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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 307 records · Page 17Linked to original sources
PubMed1989

Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast.

A small number of patients with early stage breast cancer are found on presentation to have two or more separate carcinomas within the breast. To assess the effectiveness of conservative surgery and radiation therapy in these patients we compared treatment outcome among 10 patients with multiple lesions (21 cancers) and 707 patients with single lesions, treated at the Joint Center for Radiation Therapy between 1968-1981. Median follow-up was 64 months and 75 months for the multiple and single lesion groups, respectively. In each patient with multiple lesions, both (or all 3) lesions had similar histologic features. Eight of these ten patients (80%) had an infiltrating ductal carcinoma (IDC) compared to 72% of patients with single lesions. Six of these 8 patients with IDC had at least 1 lesion with an extensive intraductal component (EIC), compared to a 33% incidence of an EIC in solitary lesions. All lesions were grossly excised. Radiotherapy was given to the entire breast in all patients, with the majority also receiving a boost dose to the tumor bed site. Four of the 10 patients with multiple lesions recurred in the treated breast (40%) compared to 77 of the 707 patients (11%) with single lesions (p = 0.019, Fisher exact test). In the six patients with multiple lesions who had an EIC, three developed a local failure. In comparison, 43 of 167 patients (26%) with a single lesion with EIC developed a local failure. In patients with multiple lesions, 0 of 2 with IDC without an EIC, and 1 of 2 with histologies other than IDC had recurrence in the treated breast compared to 19 of the 342 (6%) and 15 of the 198 (8%) patients with single lesions with similar histologic features, respectively (p = NS). These results suggest that the presence of 2 or more separate primary tumors in the breast is associated with a high likelihood of local recurrence after treatment with conservative surgery and radiation therapy, even when all identified tumors are grossly resected. This may reflect the common finding of an EIC in these tumors. We conclude that the use of conservative surgery and radiation therapy for patients with more than one primary cancer in the breast should be considered with caution.

Adult↗
PubMed1989

Late cosmetic outcome after conservative surgery and radiotherapy: analysis of causes of cosmetic failure.

Although the majority of patients with early breast cancer treated with conservative surgery and radiotherapy have acceptable cosmetic outcomes, the specific causes of a less-than-acceptable result are not well known. To assess the technical factors associated with late cosmetic failure, we reviewed the records of 593 patients treated with conservative surgery and radiotherapy at the Joint Center for Radiation Therapy, Boston, between 1968 and 1981. Median follow-up was 76 months with a range of 37-186 months. Using a 4-point scoring system (excellent, good, fair, poor) patients were noted to have cosmetic "failure" if scored as either fair or poor. Cosmetic results were similar at 3, 5, and 7 years with excellent or good scores seen in 88%, 90%, and 78% of patients, respectively. Three technical factors were associated with a significant worsening of the cosmetic results. The resection of 70 cm3 or more of breast tissue was more common among the failed patients than among matched patients with good or excellent results (p = 0.03). Eighty-nine percent of patients treated with a tangent pair technique had excellent results at 5 years compared to 69% of patients treated with a three-field technique (p = 0.004). The use of a larger volume implant was associated with a greater risk of a fair or poor cosmetic result compared to the use of a smaller volume implant. We conclude that overall cosmesis has been acceptable in this series, but there are technical (surgery and radiotherapy) factors which can be modified to optimize the cosmetic result without compromising local tumor control.

Breast Neoplasms↗
PubMed1989

The predictors of distant relapse following conservative surgery and radiotherapy for early breast cancer are similar to those following mastectomy.

