Tubular intestinal duplication extending from the stomach to the ileum associated with multiple intestinal atresia and situs inversus: a case report.

BACKGROUND: Duplication of the alimentary tract can occur in any of its parts. For duodenal duplication, complete resection is particularly difficult when the ampulla of Vater is on the duplicated lumen and a deliberate management is necessary. CASE PRESENTATION: A 0-day female baby was referred to our department due to abdominal distention. The X-ray examination showed dextrocardia and opacity of the liver on the left side and abdominal ultrasonogram revealed remarkable intestinal dilatation. Therefore, urgent laparotomy was performed on the day of birth. Complete situs inversus of the abdominal organs was revealed, and the origin of the jejunum was on the left side and was accompanied by tubular intestinal duplication. The origin of the duplicated intestine was at the pancreatic head's dorsal area. There were two points of type Шa atresia on the ileum. Therefore, we spared the duplicated intestine with a length of 3 cm to secure the passage of the biliary and pancreatic juices by a functional-side-to-side anastomosis with a 45-mm Endo-GIA™ camel load (Medtronic, Minneapolis, MN, USA). The ileum was transected at the distal side of the atresia point, and end-to-end jejunoileostomy was performed. Postoperative gastrointestinal series revealed remnants of the duplicated alimentary tract on the dorsal area of the stomach. CONCLUSIONS: Identifying the position of the ampulla of Vater is crucial in the surgery of alimentary tract duplication with duodenal involvement. However, in the present case, it was difficult to identify whether the ampulla of Vater was on the true or duplicated lumen, and we had to spare the duplicated duodenum. Stapler anastomosis could be performed safely even in neonatal cases.

Correlation of medial longitudinal arch morphology with body characteristics and locomotive function in community-dwelling older women: A cross-sectional study.

PURPOSE: This cross-sectional study aimed to investigate the effects of foot arch deformities on physical characteristics, muscular strength, and motor function in older women depending on the presence or absence of pain. METHODS: Overall, 145 community-dwelling women aged 65 to 90 years were included in this study. We measured the foot arch height ratio (AHR, dorsal height/truncated foot length) and classified participants with AHR values above, below, or within 1.5 standard deviations into the high-arched group (HAG), Low-Arched Group (LAG), or normal-arched group (NAG), respectively. We also compared body characteristics (age, height, weight, body mass index (BMI), and skeletal mass index), muscle strength (handgrip strength and intrinsic foot strength (IFS)), and locomotive function (two-step value and gait speed) among the three groups. RESULTS: Locomotive examination and muscle strength showed significant differences among the three groups only in the presence of pain; in the two-step test, HAG, NAG, and LAG values were 0.98 cm/cm, 1.19 cm/cm, and 1.18 cm/cm, respectively. The IFS measured 19.2 N, 24.2 N, 31.0 N, respectively, in the HAG, NAG, and LAG. CONCLUSION: This study suggests that decreased IFS affects the mobility function of high-arched feet in older women. Although there was no significant difference in the evaluation of pain, HAG showed the highest average value, which is considered to contribute to the decreased two-step value. It has been suggested that a high-arched foot in the presence of pain is associated with IFS weakness and may affect the decline of mobility function in older women.

A phenylphthalimide derivative, TC11, induces apoptosis by degrading MCL1 in multiple myeloma cells.

To date, the prognosis of multiple myeloma (MM) in patients harboring cytogenetic abnormalities (CA) involving t (4; 14) and deletion of chromosome 17 remains poor despite recent advances in drug development that include the use of immunomodulatory drugs (IMiDs) such as lenalidomide for MM. To address this issue, we have developed a novel phenylphthalimide derivative, TC11, that is structurally related to IMiDs. It remains unclear how TC11 induces apoptosis of MM cells with high-risk CA. Here, we show that TC11 does not induce degradation of CRBN's substrates, IKZF1/3 and CK1α, and induces apoptosis of CRBN-silenced MM; this effect was independent of the cereblon (CRBN) pathway, which is involved in the mechanism of action of IMiDs used for the treatment of MM. We also revealed that TC11, in contrast to existing IMiDs, induced degradation of MCL1 and activation of caspase-9. Furthermore, inhibition of CDK1 by CGP74514A prevented TC11-induced MCL1 degradation, caspase-9 activation, and the subsequent apoptotic cell death. We showed that ectopic MCL1 expression rescued apoptosis of MM. These observations suggest that TC11 induces apoptotic death caused by degradation of MCL1 during prolonged mitotic arrest. Therefore, our findings suggest that TC11 is a potential drug candidate for high-risk MM.

