Sentinel lymph node biopsy in early breast cancer surgery--working with the risks of vital blue dye to reap the benefits.

AIMS: Sentinel lymph node biopsy (SLNB) is an important method of staging early breast cancer because of the inherent benefits it confers on patients in terms of arm function and quality of life. Its success depends on a high level of accuracy in detecting the sentinel node. This is achieved by a dual mapping technique that employs a radio-labelled nanocolloid and a vital blue dye. The vital dyes however carry the risk of anaphylaxis, and as more surgeons employ SLNB in their daily practice, a proportionate rise in the number of anaphylactic reactions can be expected. A comprehensive review of risks and benefits associated with using vital blues dyes has not been published and therefore a retrospective review was undertaken of the different levels of anaphylaxis associated with vital dyes as well as their benefits in SLNB. METHODS: An OVID MEDLINE search was performed of the English published literature using appropriate search terms to find published trial data and case series that focused on adverse reactions to vital blue dyes. RESULTS: The risk of severe anaphylaxis (grade 3) can be as low as 0.06%, and up to 0.4% for patients undergoing SLNB when data is analysed from large trials. Furthermore, adverse reactions associated with blue dyes are reversible with appropriate management. CONCLUSIONS: Surgeons should continue to use vital dyes to ensure that SLNB remains a highly sensitive procedure.

Breast cancer multi-disciplinary teams in England: much achieved but still more to be done.

OBJECTIVE: To look at the national coverage, composition and discussion of breast cancer multi-disciplinary teams (MDTs) in England. DESIGN AND DATA SOURCE: All breast units in England both symptomatic and screening were sent a questionnaire. MAIN OUTCOME MEASURES: Attendance of core members at MDT meetings; Percentage of patients discussed with a treatment plan; Private patients discussed; Reconstructive surgery. RESULTS: The majority of core members of the breast MDT attend weekly meetings to discuss the multidisciplinary management of patients with breast cancer, although attendance by medical oncologists and reconstructive breast surgeons is limited. Three MDTs never had a radiologist present and 3 never had a pathologist present at the MDT meeting. Most breast MDTs have a meeting coordinator to collect case-notes, radiographs and pathology reports to facilitate the meeting. Seventy-nine out of 134 teams discuss every cancer patient and 118 also discuss private patients. Twenty-seven teams record the outcome of the MDT meeting electronically, 32 teams book surgery, 16 radiotherapy and 15 book chemotherapy direct from the MDT meeting.

All radial scars/complex sclerosing lesions seen on breast screening mammograms should be excised.

AIM: To determine the incidence of pre-malignant and malignant conditions in radial scars identified from screening mammograms in women taking part in the UK NHS breast cancer screening programme. METHODS: All women in our screening population from 1988 to 2002 with a radiological diagnosis of radial scar or complex sclerosing lesion confirmed on subsequent histopathology were included in this study. Patients were investigated with fine needle aspiration cytology then localisation biopsy (n=46) or straight to localisation biopsy (n=78). Patients where divided into two groups, one with pure RS/CSL with no associated epithelial features and the second with associated ADH, DCIS or invasive cancer. RESULTS: One hundred and twenty-four lesions were confirmed histologically as radial scar or complex sclerosing lesions. The median age was 58 years. Of the 124 patients, 82 were pure RS/CSL. Forty-two had associated epithelial lesions, 22 patients had ADH and 20 patients had either in situ or invasive carcinoma. Where FNA was performed (n=46), mammograms had shown three lesions suspicious of cancer, which were not proven histologically. Mammograms picked up five malignancies out of the nine RS/CSL with associated cancers. Of these, FNA confirmed malignancy in only two patients. Where FNA was not done (n=78), mammogram had read five pure RS/CSL as cancers. It picked up only four cancers in RS lesions with DCIS/Ca out of 11. CONCLUSION: All screen-detected stellate lesions should be excised due to their association with pre-malignant and malignant conditions.

Granulomatous mastitis can mimic breast cancer on clinical, radiological or cytological examination: a cautionary tale.

In both women and men, breast lumps are the most common presentation of breast cancer. The following cases illustrate the pathological entity of granulomatous mastitis, which can present simulating breast cancer - including the first description of this condition in a male. These cases demonstrate the difficulty in clinical diagnosis and emphasizes that although there may be clues from the history, clinical awareness that this condition can mimic breast cancer in all aspects of the triple assessment process should arouse suspicion. The importance of histological diagnosis by core or excision biopsy is stressed, as with accurate diagnosis of granulomatous mastitis there is a mandate to avoid unnecessary surgery.

Serum adrenal androgens in women with primary operable breast cancer and their relationship with age and body mass index.

