Pre-operative chemoradiotherapy using capecitabine and cetuximab followed by definitive surgery in patients with operable rectal cancer

Background: Achieving a high rate of complete pathological response with pre-operative chemoradiotherapy in rectal cancer is an unmet need. We evaluated the efficacy and toxicity of the combination of cetuximab, capecitabine and radiation therapy in the pre-operative setting of localized rectal cancer

Patients and methods: Patients with clinically staged T3, T4 or nodepositive rectal cancer were treated with concurrent capecitabine and radiotherapy with weekly cetuximab starting one week before the start of radiation. This was followed by total mesorectal excision within 6-8 weeks. All patients achieving R0 resection received adjuvant capecitabine for 6 cycles

Results: Fifteen patients were treated and all underwent surgery. Sphincter preservation was achieved in 11 patients [73.3%] and pathological complete response in two. With a median follow up of 48 months [range 8.4-57.5], 12 patients were relapse-free and 14 were alive with 4- year relapse free survival of 80%. Overall survival was 93%. Significant grade 3 and 4 toxicity was mainly cetuximab-induced skin reactions [33%], radiation-induced skin toxicity [13%] and diarrhea [20%]

Conclusions: Adding cetuximab to pre-operative concurrent capecitabine and radiotherapy provides modest efficacy with manageable toxicity

Detection of a point mutation at codon 12 of the Kirsten-Ras [K-ras] oncogen in myelodysplastic syndrome

Mutations in ras genes have been observed in a variety of cancers and were found to play an important role in human leukemogenesis and in preleukemic disease as myelodysplastic syndrome [MDS]. The purpose of this study was to determine the prevalence of mutated K-ras oncogene in myelodysplastic syndrome [MDS]; with a special emphasis on their possible role in affecting clinical status, relation to karyotypic pattern; response to therapeutic measures; its impact on the fate of the disease and overall survival. Detection of point mutation of Kirsten-ras [K-ras] gene in 30 patients suffering from myelodysplastic syndrome was carried out using quantitative enriched polymerase chain reaction [QEPCR] and was confirmed by sequencing. QEPCR is a two- stage PCR procedure with modified primers that enriches mutant alleles, via restriction endonuclease digestion of normal alleles and enables identification of one mutant allele among 100,000 normal alleles. Activating mutations of the codon 12 of K-ras gene were detected in 7/30 [23.3%] cases of MDS, the most common mutation involved a substitution of aspartic acid for glycine [GGTGAT]. The incidence of K-ras mutations was found to be significantly associated with refractory anemia with excess blasts type II [RAEBII] and unclassified [UC] MDS than other subtypes [p=0.005], and was significantly associated with hypercellular bone marrow [p=0.04] showing marked dyserythropoitic changes. Furthermore, mutant K-ras gene was found to be significantly associated with abnormal karyotypes [p=0.04]. Patients with mutated K-ras gene were significantly associated with either high or intermediate risk according to International Prognostic Scoring System [IPSS] [p=0.001]. 6/7[85.7%] of those carrying the mutation showed poor response to treatment compared to non carriers with a statistical significant difference [p=0.009]. Five out of eight [62.5%] patients who were transformed to AML carried the mutant K-ras gene, their subtypes were RAEBII and unclassified MDS with abnormal cytogenetics mainly Monosomy 7. Overall survival was detected using Kaplan-Meier curve and the mean survival time of patients who carried K-ras mutations were significantly lower than those without the mutation [Log rank test=12.7; p=0.0004]. MDS patients bearing an mutated K-ras oncogene frequently showed poor response to treatment; leukemic progression of the disease and shorter overall survival, suggesting that an activated K-ras oncogene is a critical factor for prognostic evaluation; therapeutic decision and monitoring of response to treatment of MDS patients

Clinical outcome of inferior vena caval greenfield filters in patients with deep vein thrombosis

Twenty-five patients with deep vein thrombosis [DVT] were included in this study. Gray scale and Doppler ultrasonography were used to diagnose the lower limbs DVT. In these patients, contraindication or complication to anticoagulation was the indication of filter placement. Greenfield filters were implanted percutaneously via transfemoral or transjugular approaches. Infrarenal implantation was performed in 22 patients, while suprarenal implantation was done in the remaining 3 patients. All patients were followed up for 12 months for the development of pulmonary embolism [PE] and for post-filter complications. The study concluded that IVC filters, when properly implanted, provide an effective protection from life-threatening pulmonary thromboembolism with minimal morbidity