Differential Expression of Claudin 1 and 4 in Basal Cell Carcinoma of the Skin.

Basal cell carcinoma (BCC) is the most common human malignancy. The biological behavior of this entity is remarkably indolent. Claudin plays an important role in tight junctions, regulating paracellular passage of variable substance including growth factors and maintaining the polarity of epithelia. Up- or downregulated claudin expression has been reported in many cancers. Nevertheless, claudin expression in BCC of the skin remains unclear. We therefore examined the status of claudin 1 and 4 expressions in BCC and adjacent normal skin by immunohistochemistry (IHC). Our IHC results demonstrated high claudin 1 expression and low claudin 4 expression in 33 of 34 lower-grade BCCs. In lower-grade BCC, claudin 1 was increased and claudin 4 was decreased compared with the normal skin. Claudin 1 was inclined to be highly expressed in the membrane and cytoplasm of tumour cells in the periphery of tumour nest. Conversely, almost all lower-grade BCCs (33/34) and one of two higher-grade BCC lacked or showed focal positivity for claudin 4. These results imply that the expression pattern is characteristics of lower-risk BCC. Interestingly, one of the two higher-grade BCCs demonstrated the converse expression patterns of claudins, with decreased claudin 1 and increased claudin 4. The combination of immunohistochemical claudin 1 and 4 expression may offer a useful ancillary tool for the pathological diagnosis of BCC. Furthermore, membranous and intracellular claudins may present future therapeutic targets for uncontrollable BCC.

High levels of DNA polymerase ß mRNA corresponding with the high activity in Graves' thyroid tissue.

INTRODUCTION: High DNA polymerase ß activity has been observed in the thyroid tissue of patients with Graves' disease (Nagasaka et al. in Metabolism 37:1051-1054, 1988). This fact aroused our interest in whether the alteration of DNA polymerase ß activity depends on DNA polymerase ß (DNA poly ß) mRNA levels, which may be modulated by thyroid-stimulating hormone (TSH) or thyroid-stimulating substances, i.e. TSH receptor antibody (TRAb). RESULT: Addition of TSH or TRAb to primary cultures of Graves' disease thyroid cells for 4 h led to no increase in DNA poly ß mRNA levels. In contrast, thyroid hormone synthesizing enzyme, peroxidase, mRNA levels increased fivefold after coculture with TSH and TRAb, even though DNA poly ß activity and mRNA levels are already significantly higher in Graves' disease thyroid tissues, compared with normal thyroid tissue. DISCUSSION: These results indicate that DNA poly ß expression in Graves' disease thyroid cells may be maximally activated or plateau in response to thyroid-stimulating immunoglobulins, or that the activation of to poly ß expression may occur via pathways other than the G protein and cyclic AMP system.

Prognostic value of histological type in stage IV ovarian carcinoma: a retrospective analysis of 223 patients.

BACKGROUND: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). METHODS: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. RESULTS: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P<0.001). Six patients (2.7%), all with non-S/E tumours, died within 6 weeks after the initial surgery. Multivariate OS analysis revealed that performance status, residual tumor, metastatic sites, no debulking surgery, and non-S/E tumours were independent poor prognostic factors. For patients with non-S/E tumours, prognosis was more favourable for single-organ metastasis, except for liver or distant lymph nodes, no residual tumor, and resection of metastasis (median OS: 4.1, 4.6, and 2.6 years, respectively). CONCLUSIONS: In stage IV ovarian carcinoma, non-S/E tumours are associated with a significantly poorer prognosis and higher rates of early mortality compared to S/E tumours. Therefore, careful management and development of new strategies are required.

Five-year clinical results for treatment of intrabony defects with EMD, guided tissue regeneration and open-flap debridement: a case series.

