patients with genotype-matched therapy under public insurance (17.8%, n = 8) than those without it (median: not reached vs. 18.1 months; P = 0.003). Five (62.5%) out of the eight patients with genotype-matched therapy under public insurance had BRCA1 or 2 deleterious alteration. Multivariate analyses showed that BRCA deleterious alteration (17.8%, n = 8) was an independent risk factor for shorter time to castration-resistant prostate cancer (hazard ratio: 2.46, 95% confidence interval: 1.04-5.87; P = 0.041), and no patients with the alteration had ≤5 bone metastases. CONCLUSIONS: the results of this study showed the promising survival outcomes in patients with genotype-matched therapy under public insurance, even in the castration-resistant prostate cancer setting. Further detection of promising therapeutic target gene is expected to increase the number of patients who reach genotype-matched therapies.

The efficacy and safety of multi-loop traction device for gastric endoscopic submucosal dissection: a single center prospective pilot study.

Although gastric endoscopic submucosal dissection (ESD) is widely used, the degree of difficulty varies greatly depending on the lesion. Since the multi-loop traction device (MLTD) has been suggested to shorten the procedure time in colorectal ESD, we examined the efficacy and safety of using the MLTD in gastric ESD. Thirty patients with gastric neoplasms were prospectively enrolled from February 2022 to December 2022, and the outcomes of ESD with the MLTD were evaluated. The primary outcomes were procedure time and dissection speed. The secondary outcomes were en bloc and R0 resection rates, MLTD attachment time, and complications of ESD with the MLTD. After excluding 1 patient, 29 patients (29 lesions) were treated by ESD with the MLTD. The median procedure time was 26 min (range, 9-210 min), and the median submucosal dissection speed was 39.9 mm2/min (12.4-102.7 mm2/min). The rate of en bloc resection was 100%, the median MLTD attachment time was 3 min (1-7 min), and none of the patients showed intraoperative or postoperative perforations. Thus, gastric ESD with the MLTD showed a favorable procedure time and dissection speed and an acceptable complication rate. Hence, the MLTD may be effective for gastric ESD.

Optimal medical therapy after percutaneous coronary intervention in very elderly patients with coronary artery disease.

BACKGROUND: It is still unclear whether optimal medical therapy (OMT) after percutaneous coronary intervention (PCI) has beneficial effects on long-term clinical outcomes in patients aged ≥80 years with coronary artery disease (CAD). METHODS: This study analyzed the time to the first major adverse clinical event including death or nonfatal myocardial infarction (MI), for up to 3 years after PCI using multicenter registry data. Data for 1056 patients aged > 80 years successfully treated with PCI were included in the analysis. OMT was defined as a combination of antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. RESULTS: In total, 204 (19%) patients in this study received OMT and 852 (81%)　received sub-OMT. During a median follow-up of 725 days, adverse clinical events occurred in 183 patients (death, n=177; nonfatal MI, n=6). Kaplan-Meier analysis showed that patients who received OMT had a lower probability of adverse clinical events than those who received sub-OMT (p<0.01, log-rank test). Propensity score matching yielded 202 patient-pairs treated with OMT or sub-OMT, in whom 64 adverse clinical events (death, n=56, nonfatal MI, n=4) occurred during follow-up. OMT remained significant in the reduction of the risk of adverse clinical events in a multivariate Cox proportional hazards model (hazard ratio 0.44; 95% confidence interval 0.26-0.75; p=0.003). CONCLUSIONS: OMT after PCI was associated with significantly fewer adverse clinical events, including all-cause death and nonfatal MI, in patients aged ≥ 80 years with CAD. OMT might be safe and effective for these very elderly patients.

Evaluation of Prognostic Factors for Unresectable or Recurrent Gastric Cancer Treated with Nivolumab.

