Pharmacogenetic assessment of clinical outcome in patients with metastatic breast cancer treated with docetaxel plus capecitabine

Purpose

Docetaxel plus capecitabine, a commonly used chemotherapeutic regimen for metastatic breast cancer (MBC), is highly variable in its effectiveness. We aimed to investigate whether allelic variants of cytochrome P450 (CYP450) affected objective response, progression-free survival (PFS), and overall survival (OS) in MBC.

Patients and methods

79 SNPs in CYP450, whose minor allele frequency were ≥10%, were genotyped in 69 MBC patients who were treated with docetaxel plus capecitabine. Pearson’s χ² test or Fisher’s exact test was used to investigate the influence of SNPs on objective response as appropriate. Log-rank test was used to assess the association between SNPs and survival outcomes.

Results

There is no significant association between polymorphisms and both objective response and OS. Only one SNP, CYP1A1 rs1048943 A>G (Ile462Val), was significantly associated with PFS (P?=?0.0003). Multivariate analysis confirmed its prognostic significance for PFS (P?=?0.004).

Conclusion

CYP1A1 rs1048943 A>G (Ile462Val) polymorphism is a potential prognostic marker for survival outcome after docetaxel plus capecitabine chemotherapy in MBC patients. However, confirmatory study is needed to validate this finding.     

HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased insulin secretion

Aims/hypothesis

We sought to identify the physiological implications of genetic variation at the HLA-DRB1 region in full-heritage Pima Indians in Arizona.

Methods

Single-nucleotide polymorphisms from the HLA region on chromosome 6p were tested for association with skeletal muscle mRNA expression of HLA-DRB1 and HLA-DRA, and with type 2 diabetes mellitus and prediabetic traits.

Results

The A allele at rs9268852, which tags HLA-DRB1*02(1602), was associated both with higher HLA-DRB1 mRNA expression (n?=?133, p?=?4.27?×?10^?14) and decreased risk of type 2 diabetes (n?=?3,265, OR 0.723, p?=?0.002). Among persons with normal glucose tolerance (n?=?266) this allele was associated with a higher mean acute insulin response during an intravenous glucose tolerance test (p?=?0.005), higher mean 30?min insulin concentration during an oral glucose tolerance test (p?=?0.017) and higher body fat percentage (p?=?0.010). The polymorphism was not associated with HLA-DRA mRNA expression or insulin sensitivity.

Conclusions/interpretation

HLA-DRB1*02 is protective for type 2 diabetes, probably by enhancing self tolerance, thereby protecting against the autoimmune-mediated reduction of insulin secretion.     

Branched-chain amino acid-enriched nutrients improve nutritional and metabolic abnormalities in the early post-transplant period after living donor liver transplantation

Background/purpose

Malnutrition and metabolic disorder of patients undergoing living donor liver transplantation (LDLT) can affect post-transplant prognosis. The aim of this study was to establish whether perioperative usage of branched-chain amino-acid (BCAA)-enriched nutrients improve metabolic abnormalities of patients undergoing LDLT.

Methods

We designed a randomized pilot study (UMIN registration number; 000004323). Twenty-five consecutive adult elective LDLT recipients were enroled and divided into two groups: the BCAA group (BCAA-enriched nutrients, n?=?12) and the control group (standard diet, n?=?13). Metabolic and nutritional parameters, including BCAA-to-tyrosine ratio (BTR), retinol binding protein (RBP), and prealbumin were regularly measured from 1?week before to 4?weeks after LDLT. Non-protein respiratory quotient (npRQ) was measured before and 4?weeks after LDLT.

Results

BTR and RBP improved considerably in the BCAA group compared with the controls. npRQ significantly increased from 1?week before LDLT to 4?weeks after LDLT in the BCAA group (0.77?±?0.05 to 0.84?±?0.06, P?=?0.002), but not in the control group (0.78?±?0.04 to 0.81?±?0.05).

Conclusions

Supplementation with BCAA-enriched nutrients might improve persistent nutritional and metabolic disorders associated with end-stage liver disease in the early post-transplant period, and consequently shorten the post-transplant catabolic phase after LDLT. A larger multicenter trial is needed to confirm these findings.     

Cost analysis of adult�Cadult living donor liver transplantation in Tokyo University Hospital

Background and purpose

Living donor liver transplantation (LDLT) is now a well established treatment modality for end-stage liver diseases, but the financial aspects of LDLT have not yet been fully investigated. The purpose of this study was to determine the overall direct cost of adult?Cadult LDLT in Japan and to identify the factors associated with the high cost.

