Lenny Tan

Using Whole Genome Amplification (WGA) of Low-Volume Biopsies to Assess the Prognostic Role of EGFR, KRAS, p53, and CMET Mutations in Advanced-Stage Non-small Cell Lung Cancer (NSCLC)

Background: Progression of non-small cell lung cancer (NSCLC) from early- to late-stage may signify the accumulation of gene mutations. An advanced-stage tumor’s mutation profile may also have prognostic value, guiding treatment decisions. Mutation detection of multiple genes is limited by the low amount of deoxyribonucleic acid extracted from low-volume diagnostic lung biopsies. We explored whole genome amplification (WGA) to enable multiple molecular analyses. Methods: Eighty-eight advanced-stage NSCLC patients were enrolled. Their low-volume lung biopsies underwent WGA before direct sequencing for epidermal growth factor receptor (EGFR), KRAS (rat sarcoma virus), p53, and CMET (mesenchymal-epithelial transition factor) mutations. Overall survival impact was examined. Surgically-resected tumors from 133 early-stage NSCLC patients were sequenced for EGFR, KRAS and p53 mutations. We compared the mutation frequencies of both groups. Results: It is feasible for low-volume lung biopsies to undergo WGA for mutational analysis. KRAS and CMET mutations have a deleterious effect on overall survival, hazard ratios 5.05 (p = 0.009) and 23.65 (p = 0.005), respectively. EGFR and p53 mutations, however, do not have a survival impact. There also does not seem to be significant differences in the frequency of mutations in EGFR, KRAS, and p53 between early- and advanced-stage disease: 20% versus 24% (p = 0.48), 29% versus 27% (p = 0.75), 10% versus 6% (p = 0.27), respectively. Conclusions: In advanced-stage NSCLC, KRAS, and CMET mutations suggest poor prognosis, whereas EGFR and p53 mutations do not seem to have survival impact. Mutations in EGFR, KRAS and p53 are unlikely to be responsible for the progression of NSCLC from early- to late-stage disease. WGA may be used to expand starting deoxyribonucleic acid from low-volume lung biopsies for further analysis of advanced-stage NSCLC.

Case report: Computed tomography and ultrasound diagnosis of mycotic aneurysm of the abdominal aorta due to salmonella

The case of a 56 year old diabetic Chinese male, with a Salmonella bovismorbificans (serogroup C) mycotic aneurysm of the abdominal aorta is presented. The lesion was seen by computed tomography and ultrasound and the patient was successfully treated by primary resection, debridement and grafting. Computed tomography criteria for the diagnosis of mycotic aneurysms of the abdominal aorta are discussed. Ultrasound identified the aortic aneurysm correctly but was unable to demonstrate the associated psoas abscess in this case.

An Alternative Approach to Determining Therapeutic Choices in Advanced Non-small Cell Lung Carcinoma (NSCLC): Maximizing the Diagnostic Procedure and the Use of Low-Volume Lung Biopsies

Background: Accurate mutational analysis, especially epidermal growth factor receptor (EGFR) mutations, of diagnostic biopsies from all Asian NSCLC patients is crucial to their clinical management, but faces problems. Here, we explore, within usual hospital constraints, the practicalities of incorporating mutational analysis in every newly diagnosed case of NSCLC, namely, maximizing tissue acquisition during the diagnostic procedure and determining the maximum quantity and quality of DNA sequence data available from these biopsies. Methods: Sixty-eight Chinese patients were enrolled. Thirty-five underwent surgical resections for early-stage tumors. Thirty-three underwent diagnostic procedures, i.e., needle aspirates under bronchoscopic or computed tomographic/fluoroscopic guidance, or forceps biopsies via bronchoscopy. Separate samples for research purposes were obtained from these 33 patients during the diagnostic procedure. All samples were analyzed for mutations in EGFR exons 18 to 21, p53 exons 4 to 9, and Kras exon 2. Results: No deaths occurred in this study. Success rates in obtaining sequence data from surgical samples versus low-volume samples for EGFR, p53, and Kras were 100% versus 85%, 100% versus 82%, and 100% versus 85%, respectively. Sequencing nine polymerase chain reaction products from each low-volume sample resulted in the exhaustion of all extracted DNA from three samples. Conclusions: Acquiring a separate low-volume lung biopsy sample for mutational analysis in lung cancer patients during the diagnostic procedure is feasible and may be a valuable complement to the usual diagnostic workflow in future.

Endovascular Management of Traumatic Thoracic Aortic Transection

The conventional treatment of traumatic thoracic aortic transection is open surgical repair but it is associated with high rates of morbidity and mortality, particularly in patients with multiple injuries. We reviewed our experience of endovascular repair of traumatic thoracic aortic transection. Between March 2002 and December 2007, 7 patients (male 6, female 1; mean age 40 years) with multiple injuries secondary to blunt trauma underwent endovascular stenting. One patient required adjunctive surgery to facilitate endovascular stenting. Mean intensive care unit stay was 8.6 days (range, 3–16 days). Arterial access in all patients was obtained by femoral cut-down. The mean operating time was 122 min. Technical success was achieved in all cases. There was no mortality. One patient suffered a right parietal stroke, but none developed procedure-related paralysis. The mean follow-up period was 18.6 months (range, 6–48 months). There was no evidence of endoleak, stent migration, or late pseudoaneurysm formation on follow-up computed tomography. Endovascular stents can be used to treat traumatic thoracic aortic transection, with low rates of morbidity and mortality. Although early and midterm results are promising, the long-term durability of endovascular stenting for traumatic thoracic aortic transection remains unknown.