PURPOSE: Nivolumab is useful for the treatment of unresectable/recurrent gastric cancer as third-line or later chemotherapy. However, the factors that predict the efficacy of nivolumab monotherapy remain unclear. METHODS: We retrospectively studied the predictive factors of response in 59 consecutive patients treated with nivolumab as third-line or later chemotherapy for unresectable/recurrent gastric cancer at our hospital from October 2017 to May 2020. RESULTS: The median follow-up was 5.9 months. The study included 45 men and 14 women (median age: 71 years). We observed that 7 patients had an Eastern Cooperative Oncology Group performance status of 0 and 52 patients had a performance status of 1-2. Forty-three patients were treated with third-line therapy, seven with fourth-line therapy, and three with fifth-line therapy. The response rate to nivolumab was 6.7% and disease control rate was 35.5%. There were 19 (32.2%) immune-related adverse events for all grades and 9 (15.2%) for grades 3 and 4. Progression-free survival was 1.90 months, and overall survival was 6.30 months. Patients with immune-related adverse events had significantly longer overall survival than those without immune-related adverse events. Multivariate analysis showed that the occurrence of immune-related adverse events and a ratio for neutrophil-to-lymphocyte ratio after 8 weeks of nivolumab treatment to the baseline neutrophil-to-lymphocyte ratio before treatment of ≤ 1.5 were independent prognostic factors for overall survival. CONCLUSIONS: Occurrence of immune-related adverse events and changes in neutrophil-to-lymphocyte ratio during nivolumab treatment may help predict the therapeutic efficacy of nivolumab monotherapy for unresectable or recurrent gastric cancer.

A Stratified Analysis of the Risk Associated With Low Body Mass Index for Patients After Percutaneous Coronary Intervention.

AIMS: The relationship between low body mass index (BMI) and prognostic factors for patients with coronary artery disease, commonly observed in elderly individuals in Japan, is important. Few studies have evaluated the prognosis for patients with low BMI after percutaneous coronary intervention (PCI). Using a multivariable-adjusted model and data from a prospective cohort registry, we analyzed the risk associated with low BMI for patients after PCI. METHODS: This prospective, multicenter registry included 5965 consecutive patients with coronary artery disease who underwent successful PCI. The patients were followed-up clinically for up to 3 years or until the occurrence of major adverse cardiac events. The primary endpoint was all-cause death and nonfatal myocardial infarction composite. RESULTS: Primary events occurred in 639 (10.7%) patients during the follow-up period. A risk analysis of the primary endpoint adjusted for the multivariable model showed a significant increase in risk for elderly individuals, underweight individuals [HR 1.43 (95% confidence interval (CI), 1.10-1.85), P＜0.001], those with diabetes mellitus (DM), peripheral artery disease, low left ventricular ejection fraction or acute coronary syndrome (ACS), and smokers. A stratified adjusted risk analysis based on BMI levels showed that the risk associated with underweight status was significantly pronounced for male patients, those aged 60-74 years, and those with DM or ACS. CONCLUSION: Underweight patients with several risk factors significantly increased risk after PCI. Furthermore, the risk associated with low BMI was significantly more pronounced for men, individuals aged 60-74 years, and patients with DM or ACS.

A Propensity Score Matched Analysis of Statin Effects on Major Adverse Cardiac Events after Percutaneous Coronary Intervention in Patients Over 75 Years Old.

Objective In an extremely aging society, it is beneficial to reconsider the value of medical treatment for extremely elderly patients. We therefore focused on the efficacy of statin therapy in extremely elderly patients. This study investigated the efficacy of statins for secondary prevention in patients over 75 years old. Methods This prospective multicenter registry included 1,676 consecutive extremely elderly patients with coronary artery disease who underwent successful percutaneous coronary intervention (PCI). The patients were followed up clinically for up to three years or until the occurrence of major adverse cardiac events (MACEs), defined as a composite of all-cause death and non-fatal myocardial infarction. Using propensity score methodology to eliminate selection bias, in a 1:1 matching ratio, we selected 466 pairs of patients for the analysis. Results During the median follow-up period of 25 months, MACEs occurred in 176 patients. The Kaplan-Meier analysis showed that statin treatment correlated with a lower probability of initial MACE occurrences within 30 days compared with no statin treatment (log-rank test, p<0.001). According to a landmark analysis at day 30, statin treatment still showed consistent effectiveness for reducing MACE occurrence during the follow up period (p=0.04). A multivariable Cox hazard analysis showed that statin therapy significantly reduced MACE occurrence (hazard ratio 0.55 [0.40-0.75], p<0.001). In the stratification analysis, statin therapy was especially beneficial in patients without symptomatic heart failure. Conclusion Statins were effective in preventing MACEs in extremely elderly patients after PCI.

