Potential mechanism of left ventricular spherical remodeling: association of mitral valve complex-myocardium longitudinal tissue remodeling mismatch.

Since mitral valve (MV) complex (MVC) longitudinally bridges left ventricular (LV) base end and its middle, insufficient MVC longitudinal tissue length (TL) elongation relative to whole LV myocardial longitudinal TL elongation could limit LV-base-longitudinal-TL elongation, leading to predominant LV-base-transverse-TL elongation, constituting LV spherical remodeling. In 30 patients with dilated cardiomyopathy (DCM), 30 with aortic regurgitation (AR), and 30 controls, LV sphericity, LV-apex- or base-transverse- and longitudinal-TL, MVC-longitudinal-TL, and whole-LV-longitudinal-TL were measured by three-dimensional (3D) echocardiography. Ratio of each measure versus mean normal value (i.e., LV-apex-transverse-TL ratio) was considered to express the directional and regional tissue elongation. [LV-base-longitudinal-TL ratio/global-LV-TL ratio] and [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] were obtained as the degree of LV-base-longitudinal-TL or MVC-longitudinal-TL elongation relative to the whole LV elongation. LV-apex-transverse-, LV-apex-longitudinal-, and LV-base-transverse-TL ratios were significantly increased (1.27 to 1.42, P < 0.01) in both DCM and AR, while the LV-base-longitudinal-TL ratio was not increased in DCM [1.04 ± 0.19, not significant (ns)] and only modestly increased in AR (1.12 ± 0.21, P < 0.01). Whole-LV-longitudinal-TL ratio was significantly increased in both DCM and AR (1.22 ± 0.18 and 1.20 ± 0.16, P < 0.01), while MVC-longitudinal-TL ratio was not or only modestly increased in both groups (1.07 ± 0.15, ns, and 1.12 ± 0.17, P = 0.02, respectively). Multivariable analysis revealed that LV sphericity was independently related to a reduced [LV-base-longitudinal-TL ratio/global-LV-TL ratio] (standard ß = -0.42, P < 0.01), which was further related to a reduced [MVC-longitudinal-TL ratio/whole-LV-longitudinal-TL ratio] (standard ß = 0.72, P < 0.01). These are consistent with the hypothesis that relatively less MVC-longitudinal-TL elongation in the process of primary LV myocardial tissue elongation may limit LV-base-longitudinal-TL elongation, contributing to LV spherical remodeling.NEW & NOTEWORTHY Left ventricular (LV) spherical remodeling is associated with poor prognosis and less-effective cardiac performance, which commonly develops in dilated cardiomyopathy. However, its mechanism remains unclear. We hypothesized and subsequently clarified that less mitral valve complex (MVC) tissue longitudinal elongation relative to whole LV myocardial tissue longitudinal elongation is related to disproportionately less LV base longitudinal versus transverse myocardial tissue elongation, constituting spherical remodeling. This study suggests modification of MVC tissue elongation could be potential therapeutic targets.

Estimation of B-type Natriuretic Peptide Values from N-Terminal proBNP Levels.

Both brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are established biomarkers that are necessary in the diagnosis and management of heart failure (HF). However, it is difficult to infer BNP concentration from NT-proBNP concentration for a clinician who is familiar with BNP. We investigated whether estimated BNP concentration from NT-proBNP has an equivalent prognostic strength compared with the actual BNP concentration in the prediction of future outcomes. We created a formula for estimating BNP concentration using multivariate analysis in a derivation cohort with known or suspected HF (n = 374). We determined whether the estimated BNP level had a similar prognostic power compared with the actual BNP and NT-proBNP levels in a validation cohort (n = 375). There was a strong correlation between log-transformed BNP and log-transformed NT-proBNP (r = 0.90) in the derivation cohort. We created two types of equation from the derivation cohort. During a median of 1 year of follow up, 49 major adverse cardiac events developed in the validation cohort. Cox proportional analysis revealed that the actual and estimated BNP levels represented equivalent and significant predictors of the future cardiovascular outcome. The estimated BNP levels calculated by our new formula showed a prognostic power similar to the actual BNP levels. This equation will be useful, especially for a physician who is not familiar with NT-proBNP testing.

Usefulness of Cibenzoline Stress Echocardiography to Determine Severity of Aortic Stenosis in a Patient with Combined Left Ventricular Outflow Tract Obstruction and Aortic Stenosis.

