Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern.

A 50-year-old female was diagnosed with gastric hyperplastic polyps 7 years before and was followed up at another hospital. She was referred to our hospital because of the growth of gastric polyps and progression of anemia. She had no family history of polyposis. The polyps were observed only in the stomach, increased in size and number, and the erythematous edema got worse. Endoscopic mucosal resection (EMR) of the gastric polyp was performed. Pathologically, the gastric polyp was hamartomatous polyp, and the intervening mucosa between polyps showed no atypical structure without inflammation. Given that gastric juvenile polyposis (GJP) was clinically suspected, a genetic test using peripheral blood was performed. Target resequencing and Sanger sequencing analysis revealed a nonsense mutation in the SMAD4 gene at codon 169. The mutation was detected at a low frequency of 11%, and considered a mosaic mutation. Therefore, she was diagnosed with a sporadic GJP, and total gastrectomy was performed. Immunostaining of SMAD4 for the resected specimen showed a mixture of stained and unstained area in the epithelium of the polyp, indicating partial loss of SMAD4 expression. To our knowledge, this is the first reported case of GJP with a nonsense SMAD4 mutation at codon 169 in a mosaic pattern.

A case of hepatic reactive lymphoid hyperplasia: the review of 23 cases from the literatures.

A 70-year-old woman was referred to our hospital because of slight elevation of soluble interleukin-2 receptor (sIL-2R) and accumulation of 18F-fluorodeoxyglucose (FDG) in S8 of the liver on positron emission tomography. The mass was strongly suspected to be malignant because of contrast enhancement and enlargement in size of the mass, and suspicion of portal vein invasion. Hepatic S8 subsegmentectomy was performed for diagnostic and therapeutic purposes. Hematoxylin and eosin staining of the resected specimen showed small lymphocytes with no atypia and no formation of lymphoid follicles. Immunostaining showed CD3-positive cells in the interfollicular region and CD20-positive cells in the lymphoid follicles. Both CD10 and BCL-2 were negative in the follicular germinal center. CD138-positive plasma cells were observed and there was no light chain restriction. Based on polyclonal growth pattern of lymphocytes in the lymphoid follicles and interfollicular region, she was diagnosed with hepatic reactive lymphoid hyperplasia (RLH).Review of the English literature of hepatic RLH which referred to imaging findings yielded 23 cases, including this case. As a result, we suggest that liver biopsy should be performed for definitive diagnosis, when hepatic RLH is suspected by imaging findings and backgrounds.

Endovascular Aortic Repair for Thoracic Aortic Compression Resulting From Chance Fracture of the Thoracic Spine.

Blunt aortic injury is a serious condition with a high mortality rate. Although rare, blunt aortic injury associated with spinal fracture has also been reported, and appropriate management of aortic disease is key to a good outcome. This report is a case of a 78-year-old man who was found to have a transverse fracture (Chance fracture) in the ninth thoracic vertebra, with a sharp bone fragment compressing the thoracic aorta. Early spinal surgery was needed; however, there was concern about the possibility of bleeding from the aorta and surrounding small arteries associated with the bone fragment during spinal surgery. Therefore, thoracic endovascular aortic repair was performed before spinal surgery. The next day after thoracic endovascular aortic repair, posterior spinal instrumentation was performed, and the postoperative course was uneventful. Because aortic injury associated with vertebral fracture can lead to massive bleeding and spinal cord injury, endovascular repair before spinal surgery is reasonable.

[A case of SIADH due to pancreatic cancer was improved by tolvaptan].

We report the case of a 68-year-old man, who presented in emergency care with inarticulate speech. The patient was diagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) associated with pancreatic cancer. All diagnostic criteria for SIADH were met, and cancer of the pancreatic tail was identified by computed tomography. Standard treatment for SIADH includes water restriction, oral NaCl, continuous intravenous infusion of 3% NaCl, and intravenous infusion of furosemide. However, these treatments have varying effectiveness and are difficult for both patients and medical staff. Furthermore, unless treatment of the underlying disease is successful, continued hospitalization is needed and the patient's quality of life is significantly impaired. In this case, hyponatremia improved with this standard treatment, but ascites and edema developed. We treated the patient with tolvaptan due to decreased cardiac function, and symptoms improved rapidly. Although surgery and chemotherapy could not be performed for pancreatic cancer, the SIADH was treated for 7 months without relapse. In summary, a case of SIADH complicated by pancreatic cancer was difficult to control with standard treatment, but responded rapidly to tolvaptan, and outpatient treatment could be continued for a long period. Tolvaptan is useful for the treatment of SIADH associated with cancer.

