Dectin-1-mediated suppression of RANKL-induced osteoclastogenesis by glucan from baker's yeast.

Immunoreceptors expressed on osteoclast precursor cells modify osteoclast differentiation and bone resorption activity. Dectin-1 is a lectin receptor of ß-glucan and is specifically expressed in osteoclast precursor cells. In this study, we evaluated the bioactivity of ß-glucan on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and observed that glucan from baker's yeast inhibited this process in mouse bone marrow cells and dectin-1-overexpressing RAW264.7 (d-RAW) cells. In conjunction, RANKL-induced nuclear factor of activated T cell c1 expression was suppressed, subsequently downregulating TRAP and Oc-stamp. Additionally, nuclear factor-kappa B activation and the expression of c-fos and Blimp1 were reduced in d-RAW cells. Furthermore, glucan from baker's yeast induced the degradation of Syk protein, essential factor for osteoclastogenesis. These results suggest that glucan from baker's yeast suppresses RANKL-induced osteoclastogenesis and can be applied as a new treatment strategy for bone-related diseases.

Multidisciplinary team management for prevention of pneumonia and long-term weight loss after esophagectomy: a single-center retrospective study.

BACKGROUND: In April 2017, we launched the multidisciplinary Hamamatsu Perioperative Care Team (HOPE) for all surgical patients. We developed a reinforced intervention strategy, particularly for esophagectomy. We herein report the outcomes of the HOPE at 2 years after commencement. METHODS: A total 125 patients underwent esophagectomy and gastric conduit reconstruction for esophageal or esophagogastric junction cancer between January 2014 and December 2018 at the Department of Surgery in Hamamatsu University School of Medicine. The patients were divided into the pre-HOPE group including 62 patients who underwent esophagectomy before the introduction of the HOPE and the HOPE group including 63 patients who underwent esophagectomy after the introduction of the HOPE. The outcomes of surgery were compared between the two groups. RESULTS: There were no significant differences in the clinicopathological characteristics between the two groups. The incidence rates of atrial fibrillation and pneumonia were significantly lower in the HOPE group than in the pre-HOPE group (6% vs. 19%, p = 0.027 and 14% vs. 29%, p = 0.037, respectively). The estimated calorie doses at the time of discharge were approximately 750 and 1500 kcal/day in the pre-HOPE group and the HOPE group, respectively. The body weight loss was significantly less in the HOPE group than the pre-HOPE group at 1, 3, 6, and 12 months postoperatively than that before the surgery (p < 0.001). CONCLUSIONS: The introduction of the multidisciplinary HOPE was associated with a significant reduction in the incidence of postoperative pneumonia and significantly less weight loss.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir in dialysis patients with genotype 1b chronic hepatitis C.

AIM: From a pharmacokinetic viewpoint, the use of ombitasvir/paritaprevir/ritonavir, one of the standards of care for genotype 1b chronic hepatitis C in Japan, could be possible in patients with impaired renal function. The aim of this study was to assess the efficacy and safety of this combination that have not yet been addressed in patients undergoing dialysis. METHODS: A retrospective, multicenter study evaluated the outcome of 12-week ombitasvir (non-structural protein [NS]5A inhibitor)/paritaprevir (NS3/4A protease inhibitor)/ritonavir combination therapy for dialysis patients. The primary end-point was sustained virologic response 12 weeks after therapy (SVR12). RESULTS: The subjects were 31 patients with a median age of 64 years (range, 49-85 years), including 10 cirrhotic patients. All of the 31 patients had an estimated glomerular filtration rate level <15 mL/min/1.73 m2 , defined as end-stage renal disease (ESRD). Pre-existing resistance-associated substitutions at position L31 and Y93 of the NS5A region were detected in 0% and 3.6% (1/28), respectively. The rates of rapid virologic response, end-of-treatment response, and SVR12 were 93.5% (29/31), 100% (31/31), and 96.8% (30/31), respectively. The incidence of adverse events was 35.5% (11/31). Of the 11 patients, one discontinued the treatment due to erythema multiforme and thereafter relapsed. The most frequent adverse event was pruritus (6.5%; 2/31). CONCLUSIONS: The present study suggests that ombitasvir/paritaprevir/ritonavir combination therapy is effective and safe for genotype 1b chronic hepatitis C patients undergoing dialysis due to ESRD.

Two-devices-in-one-channel method for fractured pancreatic duct stent retrieval in a case of severe chronic pancreatitis.