Left ventricular outflow tract obstruction (LVOTO) is sometimes accompanied by aortic stenosis (AS). Reliable estimation of the true severity of AS is often difficult because it cannot be discriminated from dual stenosis. A 75-year-old woman was referred to our hospital due to traumatic hemopneumothorax with exertional dyspnea. Echocardiography revealed AS and LVOTO by chance. A continuous Doppler echocardiography revealed a late-systolic peaking dagger-shaped profile with a 6.0 m/s of peak jet velocity across the LVOT and aortic valve, but it was difficult to discriminate between the coexisting peak flows. For an accurate evaluation of AS, we performed landiolol (short acting beta-blocker) and cibenzoline (Na+ channel-blocking agent) stress echocardiography with simultaneous recordings of both left ventricular and aortic pressure by catheter examination. Cibenzoline successfully eliminated the LVOTO, but landiolol did not. Cibenzoline stress echocardiography enabled us to evaluate the AS severity as less than moderate, resulting in proper decision-making. The findings in this case clearly showed that cibenzoline stress echocardiography has a potential utility for determining AS severity in a patient with coexistent dynamic LVOTO.

Histological and molecular characterization of intrahepatic bile duct cancers suggests an expanded definition of perihilar cholangiocarcinoma.

BACKGROUND: Growing evidence has suggested that intrahepatic cholangiocarcinoma (iCCA) can be classified into small- and large-duct types. The present study aimed to elucidate how large-duct iCCA is similar and dissimilar to perihilar cholangiocarcinoma (pCCA). METHODS: The study cohort consisted of iCCA (n = 58) and pCCA (n = 44). After iCCA tumors were separated into small- (n = 36) and large-duct (n = 22) types based on our histologic criteria, genetic statuses of the three types of neoplasms were compared. Locations of iCCA were plotted on a three-dimensional image and their distances from the portal bifurcation were measured. RESULTS: Large-duct iCCA was distinct from small-duct iCCA in terms of frequency of bile duct reconstruction required, perineural infiltration, and survival, with these features more similar to pCCA. Large-duct iCCA and pCCA more frequently had the loss of SMAD4 expression and MDM2 amplifications than small-duct iCCA, whereas the loss of BAP1 expression and IDH1 mutations were mostly restricted to small-duct iCCA. From imaging analysis, most tumors of large-duct iCCA were present around the second branches of the portal vein. CONCLUSION: Large-duct type iCCA shared the molecular features with pCCA, and it may be reasonable to expand the definition of pCCA to include cancers originating from the second bile duct branches.

Transbronchial lung biopsy for the diagnosis of IgG4-related lung disease.

AIMS: The diagnosis of IgG4-related disease (IgG4-RD) requires a multidisciplinary approach, in which histology plays an important role. Although a diagnosis was previously established by the use of surgically resected specimens, there is increasing clinical demand to diagnose this systemic condition by the use of biopsies. The aim of the present study was to elucidate how useful transbronchial lung biopsies (TBLBs) are for this diagnostic purpose. METHODS AND RESULTS: The study cohort consisted of 20 consecutive patients diagnosed with IgG4-RD in other organs who underwent TBLB for potential pulmonary involvement. One case showing multiple granulomas suggestive of other conditions was excluded. Seven of the remaining 19 cases (37%) showed apparently normal lung tissue, indicating a sampling error, and 12 (63%) had microscopic abnormalities. Nine cases (47%) with a dense lymphoplasmacytic infiltrate met the number and ratio criteria for IgG4-positive plasma cell infiltration (>20 cells/high-power field, and an IgG4/IgG-positive plasma cell ratio of >40%). Obliterative phlebitis and storiform fibrosis were observed in one case each. In 43 control cases of various inflammatory conditions, tissue IgG4 elevations appeared to be uncommon, with only two cases (5%) each meeting the number or ratio criterion, and one case (2%) fulfilling both. All control cases with tissue IgG4 elevations were of eosinophilic pneumonia. CONCLUSIONS: Transbronchial lung biopsies provided histological findings that were supportive for the diagnosis of IgG4-RD in 47% of cases, with 98% diagnostic specificity. Therefore, they have potential as a useful and acceptable diagnostic approach for IgG4-related lung disease.

Interleukin-33 overexpression reflects less aggressive tumour features in large-duct type cholangiocarcinomas.

