Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint cytology and immunohistochemistry. Part II. Results.

AIM: In order to operate selectively on positive axillae during the initial operative session for early breast cancer, an accurate and rapid intraoperative method to examine an axillary node sample (ANS) or a sentinel node biopsy (SNB) is required. The aim of this study was to determine the feasibility and accuracy of Immunohistochemistry (IHC)-stained touch imprints in detecting metastatic axillary nodes intraoperatively. MATERIAL AND METHODS: Four hundred and thirty-two axillary nodes from 52 patients (23 axillary node clearance (ANC), 15 ANS and 14 SNB) were bisected, imprinted and stained with anti-cytokeratin 19 IHC. Results were compared with those of routine haematoxylin and eosin (H&E)-stained sections. RESULTS: IHC imprints detected 32 positive nodes from 12 patients. H&E sections detected 31 positive nodes from 11 patients. IHC imprints missed metastases in three nodes and missed the diagnosis of positive axillae in two patients. H&E missed metastases in four nodes and missed the diagnosis of positive axillae in 3 patients. On a node-basis, sensitivities were 91.4 and 88.5%, negative predictive values (NPV) were 99.2 and 99.0% and overall accuracies were 99.3 and 99.1% for IHC imprints and H&E sections, respectively. On a patient-basis, sensitivities were 85.7 and 78.5%, NPVs were 95.2 and 93.1% and overall accuracies were 96.1 and 94.2% for IHC imprints and H&E sections respectively. There were no false positives. Interpretation of the results by a non-histopathologist was concordant with that of a histopathologist. Results might be obtained within 30-45 min depending on the number of examined nodes. CONCLUSION: Intraoperative IHC staining of touch imprints of axillary sentinel nodes is feasible and is a reliable method for evaluating axillary nodes. Slides can be reliably interpreted by a trained non-histopathologist.

Patient demographics and treatment for early breast cancer: an observational study.

This study aims to examine relationships between demographic factors and treatment choice for early breast cancer (T2/N<1). Two hundred and two patients were offered modified radical mastectomy (MRM), breast conserving therapy (BCT) or MRM and reconstruction and interviewed at a University Hospital and oncology centre in South Wales. Median age at treatment was 57 (32-90) years. Seventy-one patients (35%) choose MRM, 10 (5%) MRM and reconstruction and 121 (60%) BCT. Median age of women choosing MRM was 61 and 55 for BC (P<0.0001). Single women (P=0.009) and those with no family history of breast cancer (P=0.02) were more likely to choose MRM. There was no difference between treatment choice and method of cancer detection and the age at which the patient left education (P=0.065). Mean histological tumour diameter was smaller for women choosing BC (15 mm) than for women choosing mastectomy (17 mm; P=0.014). There was no association between tumour grade and treatment choice.

Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint cytology and immunohistochemistry: I. Protocol of rapid immunostaining of touch imprints.

AIMS: Sentinel Node Biopsy (SNB) is considered an accurate method of detecting axillary lymph node status in patients with small breast cancer. Combined with an accurate and rapid histopathology tool, it could spare this group of patients unnecessary Axillary Node Clearance (ANC) with its associated hazards. Intraoperative examination of SNB for cancer cells has been investigated using both Frozen Sections (FS) and Imprint Cytology (IC) stained with different stains. This study is devoted to establish a reliable and rapid protocol for immunostaining of touch imprints from SNB. METHODS: We investigated two different EPOS (Enhanced Polymer One-Step staining--DAKO) anticytokeratin antibodies, five different tissue fixatives and different incubation periods and temperatures with both positive and negative controls. RESULTS: We have developed a protocol, which produced good and consistent immunostaining of touch imprints. The initial results using this protocol are concordant with those of permanent Haematoxylin and Eosin (H&E) sections. CONCLUSIONS: We propose this protocol for rapid immunostaining of touch imprints of SNB.

Evaluation of axillary lymph nodes using touch imprint cytology and immunohistochemistry.