Although previous studies have indicated that the predictors of local recurrence following conservative surgery (CS) and radiotherapy (RT) are not the same as those following mastectomy, it remains unclear whether the predictors of distant relapse differ by local treatment modality. Clinical and pathologic features predictive of distant relapse for patients treated with mastectomy have been well established and include lymph node involvement, histologic grade, and peritumoral lymphatic vessel invasion (LVI). To study the influence of these and other factors on the rate of distant relapse in patients treated with CS and RT, we have identified a group of 438 patients treated between 1968 and 1981 who met the following criteria: primary tumor size less than or equal to 5 cm, excision of the primary tumor, infiltrating ductal carcinoma as the most aggressive histologic subtype, histology evaluable for the presence of an extensive intraductal component, and a dose to the primary site greater than or equal to 60 Gy. Estrogen receptor status was available in 58% of cases, 76% had an axillary dissection, and 23% were treated with adjuvant chemotherapy. With a median follow-up of 89 months, 107 patients (24%) developed a distant relapse. The 5-year actuarial freedom from distant relapse (FDR) was 80%. Stepdown Cox proportional hazards regression analysis identified several factors associated with a significantly (p less than 0.01) increased risk for distant relapse: positive lymph nodes, histologic grade, necrosis, and lymphatic vessel invasion. The magnitude of each effect was then examined with a lifetable calculation. Five-year freedom from distant relapse was 86% for the node-negative subgroup, 78% for patients with one to three positive nodes, and 45% for patients with four or more positive nodes. For histologic grades I, II, and III, 5-year freedom from distant relapse was 96%, 97%, and 75%, respectively. For necrosis scored as absent, scant, moderate, or marked, 5-year freedom from distant relapse was 90%, 78%, 77%, and 66%, respectively. For lymphatic vessel invasion scored as absent or present, 5-year freedom from distant relapse was 85% and 63%, respectively. We conclude that the clinico-pathologic predictors for distant relapse following conservative surgery and radiotherapy appear to be the same as those following mastectomy. This observation is consistent with the notion that distant relapse is caused by the presence of micrometastases at the time of initial patient sentation and is not greatly influenced by selection of local treatment.

Breast Neoplasms↗
PubMed1989

Can the clinical and mammographic findings at presentation predict the presence of an extensive intraductal component in early stage breast cancer?

The presence or absence of an extensive intraductal component (EIC) in early stage infiltrating ductal breast carcinoma has been considered to be an important factor in determining the extent of breast resection required prior to radiation therapy. It would therefore be useful if the presence or absence of an extensive intraductal component in a breast tumor could be predicted pre-operatively. To determine whether selected radiographic features might be correlated with whether or not a cancer is EIC+, we reviewed the pre-operative mammographic findings in 105 cases of Stage I and II infiltrating ductal carcinoma. Forty-one cases were EIC+ and 64 were EIC-. Both EIC+ and EIC- tumors were commonly detectable by mammography (93% and 83%, respectively, p = NS). EIC+ cancers, however, were significantly more likely to show microcalcifications with or without a mass compared to EIC- cases (83% vs 27%, p less than 0.0001). In particular, the presence of microcalcifications without a mammographic mass was more common for EIC+ cancers than EIC- cancers (34% vs 5% p = 0.0002). Conversely, a soft tissue mass without microcalcifications was seen mammographically in 56% of EIC- cases, compared to only 10% of EIC+ cases (p less than 0.0001). Predictive value calculations showed that the presence of microcalcifications in the absence of a mammographic mass conveys a 73% likelihood a cancer will be EIC+ (95% confidence interval = 39-94%). The positive predictive value of a mammographic mass or architectural distortion without microcalcifications for an EIC- cancer was 92% (95% confidence interval = 79-98%). We conclude that the mammographic findings may be useful pre-operatively in differentiating between patients with and without an EIC. Microcalcifications are much more commonly associated with EIC+ cancers than EIC- cancers, and the presence of an EIC- cancer without a mammographic mass is infrequent. Further characterization of the extent and pattern of microcalcifications might improve the predictive value of mammography in the pre-operative identification of patients with an EIC.

Adult↗
PubMed1989

Three-dimensional photon dose distributions with and without lung corrections for tangential breast intact treatments.

The influence of lung volume and photon energy on the 3-dimensional dose distribution for patients treated by intact breast irradiation is not well established. To investigate this issue, we studied the 3-dimensional dose distributions calculated for an 'average' breast phantom for 60Co, 4 MV, 6 MV, and 8 MV photon beams. For the homogeneous breast, areas of high dose ('hot spots') lie along the periphery of the breast near the posterior plane and near the apex of the breast. The highest dose occurs at the inferior margin of the breast tissue, and this may exceed 125% of the target dose for lower photon energies. The magnitude of these 'hot spots' decreases for higher energy photons. When lung correction is included in the dose calculation, the doses to areas at the left and right margin of the lung volume increase. The magnitude of the increase depends on energy and the patient anatomy. For the 'average' breast phantom (lung density 0.31 g/cm3), the correction factors are between 1.03 to 1.06 depending on the energy used. Higher energy is associated with lower correction factors. Both the ratio-of-TMR and the Batho lung correction methods can predict these corrections within a few percent. The range of depths of the 100% isodose from the skin surface, measured along the perpendicular to the tangent of the skin surface, were also energy dependent. The range was 0.1-0.4 cm for 60Co and 0.5-1.4 cm for 8 MV. We conclude that the use of higher energy photons in the range used here provides lower value of the 'hot spots' compared to lower energy photons, but this needs to be balanced against a possible disadvantage in decreased dose delivered to the skin and superficial portion of the breast.

