Nodal staging affects adjuvant treatment choices in elderly patients with clinically node-negative, estrogen receptor-positive breast cancer.

Background: In response to Choosing Wisely recommendations that sentinel lymph node biopsy (slnb) should not be routinely performed in elderly patients with node-negative (cN0), estrogen receptor-positive (er+) breast cancer, we sought to evaluate how nodal staging affects adjuvant treatment in this population. Methods: From a prospective database, we identified patients 70 or more years of age with cN0 breast cancer treated with surgery for er+ her2-negative invasive disease during 2012-2016. We determined rates of, and factors associated with, nodal positivity (pN+), and compared the use of adjuvant radiation (rt) and systemic therapy by nodal status. Results: Of 364 patients who met the inclusion criteria, 331 (91%) underwent slnb, with 75 (23%) being pN+. Axillary node dissection was performed in 11 patients (3%). On multivariate analysis, tumour size was the only factor associated with pN+ (p = 0.007). Nodal positivity rates were 0%, 13%, 23%, 33%, and 27% for lesions preoperatively sized at 0-0.5 cm, 0.5-1 cm, 1.1-2.0 cm, 2.1-5.0 cm, and more than 5.0 cm. Compared with patients assessed as node-negative, those who were pN+ were more likely to receive axillary rt (lumpectomy: 53% vs. 1%, p < 0.001; mastectomy: 43% vs. 2%, p < 0.001), and adjuvant systemic therapy (endocrine: 82% vs. 69%; chemotherapy plus endocrine: 7% vs. 2%, p = 0.002). Conclusions: Of elderly patients with cN0 er+ breast cancer, 23% were pN+ on slnb. Size was the primary predictor of nodal status, and yet significant rates of nodal positivity were observed even in tumours preoperatively sized at 1 cm or less. The use of rt and systemic adjuvant therapies differed by nodal status, although the long-term oncologic implications require further investigation. Multidisciplinary input on a case-by-case basis should be considered before omission of slnb.

Selected medical interventions in women with a deleterious BRCA mutation: a population-based study in British Columbia.

Background: We examined the uptake of risk-reducing interventions, including bilateral mastectomy, risk-reducing salpingo-oophorectomy, oral contraceptive pills, tamoxifen, and raloxifene, for the entire population of women with a deleterious BRCA1 or BRCA2 mutation in the Canadian province of British Columbia. Methods: This retrospective population-based study used data available in British Columbia for all women who, between 1996 and 2014, were tested and found to have a BRCA mutation. Rates of risk-reducing interventions stratified according to the type of BRCA mutation and prior history of breast or gynecologic cancer (ovary, fallopian tube, peritoneal) are presented. Cancers diagnosed in women with a BRCA mutation after disclosure of their mutation status are also presented. Results: The final study cohort consisted of 885 patients with a deleterious BRCA1 (n = 474) or BRCA2 (n = 411) mutation. Of the women with no prior breast cancer, 30.8% carrying a BRCA1 mutation and 28.3% carrying a BRCA2 mutation underwent bilateral mastectomy. Of women with no prior gynecologic cancer, 64.7% carrying a BRCA1 mutation and 62.2% carrying a BRCA2 mutation underwent risk-reducing bilateral salpingo-oophorectomy. Rates of chemoprevention with oral contraceptive pills and tamoxifen or raloxifene were low in all groups. In this cohort, 23 gynecologic and 70 breast cancers were diagnosed after disclosure of BRCA mutation status. Conclusions: Our results suggest reasonable uptake of risk-reducing interventions in high-risk women. To minimize the occurrence of breast and ovarian cancer in women with a BRCA1 or BRCA2 mutation, more attention could be paid to ensuring that affected women receive proper counselling and follow-up.

Comparison of computer-assisted instruction (CAI) versus traditional textbook methods for training in abdominal examination (Japanese experience).

