Localized esophageal ulcerations after CyberKnife treatment for metastatic hepatic tumor of colon cancer.

CyberKnife is an image-guided robotic system designed for stereotactic radiosurgery. It uses the combination of robotics and image guidance to deliver concentrated and accurate beams of radiation to intracranial and extracranial targets. Although the frameless nature of the CyberKnife allows tumors in the chest and abdomen to be treated as well, complications associated with CyberKnife treatment have not been established yet due to its short clinical experience. We describe a case of localized esophageal ulcerations after CyberKnife treatment for metastatic hepatic tumor of colon cancer.     

DEVOTE 3: temporal relationships between severe hypoglycaemia,cardiovascular outcomes and mortality

Aims/hypothesis

The double-blind Trial Comparing Cardiovascular Safety of Insulin Degludec vs Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE) assessed the cardiovascular safety of insulin degludec. The incidence and rates of adjudicated severe hypoglycaemia, and all-cause mortality were also determined. This paper reports a secondary analysis investigating associations of severe hypoglycaemia with cardiovascular outcomes and mortality.

Methods

In DEVOTE, patients with type 2 diabetes were randomised to receive either insulin degludec or insulin glargine U100 (100 units/ml) once daily (between dinner and bedtime) in an event-driven, double-blind, treat-to-target cardiovascular outcomes trial. The primary outcome was the first occurrence of an adjudicated major adverse cardiovascular event (MACE; cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Adjudicated severe hypoglycaemia was the pre-specified secondary outcome. In the present analysis, the associations of severe hypoglycaemia with both MACE and all-cause mortality was evaluated in the pooled trial population using time-to-event analyses, with severe hypoglycaemia as a time-dependent variable and randomised treatment as a fixed factor. An investigation with interaction terms indicated that the effect of severe hypoglycaemia on the risk of MACE and all-cause mortality were the same for both treatment arms, and so the temporal association for severe hypoglycaemia with subsequent MACE and all-cause mortality is reported for the pooled population.

Results

There was a non-significant difference in the risk of MACE for individuals who had vs those who had not experienced severe hypoglycaemia during the trial (HR 1.38, 95% CI 0.96, 1.96; p = 0.080) and therefore there was no temporal relationship between severe hypoglycaemia and MACE. There was a significantly higher risk of all-cause mortality for patients who had vs those who had not experienced severe hypoglycaemia during the trial (HR 2.51, 95% CI 1.79, 3.50; p < 0.001). There was a higher risk of all-cause mortality 15, 30, 60, 90, 180 and 365 days after experiencing severe hypoglycaemia compared with not experiencing severe hypoglycaemia in the same time interval. The association between severe hypoglycaemia and all-cause mortality was maintained after adjustment for the following baseline characteristics: age, sex, HbA_1c, BMI, diabetes duration, insulin regimen, hepatic impairment, renal status and cardiovascular risk group.

Conclusions/interpretation

The results from these analyses demonstrate an association between severe hypoglycaemia and all-cause mortality. Furthermore, they indicate that patients who experienced severe hypoglycaemia were particularly at greater risk of death in the short term after the hypoglycaemic episode. These findings indicate that severe hypoglycaemia is associated with higher subsequent mortality; however, they cannot answer the question as to whether severe hypoglycaemia serves as a risk marker for adverse outcomes or whether there is a direct causal effect.

Trial registration

ClinicalTrials.gov NCT01959529

     

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.     

Efficacy and safety of argatroban with or without glycoprotein IIb/IIIa inhibitor in patients with heparin induced thrombocytopenia undergoing percutaneous coronary intervention for acute coronary syndrome