AIMS: The aim of the present study was to elucidate the clinicopathological significance of interleukin (IL)-6 and IL-33 expression in intrahepatic cholangiocarcinomas (iCCAs) and perihilar cholangiocarcinomas (pCCAs). METHODS AND RESULTS: IL-6 and IL-33 mRNA expression levels were examined in iCCAs (n = 55) and pCCAs (n = 32) by the use of quantitative real-time polymerase chain reaction and a highly sensitive in-situ hybridisation protocol (RNAscope), and expression levels were correlated with clinicopathological features. According to a recently proposed classification scheme, iCCAs were separated into small-duct (n = 33) and large-duct (n = 22) types. IL-6 and IL-33 expression levels were higher in large-duct iCCAs and pCCAs than in small-duct iCCAs, and there was a positive correlation between the expression levels of these cytokines. Double in-situ hybridisation/immunostaining showed that IL-6 mRNA was expressed in actin-positive (myo)fibroblasts, whereas IL-33 mRNA was mainly produced by CD31-positive endothelial cells. With the average expression level as a cut-off point, cases were classified as IL-6high and IL-6low or IL-33high and IL-33low . In the combined cohort of large-duct iCCAs and pCCAs, IL-6high and IL-6low cholangiocarcinomas shared many features, whereas IL-33high cases had less aggressive characteristics than IL-33low cases, as shown by lower tumour marker concentrations, smaller tumour sizes, less common vascular invasion, lower pT stages, and higher lymphocyte/monocyte ratios in blood. KRAS mutations were slightly less common in IL-33high cases than in IL-33low cases (9% versus 29%; P = 0.061). The strong expression of IL-33 in tissue appeared to be an independent favourable prognostic factor. CONCLUSIONS: IL-33high cholangiocarcinomas may represent a unique, less aggressive carcinogenetic process of the large bile ducts.

Dichotomy in intrahepatic cholangiocarcinomas based on histologic similarities to hilar cholangiocarcinomas.

Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type. The perihilar type had higher pT stages and more frequently showed a periductal-infiltrating gross appearance and microscopic perineural infiltration than peripheral cholangiocarcinomas. The presence of low-grade biliary intraepithelial neoplasia in the adjacent bile ducts was only found in perihilar cholangiocarcinomas (6/21, 29%). The immunophenotype also differed between the two types with MUC5AC and MUC6 being more commonly expressed in the perihilar type. One-third of perihilar cholangiocarcinomas lacked the expression of SMAD4, suggesting SMAD4 mutations, whereas the loss of BAP1 expression and IDH1 mutations were almost restricted to the peripheral type (35 and 15%, respectively). Patients with perihilar cholangiocarcinoma had worse overall survival than those with peripheral cancer (P=0.027). A multivariate analysis identified the histologic classification as an independent prognostic factor (P=0.005, HR=3.638). Comparisons between intrahepatic and hilar cholangiocarcinomas also revealed that the molecular features and prognosis of perihilar cholangiocarcinomas were very similar to those of hilar cholangiocarcinomas. In conclusion, this histology-based classification scheme of intrahepatic cholangiocarcinomas will be useful and clinically relevant because it represents different underlying molecular features and has an independent prognostic value.

Pancreatic Duct Involvement in Well-Differentiated Neuroendocrine Tumors is an Independent Poor Prognostic Factor.

BACKGROUND: The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs. METHODS: The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection. RESULTS: MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P < 0.001), with a 5 years recurrence-free rate of 41%. On multivariate analysis, MPD involvement was significantly associated with nodal metastasis [odds ratio (OR) 16; 95% confidence interval (CI) 3.8-89; P < 0.001] and recurrence (OR 8.0; 95% CI 1.7-46; P = 0.009). The radiology-pathology correlation revealed that stenosis of the MPD was due to periductal and/or intraductal tumor invasion. Cases with MPD involvement had microscopic venous invasion (P = 0.010) and perineural infiltration (P = 0.002) more frequently than did those with no ductal infiltration. CONCLUSIONS: MPD involvement in PNETs may serve as an imaging sign indicating an aggressive clinical course.

Baseline plasma chromogranin A levels in patients with well-differentiated neuroendocrine tumors of the pancreas: A potential predictor of postoperative recurrence.

BACKGROUND: The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). METHODS: Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients' survival. RESULTS: Plasma CgA levels ranged 2.9-30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). CONCLUSIONS: Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence.

Comparative clinicopathological study of biliary intraductal papillary neoplasms and papillary cholangiocarcinomas.