Materials and methods

The direct cost of initial admission for LDLT was determined in a retrospective analysis of data from hospital charts and databases. The records for 100 consecutive adults who underwent LDLT from January 2004 to February 2006 at our center were reviewed, and clinical and financial data of all recipients and donors were analyzed.

Results

The median direct total cost for LDLT was $82,017 (range $51,189?C438,295). Of this, the median cost for donors was $15,011 (range $12,354?C23,251). A multivariate stepwise logistic regression model for overall cost of transplantation revealed that donor age [odds ratio (OR)?=?1.1, p?=?0.02], acute renal failure (OR?=?24, p?=?0.007), and posttransplant plasma exchange (OR?=?72, p?=?0.01) were associated with higher cost. When the models were repeated with preoperative patient and donor factors alone, donor age (OR 1.1, p?=?0.008) and model for end stage liver disease score (OR 1.2, p?=?0.003) were associated with higher cost.

Conclusions

Donor age, acute renal failure, and posttransplant plasma exchange were independent risk factors for the high cost of LDLT in Japan.     

Use of stepwise versus straightforward clamping of biliary drainage tubes after living-donor liver transplantation: a prospective, randomized trial

Background/purpose

There has been no report describing the optimal clamping method for biliary drainage tubes in living-donor liver transplantation (LDLT), although biliary splinting and drainage plays an important role in this procedure.

Methods

When performing LDLT, we generally use a 2-mm drainage tube for the splint at the biliary anastomosis, and externalize it through the lower common bile duct. In the present study, when the serum levels of total bilirubin were lower than 5?mg/dl, and negativity for biliary complications and good passage of contrast media to the duodenum were confirmed, the drainage tubes were clamped. To determine the optimal clamping method, patients were randomly divided into two groups; those whose drainage tubes were subjected to stepwise clamping for 3, 6, 12, and 24?h per day (n?=?20), and those whose drainage tubes were subjected to straightforward clamping (n?=?20).

Results

The results of liver function tests and rates of clamping failure were not different between the two groups after the different clamping methods were used.

Conclusions

Straightforward clamping could be a simple and reasonable method to close a biliary drainage tube after LDLT.     

The risk factors of fungal infection in living-donor liver transplantations

Purpose

The aim of the study was to retrospectively assess in a Japanese university hospital the risk factors for fungal infections and mortality in living-donor liver transplantations (LDLTs). Although fungal infections are an important complication associated with high mortality in liver transplantation, the risk factors for fungal infections developing after LDLT remain poorly understood.

Methods

Patient records for a total of 156 patients undergoing LDLT over a 6-year period in our institution were retrospectively evaluated. All transplant recipients were routinely observed for fungal infections with close monitoring for febrile episodes and collection and culture of saliva, pharynx, sputum, urine, feces, and drain discharge specimens undertaken. Fungal infection was defined as proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group. Patients with definite or probable infection were diagnosed as having specific invasive fungal infection in this study. Data were reviewed and collated from these patients’ records, and multivariate analyses were performed to identify possible risk factors for mortality and the development of fungal infections.

Results

Nineteen of 156 patients (12.2%) developed invasive fungal infections, involving Candida spp. (n?=?13), Pneumocystis jiroveci (n?=?4), and Aspergillus spp. (n?=?2). Eight of these 19 patients died, 4 from pneumonia, and 1 each from cerebral hemorrhage, chronic rejection, virus-associated hemophagocytic syndrome, and cancer recurrence. The 5-year survival rate was significantly lower in patients with fungal infections than in those without (53 vs. 90%; p?p?=?0.004), posttransplant dialysis (5.62, 1.51–20.88, p?=?0.009), and bacterial infection (3.94, 1.02–15.26, p?=?0.04).

Conclusion

Independent risk factors of fungal infection after LDLT are reoperation, posttransplant dialysis, and bacterial infection.     

Peppermint Oil Solution Is Useful as an Antispasmodic Drug for Esophagogastroduodenoscopy, Especially for Elderly Patients

Background

Although hyoscine butyl bromide (HB) and glucagon (GL) are often used as antispasmodic drugs during esophagogastroduodenoscopy (EGD), these agents may cause adverse effects. Recently, it was reported that peppermint oil solution (PO) was very effective and had few side effects.