Breast Neoplasms↗
PubMed1989

Initial results of a phase I trial of continuous infusion SR 2508 (etanidazole): a radiation therapy oncology group study.

To exploit both the oxygen-mimetic and "pre-incubation" or continuous exposure effects of the 2-nitroimidazole radiosensitizers, we are conducting a Phase I trial of continuous infusion SR 2508 for patients receiving brachytherapy. Following the administration of a loading dose of 2 g/m2, SR 2508 is administered by continuous infusion for 48 hr. Twenty-one patients have completed treatment. The initial total dose was 8 g/m2 with patients currently receiving 15 g/m2. No toxicity has been observed. At the higher doses the steady-state plasma concentrations have been between 50 and 70 micrograms/ml. It is not yet known whether or not hypoxic sensitizers will be of benefit clinically, and if so, when during a course of treatment is the optimal time to use them. Given the lack of toxicity and plasma concentrations achievable with continuous infusion, future studies will be conducted using SR 2508 during both the external beam and brachytherapy aspects of treatment.

Brachytherapy↗
PubMed1989

The role of Chlamydia trachomatis in chronic abacterial prostatitis: a study using ultrasound guided biopsy.

We studied 50 patients with chronic abacterial prostatitis as defined by the Stamey procedure via transrectal prostatic ultrasound and subsequent transperineal biopsy of the abnormal areas of the prostate to ascertain the role of Chlamydia trachomatis organisms (chlamydiae) in this condition. Chlamydiae were detected by an immunofluorescence technique in the urethra of 1 patient (2 per cent) but they were not recovered in McCoy cell culture from the prostatic tissue of any patient nor were they detected in the tissue by immunofluorescence. In addition, serum antibody to Chlamydia trachomatis was not found even in moderate titer. The approach in this study has overcome the problem of urethral contamination in the assessment of prostatic specimens from patients with chronic abacterial prostatitis. There is no evidence that chlamydiae are directly implicated in the disease, although the possibility of an earlier active role cannot be excluded.

Adult↗
PubMed1989

Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines.

We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a randomized, double-blind field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines among 62,285 rural Bangladeshi participants. At one year of follow-up estimates of vaccine protective efficacy (PE = 60%, P less than 0.0001 for BS-WC; PE = 54%, P less than 0.0001 for WC) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinically typical and unassociated with additional enteric pathogens (PE = 62%, P less than 0.0001 for BS-WC; PE = 52%, P less than 0.0001 for WC). In contrast, estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 (LT-ETEC, non-cholera Vibrio sp, Aeromonas sp) were substantially reduced when mixed infections with V. cholerae 01 were excluded. We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01, but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens.

Administration, Oral↗
PubMed1989

The common occurrence of human papillomavirus infection and intraepithelial neoplasia in women infected by HIV.

Eighteen out of 19 women who were clinically well but infected by HIV showed abnormalities of the lower genital tract. Seven patients had intraepithelial neoplasia, histologically verified in five, involving the cervix in four, the vulva in three and the perineum in one. Lesions (clinical and/or subclinical) compatible with human papillomavirus (HPV) infection were identified in these women, as well as in 10 out of the other 11 women infected with HIV. Disease at more than one site was detected in half of the patients and would have remained covert in more than half, had colposcopy not been undertaken. Women with HIV infection are at high risk of harbouring HPV and of developing lower genital tract neoplasia.

Adult↗
PubMed1989

Acute epididymitis: a microbiological and ultrasonographic study.

In a prospective study of 24 men (mean age 28.3 years) with acute epididymitis who underwent epididymal aspiration, micro-organisms were detected in 15 (62.5%). Chlamydia trachomatis accounted for 10 (42%) of the cases, being located in both the urethra and epididymis in 5 individuals. Chlamydial serology supported the diagnosis of chlamydial infection, there being a strong correlation between the detection of C. trachomatis and elevated titres of both chlamydial IgG and IgM antibodies. In 4 patients (mean age 55.5 years), Escherichia coli was cultured from both mid-stream urine and epididymal aspirate. Transrectal ultrasound revealed abnormal prostatic scans in 19 patients (79%). These data confirm the aetiological role of C. trachomatis, support the notion that micro-organisms spread intra-canalicularly and suggest that the prostate is also involved in the inflammatory process in acute epididymitis.

Acute Disease↗
PubMed1989

A search for infectious agents in chronic abacterial prostatitis using ultrasound guided biopsy.

A series of 60 patients with a diagnosis of chronic abacterial prostatitis, as defined by the Stamey procedure, was studied by transrectal prostatic ultrasound and subsequent transperineal biopsy of the abnormal areas of the prostate in order to ascertain the role of micro-organisms in this condition. Histological assessment revealed a chronic inflammatory infiltrate, generally of low grade, in 53 patients (88%). Organisms were isolated from the prostatic tissue of only 9 patients (15%) and were considered to be contaminants from the perineal skin, since treatment with an appropriate antimicrobial agent failed to alter symptoms or affect the leucocyte count in the urine or prostatic fluid. Chronic abacterial prostatitis may be a non-organismal inflammatory process.

Adult↗
PubMed1989

Randomised controlled trial of interferon alfa 2A (rbe) (Roferon-A) for the treatment of chronic hepatitis B virus (HBV) infection: factors that influence response.

In a randomised controlled trial recombinant interferon alpha 2A (Roferon-A, rIFN alfa A) given at a dosage of 10 million units (MU)/m2 thrice weekly for six months was significantly better (p less than 0.02) than no treatment in producing a sustained loss of hepatitis Be antigen (HBeAg) in hepatitis B virus (HBV) chronic carriers. Although lower doses (5 MU/m2 and 2.5 MU/m2) also produced some responses, the seroconversion rate was not significantly greater than that observed in the control group. Sixteen of the 45 patients receiving interferon were human immunodeficiency virus (HIV) antibody positive: none of these responded. Forty one per cent of the anti-HIV negative patients receiving interferon (12/29, p less than 0.005) lost HBeAg and 17% (5/29) lost hepatitis B surface antigen (HBsAg). The response rate among these anti-HIV negative patients receiving at least three months therapy was 46% and 19% respectively. Low pretreatment HBV-DNA and absence of anti-HIV were the only significant independent variables predicting response to therapy (p less than 0.03 and p less than 0.05 respectively). In six patients, neutralising antibodies to alpha interferon were detected during therapy, the majority being non-responders.

Adult↗
PubMed1989

Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.

Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Value of colposcopy in sexually transmitted diseases clinic based on first year's experience.

Two hundred and thirty two patients underwent cervical colposcopy within the first year of establishing a colposcopy service in the sexually transmitted diseases clinic at St Mary's Hospital, London. Their mean age was 27 years. Cervical intraepithelial neoplasia (CIN) was identified in 68 of 81 (84%) patients whose smears showed dyskaryosis and who underwent biopsy. CIN was also detected in 14 of 41 (34%) patients who underwent biopsy and whose repeat smears were reported as giving normal results. The value of assessing two consecutive smears was evident, however, because none of the 99 patients with CIN had two normal smear results consecutively. Patients requiring treatment underwent laser ablation, which was provided in the department of gynaecology. These results show that colposcopy plays a vital part in managing patients with abnormal smears and indicate that genitourinary physicians need to give priority to developing colposcopy services in their specialty.

Adolescent↗
PubMed1989

In situ carcinoma of the breast.

In situ carcinoma of the breast is a proliferation of potentially malignant cells within the lumen of the ductal-lobular system and is classified as ductal or lobular in type. It has become an increasingly frequent clinical management problem, primarily because of its enhanced detection by screening mammography. In this paper, we discuss the problems in histologic diagnosis, the natural history, presentation, and options for management of these two forms of in situ carcinoma.

Breast Neoplasms↗
PubMed1989

Clinically occult ductal carcinoma in situ detected with mammography: analysis of 100 cases with radiologic-pathologic correlation.

One hundred consecutive cases of clinically occult ductal carcinoma in situ (DCIS) detected with mammography were retrospectively analyzed to determine the spectrum of mammographic appearances and to study pathologic correlations. Seventy-two percent of the lesions appeared as microcalcifications, 10% as soft-tissue abnormalities, and 12% as a combination of the two. Six percent of lesions were found incidentally in the biopsy specimen. On the basis of mammographic measurements, 22% of the lesions were 5 mm or smaller, and 75% were 20 mm or smaller. Thirty-five percent of the microcalcification clusters were categorized as predominantly casts (linear), 52% as granular, and 13% as granular with several casts. Related pathologic features included the location of the tumor within the ductal system, pattern of growth (histologic subtype), amount and distribution of calcium formation, and presence or absence of reactive changes. Women aged 49 years or less with DCIS were more likely to have microcalcifications and less likely to have a soft-tissue mass than women aged 50 years or more (P = .04). The authors conclude that there is a wide spectrum of mammographic appearances of clinically occult DCIS.

Adult↗