AIMS: The aim of this study was to achieve a better definition of intraductal papillary neoplasms of the bile duct (IPNBs). METHODS AND RESULTS: Biliary tumours that showed predominantly intraductal papillary growth were provisionally classified as IPNBs (n = 25) and papillary cholangiocarcinomas (n = 27). IPNB was defined as a neoplasm that is confined to the epithelium or is regularly arranged in a high-papillary architecture along thin fibrovascular stalks, whereas the term 'papillary cholangiocarcinoma' was used for tumours with more complex papillary structures (e.g. irregular papillary branching or mixed with solid-tubular growth). In our consecutive cohort of biliary neoplasms, 5% were classified as IPNBs, and 10% as papillary cholangiocarcinomas. IPNBs differed from papillary cholangiocarcinomas by less advanced invasion, gross mucin overproduction (72% versus 7%), and their prevalent location (84% of IPNBs in intrahepatic/hilar ducts; 70% of papillary cholangiocarcinomas in extrahepatic ducts). Gastric-type and oncocytic-type tumours were only detected in IPNBs. Expression of mucin core proteins and cytokeratin 20 significantly differed between the two groups. KRAS and GNAS were wild-type genotypes in all but one case of KRAS-mutated IPNB. Patients with IPNB had better recurrence-free survival than those with papillary cholangiocarcinoma (P = 0.007). In multivariate analysis, in which several other prognostic factors (e.g. stromal invasion and lymph node metastasis) were applied, the classification of the two papillary tumours was an independent prognostic factor (P = 0.040). CONCLUSIONS: Given the significant contrast in clinicopathological features between IPNBs and papillary cholangiocarcinomas, it may be more appropriate to use the diagnostic term 'IPNB' for selected tumours that show regular papillary growth, separately from papillary cholangiocarcinomas.

Microscopic venous invasion in patients with pancreatic neuroendocrine tumor as a potential predictor of postoperative recurrence.

BACKGROUND: Microscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear. METHODS: Thirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival. RESULTS: Venous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion (P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival (P = 0.021). CONCLUSIONS: Microscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.

Left Atrial Remodeling in Segmental vs. Global Mitral Valve Prolapse　- Three-Dimensional Echocardiography.

BACKGROUND: Segmental and global mitral valve prolapse (MVP) comprise 2 representative phenotypes in this syndrome. While mitral regurgitation (MR) severity is a major factor causing left atrial (LA) remodeling in MVP, prominent mitral valve (MV) annulus dilatation in global MVP may specifically cause inferiorly predominant LA remodeling. We compared MV annulus and LA geometry in patients with segmental and global MVP.Methods and Results:LA volume as well as inferior, middle, and superior LA cross-sectional areas (CSA) were measured on 3-D echocardiography in 20 controls, in 40 patients with segmental MVP, and in 18 with global MVP. On multivariate analysis, MR severity was primarily associated with LA dilatation in segmental MVP (P<0.001), while MV annular dilatation was primarily associated with LA dilatation in global MVP (P<0.001). Although there was no regional predominance in LA dilatation in segmental MVP, inferior predominance of LA dilatation was significant in global MVP (increase in inferior, middle, and superior LA-CSA relative to mean of the controls: +220±70% vs. +171±55% vs. +137±37%, P<0.001). CONCLUSIONS: LA remodeling in segmental and global MVP is considerably different regarding its association with MR volume or MV annular dilatation and its regional predominance. While MR volume may mainly contribute to LA remodeling in segmental MVP, MV annular dilatation seems to have an important role in LA remodeling in global MVP. (Circ J 2016; 80: 2533-2540).

Sclerosing mesenteritis: A real manifestation or histological mimic of IgG4-related disease?

We present three cases of sclerosing mesenteritis and review the literature to learn whether or not sclerosing mesenteritis is an IgG4-related disease (IgG4-RD). Our patients were all adult males. Their mesenteric masses ranged from 6.5 to 14.5 cm in the greatest diameter. Tissue specimens showed moderate to severe lymphoplasmacytic infiltration with occasional eosinophils against a background of irregular fibrosis. Both obliterative phlebitis and storiform fibrosis were noted in all cases. IgG4+ plasma cells were moderately increased in number (46 to 85 cells/high-power field). However, unlike IgG4-RD, the IgG4+/IgG+ plasma cell ratio was <40% (28% to 35%). Serum IgG4 concentrations were also within the normal range (43.2 to 105 mg/dL; normal range <135 mg/dL). Two biopsy cases showed spontaneous regression on imaging approximately 5 months later. No sclerosing conditions were found in other organs. The literature review identified 11 additional cases of sclerosing mesenteritis with IgG4+ plasma cell infiltration. However, conclusive cases with four characteristic features (high serum IgG4 levels, tissue IgG4 elevation, multi-organ involvement, and effective response to glucocorticoid therapy) have never been reported. In conclusion, although sclerosing mesenteritis shares histological features with IgG4-RD, most cases are less likely to be IgG4-related. IgG4-RD seemingly seldom, if ever, affects this anatomical site.

