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Early cholecystectomy is currently the gold standard treatment for acute cholecystitis (AC). However, the acceptability and safety of this strategy remain in dispute. The aim of this study was to clarify the role of percutaneous transhepatic gallbladder aspiration (PTGBA) in the early management of AC in a single center.A total of 147 consecutive patients who were treated with PTGBA for AC from 2008 to 2012 were included in the study. The therapeutic outcomes and adverse events were evaluated.A single PTGBA was adequate for 96 (65.3%) patients with AC. Of the remaining 51 patients, 43 (29.3%) showed an improvement after repeated PTGBA and/or percutaneous transhepatic gallbladder drainage (PTGBD), while semi-emergency cholecystectomy was needed in eight patients. Although five patients experienced adverse events (intra-abdominal hemorrhage in two, bile leakage in two and gallbladder hemorrhage in one), no patient died of treatment-related complications. Subsequently, 87 (59.2%) patients underwent cholecystectomy after PTGBA (a single PTGBA in 48 and repeated PTGBA and/or PTGBD in 39 patients). No significant differences were observed in the conversion rate from laparoscopic surgery to open cholecystectomy, operative time or intraoperative hemorrhage volume between the two groups.The present study demonstrated the safety and acceptability of treatment with PTGBA for AC at our center. This elective treatment strategy may be a useful alternative option in the treatment of AC.

Esophagojejunostomy in laparoscopic total gastrectomy (LTG) is a technically demanding procedure. Although several methods have been reported to date, none is considered consistently reliable. We developed a simple method for intracorporeal circular-stapled esophagojejunostomy using a modified over-and-over suture technique. The surgical outcomes of our technique were evaluated in comparison with those of open total gastrectomy (OTG).From April 2012 to August 2014, reconstruction using this method in LTG was performed for 21 consecutive patients with gastric cancer (LTG group). Their surgical outcomes were compared with those of 27 patients with gastric cancer who underwent OTG without splenectomy (OTG group) between January 2011 and April 2014.Estimated blood loss was significantly lower, and the postoperative hospital stay was significantly shorter in the LTG group than in the OTG group. The operating time and the number of harvested lymph nodes were similar between the two groups. The incidence of overall complications did not differ significantly between the two groups. Anastomotic leakage developed in one of the 21 patients in the LTG group and in two of the 27 patients in the OTG group. Anastomotic stenosis was observed in one patient in the LTG group.We consider this method as simple and feasible for most laparoscopic surgeons with basic laparoscopic suturing skills. This method might help LTG to become an accepted standard surgical option for treatment of patients with gastric cancer.

Laparoscopic lymph node (LN) dissection around the middle colic vessels is technically demanding, thus raising controversy regarding the role of laparoscopic surgery for transverse colon cancer. We herein describe a cranial approach method to perform radical LN dissection around the middle colic vessels. The key characteristic of this approach is early division of middle colic vessels prior to mobilization of the colon. From April 2010 to September 2013, 27 patients with colon cancer received laparoscopic LN dissection around the middle colic vessels using this cranial approach. Their surgical and short-term outcomes were reviewed. The mean number of harvested LNs was 29 (range, 6–50). The mean operative time and intraoperative blood loss were 274 min (range, 160–362 min) and 42 mL (range, 3–247 mL), respectively. There were no serious intraoperative complications or conversions to open surgery. There were two patients with stage 0, 7 with stage I, 12 with stage II, and 6 with stage III. No recurrent case was observed with a median follow-up period of 30 months (range, 9–48 months). We consider this approach feasible and useful for radical LN dissection around the middle colic vessels during laparoscopic colon cancer surgery.

Background: Complete hepatic venous isolation and extracorporeal charcoal hemoperfusion (HVI·CHP) can limit systemic exposure to high-dose chemotherapeutic agents when given by hepatic arterial infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (STS) could further expand the advantages of pharmacologic delivery of HVI·CHP for cisplatin (CDDP) during HAI chemotherapy. Methods: CDDP (4mg/kg) was administered over 20 minutes via HAI under conditions of HVI·CHP in 14 mongrel dogs. HVI·CHP was performed for 30 minutes after initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/kg STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (STS group) circuit line, while the remaining 7 dogs (controls) received no STS. Blood samples were taken serially from the prefilter circuit line (hepatic venous blood), postfilter line, and the left carotid artery (systemic blood). The free and total CDDP concentrations in these samples were determined by flameless atomic absorption spectrophotometry. Results:During 20 minutes HAI of CDDP, the mean CDDP extraction ratios (ER) by CHP filter were always higher in the STS group than in the control group, regardless of the form (free or total) of CDDP. The differences between the STS and control groups in the extraction ratios of free and total CDDP were significant at all time points measured (P < .05). Consequently, systemic exposure to CDDP, as assessed by area under the time-concentration curve of total CDDP, was significantly lower in the STS group than in the control group (P < .05). Conclusions: These results indicated that concomitant STS infusion could further increase the effect of HVI·CHP on CDDP removal after HAI.