Tumor thickness as a prognostic factor in extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is a rare tumor and a widely accepted classification system specific for the disease has not been established. To elucidate prognostic factors of EMPD, we conducted a retrospective review of 145 patients with 155 EMPD lesions and investigated clinicopathological factors using univariate and multivariate analyses. We also explored tumor thickness and metastatic lymph nodes using detection analysis to determine cut-off points for survival. All patients were Japanese (88 men and 57 women), with EMPD in the genital (82.8%), perianal (3.4%) and axillary regions (1.4%). In the remaining cases (12.4%), there were lesions at two or more regions. Univariate analysis revealed the following prognostic factors: perianal location, presence of nodules, invasion depth, tumor thickness, number of metastatic nodes and serum carcinoembryonic antigen level. Both tumor thickness and perianal location retained statistical significance in multivariate analysis (hazard ratio, 1.39; 95% confidence interval, 1.12-1.72; P = 0.0024; hazard ratio, 50.72; 95% confidence interval, 4.20-612.63; P = 0.0020; respectively). The signal detection analysis indicated tumor thickness of more than 3 mm and three or more metastatic lymph nodes as cut-off points for survival. In conclusion, tumor thickness and the number of metastatic lymph nodes closely correlated with patient outcome and these factors could be suitable for the tumor and node classification.

Acral lentiginous melanoma: who benefits from sentinel lymph node biopsy?

BACKGROUND: There are significant clinicopathological, genetic, and biological differences between acral lentiginous melanoma (ALM) and other types of melanoma. OBJECTIVE: We sought to investigate the use of sentinel lymph node (SLN) biopsy for patients with ALM. METHODS: This was a retrospective review of 116 patients with primary ALM. Melanoma-specific and disease-free survival were estimated using the Kaplan-Meier method, together with multivariate analyses using the Cox proportional hazards regression model. RESULTS: All patients were Japanese (48 male and 68 female). Metastases in SLN were noted in 13 of 84 patients who underwent SLN biopsy. No patients with thin ALM (≤1 mm) and only 2 patients with nonulcerated ALM had tumor-positive SLN. Patients with positive SLN had significantly shorter melanoma-specific survival (5-year survival rate, 37.5% vs 84.3%; P < .0001) and disease-free survival (5-year survival, 37.5% vs 77.9%; P = .0024). Among patients with thick (>1 mm) ALM, the influence of SLN positivity on melanoma-specific survival was increased (5-year survival, 22.7% vs 80.8%; P = .0005). LIMITATIONS: This was a retrospective study and had a small sample size. CONCLUSIONS: SLN biopsy should be considered for patients with thick or ulcerated ALM. For patients with thin or nonulcerated ones, it may be of limited importance.

3,4-Dihydroxybenzaldehyde Derived from Prunus mume Seed Inhibits Oxidative Stress and Enhances Estradiol Secretion in Human Ovarian Granulosa Tumor Cells.

Granulosa cells form ovarian follicles and play important roles in the growth and maturation of oocytes. The protection of granulosa cells from cellular injury caused by oxidative stress is an effective therapy for female infertility. We here investigated an effective bioactive compound derived from Prunus mume seed extract that protects granulosa cells from hydrogen peroxide (H2O2)-induced apoptosis. We detected the bioactive compound, 3,4-dihydroxybenzaldehyde (3,4-DHBA), via bioactivity-guided isolation and found that it inhibited the H2O2-induced apoptosis of granulosa cells. We also showed that 3,4-DHBA promoted estradiol secretion in granulosa cells and enhanced the mRNA expression levels of steroidogenic factor 1, a promoter of key steroidogenic enzymes. These results suggest that P. mume seed extract may have clinical potential for the prevention and treatment of female infertility.

Up-regulation of urinary-type plasminogen activator correlates with high-risk papillary thyroid carcinoma with BRAF(V600E) mutation and its possible molecular mechanism.

