Postmastectomy Electron-Beam-Rotation Irradiation in Locally Advanced Breast Cancer

BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.     

Measurement of vocal fold collision forces during phonation: methods and preliminary data.

Forces applied to vocal fold tissue as the vocal folds collide may cause tissue injury that manifests as benign organic lesions. A novel method for measuring this quantity in humans in vivo uses a low-profile force sensor that extends along the length and depth of the glottis. Sensor design facilitates its placement and stabilization so that phonation can be initiated and maintained while it is in place, with minimal interference in vocal fold vibration. In 2 individuals with 1 vibrating vocal fold and 1 nonvibrating vocal fold, peak collision force correlates more strongly with voice intensity than pitch. Vocal fold collision forces in 1 individual with 2 vibrating vocal folds are of the same order of magnitude as in previous studies. Correlations among peak collision force, voice intensity, and pitch were indeterminate in this participant because of the small number of data points. Sensor modifications are proposed so that it can be used to reliably estimate collision force in individuals with 2 vibrating vocal folds and with changing vocal tract conformations.     

Feasibility and construct validity of a novel laparoscopic skills testing and training model

The apprentice–tutor model was useful for training surgeons for many years, but the complexity of surgical technology in the 21st century, especially endoscopic surgery, has exponentially increased the demands for surgical education. Therefore, more and more people now accept that endoscopic surgery, demanding as it requires specific skills, should also be taught outside the operating theatre. Although many systems, including animal models and simulators, have been proposed, an in-house structured and validated method for testing and training laparoscopic skills is missing in gynaecology. We have developed a laparoscopic skills testing and training (LASTT) model and performed two studies evaluating its feasibility and the construct validity of three different exercises (camera navigation, camera navigation and forceps handling, and forceps handling and bi-manual coordination), specifically selected to test and train laparoscopic psychomotor skills (LPS). In the first study, ten experts and 14 novices repeated each exercise between 20 and 30 times. The results demonstrated that the model is useful for testing and training laparoscopic skills. Clear learning curves were observed for both experts and novices, with better scores for the former at the beginning and the end of the study, proving the construct validity of the model. In the second study, 42 experts and 241 novices repeated each exercise three times during skill evaluation workshops organised by the European Academy of Gynaecological Surgery. The results confirmed the construct validity of the model. In conclusion, the LASTT model seems a cost-effective tool for providing an in-house program for continuous training and evaluation of LPS in all surgical disciplines in which laparoscopic procedures are, or might be, performed.     

Prospective study of serum selenium levels and incident esophageal and gastric cancers

BACKGROUND: From March 1986 through May 1991, we conducted a randomized nutritional intervention trial, the General Population Trial, in Linxian, China, a region with epidemic rates of squamous esophageal and adenomatous gastric cardia cancers. We found that participants who received selenium, beta-carotene, and vitamin E had significantly lower cancer mortality rates than those who did not. In the current study, we examined the relationship between selenium levels measured in pretrial (1985) sera from participants and the subsequent risk of developing squamous esophageal, gastric cardia, and gastric non-cardia cancers during the trial. METHODS: This study was designed and analyzed in accord with a stratified case-cohort sampling scheme, with the six strata defined by sex and three age categories. We measured serum selenium levels in 590 case subjects with esophageal cancer, 402 with gastric cardia cancers, and 87 with gastric non-cardia cancers as well as in 1062 control subjects. Relative risks (RRs), absolute risks, and population attributable risk for cancers were estimated on the basis of the Cox proportional hazards models. All statistical tests are two-sided. RESULTS: We found highly significant inverse associations of serum selenium levels with the incidence of esophageal (P: for trend <10(-4)) and gastric cardia (P: for trend <10(-6)) cancers. The RR and 95% confidence interval (CI) for comparison of highest to lowest quartile of serum selenium was 0.56 (95% CI = 0.44-0.71) for esophageal cancer and 0.47 (95% CI = 0.33-0.65) for gastric cardia cancer. The population proportion of these cancers that is attributable to low selenium levels was 26.4% (95% CI = 14.45-38.36). We found no evidence for a gradient of serum selenium associated with incidence of gastric non-cardia cancer (P: for trend =.96), with an RR of 1.07 (95% CI = 0.55-2.08) for the highest to lowest quartile of serum selenium. CONCLUSIONS: Our study supports findings from previous prospective studies and randomized trials that variations in selenium levels affect the incidence of certain cancers. In the United States, where intervention trials of selenium are in the planning stages, consideration should be given to including populations at high risk for squamous esophageal and gastric cardia cancers.     

Serum tocopherols, selenium and lung cancer risk among tin miners in China

Objective: To evaluate the association of prediagnostic serum antioxidants and lung cancer risk we conducted a case–control study nested in an occupational cohort of tin miners. Methods: Male workers free of cancer enrolled in the cohort. During up to 6 years of follow-up, 339 lung cancer cases were diagnosed and, among these cases, those who donated blood prospectively (n = 108) were eligible for this study. For each case, two controls alive and free of cancer at the time of case diagnosis were matched on age and date of blood collection. Results: Overall, we observed no association between serum alpha-tocopherol, gamma-tocopherol or selenium levels and lung cancer risk. However, a significant gradient of decreasing lung cancer risk with increasing serum alpha-tocopherol was apparent for men less than 60years old (odds ratio by tertile: 1.0, 0.9, 0.2; trend p = 0.002). Alpha-tocopherol was also protective in men who reported no alcohol drinking (OR by tertile: 1.0, 0.6, 0.3; trend p = 0.008). Conclusion: Although there were no significant overall associations between prospectively collected serum alpha-tocopherol, gamma-tocopherol or selenium and incidence of lung cancer, results from this study suggest that higher alpha-tocopherol levels may be protective in men less than 60 years old and in those who do not drink alcohol.     

Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin- mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3- fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo- substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3- fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.