Hypothermia causes vascular endothelial damage that leads to graft microcirculation disorder and eventually thrombosis after reperfusion. The two-layer cold storage method (TL) was previously demonstrated to supply oxygen to the pancreas graft and maintain high adenosine triphosphate tissue concentration. In this study, we evaluated whether mild hypothermic (20 degrees C) preservation using the TL method could reduce endothelial damage while maintaining parenchymal viability. Graft survival by 20 degrees C preservation was investigated using a dog segmental pancreas autotransplantation model (simple storage in University of Wisconsin solution (UW) for 5 and 8 hours or TL for 5, 8, 12, and 24 hrs. respectively). Subsequently, the grafts were preserved in four different conditions (4 and 20 degrees C UW. 4 and 20 degrees C TL) for 8 hours to evaluate microvascular endothelial damage. Trypan blue uptake of vascular endothelium and pancreatic tissue perfusion were evaluated. No graft preserved by 20 degrees C UW for 5 and 8 hours survived (0/7 and 0/4). In contrast, the graft survival rates by 20 degrees C TL for 5, 8, 12, and 24 hours were 100% (5/5), 80% (4/5), 20% (1/5), and 0% (0/4), respectively. In trypan blue uptake analysis, there were significant differences between 4 and 20 degrees C in both UW and TL (4 degrees C UW, 37% [n = 5) vs. 20 degrees C UW, 13% [n = 4] [p < 0.01]; 4 degrees C TL, 29% [n = 5] vs. 20 degrees C TL, 10% [n = 5] [p < 0.011). The perfusion values in 20 degrees C TL were significantly higher than those in other groups at least for up to 120 minutes after reperfusion (p < 0.01 ). In short-term pancreas preservation, mild hypothermic TL reduced vascular endothelial cell damage and ameliorated graft microcirculation while maintaining parenchymal viability. Mild hypothermic TL may lessen vascular complications in clinical pancreas transplantation when used for several-hour preservation.

Various oxiranes reacted with carbon dioxide at 100 °C using lithium bromide as a catalyst under atmospheric pressure to afford the corresponding five-membered cyclic carbonates quantitatively. The rate of the reaction increased as the bulkiness of substituents on the oxirane ring was reduced or an electron-withdrawing group was introduced on the oxirane ring. The stereochemistry of the reaction of oxirane and carbon dioxide was retention without loss of optical purity. When substituted phenylethylene carbonates were reacted with benzylamine, the selectivity to afford secondary alcohol increased as the electron-withdrawing ability of the para-substituent increased.

An inhalation exposure system, consisting of an inhalation chamber and an generating and feeding device for welding fumes and gases with a welding robot, was constructed and examined for its application to experimental toxicology for ventilatory responses of conscious rats to welding fumes and gases. The exposure system allowed an inhalation of fresh welding fumes and gases, and could supply airflow containing stable concentrations of fumes and ozone even the levels exceeding those corresponding occupational exposure limit values were supplied into the exposure chamber. The air temperature in the chamber was kept constant under rat's physiological conditions. Rats were exposed to fresh welding fumes and gases and examined for their ventilatory responses with a body plethysmograph in the chamber. A transient increase in breathing frequency with a concomitant decrease in the tidal volume was observed within several minutes immediately after the start of welding operation. The rapid, shallow breathing response disappears after repeated exposures, indicating rapid adaptation of this ventilatory response to inhalation of welding fumes and gases.

An ent-Kaurane-type diterpenoid, ent-kaurane-3,15-dione has been isolated from cell cultures of the liverwort Jungermannia subulata. Its structure was established by spectroscopic methods.

Comment on ‘Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus’

Practical cationic polymerization and block-copolymerization of vinyl ethers have been achieved at -25 degrees C by using CF(3)SO(3)H initiator in microsystems with high level of molecular weight distribution control.

The adaptation of cardiovascular and thermoregulatory responses to ozone (O3) was examined by repeated exposure of electrocardiographic (ECG) electrode- and thermistor sensor-implanted rats to O3 for 4 consecutive days (8 hrs/day). Circadian rhythms of heart rate (HR) and abdominal core temperature (Tco) were disrupted on the first and second O3 exposure days in a concentration dependent manner. The 8-hr and 12-hr averaged values of HR and Tco during the exposure period and the dark post-exposure period, respectively, decreased significantly on the first and second exposure days. The decreased HR and Tco recovered to respective control values after small but significant rebound increases on the third and fourth days of O3 exposure. The adaptation of the extrapulmonary responses to O3 exposure was discussed in light of the previously reported time periods required to abolish the spontaneous breathing, biochemical, cellular, and morphological responses to O3.

Background Approximately 80% of Merkel cell carcinomas (MCCs) harbor Merkel cell polyomavirus (MCPyV) which monoclonally integrates into the genome and has prognostic significance. The presence or absence of MCPyV is usually diagnosed using CM2B4 immunohistochemistry (IHC) for MCPyV-large T antigen (LT) protein. However, this method poses a risk of misdiagnosis. Methods In this study, we determined MCPyV infection in MCCs using real-time PCR for MCPyV-LT DNA and prepared 16 cases of MCPyV-DNA-positive and -negative groups. Diagnostic sensitivity and specificity of conventional PCR for MCPyV-small T antigen (MCPyV-ST), IHC using a newly developed polyclonal antibody (ST-1) for MCPyV-ST protein (MCPyV-ST) (aa: 164–177), and in situ hybridization (ISH) as well as real-time PCR for MCPyV-ST mRNA were compared against CM2B4-IHC for sensitivity (0.94, 15/16) and specificity (0.94, 15/16). Results The followings are the respective sensitivity and specificity results from examinations for MCPyV-ST gene: conventional PCR for the MCPyV-ST (0.94, 1.0), ST-1-IHC (0.69, 1.0), real-time PCR for ST mRNA (1.0, no data), ST mRNA ISH (0.94, 1.0). Each of the MCPyV-pseudonegative (1/16) and -pseudopositive (1/16) diagnoses evaluated using CM2B4-IHC were accurately corrected by examinations for MCPyV-ST or its expression as well as real-time PCR for MCPyV-LT. Sensitivity of CM2B4-IHC (0.94) was superior to that of ST-1-IHC (0.69) but equal to that of ST mRNA-ISH (0.94). Specificities of ST-1-IHC (1.0) and ST mRNA-ISH (1.0) were superior to that of CM2B4-IHC (0.94). Conclusions Therefore, combined application of ST mRNA-ISH and ST-IHC as well as CM2B4-IHC is recommended and will contribute to the diagnostic accuracy for MCPyV infection in MCCs. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9966295741144834