BACKGROUND AND OBJECTIVE: Although regenerative periodontal surgery with EMD or guided tissue regeneration (GTR) has been shown to enhance periodontal regeneration, there are limited data on the long-term results following these treatment modalities. The purpose of the present study was to investigate the long-term clinical outcomes in intrabony defects following regenerative periodontal surgery with EMD or GTR compared with open-flap debridement (OFD). MATERIAL AND METHODS: Data from 40 subjects (44 teeth), with no history of smoking or systemic diseases that could interfere with periodontal disease and who received one of three surgical procedures (EMD, GTR or OFD) for two- or three-wall intrabony defects, were analyzed. Postoperative reduction in probing pocket depth, gain in clinical attachment level, gingival recession and percentage bone fill were compared at 1, 3 and 5 years. RESULTS: Reduction in probing pocket depth after GTR was significantly higher than after OFD at 1 and 3 years postoperatively, but there was no difference between the groups at 5 years. The gains in clinical attachment level for EMD (at 3 and 5 years) and for GTR (at 1, 3 and 5 years) were significantly greater than for OFD. Gingival recession after treatment with EMD and GTR showed a tendency toward positive results, whereas no such tendency was observed for OFD. Postoperative percentage bone fill for EMD and GTR was significantly greater than for OFD at 3 and 5 years. CONCLUSIONS: This is a retrospective study and an exploratory report with a high risk of bias. Within the limits of the current study, it may be concluded that superior gains in clinical attachment level and improved percentage bone fill can be obtained with EMD and GTR when compared with OFD, and these can be maintained over a period of 5 years.

Ion-induced gamma-ray detection of fast ions escaping from fusion plasmas.

A 12 × 12 pixel detector has been developed and used in a laboratory experiment for lost fast-ion diagnostics. With gamma rays in the MeV range originating from nuclear reactions (9)Be(α, nγ)(12)C, (9)Be(d, nγ)(12)C, and (12)C(d, pγ)(13)C, a high purity germanium (HPGe) detector measured a fine-energy-resolved spectrum of gamma rays. The HPGe detector enables the survey of background-gamma rays and Doppler-shifted photo peak shapes. In the experiments, the pixel detector produces a gamma-ray image reconstructed from the energy spectrum obtained from total photon counts of irradiation passing through the detector's lead collimator. From gamma-ray image, diagnostics are able to produce an analysis of the fast ion loss onto the first wall in principle.

Minimally invasive approach with tissue engineering for severe alveolar bone atrophy case.

The gold standard of bone augmentation for dental implants in severe alveolar bone atrophy is autogenous bone graft, but it has disadvantages such as limited amounts of grafted bone, poor morphological and aesthetic outcomes, and donor-site morbidity and invasiveness, especially in cases with diseases. In this reported case, the authors applied a novel tissue engineering method as minimally invasive surgery for a 58-year-old patient who had severe bone atrophy. The method, tissue-engineered bone (TEB), composed of mesenchymal stem cells as stem cells, platelet-rich plasma as growth factor and guided bone regeneration membrane. After bone regeneration by TEB, three 13 mm long dental implants were inserted. Adequate bone regeneration was shown by radiological analysis and histological observation. The augmented bone height was 4.2mm after the operation and the radiopaque areas were increased. The clinical progress over 2 years showed a good course without bone resorption. These results indicated that TEB, as bone regeneration treatment with minimal invasiveness, could be useful as one of the novel options in dental implant treatment with severe bone atrophy.

A case report of placental mesenchymal dysplasia with an increased VEGF-D expression.

The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This report presents a case of PMD with a female fetus complicated with intrauterine growth restriction (IUGR). The ultrasound findings were similar to molar pregnancies, but PMD was suspected based on the presence of low ß-hCG levels and a normal karyotype. After delivery, pathological examination of the placenta showed dilated villi and thick-walled vessels lacking trophoblast proliferation, which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was found to have increased in the abnormal villi. Whether this is an incidental or X-linked gene specific event in, IUGR complicated, PMD pathogenesis warrants further investigation of VEGF-D expression in PMD.

