Overexpression of Cripto and its prognostic significance in breast cancer: a study with long-term survival.

INTRODUCTION: Cripto is a founding member of the EGF-CFC family, and plays an important role in tumourigenesis, tumour cell proliferation and migration. We aimed to determine the significance of Cripto expression on the survival of patients with breast cancer. METHODS: Immunohistochemical detection of Cripto was performed by using mAb C13 on 120 formalin-fixed paraffin-embedded breast tumour specimens in tissue microarrays. This cohort comprises a series of 120 patients with primary operable breast cancer diagnosed between 1989 and 1995, retrieved from the Concord Repatriation General Hospital breast carcinoma database. RESULTS: Using a cutoff value of 80%, Cripto overexpressed in 57 of the 120 (47.5%) patients. We found significant associations between overexpression of Cripto and the Nottingham Prognostic Index (NPI, p<0.01), histological grade (p<0.01), pathological tumour type (p=0.04), PR (p=0.02) as well as Ki-67 (p=0.02). Univariate analysis reveals that there is a significant correlation between overexpression of Cripto and survival (p=0.0003). Cox regression analysis indicates that the overexpression of Cripto is an independent prognostic factor in breast cancer (HR 2.79, 95%CI 1.20-6.50). CONCLUSION: The unique epitope recognized by mAb C13 is overexpressed on breast tumour tissues. In this series of invasive breast cancers, overexpression of Cripto was more often found in high grade and poor prognosis tumours compared to low grade and good prognosis breast cancers. Moreover, overexpression of Cripto was significantly associated with decreased patient survival.

Patterns of breast cancer relapse.

AIMS: Although breast cancer is the major cause of cancer-related death in women, there is little comprehensive information on long-term outcomes, particularly pertaining to site of relapse. The Strathfield Breast Centre (TSBC) is a multidisciplinary breast clinic that has collected patient data prospectively over 14 years. METHODS: All women with invasive, non-metastatic breast cancer, referred to TSBC from 1989 until 2002, were studied (n=2509). After initial treatment, patients were reviewed at 3-12-month intervals, including annual mammography and/or breast ultrasound. Information was collected on demographics, pre- and post-operative management and patient outcomes. Survival was analysed by the method of Kaplan and Meier. RESULTS: The mean age was 58 years and median follow-up 4 years (range <1-14) with complete data for 81%. In total, 456 patients (18%) had a local, nodal or distant relapse. The most common site of first relapse was to bone (in 125 patients), followed by local recurrence (124), lung (73) and liver (57). The median interval from primary breast surgery until recurrence was 2.3 years and disease-free intervals correlated to survival (p<0.0001). After local recurrence the 5-year survival was 41%, vs. 20% for nodal and 13% for distant recurrence (p<0.0001). Following breast-conserving surgery, the 5-year disease-free survival after local recurrence was 49.4%, vs. 33.1% after chest wall recurrence (p=0.0361). Of distant relapses, bone metastases had the best prognosis, with median survival 2.4 years. CONCLUSION: These data provide information on treatment outcomes in a multidisciplinary setting and statistical information that will be useful when discussing the fears and expectations of patients after the diagnosis of breast cancer.

Evaluation of a breast cancer nomogram for prediction of non-sentinel lymph node positivity.

AIMS: This study evaluates the breast cancer nomogram (BCN), an online tool developed by Memorial Sloan-Kettering Cancer Center to determine the rate of non-SLN positivity, in an independent cohort of SLN positive patients. MATERIAL AND METHODS: Available data between 02/2000 and 06/2004 in two prospective databases, 749 cases had successful SLN biopsy including 149 axillary-SLN metastases study cases. These cases had accurately graded tumours up to 9 cm in size and CAD with a minimum total 10 nodes removed. Histopathological assessment of nodes included hematoxylin and eosin staining and/or immunohistochemistry. Computerized BCN was used to estimate probability of non-SLN positivity and compared with actual probability after grouping into deciles. RESULTS: The trend of actual probability in various decile groups was comparable to the predicted probability. An area under the receiver operating characteristic curve was 0.75 as compared to 0.76 in the original study. CONCLUSION: Although this study is small, the results are encouraging and suggest the nomogram is a useful tool to estimate the likelihood of positive axillary non-SLN. However, variations in pathological assessment between centres are the major impediment to widespread application of BCN. If SLN positive patients decline the standard recommendation of CAD or entry into clinical trials evaluating the significance of CAD then the BCN could help in decision making.

