Anatomical approach to suppression of para-Hisian ventricular arrhythmias with changes in QRS morphology after ablation at the earliest activation site.

BACKGROUND: The anatomical approach for the management of para-Hisian ventricular arrhythmias (VAs) with QRS morphological changes after catheter ablation (CA) has not been well investigated. OBJECTIVE: We aimed to evaluate the electrocardiographic and electrophysiological findings and ablation outcomes of para-Hisian VAs with QRS morphological changes after CA. METHODS: Of the 30 patients who underwent CA for para-Hisian VAs at 4 institutions, 10 (33%) had QRS morphological changes after ablation. All 10 patients underwent an anatomical approach, targeting the site anatomically opposite to the site where the QRS morphology had been changed by ablation. We investigated the safety and efficacy of the anatomical approach. RESULTS: Of the 10 patients evaluated, the approach was switched from the right ventricular septum to the left ventricular septum/aortic root in 7 (70%) (RL group) whereas 3 (30%) underwent left-to-right switches (LR group). After CA, the precordial transition zone tended to be earlier in the RL group and later in the LR group. In the RL group, successful VA suppression was achieved, despite suboptimal pace map concordance from the left side or a relatively delayed earliest activation time. Of the 10 patients who underwent an anatomical approach, 8 (80%) had procedural success, and ablation was discontinued in 1 (10%) because of the risk of atrioventricular block. CONCLUSION: The anatomical approach showed promising results regarding safety and efficacy. Therefore, it should be considered when QRS morphological changes are observed during or after CA of para-Hisian VAs.

Consecutive electrocardiographic changes during percutaneous coronary intervention for acute coronary syndrome with high-grade atrioventricular block: a case report.

BACKGROUND: Acute coronary syndrome (ACS) with high-grade atrioventricular block (HAVB) still has a poor mortality risk, even in the current percutaneous coronary intervention (PCI) era. However, early PCI for ACS with HAVB is associated with improved in-hospital survival and a 6-month survival similar to that of ACS without HAVB. CASE PRESENTATION: A 70-year-old man was admitted to our hospital for ACS with HAVB. ECG showed complete AV block, complete right bundle branch block (CRBBB), and left axis deviation. Cardiac enzymes were elevated. He underwent temporary pacemaker insertion and coronary angiography, which showed severe stenosis of the proximal right coronary artery (RCA), 99% stenosis of the distal RCA with Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow, and total occlusion of the proximal left anterior descending artery (LAD). We performed primary PCI in both the RCA and LAD, which resulted in TIMI grade 3 flow in both. After PCI, the HAVB recovered to normal sinus rhythm with CRBBB; a normal QRS interval returned within three days. The patient was discharged from the hospital without complications. CONCLUSION: In this case of ACS with HAVB, early intensive coronary artery reperfusion resulted in long-term patient survival. The blood supply to the AV node and bilateral bundle branches is complex. Multivessel ischemia may compromise both primary and collateral blood flows to the AV node and septum, resulting in severe conduction impairment. Clinicians performing PCI should be aware of this anatomy and physiology.

The potential hazard of a non-slip element balloon causing distal longitudinal stent deformation: the first clinical experience and in vitro assessment.

BACKGROUND: A new complication, longitudinal stent deformation (LSD), is increasingly reported with recent intracoronary stent designs. There have been experiences of unusual cases of distal LSD caused by entrapment of a Lacrosse® non-slip element (NSE) balloon (Goodman Co., Ltd., Nagoya, Japan), which has three flexible nylon elements to prevent slippage. Accordingly, the aim of this study is to report the clinical experience of distal LSD caused by the NSE in the documented center and to investigate the incidence and mechanisms involved. METHODS: Coronary intervention cases were retrospectively reviewed using the NSE balloon in hospital between May 2014 and June 2017. In bench testing, distal LSD was reproduced in a silicon tube model to identify its mechanism. RESULTS: A total of 95 patients with 107 lesions underwent coronary interventions with NSE. Of these, 72 lesions (12 de-novo lesions and 60 in-stent restenosis) were treated using in-stent dilatation. Two distal LSD cases occurred, representing an incidence of 2.78% (2/72) among all procedures; 16.7% (2/12) of the de-novo lesions developed LSD. In vitro experimentation allowed indentification of the mechanisms involved and bailout strategies. CONCLUSIONS: This is the first study to evaluate NSE balloon catheter entrapment complicated by distal LSD in which reconstruction of the deformed stent and retrieval of the NSE could be achieved successfully. There is a potential hazard for distal LSD during post-dilatation using the NSE balloon due to its structural characteristics. Careful assessment is needed to prevent this complication.