Background There is limited experience with the use of argatroban in combination with glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor in acute coronary syndrome (ACS) patients with heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention (PCI). Materials and methods This single-center, retrospective study evaluated the efficacy (composite of death, myocardial infarction, or urgent revascularization) and safety (evaluated by TIMI major bleeding) of the argatroban with or without a GPIIb/IIIa inhibitor during PCI. Among 102 consecutive ACS patients (71.6% unstable angina or NSTEMI and 28.4% STEMI) who received argatroban (239 ± 104 μg/kg bolus, followed by a 17 ± 11 μg/kg/min infusion) for confirmed or suspected HIT during PCI, 52 patients (51%) received a GPIIb/IIIa inhibitor simultaneously (86% integrilin, 10% tirofiban, 4% abciximab) and 50 patients (49%) did not. Results There was no difference between the groups in the efficacy endpoint, which occurred in nine patients (17.3%) who received GPIIb/IIIa inhibitor and in eight patients (16%) who did not (P = 0.70). TIMI major bleeding occurred in three (5.8%) patients in the GPIIa/IIIb inhibitor group versus 0 (0%) patients in the argatroban alone group (P = 0.085). Conclusion In patients with suspected or confirmed HIT undergoing PCI for ACS, argatroban with or without GPIIb/IIIa appears to provide adequate anticoagulation and is well tolerated with a low rate of bleeding.     

KML001, an arsenic compound,as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Background

Sodium meta-arsenite (NaAsO₂, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer (BTC) resistant to gemcitabine-based chemotherapy.

Expression of hedgehog proteins in periampullary cancer]

BACKGROUND/AIMS: Hedgehog protein is an essential molecule for gastrointestinal tract development, and disruption of hedgehog signaling pathway is linked to some gastrointestinal tumorigenesis. Here, we performed hedgehog immunostaining in periampullary cancer to evaluate the differences according to the location type of cancer and the differentiation of adenocarcinoma. METHODS: We retrieved surgical specimens from 43 periampullary cancer patients (15 ampulla of Vater cancer, 12 distal common bile duct cancer, 13 pancreatic head cancer, and 3 combined ampulla of Vater/bile duct cancer). Immunohistochemical stain was performed in both normal and cancerous tissue portions of each case using Sonic hedgehog (H-160) rabbit polyclonal antibody. Immunohistochemical stain results were grouped into three groups according to the percentage of positive cytoplasmic stain in tumor volume (unstained: <5%, weakly stained: 5-50%, and strongly stained: >50%). RESULTS: All of the normal tissue revealed negative immunohistochemical stain while cancerous tissue revealed positivity in 95.3% (41/43 cases). Strongly stained cases were more frequently seen in ampulla of Vater cancers (13/15) and in combined ampulla of Vater/bile duct cancers (3/3) than in distal common bile duct cancers (4/12) and in pancreatic head cancers (3/13) (p=0.002). In addition, strongly stained cases were more frequently seen in well-differentiated adenocarcinoma than the others (p<0.001). CONCLUSIONS: Most of the periampullary cancers show hedgehog protein expression. In addition, hedgehog protein immunostainings shows stronger expression in ampulla of Vater cancers and in well-differentiated adenocarcinoma.     

Comparison of Helicobacter pylori eradication rate according to different PPI-based triple therapy--omeprazole, rabeprazole, esomeprazole and lansoprazole--]

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is an important cause of various gastrointestinal diseases. H. pylori eradication is essential for the cure and prevention of associated diseases. Nowdays, proton pump inhibitor (PPI)-based triple therapy is the standard eradication regimen. The aims of this study were to compare the H. pylori eradication rate of different PPI-based triple therapies and to find out the factors influencing the eradication rate. METHODS: From May 2002 through February 2004, H. pylori infected patients were treated with the eradication regimen based on one of the four PPIs (omeprazole, rabeprazole, esomeprazole and lansoprazole) for 1 or 2 weeks. After two weeks, drug compliance, adverse effects, and smoking history during the eradication therapy were obtained. The follow-up H. pylori test was performed 4 weeks after the completion of therapy. The data were analyzed by Chi-square test and multiple logistic regression analysis. RESULTS: Overall eradication rate was 83.5%. There was no significant difference in eradication rate among four PPIs (p=0.379). Odds ratio (OR) for omeprazole and rabeprazole was 1.15 (95% CI 0.50-2.68); for omeprazole and esomeprazole, OR 1.63 (95% CI 0.68-3.89); and for omeprazole and lansoprazole, OR 1.13 (95% CI 0.50-2.56). Smoking habit, site of ulcer, and the duration of therapy affected the eradication rate significantly. CONCLUSIONS: The efficacy of four different PPIs for H. pylori eradication is similar to each other. Smoking, site of ulcer, and the duration of treatment have significant effects on eradication rates.     