Several studies have found elevated levels of adrenal androgens in postmenopausal women and depressed levels in premenopausal women with breast cancer, suggesting a role for adrenal androgens in the aetiology of breast cancer. We have measured serum dehydroepiandrosterone sulphate and androstenedione in 81 women with primary operable breast cancer and 62 age-matched controls. Results showed that serum levels of both adrenal androgens fell significantly with age in women with breast cancer (P=0.003). However, no relationship was observed between serum adrenal androgen levels and body mass index in either women with breast cancer or controls. Dehydroepiandrosterone sulphate levels were elevated in postmenopausal women with breast cancer compared to controls, and this was not due to preoperative stress. No differences were observed in androstenedione levels between premenopausal or postmenopausal women with breast cancer and controls, nor were dehydroepiandrostenedione sulphate levels significantly different between premenopausal women with breast cancer and controls. These results suggest that dehydroepiandrosterone sulphate has a role in the aetiology of postmenopausal breast cancer.

Rectal retroflexion: an essential part of lower gastrointestinal endoscopic examination.

PURPOSE: Retroflexion of the endoscope during rectal examination may increase diagnostic yield but is not routinely performed because of concerns about safety and a lack of appreciation of its importance. The purpose of this study was to examine the yield, safety, and tolerance of endoscopic rectal retroflexion. METHODS: Prospective cohorts of subjects undergoing unsedated screening flexible sigmoidoscopy were examined with and without routine retroflexion. Pain scores were recorded. RESULTS: A total of 526 subjects (mean age 60 (range, 55-66) years) underwent flexible sigmoidoscopy in the first period when the endoscope was not routinely retroflexed. Of these, 480 (mean age 60 (range, 55-66) years) were subsequently examined with routine retroflexion. Retroflexion was impossible in 17 subjects (3.5 percent) because of discomfort. In the second group, 12 subjects (2.5 percent) had polyps in the lower rectum seen only on retroflexion. Of these, eight had metaplastic and four had adenomatous polyps (3 tubular <5 mm, 1 tubulovillous 15 mm). There was no difference in mean pain scores between the groups (no retroflexion = 2.13, retroflexion = 2.18). CONCLUSION: With an adenoma pick-up rate of 8 to 12 percent for screening flexible sigmoidoscopy, retroflexion increases adenoma detection by approximately 1 percent without adverse effects and should be an integral part of flexible sigmoidoscopy.

The use of a standard proforma in breast cancer reporting.

AIM: To determine whether the introduction of a standard reporting proforma has led to an improvement in the completeness of histopathology reports for breast cancer excision specimens. METHODS: A standard reporting proforma was designed using the Royal College of Pathologists' minimum dataset for breast cancer histopathology reports and the national histopathology reporting form of the National Health Service (NHS) breast screening programme. This was introduced into our department in June 1999, with reports generated from the proforma replacing the standard text reports. The pathological information contained in 50 text reports issued before the introduction of the proforma and 50 reports generated using the proforma was compared with the minimum dataset and NHS breast screening programme guidelines. RESULTS: A general improvement in documentation of individual pathological features was noted after introduction of the proforma. This was most significant in relation to documentation of features, such as microcalcification and ductal carcinoma in situ. In addition, important features such as tumour grade, tumour size, and hormone receptor status were documented more frequently in the proforma group. There was an overall increase in the number of reports regarded as complete after introduction of the proforma. CONCLUSIONS: The introduction of a standard proforma led to a significant improvement in the completeness of breast cancer histopathology reports in this centre, but continued vigilance is needed to ensure that standards continue to improve.

Aggressive local treatment for screen-detected DCIS results in very low rates of recurrence.

AIMS: To review our institution's practice of treatment of a mammographically detected population of ductal carcinoma in situ (DCIS) patients and to determine the outcome. METHODS: Between April 1989 and March 1994, 304 women with median age 59 years (range 51-65) with DCIS detected on screening mammogram, were treated in the Newcastle General and Royal Victoria Infirmary Hospitals, Newcastle-upon-Tyne, UK. More than half of the women (n=176, 57.8%) decided to have mastectomy. Other treatment options were wide local excision (WLE) with radiotherapy (n=97, 32%) and WLE alone (n=31, 10.2%). All except five received adjuvant hormone treatment. RESULTS: Predominant DCIS was comedo in 122 (42%), followed by cribriform in 87 (30%) and micropapillary in 44 (15%) cases. Grade I was found to be commonest grade (54%) followed by grade II (27%) and grade III (11%). With a median follow-up of 88 months, there were six (2%) recurrences, all of which were in women who were given breast conservation treatment, WLE with radiotherapy (n=1, 1%) and without radiotherapy (n=5, 16.6%). Mastectomy in this series was not associated with any recurrence at all. In three cases the recurrence was invasive, one of who also had distant metastasis. CONCLUSIONS: The findings of this study suggest that in women with DCIS suitable for breast conservation, WLE when combined with radiotherapy is associated with a very low recurrence rate.