Graves’ disease is an autoimmune hyperthyroidism caused by thyrotropin receptor antibodies (TRAbs). Because Epstein–Barr virus (EBV) persists in B cells and is occasionally reactivated, we hypothesized that EBV contributes to TRAbs production in Graves’ disease patients by stimulating the TRAbs-producing B cells. In order for EBV to stimulate antibody-producing cells, EBV must be present in those cells but that have not yet been observed. We examined whether EBV-infected (EBV(+)) B cells with TRAbs on their surface (TRAbs(+)) as membrane immunoglobulin were present in peripheral blood of Graves’ disease patients. We analyzed cultured or non-cultured peripheral blood mononuclear cells (PBMCs) from 13 patients and 11 healthy controls by flow-cytometry and confocal laser microscopy, and confirmed all cultured PBMCs from 8 patients really had TRAbs(+) EBV(+) double positive cells. We unexpectedly detected TRAbs(+) cells in all healthy controls, and TRAbs(+) EBV(+) double positive cells in all cultured PBMC from eight healthy controls. The frequency of TRAbs(+) cells in cultured PBMCs was significantly higher in patients than in controls (p = 0.021). In this study, we indicated the presence of EBV-infected B lymphocytes with TRAbs on their surface, a possible player of the production of excessive TRAbs, the causative autoantibody for Graves’ disease. This is a basic evidence for our hypothesis that EBV contributes to TRAbs production in Graves’ disease patients. Our results further suggest that healthy controls have the potential for TRAbs production. This gives us an important insight into the pathogenesis of Graves’ disease.

International audience; BACKGROUND: Langerhans cell (LC) sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytologic features and an LC phenotype. We very recently suggested that LC behaves as a reservoir for common dermotropic Merkel cell polyomavirus (MCPyV) and determined the relationship between LC histiocytosis (LCH), which has an underlining oncogenic capacity, and MCPyV as a trigger for a reactive process rather than a neoplastic process. We propose LC to be a reservoir for MCPyV and hypothesize that some LCS subtypes may be related to the MCPyV agent. FINDINGS: We examined seven LCS tissues using multiplex quantitative PCR (Q-PCR) and immunohistochemistry with anti MCPyV large-T (LT) antigen antibody. High viral loads of MCPyV DNA sequences (viral load = relative levels of MCPyV) were detected (0.328-0.772 copies/cell (Merkel cell carcinoma (MCC) = 1.0)) using Q-PCR in 43% (3/7) tissues, but LT antigen expression was not observed (0/7). CONCLUSIONS: Frequent MCPyV-DNA amplification suggests that LCS in some patients may be related to MCPyV infection. Moreover, the higher viral load of LCS (median, 0.453 copies/cell) than low load of LCH (0.003, median of 12 cases) (P

Six l,3,4-oxadiazole-containing polyethers with reduced viscosities of 0,65-1,17 dL . g -1 were synthesized by high-temperature solution polycondensation of an activated difluoride, 2,5-bis(4-fiuorophenyl)-1,3,4-oxadiazole, with aromatic diols possessing a variety of ring structures. The expected chemical structures were confirmed by IR and l H NMR spectroscopy and elemental analysis. Of all the polymers, two polyethers were highly crystalline and soluble only in limited solvents such as o-chlorophenol and conc. sulfuric acid. The other polyethers were amorphous and dissolved readily in a variety of organic media including polar aprotic solvents, phenols and chlorinated hydrocarbons. Colorless to slightly yellow-colored, transparent and tough films could be cast from the N-methyl-2-pyrrolidone or o-chlorophenol solutions. The mechanical properties were excellent and their tensile strength, elongation at break and tensile moduli were in the ranges of 53-80 MPa, 4-12% and 1,3-2,0 GPa, respectively. The amorphous polyethers had high glass transition temperatures of 195-259°C. All the polyethers were highly thermally and thermooxidatively stable and exhibited no weight loss up to 400°C, with 10% weight loss being recorded at 464-514 °C in air.

A single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique.Sixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter.All patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P0.01).The single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm characterized by clonal proliferation of Langerhans cells in multi-organ systems including skin, bone, pituitary gland, liver and spleen. Skin-limited involvement of LCH usually indicates an indolent clinical course; however, in rare cases, LCH is accompanied by other myeloproliferative disorders, which may determine the prognosis. An 82-year old Japanese man presented with numerous asymptomatic facial papules clinically simulating rhinophyma. Although findings of histopathology and general examination including bone marrow biopsy led to the diagnosis of cutaneous LCH, he died from chronic myelomonocytic leukemia, which emerged 10 months after the initial diagnosis of LCH. The previously reported cases of LCH concomitant with other hematological disorders are also summarized and described compared with the present case.

Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication after transplantation. A living donor liver transplantation was performed on a 31-year-old man for fulminant hepatitis. He again developed liver dysfunction after 7 months. He was diagnosed as having acute cellular rejection and the steroid pulse therapy introduced resulted in little improvement. He gradually developed a high fever and right axillary lymphadenopathy appeared. Chest computed tomography (CT) was performed revealing small lung nodules and axillary lymphadenopathy. Because his serological status for Epstein-Barr virus was positive, PTLD was highly suspected and immunosuppression treatment was withdrawn with little improvement. One week later, he developed tachycardia. Chest CT was re-performed revealing an infiltration to the left cardiac chamber. For diagnosis, axillary lymph node biopsy was performed and during the procedure, he developed ventricular tachycardia (VT). Immunohistological staining revealed PTLD of T lymphocytes, and chemotherapy was introduced on the same day he developed VT. After two cycles of tetrahydropyranyl, adriamycin, cyclophosphamide, vincristine, prednisolone and etoposide treatment, he completely recovered. This is a first case report of severe PTLD with VT, and our case implies the feasibility of chemotherapy after the appearance of dissemination symptoms.

