Quantification of Pancreatic Stiffness on Intraoperative Ultrasound Elastography and Evaluation of its Relationship With Postoperative Pancreatic Fistula

“Soft pancreas” has often been reported as a predictive factor for postoperative pancreatic fistula (POPF) after pancreatectomy. However, pancreatic stiffness is judged subjectively by surgeons, without objective criteria. In the present study, pancreatic stiffness was quantified using intraoperative ultrasound elastography, and its relevance to POPF and histopathology was investigated. Forty-one patients (pancreatoduodenectomy, 30; distal pancreatectomy, 11) who underwent intraoperative elastography during pancreatectomy were included. The elastic ratio was determined at the pancreatic resection site (just above the portal vein) and at the remnant pancreas (head or tail). Correlations between the incidence of POPF and patient characteristics, operative variables, and the elastic ratio were examined. In addition, the relationship between the elastic ratio and the percentage of the exocrine gland at the resection stump was investigated. For pancreatoduodenectomy patients, main pancreatic duct diameter < 3.2 mm and elastic ratio < 2.09 were significant risk factors for POPF. In addition, the elastic ratio, but not main pancreatic duct diameter, was significantly associated with the percentage of exocrine gland area at the pancreatic resection stump. Pancreatic stiffness can be quantified using intraoperative elastography. Elastography can be used to diagnose “soft pancreas” and may thus be useful in predicting the occurrence of POPF.Key words: Elastography, Exocrine gland, Pancreatectomy, Pancreatic stiffness, Postoperative pancreatic fistulaDespite current advances in surgical techniques, pancreatectomy is a very difficult procedure associated with the risk of multiple postoperative complications. The morbidity and mortality are reported to be 20–50% and 1–5%, respectively.¹ In particular, a postoperative pancreatic fistula (POPF) can sometimes lead to life-threatening complications, such as hemoperitoneum and sepsis. The worldwide incidence of POPF is reported to be 5–50%. Several predictive factors for POPF have been reported to date, and, of these, “soft pancreas” has often been mentioned.^2–4 However, in all of these reports, evaluation of pancreatic stiffness has depended on subjective judgment by the surgeon, without objective parameters as criteria.Elastography has recently been developed to enable real-time visualization of the relative stiffness of tissue elasticity, and its usefulness in various clinical disciplines for tumor diagnosis and differential diagnosis has been described.⁵ In gastroenterology, evaluation of liver fibrosis and diagnosis of pancreatic tumors and chronic pancreatitis using endoscopic ultrasound (EUS) have been reported,^6,7 but the use of elastography in surgery has not been reported. An objective assessment of pancreatic stiffness as a predictive risk factor for POPF can help in choosing the intraoperative surgical technique and in planning the postoperative management strategy. Therefore, in the present study, pancreatic stiffness was quantified using intraoperative ultrasound elastography, and its relevance to POPF and histopathology was investigated.     

Development of 18 novel polymorphic microsatellite markers for the mysid crustacean Mesopodopsis orientalis

Conservation Genetics Resources - We have developed microsatellite DNA markers for Mesopodopsis orientalis (Tattersall 1908), a widely distributed mysid crustacean in shallow waters of the coastal...     

Presence of anti-DNA antibody in diabetes mellitus: its relation to the duration of diabetes and diabetic complications

In seven patients with insulin-dependent diabetes mellitus (IDDM) and 86 patients with non-insulin-dependent diabetes mellitus (NIDDM), serum anti-DNA antibody was measured by a semiquantitative radioimmunoassay (RIA) method. Prevalence of positive anti-DNA antibody (more than 20 U/mL) was five of seven in IDDM patients, 15 of 36 in NIDDM patients with insulin therapy, and seven of 50 in NIDDM patients without insulin therapy. None of normal subjects or patients with impaired glucose tolerance (IGT) showed positive anti-DNA antibody. The titer of anti-DNA antibody was higher in IDDM patients than in age-matched normal subjects (mean +/- SD; 22.1 +/- 15.3 v 6.5 +/- 2.2 U/mL, P less than .05). In patients with NIDDM, the antibody titer regardless of insulin treatment, was higher than in age-matched subjects with IGT (18.5 +/- 13.1 U/mL in NIDDM patients receiving insulin, 14.8 +/- 8.1 U/mL in NIDDM patients not receiving insulin, and 8.8 +/- 3.9 U/mL in IGT patients [P less than .001] for either of NIDDM groups v IGT). The titer of anti-DNA antibody was positively correlated with the duration of diabetes (r = .413, P less than .001) and with the postprandial blood glucose level (r = .311, P less than .01) in NIDDM patients when all of them were combined and analyzed as a group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene,OCTN2

The purpose of this study was to test whether heterozygotes of juvenile visceral steatosis mice, a model for systemic carnitine deficiency, may develop age-associated cardiomyopathy. Tissue morphological observations were carried out by light and electron microscopy to compare the heterozygous and age-matched control mice at periods of 1 and 2 years. Possible effects of the pathological mutation on lipid and glucose levels was also evaluated in humans and mice. Except mild increases in serum cholesterol levels in male heterozygous mice and humans, no changes were found in other factors, indicating that none of the confounding factors seems to be profound. Results demonstrated that heterozygous mice had larger left ventriclular myocyte diameters than the control mice. Morphological changes in cardiac muscles by electron microscopy revealed age-associated changes of lipid deposition and abnormal mitochondria in heterozygous mice. Two out of 60 heterozygous cohort and one out of nine heterozygous trim-kill mice had cardiac hypertrophy at ages older than 2 years. The present study and our previous work suggest that the carrier state of OCTN2 pathological mutations might be a risk factor for age-associated cardiomyopathy.     