Stratification Analysis of Statin Effect on Major Adverse Cardiac Events After Percutaneous Coronary Intervention in Patients on Hemodialysis.

ABSTRACT: The statin use in patients on hemodialysis remains controversial, and no beneficial effects of statin on the reduction of adverse cardiovascular events have been reported in these patients. This study used stratification analysis to examine the clinical factors in patients on hemodialysis who could benefit from statin for secondary prevention. This prospective multicenter study included 234 consecutive patients on hemodialysis with coronary artery disease who underwent successful reperfusion therapy with percutaneous coronary intervention. The patients were followed up for up to 3 years or until the occurrence of major adverse cardiac events (MACEs; defined as a composite of all-cause death and nonfatal myocardial infarction). Inverse probability of treatment weighting adjustment was used to remove the selection bias. During the median follow-up period of 30 months, MACEs occurred in 55 patients. Patients with MACEs had significantly lower statin therapy (P < 0.001). Multivariable Cox proportional hazards analysis showed that the patients on statins had a significantly reduced rate of MACE occurrence [adjusted hazard ratio 0.30 (0.11-0.81), P = 0.02]. The stratification analysis of outcomes according to the presence of clinical factors showed that beneficial effects of statin were associated with man, elderly, lower body mass index, lower abdominal circumference, hypertension, diabetes, higher C-reactive protein, symptomatic heart failure, lower left ventricular function, nonacute coronary syndrome, and shorter stent length. Statin was effective for the prevention of MACEs in patients on hemodialysis who underwent percutaneous coronary intervention. We identified specific clinical factors affecting statin effectiveness for secondary prevention.

Healing of iatrogenic double-barrel left main coronary artery dissection extending to the left anterior descending artery.

Iatrogenic left main coronary artery (LMCA) dissection is a complication inadvertently caused by the interventional cardiologist and can have significant consequences. A 38-year-old man presented to hospital with non-ST-elevation myocardial infarction. Coronary angiography (CAG) revealed an obstructed proximal left circumflex artery (LCx) that was successfully treated with revascularization using a drug-eluting stent (DES). However, CAG after recanalization of the LCx demonstrated a spiral dissection of the left coronary artery from the mid-LMCA to the left anterior descending (LAD) artery and LCx. The dissection was classified as National Heart, Lung and Blood Institute type D in LAD and type F in LCx. Immediate exclusion stenting of the dissection flap by another DES and thrombolysis in myocardial infarction 3 flow were achieved in the LAD and LCx. The patient achieved hemodynamic stability with improvement in symptoms, despite residual dissection in the LAD. We, therefore, preferred careful observation over revascularization. The false lumen remained visible with a double-barrel appearance in the LAD on 6-month follow-up CAG, which disappeared at the 2-year follow-up. We report a rare case of a large double-barrel dissection that spontaneously occluded over time without any aggressive interventions. .

Renal Dysfunction as a Predictor of Slow-Flow/No-Reflow Phenomenon and Impaired ST Segment Resolution After Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction With Initial Thrombolysis in Myocardial Infarction Grade 0.