When a pancreatic plastic stent for symptomatic chronic pancreatitis breaks during its removal, severe pancreatic duct stenosis may complicate its retrieval. Takuma and colleagues report on the successful retrieval of a fragmented and displaced pancreatic plastic stent by applying the two-device-in-one-channel method using forceps and a snare.

On the preparation of indoxyl red from indican and some new characteristics.

An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, UV-visible spectra, and IR spectra. Although indoxyl red was first synthesized by Seidel(9) 70 years ago, very little information has been available on its characteristics. We repot here that the compound was purple-red colored at acidic pH and green at pH 13, and showed antiproliferative and cytotoxic activities to the mouse B cell lymphoma cell line NSF202.

[Prevention of spinal hypotension associated with cesarean section by aortocaval compression--left 15 degree table tilt vs. uterine displacement by hand].

Women undergoing elective cesarean delivery were randomly assigned to receive a spinal anesthesia in either the semi-lateral (group SL) position or the supine position with uterine displacement (group UD). After spinal injection, group SL patients were turned to a 15 degrees left lateral supine position, and group UD patients had uterine displacement by hand. Ephedrine 4 mg i.v. was administered in case of nausea/vomiting and/or hypotension, defined as a systolic blood pressure below 100 mmHg. Arm systolic arterial pressure and leg systolic arterial pressure were similar in both groups, but the lowest leg systolic arterial pressure until delivery was significantly lower in the UD group (P < 0.05). Mean ephedrine requirement was significantly less in the SL group (P < 0.05). Apgar scores did not differ, but umbilical artery pH values were significantly higher in patients of the group SL (P < 0.01).

Comparison of the course of biomarker changes and kidney injury in a rat model of drug-induced acute kidney injury.

OBJECTIVE: To aid in evaluating the performance of biomarkers, we measured kidney injury biomarkers in rat models of drug-induced acute kidney injury. METHODS AND RESULTS: Rats were treated with site-specific nephrotoxins, puromycin, gentamicin, cisplatin, or 2-bromoethylamine. Fifteen biomarkers (ß-2-microglobulin, calbindin, clusterin, cystatin-C, KIM-1, GST-α, GST-µ, NGAL, osteopontin, EGF, TIMP-1, VEGF, albumin, RPA-1, and urinary total protein) were examined in comparison with BUN, serum creatinine, and NAG. Some biomarkers, which were different depending in each nephrotoxin, showed ability to detect the prodromal stage of drug-induced kidney injury. Characteristic changing patterns of biomarkers were also found depending on the specific lesion site in the kidney. CONCLUSION: These data suggested that establishment of a suitable biomarker panel would facilitate detection of site-specific kidney injury with high sensitivity.

Efficacy of Hypertonic Saline-Epinephrine Local Injection Around the Anal Side before Endoscopic Papillectomy for Ampullary Tumors.

BACKGROUND/AIMS: Bleeding is a complication of endoscopic snare papillectomy for ampullary tumors. This study aimed to investigate the clinical efficacy of hypertonic saline-epinephrine (HSE) local injection before endoscopic papillectomy for prevention of bleeding. METHODS: We retrospectively reviewed the data of 107 consecutive patients with ampullary tumors who underwent endoscopic papillectomy. The rates of en bloc resection, pathological resection margins, and prevention of immediate or delayed bleeding in the simple snaring resection group (Group A) and the HSE injection group (Group B) were compared. RESULTS: A total of 44 and 63 patients were enrolled in Groups A and B, respectively. The total complete resection rate was 89.7% (96/107); the clinical complete resection rates in Group A and Group B were 86.3% (38/44) and 92.1% (58/63), respectively (p=0.354). Post-papillectomy bleeding occurred in 22 patients. In Groups A and B, the immediate bleeding rates were 20.5% (9/44) and 4.8% (3/63), respectively (p=0.0255), while the delayed bleeding rates were 7% (3/44) and 11% (7/63), respectively (p=0.52). The rates of positive horizontal and vertical pathological margin in both groups were 27% and 16%, respectively. CONCLUSION: HSE local injection was effective in preventing immediate bleeding and was useful for safely performing endoscopic papillectomy for ampullary tumors.

Plectin stabilizes microtubules during osteoclastic bone resorption by acting as a scaffold for Src and Pyk2.