Clinical outcome of endoscopic aspiration mucosectomy for early stage gastric cancer

BACKGROUND: Endoscopic mucosal resection is an established treatment option for early stage gastric cancer. However, several problems with endoscopic mucosal resection remain to be solved, such as appropriate treatment for recurrence and incomplete tumor resection. The outcome for patients undergoing endoscopic aspiration mucosectomy (endoscopic mucosal resection) by a modification of the cap-fitted technique was evaluated retrospectively to determine factors associated with complete resection and tumor recurrence. METHODS: Endoscopic mucosal resection was performed in 106 patients with early stage gastric cancers up to 20 mm in diameter that were well or moderately differentiated adenocarcinoma. All were superficial lesions without ulceration, distinct signs of submucosal invasion, or a poorly demarcated border. En bloc (tumors <10 mm in diameter) or piecemeal (tumors 10-20 mm in diameter) resection was performed. Follow-up endoscopy was performed at 2, 6, 12, 18, and 24 months and thereafter once per year. Outcome and factors associated with complete resection and tumor recurrence were assessed retrospectively. RESULTS: Sixty-eight patients (64%) underwent en bloc resection and 38 (36%) piecemeal resection. The mean longest dimension (SD) of the resected lesions was significantly greater after piecemeal resection (12.3 [4.0] mm) than after en bloc resection (7.6 [4.0] mm; p < 0.01). In patients with tumors completely resected, there was no recurrence after either en bloc or piecemeal resection. Six of 8 patients found to have submucosal invasion after endoscopic mucosal resection underwent surgery. Patients with incompletely resected intramucosal lesions underwent additional endoscopic treatment. Cancer recurred in 3 patients (2.8%), all of whom had lesions measuring more than 15 mm in diameter. CONCLUSIONS: Endoscopic mucosal resection is safe and useful for the management of early stage gastric cancer. Further improvement in outcome requires more accurate preoperative diagnosis and postoperative histopathologic evaluation. Patients with incompletely resected lesions should undergo aggressive additional treatment.     

Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential

Insulin release from pancreatic islet beta-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, a novel acylated 28-amino acid peptide isolated from stomach, is the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelin is produced predominantly in stomach. Ghrelin is a potent stimulator of GH release and feeding as well as exhibiting positive cardiovascular effects. In relation to the glucose metabolism, initial studies indicated that low plasma ghrelin levels are associated with elevated fasting insulin levels, insulin resistance, and obesity. It has recently been demonstrated that ghrelin suppresses glucose-induced insulin release via G alpha(i2) subtype of GTP-binding proteins and delayed outward K(+) (Kv) channels, representing a novel signaling mechanism, and that the ghrelin originating from islets regulates insulin release and thereby glycemia. Furthermore, elimination of ghrelin enhances insulin release to prevent or ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the physiological roles of ghrelin in regulating insulin release and glycemia, the insulinostatic mechanisms of ghrelin in islet beta-cells, and the potential of ghrelin-GHS-R system as the therapeutic target to treat type 2 diabetes.     

Analysis of BRCAness with multiplex ligation-dependent probe amplification using formalin-fixed and paraffin-embedded pancreatic ductal adenocarcinoma tissue obtained via endoscopic ultrasound-guided fine-needle aspiration biopsy

Background/Objectives

A breakthrough in chemotherapy for pancreatic ductal adenocarcinoma (PDAC) may be achieved using precision medicine, which involves identifying cases that are highly likely to respond to a certain treatment and then performing that treatment. BRCAness has been receiving attention as a novel predictor of anticancer drug sensitivity in PDAC, making the screening of BRCAness paramount.

Susceptibility of muridae cell lines to ecotropic murine leukemia virus and the cationic amino acid transporter 1 viral receptor sequences: implications for evolution of the viral receptor

Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV infection, and treatment of rat and hamster cells with a glycosylation inhibitor, tunicamycin, enhances Eco-MLV infection. Although the mouse CAT1 is also glycosylated, it does not inhibit Eco-MLV infection. Comparison of amino acid sequences between the rat and mouse CAT1s shows amino acid insertions in the rat protein near the Eco-MLV-binding motif. In addition to the insertion present in the rat CAT1, the hamster CAT1 has additional amino acid insertions. In contrast, tunicamycin treatment of mink and human cells does not elevate the infection, because their CAT1s do not have the Eco-MLV-binding motif. To define the evolutionary pathway of the Eco-MLV receptor, we analyzed CAT1 sequences and susceptibility to Eco-MLV infection of other several murinae animals, including the southern vole (Microtus rossiaemeridionalis), large Japanese field mouse (Apodemus speciosus), and Eurasian harvest mouse (Micromys minutus). Eco-MLV infection was enhanced by tunicamycin in these cells, and their CAT1 sequences have the insertions like the hamster CAT1. Phylogenetic analysis of mammalian CAT1s suggested that the ancestral CAT1 does not have the Eco-MLV-binding motif, like the human CAT1, and the mouse CAT1 is thought to be generated by the amino acid deletions in the third extracellular loop of CAT1.     

Usefulness of autotaxin for the complications of liver cirrhosis

BACKGROUND Autotaxin(ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC) are scant.AIM To assess the clinical usefulness of ATX for assessing the complications of LC.METHODS This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve(AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin(ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index.RESULTS The mean age was 68.4 ± 11.4 years, 240 patients(60.0%) were male. A total of 213(53.3%) and 187(46.8%) patients were compensated and decompensated,respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35(8.8%), 131(32.8%), and 103(25.8%),respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX.CONCLUSION ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.