Aim

We clarified the efficacy and usefulness of PO as an antispasmodic during upper endoscopy, especially for elderly patients.

Methods

This study was a non-randomized prospective study. The antispasmodic score (1–5, where 5 represents no spasm) was defined according to the degree of spasms of the antrum and difficulty of biopsy. We compared the antispasmodic scores between non-elderly patients (younger than 70) and elderly patients (70?years old or older) according to the antispasmodic agent.

Results

A total of 8,269 (Group PO: HB: GL: NO (no antispasmodic)?=?1,893: 6,063: 157: 156) EGD procedures were performed. There was no significant difference in the antispasmodic score between Group PO (mean score?±?standard deviation: 4.025?±?0.925) and Group HB (4.063?±?0.887). Among the non-elderly patients, those in Group PO (n?=?599, 3.923?±?0.935) had a worse antispasmodic score than those in Group HB (n?=?4,583, 4.062?±?0.876, P?n?=?1,294, 4.073?±?0.917) had similar scores to those in Group HB (n?=?1,480, 4.064?±?0.921, P?=?0.83), and significantly better scores than those in Group GL (n?=?69, 3.797?±?0.933, P?Conclusion Peppermint oil was useful as an antispasmodic during EGD, especially for elderly patients.     

Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma

Background

Transcatheter arterial infusion chemotherapy (TAI) using a combination of iodized oil (lipiodol) and degradable starch microspheres (DSMs) has been reported to be superior to TAI with either lipiodol or DSMs separately for the treatment of hepatocellular carcinoma (HCC), based on the results of a prospective randomized study. In the study reported here, we investigated the predictors influencing response and survival in HCC patients receiving TAI using lipiodol and DSMs.

Methods

A total of 50 HCC patients [Child–Pugh A/B,?34/16 patients; maximum tumor size 2.9?cm (mean); tumor number <5/≥5?=?29/21 patients] were administered a mixture of cisplatin and lipiodol, followed by the injection of DSMs.

Results

According to the criteria of the Liver Cancer Study Group of Japan, the response [complete response (CR)?+?partial response (PR)] rate and CR rate were 72 and 38%, respectively [CR, 19 patients; PR, 17; stable disease, 9; progressive disease, 5]. The 1-, 2-, 3-, and 4-year cumulative survival rates were 85, 67, 41, and 35%, respectively, and the median survival time was 32.6?months. Multivariate analysis identified tumor number <5 nodules [odds ratio 10.651, 95% confidence interval (CI) 2.168–52.317; P?=?0.004] as an independent predictor of response and des-γ-carboxyprothrombin level <100 mAU/mL [hazard ratio (HR), 0.268, 95% CI 0.091–0.786, P?=?0.017] and therapeutic effect CR or PR (HR 0.255, 95% CI 0.099–0.659; P?=?0.005) as independent predictors of survival.

Conclusion

Transcatheter arterial infusion chemotherapy using lipiodol and DSMs might be considered as a potential intervention in HCC patients, especially those with tumors of <5 nodules.     

Assessment of peripheral blood CD4+ adenosine triphosphate activity in patients with rheumatoid arthritis

Objective

The ability of the ImmuKnow (Cylex) assay to predict the risk of infection in rheumatoid arthritis (RA) patients receiving synthetic or biological disease-modifying antirheumatic drugs (DMARDs) was examined.

Methods

The amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin was measured in whole blood from 117 RA patients without infection versus 17 RA patients with infection, and compared with results in 75 healthy controls.

Results

The mean ATP level was significantly lower in patients with infection compared to both healthy controls (P < 0.0005) and patients without infection (P = 0.040). Also, the mean ATP level in patients without infection was significantly lower than that in healthy controls (P = 0.012). There was no correlation between the ATP level and the Disease Activity Score in 28 joints.

Conclusion

ImmuKnow assay results may be effective in identifying RA patients at increased risk of infection, but the results showed no correlation with RA activity. Larger studies are required to establish the clinical advantages of this assay in RA treatment.     

Perioperative outcomes after ultra low anterior resection in the era of neoadjuvant chemoradiotherapy

Purpose

Data on perioperative outcomes of sphincter preserving ultra low anterior resections (ULAR) following neoadjuvant chemoradiotherapy (NA-CTRT) is sparsely reported in literature.

Methods

Prospective data of 68 patients was reviewed retrospectively. Patients who received preoperative chemoradiotherapy (CTRT, Group A, n?=?45) were compared with those who were operated upfront (Group B, n?=?23).