A new combination technique of the modified Robicsek wire fixation and plate fixation achieves effective repair of transverse sternal fracture: a report of two cases.

BACKGROUND: To maximize the therapeutic effect for complicated sternal fracture, we should know advantages and disadvantages of each surgical repositioning technique, and the choice of an appropriate procedure is essential. We report two successful cases for which a combination of two existing techniques, modified Robicsek wire fixation and locked titanium plate fixation, was applied to transverse sternal fracture with flail chest. CASE PRESENTATION: One patient experienced a transverse sternal and rib fracture due to a traffic injury. Flail chest due to a highly displaced transverse sternal fracture made withdrawal of the ventilator impossible. Another patient, who developed fulminant myocarditis, experienced a transverse sternal fracture resulting from chest compression during cardiopulmonary resuscitation. Severe paradoxical respiratory movement was a limiting factor for cardiac and respiratory rehabilitation. In both cases, a transverse sternal fracture was difficult to correct non-invasively and indicated surgical repair. The surgical repositioning and fixation greatly contributed to the improvement of the respiratory movement, and the patients were successfully withdrawn ventilator support. CONCLUSION: The combination of modified Robicsek wire fixation and locked titanium plate fixation for a complicated sternal fracture employs the complementary and comparative advantages of each procedure and effective fixation may be achieved.

Differential effects of the formin inhibitor SMIFH2 on contractility and Ca2+ handling in frog and mouse cardiomyocytes.

Genetic mutations in actin regulators have been emerging as a cause of cardiomyopathy, although the functional link between actin dynamics and cardiac contraction remains largely unknown. To obtain insight into this issue, we examined the effects of pharmacological inhibition of formins, a major class of actin-assembling proteins. The formin inhibitor SMIFH2 significantly enhanced the cardiac contractility of isolated frog hearts, thereby augmenting cardiac performance. SMIFH2 treatment had no significant effects on the Ca2+ sensitivity of frog muscle fibers. Instead, it unexpectedly increased Ca2+ concentrations of isolated frog cardiomyocytes, suggesting that the inotropic effect is due to enhanced Ca2+ transients. In contrast to frog hearts, the contractility of mouse cardiomyocytes was attenuated by SMIFH2 treatment with decreasing Ca2+ transients. Thus, SMIFH2 has opposing effects on the Ca2+ transient and contractility between frog and mouse cardiomyocytes. We further found that SMIFH2 suppressed Ca2+ -release via type 2 ryanodine receptor (RyR2); this inhibitory effect may explain the species differences, since RyR2 is critical for Ca2+ transients in mouse myocardium but absent in frog myocardium. Although the mechanisms underlying the enhancement of Ca2+ transients in frog cardiomyocytes remain unclear, SMIFH2 differentially affects the cardiac contraction of amphibian and mammalian by differentially modulating their Ca2+ handling.

Successful papillary muscle approximation for severe mitral regurgitation via apical cuff hole in HeartMate 3 implantation via left anterior thoracotomy.

We herein report a case of successful papillary muscle approximation for severe mitral regurgitation and HeartMate 3 left ventricular assist device implantation via left anterior thoracotomy in a 39-year-old man diagnosed with dilated cardiomyopathy. He underwent papillary muscle approximation in the mitral valve for severe functional regurgitation via the apical cuff hole. The postoperative course was uneventful. Echocardiography revealed that mitral regurgitation has disappeared. He was awaiting heart transplantation while working.

Determinants of Changes in Arterial Stiffness after Thoracic Endovascular Aortic Repair.