The aim of the present study is to investigate the relationship between urinary-type plasminogen activator (uPA) expression and clinicopathological features in papillary thyroid carcinoma (PTC) and to determine the signal transduction of PTC cells in vitro. PTC tissues from 42 patients were analyzed for the expression of uPA and the BRAF(V600E) mutation. BCPAP, a PTC cell line harboring the BRAF(V600E) mutation, was used to study MAPK signaling. PCR and direct sequencing were applied to analyze BRAF(V600E) mutation status. uPA mRNA expression was measured using a quantitative RT-PCR method, and uPA protein was localized using an immunohistochemical method. The ERK protein status was detected by Western blot analysis. uPA gene expression was significantly increased in PTC tissues as compared to the corresponding non-tumor tissues. Furthermore, the up-regulation of uPA mRNAs was correlated with high-risk clinicopathological features, including extrathyroid invasion, loss of cellular polarity/cohesiveness, and the BRAF(V600E) mutation. Marked dephosphorylation of ERK1/2 and down-regulation of uPA expression were detected when BCPAP was treated with a MEK inhibitor, U0126. MEK inhibitors might be a potential treatment strategy for aggressive PTC with BRAF(V600E) through inhibition of uPA expression.

S100A6 and c-Kit-Positive Spindle Cell Melanoma of the Dorsal Foot.

Spindle cell melanoma, which is a rare form of melanoma, is clinically and histopathologically difficult to diagnose from a variety of nonmelanocytic spindle cell tumors. We describe a 42-year-old Japanese woman with amelanotic melanoma that comprised spindle cells with positive c-kit and S100A6 staining. The use of c-kit and S100A6 might be useful for improving the diagnosis.

Loss of cellular cohesion in cytology composes a special subgroup of breast tumors - analysis of 37 cases.

OBJECTIVE: We analyzed smears by fine needle aspiration (FNA) from 37 cases that displayed numerous dissociated cells and correlated the results with histological findings. STUDY DESIGN: Between 1996 and 2005, 1,583 patients underwent breast FNA and resection. Loss of cellular cohesion was observed in 37 of these cases. RESULTS: From the cytological findings, we classified cases into 3 groups according to cell size and shape. Type A: numerous isolated spindle cells with a necrotic background. Four cases were classified into this group (3 cases of intraductal papilloma and 1 case of adenomyoepithelioma). Type B: lymphocytes and large isolated cells such as medullary carcinoma. Five cases were classified into this group [1 case of classic medullary carcinoma, 1 case of ductal carcinoma in situ (DCIS) and 3 cases of invasive carcinoma of no special type (NST)]. Type C: numerous uniform small round cells. Twenty-eight cases were classified into this group (2 cases of lobular carcinoma, 1 case of DCIS, 22 cases of invasive carcinoma NST, and 3 cases of solid papillary carcinoma). CONCLUSION: Numerous isolated cells are sometimes seen in both benign and malignant cytology.

Peach (Prunus persica) extract inhibits angiotensin II-induced signal transduction in vascular smooth muscle cells.

Angiotensin II (Ang II) is a vasoactive hormone that has been implicated in cardiovascular diseases. Here, the effect of peach, Prunus persica L. Batsch, pulp extract on Ang II-induced intracellular Ca(2+) mobilization, reactive oxygen species (ROS) production and signal transduction events in cultured vascular smooth muscle cells (VSMCs) was investigated. Pretreatment of peach ethyl acetate extract inhibited Ang II-induced intracellular Ca(2+) elevation in VSMCs. Furthermore, Ang II-induced ROS generation, essential for signal transduction events, was diminished by the peach ethyl acetate extract. The peach ethyl acetate extract also attenuated the Ang II-induced phosphorylation of epidermal growth factor receptor and myosin phosphatase target subunit 1, both of which are associated with atherosclerosis and hypertension. These results suggest that peach ethyl acetate extract may have clinical potential for preventing cardiovascular diseases by interfering with Ang II-induced intracellular Ca(2+) elevation, the generation of ROS, and then blocking signal transduction events.

Retinoid X receptor γ up-regulation is correlated with dedifferentiation of tumor cells and lymph node metastasis in papillary thyroid carcinoma.

The expression of retinoid X receptor γ (RXRγ) and the clinicopathological parameters of total 69 patients with papillary thyroid carcinoma (PTC) larger than 1 cm were examined. The PTCs were classified into two groups according to the presence of loss of cellular polarity/cohesiveness (LOP/C). The expression of RXRγ mRNA was examined by reverse transcriptase polymerase chain reaction and quantitative real-time PCR. The RXRγ mRNA up-regulation was found to be positively correlated with extrathyroid invasion (r = 0.293, P = 0.019), advanced tumor stage (r = 0.318, P = 0.016) and lymph node metastasis (LNM) (r = 0.338, P = 0.005), as well as LOP/C (r = 0.345, P = 0.004), which was proposed as a histological characteristic of poor cellular differentiation. The RXRγ mRNA expression, as well as extrathyroid invasion, LOP/C and advanced tumor stage, was further confirmed to be one of the independent predictive factors (Odds ratio: 6.545; 95% confidence interval: 1.575-27.208) of LNM using multivariate analysis. These results suggest that RXRγ may play a role in the dedifferentiation and metastasis of PTC.

Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called well-differentiated tumor of uncertain malignant potential: a morphological, immunohistochemical, and molecular appraisal.

There is a continuous debate regarding the classification of thyroid follicular lesions and the term "well-differentiated tumor of uncertain malignant potential (WDT-UMP)" was recently introduced to cover this problematic spectrum of tumors. The objective of this study was to reappraise WDT-UMP using morphological, immunochemical, and molecular analysis and to shed more light on encapsulated thyroid follicular-patterned tumors. A total of 30 cases of WDT-UMP with equivocal papillary thyroid carcinoma-type nuclear changes (PTC-N) or focal unequivocal PTC-N were examined. As a control, follicular adenoma (n = 29), follicular carcinoma (n = 8), hyalinizing trabecular adenoma (n = 5), and PTC (n = 48) were included. HBME-1, cytokeratin 19, and galectin-3 were positive in 12 (40.0%), 10 (33.3%) and 11 (36.7%) cases of WDT-UMP, respectively. According to the positivity of those markers, significant differences were obtained between WDT-UMP and PTC encapsulated common type (P = 0.028, 0.010, and 0.004, respectively), infiltrative follicular variant (P = 0.020, 0.026, and 0.008, respectively), and infiltrative common type (P = 0.004, 0.001, and 0.005, respectively), but not between WDT-UMP and follicular adenoma or follicular carcinoma. BRAF(V600E) mutation was absent but RET/PTC1 rearrangement was found in only two (6.7%) cases of WDT-UMP. None of the 20 patients with WDT-UMP developed recurrence, with an average follow-up of 80 months. These findings indicate that WDT-UMP has a favorable outcome and is distinct from PTC in morphological, immunohistochemical, and molecular characteristics. We propose that WDT-UMP should be classified as "well-differentiated tumor with uncertain behavior".

Novel isoforms of periostin expressed in the human thyroid.

Periostin is an extracellular matrix protein. Five isoforms of human periostin cDNA have been reported, but the expression of periostin isoforms in the human thyroid tissue is by far unknown. A group of primer sets were designed to amplify the full length of cDNA sequence of periostin. Using human thyroid carcinoma and their paired non-neoplastic tissues together with anaplastic thyroid carcinoma cell lines, we examined the presence of periostin cDNA isoforms by RT-PCR and direct DNA sequence analysis. We identified eight coexisting cDNA isoforms in all the tissue samples and cell lines. Three of them were unique to this study. Especially two of them haven't been previously reported in any species. The eight periostin isoforms differ in the C-terminus from exon XII to exon XXI where alternative splicing usually happens. This is the first report that demonstrates all the eight isoforms of periostin cDNA expressed in the human thyroid gland and identifies three novel isoforms.

Targeting of the BRAF gene in papillary thyroid carcinoma (review).

Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy and includes several histological variants. Patients suffering from PTC usually have a good outcome. However, a group of PTC patients still encounter high rates of recurrence and mortality. The BRAFV600E mutation is the most common genetic alteration identified in PTC, ranging from 29 to 83%, with the average rate about 40%. To date, a growing body of evidence has suggested that the BRAFV600E mutation plays an important role in the carcinogenesis of PTC, and it tends to be associated with special subtypes of PTC and predicts poor prognosis. Therefore, mutant BRAF has become an attractive cancer target for PTC. This article is focuses on reviewing the impact of the BRAFV600E mutation in the tumorigenesis of PTC, differences in the prevalence of the BRAFV600E mutation in variants of PTC, and its detection methods. The novel advantages of the BRAFV600E mutation-targeted therapies in studies of PTC are also discussed.

Effect of dehydroepiandrosterone on atherosclerosis in apolipoprotein E-deficient mice.