BACKGROUND: The slow-flow/no-reflow phenomenon and impaired ST segment resolution (STR) following primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) predict unfavorable prognosis and are characterized by obstruction of the coronary microvascular. Several predictors of slow-flow/no-reflow have been revealed, but few studies have investigated predictors of slow-flow/no-reflow and STR exclusively in acute myocardial infarction patients with initial Thrombolysis in Myocardial Infarction (TIMI) Grade 0.Methods and Results:In all, 279 STEMI patients with initial TIMI Grade 0 were enrolled in the study. Slow-flow/no-reflow was defined as TIMI Grade <3 by angiography after PCI, and impaired STR was defined as STR <50% on an electrocardiogram after PCI. Slow-flow/no-reflow was observed in 31 patients. In multivariate analysis, estimated glomerular filtration rate (eGFR; odds ratio [OR] 0.97; P=0.007), a history of cerebrovascular disease (OR 4.65, P=0.007), time to recanalization ≥4 h (OR 2.76, P=0.023), and systolic blood pressure ≤90 mmHg (OR 3.45, P=0.046) were independent predictors of slow-flow/no-reflow. Impaired STR was observed in 102 of 248 patients with TIMI Grade 3. In multivariate analysis, eGFR (OR 0.94, P<0.001) and occlusion of the left anterior descending artery (OR 4.48, P<0.001) were independent predictors of impaired STR; eGFR was the only independent predictor of both slow-flow/no-reflow and impaired STR. CONCLUSIONS: Renal dysfunction may be related to coronary microvascular dysfunction and obstruction.

Effects of empagliflozin in different phases of diabetes mellitus-related cardiomyopathy: a prospective observational study.

BACKGROUND: Diabetes mellitus-related cardiomyopathy (DMCMP), defined as left ventricular (LV) dysfunction caused by hyperglycemia in the absence of coronary artery disease, leads to heart failure (HF). Previous studies have shown that treatment with sodium-glucose co-transporter 2 inhibitor (SGLT2i) reduces the risk of exacerbation of HF. The beneficial effects of SGLT2i on HF depend not only on indirect actions such as osmotic diuresis but also on direct actions on the myocardium, leading to improvements in LV function. However, it remains unclear whether SGLT2i treatment is equally effective in any phase of DMCMP. The aim of this observational study was to compare the efficacy of SGLT2i treatment on LV dysfunction between early and advanced DMCMP. METHODS: Thirty-five symptomatic non-ischemic HF patients with LV ejection fraction > 40% and type 2 diabetes mellitus (T2DM) treated with empagliflozin (EMPA group) and 20 controls treated without SGLT2i were enrolled. According to the myocardial extracellular volume fraction (ECV), a reliable marker of cardiac fibrosis quantified by cardiac magnetic resonance, the EMPA group was further divided into early DMCMP (n = 16, ECV ≤ 30%) and advanced DMCMP (n = 19, ECV > 30%) groups and followed up prospectively. Echocardiography was performed at baseline and after 12 months. LV function assessed as LV global longitudinal strain (LVGLS) and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e') were compared. RESULTS: ECV was strongly correlated with T2DM duration (r2 = 0.65, p < 0.001). At baseline, each group had a similar background. After 12 months, the EMPA group, especially the early DMCMP group, showed remarkable improvements in LVGLS (ΔLVGLS: 2.9 ± 3.0% (EMPA) vs. 0.6 ± 2.2% (controls), p = 0.005, and 4.6 ± 1.5% (early DMCMP) vs. 1.6 ± 3.3% (advanced DMCMP), p = 0.003) and E/e' (ΔE/e': - 1.5 ± 4.7 vs. - 0.3 ± 3.0, p = 0.253, and - 3.4 ± 5.5 vs. - 0.1 ± 3.5, p = 0.043). CONCLUSIONS: The positive effects of empagliflozin on LV dysfunction were more remarkable in early than in advanced DMCMP. Early intervention of SGLT2i for DMCMP may be preferable.

Usefulness of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients: a single-center retrospective cohort study.

