Clinical Experience of Percutaneous Patent Foramen Ovale Closure Using the Amplatzer PFO Occluder in Japanese Patients to Prevent the Recurrence of Cryptogenic Stroke

Objective Percutaneous patent foramen ovale (PFO) closure is a procedure widely used to prevent recurrence of cryptogenic stroke. Since December 2019, the Amplatzer PFO occluder device has been available in Japan through medical insurance. However, data on the clinical experience with this device are lacking, as it has been approved for use in only a limited number of institutions. This study assessed the clinical data of Japanese patients who underwent PFO closure using the Amplatzer PFO occluder. Methods Between February and October 2020, 14 patients at our institution underwent percutaneous PFO closure using the Amplatzer PFO occluder. The procedural characteristics, safety, and adverse events were retrospectively analyzed. Results The mean age of the patients was 52.4±13.3 years old, and 57.1% were women. Deep vein thrombosis was revealed in 2 patients, and the risk of paradoxical embolism score was 6.6±1.2 points. The PFO height and tunnel length were 2.3±1.4 mm and 11.5±4.1 mm. All patients had a PFO during the bubble study of grade >3 at the Valsalva maneuver on transthoracic echocardiography or transesophageal echocardiography. The average diameter of the PFO measured using a stiff guidewire and sizing balloon was 5.1±1.3 and 7.9±2.3 mm, respectively. Almost all cases (92.9%) were performed with a 25-mm device and without significant complications within approximately 1 hour. Conclusion Percutaneous closure using Amplatzer PFO occluder is a safe procedure for Japanese patients. However, further investigations with a larger sample and longer follow-up are needed to confirm this result.     

Clinicopathological Characteristics and Prognostic Factors of Patients with Siewert Type II Esophagogastric Junction Carcinoma: A Retrospective Multicenter Study

Background

The incidence of esophagogastric junction (EGJ) carcinoma is increasing, but its optimal surgical management remains controversial.

Methods

We retrospectively reviewed the database of 400 patients with Siewert type II EGJ carcinoma who were treated surgically at 7 institutions between March 1986 and October 2010. We examined the clinicopathological characteristics, prognostic factors, and risk factors associated with each recurrence pattern.

Results

The 5-year overall survival rate of all patients with Siewert type II EGJ carcinoma was 58.4 %. Multivariate analysis showed that T and N stages were independent prognostic factors. We also found that the incidence of lower mediastinal lymph node metastasis (17.7 %) and para-aortic lymph node metastasis (16.1 %) was relatively high. In addition, the para-aortic lymph nodes (N = 39, 9.8 %) were the most frequent node recurrence site, followed by the mediastinal lymph nodes (N = 23, 5.8 %). Lung recurrence was more common than was peritoneal recurrence. Considering each type of recurrence, multivariate analysis showed that the differentiated type was associated with a higher risk of lung recurrence than was the undifferentiated type, and N stage (pN2–3) and positive venous invasion were independent risk factors for liver recurrence.

Conclusions

This study is one of the largest retrospective studies to evaluate patients with Siewert type II EGJ carcinoma. Para-aortic and mediastinal lymph node metastasis and recurrence rates were relatively high. During the postoperative follow-up of patients with differentiated Siewert type II EGJ carcinoma, patients should be monitored for lung recurrence more closely than that for peritoneal recurrence.

     

SCRUM-Japan GI-SCREEN and MONSTAR-SCREEN: Path to the realization of biomarker-guided precision oncology in advanced solid tumors

