Left coronary artery occlusion caused by a large thrombus on the left coronary cusp in a patient with a continuous-flow ventricular assist device

Despite continual improvements in ventricular assist device (VAD) therapy, various clinical issues are emerging. Importantly, various types of thromboembolic complications have been reported to date. Recently, we encountered a rare continuous-flow VAD-related thromboembolic event that resulted in acute myocardial infarction. A 26-year-old female who just underwent HeartMate II^® VAD implantation suddenly developed widespread anterolateral myocardial infarction on postoperative day 16. Echocardiography and aortography revealed a large thrombus on the left coronary cusp of the aortic valve that almost completely occluded the left coronary ostium. After VAD implantation, her aortic valve did not open, even at relatively low pump speeds; this was thought to be one of the causes for thrombus formation. Continuous suction of blood from the left ventricle and non-pulsatile flow into the ascending aorta resulted in a continuously closed aortic valve and stagnation of blood in the coronary cusp. Furthermore, both small body size (body surface area <1.3 m²) and postoperative right ventricular failure may have exacerbated blood stagnation and thrombus formation in this patient. We should have adjusted the anticoagulation and antiplatelet therapy protocols based on the patient’s condition. She underwent off-pump coronary artery bypass surgery and remained in clinically stable condition afterwards.     

Circadian variation of motor current observed in fixed rotation speed continuous-flow left ventricular assist device support

The algorithm for the physiological control provided by left ventricular assist devices (LVADs) has been controversial. In particular, little is known about the physiological control algorithm (such as for achieving physiological circadian rhythms) in continuous-flow LVADs. To investigate the existence of circadian variation, we retrospectively evaluated the LVAD flow-correlated motor current of patients supported by continuous-flow LVADs. The motor current and the pump speed were collected from the external controller every 10 min after device implantation, and the data were divided for every 30-day period, which began on midnight on the first post-operative day. The subjects were 18 patients (mean age 37.7, mean body surface area 1.71 m² at the time of operation) with dilated cardiomyopathy or dilated phase of hypertrophic cardiomyopathy. As of August 1, 2013, the patients’ median support duration was 889 days. The mean calculated dominant period of motor current variation was 24.0 h and the mean amplitude was 11.7 mA for the entire duration. The amplitude of the motor current circadian variation tended to be increased until around the fifth month. The motor current had a tendency to be relatively low during the night time and high during the day time. A significant difference was found between the night-time and day-time mean motor current for the entire duration (p < 0.05). In conclusion, the circadian variation of the motor current could be observed over long term in patients with fixed rotation speed continuous-flow LVAD support.     

Histological features of primary tumors after induction or high-dose chemotherapy in high-risk neuroblastoma

Purpose

In the recent years in Japan, an increasing number of patients with neuroblastoma (NB) are being treated by the “delayed local treatment (DL)” policy, undergoing surgery after the completion of high-dose chemotherapy with hematopoietic stem cell rescue (HDC). We reviewed the histopathological findings of second-look operations, including those of patients treated with DL.

Patients

From 1998 to 2013, 26 patients with high-risk NB underwent radical operation following chemotherapy. Surgery was performed after induction chemotherapy in 17 cases (standard; STD), whereas 9 cases completed induction chemotherapy and HDC before undergoing tumor resection (DL). The amount of necrosis and the degree of differentiation within the post-treatment tumor were assessed.

Results

Eighty-eight percent of the tumors showed necrosis in more than 1/3 of the specimen. Two DL cases showed complete disappearance of viable tumor cells. Amount of necrosis did not affect the prognosis of the patient. Tumors with immature, poorly differentiated phenotypes showed an extremely aggressive thereafter. Though not statistically proven, ¹²³I-MIBG (metaiodobenzylguanidine) uptake may be correlated with the amount of viable cells remaining within the tumor, but not with the degree of differentiation.

Conclusions

Our results support the previous reports advocating that tumors that sustain unfavorable histology after chemotherapy behave aggressively thereafter.     

Different degradation rates of nanofiber vascular grafts in small and large animal models

Nanofiber vascular grafts have been shown to create neovessels made of autologous tissue, by in vivo scaffold biodegradation over time. However, many studies on graft materials and biodegradation have been conducted in vitro or in small animal models, instead of large animal models, which demonstrate different degradation profiles. In this study, we compared the degradation profiles of nanofiber vascular grafts in a rat model and a sheep model, while controlling for the type of graft material, the duration of implantation, fabrication method, type of circulation (arterial/venous), and type of surgery (interposition graft). We found that there was significantly less remaining scaffold (i.e., faster degradation) in nanofiber vascular grafts implanted in the sheep model compared with the rat model, in both the arterial and the venous circulations, at 6 months postimplantation. In addition, there was more extracellular matrix deposition, more elastin formation, more mature collagen, and no calcification in the sheep model compared with the rat model. In conclusion, studies comparing degradation of vascular grafts in large and small animal models remain limited. For clinical translation of nanofiber vascular grafts, it is important to understand these differences.     

