Attitude after a mild aortic valve lesion during rheumatic mitral valve surgery

ObjectiveWe evaluated whether rheumatic aortic valve disease of mild degree should be treated in patients undergoing mitral valve surgery.MethodsFrom 1992 to 2010, 197 patients (aged 52 [19-82] years, male:female = 60:137) who had rheumatic mitral valve disease and mild aortic valve disease were enrolled. The aortic valve was untreated in 114 patients (no treatment group), repaired in 40 patients (aortic valvuloplasty group), and replaced in 43 patients (aortic valve replacement group).ResultsOperative mortality occurred in 4 patients (2.0%). There were no differences in early mortality and postoperative complications among the 3 groups. Overall survival at 5, 10, and 15 years was 96.3%, 92.1%, and 85.7%, respectively. In the no treatment group, progression-free survival in significant aortic valve disease at 5, 10, and 15 years was 98.7%, 91.3%, and 81.1%, respectively. This was not superior in the aortic valvuloplasty group (85.9%, 77.6%, and 69.8%, respectively) than in the no treatment group. Freedom from aortic valve disease was lower in patients with aortic stenosis than in those with aortic regurgitation in univariate and multivariable analyses (P < .001). Reoperation was performed in 19 patients, including 2 aortic valve reoperations. Aortic valve–related event-free survival was similar among the 3 groups.ConclusionsMild aortic valve disease in patients undergoing rheumatic mitral valve surgery could be left untreated, because preventive aortic valve operation does not result in better clinical and echocardiographic outcomes

Treatment Results of Major Salivary Gland Cancer by Surgery with or without Postoperative Radiation Therapy

ObjectivesThis is to report treatment results of major salivary gland cancer by surgery with or without postoperative radiation therapy (PORT).MethodsBetween March 1995 and January 2006, 94 patients with primary major salivary cancer underwent curative surgical resection at Samsung Medical Center. The parotid gland was the most commonly involved (73, 77.7%), followed by the submandibular and the sublingual. Neck dissection was added in 28 patients, and PORT was individually recommended to those with risk factors. Seventy-five (79.8%) patients received PORT. PORT volume included primary tumor bed and pathologically involved regional lymphatics, and no additional effort was made for elective nodal irradiation. The median total doses were 56.0 Gy to primary site and 58.7 Gy to regional lymphatics.ResultsAfter median follow-up of 49 months, 21 patients had relapsed: 20 in PORT; and one in surgery alone group. As the first site of failure, distant metastasis was the most common (17 patients). Local recurrence occurred in three, and regional relapse in one. The lung was the most common site (10 patients), followed by the bone, and the brain. Five-yr disease free survival (DFS), local control, and overall survival (OS) rates were 74.4% and 94.7%, 96.0% and 100%, and 78.2% and 100% in PORT and surgery alone groups, respectively. On multivariate analysis, DFS was significantly affected by pN+ (hazard ratio [HR], 3.624; P=0.0319), while OS was by pN+ (HR, 7.138; P=0.0034) and perineural invasion (HR, 5.073; P=0.0187).ConclusionBased on our experience, the patients with early stage major salivary gland cancer with low risk can be effectively treated by surgery alone, and those who with risk factors can achieve excellent local and regional control by adding PORT. Omitting elective neck irradiation in patients with N0 disease seems a feasible strategy under accurate clinical evaluation. An effort is needed to decrease distant metastasis through further clinical trials

Functional Benefit after Modification of Radial Forearm Free Flap for Soft Palate Reconstruction

ObjectivesTo compare the velopharyngeal function, swallowing and speech of the conventional and modified radial forearm free flap (RFFF) for soft palate reconstruction.MethodsRetrospective clinical study. Twenty-eight patients who underwent oropharyngeal reconstruction with RFFF were divided into two groups: 10 patients had conventional folded RFFF and 18 patients underwent modified method.ResultsThe average speech intelligibility score in modified RFFF group was 8.0±2.4, and 6.2±2.2 in conventional RFFF group (P<0.05). The nasalance was 27.4±7.8% in modified group and 38.6±2.7% in conventional group during no nasal passage reading and 43.6±7.3% in modified group, 55.2±7.6% in conventional group during high nasal passage reading (P<0.05). The subjective swallowing functional score was 2.8 in modified group and 2.1 in conventional group.ConclusionThe speech assessment and nasalance demonstrate a more favorable outcome in modified group than conventional group

Calpain-mediated proteolysis of polycystin-1 C-terminus induces JAK2 and ERK signal alterations

AbstractAutosomal dominant polycystic kidney disease (ADPKD), a hereditary renal disease caused by mutations in PKD1 (85%) or PKD2 (15%), is characterized by the development of gradually enlarging multiple renal cysts and progressive renal failure. Polycystin-1 (PC1), PKD1 gene product, is an integral membrane glycoprotein which regulates a number of different biological processes including cell proliferation, apoptosis, cell polarity, and tubulogenesis. PC1 is a target of various proteolytic cleavages and proteosomal degradations, but its role in intracellular signaling pathways remains poorly understood. Herein, we demonstrated that PC1 is a novel substrate for μ- and m-calpains, which are calcium-dependent cysteine proteases. Overexpression of PC1 altered both Janus-activated kinase 2 (JAK2) and extracellular signal-regulated kinase (ERK) signals, which were independently regulated by calpain-mediated PC1 degradation. They suggest that the PC1 function on JAK2 and ERK signaling pathways might be regulated by calpains in response to the changes in intracellular calcium concentration

Transient receptor potential channel TRPV4 mediates TGF-β1-induced differentiation of human ventricular fibroblasts