Thermodynamic estimation of minor element distribution between immiscible liquids in Fe-Cu-based metal phase generated in melting treatment of municipal solid wastes.

Waste electrical and electronic equipment (WEEE) has become an important target in managing material cycles from the viewpoint of not only waste management and control of environmental pollution but also resource conservation. This study investigated the distribution tendency of trace elements in municipal solid waste (MSW) or incinerator ash, including valuable non-ferrous metals (Ni, Co, Cr, Mn, Mo, Ti, V, W, Zr), precious group metals (PGMs) originated from WEEE (Ag, Au, Pd, Pt), and others (Al, B, Pb, Si), between Fe-rich and Cu-rich metal phases by means of simple thermodynamic calculations. Most of the typical alloying elements for steel (Co, Cr, Mo, Nb, Ni, Si, Ti, V, and W) and Rh were preferentially distributed into the Fe-rich phase. PGMs, such as Au, Ag, and Pd, were enriched in the Cu-rich phase, whereas Pt was almost equally distributed into both phases. Since the primary metallurgical processing of Cu is followed by an electrolysis for refining, and since PGMs in crude copper have been industrially recovered from the resulting anode slime, our results indicated that Ag, Au, and Pd could be effectively recovered from MSW if the Cu-rich phase could be selectively collected.

CT findings of intraductal papillary neoplasm of the bile duct: assessment with multiphase contrast-enhanced examination using multi-detector CT.

AIM: To evaluate multi-detector computed tomography (MDCT) findings of intraductal papillary neoplasm of the bile duct (IPNB), a neoplasm that is considered to be the biliary counterpart of pancreatic intraductal papillary mucinous neoplasm. MATERIALS AND METHODS: Two radiologists retrospectively evaluated multiphase contrast-enhanced CT images with 0.5 or 1mm collimation in 37 consecutive patients with resected IPNB diagnosed by a single pathologist. The CT findings were correlated with the pathological findings concerning invasion of the surrounding organs and vessels. RESULTS: All patients showed bile duct dilatation. An intraductal mass was detected in 36 patients and the following findings were observed: extensive infiltration along the bile duct more than 20mm (n=32), compared with normal hepatic parenchyma, isodense or hyperdense during the late arterial phase (n=31), not hyperdense during the portal-venous and delayed phases (n=36), and intense enhancement rim at the base of the mass during the portal-venous or delayed phase (n=27). Parenchymal invasion of the surrounding organs was seen in eight of 16 tumours showing irregular or bulging margins. Vascular invasion was false positive in four of eight tumours. CONCLUSIONS: IPNB exhibits relatively characteristic findings with multiphase contrast-enhanced examination using MDCT. A tendency to overestimate invasion of the surrounding organs and vessels was seen.

Long-term survival of young women receiving fertility-sparing surgery for ovarian cancer in comparison with those undergoing radical surgery.

OBJECTIVES: To compare the clinical outcome of patients with stage I epithelial ovarian cancer (EOC) who received with fertility-sparing surgery (FSS) with those who underwent radical surgery (RS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 572 patients were retrospectively evaluated. All patients were divided into three groups: group A {FSS (n=74); age, ≤ 40}; groups B and C [RS; age, 40 ≥{(B), n=52}; 40<{(C), n=446}]. RESULTS: Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 90.8% (OS)/87.9% (DFS); group B, 88.3% (OS)/84.4% (DFS); group C, 90.6% (OS)/85.3% (DFS), respectively (OS, P=0.802; DFS, P=0.765). Additionally, there was no significant difference in OS and DFS among the three groups stratified to stage IA or IC (OS (IA), P=0.387; DFS (IA), P=0.314; OS (IC), P=0.993; DFS (IC), P=0.990, respectively). Furthermore, patients with a grade 1-2 or 3 tumours in the FSS group did not have a poorer prognosis than those in the RS group. CONCLUSIONS: Stage I EOC patients treated with FSS showed an acceptable prognosis compared with those who underwent RS.