Osteoclasts are multinuclear cells which maintain bone homeostasis by resorbing bone. During bone resorption, osteoclasts attach to the bone matrix via a sealing zone formed by an actin ring. Rous sarcoma oncogene (Src) is essential for actin ring formation and bone resorption. Recently, we demonstrated that plectin, a cytolinker protein, is a Src-binding protein in osteoclasts. However, the function of plectin in osteoclasts remains unknown. In this study, we demonstrated that shRNA knockdown of plectin in RAW 264.7 cells resulted in tartrate resistant acid phosphatase positive multinuclear cells (TRAP (+) MNCs) with impaired actin ring formation and bone resorption activity. Moreover, we found that in plectin-silenced TRAP (+) MNCs, Src and protein tyrosine kinase 2 beta (Pyk2), two critical kinases in osteoclastic bone resorption, were inactivated and microtubule polarity was disturbed. These results suggest that plectin plays a critical role in osteoclast biology by acting as a scaffold to facilitate Src and Pyk2 activation during microtubule organization.

Therapeutic efficacy of continuous arterial infusion of the protease inhibitor and the antibiotics and via celiac and superior mesenteric artery for severe acute pancreatitis--pilot study.

BACKGROUND/AIMS: Severe acute pancreatitis is poor prognosis. Continuous regional arterial infusion of protease inhibitors and antibiotics were developed in Japan. We evaluated whether arterial infusion both celiac artery and superior mesenteric artery for this disease would reduce mortality. METHODOLOGY: Seventeen patients were treated arterial infusion of protease inhibitor and antibiotics via both celiac artery and superior mesenteric artery. Changes of Acute Physiology and Chronic Health Evaluation II score and mortality were evaluated. RESULTS: Arterial infusion via two routes reduced the mortality rate and improved Acute Physiology and Chronic Health Evaluation II score. The overall mortality rate was 11.8%. The mortality rate in patients in whom were treated within 3days after the onset was significantly lower than that in patients in whom were treated without 3days after the onset. CONCLUSIONS: Arterial infusion via superior mesenteric artery might prevent both bacterial translocation and non-occlusive mesenteric ischemia. Continuous arterial infusion both celiac artery and superior mesenteric artery might be effective for reducing mortality and preventing the development of pancreatitis, especially when initiated within 3 days after the onset. Further prospective randomized studies using a larger number of patients are required.

BodyMap-Xs: anatomical breakdown of 17 million animal ESTs for cross-species comparison of gene expression.

BodyMap-Xs (http://bodymap.jp) is a database for cross-species gene expression comparison. It was created by the anatomical breakdown of 17 million animal expressed sequence tag (EST) records in DDBJ using a sorting program tailored for this purpose. In BodyMap-Xs, users are allowed to compare the expression patterns of orthologous and paralogous genes in a coherent manner. This will provide valuable insights for the evolutionary study of gene expression and identification of a responsive motif for a particular expression pattern. In addition, starting from a concise overview of the taxonomical and anatomical breakdown of all animal ESTs, users can navigate to obtain gene expression ranking of a particular tissue in a particular animal. This method may lead to the understanding of the similarities and differences between the homologous tissues across animal species. BodyMap-Xs will be automatically updated in synchronization with the major update in DDBJ, which occurs periodically.

[Gemcitabine treatment in patients with stage IV pancreatic cancer and prognostic factors for survival of patients with stage IVb(a retrospective survey at 15 hospitals in Niigata Prefecture)].

We performed a retrospective survey at 15 hospitals in Niigata Prefecture to assess the effectiveness of gemcitabine in patients with stage IV pancreatic cancer and to analyze prognostic factors impacting survival in patients with stage IVb. The subjects were 244 unresectable or metastatic pancreatic cancer patients(IVa 68, IVb 176)who were treated with gemcitabine as first-line therapy. The overall response rate was 6.1% and the median survival time(MST)was 194 days. The MST of stage IVa(312 days)was double that of stage IVb(167 days). Prognostic factors for survival of patients with stage IVb were analyzed(performance status, response rate, liver metastasis, peritonitis carcinomatosa, paraaortic lymph node metastasis)with the Cox proportional hazards model. Performance status, response rate, and liver metastasis were significant factors influencing survival. When we compare an effect of other chemotherapy with GEM, we should treat stage IVa and stage IVb separately, and subdivision is necessary for stage IVb.

Angiotensin-II administration is useful for the detection of liver metastasis from pancreatic cancer during pharmacoangiographic computed tomography.

