A feasibility trial of Acetic acid-targeted Biopsies versus nontargeted quadrantic biopsies during BArrett's surveillance: the ABBA trial.

BACKGROUND: The aims of this study were to compare neoplasia detection rates for nontargeted biopsies (Seattle protocol) versus acetic acid-targeted biopsies (Portsmouth protocol) during Barrett's surveillance and to explore feasibility, patient/clinician experience, acceptance, and barriers/enablers to study participation and implementation of the acetic acid technique. METHODS: This was a mixed-methods feasibility study including a pilot multicenter, randomized, crossover trial with qualitative interviews. Patients under Barrett's surveillance with no history of neoplasia were included. Patients underwent two endoscopies, one with each protocol, 8 weeks apart. Outcomes included recruitment and retention rates, neoplasia yield, and number of biopsies. RESULTS: 200 patients were recruited from 6 centers, and 174 (87.0 %) underwent both procedures. Neoplasia prevalence was 4.7 % (9/192). High grade dysplasia and cancer were detected with both protocols. Five low grade dysplasias were detected (two with acetic acid, four with nontargeted biopsies; one lesion was detected with both techniques). A total of 2139 biopsies were taken in the nontargeted arm and 226 in the acetic acid arm. Both patients and clinicians found the acetic acid technique acceptable. Based on these data, a noninferiority, tandem, crossover trial would require an estimated 2828 patients. CONCLUSIONS: We demonstrated the feasibility of performing a crossover endoscopy trial in Barrett's surveillance. Low neoplasia yield makes this design necessary and qualitative results demonstrated patient and clinician acceptance. The reduced numbers of biopsies suggest that the acetic acid technique could result in cost savings, providing the lack of missed pathology can be proven in a fully powered definitive trial.

High-definition endoscopy with i-Scan for evaluation of small colon polyps: the HiSCOPE study.

BACKGROUND: Traditional white-light endoscopy cannot reliably distinguish between small (<10 mm) adenomatous and hyperplastic colon polyps. High-definition white-light (HDWL) endoscopy and i-Scan may improve in vivo characterization of small colon polyps. OBJECTIVE: To compare HDWL endoscopy and HDWL plus i-Scan for the assessment of small colon polyps and to measure performance against the American Society for Gastrointestinal Endoscopy (ASGE) thresholds for assessment of diminutive colon polyps. DESIGN: Prospective cohort study. SETTING: Single academic hospital. PATIENTS: Patients undergoing bowel cancer screening colonoscopy. INTERVENTION: In vivo assessment of all polyps <10 mm by using HDWL and i-Scan image enhancement. MAIN OUTCOME MEASUREMENTS: The primary outcome measure was overall diagnostic accuracy of in vivo assessment of colon polyps <10 mm. Secondary outcome measures were sensitivity and specificity for adenomatous histology, negative predictive value for adenomatous histology of diminutive rectosigmoid polyps, and accuracy of prediction of polyp surveillance intervals. RESULTS: A total of 209 polyps in 84 patients were included. There were no significant differences between HDWL endoscopy and i-Scan in characterization of polyps <10 mm (accuracy 93.3% vs 94.7%; P = 1.00; sensitivity 95.5% vs 97.0%; P = .50; specificity 89.3% vs 90.7%; P = 1.00). The negative predictive value for adenomatous histology of diminutive rectosigmoid polyps was 100% with both HDWL endoscopy and i-Scan. U.K. and U.S. polyp surveillance intervals were predicted with 95.2% accuracy with HDWL endoscopy and 97.2% accuracy with i-Scan. LIMITATIONS: Single-center study. CONCLUSION: HDWL endoscopy may be as accurate as HDWL with i-Scan image enhancement for the in vivo characterization of small colon polyps. Both modalities fulfil the ASGE performance thresholds for the assessment of diminutive colon polyps. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01761279.).

Role of chest CT in staging of oropharyngeal cancer: a systematic review.

BACKGROUND: The prevalence of synchronous or metastatic tumors in patients with head and neck squamous cell carcinoma (HNSCC) ranges from 6% to 20% and has implications for prognosis and management of the primary disease. There is no consensus about the role of chest CT prior to definitive treatment patients with HNSCC. METHODS: A systematic review of all chest CT studies in relation to HNSCC was performed, together with a review of our local database. RESULTS: Twenty-four studies were identified in addition to our local data. Prevalence of positive chest CT was 7.93%. Patients were significantly more likely to have a positive chest CT with N2 or N3 neck disease (p = .0062) and stage III or IV disease (p = .0001), and significantly less likely with tumors of the oral cavity (p = .0007). CONCLUSION: We advocate chest CT as part of the initial investigations for patients with HNSCC.

Continuous ambulatory peritoneal dialysis patients are unable to increase dietary intake to recommended levels.