A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer

Known breast-cancer risk factors account for only part of the variability in breast-cancer incidence. Tobacco smoke is not commonly considered a breast carcinogen, but many of its constituents, such as N-nitrosamines, are carcinogenic in laboratory animal studies. Herein, we assessed a cytochrome P4502E1 (CYP2E1) genetic polymorphism (a Dral restriction enzyme site in intron 6) as a risk factor for breast cancer in both premenopausal and postmenopausal women. Because N-nitrosamines are metabolically activated by CYP2E1, the risk among women smokers was investigated. Caucasian women were enrolled in a case-control study of breast cancer between 1986 and 1991. A subset of the women (219 premenopausal and 387 postmenopausal women) consented to phlebotomy. The allelic frequencies for the premenopausal women (D allele = 0.91 and C allele = 0.09) and postmenopausal women (D allele = 0.93 and C allele = 0.07) were similar to those previously reported. There was no statistically significant association between the CYP2E1 polymorphism and breast-cancer risk for premenopausal or postmenopausal women (adjusted odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.48, 2.24, and OR = 1.01, 95% CI = 0.55, 1.84, respectively). When the women were categorized as nonsmokers versus smokers (those who smoked more than one cigarette per week for more than 1 yr), premenopausal women with one or two C alleles who had a history of smoking were found to be at increased risk (unadjusted OR = 7.00, 95% CI = 0.75, 14.53, and adjusted OR = 11.09, 95% CI = 1.51, 81.41), although the number of study subjects with those genotypes was small. The small number of study subjects with a C allele precluded meaningful classification by level of smoking, but categorizing the smokers into two groups (above and below the median) also suggested an increased risk. Premenopausal women with the DD genotype and postmenopausal women with any genotype were not at increased risk. Breast-cancer risk was not related to the CYP2E1 genotype in either premenopausal nonsmokers or smokers (adjusted OR = 0.66, 95% CI = 0.20, 2.17, and OR = 2.13, 95% CI = 0.60, 7.59, respectively) or postmenopausal nonsmokers or smokers (OR = 0.90, 95% CI = 0.34, 2.35, and OR = 1.02, 95% CI = 0.46, 2.23, respectively), although the difference in the ORs for premenopausal nonsmokers and smokers suggests an increased risk for smokers. While there are limitations to this study, particularly related to the small number of subjects with the DC and CC genotypes, the study suggests that some women may be susceptible to tobacco smoke because of a CYP2E1 polymorphism. However, these results are preliminary and must be replicated. © 1996 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Clinical characteristics of subglottic cancer: emphasis on therapeutic management strategies for stage II subglottic cancer*

Abstract

Background: Subglottic cancer (SGC) is extremely rare, as most laryngeal cancers are localized to the glottic region. Accordingly, the clinical characteristics of SGC have not been well characterized.

Objectives: In the current study, SGCs were clinically evaluated, and the outcomes of radiotherapy (RT) in patients with stage II SGC were assessed.

Materials and Methods: Medical data derived from 11 patients with SGC, who were treated at our hospital between 1995 and 2019, were retrospectively reviewed.

Results: In our department SGC accounted for 3.9% of the 280 laryngeal cancer patients treated during the study period. At the time of SGC diagnosis, 9 (81.8%) had stage II cancer, 1 had stage III cancer, and 1 had stage IV cancer. Stage II SGC patients treated with concurrent chemoradiotherapy (CCRT) showed a significantly higher local control rate (p?=?.026) and laryngeal dysfunction free rate (p?=?.026) than those treated with RT alone. Salvage surgery, performed in 4 patients whose disease was not locally controlled with CCRT/RT, was successful in 3 patients.

Conclusion: As a treatment strategy for stage II SGC, CCRT is an acceptable initial treatment for laryngeal function and preservation while salvage surgery is effective for recurrence after CCRT/RT treatment.     

Integrin α11 in non–small cell lung cancer is associated with tumor progression and postoperative recurrence

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11β1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non–small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT‐PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence‐free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.     

KRAS mutations in tongue squamous cell carcinoma

Background: p16^INK4a (p16) expression in tongue cancer (TC) is reportedly not associated with human papilloma virus (HPV). Mutations of KRAS in cancer cells are most frequently observed within codon 12. However, few reports have investigated the association between KRAS mutations and p16 status in TC.

Objectives: This study aimed to evaluate the influence of KRAS mutations on TC.

Methods: Clinical records and surgically resected specimens of 85?TC patients were analyzed. Tumor samples were analyzed for mutations of KRAS located within codons 12 and 13. p16 staining was performed and considered positive in cases with moderate to strong nuclear and cytoplasmic staining.

Results: Positive p16 staining was observed in 10 cases (11.8%). A KRAS mutation was detected in one case (1.2%). The case with KRAS mutation showed negative p16 staining. Despite being at an early stage, the patient died of lung metastasis at 43 months from initial treatment.

Conclusions and Significance: KRAS mutations are not associated with p16 expression in TC and may predict poor prognosis in TC patients. Further analysis of mutations in regions other than codons 12 and 13 of KRAS will be necessary to determine the relationship between KRAS mutations and prognosis of this disease.     

Dialysate Vascular Endothelial Growth Factor Is an Independent Determinant of Serum Albumin Levels and Predicts Future Withdrawal From Peritoneal Dialysis in Uremic Patients

Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium‐derived factor (PEDF) has anti‐vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty‐seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels (P < 0.001). In multiple stepwise regression analysis, age (P = 0.002) and dialysate VEGF levels (P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤3.31 g/dL) and low hemoglobin (≤11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients.