Recurrence rates after DCE-MRI image guided planning for breast-conserving surgery following neoadjuvant chemotherapy for locally advanced breast cancer patients.

BACKGROUND: Neoadjuvant therapy results in a significant increase in breast-conserving surgery. However, traditional imaging methods are unable to accurately predict the extent of viable residual disease leading to uncertainty in surgical planning and some previous studies have shown a disproportionately high incidence of locoregional recurrence. Dynamic contrast enhanced-MRI (DCE-MRI) has been shown to provide a potentially more accurate prediction of residual disease. RESULTS: Patients undergoing neoadjuvant chemotherapy for breast cancer in our unit are staged with the DCE-MRI of the breast performed at 1.5 T before, during and after treatment and the final result was used to plan surgery. Two hundred and four patients with breast cancer were treated with neoadjuvant chemotherapy between 1996 and April 2005. Eighteen of these patients had distant metastases at the time of initial diagnosis and so were excluded from the present study. Following neoadjuvant chemotherapy, 186 patients underwent surgical treatment. Of these, 68 patients had breast-conserving surgery. At a median follow up of 30 months (range: 5.6-72 months) 21 patients in this group developed subsequent recurrence (21/68 - 30%) of whom 9 (9/68 - 13%) had locoregional recurrence, 7 had local recurrence (7/68 - 10%), and 17 (17/68 - 25%) had distant recurrence. Logistic regression analysis revealed only vascular invasion (p=0.006) of the tumour to be significantly associated with overall recurrence. None of the pathological factors (ER, PR status, vascular invasion, lymph node metastases, pathological complete response to neoadjuvant chemotherapy) showed a significant association with locoregional recurrence. CONCLUSION: Breast-conserving surgery with DCE-MRI planning after neoadjuvant chemotherapy provides an acceptable level of local recurrence without the need for mastectomy.

Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer?

The cloning of a second estrogen receptor (ER), ER beta, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n = 23) and malignant (n = 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ER beta predominated, with 22% of samples exclusively expressing ER beta; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ER alpha, either alone or in combination with ER beta. Interestingly, those tumors that coexpressed ER alpha and ER beta were node positive (P = 0.02; Fisher's exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ER beta in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ER beta may be a useful prognostic factor in patients with breast cancer.

Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer.

7Alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (ICI 182,780; Faslodex) is a novel steroidal antiestrogen. This partially blind, randomized, multicenter study compared the effects of single doses of long-acting ICI 182,780 with tamoxifen or placebo on estrogen receptor (ERalpha) and progesterone receptor (PgR) content, Ki67 proliferation-associated antigen labeling index (Ki67LI), and the apoptotic index in the primary breast tumors of postmenopausal women. Previously untreated patients (stages T(1)-T(3); ER-positive or -unknown) were randomized and received a single i.m. dose of ICI 182,780 50 mg (n = 39), ICI 182,780 125 mg (n = 38), or ICI 182,780 250 mg (n = 44) or oral tamoxifen 20 mg daily (n = 36) or matching tamoxifen placebo (n = 43) for 14-21 days before tumor resection surgery with curative intent. The ER and PgR H-scores, together with the Ki67LI were determined immunohistochemically in the matched pretreatment biopsy and the posttreatment surgical specimens. The apoptotic index was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling on the same samples. The effects of treatment on each of these parameters were compared using analysis of covariance. ICI 182,780 produced dose-dependent reductions in ER and PgR H-scores and in the Ki67LI. The reductions in ER expression were statistically significant at all doses of ICI 182,780 compared with placebo (ICI 182,780 50 mg, P = 0.026; 125 mg, P = 0.006; 250 mg, P = 0.0001), and for ICI 182,780 250 mg compared with tamoxifen (P = 0.024). For PgR H-score, there were statistically significant reductions after treatment with ICI 182,780 125 mg (P = 0.003) and 250 mg (P = 0.0002) compared with placebo. In contrast, tamoxifen produced a significant increase in the PgR H-score relative to placebo, and consequently, all doses of ICI 182,780 produced PgR values that were significantly lower than those in the tamoxifen-treated group. All doses of ICI 182,780 significantly reduced Ki67LI values compared with placebo (ICI 182,780 50 mg, P = 0.046; 125 mg, P = 0.001; 250 mg, P = 0.0002), but there were no significant differences between any doses of ICI 182,780 and tamoxifen. ICI 182,780 did not alter the apoptotic index when compared with either placebo or tamoxifen. Short-term exposure to ICI 182,780 reduces the ERalpha in breast tumor cells in a dose-dependent manner by down-regulating ER protein concentration. The reductions in tumor PgR content by ICI 182,780 demonstrate that ICI 182,780, unlike tamoxifen, is devoid of estrogen-agonist activity. Reductions in tumor cell proliferative activity (as indicated by Ki67LI) show that ICI 182,780 is likely to have antitumor activity in the clinical setting.

Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status.

PURPOSE: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. In breast cancer, tumor VEGF has been shown to have a good correlation with relapse-free survival. The aim of this study was to determine the relation of serum VEGF levels to the various indices of breast cancer and known tumor markers carcinoembryonic antigen and CA15.3. EXPERIMENTAL DESIGN: Preoperative serum VEGF levels were determined in 200 women with breast cancer and compared with serum VEGF levels in 88 healthy female controls. RESULTS: The serum VEGF levels of the cancer patients as a group were significantly elevated compared with those of the controls (P < 0.0005). VEGF levels were elevated in patients with invasive cancer of ductal/no specific type, ductal carcinoma in situ, and estrogen receptor (ER)-positive tumors. Patients with lobular carcinoma and ER-negative tumors had serum VEGF levels comparable with those in the controls. VEGF was more sensitive than CA15.3 and carcinoembryonic antigen in detecting breast cancer. CONCLUSIONS: Preoperative serum VEGF detects breast cancer with a sensitivity of 62.1%. The relationship to cancer type and ER status may have future therapeutic implications. Additional long-term studies are required to determine the prognostic significance of serum VEGF.

Dynamic contrast-enhanced magnetic resonance imaging of the breast combined with pharmacokinetic analysis of gadolinium-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma.

RATIONALE AND OBJECTIVES: This study was designed to assess the efficacy of dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast combined with pharmacokinetic analysis of gadolinium (Gd)-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma. METHODS: Fifty women treated with breast-conserving surgery and radiotherapy underwent breast MRI. Dynamic magnetic resonance data obtained at four preselected slice locations were analyzed to examine Gd-DTPA uptake based on a pharmacokinetic model using three parameters: wash-in rate, wash-out rate, and amplitude of uptake. Synthetic images were produced from the above parameters and their derivatives--maximum uptake and reciprocal of half the time to maximum. For each region of interest (ROI), median parameter values were calculated. The mean pixel signal intensity of each ROI was plotted against time, and an enhancement index was determined. RESULTS: Sixty ROIs were selected: 49 lesions were benign, and 11, malignant. Significant differences between benign and malignant lesions were found for the enhancement index (P < 0.0001), maximum uptake (P < 0.0001), amplitude of uptake (P < 0.0001), wash-in rate (P = 0.03), wash-out rate (P = 0.01), and the reciprocal of half the time to maximum (P = 0.0005). The respective sensitivities and specificities were as follows: for the enhancement index, 1.00 and 0.96; for maximum uptake, 1.00 and 0.96; for amplitude of uptake, 0.91 and 0.94; for wash-in rate 0.82 and 0.47; for wash-out rate 0.91 and 0.59; and for the reciprocal of half the time to maximum, 1.00 and 0.51. CONCLUSIONS: Dynamic scanning proved essential for the detection and differential diagnosis of local tumor recurrence. Pharmacokinetic analysis of Gd-DTPA uptake can be used to produce parametric images that retain the spatial resolution of the original images while providing additional information about lesion permeability and vascularity, and helping to avoid the observer variability associated with ROI analysis.

Evaluation of response to neoadjuvant chemoradiotherapy for locally advanced breast cancer with dynamic contrast-enhanced MRI of the breast.