Background Along with an increased number of cases of liver transplantation (LT), perioperative mortality has decreased and short-term survival has improved. However, long-term complications have not been fully elucidated today. Purpose Chronic complications were analyzed individually to find risk factors and to improve long-term outcomes after LT. Subjects There were 63 cases of LT from our outpatient clinic that were included in this study. Among them, 58 were performed using living donor LT and 5 were performed using deceased donor LT. Original diseases mainly consisted of hepatitis C virus (HCV; 45.9%) and hepatitis B virus (23.0%). Findings The median follow-up was 5.4 ± 3.3 years (range, 0.1∼17 years). Overall survival at 2, 3, 5, and 10 years was 89.3%, 83.4%, 81.3%, and 81.3%, respectively. Long-term complications mainly consisted of renal dysfunction (62.7%), dyslipidemia (29.4%), diabetes mellitus (21.6%), and arterial hypertension (21.6%). In univariate analysis, HCV (P = .03) and elapsed years after LT (P = .02) were identified as predictive factors for arterial hypertension and recipient age >50 (P = .03), and elapsed years after LT for renal dysfunction (P = .03), respectively. In multivariate Cox regression analysis, HCV (odds ratio [OR] 5.25, 95% confidence interval [CI] 1.05–34.06, P = .04) was identified as a predictive factor for arterial hypertension, and recipient age older than 50 years for renal dysfunction (OR 5.67, 95% CI 1.34–28.88, P = .02). The number of elapsed years after transplantation was also identified as a predictive factor for arterial hypertension/dyslipidemia/renal dysfunction (OR 13.88/14.15/4.10, 95% CI 1.91–298.26/2.18–290.78/1.09–18.03, P = .01/.003/.04). Fifty percent of the recipients developed renal dysfunction within 8 years after LT, and fluctuation of estimated glomerular filtration rate (eGFR) within 3 months after LT was successfully associated with an annual decrease of eGFR (r2 value = 0.574, P Conclusion Renal dysfunction is the most frequent chronic complication after LT. As chronic individual eGFR can be now accurately predicted with deterioration speed, recipient strata for renal protection strategies should be precisely targeted.

Most of merkel cell carcinomas (MCC), a rare, aggressive skin cancer with neuroendocrine features, harbor merkel cell polyomavirus (MCPyV). Seroepidemiological studies suggested high prevalence of MCPyV in the human population. More than ten sequence data on MCPyV strains in Japan have been available, whereas most sequence data were detected from patients living in Europe or European ancestry. Analysis of nine almost complete and 19 partial sequences from two oncogenes, small T antigen (ST) and large T antigen (LT) genomes obtained from 32 Japanese MCPyV-infected MCC revealed that each Japanese MCPyV-infected MCC harbored a specific MCPyV strain with some synonymous or, silent mutations and stop codons or deletions, but functional domains of T antigen had no amino acid changes. All stop codons were localized after retinoblastoma protein-binding domain. These Japanese MCPyV strains were very closely interrelated to themselves and a consensus sequence of Japanese strain was generated. Phylogenetic analysis of our nine sequences and 70 other sequences for ST and LT gene registered in GenBank indicated that Japanese or Asian MCPyV strains formed distinct clades from Caucasian clade, and phylogenetic tree of our nine and 75 other sequences for ST gene formed characteristic three clades and showed that all Japanese or Asian strains were included in the dominant clade. These suggested the possibility of geographically related genotypes of MCPyV. The genomic characterization of MCPyV variants will provide an important database and insights for illuminating their evolutional and biological differences.

A 78-year-old man was admitted for workup for a liver tumor. Both serum AFP and PIVKA-II levels were high (2260ng/ml and 806mAU/ml, respectively). Contrast-enhanced CT scan and MRI using Gd-EOB-DTPA demonstrated a liver tumor in segment 6 resembling the imaging patterns of hepatocellular carcinoma (HCC), while the upper gastrointestinal endoscopy revealed a type 2 gastric cancer in the gastric antrum. Although the liver metastasis of the gastric cancer was undeniable, we performed partial resection of segment 6 of the liver and distal gastrectomy under a preoperative diagnosis of double cancer. Histopathologically, gastric tumor consisted of two components, such as well differentiated adenocarcinoma and hepatoid adenocarcinoma. The histology of the liver tumor was similar to that of the hepatoid component in the stomach lesion. Immunohistochemical staining revealed both the gastric and the liver tumors to be positive for AFP and PIVKA-II, yielding a definite diagnosis of AFP and PIVKA-II producing gastric cancer with liver metastasis. Because many cases of this disease have liver metastases at presentation with confusing images with HCC, the diagnosis of liver tumors should be carefully differentiated in the gastric cancer patients with liver tumors, high serum AFP and PIVKA-II levels.

Summary Langerhans cell histiocytosis (LCH) is a group of granulomatous disorders in which abnormal Langerhans cells proliferate as either a localized lesion in a single bone or disseminated disease involving two or more organs or systems. Because the different LCH forms exhibit significantly elevated levels of inflammatory molecules, including pro-inflammatory cytokines and tissue-degrading enzymes, we investigated for a possible viral trigger in LCH pathogenesis. We looked for Merkel cell polyomavirus (MCPyV) in peripheral blood cells and tissues using quantitative real-time PCR and immunohistochemistry staining with anti-MCPyV large T-antigen antibody. Our findings revealed elevated amounts of MCPyV DNA in the peripheral blood cells of 2 of 3 patients affected by LCH with high-risk organ involvement (RO+) and absence of MCPyV DNA in the blood cells in all 12 LCH-RO− patients ( P = . 029). With lower viral loads (0.002-0.033 copies/cell), an elevated number of MCPyV DNA sequences was detected in 12 LCH tissues in comparison with control tissues obtained from patients with reactive lymphoid hyperplasia (0/5; P = . 0007), skin diseases not related to LCH in children younger than 2 years (0/11; P = . 0007), or dermatopathic lymphadenopathy (5/20; P = . 0002). The data, including frequent but lower viral loads and low large-T antigen expression rate (2/13 LCH tissues), suggest that development of LCH as a reactive rather than a neoplastic process may be related to MCPyV infection.