Development and irradiation test of lost alpha detection system for ITER.

We developed a lost alpha detection system to use in burning plasma experiments. The scintillators of Ag:ZnS and polycrystalline Ce:YAG were designed for a high-temperature environment, and the optical transmission line was designed to transmit from the scintillator to the port plug. The required optical components of lenses and mirrors were irradiated using the fission reactor with the initial result that there was no clear change after the irradiation with a neutron flux of 9.6×10(17) nm(-2) s(-1) for 48 h. We propose a diagnostic of alpha particle loss, so-called alpha particle induced gamma ray spectroscopy. The initial laboratory test has been carried out by the use of the Ce doped Lu(2)SiO(5) scintillator detector and an Am-Be source to detect the 4.44 MeV high energy gamma ray due to the (9)Be(α,nγ)(12)C reaction.

CT findings in autoimmune pancreatitis: assessment using multiphase contrast-enhanced multisection CT.

AIM: To assess the spectrum of findings using multiphase contrast-enhanced computed tomography (CT) in patients with autoimmune pancreatitis (AIP). MATERIALS AND METHODS: Fifty patients (four female and 46 male, mean age 65 years) were retrospectively identified from consecutive patients with abnormal CT findings of the pancreas and negative work-up for known causes. These patients had at least one finding supporting the diagnosis of AIP: serological abnormality, histopathological abnormality, or response to steroid. Two radiologists evaluated multiphase contrast-enhanced CT images in consensus. RESULTS: The pancreas showed diffuse enlargement (n=16; 32%), focal enlargement (n=18; 36%), or no enlargement (n=16; 32%). Forty-nine (98%) patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the pancreatic phase (n=45; 90%) and hyperattenuation during the delayed phase (n=39; 87%). The following findings were also seen in the pancreas: a capsule-like rim (n=24; 48%); no visualization of the main pancreatic duct lumen (n=48; 96%); ductal enhancement (n=26; 52%); upstream dilatation of the main pancreatic duct (n=27; 54%); upstream atrophy of the pancreatic parenchyma (n=27; 54%); calcification (n=7; 14%); and cysts (n=5; 10%). Forty-two (84%) patients showed one or more of the following extrapancreatic findings: biliary duct or gallbladder abnormality (n=40; 80%); peripancreatic (n=8; 16%) or para-aortic (n=10; 20%) soft-tissue proliferation; and renal involvement (n=15; 30%). CONCLUSION: Patients with AIP presented with a variety of CT findings in the pancreas and the extrapancreatic organs. The present study highlights pancreatic ductal enhancement in a subset of patients with AIP.

Fertility-sparing surgery in young women with invasive epithelial ovarian cancer.

OBJECTIVES: The purpose of this study was to clarify the clinical outcome of patients with stage IA or more advanced epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 60 stage I EOC patients treated with FSS were retrospectively evaluated in the current study. RESULTS: The median age was 30 years (range: 12-40 years). The median follow-up time was 54.7 months (range: 4.8-243.8 months). The stage was IA in 30, IB in one, and IC in 29 patients. Fifty-two patients were alive without relapse and 8 patient experienced recurrences {IA, 2; IB, 1; IC(surface involvement), 1; and IC(positive cytology), 4}. However, all patients with stage IC(capsule rupture) (n=17) were alive without recurrence. Collectively, there was no significant difference in the overall survival between the stage IA and IC groups (P=0.256). Moreover, there was no significant difference in DFS and OS between patients with stage IC(capsule rupture) and those with stage IA. In contrast, DFS and OS of the patients with stage IC(surface involvement/positive cytology) were poorer than those of patients with stage IA {OS; P=0.030, and DFS; P=0.005, respectively}. Thirteen pregnancies were observed in 9 patients. CONCLUSIONS: FSS may be considered a treatment option in women with stage I EOC, even in those with stage IC(capsule rupture) or more wishing to bear children.