BACKGROUND: The effectiveness of endoscopic treatment for superficial esophageal squamous cell carcinoma in the elderly is unclear. METHODS: We retrospectively studied efficacy and safety of endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in 358 patients at our hospital from July 2005 to December 2018. Patients were divided into elderly (≥75 years) and young (≤74 years) groups. Efficacy was evaluated based on overall survival and disease-specific survival, whereas safety was investigated based on the frequency of endoscopic submucosal dissection-related adverse events. RESULTS: The median observation period was 50 months. The elderly group comprised 111 patients, and young group comprised 247 patients. In the elderly and young groups, 76 (68.5%) and 159 (64.4%) underwent curative resection (P = 0.450), 8 (7.2%) and 34 (13.8%) underwent non-curative resection plus additional treatment and 12 (10.8%) and 15 (6.0%) underwent follow-up, respectively. The frequency of additional treatment for non-curative resection was significantly lower in the elderly group (P = 0.023). The 3-year overall survival of the elderly and young groups was 85.6 and 94.1%, respectively (P = 0.003). The 3-year disease-specific survival of the elderly and young groups was 98.4 and 98.5% (P = 0.682), respectively. The frequency of endoscopic submucosal dissection-related adverse events did not differ significantly between the groups (P = 0.581). The Charlson Comorbidity Index ≥2 was an independent prognostic factor for survival in the elderly group (P = 0.010; hazard ratio, 5.570; 95% confidence interval, 1.519-20.421). CONCLUSIONS: Endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma in elderly patients is as safe as that for young patients. The evaluation of Charlson Comorbidity Index was considered to help estimate the prognosis of elderly patients.

Tracheobronchial Obstruction Due to Blood Clots in Acute Pulmonary Embolism with Cardiac Arrest Managed with Extracorporeal Membrane Oxygenation.

A 66-year-old Japanese woman developed pulseless electrical activity following an acute pulmonary embolism and was treated with thrombolytic therapy. She remained hemodynamically unstable and therefore underwent extracorporeal membrane oxygenation (ECMO). While receiving treatment with ECMO, blood clots induced by endobronchial hemorrhage caused tracheobronchial airway obstruction, leading to ventilatory defect. Furthermore, her cardiac function improved, resulting in cerebral hypoxemia progression. Therefore, the blood clots were removed with a Fogarty balloon catheter and endobronchial urokinase administration, resulting in improvement in her respiratory condition. Finally, ECMO was decannulated, and the patient was discharged from our hospital without difficulties in her activities of daily living.

Painful Left Bundle Branch Block Syndrome Complicated by Iron-Overload Cardiomyopathy.

Painful left bundle branch block (LBBB) syndrome is a rare disease that presents as simultaneous chest pain and transient LBBB without myocardial ischemia. We diagnosed a 72-year-old Japanese man with painful LBBB syndrome complicated by iron-overload cardiomyopathy. Phlebotomy was initially performed to improve myocardial iron deposition and conductive disturbance. Ironically, his chest pain was fully improved by the completion of incessant LBBB and walk-through phenomenon. However, this case demonstrates a clinically significant therapeutic strategy for cardiomyopathy-induced painful LBBB syndrome. Due to the lack of treatment guidelines, individualized treatment is required for each case of painful LBBB.

Rate Versus Rhythm Control in Tachycardia-Induced Cardiomyopathy Patients with Persistent Atrial Flutter.

Tachycardia-induced cardiomyopathy (TIC) is a potentially reversible cardiomyopathy caused by tachyarrhythmia. For atrial flutter (AFL) -induced TIC, a rhythm control strategy, such as catheter ablation, has been recommended. However, the efficacy of rate control has remained unclear due to the difficulty of achieving control using arrhythmic medications.We prospectively assessed 47 symptomatic heart failure (HF) patients with left ventricular ejection fraction (LVEF) < 50% and suspected persistent AFL-induced TIC. Patients were divided into the rhythm control strategy (n = 22; treatment with catheter ablation or electrical cardioversion) and rate control strategy (n = 25; treatment with bisoprolol) groups. The latter was further divided into the strict rate control strategy (average heart rate < 80 bpm) and lenient rate control strategy (average heart rate < 110 bpm) subgroups. The primary outcome was left ventricular (LV) function recovery, which was defined as an increase in LVEF ≥ 20% or to a value of ≥ 55% after 6 months.In the rhythm control strategy group, more patients achieved LV function recovery after 6 months (95.2% versus 60.9%, P = 0.010). The cumulative incidence of worsening HF events was significantly higher in the rate control strategy group than in the rhythm control strategy group (hazard ratio, 4.66; 95% confidence interval, 1.01-21.57). The subgroup study revealed the advantage of the strict rate control strategy for achieving LV function recovery (83.3% versus 36.4%, P = 0.036).The rate control strategy was significantly inferior to the rhythm control strategy for the LV function recovery in TIC patients with persistent AFL. Our findings suggest that the strict rate control strategy should be aimed if the rhythm control strategy cannot be performed.

Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer.

PURPOSE: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). RESULTS: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). CONCLUSIONS: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

Randomized study of prevention of gastrointestinal toxicities by nutritional support using an amino acid-rich elemental diet during chemotherapy in patients with esophageal cancer (KDOG 1101).

BACKGROUND: This randomized study was designed to evaluate the clinical effect of an elemental diet during chemotherapy in patients with esophageal cancer. METHODS: The inclusion criteria were as follows: (1) esophageal squamous cell carcinoma, (2) stage IB-IV, (3) schedule to receive docetaxel, cisplatin, and 5-fluorouracil (DCF chemotherapy), (4) 20-80 years old, (5) performance status of 0-2, (6) oral intake ability, and (7) written informed consent. Patients were divided into two groups: the elemental supplementary group and the non-supplementary group. Patients received ELENTAL® (160 g/day) orally 9 weeks after the start of chemotherapy. Primary endpoint was the incidence of grade 2 or higher gastrointestinal toxicity according to the Common Terminology Criteria for Adverse Events, version 4.0. Secondary endpoints were the incidence of all adverse events and the evaluation of nutritional status. RESULTS: Thirty-six patients in the elemental supplementary group and 35 patients in the non-supplementary group were included in the analysis. The incidence of grade 2 or higher gastrointestinal toxicity and all grade 3 or 4 adverse events did not differ significantly between the groups. In the elemental supplementary group, the body weight (p = 0.057), muscle mass (p = 0.056), and blood levels of transferrin (p = 0.009), total amino acids (p = 0.019), and essential amino acids (p = 0.006) tended to be maintained after chemotherapy. CONCLUSION: Nutritional support provided by an amino acid-rich elemental diet was ineffective for reducing the incidence of adverse events caused by DCF chemotherapy in patients with esophageal cancer.

A management of neutropenia using granulocyte colony stimulating factor support for chemotherapy consisted of docetaxel, cisplatin and 5-fluorouracil in patients with oesophageal squamous cell carcinoma.

BACKGROUND: An exploratory study was designed to evaluate the efficacy of granulocyte colony stimulating factor support for chemotherapy consisting of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer. METHODS: The inclusion criteria were as follows: (1) oesophageal squamous cell carcinoma, (2) a schedule to receive three courses of induction chemotherapy (docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, 5-fluorouracil 750 mg/m2 days 1-5, every 3 weeks), (3) stage IB-III, (4) 20-75 years old, (5) 0-1 performance status, (6) preserved organ functions and (7) written informed consent. The endpoints were to evaluate the efficacy of granulocyte colony stimulating factor support including secondary prophylactic usage for docetaxel, cisplatin and 5-fluorouracil chemotherapy. Patients who previously had 'febrile neutropenia', or 'Grade 3 or 4 infection accompanied by grade 3 or 4 neutropenia' prophylactically received granulocyte colony stimulating factor support from day 7. RESULTS: A total of 91 patients were included in the analysis. Granulocyte colony stimulating factor support was given to 81.3%. The incidence of grade 4 neutropenia and febrile neutropenia were 81.3 and 32.9%, respectively. The dose of anticancer agents was reduced in 48.4%. There were no treatment-related deaths. The relative dose intensity of docetaxel, cisplatin and 5-fluorouracil were 92.7 ± 9.8%, 86.0 ± 15.6% and 91.8 ± 10.0%, respectively. In the secondary prophylactic granulocyte colony stimulating factor support group, the neutrophil count significantly increased between day 7 and day 13 as compared with the non-prophylactic granulocyte colony stimulating factor support group (P < 0.05 for each day). CONCLUSIONS: Granulocyte colony stimulating factor support including secondary prophylactic usage may be feasible for maintaining the intensity of docetaxel, cisplatin and 5-fluorouracil chemotherapy in patients with oesophageal cancer.