Roles for both cyclic GMP and cyclic AMP in the inhibition of collagen-induced platelet aggregation by nitroprusside

In studies on human platelets, nitroprusside (NP) alone at 1-10 micromol/l increased platelet cyclic AMP (cAMP) by 40-70%, whereas increases in cyclic GMP (cGMP) were much larger in percentage though not in concentration terms. Collagen enhanced these increases in cAMP up to fourfold, without affecting cGMP. This effect was partly prevented by indomethacin or aspirin, indicating that platelet cyclo-oxygenase products acted synergistically with NP to increase cAMP. ADP released from the platelets by collagen tended to restrict this cAMP accumulation. Addition of 2',5'-dideoxyadenosine (DDA), an inhibitor of adenylyl cyclase, decreased both the inhibition of collagen-induced platelet aggregation by NP and the associated accumulation of cAMP without affecting cGMP, indicating that cAMP mediates part of the inhibitory effect of NP. Unlike DDA, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of guanylyl cyclase, blocked all increases in both cGMP and cAMP caused by NP, as well as the inhibition of platelet aggregation, suggesting that cAMP accumulation was secondary to that of cGMP. Human platelet cGMP-dependent protein kinase (PKG) coelectrophoresed with the purified bovine type Ibeta isoenzyme. An inhibitor of this enzyme (Rp)-beta-phenyl-1,N2-etheno-8-bromoguanosine 3',5'-cyclic-monophosphorothioate, diminished the inhibition of collagen-induced platelet aggregation by NP, but had little additional effect when DDA was present. This showed that both PKG and cAMP participate in the inhibition of collagen-induced platelet aggregation by NP. Moreover, selective activators of PKG and cAMP-dependent protein kinases had supra-additive inhibitory effects, suggesting that an optimal inhibitory effect of NP requires simultaneous activation of both enzymes.     

Relationship between pepsinogen I/II ratio and age or upper gastrointestinal diseases in Helicobacter pylori-positive and -negative subjects]

BACKGROUND/AIMS: Although previous reports suggested that pepsinogen (PG) I/II ratio was the index of gastric atrophy, PG I/II ratio was also related to other factors such as Helicobacter pylori (H. pylori) infection, various gastrointestinal diseases, and aging. The aim of this study was to evaluate the relationship between serum PG I/II ratio and age or upper gastro-intestinal diseases according to H. pylori infection status. METHODS: A total of 529 individuals (307 male; mean age, 57.2 years) were divided into 4 groups (94 gastric ulcers, 35 duodenal ulcers, 105 reflux esophagitis, and 295 atrophic gastritis) according to endoscopic diagnosis. H. pylori infection was determined by H. pylori IgG antibody (ELISA) and PG was measured by latex immunoassay. RESULTS: H. pylori infected patients showed markedly increased serum PG II levels (24.0+/-14.7 ng/mL vs. 13.8+/-16.6 ng/mL, p0.001) and low PG I/II ratio (3.9+/-2.0 vs. 6.0+/-2.5, p0.001) than non-infected subjects. In H. pylori infected patients, mean PG I/II ratios in the gastric ulcer and atrophic gastritis group were significantly lower than those of the duodenal ulcer and reflux esophagitis group (p0.001, ANOVA, Turkey's multiples comparison test). The mean ratio of open type atrophic gastritis was lower than that of close type atrophic gastritis (3.0+/-1.4 vs. 3.8+/-1.7, p0.005). PG I/II ratio gradually decreased with age in H. pylori-infected patients with atrophic gastritis (R(2)=0.9, p=0.005, linear regression analysis). CONCLUSION: Serum PG I/II ratio reflects H. pylori infection and gastric atrophy. In the presence of H. pylori infection, gastric atrophy progresses with age.