The results of treating 12 consecutive patients with unresectable colorectal hepatic metastases with a hepatic arterial infusion of high-dose Adriamycin, 100–120 mg/m2, using hepatic venous isolation (HVI) and charcoal hemoperfusion (CHP) are reported herein. Adriamycin was administered over 5–15 min under extracorporeal drug elimination by HVI-CHP. HVI was percutaneously accomplished by either the double-balloon technique using a Fogarty occlusion catheter (8/22F) or a balloon-tipped catheter (16F). During the infusion, isolated hepatic venous blood was filtered by CHP and pumped into the left axillary vein. There were no lethal complications, and good hemodynamic tolerance to HVI-CHP was confirmed. Tumor liquefaction accompanied by a sharp decrease in serum carcinoembryonic antigen levels by more than 50% of pretreatment levels was observed in 6 of the 12 patients 1 month after treatment. Apart from chemical hepatitis, which developed in 11 (92%) of the patients, the Adriamycin toxicities were well controlled following the development of nausea and vomiting in 2 patients (17%), leukopenia

Although 2-[2-(2-pyridyl) ethenyl] indole undergoes one-way E → Z isomerization in the excited singlet state, it isomerizes between the E and Z isomers in the excited triplet state. On the basis of the determination of the quantum yields of isomerization and the photostationary state isomer ratios, as well as transient spectroscopic measurements, the potential energy surfaces for E - Z isomerization in the triplet state have been proposed. Specific rotamers of the E and Z isomers are found to be responsible for the triplet state isomerization reactions.

In the ductwork of local exhaust systems, 90 degrees elbow pipes (JIS K 6739) are commonly used to alter the direction of airflow; thus, are important components of polyvinyl chloride (PVC) ducts. Pressure loss in 90 degrees PVC elbow pipes was investigated by measuring static pressure, and the characteristics of airflow was determined. First, a linear decrease in static pressure was observed at points of the downstream side beyond a distance of 10 times the diameter (10d) from the flanged round opening of the smooth VU ducts (JIS K6741). The linear decrease was also observed at points of the downstream side located at distances of greater than 30d from the elbow pipe. Coefficients of loss in the PVC elbow pipes were found to be constant for the Reynolds numbers ranging from 3.38 x 10(4) to 5.96 x 10(5) for all diameters examined, and a chart of pressure loss was constructed with these coefficients. The coefficients of loss in PVC elbow pipes were not equivalent to those of metal stamped elbows for any R/d. However, the differences in the coefficients between the metal stamped elbow and the PVC elbow were smaller with larger R/d values.

The polymerizations of three nitrogen-containing heterophanes such as [2.2](2,5)pyridinophane (1), [2.2](2,5)pyrazinophane (2) and N, N′-dimethyl-[2.2](2,5)pyrrolophane (3) by the vapor deposition method were carried out. Compounds1, 2 and3 gave poly(2,5-pyridinediyl-ethylene), poly(2,5-pyrazinediylethylene), and poly(N-methyl-2,5-pyrrolediyl-ethylene) as tough films, respectively. The transformation of the ethylene unit in the polymer films to the vinylene one by the dehydrogenation reaction using 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) failed in the former two polymeric films and succeded to a certain extent in the latter one. The electrical conductivity of a poly(N-methyl-2,5-pyrrolediyl-vinylene) film obtained by the dehydrogenation reaction was measured to be 4×10-4 S/cm at room temperature and increased up to 1×10-2 S/cm on doping with iodine.

Background. We recently developed a novel system of direct hemoperfusion under hepatic venous isolation in an attempt to achieve high-dose intraarterial chemotherapy for patients with malignant liver tumors. We report here the results of treatment of these patients with advanced hepatocellular carcinoma. Methods. Adriamycin (100 to 150 mg/m2) was administered into the hepatic artery of 15 patients, under conditions of extracorporeal drug elimination by direct hemoperfusion under hepatic venous isolation. Hepatic venous isolation was accomplished mainly by the double-balloon technique with an occlusion catheter and a balloon catheter. The isolated hepatic venous blood was filtered by direct hemoperfusion and pumped to the left axillary vein. Results. During 5 minutes of adriamycin infusion, the mean drug extraction ratios of the direct hemoperfusion filters were 91%±9% (mean±SD). The amount of drug removed by the system was 26.4%±16.0% of the amount of drug administered. Two patients died, one of necrotizing pancreatitis and the other of hepatic arterial thrombosis. Both deaths were related directly to the hepatic arterial catheter. Other side effects included hemolysis related to the system of hemoperfusion (87%), chemical hepatitis (80%), leukopenia less than 3000/mm3 (67%), alopecia (33%), and nausea and vomiting (20%). Nine (64%) of 14 evaluable patients had objective tumor responses, with a median duration of response of 6.2 months. Conclusions. This approach offers an effective therapeutic option for patients with advanced hepatocellular carcinoma.

For adult patients with end-stage liver disease, living-donor liver transplantation (LDLT) of right-lobe grafts with or without the middle hepatic vein (MHV) has been increasingly used in recent years. We investigated the role of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has not been described in previous studies. A total of eight living donors were included in this study of right-lobe LDLT. Four donors underwent right lobectomy (without MHV), and the remaining four underwent extended right lobectomy (with MHV). Regeneration of the donor remnant liver was assessed by volumetric computed tomography studies before and 90 days after LDLT. Comparison between the right-lobe and extended right-lobe donors did not show a clear-cut difference in the net increase of remnant liver volume at 3 months. However, the mean volume increase of the medial segment at the 90th postoperative day was 7% in the extended right-lobe donors and 61% in the right-lobe donors, showing a lower value in the remnant livers without MHV. The MHV plays a specific role in remnant liver regeneration of right-lobe living donors. We expect that this knowledge will contribute to securing a margin of safety in right-lobe LDLT.