Infiltrating lobular carcinoma--a comparison of diagnosis, management and outcome with infiltrating duct carcinoma.

The treatment and outcomes for 182 patients with lobular carcinoma were compared with 1612 patients with infiltrating ductal carcinoma managed concurrently at The Strathfield Breast Centre. The lobular carcinomas were larger (P < 0.0001) but of lower grade (P < 0.0001). Diagnosis with mammography and FNA was less sensitive in ILC (mammography P = 0.0002, FNA P < 0.0001). Although similar numbers of patients underwent initial attempted conservation, patients with ILC were more likely to have positive margins at attempted breast conservation surgery and the final mastectomy rate was higher (58.2% ILC versus 47% IDC, P = 0.0041). Of the patients who had successful conservation, the local recurrence rates for ILC (3.9%) were equivalent to the patients with IDC (5.3%). There was no significant difference in overall survival (90% ILC, 87% IDC, median follow-up 3.6 years ILC, 4.3 years IDC) or disease free survival (87.9% ILC, 81.6% IDC). Although mastectomy is more likely to be necessary to obtain clear margins, breast conservation therapy is reasonable in patients with infiltrating lobular carcinoma where clear margins can be obtained.

Implications of extranodal spread in node positive breast cancer: a review of survival and local recurrence.

An evaluation of extra nodal spread (ENS) in predicting overall survival and locoregional relapse rates in 311 node positive breast cancer patients was undertaken: the study group comprised 71 patients with ENS and the control group comprised 240 patients with no ENS. A review of pathology reports that described ENS was performed and a scoring system to categorize focal involvement, extensive axillary fat involvement, and positive axillary surgical margins was devised. Median follow up time was 3.1 years. Overall survival, disease specific survival and disease-free survival rates were significantly worse in the study group in comparison with the control group. Poorer survival with more extensive pathological invasion of ENS was demonstrated. Multivariate analysis of disease specific survival in those patient with 1-3 involved lymph nodes demonstrated that ENS positivity was prognostically significant (P=0.013). Although locoregional relapse was increased in the presence of ENS, axillary relapses were uncommon and do not warrant axillary radiation.

Screen-detected breast cancer compared to symptomatic presentation: an analysis of surgical treatment and end-points of effective mammographic screening.

BACKGROUND: Mammographic screening has been shown to reduce mortality from breast cancer and to offer more opportunity for breast conservation surgery (BCS). The minimum standards (or surrogate end-points) that need to be achieved by a screening programme if it is to reduce mortality have been derived from the Two County Study. Three surrogate end-points that can be used to gauge the quality of the screening service are that 50% of the identified infiltrating cancers should be < 15 mm; at least 30% of grade 3 cancers should be < 15 mm; and 70% of screen-detected cancers should have a negative axillary dissection. The present study assesses these end-points of effective screening in an urban population referred to The Strathfield Breast Centre (TSBC). The screening end-points and surgical treatment of one group of women referred with a BreastScreen New South Wales (NSW)-detected breast cancer (screen group) were compared to all the other, mostly symptomatic, breast cancer referrals (symptom group). The problems with the current pattern of acceptance of mammographic screening in TSBC's referral area are discussed. METHODS: A prospective non-randomized study was done via analysis of the prospective database at The Strathfield Breast Centre (TSBC). RESULTS: There were 224 women in the screen group and 657 women in the symptom group. The mean tumour size was 18.1 mm in the screen group and 22.1 mm in the symptom group. There were significantly more small invasive cancers (< 15 mm) in the screen group (58%) compared with the symptom group (33%; P < 0.001). In the screen group there were more low-grade tumours but 30% of grade 3 tumours were < 15 mm compared with 16% in the symptom group (P = 0.009). In patients with invasive cancers who underwent axillary dissection, there was a significant difference in axillary node negativity, being 72% in the screen group and 59% in the symptom group (P = 0.003). In the screen group 64% of women had BCS compared with 51% in the symptom group (P = 0.002). CONCLUSIONS: These end-points of effective mammographic screening were met in the BreastScreen NSW group of women who were referred to TSBC despite the biases involved which could lessen the effectiveness of the screening programme. This crudely translated into a significant reduction in breast cancer mortality but selection and lead time bias has to be taken into account in evaluation of these data. There was a significantly greater chance of BCS in the screen group.

