Implications of arterial anatomy in patients with cancer of the periampullary region

BACKGROUND/AIMS: Preoperative information on arterial anatomy in the peripancreatic and hepatic areas is valuable to any surgeon performing pancreatoduodenectomy. METHODOLOGY: Between 1994 and 1998, 49 patients with periampullary cancer (31 distal bile duct and 18 ampullary tumors) underwent visceral angiography and radical pancreatoduodenectomy with lymphadenectomy. Surgically "significant" arterial variations and their effects on operative management and results were examined retrospectively. RESULTS: Arterial variations were found in 18 patients (37%); 15 (31%) were "significant" and 3 (6%) were "nonsignificant." All 15 patients with "significant" variants required specific type of various preservations of the hepatic arterial system. Intraoperative blood loss, transfused blood units, and operation time were greater in patients with "significant" variations than in patients without (P<0.05). Histopathologic diagnosis, tumor staging, morbidity, and mortality did not differ between the 2 groups. The 5-year survival was 33% for patients with "significant" variations and 63% for patients without (P<0.05). CONCLUSIONS: Information on arterial anatomy in the peripancreatic and hepatic areas is necessary for preoperative evaluation in patients requiring radical pancreatoduodenectomy. Presence of "significant" arterial variations may be considered as one of the negative prognostic factors in patients with periampullary cancer.     

An extramural gastrointestinal stromal tumor of the duodenum mimicking a pancreatic head tumor

We report the case of a 53‐year‐old woman with a gastrointestinal stromal tumor (GIST) of the duodenum that showed only extramural growth, mimicking a pancreatic tumor. Preoperatively, computed tomography (CT) and angiography revealed a hypervascular mass, 3.0 cm in diameter, in the pancreatic head. Hypotonic duodenography showed compression of the second and third portions of the duodenum by the pancreatic lesion. Endoscopic examination showed no specific mucosal abnormalities in the duodenal lumen. The pancreatic head tumor was diagnosed preoperatively as a nonfunctioning islet cell tumor of the pancreas, and the patient underwent pylorus‐preserving pancreaticoduodenectomy. A hard mass was palpated intraoperatively in the pancreatic head region, and neither peritoneal dissemination nor metastasis was detected. Histologically, the tumor was composed of spindle‐shaped cells with a fascicular growth pattern, and only a few mitotic features were seen. Immunohistochemically, most of the tumor cells were positive for c‐kit oncoprotein and CD34, but negative for alpha‐smooth muscle actin and S‐100 protein. Therefore, this neoplasm was finally diagnosed as a duodenal GIST of the uncommitted type. This is a rare case of a duodenal GIST with exclusively extramural growth mimicking a pancreatic head tumor.     

Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients.     

Absorption,distribution, metabolism and excretion of novel phosphodiesterase type 4 inhibitor ASP3258 in rats

The potent and selective phosphodiesterase 4 inhibitor ASP3258 is a novel therapeutic agent for asthma and chronic obstructive pulmonary disease (COPD). After a single oral administration to rats, ASP3258 is rapidly absorbed with a bioavailability of 106%. In situ absorption data indicated that ASP3258 is mainly absorbed in the small intestine. Tissue distribution data after oral administration of ¹⁴C‐ASP3258 showed rapid and extensive distribution to various tissues. Excluding the gastrointestinal tract, the tissues with the highest concentrations were liver, heart and plasma. Liquid chromatography‐nuclear magnetic resonance spectroscopy data revealed that O‐glucuronidation of the carboxylic acid moiety of ASP3258 (formation of an acyl glucuronide) plays a key role in metabolism. No indication was found that the acyl glucuronide reacted with proteins in plasma or tissues. When ¹⁴C‐ASP3258 was orally administered to intact rats, urinary and fecal excretion accounted for 1.3% and 100.6% of the administered radioactivity, respectively. After a single oral administration of ¹⁴C‐ASP3258 to bile‐cannulated rats, urinary and biliary excretion accounted for 0.7% and 93.8% of the administered radioactivity, respectively. These findings suggest that fecal excretion via bile plays an important role in the elimination of ASP3258‐derived radioactivity. In vitro metabolic profiles were relatively similar among the species examined, suggesting that our findings in rats may help us to understand pharmacokinetics, efficacy and safety profiles in humans and other species. Copyright © 2014 John Wiley & Sons, Ltd.     