Comprehensive genomic profiling enables the detection of genomic biomarkers in advanced solid tumors. However, efficient patient screening for the success of precision oncology remains challenging due to substantial barriers, such as genotyping costs and accessibility to matched therapies. To address these challenges, we launched GI-SCREEN, a nationwide gastrointestinal cancer genomic screening project within the SCRUM-Japan network in 2015 with the specific purpose of matching patients with a diverse portfolio of affiliated interventional targeted therapy trials. Subsequently, we initiated the molecular profiling projects GOZILA, MONSTAR-SCREEN-1, and MONSTAR-SCREEN-2, which incorporate tissue and plasma multiomics approaches to accurately identify patients with advanced solid tumors who would benefit from matched therapies. These projects have led to a significant increase in patient participation in targeted clinical trials and the approval of several therapeutics and companion diagnostics. Additionally, clinicogenomic analyses utilizing the SCRUM-Japan database have provided new insights into the molecular mechanisms of advanced solid tumors. In this review, we describe the path to the realization of cancer precision medicine for patients with advanced solid tumors based on the SCRUM-Japan GI-SCREEN and MONSTAR-SCREEN platforms.     

Real-world data on microsatellite instability status in various unresectable or metastatic solid tumors

Microsatellite instability-high (MSI-H) is an important biomarker for predicting the effect of immune checkpoint inhibitors (ICIs) on advanced solid tumors. Microsatellite instability-high is detected in various cancers, but its frequency varies by cancer type and stage. Therefore, precise frequency is required to plan ICI therapy. In this study, the results of MSI tests actually carried out in clinical practice were investigated. In total, 26 469 samples of various cancers were examined between December 2018 and November 2019 to determine whether programmed cell death-1 blockade was indicated. The results of MSI tests were obtained for 26 237 (99.1%) of these samples. The male : female ratio was 51:49 and mean age was 64.3 years. In all samples, the overall frequency of MSI-H was 3.72%. By gender, the frequency of MSI-H was higher in female patients (4.75%) than in male patients (2.62%; P < .001). A comparison by age revealed that the frequency of MSI-H was significantly higher in patients younger than 40 years of age (6.12%) and 80 years or older (5.77%) than in patients aged between 60 and 79 years (3.09%; P < .001). Microsatellite instability-high was detected in 30 cancer types. Common cancer types were: endometrial cancer, 16.85%; small intestinal cancer, 8.63%; gastric cancer, 6.74%; duodenal cancer, 5.60%; and colorectal cancer, 3.78%. Microsatellite instability-high was detected in cancer derived from a wide variety of organs. The frequency of MSI-H varied by cancer type and onset age. These data should prove especially useful when considering ICI treatment.     

Therapeutic Plasma Exchange Improved Pregnancy-associated Thrombotic Microangiopathy but not the Pregnancy Outcome in Patient with Systemic Lupus Erythematosus

Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.     

Usefulness of plasma brain natriuretic peptide concentration for predicting subsequent left ventricular remodeling after coronary angioplasty in patients with acute myocardial infarction

To determine the relation between plasma brain natriuretic peptide (BNP) and remodeling in terms of infarct-related artery (IRA) patency, 106 patients with a first anterior wall acute myocardial infarction with a patent IRA at 1 month were studied. The IRA reoccluded at 6 months in 17 patients (reoccluded IRA) and was patent in 89 patients (patent IRA). The 2 groups did not differ with respect to clinical characteristics, hemodynamic variables, and left ventricular function at 1 month, except for left ventricular end-diastolic and systolic volumes, which were significantly greater in the reoccluded IRA group. Plasma BNP concentration in the reoccluded IRA group (336 +/- 288 pg/ml) was significantly higher than that in the patent IRA group (116 +/- 106 pg/ml) at 1 month. BNP concentration decreased significantly at 6 months in the 2 groups (reoccluded IRA vs patent IRA 152 +/- 162 vs 44 +/- 58 pg/ml, p <0.05). The increase in left ventricular volume from 1 to 6 months was significantly correlated with plasma BNP concentration at 1 month in the patent IRA group (r = 0.314, p < 0.01) and the reoccluded group (r = 0.634, p < 0.01). Linear regression analysis showed that the correlation between the 2 parameters in the 2 groups was similar. Based on stepwise multivariate linear regression analysis, only plasma BNP concentration was significantly correlated with the increase in left ventricular volume from 1 to 6 months in the 2 groups. In conclusion, these results suggest that plasma BNP concentration predicts left ventricular dilation independently of IRA patency.