A large cavernous malformation of the third ventricle floor: A case report.

Suprasellar and third ventricular region cavernous malformations originating from the floor of the third ventricle are extremely rare. We report a case of third ventricular cavernous malformation arising from the ventricle floor in a 24-year-old woman who presented with short-term memory loss and disorientation. Computed tomography revealed a suprasellar mass with calcification in the posterior chiasmatic region. T2-weighted magnetic resonance imaging revealed a mass with heterogeneous intensity and without hydrocephalus. The mass was slightly enhanced subsequent to gadolinium infusion. Using a basal interhemispheric translamina terminalis approach and a neuroendoscope, we confirmed that the tumor was located at the floor of the third ventricle and removed it. Histopathological examination confirmed the diagnosis of cavernous malformation. The postoperative course was uneventful, but the patient's short-term memory loss persisted. Despite its rarity, cavernous malformation should be suspected when a tumor is detected in the vicinity of the third ventricle floor. It is treatable through surgical resection.

Evidence of a vicious cycle in mitral regurgitation with prolapse: secondary tethering attributed to primary prolapse demonstrated by three-dimensional echocardiography exacerbates regurgitation.

BACKGROUND: In patients with mitral valve prolapse, nonprolapsed leaflets are often apically tented. We hypothesized that secondary left ventricular dilatation attributed to primary mitral regurgitation (MR) causes papillary muscle (PM) displacement, resulting in this leaflet tenting/tethering, and that secondary tethering further exacerbates malcoaptation and contributes to MR severity. METHODS AND RESULTS: Three-dimensional transesophageal echocardiography was performed in 25 patients with posterior mitral leaflet prolapse with an intact anterior mitral leaflet (AML) and 20 controls. From 3D zoom data sets, 11 equidistant antero-posterior cut planes of the mitral valve at midsystole were obtained. In each plane, tenting area of nonprolapsed leaflet and prolapse area of prolapsed leaflet were measured. Prolapse/tenting volume of each region was obtained as the product of interslice distance and the prolapse/tenting area. AML tenting volume and whole leaflet prolapse/tenting volume were then obtained. The PM tethering distance between PM tips and anterior mitral annulus was measured from 3D full-volume data sets. The severity of MR was quantified by vena contracta area extracted from color 3D transesophageal echocardiography data sets. AML tenting volume was significantly larger in patients with posterior mitral leaflet prolapse compared with that in controls (1.2 ± 0.5 versus 0.6 ± 0.2 mL/m(2); P<0.001). Multivariate regression analysis identified independent contribution to AML tenting volume from an increase in PM tethering distance. Multivariate regression analysis identified independent contributions to MR severity (vena contracta area) from both whole leaflet tenting volume (r=0.44; P<0.05) and prolapse volume (r=0.44; P<0.05). AML tenting volume decreased along with left ventricular volume and PM tethering distance postrepair (n=8; P<0.01). CONCLUSIONS: These results suggest that primary mitral valve prolapse with MR causes secondary mitral leaflet tethering with PM displacement by left ventricular dilatation, which further exacerbates valve leakage, constituting a vicious cycle that would suggest a pathophysiologic rationale for early surgical repair.

Different influences of left ventricular remodeling on anterior and posterior mitral leaflet tethering.

BACKGROUND: Different influences of left ventricular (LV) remodeling on anterior and posterior mitral leaflet (AML and PML) tethering in ischemic mitral regurgitation (MR) has not been fully investigated. We hypothesized that progressive outward displacement of papillary muscles, including posterior vector, may cause greater tethering to PML compared to AML. METHODS AND RESULTS: In 79 patients with LV ejection fraction <50% and 20 controls, LV sphericity, AML and PML tethering angles, apical and posterior displacement of coaptation, mitral annular area, and severity of MR (vena contracta width) were measured using 3-D echocardiography. To examine different influences of LV remodeling on AML and PML tethering, interaction between AML/PML and LV sphericity was tested using multiple regression analysis. Both AML and PML tethering significantly increased with increased LV sphericity (r=0.59 and 0.65, P<0.001). Multiple regression yielded a significant interaction term between AML vs. LV sphericity and PML vs. LV sphericity (t=3.69, P<0.001), indicating greater influence from LV remodeling on PML compared to that for the AML. Multivariate analysis demonstrated independent contributions to MR severity from PML tethering primarily along with posterior and apical displacement of coaptation. CONCLUSIONS: LV remodeling augments tethering of both AML and PML, with greater influence on PML.

