Efficacy of doxycycline in the treatment of early stages of mycosis fungoides: a randomized controlled trial.

BACKGROUND: Mycosis fungoides is the most common type of primary cutaneous T cell lymphomas. Doxycycline promoted apoptosis in different human malignant cell lines and in vivo models. OBJECTIVES: To test for the therapeutic efficacy of doxycycline in comparison to PUVA in early stages of classic MF and its effect on T cell apoptosis. METHODS: Thirty-six patients were randomized into either: doxycycline 200 mg daily (n = 18) or PUVA (3 weekly sessions) (n = 18) for 12 weeks. The primary outcome (therapeutic efficacy) was defined in terms of objective response rate (ORR) which was measured according to changes in the modified severity weighted assessment tool (mSWAT). RESULTS: Doxycycline achieved significantly less ORR (partial response) in comparison to PUVA (11.1%, 50%, respectively, p = .016). The percent reduction in mSWAT, CAILS, histopathology score and CD3 expression was significantly less in the doxycycline group (p = .001, p = .001, p ˂ .001, and p = .004, respectively). Within the doxycycline group, changes in mSWAT and CAILS showed no correlation with changes in the CD3 or Bcl-2 expression. Gastric upset was significantly more encountered in the doxycycline group (p = .001). CONCLUSION: Doxycycline is not suitable as a sole agent in the treatment of early stages of classic MF, acting mainly by anti-inflammatory rather apoptotic function. REGISTER NUMBER: NCT03454945 (www.clinicaltrials.gov).

Are normolipidaemic patients with xanthelasma prone to atherosclerosis?

BACKGROUND: When patients with xanthelasma are found to have normal lipid levels, dermatologists usually proceed with their treatment without further investigations. However, there is some evidence that normolipidaemic patients with xanthelasma (NPX) have a similar cardiovascular risk to hyperlipidaemic patients with xanthelasma (HPX). AIM: To evaluate the risk of atherosclerosis in Egyptian NPX compared with HPX and controls. METHODS: In total, 20 NPX, 20 HPX and 40 normolipidaemic controls were enrolled. All participants were matched for age and sex. Diabetes was an exclusion factor. Carotid ultrasonography was used to measure intima-media thickness (IMT). Other risk factors of atherosclerosis such as high blood pressure, obesity and smoking were also assessed, as well as atherosclerotic markers, including total leucocytic count (TLC), C-reactive protein and lipoprotein a. RESULTS: Although still within the normal range, total cholesterol and triglycerides were significantly higher in NPX compared with controls. IMT was significantly higher in NPX compared with controls, but lower than that of HPX. The increased IMT in NPX was not related to any of the studied risk factors. Apart from significantly higher body mass index and TLC, NPX showed no significant differences from controls for other risk factors of atherosclerosis or for atherosclerotic markers. CONCLUSION: NPX seem to have a higher risk of atherosclerosis independent of lipid concentrations, and should therefore be fully investigated in order to allow detection and early management of such risk.

Transforming growth factor-ß1 gene polymorphism in mycosis fungoides.

BACKGROUND: Dysregulation in transforming growth factor (TGF)-ß1 signalling pathways has been linked to cancer. AIM: To study the association between single nucleotide polymorphisms (SNPs) of the TGF-ß1 gene and mycosis fungoides (MF). METHODS: Using restriction fragment length polymorphism analysis, SNPs in the TGF-ß1 gene were studied in 55 patients with MF of different stages and in 100 apparently healthy controls. RESULTS: A significant difference was found between patients and controls in distribution of the different TGF-ß1 genotypes, with mutant forms (T/C, T/T) encountered significantly more often in patients with MF (P < 0.001). The heterozygous genotype (T/C) was significantly associated with patch stage MF, whereas the homozygous genotype (T/T) was significantly associated with tumour stage (stage IIb) MF (P = 0.001), although this study included only a small number of these patients. CONCLUSIONS: Mutant TGF-ß1 genotypes are significantly associated with MF in Egyptian patients, with the homozygous genotype (T/T) having a stronger association with tumour stage (stage IIb).

Impact of laparoscopic right hemicolectomy for colon cancer.

INTRODUCTION: This study specifically examined right colonic cancer resection, a common operation for colorectal surgeons starting laparoscopic resection, to assess the impact of commencing laparoscopy. PATIENTS AND METHODS: A total of 56 patients undergoing open (n = 34) and attempted laparoscopic (n = 22) elective right hemicolectomy for colorectal cancer between November 2003 and March 2007 were compared. Postoperative stay was the primary outcome. Secondary outcomes included analgesic requirements, bowel recovery, morbidity and mortality. Frequency of laparoscopic versus open surgery over time was also examined. RESULTS: Resections attempted laparoscopically increased from 9.1% to 75% in the first and last quarters of the study period, respectively (P = 0.0002). Uptake of 'enhanced recovery' was mainly in the laparoscopic group. Conversion was required in two of 22 patients. Attempted laparoscopic cases had a shorter median postoperative stay (6 vs 10 days; P < 0.0001), duration of parenteral or epidural analgesia (48 vs 72 h; P < 0.0001) and time to first bowel action (3 vs 4 days; P = 0.001) compared with open cases. Demography, tumour characteristics, morbidity and mortality were comparable between groups. Multivariate analysis identified decreased age, attempted laparoscopic surgery, use of enhanced recovery and absence of complications as independently shortening postoperative stay. CONCLUSIONS: Advantages of laparoscopic surgery and enhanced recovery, even early in a surgeon's experience, suggest this is the preferred mode for elective right colon cancer resection.

Expression of insulin-like growth factor-I in lesional and non-lesional skin of patients with morphoea.

BACKGROUND: Morphoea (scleroderma) is a chronic disorder characterized by circumscribed sclerotic plaques with the hallmark of increased fibroblast activation and fibrosis. Through its effect on connective tissue cells and immune cells, insulin-like growth factor (IGF)-I has been found to play a role in some autoimmune connective tissue diseases and has been implicated in the pathogenesis of several fibrotic disorders. OBJECTIVES: To evaluate the role of IGF-I in the pathogenesis of morphoea. METHODS: The study was carried out on 15 patients with morphoea and nine healthy controls. Two 5-mm punch skin biopsies were taken from every patient (one from lesional and one from non-lesional skin) and a single biopsy was taken from the normal skin of each control. A 10-mL blood sample was also taken from each patient and control. Quantitative detection of tissue and serum levels of IGF-I was done using an enzyme-linked immunosorbent assay technique. RESULTS: IGF-I in lesional skin was significantly higher than in non-lesional and control skin (P = 0.001 and P = 0.021, respectively). Moreover, a significantly higher level of IGF-I was detected in patient serum when compared with control serum (P < 0.001). A direct significant correlation existed between lesional and non-lesional skin level (r = 0.618, P = 0.014), and between lesional skin level and Rodnan score (r = 0.538, P = 0.039). CONCLUSIONS: Despite the small sample size, this study suggests that IGF-I plays an important role in the pathogenesis of fibrosis, characteristic of morphoea. Studies on a larger number of patients with morphoea as well as on patients with systemic sclerosis are recommended. Furthermore, therapeutic trials using IGF-I antagonist (octreotide) are highly recommended in patients with morphoea.