AIM: To improve the preoperative diagnosis of liver metastasis from pancreatic cancer, we estimated computed tomography during arterial angiography (CTA) with/without administration of angiotensin-II (AT- II). METHODS: Thirty-five patients with pancreatic cancer were examined in this study. After conventional CTA was performed, pharmacoangiographic CTA was performed with a 1-3 microgram/5 mL solution of angiotensin II injected through a catheter into the celiac artery during spiral computed tomography. We prospectively analyzed the relative region of interest (ROI) ratio of tumor to liver with/without AT-II. RESULTS: In all patients, the relative ratio of each computed tomography (CT) number in the ROI was larger at pharmacoangiographic CT than at conventional angiographic CT. Administration of angiotensin-II enhanced the metastatic liver tumor as compared with normal tissue. Intratumoral blood flow increased in all patients with malignant tumors due to the pressure effect of AT-II. Furthermore, the metastatic lesions in the liver of three patients were represented by only pharmacoangiographic CT, not by conventional CT and conventional CT angiography. In even peripheral and central areas of metastatic liver tumor, the lesions were enhanced after administration of AT-II. CONCLUSION: These results support that high detection rate of liver metastasis revealed by pharmacoangiographic CT suggests the improvement of diagnosis on preoperative staging. Moreover, chemotherapy under AT-II induced hypertension may have a better effect on the treatment of metastatic liver tumors.

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: a pilot study.

AIM: To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil. RESULTS: The mean course of chemotherapy was 14.4 (range, 9-21) mo. One patient showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the two patients showed partial response (PR), response rate (CR + PR/All cases 30%). The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable. CONCLUSION: Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.

Clinical efficacy of intra-arterial pharmacokinetic chemotherapy with 5-fluorouracil, CDDP, gemcitabine, and angiotensin-II in patients with advanced pancreatic cancer.

BACKGROUND/AIMS: To deliver anticancer drugs more selectively into cancer tissues and to improve survival time, we have developed a new method of intra-arterial chemotherapy for unresectable pancreatic cancer. METHODOLOGY: From April 2002 to June 2006, twenty patients with pancreatic cancer with liver metastases were given intra-arterial infusions consisting of gemcitabine, 5-FU, and cisplatin mixed with angiotensin-II with the intent of increasing the blood flow into the tumor tissue but decreasing that to the non-tumor tissues. Simultaneously, tegafur/uracil was administered. A tumor marker and computed tomography (CT) findings were used to evaluate the efficacy of this chemotherapy. RESULTS: The median survival was 365 days, and 6-months and 1-year survival rates were 80.0% and 44.7%, respectively. In 12 of 20 cases, the tumor marker level was decreased after this chemotherapy. In 10 of 20 cases, computed tomography showed a decrease in the tumor size. In 6 patients, back pain was the chief complaint and was reduced to a self-controlled level in 20 patients. No major complications were encountered. CONCLUSIONS: Compared with the previously reported data in traditional chemotherapies, our method of intra-arterial chemotherapy appears to be quite useful not only for prolonging patient survival but also for improving the quality of life. Intra-arterial regional chemotherapy including changes in distribution of blood flow induced by angiotensin-II appears to be an effective palliative treatment for advanced pancreatic cancer.

[A resected case of fibrolamellar hepatocellular carcinoma with chronic hepatitis (type B)].

We report a case of a 34-year-old woman who tested positive for HBs Ag with fibrolamellar hepatocellular carcinoma of the liver. The sister of this patient, who was also positive for HBs Ag, died of hepatocellular carcinoma (HCC). The patient showed elevation of alpha-fetoprotein. Abdominal CT scan showed a tumor in the posterior segment of the liver and hepatic angiography revealed marked neovascularity in the tumor. Partial resection of the liver was performed, and the histological diagnosis was fibrolamellar hepatocellular carcinoma. The patient is now tumor free and doing well 20 months after the operation.

[A case of splenic inflammatory pseudotumor].

A 59-year-old man was admitted to our hospital because of continuous C-reactive protein elevation. Abdominal computed tomography scan revealed a low density mass on the surface of the spleen. Magnetic resonance imaging showed low intensity at peripheral area and slightly high intensity in the central area of the mass lesion on T1 and T2-weighted image. Splenectomy was performed since we could not rule out the possibility of malignant neoplasm only by diagnostic imaging. The pathological diagnosis of the tumor was inflammatory pseudotumor. Splenectomy is considered to be significant from the standpoints of both diagnosis and therapy in cases in which diagnostic imaging is difficult to interpret.

Comparison of a new aspiration needle device and the Quick-Core biopsy needle for transjugular liver biopsy.