The effectiveness of super-selective injection with anchor balloon technique for collateral channel assessment.

The careful assessment of collateral channels is important for a retrograde approach for a chronic total coronary occlusion (CTO). This case report describes a percutaneous coronary intervention for CTO of the distal right coronary artery with good collateral circulation. All visible collateral channels failed by the retrograde approach; however, the procedure was successful using the distal atrial circumflex (AC) channel. Although this distal channel was poorly visualized on standard coronary angiography, it was clearly contrasted retrogradely from the CTO exit using a super-selective injection through the proximal AC channel as the antegrade flow was obstructed by the anchor balloon. This case highlights a unique super-selective injection with anchor balloon technique for collateral channel assessment.

The potential hazard of drug-eluting stent-induced coronary vasospasm causing subacute stent thrombosis: a case report.

BACKGROUND: Drug-eluting stent (DES) -induced coronary vasospasm is a well known phenomenon after stent implantation; however, the extent of this risk is still unknown. We report a case in which DES-induced severe coronary vasospasm was clinically suspected as a cause of subacute stent thrombosis (ST). CASE PRESENTATION: A 67-year-old man came to our hospital due to chest pain with mild exercise. He was diagnosed with effort angina by coronary angiography and underwent DES implantation in the mid-left ascending artery (LAD) after the administration of dual anti-platelet therapy. The procedure was uneventful, but his symptoms changed from effort angina to rest angina after stenting. Five days after the procedure, subacute ST occurred, requiring aspiration thrombectomy and balloon angioplasty. Thereafter, he continued to report early morning chest discomfort. We performed a spasm provocation test to evaluate the coronary vasomotor response; it revealed severe stent-edge spasm in the left main trunk to the LAD, except for the stented lesion, and total occlusion of the left circumflex artery. CONCLUSIONS: To our knowledge, the present case is the first report describing in-stent thrombosis secondary to stent-edge spasm. This case describes the potential hazard of DES-induced coronary vasospasm. Although there are several overlapping risk factors for ST development, we consider that stent-edge spasm also plays an important role in ST development. Therefore, we should monitor new-onset rest angina after stent implantation and carefully assess DES-induced coronary vasospasm.

Acute myocardial infarction with "wrap around" right coronary artery mimicking Takotsubo cardiomyopathy: a case report.

BACKGROUND: Takotsubo cardiomyopathy (TC) is a cardiomyopathy that shows distinctive clinical conditions first described more than 20 years ago. Because clinical features of TC mimic those of anterior acute myocardial infarction (AMI), the differential diagnosis is important in selecting the appropriate treatment strategy in the acute phase. But it was difficult to differentiate those two diseases because the TC-like findings; such as the electrocardiogram (ECG) changes and left ventricular wall motion abnormality can occur in AMI especially with the anatomical variance of the coronary artery. CASE PRESENTATION: A 63-year-old man was admitted due to sudden onset of chest pain and was in a cardiogenic shock state. His ECG showed ST-segment elevation in precordial (V2-6) and inferior leads (II, III, and aVF) and ST-segment depression in lead aVR. Blood biochemistry showed that cardiac enzymes were not elevated. Ultrasonic cardiography showed that the left ventricular apical level was akinetic, papillary muscle level was severely hypokinetic, and basal level was hyperkinetic, mimicking TC. However, coronary angiogram showed total occlusion of his right coronary artery wrapping around the cardiac apex. Successful percutaneous coronary intervention reversed his critical status. CONCLUSION: To our knowledge, the present case is the first report described AMI with wrap-around RCA, mimicking TC. Although TC is increasingly recognized as a true but relatively infrequent clinical entity, it is still important to carefully rule out obstructive coronary artery disease.

Clinical significance of induced left atrial macro-reentrant tachycardia after pulmonary vein isolation.