AIMS: This study aimed to examine the feasibility of utilizing dynamic contrast-enhanced MRI (DCE-MRI) of the breast for the planning of surgical intervention following neoadjuvant therapy for locally advanced breast cancer (LABC). METHODS: Following their neoadjuvant therapy, women with LABC were followed-up by DCE-MRI in addition to clinical examination and mammography. If any modality suggested residual disease, surgery was carried out--initially salvage mastectomy and then breast-conserving surgery where appropriate. RESULTS: Seventeen women were recruited: stage III (n=16), stage IV (n=1) mean age 55 (range 34-74). Following neoadjuvant therapy, 10 mastectomies and two local excisions were performed for 10 histologically confirmed residual cancers. Median follow-up for those women not undergoing surgery is 3.24 (IQR 2.8-3.5) years. DCE-MRI proved 100% accurate for the delineation of residual disease and facilitated the planning of the local excisions. Clinical examination and mammography proved inaccurate (PPV 83% and 75% and NPV 55% and 80%, respectively). CONCLUSIONS: DCE-MRI is a potentially accurate method of delineating residual tumour following neoadjuvant therapy for LABC and may be used to plan appropriate operative intervention where required.

Interactive multimedia information program for use by breast-care nurses--a patient acceptability study.

AIMS: To design an interactive multimedia program for use by breast-care nurses and evaluate the acceptability of this technology to patients in the clinical setting. METHODS: In order to ensure that the clarity of the information was maintained the multimedia program was developed by a multidisciplinary team, including non-medical personnel and patients. A prospective analysis of the subjective impressions of patients with symptomatic breast disorders and breast-care nurses to a multimedia patient information system was then performed using a standard questionnaire and semi-structured interviews. RESULTS: Fifty women were recruited for the study. Thirty-six (72%) considered the multimedia counselling to be superior to the traditional modalities. Forty-nine (98%) graded the system as good or better. No patient regarded the technology as anxiety-provoking or inferior to the traditional leaflet-based approach. Women over 55 years old found the system as acceptable and easy to use as the younger women. CONCLUSIONS: The multimedia breast counselling programme was acceptable to patients and was considered superior to the traditional leaflet-based approach by the majority. The inherent advantages of this technology will lead to its increasing utilization in the clinical setting.

Dynamic contrast-enhanced and fat suppressed magnetic resonance imaging in suspected recurrent carcinoma of the breast: preliminary experience.

20 women with suspected recurrent breast cancer who had undergone previous breast-conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast.

Pigmented skin lesions in black newborn infants.

Three findings from a study of one hundred black newborn infants examined for pigmented lesions are presented herein: significantly higher incidence than in prior neonatal examinations, a frequent clinical pattern of grouped macules, and an unusual histologic distribution of nevus cell theques. Fifty-one percent of the infants had congenital pigmented lesions. Biopsy specimens of thirty-two lesions were obtained, twenty-six showing histologic changes of lentigo, four melanocytic nevi (nevus-cell nevi), and two ephelides. Three of the four nevi were less than 1.5 cm in diameter and all were of the predominantly junctional type. Clinical appearance was not a consistent guide for classification in the newborn.

Pancreatic function in domestic cats with pancreatic fluke infection.

Thirty-one of 290 cats (10.7%) from the area around St Louis, Mo, were infected with Eurytrema procyonis. In some cats, the pancreas was severely affected, with almost complete atrophy and fibrous replacement of the gland. Both bicarbonate and protein secretions were impaired, although clinically evident pancreatic insufficiency was not seen.

Jejunal perforation as a result of massive gastrointestinal bleeding from a duodenal ulcer.

A complication of massive upper gastrointestinal bleeding is presented as a case report of a patient who developed a spontaneous perforation of the small intestine as a result of massive bleeding from a duodenal ulcer.

An American Board of Orthodontics case report. A nonsurgical and nonextraction approach in the treatment of a skeletal and dental Class III malocclusion in a growing patient.

This case report is presented following the specifications of the American Board of Orthodontics. The patient had a true maxillary retrognathism, a mandibular prognathism, and a lower anterior height deficiency. She was treated with a fixed orthopedic appliance, fixed orthodontic appliances, and intermaxillary elastics. [This case was presented to the American Board of Orthodontics in partial fulfillment of the requirement for the certification process conducted by the Board.

The hard penile circumferential fold as the presenting finding in primary syphilis: report of six cases.

BACKGROUND: Six patients with firm circumferential folds located in the balanic sulcus of the penis were studied. OBJECTIVE: The purpose of the study was to determine the origin of the lesions. METHODS: These patients were examined clinically, with dark-field examination when possible and with a serologic test for syphilis. RESULTS: All patients had reactive serologic tests for syphilis and had enlarged, firm, nontender, inguinal lymph nodes. CONCLUSION: Although we were unable to prove with certainty that the origin of these folds was syphilitic, all patients had clinical and serologic findings that supported the diagnosis of primary syphilis.