BACKGROUND: Aortic stent grafting can cause aortic stiffening and increase pulse wave velocity (PWV), which can potentially affect long-term cardiovascular outcomes. The aim of this study was to clarify the factors contributing to increases in PWV after thoracic endovascular aortic repair (TEVAR). METHODS: We included 64 patients with thoracic aortic pathology (51 men; mean age, 73 years) who underwent elective TEVAR, in this study. TEVAR was performed for degenerative aortic aneurysm (n = 43) or aortic dissection (n = 21), and the treatment length was 175 ± 52 mm. Brachial-ankle PWV (baPWV) was obtained before and 1 week after TEVAR. Univariable and multivariable logistic regression analyses were used to determine the predictors of increases in baPWV of ≥100 cm/sec after TEVAR. RESULTS: baPWV increased from 1,851 ± 392 cm/sec to 2,047 ± 479 cm/sec, and the change in baPWV (ΔbaPWV) was 195 ± 339 cm/sec (95% confidence interval, 111-280). Thirty-seven patients (58%) had ΔbaPWV ≥100 cm/sec after TEVAR. In the multivariable analysis, in addition to Δheart rate and Δsystolic blood pressure, age (odds ratio, 1.21/year; 95% confidence interval, 1.05-1.40) and coronary artery disease (odds ratio, 12.0; 95% confidence interval, 1.20-121) were independent determinants of ΔbaPWV ≥100 cm/sec after TEVAR, whereas ΔbaPWV ≥100 cm/sec was not associated with treatment length or device type. CONCLUSIONS: TEVAR was associated with PWV progression, especially in older patients with coronary artery disease, whereas treatment length or device type was not a predictor of PWV progression after TEVAR.

Aortic root morphology can cause early bioprosthetic valve failure of externally mounted pericardial bioprosthesis.

A 73-year-old woman with a narrow aortic root had undergone aortic valve replacement with a 19-mm Mitroflow valve. Aortic annular enlargement with Manouguian's technique was performed, and the bioprosthesis had been implanted on the tilt in a supra-annular position. Four years after the implantation, echocardiography showed a significant de novo aortic regurgitation, which had not been detected 1 year earlier. In the reoperation, the left coronary leaflet of the bioprosthesis had attached and fused to the wall of the sinus of Valsalva, causing deformation of the valve leaflet and a commissural gap between the left and right coronary leaflets, which appeared to have caused the de novo aortic regurgitation. We assessed the cause of early valve deterioration by focusing on the morphology of the aortic root. Preoperative understanding of the aortic root morphology would help to avoid early valve dysfunction for aortic valve replacement with an externally mounted bioprosthesis.

Preoperative distal aortic diameter is a significant predictor of late aorta-related events after endovascular repair for chronic type B aortic dissection.

OBJECTIVES: Long-term therapeutic effects of thoracic endovascular aortic repair (TEVAR) for chronic type B aortic dissection remain controversial. This study aimed to evaluate the possible predictors of late aortic rupture and re-interventions after TEVAR. METHODS: We retrospectively reviewed the operative outcomes of 40 patients who underwent TEVAR for chronic type B aortic dissection at Kyushu University Hospital. During a mean follow-up period of 39.2 months, we assessed aortic morphology via computed tomography and then employed a multivariable Cox regression analysis in an attempt to identify the predictors of late aorta-related events. RESULTS: The early success rate of TEVAR was 100%. During the follow-up, however, three patients died from aortic rupture. Eight patients required aortic re-intervention, including thoraco-abdominal aortic graft replacement, repeated TEVAR, total arch replacement and EVAR. Multivariable Cox regression analysis revealed that the preoperative maximum distal aortic diameter was a significant predictor of late aorta-related events. The cutoff value of the distal aortic diameter was 40 mm. Freedom from aorta-related events was 94.6% at 1 year and 78.3% at 3 years. The survival rate was not significantly different despite the re-intervention. CONCLUSIONS: TEVAR is an effective treatment for chronic type B dissection, with acceptable mid-term results. The preoperative distal aortic diameter is a significant risk factor for late aorta-related events. When the maximum distal aortic diameter is ≥ 40 mm, a therapeutic strategy should be developed taking into consideration the possible need for aortic re-intervention.

A case of giant right coronary artery aneurysm due to IgG4-related disease.