Can breast surgeons read mammograms of symptomatic patients in the one-stop breast clinic?

AIM: To establish how accurate surgeons were when compared to the radiologists in interpreting symptomatic mammograms in one-stop clinics. METHODS: The surgeons were asked to write their opinion on the mammograms which was compared with the radiologists' report. 144 patients were involved in the study and the data were analysed by McNemara's test for paired categorical data. RESULTS AND CONCLUSIONS: Surgeons were accurate in interpreting most of the mammographic findings. However, they underestimated the presence of benign calcification which was statistically significant. Surgeons can, therefore, be involved in double reading of mammograms in symptomatic breast disease patients and improve the sensitivity which has been the case in double reading by radiologists in the breast screening programme.

p53 protein expression in ductal carcinoma in situ (DCIS) of the breast.

Abnormalities in p53 gene expression have been implicated in many inherited and sporadic forms of malignancies in humans. Immunohistochemical staining using monoclonal antibody D0-7 for the p53 protein expression was performed in 81 cases of pure DCIS, 14 benign breast lesions and 2 cases with normal breast tissue. Expression of p53 protein was detected in 15 (18.5%) cases of pure DCIS. Thirteen (25%) of the 52 comedo type DCIS showed p53 protein expression compared with 2 (6.9%) of the 29 non-comedo types (P < 0.02). p53 protein expression was also associated with high nuclear grade (P < 0.001) and high mitotic index (P < 0.05). The pattern of p53 protein staining was diffuse in one comedo type DCIS, regional in 6 comedo types, and focal in the remaining 8 cases (6 comedo type and 2 micropapillary type DCIS). The patient with comedo type DCIS showing diffuse staining has a family history of breast cancer in the first and second degree relatives (sister and maternal aunt). Clinical follow-up data was available in 52 cases. Follow-up period ranged from 9 to 55 months. Three patients, who were primarily treated by local excision, have had a documented local recurrence in the form of residual tumor within a short interval of 5 to 11 months. In all these three patients both the original and the recurrent tumors are negative for p53 protein expression. The difference in the local recurrence rate between p53 positive (0/15) and p53 negative (3/37) cased does not reach statistical significance (p > 0.05). We interpret that the local tumor recurrence in these three cases within a short period after primary excision is due to the presence of residual tumor at the excision site and is independent of the p53 gene alteration. It is concluded that p53 protein expression in DCIS is associated with comedo subtype, high nuclear grade, and high mitotic index, and is a promising new parameter to evaluate the cellular biology and prognosis of DCIS.

Dilatation of the left colon with a Foley catheter: an aid to staple anastomosis.

Balloon dilatation of the left colon using a Foley catheter was performed in 26 patients prior to staple anastomosis. A 28-mm stapler was then used in six (23%) patients, a 29-mm in seven (27%), a 31-mm in eleven (42%) and a 33-mm in two (8%). Two anastomoses failed (7.9%) and one patient developed local recurrence. None of the remainder developed a symptomatic stricture. Flexible sigmoidoscopy was performed on 18 patients at least 3 months after surgery, revealing that one (5.5%) had developed an asymptomatic stricture. A 28-mm stapler had been used in this case. This technique of dilating the left colon with a Foley catheter is a useful aid to staple anastomosis in large bowel surgery.

Assessment of a specimen mount for biopsy of impalpable breast lesions.

Biopsy of the impalpable breast lesion is an increasing part of the surgical workload as a result of the National Breast Cancer Screening Programme. A specimen mount card has been described to orientate such specimens in three dimensions prior to radiological and pathological examination. Experience with 243 biopsies in this unit has shown it to be a useful aid in determining completeness of excision. It may also be used as a guide to further surgery when excision is incomplete and breast conservation is the treatment option of choice.

Should breast biopsy cavities be drained?

A total of 112 women was entered into a randomised study to investigate the effects of suction drainage on haematoma formation in breast biopsy wounds. Of 107 evaluable patients, 52 received drainage and 55 had no drain. The wounds were examined 1 week after operation when the volume of wound haematoma was measured using ultrasonography. Haematomas were present in 48 (87%) patients with undrained wounds compared with 34 (65%) patients with drained wounds (P = 0.014, chi 2 test). Median haematoma volume was 20 ml (range 0-172.5 ml) in the undrained group compared with 2 ml (range 0-100 ml) in the drained group (P = 0.001, Mann-Whitney U test). There was one wound infection in each group. There was no difference in median pain score or duration of pain between the groups. While suction drainage significantly reduces the incidence and volume of wound haematomas, this does not appear to influence outcome.