Lymphoplasmacytic sclerosing cholangitis: assessment of clinical, CT, and pathological findings.

AIM: To assess the clinical, computed tomography (CT), and pathological findings in patients with lymphoplasmacytic sclerosing cholangitis. MATERIALS AND METHODS: Fifteen consecutive patients (four women and 11 men, mean age 71 years) with lymphoplasmacytic sclerosing cholangitis and without the characteristic features of underlying disorders causing benign biliary strictures were retrospectively recruited. Two radiologists evaluated multiphase contrast-enhanced CT images acquired with 0.5 or 1-mm collimation. One pathologist performed all histological examinations, including IgG4 immunostaining. RESULTS: The intrahepatic biliary ducts showed dilatation in all 15 patients, but only seven presented with jaundice. Although laboratory data were not available in all patients, serum gammaglobulin and IgG levels were elevated in five of six patients and six of eight patients, respectively. Anti-nuclear antibody was detected in three of six patients. The involved biliary ducts showed the following CT findings: involvement of the hilar biliary duct (14/15), a mean wall thickness of 4.9 mm, a smooth margin (10/15), a narrow but visible lumen (6/15), hyper-attenuation during the late arterial phase (9/15), homogeneous hyper-attenuation during the delayed phase (11/11), and no vascular invasion (14/15). Abnormal findings in the pancreas and urinary tract were detected in eight of 15 patients. In 13 patients with adequate specimens, moderate to severe lymphoplasmacytic infiltration associated with dense fibrosis was observed. Infiltration of IgG4-positive plasma cells was moderate or severe in nine patients and minimal or absent in four patients. CONCLUSION: Lymphoplasmacytic sclerosing cholangitis exhibits relatively characteristic clinical and CT findings, although they are not sufficiently specific for differentiation from other biliary diseases.

Methylation in p14(ARF) is frequently observed in colorectal cancer with low-level microsatellite instability.

Colorectal cancer (CRC) can be classified as high-level microsatellite instability (MSI-H), low-level MSI (MSI-L) and microsatellite stable (MSS) depending on levels of MSI. MSI-H CRC relies on a distinct molecular pathway due to the mismatch repair (MMR) deficiency and shows methylation in multiple gene promoters. The genetic pathway leading to MSI-L is unknown, although higher levels of promoter methylation are observed in this group compared with MSS CRCs. This study explored how promoter methylation affects MSI phenotype, by analysing the methylation status of eight CRC-related promoters, MSI phenotype and KRAS/BRAF mutations in a series of 234 CRCs. Promoter methylation of p14(ARF) was significantly related to MSI-L CRC with KRAS mutation. The MSI-H phenotype was related to methylation of MLH1 as expected, while the MSS phenotype was related to methylation of p16(INK4a) and O(6)-methylguanine-DNA methyltransferase, although this was not statistically significant. Thus, promoter methylation of p14(ARF) could be a significant alteration leading to CRC with MSI-L.

The concept of perihilar cholangiocarcinoma is valid.

BACKGROUND: The term perihilar cholangiocarcinoma has been used for all tumours involving or requiring resection of the hepatic confluence. However, it does not distinguish between intrahepatic and extrahepatic hilar tumours, and has no clinicopathological basis. This retrospective study examined whether the concept of perihilar cholangiocarcinoma is valid clinically. METHODS: Some 250 patients with perihilar cholangiocarcinoma were divided into extrahepatic (EHC, 167 patients) and intrahepatic (IHC, 83) groups based on tumour location. Clinicopathological data were compared between these groups. RESULTS: Liver, portal vein, venous and lymphatic invasion, and nodal metastasis were more common in IHCs than EHCs, whereas histological grade and incidence of perineural invasion were similar. IHCs were more advanced at the time of surgery; stage III or IV disease was found in 37.7 per cent of EHCs and 59 per cent of IHCs. Survival was marginally better for patients with EHCs than for those with IHCs (29.3 versus 20 per cent at 5 years; P = 0.057), but survival rates were similar for each tumour stage in the American Joint Committee on Cancer classification. CONCLUSION: Combining EHC and IHC under the term perihilar cholangiocarcinoma is valid, as these tumours have comparable biological behaviour, with similar clinical management depending on stage and invasion.