Merkel cell polyomavirus (MCPyV) monoclonally integrates into genomes of approximately 80% of Merkel cell carcinomas (MCCs) and undergoes mutation. We previously demonstrated statistically significant differences in tumor cell morphology and biology between MCPyV-positive and MCPyV-negative MCCs. We reassessed the usefulness of our morphologic criteria in differentiating MCPyV-negative and MCPyV-positive MCCs for practical diagnosis. Two trainees and 4 pathologists challenged estimations (5-point confidence scale) of MCPyV infection in MCCs using hematoxylin and eosin-stained slides of 43 new MCC cases and 2 morphologic criteria: (1) nuclear polymorphism is higher and cytoplasm is more abundant in MCPyV-negative MCC cells, and (2) MCC combined with squamous cell carcinoma is defined as MCPyV negative, regardless of tumor cell morphology of MCC. Subsequently, immunohistochemistry for MCPyV large T antigen and polymerase chain reaction for MCPyV DNA yielded concordant results (MCPyV positivity was 30/43 and 32/43, respectively) for 41 (96%) of 43 cases. The mean accuracy, sensitivity, and specificity of the trainees and pathologists were 92.4% ± 1.5% and 81.5% ± 11.0%, 95.6% ± 6.2% and 90.2% ± 8.3%, and 83.3% ± 11.8% and 74.6% ± 14.1%, respectively. Values of the areas under the curve were 0.80 to 0.95, indicating good informative scores. Using our morphologic criteria, observers can predict the absence of MCPyV infection and diagnose MCPyV-negative MCCs with poor prognosis. Unexpectedly, the performance of trainees was superior to that of pathologists, implying that our morphologic criteria are useful even for practitioners having little experience. Our morphologic criteria will provide pathologists with convenient and reliable hallmarks for accurate MCC diagnosis.

It has recently been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus (MCPyV). MCPyV has been detected in human tissue samples. However, detailed distribution of MCPyV in non-neoplastic Japanese human tissues remains unclear. To address this, we used single or real-time quantitative polymerase chain reaction (PCR) for 41 autopsy cases. PCR revealed MCPyV-DNA in non-neoplastic samples: total, 29/41 (71%); adult, 29/39 (74%); fetus or infant, 0/2; men, 24/28 (86%); women, 5/13 (38%); total human tissues, 66/572 (12%); skin, 8/15 (53%); adrenal gland, 9/33 (27%), and other 16 organs (4–25%). This study first reported the presence of MCPyV-DNA in non-neoplastic tissues of thyroid gland, adrenal gland, spleen, bone marrow, stomach, gallbladder, pancreas, heart, and aorta. PCR revealed that viral load ranged from 0.00026 to 0.22 in all MCPyV-positive tissues compared with Merkel cell carcinoma samples. These detailed PCR data showed higher prevalence of MCPyV infection in Japanese men than women (p = 0.004) and broad distribution of MCPyV with low viral load in more non-neoplastic human tissues than in the previous reports. These data provide valuable insights for further studies of MCPyV infection and MCPyV-related diseases.

Merkel cell polyomavirus is a novel polyomavirus that is monoclonally integrated into genomes of up to 80% of human Merkel cell carcinomas. Merkel cell polyomavirus-positive Merkel cell carcinomas showed less metastatic tendency and better prognosis according to some reports, whereas others disagree. In this study, we analyzed clinicopathological characteristics of 20 Merkel cell polyomavirus-positive and 6 Merkel cell polyomavirus-negative Merkel cell carcinoma cases, in which we already reported the association of Merkel cell polyomavirus infection with statistically significant morphological differences. Immunohistochemical expressions of cell cycle-related proteins, mutations of the TP53 tumor-suppressor gene (exons 4-9) and p14ARF promoter methylation status as well as detailed clinical data were analyzed and compared between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative cases. Merkel cell polyomavirus-positive Merkel cell carcinomas showed better prognosis with one spontaneous regression case and significantly higher expression of retinoblastoma protein (P = .0003) and less p53 expression (P = .0005) compared to Merkel cell polyomavirus-negative Merkel cell carcinomas. No significant differences were found in expressions of p63, MDM2, p14ARF or MIB-1 index, and p14ARF promoter methylation status. Interestingly, frequency of TP53 non-ultraviolet signature mutation was significantly higher in Merkel cell polyomavirus-negative Merkel cell carcinomas than in Merkel cell polyomavirus-positive Merkel cell carcinomas (P = .036), whereas no significant difference was detected in TP53 ultraviolet signature mutations between two groups. These results suggest that Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas likely develop through different tumorigenic pathways and that the presence or absence of Merkel cell polyomavirus in the tumor is still an important factor that affects survival in patients with Merkel cell carcinoma.

Seven 1,3,4-thiadiazole-containing polyethers with reduced viscosities of 0.27–1.44 dL/g were synthesized by the high-temperature solution polycondensation of novel activated difluoride, 2,5-bis (4-fluorophenyl)-1,3,4-thiadiazole, with aromatic diols possessing a variety of ring structures. The expected chemical structures were confirmed by IR and 1H-NMR spectroscopy and elemental analysis. Of all the polymers, three polyethers were highly crystalline and soluble only in limited solvents such as concentrated sulfuric acid. The other polyethers were amorphous and dissolved easily in a variety of organic solvents including N-methyl-2-pyrrolidone (NMP), phenols, and chlorinated hydrocarbons. Colorless to slightly yellow-colored, transparent, and tough films could be cast from the NMP solutions of the amorphous polyethers. The mechanical properties of the films were excellent, and their tensile strength, elongation at break, and tensile moduli were in the ranges of 48–72 MPa, 5–7%, and 1.3–1.9 GPa, respectively. The amorphous polyethers had high glass transition temperatures of 204–299°C. All the polyethers were highly thermally and thermooxidatively stable and exhibited no weight loss up to 400°C, with 10% weight loss being recorded at 464–513°C in air. © 1994 John Wiley & Sons, Inc.