Free peritoneal tumour cell identification in patients with gastric and colorectal cancer.

The finding of free tumour cells within the peritoneum at the time of laparotomy for gastrointestinal cancer is an important indicator of prognosis and may help select treatment. The aim of this study was to improve the methods whereby these cells could be retrieved and identified. Free peritoneal cancer cells were found in 6 out of 18 gastric cancer patients. All 6 patients had tumour invasion through to the serosa and subsequently died of tumour recurrence. None of the 18 Dukes' B and C colorectal cancer patients had free peritoneal cancer cells. Only 2 of a further 5 patients with extensive colorectal tumour spread had positive cytologies. The conventional mucin stain Periodic Acid Schiff (after diastase digestion) and the monoclonal antibody stain B72.3 were the most useful in identifying free peritoneal cancer cells. Peritoneal brushings did not offer any advantages over conventional peritoneal washings in the retrieval of free tumour cells.

Density of lymphocytic infiltration of primary breast cancer does not affect short-term disease-free interval or survival.

Lymphocytic infiltration of breast cancer is often associated with a favourable prognosis. Seventy-seven women with operable breast cancer were followed for a minimum of 3 years. Tumours were frozen and sectioned by cryostat before staining with monoclonal antibodies using an immunoperoxide technique for total lymphocytes, helper/inducer, suppressor/cytotoxic, natural killer and B subsets. Lymphocyte density was assessed by light microscopy at x400 and divided at the 50th percentile to less than 30 and greater than or equal to 30 cells per high power field to give scanty and dense lymphocytic infiltration. The helper/suppressor lymphocyte ratio was greater than 1 in 45 patients but without improvement in survival or cancer recurrence. Natural killer and B lymphocytes were rarely seen in tumour sections. Poorly differentiated tumours excited a more marked lymphocytic infiltration (P less than 0.01). Neither the density of lymphocyte infiltration nor the ratio of helper to suppressor lymphocytes correlated with improved short-term survival or recurrence. These data suggest that the immune defence is ineffective in preventing spread from the primary tumour in breast cancer patients.

Risk factors in patients with ischaemic rest pain of the lower limbs.

One hundred and three consecutive out-patients with ischaemic rest pain were studied. There were 77 men and 26 women with a mean (s.d.) age of 71 (10) years. Thirty-six (35.0%) patients had rest pain alone, 41 (39.8%) in association with an ischaemic ulcer and 26 (25.2%) with digital gangrene. A significantly increased risk of amputation was seen in those patients with an elevated serum cholesterol (greater than 5.2 mmol/l; P = 0.01), white blood cell count of greater than 10 x 10(9)/l (P = 0.05), fibrinogen greater than 4g/l (P = 0.04), and in women with elevated triglyceride levels (greater than 1.8 mmol/l; P less than 0.03). An increased risk of death for all patients was also associated with elevated triglyceride levels (P = 0.03). Few of the women smoked (P less than 0.0004), but they were more likely to have suffered a stroke (P = 0.01). They also had a significantly increased cholesterol level (P = 0.03) and tended to have a higher mortality rate than the men (P = 0.08). Surprisingly, smokers did not have a significantly higher amputation or death rate than non-smokers. Elevated plasma viscosity, packed cell volume, platelet count, haemoglobin and creatinine levels were not independent risk factors for any group. At 30 days after presentation the limb salvage rate was 73% (75/103), amputation was required in 15 (14.6%) cases and 13 (12.6%) patients died. Patients with ischaemic rest pain constitute a heterogeneous group with multiple diseases and risk factors. Early identification and treatment of risk factors may help to improve limb salvage and the mortality rate in this condition.

Intraoperative testing of anastomotic integrity after stapled anterior resection for cancer.

Sixty consecutive patients undergoing anterior restorative resection of the rectum for cancer were studied. After full mechanical bowel preparation and intravenous antibiotic prophylaxis, colorectal anastomosis was performed with the EEA (Autosuture) staple gun. The median height of the anastomosis above the anal verge was 9 cm (range 3-15 cm) and no patient had a protecting colostomy fashioned. All 'doughnuts' were checked and following instillation of saline into the pelvis the anastomosis was tested by air insufflation through the rectum. There was a statistically significant association between an incomplete 'doughnut' and peroperative anastomotic leakage (P less than 0.001); however, of the 11 patients shown to have a leak, only seven had deficient 'doughnuts'. All 11 patients had repair of the defect identified by escape of air and none of these patients developed a clinical leak.