BACKGROUND: The clinical significance of induced left atrial macro-reentrant tachycardia (LA-AT) after encircling pulmonary vein isolation (EPVI) is unclear. Our objective was to determine whether induced LA-ATs are associated with the clinical recurrence of ATs. METHODS: We studied 185 consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent their first EPVI with an 8-mm tip, nonirrigated catheter approach. AT was induced by atrial burst pacing after the completion of EPVI, and the atrial activation pattern was evaluated using EnSite NavX. Induced LA-ATs were ablated only in patients with clinical ATs of suspected LA origin. The factors associated with occurrence of AT after the procedure were examined. RESULTS: LA-ATs were induced in 38 patients and ablated in 5 patients. During a follow-up of 23 ± 7 months, the occurrence of AT did not differ between patients with nonablated LA-ATs (4/33, 12 %) and those without any inducible ATs (16/113, 14 %, p > 0.99). In multivariate analysis, the number of ablation points for completing EPVI was the only independent predictor of AT occurrence (odds ratio 1.07, p < 0.01). A repeat procedure was performed in 22 of 26 patients who developed AT. Nineteen patients became free from AT and AF after ablation of the conduction gaps (EPVI, n = 17; another line, n = 4), extra PV firing (n = 4), focal AT (n = 4), and induced LA-ATs (n = 3). CONCLUSIONS: In patients who had EPVI for PAF using an 8-mm tip, nonirrigated catheter, the occurrence of AT after EPVI was mainly due to conduction gaps in the ablation line or extra PV triggers. In patients with PAF, LA-ATs induced during the first procedure did not require ablation if they were not associated with clinical AT.

Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.

BACKGROUND: Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). METHODS: A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. RESULTS: Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. CONCLUSIONS: Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

Role of the side chain stereochemistry in the α-glucosidase inhibitory activity of kotalanol, a potent natural α-glucosidase inhibitor. Part 2.

To examine the role of the side chain of kotalanol (2), a potent natural α-glucosidase inhibitor isolated from Salacia reticulata, on inhibitory activity, four diastereomers (11a-11d) with reversed configuration (S) at the C-4' position in the side chain were synthesized and evaluated. Two of the four (11b and 11d) significantly lost their inhibitory activity against both maltase and sucrase, while the other two (11a and 11c) sustained the inhibitory activity to a considerable extent, showing distinct activity in response to the change of stereochemistry of the hydroxyls at the 5'and 6' positions. Different activities were rationalized with reference to in silico docking studies on these inhibitors with hNtMGAM. Against isomaltase, all four analogs showed potent inhibitory activity as well as 2, and 11b and 11d exhibited enzyme selectivity.

Paclitaxel-based chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy failure: a case series of 5 patients.

BACKGROUND/OBJECTIVES: Gemcitabine (GEM) is a gold-standard chemotherapy agent for advanced pancreatic cancer. Because of the malignant character of the disease, nearly all patients show disease progression despite treatment with GEM-based chemotherapy; therefore, second-line chemotherapy may be beneficial for these patients. We report a retrospective analysis of 5 patients with advanced pancreatic cancer, treated with a paclitaxel-containing regimen as second-, third- or fourth-line chemotherapy after various therapies, such as a GEM-based regimen, S-1 regimen, and chemoradiation. We retrospectively analyzed the efficacy and adverse events, and evaluated the paclitaxel-containing regimens. A review of the literature is also discussed. RESULTS: The median overall survival from the start of salvage therapy was 10.7 months. The disease control rate of the paclitaxel-containing regimen according to RECIST criteria was 60%, including complete response in 0 patients, partial response in 3, and stable disease in 2. Two patients had malignant ascites at the start of this salvage therapy, and in both of them the ascites and clinical complaints improved. Grade 3 and 4 hematological adverse events were observed in 2 patients and 1 patient, respectively. CONCLUSION: Salvage paclitaxel-based therapy could be beneficial to advanced pancreatic cancer patients who maintain good performance status after several chemotherapy failures.

[Clinical evaluation of calculating carboplatin dosage using Japanese equation for estimating GFR for gynecologic cancer].

