Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the Multidisciplinary Oncology Group on Gastrointestinal Tumors

The aim of this study was to investigate the safety profile of continuous oral capecitabine at fixed dose in patients older than 75 years, having metastatic colorectal and gastric cancer. Capecitabine was administered at a fixed dose of 2000 mg daily without interruptions. Thirty-four patients were considered evaluable for toxicity and efficacy. The median age was 81 years (range 76-85). The median duration of treatment was 113 days (range 24-238 days). No grade 4 toxicity was observed. One patient had grade 3 nausea and vomiting, and one had grade 3 diarrhea. Partial responses were observed in six patients with colorectal cancer, and in one patient with gastric cancer. This study suggests that continuous oral capecitabine at a fixed daily dose of 2000 mg is well tolerated, and that it allows for the simplification and ease of dosing in elderly patients with metastatic colorectal and gastric cancer.     

Muscle MRI findings in facioscapulohumeral muscular dystrophy

Objectives

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations.

Methods and Materials

Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD).

Results

In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients.

Conclusions

In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease.

Key Points

? Muscle MRI identifies a specific pattern of muscle involvement in FSHD patients. ? Muscle MRI may predict FSHD in asymptomatic and severely affected patients. ? Muscle MRI of upper girdle better predicts FSHD. ? Muscle MRI may differentiate FSHD from other forms of muscular dystrophy. ? Muscle MRI may show the involvement of non-clinical testable muscles.

     

The pattern of lymph node metastases in microsatellite unstable gastric cancer

Background

Microsatellite instability (MSI) is one of the new groups of molecular divisions of gastric cancer (GC). The aim of this study was to investigate the pattern of lymph node metastasis according to MSI status.

Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer

Background:

MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker.

Methods:

The 5-aza-2′-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a.

Results:

The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P=0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P=0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P=0.561.

Conclusions:

These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker.     

MSI phenotype and MMR alterations in familial and sporadic gastric cancer

Microsatellite instability (MSI) is a major pathway involved in gastric carcinogenesis occurring in 20% of gastric cancer (GC). However, it is not clear whether MSI phenotype preferentially occurs in the sporadic or familial GC, when stringent inclusion criteria are used. The aim of this study was to compare the frequency of MSI and hypermethylation of MLH1 promoter in a large series of familial GC patients (non‐HNPCC and non‐CDH1‐related) and sporadic cases. Additionally, we analysed the immunoexpression of MMR proteins in a fraction of cases. Overall, the frequency of familial GC was 7.1%, and the frequency of hereditary tumours was 4.6%. MSI phenotype and MLH1 hypermethylation frequencies were not statistical different between familial and sporadic GC settings. Further, the MSI phenotype was not associated with any clinico‐pathological features studied in the familial GC setting, whereas in the sporadic setting, it was associated with older age, female gender and intestinal histotype. Using our stringent Amsterdam‐based clinical criteria to select familial GC (number of cases, age of onset), we verified that sporadic and familial cases differed in gender but shared histopathological features. We verified that the frequency of MSI was similar in familial and sporadic GC settings, demonstrating that this molecular phenotype is not a hallmark of familial GC in contrast to what is verified in HNPCC. Moreover, we observed that the frequency of MLH1 hypermethylation is similar in sporadic and familial cases suggesting that in both settings MSI is not associated to MMR genetic alterations but in contrast to epigenetic deregulation.     

Feasibility of cuff-free measurement of systolic and diastolic arterial blood pressure

We validated a prototype cuff-free device for noninvasive estimation of blood pressure (BP). The system assumed a linear relation between BP values and the inverse of arterial blood pulse transit time, measured as time interval between the R wave on the electrocardiograph and the onset of the peripheral pulse wave on a finger plethysmogram. Thirty-three healthy subjects were analyzed at rest and during increasing stress exercise. To estimate subject-specific linear model parameters, the system was calibrated ad personam with reference to BP measures obtained by a cuff sphygmomanometer. High correlation values (R² = 0.89 and 0.78 for systolic and diastolic BP, respectively) and differences consistent with clinical requirements (mean discrepancy of −0.058 and −0.25 mm Hg; 95% confidence interval of −13.0 to +12.9 mm Hg and −11.3 to +10.8 mm Hg, for systolic and diastolic BP, respectively) were observed between device and reference measurements. Calibration parameter stability and accuracy level were confirmed in a midterm evaluation, 30 days after calibration. These findings suggest the suitability of the device for noninvasive BP monitoring and its potentiality for clinical applications. Improvements can be achieved by further investigation of the calibration procedure and sensor placement.