AIM: To evaluate sample adequacy, safety, and needle passes of a new biopsy needle device compared to the Quick-Core biopsy needle for transjugular liver biopsy in patients affected by liver disease. METHODS: Thirty consecutive liver-disease patients who had major coagulation abnormalities and/or relevant ascites underwent transjugular liver biopsy using either a new needle device (18 patients) or the Quick-Core biopsy needle (12 patients). The length of the specimens was measured before fixation. A pathologist reviewed the histological slides for sample adequacy and pathologic diagnoses. The two methods'specimen adequacy and complication rates were assessed. RESULTS: Liver biopsies were technically successful in all 30 (100%) patients, with diagnostic histological core specimens obtained in 30 of 30 (100%) patients, for an overall success rate of 100%. With the new device, 18 specimens were obtained, with an average of 1.1 passes per patient. Using the Quick-Core biopsy needle, 12 specimens were obtained, with an average of 1.8 passes per patient. Specimen length was significantly longer with the new needle device than with the Quick-Core biopsy needle (P < 0.05). The biopsy tissue was not fragmented in any of the specimens with the new aspiration needle device, but tissue was fragmented in 3 of 12 (25.0%) specimens obtained using the Quick-Core biopsy needle. Complications included cardiac arrhythmia in 3 (10.0%) patients, and transient abdominal pain in 4 (13.3%) patients. There were no cases of subcapsular hematoma, hemoperitoneum, or sepsis, and there was no death secondary to the procedure. In particular, no early or delayed major procedure-related complications were observed in any patient. CONCLUSION: Transjugular liver biopsy is a safe and effective procedure, and there was significant difference in the adequacy of the specimens obtained using the new needle device compared to the Quick-Core biopsy needle. Using the new biopsy needle device, the specimens showed no tissue fragmentation and no increment in major procedure-related complications was observed.

Involvement of prostaglandin E receptor subtype EP(4) in colon carcinogenesis.

Accumulating evidence indicates that overproduction of prostanoids attributable to overexpression of cyclooxygenase-2 (COX-2) plays an important role in colon carcinogenesis. We have shown recently that the prostaglandin (PG) E receptor, EP(1), but not EP(3), is involved in mouse colon carcinogenesis. In line with our previous study, here we examined the role of prostanoid receptors in colon carcinogenesis using six additional lines of knockout mice deficient in prostanoid receptors EP(2), EP(4), DP, FP, IP, or TP. The animals were treated with the colon carcinogen, azoxymethane (AOM), and examined for the development of aberrant crypt foci (ACFs), putative preneoplastic lesions in the colon. Formation of ACFs was decreased only in the EP(4)-knockout mice, to 56% of the wild-type level. To confirm these results, we also examined the inhibitory effects of an EP(4)-selective antagonist, ONO-AE2-227, in the diet on the formation of AOM-induced colon ACFs in C57BL/6Cr mice and on the development of intestinal polyps in Min mice. ONO-AE2-227 at a dose of 400 ppm reduced the formation of ACFs to 67% of the control level, and intestinal polyp numbers in Min mice receiving 300 ppm were decreased to 69% of the control level. Plating efficiency assays showed that addition of 1.0 microM ONO-AE1-329, an EP(4)-selective agonist, resulted in a 1.8-fold increase in the colony number of the human colon cancer cell line, HCA-7, similar to the effect of PGE(2). Moreover, EP(4) mRNA expression was clearly observed in normal colon mucosa and colon tumors in mice. Our previous and present results indicate that PGE(2) contributes to colon carcinogenesis through its actions mediated through EP(1) and EP(4) receptors; therefore, antagonists for these two receptors may be good candidates as chemopreventive agents against colon cancer.

[Gemcitabine versus combined chemotherapy with 5-fluorouracil and cisplatin in advanced pancreatic cancer].

Gemcitabine hydrochloride (GEM) is a first-line therapeutic agent for advanced pancreatic cancer, but there is no established second-line treatment after GEM failure. We assessed the clinical benefit of systemic combined chemotherapy with 5-fluorouracil and cisplatin (FP therapy) in 19 patients compared with GEM in 32 patients, respectively. Tumor response rates were 10.5% and 15.6% for FP therapy and GEM, respectively. The median survival time in the FP therapy and GEM was 137 days and 241 days, respectively. Although clinical benefit was similar in both types of therapy, median survival time was more favorable for GEM, especially for Stage IVb. Nausea and vomiting were the most commonly observed toxicity in the FP therapy group. Our data indicate that FP therapy is not considered to be a useful second-line agent in patients with GEM pretreated pancreatic cancer.