Glomerular filtration rate (GFR) is an important factor when considering carboplatin dosage adjustment. The Japanese equation for estimating GFR (eGFR) was recommended as a guideline for evaluating GFR in 2009 by The Japanese Society of Nephrology. However, benefits in the field of cancer chemotherapy with the use of eGFR have not yet been shown. To clarify the clinical benefits of eGFR, we investigated the renal function of 100 patients with gynecologic cancer who were treated with carboplatin from 2003 through 2009, and the carboplatin dosage was calculated by the Calvert formula in which eGFR was substituted for GFR. To predict the clinical benefit on the basis of carboplatin dosage using eGFR, we retrospectively divided the patients into two groups so that carboplatin dosage was within dosage in using eGFR and one was not. We compared response rates and adverse effects of the two groups. Renal function using eGFR was lower than renal function calculated by using the other formulae. Carboplatin dosage using eGFR was significantly lower than the dosage calculated with the other formulae (p<0.01). Moreover, the patients group actually, administered the dosage calculated by eGFR showed less side effects than the group of patients not treated this way, but the efficacy did not change. Thus, using eGFR in planning carboplatin dosage suggested clinical application to patients with Japanese gynecologic cancer.

[Recurrent advanced gastric cancer diagnosed 20 years after partial gastrectomy].

A 67-year-old woman underwent partial gastrectomy (por2+sig, stage IIIA) for gastric cancer. She was admitted to our hospital because of swelling of her left neck lymph nodes 20 years after surgery. A biopsy specimen revealed poorly differentiated adenocarcinoma with signet-ring cell carcinoma. We diagnosed recurrence of gastric cancer and gave chemotherapy, but she died of myelosuppression and disseminated intravascular coagulation 2 years later. On autopsy, we examined all organs except the brain, but the primary lesion was not recognized. We concluded that this case was late recurrence after partial gastrectomy for advanced gastric cancer.

High-dose dexamethasone plus antihistamine prevents colorectal cancer patients treated with modified FOLFOX6 from hypersensitivity reactions induced by oxaliplatin.

BACKGROUND: Oxaliplatin is a third-generation platinum compound and a key agent for the management of colorectal cancer. Patients treated with oxaliplatin are at risk for hypersensitivity reactions. We designed a modified premedication regimen to prevent oxaliplatin-related hypersensitivity reactions and assessed if this approach is effective. METHODS: A retrospective cohort study of patients with advanced colorectal cancer who received modified FOLFOX6 (mFOLFOX6) was performed. Patients received routine premedication with dexamethasone 8 mg and granisetron 3 mg for the first five cycles of mFOLFOX6. From the sixth cycle onward, cohort 1 received the same premedication, and cohort 2 received modified premedication (diphenhydramine 50 mg orally, followed by dexamethasone 20 mg, granisetron 3 mg, and famotidine 20 mg). We compared the incidence of hypersensitivity reactions, duration of treatment, and reasons for treatment withdrawal between the two cohorts. RESULTS: A total of 181 patients were studied (cohort 1, 81; cohort 2, 100). Hypersensitivity reactions developed in 16 patients (20%) in cohort 1 and 7 (7.0%) in cohort 2 (P = 0.0153). The median number of cycles increased from 9 in cohort 1 to 12 in cohort 2. Apart from progressive disease, neurotoxicity was the reason for discontinuing treatment in 20% of the patients in cohort 1, as compared with 53% in cohort 2. CONCLUSION: Increased doses of dexamethasone and antihistamine significantly reduced oxaliplatin-related hypersensitivity reactions. This effective approach should be considered for all patients who receive FOLFOX, allowing treatment to be completed as planned.

The expression of both peroxisome proliferator-activated receptor delta and cyclooxygenase-2 in tissues is associated with poor prognosis in colorectal cancer patients.

BACKGROUND: The role of peroxisome proliferator-activated receptor delta (PPAR δ) in the development and progression of colorectal cancer (CRC) remains controversial. AIMS: We investigated the impact of PPAR δ expression in tissues on liver metastasis of CRC. METHODS: We analyzed samples of primary CRC and matched normal adjacent tissues from 52 patients for the expression of PPAR δ, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF)-A, and CXC chemokine receptor 4 (CXCR4). Correlations of the molecules expressions with clinical characteristics and prognosis of patients were studied. RESULTS: The number of patients positive for PPAR δ, COX-2, CXCR4, and VEGF-A was 25, 33, 18, and 19, respectively. Among the PPAR δ (+)/COX-2 (+), PPAR δ (-)/COX-2 (+), PPAR δ (+)/COX-2 (-), and PPAR δ (-)/COX-2 (-) patient groups, PPAR δ (+)/COX-2 (+) patients had the highest incidence of liver metastasis (p<0.01). PPAR δ (+)/COX-2 (+) expression was a significant independent prognostic factor (HR=7.108, 95% CI 1.231-41.029, p=0.0283) by Cox proportional analysis. PPAR δ (+)/COX-2 (+) patients had the highest positivity for CXCR4 or VEGF-A in tissues (p<0.01). Among the patients in the CXCR4 (+)/VEGF-A (+), CXCR4 (+)/VEGF-A (-), CXCR4 (-)/VEGF-A (+), and CXCR4 (-)/VEGF-A (-) groups, CXCR4 (+)/VEGF-A (+) patients had the highest incidence of liver metastasis (p<0.01). CONCLUSIONS: The expression of both PPAR δ and COX-2 in tissues may lead to liver metastasis and consequent poor prognosis in CRC patients.

