Biomedical subjects
J R Harris
Publications and source records attributed to J R Harris.
The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast.
Previous studies of patients with infiltrating ductal breast cancer treated with conservative surgery (ie, limited excision) and radiotherapy have indicated that the presence of an extensive intraductal component (EIC) in the excision specimen is highly associated with subsequent breast recurrence. The reason for this association is not clear, but possible explanations include the presence of more extensive disease in the breast or increased radiation resistance among tumors with an EIC (EIC+) compared with those without (EIC-) tumors. To investigate this association further, we related the presence or absence of an EIC in the primary tumors of 214 women who underwent mastectomy to the likelihood of finding additional foci of cancer in their mastectomy specimens using a correlated pathologic-radiologic mapping technique. Primary tumors that were EIC+ were significantly more likely to have carcinoma in the remainder of the breast than those which were EIC--(74% v 42%; P = .00001). This difference was primarily due to the presence of residual intraductal carcinoma. Seventy-one percent of EIC+ patients had residual intraductal carcinoma compared with 28% of EIC-patients (P less than .00001). In particular, 44% of EIC+ patients had "prominent" residual intraductal carcinoma compared with 3% of EIC-patients (P less than .00001). We conclude that patients whose tumors contain an EIC more frequently have a large subclinical tumor burden in the remainder of the breast compared with patients whose tumors do not contain an EIC. This observation may explain the association between EIC and subsequent breast recurrence when patients are treated with a limited excision before radiotherapy.
Improved methodology for analyzing local and distant recurrence.
Studies of radiation therapy and/or surgery in the treatment of cancer frequently use actuarial methods to estimate curves of time to local failure and compare two such curves with statistical methods originally developed for survival data. In such analyses, patients who fail first in distant sites or die before local failure are considered censored for time to local failure. While the arithmetic of these calculations is usually correct, the interpretation of the results is almost universally incorrect. For example, an actuarial Kaplan-Meier curve of time to breast recurrence after breast conserving treatment consistently overestimates the percentage of patients who would benefit from a subsequent mastectomy. Actuarial methods require the assumption that time to local failure and time to distant failure are statistically independent. For most human malignancies this is not a reasonable assumption, since there are always some patient subgroups at high risk of both local and distant failure and some patient subgroups at low risk for either type of failure. Without the assumption of independence, the time to local failure distribution is not well defined. The basic problem is that estimating time to local failure falls into the category of analyzing "competing risks," since the various causes of failure are competing for the same patient. For this reason, the effects of a particular treatment on local failure cannot be assessed separately from its effects on distant failure. This report explains the concepts of statistical independence, nonidentifiability, and competing risks and illustrates the pitfalls of using actuarial methods to assess local tumor control.(ABSTRACT TRUNCATED AT 250 WORDS)
Selection of patients with early-stage breast cancer for conservative surgery and radiation.
The great majority of patients with an early-stage breast cancer can be successfully treated with conservative surgery and radiotherapy (CS + RT). Careful clinical, radiologic, and pathologic assessment of the tumor's extent and characteristics is the key to appropriate patient selection. While disagreements remain, some guidelines for who should not be so treated have emerged. Patients with multiple palpable or radiologically detected lesions or widespread microcalcifications of the breast ordinarily should undergo mastectomy. Patients who present with a nipple discharge or subareolar mass are not suitable candidates for CS + RT unless nipple-areolar resection is acceptable to the patient. The role of pathologic margins in treatment selection remains controversial. The authors believe that margins have clinical meaning only when interpreted in relation to the histology of the primary tumor and that "negative" margins are not always needed to achieve a high rate of local tumor control.
Medical and social aspects of sexual assault of males: a survey of 100 victims.
Sexual assault of males is an infrequently reported and a poorly understood phenomenon. Details of 100 victims who sought assistance from a nationwide agency set up specifically to provide help for such individuals are reported here. Twenty eight victims were aged 16 years or over at the time of assault. The assailants were known by 72 of the victims and were perceived by the victim to have a heterosexual orientation in 72% of these cases. Attacks were often multiple and in 33 cases involved disruption of skin or mucous membranes. Twenty victims received threats about the possibility of transmission of the human immunodeficiency virus and 17 victims sought medical advice following the assault, most commonly from their general practitioner. It is suggested that greater opportunities for medical and psychological support should be given to male victims of sexual assault.