A review of pathology reporting for breast cancer.

BACKGROUND: A detailed pathology report is important in the determination of treatment options and prognosis in breast cancer. Australia's first National Cancer Consensus Conference, held in 1994, recommended guidelines for the standardization of the clinical information to be provided to the pathologist, the specifications relating to the handling of specimens, and the resultant pathology report. METHODS: We examined the current status of pathology reporting in invasive breast cancer in three New South Wales hospitals from 1986 to 1994. RESULTS: Histopathologic type was documented in 99% of reports, grade was documented in 47%, size in 46%, and lymph node status in 98%. Only 27% of pathology reports reviewed documented the status of all the above parameters in the one report. Other features such as lymphatic and vascular invasion were documented in only 21% and 9% of pathology reports, respectively, while sex steroid receptor status was reported in almost 90% of cases. CONCLUSIONS: In view of the wide range in the percentage of features reported, we recommend the use of a standardized checklist for the pathological assessment of surgically resected invasive breast cancer specimens.

Sentinel node biopsy in breast cancer: results of 103 cases.

BACKGROUND: In early breast cancer the status of the axillary nodes has been shown to be one of the primary prognostic indicators. Biopsy of the sentinel node, or first draining lymph node, of a tumour has been investigated as an alternative to axillary dissection in early breast cancer. A series of sentinel node biopsies in 103 patients is reported here. METHODS: Both pre-operative lymphoscintigraphy and intra-operative blue dye were used to map the sentinel nodes. RESULTS: Mapping was successful in 87 (84.4%) cases and sentinel nodes were retrieved in 94.2% of these patients. Where lymphoscintigraphic mapping was unsuccessful, sentinel nodes were found in 37.5%. When sentinel nodes were retrieved, correlation of the sentinel node status with the axillary nodes was accurate in 97.5%. There were two false negatives, both in large tumours. The sentinel node status was an accurate predictor of axillary status in 95.7% of the node positive patients. CONCLUSIONS: If only the 86 patients with invasive carcinoma and four or more axillary nodes removed at surgery are considered, the sentinel node was accurate in assessing the axillary status in 97.7% of the total patient group (2.3% false negative rate), 97.2% of those in whom sentinel nodes were successfully retrieved (2.8% false negative rate) and 94.9% of the patients with positive axillary nodes (5.1% false negative rate). Sentinel node biopsy is a valid technique providing an accurate reflection of the axillary node status and having a low false negative rate.

Early gastric cancer.

Eighteen cases of 'early gastric cancer' have been managed over a 14-year period. This represents only 3.5% of all patients diagnosed as having adenocarcinoma of the stomach. The symptoms of early gastric cancer are similar to those of benign peptic ulcer disease and differ from those of invasive disease. The pathology of the lesions is described and the morphology shown to be similar to that seen in Japan. The overall 5-year survival rate is 82% but no patient has developed recurrence within 5 years of surgery, confirming the biological behaviour of the lesion to be identical to that noted by Japanese researchers.

Highly selective vagotomy in the treatment of complicated duodenal ulcer.

Highly selective vagotomy has been utilized urgently in 33 patients with bleeding duodenal ulcer, 16 patients with pyloric stenosis and six patients presenting with perforated ulcer. Five patients died after surgery for bleeding duodenal ulcer, and two patients rebled after surgery. Forty-eight patients were reviewed at a mean of 28 months with an excellent outcome being obtained in 45 patients. Two of the three patients with poor results had proven ulcer recurrence while the third patient required reoperation for recurrent pyloric stenosis. No patient has suffered diarrhoea after vagotomy. Highly selective vagotomy is an effective treatment for urgent management of complicated duodenal ulceration and is without troublesome post-vagotomy symptoms.