BACKGROUND: The success of sentinel node biopsy in determining axillary lymph node status necessitates an accurate and rapid method for intraoperative examination of the nodes. The aim was to determine the feasibility and accuracy of immunohistochemistry (IHC) of touch imprints in detecting axillary nodal metastases intraoperatively. METHODS: Some 344 axillary nodes from 30 patients with early breast cancer were bisected, imprinted and subjected to IHC. Results were compared with those of routine haematoxylin and eosin examination of the same nodes. RESULTS: Using IHC, 29 nodes from nine patients were positive for metastases. Using haematoxylin and eosin, 28 nodes from eight patients were positive. On a patient basis, the sensitivities of IHC and haematoxylin and eosin were 100 and 88.9 per cent, and negative predictive values (NPVs) were 100 and 95.5 per cent, respectively. On a node basis, the sensitivities were 96.7 and 93.3 per cent, and NPVs were 99.7 and 99.3 per cent, respectively. There were no false positives. The results were obtained within 30-45 min, depending on the number of nodes examined. CONCLUSION: IHC of touch imprints can provide a fast and sensitive method for detecting metastases in axillary nodes during breast cancer surgery.

Are surgeons effective counsellors for women with a family history of breast cancer?

AIM: In the TRACE (Trial of Genetic Assessment in Breast Cancer) study, the data on the time spent by the surgeon with the women with a family history of breast cancer was analysed with respect to the changes in the anxiety scores and breast cancer worry scores. We wanted to see whether longer consultation times with surgeons improved these scores. METHODS: In the TRACE study, women with a family history of breast cancer attended a standard breast clinic to be seen by a surgeon and nurse specialist. Anxiety scores and breast cancer worry scores of these women were recorded prior to attending the clinic and immediately after their appointment. RESULTS: In the 274 evaluable women, there was a significant improvement in the anxiety and breast cancer worries after surgical consultation but it did not correlate with the length of surgical consultation. However, women in the high-risk group showed a significant reduction of breast cancer worry score with longer consultation (P=0.032). CONCLUSIONS: Spending more time with the women with a family history of breast cancer does not help to reduce anxiety scores and breast cancer worry scores except in the subset of women who were told that their risk of breast cancer was high.

Randomized trial of a specialist genetic assessment service for familial breast cancer.

BACKGROUND: Because of the growing demand for genetic assessment, there is an urgent need for information about what services are appropriate for women with a family history of breast cancer. Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions. METHODS: We carried out a prospective randomized trial of surgical consultation with (the trial group) and without (the control group) genetic assessment in 1000 women with a family history of breast cancer. All P: values are from two-sided tests. RESULTS: Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group (P: =.05), differences between groups in other psychologic outcomes were not statistically significant. Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying. An initial specialist genetic assessment cost pound 14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling and genetic testing of affected relatives, plus subsequent testing of family members of affected relatives identified as mutation carriers, raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S. $96.35) over costs for the control subjects. CONCLUSIONS: There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer. Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services.

The National Breast Referral Guidelines have cut down inappropriate referrals in the under 50s.

AIMS: When the National Breast Referral Guidelines were applied to our local GPs letters immediately prior to their release in January 1996, it was shown that on the basis of the GPs own conclusions that 29% of symptomatic women could have been managed initially by their own GP without missing any carcinomas. We conducted this study at the Rapid Access Breast Clinic at the University Hospital of Wales to determine if the breast referral practices of local GPs have altered due to the breast referral guidelines. METHODS: We studied 2332 referrals from the inception of the Rapid Access Clinic in May 1995 to the issue of the guidelines, and 2421 referrals from May 1996 to the end of the year. Random samples of 600 patients were drawn from each year and the referral letters were scored as within or outside the guidelines. Family history patients were excluded. RESULTS: There was an 11% fall in referrals outside the guidelines in the under 50s (chi-squared=<0.001) but the 7% fall in the over 50s was not significant. CONCLUSIONS: The Breast Referral Guidelines seem to have been effective in reducing the higher level of inappropriate referrals in younger patients at less risk of carcinoma.

Psychological distress associated with waiting for results of diagnostic investigations for breast disease.

This paper presents the results of a multi-method research project investigating the psychological distress associated with waiting for results of diagnostic investigations in a delayed-results breast clinic. A cohort of 126 women completed standardized psychometric instruments to assess anxiety, mood and coping over 3 days. Semi-structured interviews were conducted with 20 respondents. The findings indicate that waiting sustained but did not exacerbate psychological distress. Peri-diagnostic anxiety, depression, uncertainty and confusion were associated with anxiety levels immediately following triple assessment. Women leaving the clinic with low anxiety retained this composure throughout the peri-diagnostic period. Those in the moderate and high anxiety groups recorded sustained anxiety, depression, uncertainty and confusion, with mean scores comparable to and exceeding those reported by psychiatric out-patients. Coping during the waiting period was typically accomplished by emotion-focused strategies. Qualitative data suggested the delayed-results clinic structure may facilitate psychological preparation for test results.