症例は62歳女性で食思低下と右季肋部痛を主訴に入院精査となった.血液検査所見では胆道系酵素の軽度上昇を認めたのみで黄疸はなかった.腹部X線CT, MRI検査ともにS4を中心に不整形の浸潤像を示す腫瘤影が認められた.腹部血管造影で中及び右肝動脈の不整狭窄像および腫瘍濃染像を多数認め,肝内転移を伴う胆管癌と診断した.開腹時胆嚢および肝腫瘤周囲に強い線維性癒着を認めたが胆石はなかった.超音波ガイド下に術中穿刺生検を3回反復したが迅速病理診断で悪性所見が否定されたため楔状切除生検にとどめ閉腹した.永久標本の病理組織所見では小胆管の拡張像とその周囲を層状に取り囲む線維増生を散在性に認めたが悪性所見はなく炎症性腫瘤と診断された.本例のような炎症性腫瘤は以前に報告がなく稀な例と考えられた.

A 67-year-old man underwent laparoscopic low anterior resection and open medial segmentectomy of the liver for rectal cancer and liver metastasis. During the operation, a cystic duct mass, 1cm in diameter, was found. Therefore cholecystectomy with partial resection of the common bile duct was also performed. The rectal tumor and liver tumor were diagnosed pathologically as moderately differentiated adenocarcinoma. The cystic duct mass was mainly located in the lamina propria and its histological aspects were similar to the rectal cancer. Immunohistochemical staining revealed that rectal, hepatic, and cystic duct lesions were all negative for CK7 but were all positive for CK20. These findings confirmed the diagnosis of rectal cancer with metastases to the liver and the cystic duct. Metastatic cystic duct tumor is extremely rare and has never been reported in the Japanese literature.

This case is a 69-year-old woman. We diagnosed gastric cancer and cholecystolithiasis by close inspection of abdominal pain. Because preoperative diagnosis was T2N0M0, Stage I B, we performed an operation. Many lesser tubercles were shown, and were diagnosed as peritoneal metastases pathologically. The tumor in corpus ventriculi infiltrated out of gastric serosa. We judged that curative resection was impossible and finished the operation after giving an intra-abdominal dosage of cisplatin(CDDP)at 85mg. After operation, 3 courses of performed S-1/CDDP combination chemotherapy were performed. Because we observed contraction of the main lesion and could not point out the peritoneal metastases and ascitis, we performed a second look operation. All the nodules found with peritoneal and rectouterine excavation had disappeared and we performed distal gastrectomy. The postoperative diagnosis was pT2(MP), pN0CY0, Stage I B, Cur A, therapy grade 1a. Chemotherapy does succeed, and this is a valuable case in which a radical operation could be performed.

A 60-year-old man presented with diarrhea and weight loss. Colonoscopy revealed multiple reddish polypoid lesions throughout the gastrointestinal tract and was diagnosed as Cronkhite-Canada syndrome (CCS). Prednisolone therapy caused regression of polyps. Some of them were suspected to be early colon cancers and adenomas. We endoscopically performed mucosal resection for 15 polyps after prednisolone therapy. Histological examination of one of polyps showed invasion of the submucosal layer and colon resection was performed. This case suggests that diagnosis and treatment are important in polyps of CCS.

We have reported the isolation of linking clones of HindIII and EcoRI fragments, altogether spanning a 230-kb continuous stretch of chromosome VI. The presence or absence of autonomously replicating sequence (ARS) activities in all of these fragments has been determined by using ARS searching vectors containing CEN4. Nine ARS fragments were identified, and their positions were mapped on the chromosome. Structures essential for and/or stimulative to ARS activity were determined for the ARS fragments by deletions and mutations. The organization of functional elements composed of core and stimulative sequences was found to be variable. Single core sequences were identified in eight of nine ARSs. The remaining ARS (ARS603) essential element is composed of two core-like sequences. The lengths of 3'- and 5'-flanking stimulative sequences required for the full activity of ARSs varied from ARS to ARS. Five ARSs required more than 100 bp of the 3'-flanking sequence as stimulative sequences, while not more than 79 bp of the 3' sequence was required by the other three ARSs. In addition, five ARSs had stimulative sequences varying from 127 to 312 bp in the 5'-flanking region of the core sequence. In general, these stimulative activities were correlated with low local delta Gs of unwinding, suggesting that the low local delta G of an ARS is an important element for determining the efficiency of initiation of replication of ARS plasmids.

On direct irradiation in benzene 2-[2-(2-pyridyl)ethenyl]indole undegoes trans-to-cis one-way isomerization in the excited singlet state.

Fifteen patients who were admitted to our department with hepatocellular carcinoma (HCC) and under 40 years of age were reviewed. The rate of HBs antigen positive patients was 78.6%, whereas that of association of cirrhotics was only 20.0% and most patients showed relatively good liver function. Periodic follow-up for liver dysfunction had been performed in only 3 of 8 patients. Twelve patients (80%) had abdominal pain directly caused by advanced tumors and 3 of these patients were admitted to the hospital in a state of acute abdomen due to ruptured tumor. Most patients had highly advanced HCC; 53.3% had tumors larger than 10cm in diameter and 80% had multiple intrahepatic tumor spreads. Survivals of these patients were extremely short and only 3 patients survived over one year. However, 2 patients undergoing extended hepatectomy showed relatively long-term survivals more than a year. These results indicated that younger patients with HCC were rarely admitted to the hospital because of their relatively good liver function despite higher positive rate for HBs antigen. Therefore, close follow-up in such younger patients is of particular importance for the early detection of HCC.