Persistent lymphoedema in Morbihan disease: formation of perilymphatic epithelioid cell granulomas as a possible pathogenesis.

Morbihan disease is a rare complication of rosacea, characterized by persistent lymphoedema on the upper half of the face, occurring during the chronic clinical course of rosacea. This refractory condition has been also designated as 'rosacea lymphoedema' and 'solid persistent facial oedema of rosacea'. We report a patient with Morbihan disease showing persistent lymphoedema on the upper half of the face accompanied by unique histological findings of striking dermal dilated lymphatics and damage of the lymphatics at the site of the adjacent epithelioid cell granulomas, with histiocytes bulging into the lymphatic lumen. The marked epithelioid cell granulomas forming around dermal lymphatic vessels with subsequent lymphatic damage and luminal obstruction by histiocytic infiltration may account for the development of lymphoedema in this patient.

Inflation-deflation method for endoscopic evacuation of intracerebral haematoma.

BACKGROUND: Endoscopic evacuation of intracerebral haematoma (ICH) has the advantage of being less invasive than craniotomy, but limited visualisation and difficulties in haemostasis are still a concern. The collapse of the haematoma cavity limits the visualisation of the surgical field. Inflation of the haematoma cavity with saline irrigation improves visualisation and facilitates accurate intra-operative orientation. METHOD: A unique technique, the cavity inflation-deflation method can help in exploring the residual haematoma and accessing the bleeding points. We also developed a combined irrigation-coagulation suction tube that concentrates the capabilities of suction, irrigation and monopolar coagulation. FINDINGS: The use of this multifunctional dedicated instrument and its application in the cavity inflation-deflation method allows for easy identification of residual haematoma and bleeding vessels. Secure haemostasis can also be accomplished under clear visualisation. No surgical complications and rebleeding occurred in any patient following the procedure. Our results show that the median haematoma evacuation rate was 99% and the surgical outcome was satisfactory. CONCLUSIONS: The inflation-deflation method using a combined irrigation-coagulation suction tube can facilitate optimal evacuation of ICH with secure haemostasis. Although further accumulation of patients and careful analyses are needed to be known whether this procedure improves the clinical outcomes in the patients, the preliminary results of its application have been promising.

Is there any association between retroperitoneal lymphadenectomy and survival benefit in ovarian clear cell carcinoma patients?

BACKGROUND: To estimate the survival impact of systemic retroperitoneal lymphadenectomy in patients diagnosed with International Federation of Gynecology and Obstetrics pTI-IIb clear cell carcinoma of the ovary (CCC). PATIENTS AND METHODS: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2006. Survival curves were calculated using the Kaplan-Meier method. Differences in survival rates were analyzed using the log-rank test. RESULTS: A total of 205 patients had clinical pTI-IIb CCC (median age: 52 years, range: 30-75). One hundred and four (50.7%) patients underwent systemic retroperitoneal lymphadenectomy. Lymphadenectomy was not associated with improved disease-free and overall survival in all patients (P = 0.353 and P = 0.645, respectively). Moreover, lymphadenectomy did not improve the overall survival in those with pTIc CCC (P = 0.433). Similarly, on univariate analysis, age, volume of ascites, preoperative CA 125 values, and regimen of chemotherapy were not significant factors. In addition, there was no significant difference in the ratio of positive lymph node metastases regardless of the completion of lymphadenectomy (P = 0.955). CONCLUSION: Our data suggest that patients with pTI-IIb CCC who underwent lymphadenectomy did not show a significant improvement in survival. There was no significant difference in the overall and disease-free survival rates in pTI-IIb CCC patients regardless of the completion of surgical staging lymphadenectomy.