Is there a role for surgery in the treatment of mastalgia?

Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.

Genetic Testing Considerations in Breast Cancer Patients.

Genetic testing is now feasible for a growing number of cancers. Although the implications for unaffected relatives have been widely described, the impact of the tests on affected individuals are often not recognized. We present and discuss four cases that highlight some of the issues-for example, feelings of guilt and anxiety, intrafamilial conflict, and support needs-that may arise in testing affected individuals. We offer some suggestions to aid in the approach to such testing.

The role of desmoglein 2 and E-cadherin in the invasion and motility of human breast cancer cells.

Loss of adhesion is a fundamental step in the metastatic cascade. Desmosomal cadherins, Desmoglein (Dsg) and Desmocollin (Dsc) are a novel group of adhesion molecules. Aims were to demonstrate expression of Dsg2 and E-cadherin in breast cancer cells and assess their role in invasion and motility. Immunofluorescence and Western blotting were used to demonstrate expression of Dsg2 and E-cadherin in 3 breast cancer cell lines (MDA MB 231, MCF7 and BT474). Functional studies included cell-cell aggregation, in vitro invasion and colloidal gold phagokinetic tracking assays. All 3 cell lines expressed Dsg2. MCF7 and BT474 cells were E-cadherin positive, MDA 231 was negative. Cell aggregation was reduced, in vitro invasion and motility were increased in Dsg2 or E-cadherin Mab pre-treated cells. Dsg2 present in breast cancer cells may act as a tumour suppressor molecule.

Radical surgery for advanced and recurrent breast cancer.

Locally advanced or recurrent breast cancer is commonly seen in breast clinics. One method of palliation for ulcerating tumours is a radical mastectomy with replacement of the chest wall defect with a myocutaneous flap. We report on our experience of this technique in the management of 35 women (21 advanced disease, 14 recurrent disease). The perioperative complications were minimal and there are some longterm survivors. 15 women are alive and well (range 20-96 months postoperatively, mean 55 months). This radical surgery, therefore, has a significant role in the management of selected women with breast cancer.

Inflammatory pseudotumour of the liver.

Inflammatory pseudotumours of the liver are uncommon, usually mistaken for malignant lesions and resected. This report describes the presentation of an inflammatory pseudotumour of the liver in a 28-year-old male which was demonstrated on C.T. scanning and diagnosed by percutaneous needle biopsy. This case was treated conservatively and spontaneously resolved within four months, emphasising the need to consider this lesion in the differential diagnosis of an intrahepatic mass.

Effect of tissue pressure on contact laser insults.

The effect of variations in tissue pressure transmitted through contact laser probes during tissue ablation has been investigated. Weights of 10 and 50 g were transmitted through the tip of the probes onto the gastric and colorectal wall. At all laser energies the depth of tissue vaporization was significantly greater at the higher tissue pressure with perforation of the viscus occurring at laser energies above 10 J. The lateral zones of thermal tissue necrosis were not influenced by tissue pressure. Deformation of the wall of the viscus under the pressure of the probe was identified as a sign of excessive tissue pressure likely to result in perforation of any tissue of similar thickness to the normal gastric or colorectal wall.

Preliminary evaluation of a new high power diode laser.

A high-powered semiconductor diode laser (805 nm) has recently been developed for medical use. The laser-tissue interactions of this wavelength have been compared with Nd:YAG (1064 nm). When used in the contact mode, the extent of tissue vaporization and zones of thermal necrosis produced by these two lasers were similar. The diode laser was also an effective and haemostatic laser scalpel. This compact laser unit has potential advantages over existing Nd:YAG lasers.

Parameters for and safety of contact Nd:YAG laser irradiation of early gastric cancer: an in vitro study.

Early gastric cancers have been treated by endoscopic contact Nd:YAG laser irradiation. The extent of thermal damage produced by this laser system has been inadequately investigated. In an in vitro study we have shown that contact laser probes produce consistent and reproducible thermal lesions in the human stomach wall. Contact laser energies of 40 to 60 joules are optimal for the ablation of early gastric cancer. Energies greater than 90 joules are associated with a high incidence of gastric perforation. Contact laser probes may have advantages over non-contact laser techniques for the endoscopic treatment of early gastric cancer in patients who are unfit for major surgery.