Plasma cell neoplasms in the young

Multiple myeloma, a disease of the elderly, is extremely rare in those below 30 years of age. Two patients with multiple myeloma diagnosed at 20 years and 18 years are described. Both presented with extradural cord compression, lytic bone lesions and bone marrow plasmacytosis. One patient received combination chemotherapy and radiotherapy and survived for 14 years. A literature review is presented.     

Telomerase, p53 and human papillomavirus infection in the uterine cervix

Human papillomavirus infection is postulated to be a major risk factor for cervical cancer, while more recent data have stressed the clinical significance of telomerase expression during tumorigenesis. This study therefore looked for any relationship between telomerase expression, presence of human papillomavirus (HPV) and expression of the high-risk HPV E6 protein at various phases of tumor progression in the uterine cervix. In addition, accumulation of the p53 protein and total tissue proliferative fraction were also studied. Telomerase was detected using a modified TRAP (telomerase repeat amplification protocol) assay. Expression of p53, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant-specific ELISA. Type of HPV infection was determined by polymerase chain reaction and Southern blot using type-specific primers and probes. There was a significant correlation between the expression of telomerase with histological grade (r=0.646, p=0.00003). Fisher's exact test analysis revealed that the odds ratio of a tissue sample expressing telomerase being a case (high-grade squamous intraepithelial lesion or invasive cancer) was 28.93 (p=0.0001, 95% CI: 7.22, to 115.94). High-risk HPV-infected tissues and those expressing E6 showed increased telomerase expression (r=0.555, p=0.00001). Similarly, accumulation of p53 protein and increased cell proliferation (Ki 67 index) also correlated to the presence of telomerase (r=0.661, p=0.000004 for p53 and r=0.647, p=0.000003 for Ki 67). There was no correlation between telomerase expression and presence of p53 mutation. Activation of telomerase thus appears to be associated with high-risk-HPV infection, accumulation of inactive p53 protein and increased cell proliferation in cervical lesions.     

The emerging role of endoscopic ultrasonography in cancer staging

The management of solid organ cancers relies on accurate staging. Once distal metastasis has been excluded by conventional radiographic methods, local staging of the tumor and its nodal involvement is essential to determine the most optimal therapeutic approach. Many radiographic imaging modalities are unable to determine subtle tumor involvement. However, the emergence of endoscopic ultrasonography (EUS) has given promise to improved staging with its unique ability to examine tumors from within the gastrointestinal lumen with extremely close proximity. An additional advantage is the ability to perform fine-needle aspiration (FNA) biopsy to confirm or exclude tumor involvement. Many studies have shown superior accuracy in staging with EUS and EUS-FNA for tumors of the esophagus, stomach, pancreas, rectum, and mediastinum, including lung cancer. This review illustrates the principles of EUS and its role in staging of a variety of cancers and particularly its role alongside other imaging modalities.     

Visual field defects in non-functioning pituitary adenomas

PURPOSE: To report the prevalence and pattern of visual field loss in non-functioning pituitary adenomas and to study the relationship between the tumour size and severity of field defects. METHODS: Ninety-three patients with histologically confirmed pituitary adenomas, non-functional on hormonal assessment, underwent a complete ophthalmic assessment and automated perimetry using the HFA 30-2 programme. Defects with quadrantanopic or hemianopic characteristics, defined using criteria on the threshold/pattern deviation plots were considered typical. Typical defects were graded as mild, moderate and severe. All other defects were considered atypical. A neuroradiologist measured tumour size on a CT or MRI Scan. The Chi-square test for trend was used to test association of tumour volume with severity of typical defects. RESULTS: Eighty-eight (94.6%) of the 93 patients had a field defect. Typical field defects were seen in 69 (74.2%) patients and atypical in 19 (20.4%). A severe typical defect involving at least 3 quadrants in one or both eyes was the most common (24 patients or 25.80%). All 31 patients (33.3%) with a tumour size greater than 20 cc had field defects. Severity of field defect increased with tumour volume (Chi-square test for trends significant p = 0.0096). CONCLUSIONS: Field defects occurred in 95% of patients with non-functioning pituitary macroadenoma. A severe visual field loss involving at least 3 quadrants in one or both eyes was the most common. 20% of patients had atypical field defects. Severity of field defects increased with tumour volume.     

Immunophenotype of mutant ras p21 and early response to radiotherapy in cancer of the uterine cervix

Previous studies have postulated that ras gene mutations may influence cellular response to radiotherapy. However, clinical studies have often been limited by the cumbersome methodology associated with DNA analysis. The availability of ELISA method has eventually made clinical evaluation of ras gene mutation feasible. In this study ras mutation by in vitro identification of four mutant forms of p21 ras in cervical tumor tissue extracts was analyzed. Mutant ras proteins were evaluated by an Enzyme Linked Immunosorbent Assay (ELISA). Expression of ras p21 mutations was studied in 101 patients, and a correlation between pre-treatment experimental analyses and the clinical status of the patient after radiotherapy (up to 16 months follow up) was established. There was no correlation between the presence of Val 12 p21 and tumor response to radiotherapy. Yet, presence of the other three mutant proteins had significant relationship to treatment outcome. Detection of Arg 12 mutation was more common in patients who either had residual disease or developed recurrences (28%) as compared to those remaining disease-free (1.5%). The presence of the Arg 12 mutation therefore correlated to poor prognosis (r = 0.445, p = 0.0000). Similarly, the Asp 12 mutation was also more common in patients with residual/recurrent disease (25%) as compared to patients remaining disease-free (3%). Asp 12 mutation also showed a correlation to treatment outcome (r = 0.337, p = 0.00057). Asp 13 mutation was more frequent in patients with residual or recurrent disease (28%) as compared to those remaining disease-free (4.6%). On the basis of laboratory evidence ras genes appear to be involved as modulators of tumor response to radiation therapy. This understanding of the involvement of specific genes in radioresistance will result in the improvement of potential therapies that can be targeted at specific genes, through approaches such as selective inhibition by anti-sense oligonucleotides.     

Concomitant augmentation of type 1 CD4+ and CD8+ T-cell responses during successful interferon-alpha and ribavirin treatment for chronic hepatitis C virus infection

The combined interferon-alpha (IFN-alpha) and ribavirin (IFN-alpha/ribavirin) therapy for chronic hepatitis C virus (HCV) infection results in sustained viral eradication in 31%-64% of the patients. Previous studies have strongly suggested that HCV-specific T-cell responses maybe modulated during this therapy. The objective of this study was to further define the effect of IFN-alpha/ribavirin therapy on type 1 and type 2 HCV-specific CD4(+) and CD8(+) T-cell responses during IFN-alpha/ribavirin therapy. Toward this, serial CD8(+) T-cell responses to HCV-derived epitopes and CD4(+) T-cell responses to the HCV core antigen were analyzed in four patients before (baseline), during (at 24 weeks), and at the end (at 48 weeks) of IFN-alpha/ribavirin therapy. Therapy-induced viral clearance in three patients was associated with a significant augmentation of HCV-specific type 1 CD4(+) and CD8(+) T-cell responses. In contrast, in a patient who did not respond to therapy, a significant HCV-specific CD4(+) Th2 cell reactivity was observed accompanied by a lack of augmentation of the HCV-specific CD8(+) T-cell reactivity. These results indicate that enhancement of HCV-specific CD4(+) and CD8(+) T-cell responses is an important factor in determining the response to the IFN-alpha/ribavirin therapy and the outcome of the HCV infection.