Carcinoma of the stomach: a review with special reference to total gastrectomy.

Five hundred and eleven patients with adenocarcinoma of the stomach were reviewed. Weight loss and abdominal pain were the most common symptoms. One-third of patients were found to have proximal gastric lesions with dysphagia being a major symptom in 23% of all patients. Laparotomy was performed on 88% of patients with 56% of the entire series undergoing gastric resection. The overall 5-year survival rate was 12.3% and for curative resection 43%. The 5-year survival rate of patients undergoing total gastrectomy was 53% and for patients undergoing subtotal or partial gastrectomy the 5-year survival rate was 42%. The operative mortality, similar in both groups, was 8.1% versus 5.6%. Palliation was better achieved by resection than bypass. Total gastrectomy for palliation was undertaken in 48 patients. This group of patients has achieved a good quality of life and a mean survival rate of 12.5 months.

Major hepatic resection for neoplasia. The Concord Hospital experience.

In a major hepatic resection one, or more, of the eight major anatomical segments of the liver is removed. Such procedures are a recent development and during 1972-1982, 22 such resections were performed for neoplasia at Concord Hospital, with a mortality rate of 5%. The indications for elective hepatic resection for neoplasia are discussed. Of particular importance is the excellent palliation and survival that is achieved when localized metastases of colorectal origin are resected.

Sclerosing peritonitis after practolol administration.

We have recently managed two patients with sclerosing peritonitis who had undergone a course of practolol but had ceased taking it some months prior to presentation. Publication of these cases will help to assess the extent of this complication and will increase awareness amongst surgeons who may be called upon to treat such cases.

Fine bore jejunostomy feeding following major abdominal surgery: a controlled randomized clinical trial.

A randomized controlled prospective clinical trial has been undertaken to examine the efficacy of the technique of early postoperative feeding using a fine bore catheter jejunostomy. Fifty patients undergoing surgery for gastrointestinal malignancy were randomly allocated into treatment and control groups. A low residue liquidized diet (Isocal) was administered to the patients in the treatment group. Control patients received routine intravenous therapy. Nutritional parameters (serum albumin, serum transferrin, serum prealbumin, weight, body fat and fat free mass) were measured pre-operatively and on the tenth postoperative day. Postoperative surgical complications were similar in both groups. There were 20 catheter complications and one death directly attributable to the jejunal catheter feeding. Postoperative stay was significantly longer (P less than 0.01) in the treatment group patients. Evaluation of the nutritional parameters showed no advantage for either the treatment group or a selected complication-free, 'successful treatment', subgroup. It is concluded that no significant clinical or nutritional advantage for jejunal catheter feeding has been demonstrated and because of the related complications, its routine use cannot be recommended.

Treatment of granulating wounds with silastic foam dressings.

We have examined the usefulness of a Silastic foam dressing in the management of open granulating wounds in 55 outpatients. It is an acceptable and comfortable dressing, which allows earlier discharge from hospital. The method of making the dressing, and the daily care of the wound are described. Improved wound care is achieved by providing two dressings, so that when one is in place the other is being thoroughly cleaned. This technique has been shown to reduce bacterial contamination of the wounds and to improve wound healing (p less than 0.02).

Carcinoma of the male breast: a review and recommendations for management.

BACKGROUND: Male breast cancer is rare and experience of it in any single institution is limited. The aim of this study was to evaluate the presentation, management and outcome of male patients with breast cancer treated at Concord Repatriation General Hospital hospital over a 38-year period and to determine a best-practice protocol based on the results and a review of the literature. METHODS: A total of 42 patients were retrospectively reviewed, pathology slides were re-examined and reclassified where necessary. Outcome was assessed and compared with results obtained from a literature review. RESULTS: A trend towards less radical surgery has emerged. Overall 5-year survival was 50%, but, due to the late age at presentation, more than half the deaths were non-breast cancer related. One quarter of the patients presented with locally advanced or metastatic disease. CONCLUSIONS: The presentation, diagnosis pathology and outcome of breast cancer are similar in men and women, although the disease occurs at a later age in men. Radical surgery is not required in order to gain local control, but knowledge of axillary node status is important in determining prognosis and the need for adjuvant therapy.