Results

Overall, mean distance of the tumor from anal verge was 5.1 cm (range 3–8). In Groups A and B, it was 5.2 and 5.1 cm, respectively. In Group A, 3 patients had complete response, 40 had partial response and 2 had progressive disease. Overall, the mean distance of the anastomosis performed from the anal verge was 2.8 cm (range 1–4). In Groups A and B, it was 2.7 and 2.9 cm, respectively (NS). Mean blood loss in Groups A and B was 510.5 (range 200–2,200) and 345 mL (range 50–800), respectively (p?=?0.037). Two patients in Group A required blood transfusion (range 1–2) compared to none in Group B. The overall complication rate was 26.5 % (18/68); in Groups A and B, it was 22.2 % and 34.8 %, respectively. There was no postoperative mortality. Postoperative stay for Groups A and B was 8 and 9.5 days (p?=?0.009), respectively. In Group A, 23/45 patients, earlier planned for abdominoperineal resection, ultimately received sphincter–preserving ULAR.

Conclusion

ULAR can be performed safely without added morbidity or mortality after neoadjuvant chemoradiation. In some cases, earlier deemed to be suitable for APR, the neoadjuvant approach improved chances of sphincter conservation.     

A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads

Aims/hypothesis

An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic glucose production during a hyperinsulinaemic–euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome.

Methods

rs560887 was genotyped in the Inter99 cohort (n?=?5,899), in 366 young, healthy Danes, in non-diabetic relatives of type 2 diabetic patients (n?=?196), and in young and elderly twins (n?=?159). Participants underwent an OGTT, an IVGTT or a 2 h hyperinsulinaemic–euglycaemic clamp.

Results

The rs560887 G allele associated with elevated fasting plasma glucose (p?=?2?×?10^?14) but not with plasma glucose levels at 30 min (p?=?0.9) or 120 min (p?=?0.9) during an OGTT. G allele carriers had elevated levels of serum insulin at 30 min during an OGTT (p?=?1?×?10^?4) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p?=?4?×?10^?4) during an IVGTT. Among elderly twins, G allele carriers had higher basal hepatic glucose production (p?=?0.04). Finally, the G allele associated with the risk of having IFG (OR 1.26, 95% CI 1.08–1.47, p?=?0.002), but not with IGT (OR 0.94, 95% CI 0.82–1.08, p?=?0.4) or type 2 diabetes (OR 0.93, 95% CI 0.84–1.04, p?=?0.2).

Conclusions/interpretation

The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate.     

Thiopurine methyltransferase genotyping in Palestinian childhood acute lymphoblastic leukemia patients

Background

The genetic polymorphism of thiopurine methyltransferase (TPMT) is well characterized in most populations. Four common polymorphic alleles are associated with impaired activity of the enzyme. These are TPMT*2 (238G>C), TPMT*3B (c.460G>A), TPMT*3A (c.460G>A and c.719A>G) and TPMT*3C (c.719A>G). The aim of the present study was to determine the frequency of TPMT polymorphisms and their association with the occurrence of adverse events, during 6-mercaptopurine therapy in pediatric acute lymphoblastic leukemic (ALL) patients in Gaza Strip.

Methods

A total of 56 DNA samples from all pediatric ALL patients admitted to the pediatric hematology departments of Gaza strip hospitals were analyzed. Genomic DNA from peripheral blood leukocytes was isolated and the TPMT*2, TPMT*3B TPMT*3A and TPMT*3C allelic polymorphism was determined by PCR-RFLP and allele specific PCR technique.

Results

No TPMT*2, *3B or *3C alleles were detected. Only one, out of 56 patients, was found heterozygous for the TPMT*3A allele. Thus, the frequency of TPMT*3A allele was calculated to be 0.89%. Fourteen patients of ALL were suffering from myelotoxicity during 6-MP therapy. From our results, no significant association could be established between clinical and laboratory data and/or the presence of the mutation in TPMT gene.

Conclusion

TPMT*3A was the only deficiency allele detected in our population with an allelic frequency of 0.89%. Other polymorphic alleles in TPMT gene, or factors other than TPMT polymorphisms may be responsible for the development of myelosuppression in cases that don’t carry the investigated TPMT alleles (*2, *3A, *3B and *3C). Therefore, more studies are recommended to study such factors.     