Increased DNA-incorporated thiopurine metabolite as a possible mechanism for leukocytopenia through cell apoptosis in inflammatory bowel disease patients with NUDT15 mutation

Journal of Gastroenterology - Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory...     

Interleukin-18 overproduction exacerbates the development of colitis with markedly infiltrated macrophages in interleukin-18 transgenic mice

BACKGROUND AND AIM: The authors have previously shown that production of interleukin (IL)-18 was increased in the inflamed mucosa of patients with Crohn's disease (CD) and blockade of IL-18 ameliorated the murine model of CD. This demonstrated that IL-18 plays a significant role during intestinal inflammation. However, the initial role of IL-18 during intestinal inflammation was unclear; therefore the susceptibility of IL-18 transgenic (Tg) mice to acute dextran sulfate sodium (DSS)-induced colitis was examined. METHODS: Interleukin-18 Tg and wild-type (WT) mice were fed 2.0% of DSS for 8 days. The total clinical scores (bodyweight loss, stool consistency, and rectal bleeding), colon length and histological scores were assessed. The expressions of surface markers and IL-18 on infiltrating lamina propria mononuclear cells were analyzed immunohistochemistrically. Mesenteric lymph node (MLN) cells were isolated and the expressions of CD4+ T-cell activation markers (CD69, CD25 and IL18R) were analyzed by flow cytometry. RESULTS: The IL-18 Tg mice exhibited an increased susceptibility to DSS-induced colitis, as shown by significantly increased clinical, histological scores, and more severe colonic shortening compared with WT mice. Immunohistochemical analysis revealed a significant increase of IL-18 production and CD11b+ macrophages but not CD4+ T cells in the inflamed mucosa in DSS-fed IL-18 Tg compared with DSS-fed WT mice. Furthermore, MLN cells revealed no evidence of increased CD4+ T-cell activation in DSS-fed IL-18 Tg. CONCLUSIONS: These findings suggest that IL-18 overproduction in the mucosa plays an important role in the marked infiltration of macrophages and exacerbates colitis in IL-18 Tg mice.     

Antisense oligonucleotides of hepatoma-derived growth factor (HDGF) suppress the proliferation of hepatoma cells

BACKGROUND/AIMS: Human hepatoma-derived growth factor, purified from the conditioned medium of hepatoma-derived cell line, HuH-7, stimulates the growth of Swiss 3T3 fibroblasts and HuH-7 cells. To evaluate the role of hepatoma-derived growth factor on the growth of hepatoma cells, we investigated the effects of recombinant hepatoma-derived growth factor protein and hepatoma-derived growth factor antisense oligonucleotides on the proliferation of several hepatoma cell lines. METHODOLOGY: We examined the effects of hepatoma-derived growth factor antisense oligonucleotides on the growth of hepatoma cells by cell growth assay. RESULTS: Hepatoma-derived growth factor stimulated the proliferation of some hepatoma cells (HuH-7, HLF, HepG2, AH66tc cells) about 15-70% over than the control. Hepatoma-derived growth factor antisense oligonucleotides, phosphorothioate-linked or encapsulated in liposome, can inhibit the growth of hepatoma cells. The ID50 of hepatoma-derived growth factor antisense phosphorothioate oligonucleotides for HuH-7 cells, in which hepatoma-derived growth factor expression was abundant, was 3 microM by the assay of cell proliferation and [3H]-thymidine incorporation. Their ID50 for AH66tc cells, on which the effects of exogenous hepatoma-derived growth factor were weak, was higher than 10 microM. To omit the toxic effects due to phosphorothioate modification of oligonucleotides and keep the cellular uptake more without their destruction in the culture medium, we used oligonucleotides encapsulated in cationic liposome. Hepatoma-derived growth factor antisense oligonucleotides encapsulated in liposome suppressed the growth of hepatoma cells effectively (ID50:2.0 microM). CONCLUSIONS: These findings suggest that hepatoma-derived growth factor is one of important autocrine, and/or intracrine factors for hepatoma cells, and that hepatoma-derived growth factor anti-sense oligonucleotides may be useful for human hepatocellular carcinoma as an anti-cancer agent.     