On direct irradiation in benzene 2-[2-(2-pyridyl)ethenyl]indole undegoes trans-to-cis one-way isomerization in the excited singlet state.

Recently, it has been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cell polyomavirus, thought to be a carcinogenic agent. However, it is not fully elucidated whether Merkel cell carcinomas differ with regard to the presence or absence of Merkel cell polyomavirus. To address this, we investigated morphologic differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas by morphometry. Using polymerase chain reaction and real-time quantitative polymerase chain reaction, Merkel cell polyomavirus was detected in 20 (77%) of 26 Merkel cell carcinoma cases, including 4 Merkel cell carcinomas combined with squamous cell carcinomas. Interestingly, Merkel cell polyomavirus was detected only in ordinary (pure) Merkel cell carcinomas; none of the 4 combined Merkel cell carcinomas + squamous cell carcinomas was positive for Merkel cell polyomavirus (P = .001). Morphometric analyses revealed that Merkel cell polyomavirus-negative Merkel cell carcinomas had more irregular nuclei (P.001) and more abundant cytoplasm (P = .001) than Merkel cell polyomavirus-positive Merkel cell carcinomas, which had uniform round nuclei and scant cytoplasm. Reliability of the morphometry was confirmed using intraobserver and interobserver reliability tests. These results demonstrated statistically significant differences in tumor cell morphology between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas and reconfirmed the absence of Merkel cell polyomavirus in combined tumors. Furthermore, the results strongly suggest fundamental biological differences between Merkel cell polyomavirus-positive and -negative Merkel cell carcinomas, supporting that Merkel cell polyomavirus plays an important role in the pathogenesis of Merkel cell polyomavirus-positive Merkel cell carcinoma.

A 52-year-old man underwent distal gastrectomy for gastric cancer in July 2000. In July 2005, abdominal CT and barium study of the colon revealed peritoneal recurrence, and chemotherapy of S-1 was started. Within 2 courses, the serum CEA level increased, so combination chemotherapy of S-1 and cisplatin (CDDP) was begun. After 7 courses, the regimen was switched to S-1+paclitaxel (PTX). However, the patient developed digital numbness within 8 courses and single-agent chemotherapy with S-1 was restarted. In July 2007, he developed abdominal distension, and abdominal CT showed a large amount of ascites. S-1+CDDP was administered again, however, and we had to change the regimen within 3 courses due to fatigue and appetite loss. S-1 was restarted, but soon severe fatigue and appetite loss restricted the use of chemotherapeutic agents, and he died in December. This patient had been alive for 2 years and 5 months since peritoneal recurrence was diagnosed. We concluded that S-1-based sequential chemotherapy was effective for recurrent gastric cancer.

The case is a 66-year-old woman. CT showed multiple metastasis of the liver and lung after operation by colectomy for ascending colon carcinoma. A close inspection showed progressive stomach cancer with lymph node metastasis. Metastasis was considered an effect when it was of colon cancer origin, and treatment by mFOLFOX6 was started. In the results, we confirmed contraction of the liver and lung metastasis and contraction of the regional lymph node metastasis of the stomach by CT. The gastric cancer lesion became only a cicatrix with endoscopic examination. For gastric cancer, the availability of mFOLFOX6 was suggested.

Various oxiranes reacted with carbon dioxide at 100 °C using lithium bromide as a catalyst under atmospheric pressure to afford the corresponding five-membered cyclic carbonates quantitatively. The rate of the reaction increased as the bulkiness of substituents on the oxirane ring was reduced or an electron-withdrawing group was introduced on the oxirane ring. The stereochemistry of the reaction of oxirane and carbon dioxide was retention without loss of optical purity. When substituted phenylethylene carbonates were reacted with benzylamine, the selectivity to afford secondary alcohol increased as the electron-withdrawing ability of the para-substituent increased.

A method of measuring tensile strength of a filament with a diameter of μ m order has been devised. The method allows us to measure the tensile load in the range of 20 to 1500mg with an accuracy of about 1 mg under optical-microscope observation. In oder to measure the tensile strength, the cross sectional area of the specimen is estimated from a SEM micrograph of the fractured surface taken parallel to the specimen axis. Srtain is calculated by comparing the distance of markers, i.e. tiny whiskers distriduted on a specimen, on micrographs taken at each stage of loading. The Young's modulus and the tensils strength of a pitch-based isotropic carbon filament thus obtained were about 60GPa and 850MPa, respectively.

Rapid graft dysfunction caused by hepatitis C virus (HCV) reinfection, although uncommon, is a disastrous complication in liver transplant patients. Finding an effective therapy for this subgroup of patients with severe recurrent HCV is a priority.We describe a successful rescue of a 46-year-old man with recurrent hepatitis C (HCV genotype 1b) using long-term interferon (IFN) and ribavirin. The patient had a very aggressive type of posttransplantation HCV infection, as judged by biochemical and histologic findings.Despite high pretreatment values of serum alanine aminotransferase (ALT; peak value of 901 IU/L) and HCV-RNA (2.3 x 10(6) copies/ml), the combination therapy with IFN and ribavirin produced a rapid normalization of the serum ALT values, accompanied by the clearance of serum HCV-RNA. Although HCV-RNA reappeared in the serum at 3 months, the patient had continued ALT normalization and histological improvement with follow-up of over 26 months to date after the initiation of the combination therapy.This observation suggests that IFN in combination with ribavirin may offer an effective therapeutic option for liver transplant patients with severe recurrent hepatitis C.