PURPOSE: This study aimed to compare the effects of computer-assisted, text-based and computer-and-text learning conditions on the performances of 3 groups of medical students in the pre-clinical years of their programme, taking into account their academic achievement to date. A fourth group of students served as a control (no-study) group. METHOD: Participants were recruited from the pre-clinical years of the training programmes in 2 medical schools in Japan, Jichi Medical School near Tokyo and Kochi Medical School near Osaka. Participants were randomly assigned to 4 learning conditions and tested before and after the study on their knowledge of and skill in performing an abdominal examination, in a multiple-choice test and an objective structured clinical examination (OSCE), respectively. Information about performance in the programme was collected from school records and students were classified as average, good or excellent. Student and faculty evaluations of their experience in the study were explored by means of a short evaluation survey. RESULTS: Compared to the control group, all 3 study groups exhibited significant gains in performance on knowledge and performance measures. For the knowledge measure, the gains of the computer-assisted and computer-assisted plus text-based learning groups were significantly greater than the gains of the text-based learning group. The performances of the 3 groups did not differ on the OSCE measure. Analyses of gains by performance level revealed that high achieving students' learning was independent of study method. Lower achieving students performed better after using computer-based learning methods. CONCLUSION: The results suggest that computer-assisted learning methods will be of greater help to students who do not find the traditional methods effective. Explorations of the factors behind this are a matter for future research.

Recent progress in the management of retroperitoneal sarcoma.

Retroperitoneal sarcomas (RPS) are rare tumours that typically present late and carry a poor prognosis even following grossly complete resection. In an attempt to improve the outlook for patients with RPS, sarcoma specialists have employed various adjuvant therapies, including extermal beam radiation, intraoperative radiation, brachyradiation and systemic chemotherapy. This article reviews the presentation and prognosis of RPS, and focuses on the results of new treatment strategies compared with conventional management.A Medline search of the English literature was performed to identify all retrospective and prospective reports relating to the management of adult RPS published since 1980. Series that did not analyse RPS separately from other intra-abdominal or extra-abdominal sarcomas or other malignancies were excluded, and information on investigation, presentation, prognostic factors, treatment and outcome was extracted from the remaining reports. Survival and local control data were collected from reports that contained at least 30 cases of RPS (n = 31).While surgical resection remains the cornerstone of treatment for RPS, the majority of patients will relapse and die from sarcoma within 5 years of resection. Adjuvant radiation may improve these results, but further trials are required to definitively demonstrate its benefit. Possible reasons for the failure of conventional treatment are discussed, and alternative strategies designed to overcome these obstacles are presented.

Teaching and evaluation of basic surgical techniques: the University of British Columbia experience.

Surgical technical education has traditionally followed an apprenticeship format. The need for innovative undergraduate programs using dry and wet labs prior to clinical exposure continues to be an area of debate. Specific programs have been described to improve surgical skills; however, an accepted platform for training and evaluation of surgical skills programs has not been recognized. Therefore, introduction of specific programs to teach undergraduate medical students surgical skills is essential. This article describes the Basic Surgical Technique (BST) program taught at the University of British Columbia and reports the effectiveness of this program in improving the practical skills of undergraduate medical students. The program includes BST I for third-year students performed in a dry lab setting, and BST II for medical student interns (MSI) performed at the animal laboratories using female domestic swine as subjects. A total of 87 students participated in the study. The program is designed using Piaget's and Vygotsky's pedagogical philosophy of "learning by doing." A semiquantitative method is used to measure and analyze the outcome of this project. Data were validated using student self-evaluation tests and by quantitative evaluation by surgical staff from the surgical wards. Results of this prospective project indicated that the BST program significantly (p < .05) improved the surgical performance of undergraduate students, and that the time lapse between BST I and II has had a negative impact in retention of acquired surgical skills. This study concludes that the BST program taught at the University of British Columbia significantly improves the surgical skills of medical students and improves their self-confidence during their internship.