In vitro radiosensitivity of human diploid fibroblasts derived from women with unusually sensitive clinical responses to definitive radiation therapy for breast cancer.
Between January 1985 and December 1986, 811 patients were treated for carcinoma of the breast at the Joint Center for Radiation Therapy by an identical protocol. Of these 811 patients, five patients (0.6%) were identified as having an unusually sensitive clinical response to routine external beam irradiation. This unusual clinical response was characterized by severe skin erythema and edema during the first few weeks of treatment, requiring treatment breaks. Skin fibroblast cell strains were established from these five women as well as from six women with a normal clinical response to breast irradiation (chosen at random from the population of 811 patients). Radiation survival parameters were determined by a colony formation assay from complete survival curves in coded and blinded samples. Cells from the sensitive patients were significantly more sensitive to the cytotoxic effects of radiation in vitro as determined by the parameters D0, D, D10, and n, than were the strains derived from patients with a normal response. We conclude that an unusually severe response to standard fractionated radiotherapy may be associated with greater intrinsic radiation sensitivity of the individual's somatic cells.
Fat absorption and exocrine pancreatic function in human immunodeficiency virus infection.
Exocrine pancreatic function and fat absorption were determined using a 'tubeless' test in 25 human immunodeficiency virus (HIV) antibody positive subjects (23 males, two females), CDC criteria groups II (four), III (one), and IV (20). In 12 fat absorption was poor but in only three of these were the results indicative of pancreatic insufficiency and in all three this was mild. In nine of the cases the results were compatible with small intestinal malabsorption. Mild, but not severe, exocrine pancreatic insufficiency may occur in acquired immune deficiency syndrome; however fat malabsorption is more commonly associated with a small intestinal cause.
HIV infection among sub-Saharan African patients in the UK.
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Rape and subsequent seroconversion to HIV.
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Risks of AIDS among workers in the "sex industry".
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Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy.
To determine the influence of infiltrating lobular histology on local tumor control, the authors studied 49 patients with Stages I and II infiltrating lobular breast carcinoma treated by limited excision of the tumor and radiotherapy between 1968 and 1981 (median follow-up, 75 months). Results were compared with those in 561 cases of infiltrating ductal carcinoma similarly treated during the same period. The 5-year actuarial risk of local recurrence was similar for patients with infiltrating lobular or ductal carcinoma when the latter was evaluated as a single group (12% versus 11%). However, the 12% 5-year actuarial local recurrence risk for patients with infiltrating lobular carcinoma was intermediate between that for patients with infiltrating ductal carcinomas with an extensive intraductal component (23%) and those without an extensive intraductal component (5%). The pattern of recurrence in the breast was similar in the infiltrating lobular and ductal groups. All recurrences in patients with infiltrating lobular carcinoma and 80% of recurrences in the infiltrating ductal group occurred in the vicinity of the primary tumor (P = not significant). None of the clinical or morphologic features examined significantly influenced the risk of local recurrence in patients with infiltrating lobular carcinoma. The authors conclude that combined conservative surgery and radiotherapy appear to be a reasonable treatment option for patients with infiltrating lobular carcinoma, but further follow-up will be required to confirm these results.
In-situ breast cancer: the EORTC consensus meeting.
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Anti-HIV effects of alpha-interferon.
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Conservative surgery and radiation therapy for early breast cancer. Long-term cosmetic results.
To evaluate the cosmetic outcome of conservative surgery (CS) and radiation therapy (RT) for early-stage breast cancer and its stability over time, we reviewed the records of 593 patients treated from 1968 to 1981. The breast appearance was scored as "excellent," "good," "fair," or "poor". Median follow-up was 76 months (range, 37 to 186 months). Cosmetic results were generally excellent or good. The percents of excellent, good, fair, and poor results at three years were 65%, 25%, 7%, and 3%, respectively. Patients not receiving adjuvant chemotherapy were more likely than those receiving chemotherapy to have excellent scores at five years (71% vs 40%). Tumor size also influenced cosmetic outcome: 73% of patients with T1 tumors vs 55% with T2 tumors had excellent scores at five years. Our results were stable over time: of 36 patients assessable at seven years whose cosmetic scores were good or excellent at three years, 34 (94%) continued to have good or excellent scores, and only two (5%) deteriorated to fair. We conclude that the cosmetic results achieved with CS and RT are good to excellent in approximately 90% of patients and that these results remain stable for at least seven years.