A man diagnosed with immunoglobulin G4 (IgG4)-related disease at the age of 65 years underwent abdominal aortic replacement due to an abdominal aortic aneurysm. In the same hospitalization period, a small coronary artery aneurysm was noticed. He was treated with corticosteroids and his serum IgG levels returned to normal. After experiencing sudden chest pain at age 74 years, coronary angiography showed that the size of the aneurysm had increased dramatically. He underwent coronary artery bypass graft and coronary artery resection without using cardiopulmonary bypass. Thus, we conclude that observation of aneurysms in patients with IgG4-related disease is important, even under corticosteroid therapy.

Interaction between cardiac myosin-binding protein C and formin Fhod3.

Mutations in cardiac myosin-binding protein C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C has been considered to regulate the cardiac function via cross-bridge arrangement at the C-zone of the myosin-containing A-band, the mechanism by which cMyBP-C functions remains unclear. We identified formin Fhod3, an actin organizer essential for the formation and maintenance of cardiac sarcomeres, as a cMyBP-C-binding protein. The cardiac-specific N-terminal Ig-like domain of cMyBP-C directly interacts with the cardiac-specific N-terminal region of Fhod3. The interaction seems to direct the localization of Fhod3 to the C-zone, since a noncardiac Fhod3 variant lacking the cMyBP-C-binding region failed to localize to the C-zone. Conversely, the cardiac variant of Fhod3 failed to localize to the C-zone in the cMyBP-C-null mice, which display a phenotype of hypertrophic cardiomyopathy. The cardiomyopathic phenotype of cMyBP-C-null mice was further exacerbated by Fhod3 overexpression with a defect of sarcomere integrity, whereas that was partially ameliorated by a reduction in the Fhod3 protein levels, suggesting that Fhod3 has a deleterious effect on cardiac function under cMyBP-C-null conditions where Fhod3 is aberrantly mislocalized. Together, these findings suggest the possibility that Fhod3 contributes to the pathogenesis of cMyBP-C-related cardiomyopathy and that Fhod3 is critically involved in cMyBP-C-mediated regulation of cardiac function via direct interaction.

The actin-organizing formin protein Fhod3 is required for postnatal development and functional maintenance of the adult heart in mice.

Cardiac development and function require actin-myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that directs formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here, we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development. Tamoxifen-induced conditional KO of Fhod3 in the adult heart neither led to lethal effects nor did it affect sarcomere structure and localization of sarcomere components. However, adult Fhod3-deleted mice exhibited a slight cardiomegaly and mild impairment of cardiac function, conditions that were sustained over 1 year without compensation during aging. In addition to these age-related changes, systemic stimulation with the α1-adrenergic receptor agonist phenylephrine, which induces sustained hypertension and hypertrophy development, induced expression of fetal cardiac genes that was more pronounced in adult Fhod3-deleted mice than in the control mice, suggesting that Fhod3 modulates hypertrophic changes in the adult heart. We conclude that Fhod3 plays a crucial role in both postnatal cardiac development and functional maintenance of the adult heart.

Long-term results after treatment of the ascending aorta for bicuspid aortic valve patients.

PURPOSE: We evaluated the long-term results of aortic valve replacement for bicuspid aortic valve patients with or without surgical treatment of the ascending aorta. METHODS: A total of 145 bicuspid aortic valve patients had undergone aortic valve replacement since 1974 at our institution. No surgical treatment (Group-N; n = 115) was performed in the ascending aorta if the diameter was less than 40 mm. We wrapped an ascending aorta of 40-50 mm with an artificial graft (Group-W; n = 19), and performed replacement (Group-R; n = 11) if the ascending aorta measured more than 50 mm. Follow-up was completed for 144 patients (99.3 % of the cases). RESULTS: The hospital mortality rate was 1.4 %. There were no significant differences among Groups N, W and R in the freedom from valve-related death and cardiac death at 10 years after surgery. The rates of freedom from aorta-related events in the three groups at 10 years after surgery were 98.3 % (Group-N), 100 % (Group-W) and 100 % (Group-R). CONCLUSIONS: The long-term survival was equivalent among the three groups, and the rates of freedom from aorta-related death or events were low. Our surgical protocol for the treatment of the enlarged ascending aorta associated with BAV is appropriate.

Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration.

Mesenchymal stem cell (MSC) transplantation is used for treatment of many diseases. The paracrine role of MSCs in tissue regeneration is attracting particular attention. We investigate the role of MSC exosomes in skeletal muscle regeneration. MSC exosomes promote myogenesis and angiogenesis in vitro, and muscle regeneration in an in vivo model of muscle injury. Although MSC exosomes had low concentrations of muscle-repair-related cytokines, a number of repair-related miRNAs were identified. This study suggests that the MSC-derived exosomes promote muscle regeneration by enhancing myogenesis and angiogenesis, which is at least in part mediated by miRNAs such as miR-494.

Endovascular Surgery for Traumatic Thoracic Aortic Injury: Our Experience with Five Cases, Two of Whom were Young Patients.

OBJECTIVES: We present our experience of endovascular surgery for traumatic aortic injury and the results of our procedures. MATERIALS AND METHODS: From January 2009 to December 2013, we performed endovascular repairs of traumatic thoracic aortic injury on 5 male patients 16-75 years old (mean, 50.8), two of whom were young. Three of the patients had multiple organ injuries. The mean interval time to the operation is 22.0 hours (range, 10-36). All patients underwent endovascular repair with heparinization. The isthmus regions were seen in three cases and all of them were needed left subclavian artery (LSA) coverage. In the two young patients, the deployed stent graft was 22 mm (22.2% oversizing for diameter of aorta) and 26 mm (36.8% oversizing), respectively. RESULTS: The procedures were successful in all patients, with no early mortality, paraplegia or stroke. During 3-63 months (mean, 30.8) follow-up period, no one experienced stent graft-related complications. One patient with LSA coverage experienced arm ischemia but the symptom improved with time. CONCLUSION: Endovascular surgery for traumatic thoracic aortic injury can be performed safely with low mortality or morbidity even in young small aorta. Accumulation of clinical experience and evaluation of long-term outcomes are necessary.

Cardiac energetics analysis after aortic valve replacement with 16-mm ATS mechanical valve.

The 16-mm ATS mechanical valve is one of the smallest prosthetic valves used for aortic valve replacement (AVR) in patients with a very small aortic annulus, and its clinical outcomes are reportedly satisfactory. Here, we analyzed the left ventricular (LV) performance after AVR with the 16-mm ATS mechanical valve, based on the concept of cardiac energetics analysis. Eleven patients who underwent AVR with the 16-mm ATS mechanical valve were enrolled in this study. All underwent echocardiographic examination at three time points: before AVR, approximately 1 month after AVR, and approximately 1 year after AVR. LV contractility (end-systolic elastance [Ees]), afterload (effective arterial elastance [Ea]), and efficiency (ventriculoarterial coupling [Ea/Ees] and the stroke work to pressure-volume area ratio [SW/PVA]) were noninvasively measured by echocardiographic data and blood pressure measurement. Ees transiently decreased after AVR and then recovered to the pre-AVR level at the one-year follow-up. Ea significantly decreased in a stepwise manner. Consequently, Ea/Ees and SW/PVA were also significantly improved at the one-year follow-up compared with those before AVR. The midterm LV performance after AVR with the 16-mm ATS mechanical valve was satisfactory. AVR with the 16-mm ATS mechanical valve is validated as an effective treatment for patients with a very small aortic annulus. The cardiac energetics variables, coupling with the conventional hemodynamic variables, can contribute to a better understanding of the patients' clinical conditions, and those may serve as promising indices of the cardiac function.

Rapid progression of left ventricular thrombus with left ventricular dysfunction detected by preoperative transthoracic echocardiography.

We report a successfully treated case of rapid progressive left ventricular (LV) thrombus with ischemic cardiomyopathy. Initially, the patient was scheduled to undergo only coronary artery bypass grafting. After two months, preoperative echocardiography revealed a previously undetected ball-like thrombus in the LV cavity. Surgical revascularization and thrombectomy were performed. No systemic embolism was associated with surgical manipulation during the perioperative period. Repeated preoperative evaluation for the presence of thrombus by transthoracic or transesophageal echocardiography is essential in cases of ischemic cardiomyopathy.