Haemoperitoneum caused by Meckel's diverticulum.

A case of Meckel's diverticulum presenting acutely with spontaneous haemoperitoneum is presented. This complication has not, to our knowledge, been previously reported.

Lupus profundus in children: treatment with hydroxychloroquine.

Discoid lupus erythematosus and lupus profundus, rare in children, are described in two young girls, one with onset at 3 1/2 years of age, the other at 8 years of age. Unusual nodules of the face that ultimately healed with atrophy and hyperpigmentation showed histologic and immunofluorescent confirmation of lupus erythematosus. These patients, the second and third in the English literature to be treated for childhood lupus profundus with antimalarials, responded successfully to hydroxychloroquine. No systemic involvement was found.

Drug-induced pemphigus related to angiotensin-converting enzyme inhibitors.

We report a case of drug-induced pemphigus caused by an angiotensin-converting enzyme inhibitor, captopril. The cutaneous reaction remitted after withdrawal of captopril therapy. Unique to this case, however, was the substitution of another angiotensin-converting enzyme inhibitor, enalapril, without exacerbation of the pemphigus. To the best of our knowledge, this is the first reported patient with captopril-induced pemphigus in whom no new lesions developed after subsequent treatment with enalapril. A difference in chemical structure between these two drugs, particularly of a sulfur moiety, may help explain why the drug-induced disease did not recur.

Abnormal insulin secretion in carcinoma of the pancreas: response to glucagon stimulation.

In 34 patients suspected of having pancreatic cancer glucose homeostasis and insulin secretion in response to intravenous glucagon (1 mg) were studied prospectively. Twelve patients had pancreatic cancer at laparotomy and the remainder were designated a control group. Responses were also measured in 12 healthy volunteers. There was no significant difference in the rise of blood glucose between the groups after glucagon. The mean plasma insulin concentrations rose rapidly in both groups after glucagon but were significantly lower in the pancreatic cancer group. In patients with obstructive jaundice the plasma insulin response was a better discriminator of pancreatic cancer. Abnormal pancreatic beta-cell function is detectable in patients with pancreatic carcinoma before any change in glucose homeostasis, particularly in patients with obstructive jaundice. The glucagon stimulation test may be useful in the earlier diagnosis of pancreatic carcinoma before the development of clinically overt diabetes mellitus.

Results of the first year of breast cancer screening in a district hospital.

The Humberside Breast Screening Service completed 1 year of screening by October 1990; 16,534 women were invited of whom 12,832 (77.6 per cent) attended. A group of 644 women (5.0 per cent) were called for further assessment and of these 134 underwent 135 primary surgical procedures. After assessment 25 were shown before operation to have cancer. One hundred and nine women had suspicious lesions and proceeded to surgical biopsy; 50 lesions proved malignant (benign: malignant biopsy ratio 1.2:1). The 75 malignant lesions represented a prevalence of 5.8 per 1000 of the screened population. Invasive cancer > 1 cm in diameter formed almost half of the malignant lesions. This service has cost 32 pounds per woman screened or 5533 pounds per cancer detected. The results are comparable to those of previous studies and suggest that a mammographic screening service can be successfully provided in a district hospital setting.

Conservative management of infective mastitis and breast abscesses after ultrasonographic assessment.

Current practice in this unit for a suspected breast abscess is preliminary ultrasonographic scan, aspiration of any pus, antibiotic therapy and repeat aspiration in the outpatient clinic if necessary. Inflammatory masses are treated with antibiotics alone. A retrospective review of this strategy has been made. Over a 2-year interval 53 patients were admitted to hospital with a suspected breast abscess. Twenty-two abscesses were aspirated, of which 19 resolved and three required subsequent incision and drainage. Eight patients underwent primary incision and drainage, one of whom required a second drainage procedure. In five patients the abscess discharged spontaneously before intervention. The remaining 18 patients were found on ultrasonography to have inflammation without evidence of focal pus which settled with antibiotic therapy in all but two patients. One of these was found to have an inflammatory cancer and the other developed an abscess, which was drained. Aspiration combined with ultrasonographic imaging is an effective alternative to incision and drainage.