Predicting survival after living and deceased donor liver transplantation in adult patients with acute liver failure

Background

Post-transplant outcomes for acute liver failure (ALF) are unsatisfactory, and there are debates about the most suitable type of graft. Given the critical shortage of donor organs, accurate assessment of post-transplant outcome in ALF patients is crucial to avoid a futile liver transplantation (LT).

Methods

A database of 160 consecutive adult ALF patients who underwent primary LT between 2000 and 2009 in a tertiary LT center was analyzed.

Results

The most common causes of ALF were hepatitis B virus infection (30%) and herbal/folk medicine use (30%). Thirty-six (22.5%) and 124 (77.5%) patients underwent deceased-donor LT (DDLT) and adult-to-adult living-donor LT (LDLT), respectively. During a median follow-up period of 38 (range 1–132) months, the DDLT and LDLT groups showed similar patient (P?=?0.99) and graft (P?=?0.97) survival rates. The overall 1- and 3-year patient survival rates were 78.8 and 74.6%, respectively. Five predictors of patient survival were identified by bootstrapping and multivariate analysis: vasopressor requirement, estimated glomerular filtration rate, serum sodium concentration, recipient age, and donor age, at the time of transplant. By summing scores weighted in each of these predictor categories, we designed a prognostic scoring system (scores from ?2 to 20) that estimated 1-year post-transplant mortality from 0 to 100% (c statistic 0.79).

Conclusions

Long-term outcomes after LDLT and DDLT were comparable in adult patients with ALF. A simple prognostic scoring system that includes 5 predictive variables at the time of LT may help estimate post-transplant survival in ALF patients, regardless of the type of transplant.     

The predictive value of single nucleotide polymorphisms in the VEGF system to the efficacy of first-line treatment with bevacizumab plus chemotherapy in patients with metastatic colorectal cancer

Purpose

Bevacizumab and chemotherapy is a common choice for first-line treatment of metastatic colorectal cancer (mCRC). So far, no predictive markers have been identified. The aim was to investigate the possible predictive value of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) system in this setting.

Methods

Pre-treatment blood samples and response evaluations were available from 218 of the 249 included patients. All patients received bevacizumab and chemotherapy comprising fluorouracil and leucovorin or capecitabine combined with either oxaliplatin (FOLFOX or XELOX, n?=?183) or irinotecan (FOLFIRI or XELIRI, n?=?66). Germline DNA was isolated from whole blood, and five SNPs in the VEGF-A gene, one SNP in the VEGF receptor 1 (VEGFR-1) gene and three SNPs in the VEGFR-2 gene were analysed by polymerase chain reaction. Response was evaluated according to RECIST version 1.0, and the association to genotypes was analysed using Fisher’s exact test.

Results

The VEGFR-1 319?C/A SNP was significantly associated with response. Objective response was observed in 36% of the patients with CC genotype, 40% with CA and 56% with AA, p?=?0.048. The response rates also differed significantly between patients with C-allele containing genotypes (CC?+?CA) (39%) and patients homozygous for the A-allele (AA) (56%), p?=?0.015. There was no correlation between response rates and the remaining SNPs.

Conclusions

The VEGFR-1 319?C/A SNP is a potential predictive marker for bevacizumab plus chemotherapy in patients with mCRC. Patients with the A allele appeared to have increased response rates. The results call for validation.     

HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus

Aims/hypothesis

In this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA.

Methods

Collagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype.

Results

Significantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA_1c). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients.

Conclusion

Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.     

The HLA-B*3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes

Aims/hypothesis

We investigated the risk associated with HLA-B*39 alleles in the context of specific HLA-DR/DQ haplotypes.

Methods

We studied a readily available dataset from the Type 1 Diabetes Genetics Consortium that consists of 2,300 affected sibling pair families genotyped for both HLA alleles and 2,837 single nucleotide polymorphisms across the major histocompatibility complex region.

Results

The B*3906 allele significantly enhanced the risk of type 1 diabetes when present on specific HLA-DR/DQ haplotypes (DRB1*0801-DQB1*0402: p?=?1.6?×?10^?6, OR 25.4; DRB1*0101-DQB1*0501: p?=?4.9?×?10^?5, OR 10.3) but did not enhance the risk of DRB1*0401-DQB1*0302 haplotypes. In addition, the B*3901 allele enhanced risk on the DRB1*1601-DQB1*0502 haplotype (p?=?3.7?×?10^?3, OR 7.2).