An essential dose of cisplatin for super-selective intra-arterial infusion concomitant with radiotherapy in patient with maxillary squamous cell carcinoma.

The present study investigated the efficacy and safety of using a lower dose of cisplatin (CDDP) in super-selective intra-arterial concurrent chemoradiotherapy (SSIACRT) to treat maxillary squamous cell carcinoma. 10 patients with maxillary squamous cell carcinoma (T3 n = 6, T4a n = 4) without regional or distant metastasis were treated by SSIACRT. The CDDP dose per course was 100 mg/body, i.e. 50-80 mg/m(2). 6-9 weeks after SSIACRT, partial maxillectomy was performed on all patients. Clinical and histological responses, survival rates, and adverse events were investigated. 10 (100%) of 10 patients achieved both clinical and pathological complete or partial remission. The 3-year overall and disease-free survival rates were 100 and 90%, respectively. Grade 3 toxicity was experienced by two patients. In conclusion, the SSIACRT regimen with a lower dose of CDDP (100 mg/body) had an equivalent therapeutic outcome and lower toxic outcome compared to a higher dose of CDDP. This regimen could be an effective and safe therapeutic modality for maxillary squamous cell carcinoma except T4b and N1/2 disease.

Severe functional tricuspid regurgitation due to wild-type transthyretin amyloid cardiomyopathy without left ventricular hypertrophy: a case report.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is usually characterized by left ventricular (LV) hypertrophy or LV systolic dysfunction. However, right atrial (RA) amyloidosis without LV hypertrophy, leading to severe functional tricuspid regurgitation (FTR), is extremely rare. Case summary: We present 75-year-old female with exertional dyspnoea and pre-syncope. Transthoracic echocardiography showed a normal LV function and no LV hypertrophy. A sick sinus syndrome and severe FTR due to right ventricular (RV) and RA dilatation were observed. A leadless cardiac pacemaker implantation was performed for sick sinus syndrome and the symptoms improved, but she complained of leg oedema and fatigue on effort again. A repeated transthoracic echocardiogram showed no notable changes in LV function, but progression of RV and RA dilatation was observed, with worsening FTR. Despite treatment of loop diuretics with 30 mg daily of azosemide, symptoms did not improve, and the patient underwent tricuspid valve annuloplasty. Pathological findings from right atrium led to a diagnosis of ATTR-CM, and deoxyribonucleic acid sequence analysis did not indicate any typical mutation, which supported a diagnosis of wild type of ATTR-CM (ATTRwt-CM). She has been asymptomatic after the surgical operation. She has also been treated with 80 mg daily of tafamidis meglumine to prevent further accumulation of transthyretin in the myocardium and potentially improve long-term outcomes. Discussion: Isolated atrial amyloidosis, especially occurring predominantly in the right atrium and caused by ATTRwt-CM without LV hypertrophy, is extremely rare. However, differential diagnosis should be considered for patients with unexplained dilatation of the right-sided heart or bradyarrhythmia.

A case of pulmonary leiomyosarcoma achieving long-term survival after multiple metastasectomies.

A 58-year-old man who underwent lower lobectomy of the right lung for primary pulmonary leiomyosarcoma (PPL) 4 years ago presented with epigastric pain and was diagnosed with small bowel intussusception caused by an intestinal mass. Partial resection of the small intestine was performed, and pathological examination revealed metastatic leiomyosarcoma. Masses in the left adrenal gland, subcutaneous tissue of the left upper arm, right pleura, jejunum, right trapezius muscle, and right adrenal gland were subsequently detected in the following 4 years. Resection was performed for each tumor, which was histologically confirmed as metastatic leiomyosarcoma. However, 1 month after the last surgery, multiple systemic metastases were found, thus, he is currently undergoing chemotherapy. The patient has been alive for 8 years and 4 months after the first operation for PPL. PPL is an extremely rare disease with no established treatment strategy for recurrences. Aggressive metastasectomy may be beneficial in selected cases.