Background: Cardiac fibroblasts (CFs) are principal extracellular matrix-producing cells. In response to injury, CFs transdifferentiate into myofibroblasts. Intracellular calcium (Ca2+) signaling, involved in fibroblast proliferation and differentiation, is activated in fibroblasts through transient receptor potential (TRP) channels, but the function of these channels has not been investigated in human ventricular CFs. Under evaluation in this study, was the role of TRP channels in the differentiation of human ventricular CFs induced by transforming the growth factor beta (TGF-β), a pro-fibrotic cytokine. Methods: Human ventricular CFs were used in this study. The differentiation of CFs into myofibroblast was induced with TGF-β and was identified by the expression of smooth muscle actin. Results: Results indicate that Ca2+ signaling was an essential component of ventricular CF dif­ferentiation. CFs treated with TGF-β demonstrated increased expression of a TRP channel, TRPV4, both at the mRNA and protein levels, which corresponded with CF-myofibroblast trans-differentiation, as evidenced by the upregulation of α-smooth muscle actin, a myofibroblast marker, and plasminogen activator inhibitor-1, which are fibrogenesis markers. An agonist of TRPV4 induced the conversion of CFs into myofibroblasts, whereas it’s antagonist as well a Ca2+ chelating agent reduced it, indicating that the Ca2+ influx throughTRPV4 is required for CF trans-differentiation. Overall, these results dem­onstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway. Conclusions: Overall, these results demonstrate that TRPV4-mediated Ca2+ influx participates in regulating the differentiation of human ventricular CFs into myofibroblasts through the MAPK/ERK pathway

Transcatheter Arterial Embolization Therapy for a Massive Polycystic Liver in Autosomal Dominant Polycystic Kidney Disease Patients

Polycystic liver is the most common extra-renal manifestation associated with autosomal dominant polycystic kidney disease (ADPKD), comprising up to 80% of all features. Patients with polycystic liver often suffer from abdominal discomfort, dyspepsia, or dyspnea; however, there have been few ways to relieve their symptoms effectively and safely. Therefore, we tried transcatheter arterial embolization (TAE), which has been used in treating hepatocellular carcinoma. We enrolled four patients with ADPKD in Seoul National University Hospital, suffering from enlarged polycystic liver. We embolized the hepatic arteries supplying the dominant hepatic segments replaced by cysts using polyvinyl alcohol particles and micro-coils. The patients were evaluated 12 months after embolization for the change in both liver and cyst volumes. Among four patients, one patient was lost in follow up and 3 patients were included in the analysis. Both liver (33%; 10%) and cyst volume (47.7%; 11.4%) substantially decreased in two patients. Common adverse events were fever, epigastric pain, nausea, and vomiting. We suggest that TAE is effective and safe in treating symptomatic polycystic liver in selected ADPKD patients

The efficacy of tenofovir-based therapy in patients showing suboptimal response to entecavir-adefovir combination therapy

Background/Aims: Before tenofovir (TDF) become available in South Korea, combination therapy with entecavir (ETV) and adefovir (ADV) was the most potent regimen for chronic hepatitis B (CHB) patients who fail to respond to rescue therapy for drug resistance. We analyzed the efficacy of ETV-ADV combination therapy and investigated the clinical and clonal results of TDF-based rescue therapy in CHB patients refractory to this combination. Methods: We retrospectively reviewed the medical records of CHB patients treated for up to 3 years with ETV-ADV combination therapy as a rescue therapy for drug resistance. In cases refractory to this combination, clinical and clonal analyses were performed for TDF-based rescue therapy. Results: The analysis was performed on 48 patients. Twelve patients achieved a virological response (VR) within 3 years. A VR was subsequently achieved in nine of the ten patients without a VR who switched to TDF monotherapy. A VR was also achieved in six of the seven patients who switched to lamivudine-TDF combination therapy, and in two of the two patients who switched to ETV-TDF combination therapy. In an in vitro susceptibility test, viral replication was detected with TDF monotherapy but not with ETV-TDF combination therapy. Conclusions: The efficacy of ETV-ADV combination therapy was insufficient in CHB patients who were refractory to rescue therapy. A more potent regimen such as ETV-TDF combination therapy may be considered in such refractory cases

Increased urinary Angiotensinogen/Creatinine (AGT/Cr) ratio may be associated with reduced renal function in autosomal dominant polycystic kidney disease patients

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney diseases that frequently result in renal failure. In this cross-sectional observational cohort study, we evaluated urinary angiotensinogen (AGT) as a potential biomarker to assess renal function in ADPKD. Methods Urinary AGT was measured in 233 ADPKD patients and its association with estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV) were evaluated. The localization of AGT and other renin-angiotensin system (RAS)-related molecules were identified using immunohistochemistry in human ADPKD tissues. Results Baseline urinary AGT/Cr was negatively correlated with CKD-EPI eGFR (r 2= 0.162, P < 0.001) and positively correlated with htTKV (r2 = 0.107, P < 0.001). Both urinary AGT/Cr and plasma renin activity levels were significantly elevated in hypertensive ADPKD patients. Among hypertensive subjects, urinary AGT/Cr was significantly increased in the advanced CKD stages (III-V) compared to early CKD stages (I-II) (28.6 ± 60.3 vs. 93.2 ± 139.3 μg/g, P < 0.001). Immunohistochemical study showed strong expression of AGT along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. Conclusions Our results suggested that urinary AGT/Cr may be a valuable biomarker for renal damage in ADPKD since intrarenal ischemic insults induced by cyst growth and subsequent intrarenal RAS activation may play a potential role in the development of hypertension and renal dysfunction in ADPKD