OBJECTIVE: This study's objective was to determine whether offering dietary advice was effective in supporting patients in adjusting energy intake. DESIGN: We performed a prospective, randomized, controlled trial of dietary intervention involving 59 patients on continuous ambulatory peritoneal dialysis over a 4-month follow-up period. SETTING: The study involved outpatients on home-based renal replacement therapy. PARTICIPANTS: All participants were adult patients on continuous ambulatory peritoneal dialysis. All eligible patients were invited to take part. Subjects were randomized into two groups: control and intervention. Those with diabetes mellitus, malabsorption, malignancy, or eating disorders were excluded. INTERVENTION: Baseline measurements to assess current dietary intake and nutritional status were performed in all subjects. Measurements included a 5-day food diary, subjective global assessment (SGA), anthropometry, and serum biochemistry. After analysis of the food diaries, the participants in the control group were given follow-up dietary advice that would enable them to match intake with current dietary recommendations for this group of 1.2 g of protein per kilogram of ideal body weight, 25 cal/kg ideal body weight. Participants in the intervention group were given follow-up dietary advice that would encourage them to match energy intake with an estimate of total energy expenditure based on their calculated basal metabolic rate and physical activity level as designated using information from SGA, with a significantly lower protein intake of 0.8 to 1.0 g/kg ideal body weight and an emphasis on calories from carbohydrate and fat. Both groups completed further 5-day food diaries at 2 and 4 months to assess their ability to make the recommended changes. SGA, anthropometry, and biochemistry were all remeasured at the end of the study period. MAIN OUTCOME MEASURE: Differences in energy and protein intakes between and within the two groups from baseline to 4 months were assessed. RESULTS: Protein and energy intakes did not change during 4 months in either group, and there was no significant difference in intake between the two groups. In the control group (n = 27), 18 subjects (69%) matched their reported dietary energy intake to the recommended intake. In the intervention group (n = 28), 17 subjects (63%) matched their reported dietary intake to their estimated total energy expenditure. In the control group (n = 27), 8 subjects (28%) achieved the protein intake recommended to them of 1.2 g/kg. In the intervention group (n = 28), 23 subjects (85%) achieved the protein intake recommended to them of greater than 0.8 g/kg. CONCLUSION: Patients not meeting their dietary prescription did not adjust their intake to match the recommended advice they had been given from a dietitian. Food diary analysis showed that subjects ate less than the recommended intakes for energy and protein. This inability to change suggests that subjects may be eating to the limit of their appetite. SGA sections concerning appetite, body weight, body mass index, and estimates of energy expenditure support the view that energy intake matches requirements.

Presence and phenotype of dendritic cells in uveal melanoma.

BACKGROUND: Uveal melanoma arises in an immune-privileged site and can itself add to the immunosuppressive environment. Previous studies on cutaneous melanoma have shown the presence of tolerogenic dendritic cells (DCs), which could play an important role in the progression of the tumour. AIM: To examine the presence and functional status of DCs in a small series of uveal melanomas. METHODS: 10 cases of uveal melanoma were examined for the expression of FXIIIa, CD68, human leucocyte antigen (HLA)-DR, CD40, CD83, transforming growth factor betaR1 and indolamine 2,3 dioxygenase by immunohistochemical analysis on sections embedded in paraffin wax. RESULTS: CD68-positive macrophages were present in all of the tumours and were evenly distributed throughout. DCs expressing FXIIIa-positive were seen in 7 cases, and were often found concentrated in foci within the tumour mass. These cells were dendritic and expressed high levels of HLA-DR. The DCs did not express the maturation markers CD83 or CD40. In one case, concentration of DCs around the area of tumour necrosis was observed, and some of these cells expressed CD83. CONCLUSION: Numerous tolerising antigen-presenting cells may play a role in melanoma-related immunosuppression in the eye, although activation of DCs may be associated with tumour necrosis.

Cancer cell adaptation to chemotherapy.

BACKGROUND: Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. METHODS: Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. RESULTS: In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIalpha (TOPOIIalpha). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIalpha in 6/7 colorectal tumors and 8/10 ovarian tumors. CONCLUSION: This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation to chemotherapy may explain why prediction of resistance mechanisms is difficult on the basis of tumor type alone or individual markers, and suggests that more complex predictive methods are required to improve the response rates to chemotherapy.

Presence and maturity of dendritic cells in melanoma lymph node metastases.

Immune avoidance mechanisms play a key role in the successful dissemination of melanoma. One mechanism whereby this could be achieved is by interfering with dendritic cell (DC) presentation of tumour-associated antigens to naïve T cells. In particular, immature DCs characterized by the absence of accessory molecules are known to be immunosuppressive and to be involved in the induction of tolerance. The present study has investigated the presence and activation status of DCs within melanoma metastases in the regional lymph nodes. Using image analysis techniques, the expression of Factor XIIIa (FXIIIa), CD40, CD83 and HLA-DR and the morphological features of DCs were examined in paraffin sections from 26 lymph nodes containing melanoma metastases. DCs expressing FXIIIa were found in 70% of the lymph nodes. The number of DCs identified was generally small but there were more concentrated areas of DCs designated as hotspots. In these areas of high FXIIIa staining, the percentage area occupied by DCs varied between 0.1% and 10%. The majority of FXIIIa-positive cells did not express the DC maturation markers CD83 or CD40 and morphologically were rounded with few dendrites, indicating that they were immature. The cells did, however, express high levels of HLA-DR, suggesting that they have the ability to present antigen but lack the accessory molecules required to initiate an immune response. Immature DCs, characterized by phenotypic and morphological features, are therefore present within the tumour deposits in lymph nodes infiltrated by melanoma and may specifically modulate the anti-melanoma immune response.