Conclusions/interpretation

These associations indicate that the B*39 alleles significantly increase risk when present on specific HLA-DR/DQ haplotypes, and HLA-B typing in concert with specific HLA-DR/DQ genotypes should facilitate genetic prediction of type 1 diabetes, particularly in a research setting.     

Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision: a multi-institutional analysis in an Asian population

Purpose

This study was conducted to evaluate the significance of carcinoembryonic antigen (CEA) level as a predictor for tumor response to chemoradiotherapy (CRT) and a prognosticator for survival in Asian patients with advanced rectal cancer.

Materials and methods

We enrolled 345 patients with primary rectal cancer who had undergone preoperative CRT and total mesorectal excision. We analyzed clinicopathological factors that could be associated with pathologically complete response (ypCR) and disease-free survival (DFS).

Results

A cutoff level of 5 ng/mL (p?=?0.002) for CEA was found to be significant for prediction of ypCR. Increased CEA level (p?=?0.025) was a significant negative predictor of ypCR after CRT in patients with rectal cancer. The 5-year DFS rate was significantly higher in the CEA ≤5-ng/mL group than in the CEA >5-ng/mL group (73.2 vs. 60.9 %, p?=?0.002). This is mainly due to the higher chance of distant recurrence (p?=?0.013), not locoregional recurrence (p?=?0.732), in the CEA >5-ng/mL group.

Conclusions

Elevated CEA (>5 ng/mL) is a negative predictor of ypCR and has a negative impact on DFS in Asian rectal cancer patients who underwent preoperative CRT and surgery due to an increased chance of distant recurrences.     

Influence of CYP2C19 polymorphisms in platelet reactivity and prognosis in an unselected population of non ST elevation acute coronary syndrome

Introduction and objectives

CYP2C19*2 and CYP2C19*17 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coronary syndrome.

Methods

Recruitment for the first and second objectives was 40 stable acute coronary syndrome patients under dual antiplatelet therapy at 12 months after coronary stent placement and an unselected population of 493 consecutive patients with non-ST elevation acute coronary syndrome, respectively. Platelet reactivity was assessed by optical aggregometry induced by adenosine diphosphate and thrombin receptor activating peptide, and by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Genotypes were determined with a TaqMan assay.

Results

Only the vasodilator-stimulated phosphoprotein phosphorylation measurement detected significant differences in on-clopidogrel platelet reactivity between the wild-type subjects and the CYP2C19*2 (P=.020) and *17 allele carriers (P=.048). No significant difference was found between CYP2C19*2 ([HR (95%CI): 1 (0.94-1.55)], P=.984) or *17 ([HR (95%CI): 0.93 (0.61-1.43)], P=.753) allele carriage and the occurrence of adverse events at 6-month follow-up.

Conclusions

Even though CYP2C19 genotype is associated with variable on-clopidogrel platelet reactivity, it has no significant clinical influence. Prognosis of acute coronary syndromes may be influenced by a myriad of variables.Full English text available from:www.revespcardiol.org     

Breathing irregularity during wakefulness associates with CPAP acceptance in sleep apnea

Purpose

Individuals have different breathing patterns at rest, during wakefulness, and during sleep, and patients with sleep apnea are no different. The hypothesis for this study was that breathing irregularity during wakefulness associates with CPAP acceptance in obstructive sleep apnea (OSA).

Methods

From a 2007–2010-database of patients with a diagnostic polysomnography (PSG) and prescribed CPAP (n?=?380), retrospectively, 66 patients who quit CPAP treatment at 6 months were identified. Among them, 27 OSA patients quit despite having no side effects for discontinuing CPAP (Group A) and were compared to a matched group (age, body mass index, and apnea–hypopnea index) with good 6-month CPAP adherence (Group B; n?=?21). Five minutes of respiratory signal during wakefulness at the initial PSG were extracted from respiratory inductance plethysmography recordings, and measured in a blinded fashion. The coefficients of variation (CV) for the breath-to-breath inspiration time (T _i), expiration time (T _e), T _i?+?T _e (T _tot), and relative tidal volume, as well as an independent information theory-based metric of signal pattern variability (mutual information) were compared between groups.

Results

The CV for tidal volume was significantly greater (p?=?0.001), and mutual information was significantly lower (p?=?0.041) in Group A as compared to Group B.

Conclusions

Differences in two independent measures of breathing irregularity correlated with CPAP rejection in OSA patients without nasal symptoms or comorbidity. Prospective studies of adherence should examine traits of breathing stability.