AIM: Several clinical trials have indicated that dehydroepiandrosterone (DHEA) reduces coronary events associated with atherosclerosis. The aim of this study was to examine the inhibitory effect of DHEA on atherosclerosis and the mechanisms involved. METHODS: Apolipoprotein E-knockout (apoE-KO) mice were fed an atherogenic high-cholesterol diet with or without 0.4% (w/w) DHEA for 12 weeks. RESULTS: Although the plasma cholesterol and triglyceride levels were not decreased by DHEA, atherosclerotic lesions in the aortic sinus showed a 45% reduction in area with DHEA treatment versus untreated mice (0.19 +/- 0.01 vs. 0.10 +/- 0.02 microm(2); p<0.05). Accumulation of macrophages in aortic lesions was also markedly reduced in the DHEA group, and the macrophage-positive area decreased to 0.33 +/- 0.06 microm(2) from 0.67 +/- 0.07 microm(2) (p<0.01). Furthermore, DHEA suppressed the expression of monocyte chemoattractant protein-1 in the vessel wall. Thus, inhibition of macrophage infiltration by DHEA reduced the formation of atherosclerotic lesions in apoE-KO mice. CONCLUSIONS: DHEA might be an effective agent for clinical management of atherosclerosis, but a larger controlled trial is necessary for confirmation.

Adrenomedullin, Bcl-2 and microvessel density in normal, hyperplastic and neoplastic endometrium.

Adrenomedullin (ADM) is a multifunctional 52-amino acid peptide involved in numerous physiological and pathological processes, including angiogenesis, growth regulation, differentiation, and vasodilation. ADM is thought to act through the G protein-coupled receptor calcitonin receptor-like receptor, with specificity being conferred by receptor-associated modifying protein 2. The aim of the present study was to clarify the roles of ADM status, and tumor vessels in endometrium. Specimens were examined for ADM, microvessel density (MVD), area of venules (AV) and Bcl-2 oncoprotein using an immunoperoxidase method. The difference of ADM between normal proliferative phase and hyperplasia without atypia was significant (P < 0.05). The level of Bcl-2 was significantly different between hyperplasia without atypia and hyperplasia with atypia (P < 0.05). ADM, MVD and AV in the endometrium increased in a stepwise manner from normal, simple or complex hyperplasia with or without atypia to grade 1 adenocarcinoma. In contrast, expression of Bcl-2 oncoprotein was decreased. These parameters identify the role of ADM expression and Bcl-2 protein in relation to cell growth and vasodilating in the neoplastic changes.

Survival impact of psammoma body, stromal calcification, and bone formation in papillary thyroid carcinoma.

The presence of calcification is the most significant ultrasonographic finding in evaluating thyroid nodules. Calcifications are more frequently detected in papillary thyroid carcinoma than in other thyroid lesions. However, the clinical significance of calcification, including clinical correlations and impact on survival, and the molecular mechanism responsible for calcification in papillary thyroid carcinoma remain uncertain. We performed a retrospective study of patients with primary common-type papillary thyroid carcinoma to determine the clinical correlations of calcification and its impact on survival. Histologically, calcification was classified as either psammoma bodies, stromal calcification, or bone formation. They were identified in 25, 47, and 13% of all 229 cases of papillary thyroid carcinoma, respectively. The presence of psammoma bodies was significantly correlated with gross lymph node metastasis and stage grouping. Both stromal calcification and bone formation were significantly correlated with patient age. In addition, stromal calcification was associated with pT classification and gross lymph node metastasis. Papillary thyroid carcinoma with, compared to that without, psammoma bodies was associated with poorer disease-free survival. We examined the quantitative expression of BMP-1, a metalloproteinase that is reported to be involved in bone and extracellular matrix formations, and found that its expression was significantly higher in tumors with psammoma bodies or with stromal calcification (P=0.0464 and 0.0272, respectively). These results suggest that the presence of psammoma bodies is a useful predictor of outcome for patients suffering from papillary thyroid carcinoma.

Loss of cellular polarity/cohesiveness in the invasive front of papillary thyroid carcinoma and periostin expression.

Loss of cellular polarity/cohesiveness and periostin expression are involved in the epithelial-mesenchymal transition in the epithelial malignancies. Their roles in papillary thyroid carcinoma were studied. There was a significant correlation between the loss of cellular polarity/cohesiveness in the invasive front and the up-regulation of periostin in tumors. Both of them were significantly correlated with extrathyroid invasion, pT and lymph node metastasis. Our results suggest that the loss of cellular polarity/cohesiveness is a useful parameter for predicting prognosis of patients with papillary thyroid carcinoma, and periostin could be a candidate gene for therapeutic targeting for the blockage of tumor invasion.