Acetaminophen-induced acute pancreatitis. A case report.

CONTEXT: Drug-induced acute pancreatitis is rare but should not be overlooked in a patient who presents with idiopathic acute pancreatitis. More than 100 drugs have been implicated in causing the disease: acetaminophen has been associated with acute pancreatitis in cases where there has been an overdose of drugs; however, the frequency is rare. CASE REPORT: We report the case of a 35-year-old woman who presented with acute pancreatitis and severe metabolic acidosis after overdosing on a drug containing acetaminophen. She improved dramatically after intensive care; however, she showed recurrent episodes after re-overdosing on the same drug. With her self re-challenge test, she was diagnosed as having acetaminophen-induced pancreatitis and metabolic acidosis. A review of the relevant literature is also presented. CONCLUSIONS: Drug-induced acute pancreatitis is often challenging for clinicians and a detailed mechanism is unknown. It is very important to rule out drug-induced pancreatitis when treating pancreatitis with an unknown etiology.

The simultaneous expression of peroxisome proliferator-activated receptor delta and cyclooxygenase-2 may enhance angiogenesis and tumor venous invasion in tissues of colorectal cancers.

We conducted this study to evaluate the impact of the expression of peroxisome proliferator-activated receptor delta on angiogenesis in tissue samples of colorectal cancer. We examined 52 samples of primary human colorectal carcinomas and matched normal adjacent tissues to evaluate the expression of peroxisome proliferator-activated receptor delta, cyclooxygenase-2, vascular endothelial growth factor-A, and CD34 through immunohistochemical analysis. Peroxisome proliferator-activated receptor delta was expressed in 25 (48.1%), and cyclooxygenase-2 was expressed in 26 (50.0%) of total colorectal cancer tissues. Tissue samples were divided into four groups, according to the expression of peroxisome proliferator-activated receptor delta and cyclooxygenase-2. The positive rate of vascular endothelial growth factor-A, the levels of microvascular density, and the incidence of venous vessel invasion in peroxisome proliferator-activated receptor delta (+)/cyclooxygenase-2 (+) samples exceeded significantly those in the other three groups of tissue samples (P<0.05). The results suggest that the axis of the cyclooxygenase-2/peroxisome proliferator-activated receptor delta signal pathway might play a crucial role in the development of colorectal cancers by enhancing angiogenesis.

The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds.

BACKGROUND AND AIM: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences the sensitivity of NSAID-induced apoptosis in CRCs. METHODS: In 22 CRC surgical samples from NSAID users who had been constant for more than 5 years and 28 CRC surgical samples from NSAID non-users, the expressions of 15-LOX-1, cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using immunohistochemistry. TUNEL assay was also performed for samples. The effects of the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis were certified in HCT-116 cells. The effects of adding 13-S-hydroxyoctadecadinoic acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116 cells. The levels of apoptosis were determined by the analysis of the floating-cells ratio and DNA gel electrophoresis. RESULTS: The expression of 15-LOX-1 on CRCs from NSAID users was significantly decreased compared with those from NSAID non-users; however, the expressions of other molecules were not significantly different between two groups. The levels of TUNEL scoring in samples from NSAID users were similar to those from NSAID non-users. Indomethacin (100 microM) induced less apoptosis in mocked cells, whereas the same concentrations of indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S-HODE also increased the level of indomethacin-induced apoptosis in cells. CONCLUSION: Results suggest that 15-LOX-1 expression may be one of the mechanisms which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients who are treated with the compounds.