Helicobacter pylori is a fragile bacteria when stored at low and ultra-low temperatures

BACKGROUND AND AIM: Usually, bacteria are cryopreserved for short-term storage at low and ultra-low temperatures. There are no reports as to whether Helicobacter pylori is a fragile bacteria when stored at low and ultra-low temperatures as compared with other intestinal bacteria. A study was done on seven H. pylori strains and other intestinal bacteria to compare different temperatures for storage of organisms in saline solution. METHODS: Seven H. pylori strains, specifically American Type Culture Collection (ATCC) strains 43504 and TN2GF4, and five strains isolated from the present patients were grown on a modified Skirrow's agar for H. pylori. Escherichia coli and Bacteroides distasonis, both representing isolates from the present patients, were grown on trypticase soy blood agar for E. coli, and EG agar for B. distasonis. Culture was for 4-5 days under microaerobic, aerobic and anaerobic conditions at 37 degrees C. Cells were harvested by scraping growth from the solid medium and into sterile saline. The cells were adjusted to concentrations of 109 viable cells/mL in saline and preserved at 4 degrees C, -20 degrees C, or -80 degrees C for 3 weeks before reculture under microaerobic, aerobic and anaerobic conditions at 37 degrees C for 7 days. After incubation, morphologically distinct colonies were counted, isolated, and identified by standard bacteriologic techniques. The H. pylori were morphologically analyzed by electronic microscopy before and after preservation. Mongolian gerbils were inoculated with the cryopreserved H. pylori to evaluate the bacterial infectivity. RESULTS: Six of the seven H. pylori strains failed to culture after being preserved at 4 degrees C, -20 degrees C, or -80 degrees C. Only ATCC 43504 could be cultured after freezing at -80 degrees C. The number of H. pylori ATCC 43504 before preservation was 9.0 +/- 0.5 (log10 no. organisms/mL) and decreased to 5.7 +/- 0.6 after preservation. Morphologically, all H. pylori except ATCC 43504 strains transformed from a bacillary to a coccoid form after preservation. In addition, none of the H. pylori strains could infect Mongolian gerbils after preservation. Escherichia coli and B. distasonis were recovered. Titers before and after 4 degrees C, -20 degrees C, and -80 degrees C, respectively, were 9.1 +/- 0.2, 8.9 +/- 0.5, 8.6 +/- 0.3, and 8.7 +/- 0.3 for E. coli and 9.1 +/- 0.4, 8.7 +/- 0.6, 8.6 +/- 0.5, and 8.8 +/- 0.3 for B. distasonis. CONCLUSIONS: Helicobacter pylori is a fragile bacteria for storage at low and ultra-low temperatures in comparison with other intestinal bacteria.     

Disease-specific screening for deep venous thrombosis and pulmonary thromboembolism using plasma <Emphasis Type="SmallCaps">d</Emphasis>-dimer values after total knee arthroplasty

We prospectively evaluated the disease-specific features of the early postoperative plasma D: -dimer value and the relationship with deep venous thrombosis and/or pulmonary thromboembolism (DVT/PE) in 95 patients following total knee arthroplasty. Patients in whom DVT/PE was highly suspected were diagnosed by high-resolution multi-detector row computed tomography scanning (MDCT). Forty-nine knees in 46 patients with rheumatoid arthritis (RA, 24 knees) or osteoarthritis (OA, 25 knees) were finally recruited. DVT/PE was detected in 28 (57.1%) of the 49 cases examined by diagnostic MDCT: 12 (50.0%) of the 24 cases of RA, and 16 (64.0%) of the 25 cases of OA. Of these, PE was found in 11 cases (39.2%), but none of them showed clinical symptomatic signs of dyspnea or chest pain. In both RA and OA cases, there were statistically significant differences in the D: -dimer value on postoperative day 3 (P = 0.027) and after day 28 (P = 0.037) between the groups with and without DVT/PE. In OA cases, there were significant differences between the two groups on postoperative days 1 (P = 0.034), 3 (P = 0.020), 5 (P = 0.005), and 7 (P = 0.045), respectively. At the baseline, perioperative D: -dimer levels in the RA group without DVT/PE were higher than in the OA group. However, multivariate logistic regression analysis showed that RA was not a significant risk factor of DVT/PE in comparison with OA. In conclusion, individual evaluation of the D: -dimer level between RA and OA should provide a more precise predictive indicator of early postoperative DVT/PE.