Viral release from HIV-I-induced syncytia of CD4+ C8166 cells.
Infection of the permissive C8166 CD4+ lymphoid cell line with human immunodeficiency virus (HIV)-I rapidly leads to syncytium formation. Ultrastructural features of medium-sized (40 to 60 microns) syncytia and larger syncytia are presented, with emphasis upon HIV-I release from the syncytial surface and into intrasyncytial vacuoles. Although surface release of HIV-I is shown to diminish with increasing syncytial size, it does not totally stop. Massive HIV-I release and entrapment within intrasyncytial vacuoles is clearly apparent within the "foamy" multivacuolated zones within medium and large syncytia. Numerous multicored aberrant viruses are routinely detected within the intrasyncytial vacuoles, and double-budding events likewise are readily detectable at the vacuolar membranes, but less so at the syncytial surface. It is suggested that this observation may be a reflection of the more restricted availability of vacuolar membrane area for excessive viral budding as compared with that at the syncytial surface.
Factors associated with local recurrence as a first site of failure following the conservative treatment of early breast cancer.
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Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. II. Field evaluation of cross-protection against other members of the Vibrionaceae family.
Because of demonstrable cross-reactivity of cellular antigens contained in B subunit-killed whole-cell (BS-WC) and killed whole-cell-only (WC) oral cholera vaccines with antigens of various non-cholera species of the family Vibrionaceae (NCV), the protection conferred by the vaccines against diarrhoea associated with NCV was evaluated during a randomized, double-blind field trial in Bangladesh. Children aged 2-15 years and women aged greater than 15 years (62,285 in number) received three doses of BS-WC vaccine, WC-only vaccine, or a placebo consisting of Escherichia coli K12 strain (K12). During 1 year of follow-up, the incidence of treated episodes of diarrhoea associated with non-cholera vibrios known to be enteric pathogens (non-01 Vibrio cholerae, V. fluvialis, V. parahaemolyticus, V. mimicus) in the placebo group was low (1.9 cases per 10,000 recipients) and identical to that for the two vaccine groups combined. The incidence (per 10,000 recipients) of treated diarrhoeal episodes associated with Aeromonas species was considerably higher, but nearly identical in the three groups (26.1 cases for BS-WC, 26.0 cases for WC; 25.9 cases for K12). Pleisiomonas shigelloides was not isolated from any participant. It is concluded that NCV other than Aeromonas were rarely isolated from diarrhoeal patients in our study population and that killed oral vaccines which were effective against cholera exhibited no detectable cross-protection against diarrhoea associated with NCV organisms.
Prognosis following local or regional recurrence after conservative surgery and radiotherapy for early stage breast carcinoma.
Factors which influence patient prognosis following a breast recurrence or regional nodal recurrence after initial treatment of early-stage invasive breast carcinoma with conservative surgery and radiotherapy are not well known. Ninety patients treated at the Joint Center for Radiation Therapy treated from 1968-1981 had a recurrence in the treated breast before (84) or simultaneous with (6) distant metastases. Sixty-five patients had salvage mastectomy (median subsequent follow-up in patients without further disease, 32 months; range, 1-123 months). The five-year rate of further recurrence in this group was 37%. The most important variable associated with subsequent outcome was the histology of the recurrent tumor. There were no further recurrences among 10 patients with purely non-invasive cancer or 10 patients with predominantly non-invasive disease and only focal areas of invasion. In contrast, 17/45 patients (38%) with predominantly infiltrating tumors suffered further local-regional recurrences (6) or distant metastases (11) following mastectomy (5-year actuarial rate, 55%) (p less than 0.05). Ten patients developed regional nodal failures without evidence of simultaneous breast recurrence (1 internal mammary, 3 supraclavicular, 1 both supraclavicular and axillary, and 5 axillary). Only 3 of these 10 (all with axillary node failures) did not have simultaneous distant metastases; they remain alive without evidence of further distant or local-regional recurrence following salvage treatment 1, 59, and 87 months after recurrence. We conclude that the great majority of the patients (88% in this series) who have a breast recurrence following initial conservative surgery and radiation therapy for early stage breast carcinoma will have disease limited to the breast clinically and tumors amenable to salvage mastectomy. Salvage mastectomy appears to be effective treatment for patients with an isolated breast recurrence, especially if the recurrence is predominantly or wholly non-invasive.