An animal model of benign bile-duct stricture, sclerosing cholangitis and cholangiocarcinoma and the role of epidermal growth factor receptor in ductal proliferation.

OBJECTIVE: To adapt an animal model of benign bile-duct stricture, sclerosing cholangitis and cholangiocarcinoma in order to determine if the expression of epidermal growth factor receptor (EGFr) could be used to differentiate these lesions. DESIGN: A prospective control study with blinded interpretation of liver biopsy histology and immunohistochemical staining as the criterion standards. SETTING: A university-affiliated research centre. SUBJECTS: Male Syrian Golden hamsters (40 for benign duct stricture, 29 for sclerosing cholangitis and 27 for cholangiocarcinoma). INTERVENTIONS: Ligation of the common bile duct with 6-0 catgut for benign duct stricture; injection of the biliary tree with 0.15 mL of formalin for sclerosing cholangitis; and weekly subcutaneous injections of 500 mg/kg of di-isopropanolnitrosamine for 10 weeks followed by ligation of the common bile duct with 6-0 catgut for cholangiocarcinoma. Routine histologic preparation of liver biopsies obtained at autopsy 10 weeks postoperatively then immunohistochemical staining of specimens for EGFr. MAIN OUTCOME MEASURES: The development of benign or atypical biliary ductal proliferation, including adenoma and carcinoma formation. The presence or absence of immunohistochemical staining for EGFr. RESULTS: Benign ductal proliferation without atypia was seen in 15 of 21 animals in the bile-duct-stricture group that were sacrificed, in 15 of 24 animals in the sclerosing cholangitis group and in 17 of 18 animals in the cholangiocarcinoma group. Atypical proliferation was seen in 13 of 18 animals with cholangiocarcinoma but not in the other two groups. The differential occurrence of atypical ductal proliferation was statistically significant (p < 0.00001) for both groups. No evidence of EGFr expression was found in any group. CONCLUSION: Although the animal model was valid histologically for comparing benign and malignant biliary disease, EGFr does not play a role in biliary ductal proliferation and so cannot be used to differentiate between benign and malignant lesions.

Differentiation of thyroid neoplasms by evaluating epithelial membrane antigen, Leu-7 antigen, epidermal growth factor receptor, and DNA content.

The expression of epithelial membrane antigen (EMA), Leu-7 antigen, epidermal growth factor receptor (EGFr), and deoxyribonucleic acid (DNA) content in 40 thyroid nodules was investigated to identify those factors that might differentiate these lesions or correlate to their prognosis. There were 22 carcinomas (16 papillary, 4 follicular, 1 anaplastic, 1 medullary) and 18 benign lesions prospectively obtained between 1989 and 1993. Patients' charts were reviewed to establish a database of known clinical prognostic indicators. Expression of EMA and Leu-7 was significant in malignant lesions when compared to benign lesions (P < 0.02 and P < 0.001). EMA was expressed significantly more frequently by follicular carcinomas than by follicular adenomas (P < 0.03). Leu-7 antigen was expressed by all papillary carcinomas. Neither of these antigens showed any association with known clinical prognostic indicators. EGFr expression neither differentiated benign from malignant lesions nor correlated with prognostic factors. The presence of aneuploidy correlated with poor tumor differentiation (P < 0.02), but did not distinguish benign from malignant lesions. These results suggest that EMA expression may be useful for confirming malignancy in follicular neoplasms and that the expression of Leu-7 antigen can assist in distinguishing papillary carcinoma from benign lesions with pseudopapillae.

Posttranslational modification of prothyroid hormone.

Posttranslational processing of thyroglobulin may influence its role as the prothyroid hormone. We have examined the role of glycosylation in the subsequent export and iodination of thyroglobulin. We find that glycosylation is necessary both for the movement of thyroglobulin through the cell and for iodination. During posttranslational processing, thyroglobulin is also phosphorylated and carboxymethylated. The implications of these postsynthetic modifications are discussed.