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.

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.

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.

Use of the Hasson cannula producing major vascular injury at laparoscopy.

Despite the recent demonstration that vascular lesions occur significantly more frequently in patients having closed rather than "open" laparoscopy, there never has been a published case report of injury to the great vessels associated with the open technique of initial access to the peritoneal cavity at laparoscopy. We present the first two such cases reported, along with a brief review of the literature related to such major vascular injuries (MVI) sustained at laparoscopy. Lacking appreciation of aortic anatomy and intraoperative technical factors contribute to the occurrence of these injuries. Delayed diagnosis and management contribute to poor outcomes. Secondary injury frequently is associated with MVI at laparoscopy.

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.

Breast cancer outcomes at the Strathfield Breast Centre.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer and the most common cause of cancer death in women. This report presents outcomes from a multidisciplinary breast clinic established in 1989 with the specific aim of providing a rapid, integrated assessment service for patients with breast disease. METHODS: A prospective data collection and analysis using a Microsoft Access (Microsoft Corp., North Ryde, NSW, Australia) database was established and has collected information on all patients presenting for diagnosis or ongoing management of breast cancer. Data on survival were obtained by routine follow-up visits or contact with the patient's general practitioner. RESULTS: Patient age, mode of presentation and histopathology were similar to other population-based studies in Australia. Ninety-three per cent of the patients had a diagnosis confirmed on the day of consultation. The average time between diagnosis and surgery was 11.9 days. Breast preserving surgery was attempted in 68% and achieved in 50% of cases, 67% of patients had one stage surgery. Five-year disease-free survival was 74% and is comparable with other reports. CONCLUSIONS: The centralization of services and expertise has enabled us to provide efficient service and achieve internationally comparable outcomes.

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.

A placebo controlled double blind study using perioperative prazosin in the prevention of urinary retention following inguinal hernia repair.

Acute urinary retention is a frequent complication following inguinal hernia repair. The smooth muscle of the bladder neck and the prostate have been demonstrated to be rich in alpha-1 adrenergic receptors. It has been postulated that the aetiology of acute urinary retention postoperatively is at least partially due to adrenergic stimulation; blocking these receptors may reduce the incidence of acute urinary retention. We have used prazosin in a double blind, placebo controlled study to establish its efficacy in the prevention of acute urinary retention in patients undergoing elective inguinal hernia repair. A total of 70 male patients were enrolled; 36 patients had been allocated active drug and 34 patients had been allocated placebo. Only two patients developed acute urinary retention. Both patients had been allocated prazosin and had received a general anaesthetic for their hernia surgery. In either arm of the study, a higher number of patients developing urinary retention would have been expected but this may be explained by the greater vigilance on urinary output by nursing staff aware that the trial was being conducted. On the basis of our findings, we do not recommend the routine use of perioperative prazosin with inguinal hernia repair. Further studies in high risk groups would be necessary to assess more fully the efficacy of prazosin in this situation.

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.

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.

Implantable injection port for long-term venous access.

In recent times, totally implantable devices using a Silastic right atrial catheter connected to a subcutaneous injection chamber have been introduced for long-term venous access. This study reports the experience of 39 patients in whom 41 such devices have been implanted. It totals 9697 patient days so far. There has been no incidence of major vein or catheter thrombosis and an infection rate of 0.41 per 1000 catheter days has been achieved. Catheter related complications have occurred in 20% of the cases after a mean duration of usage of 237 days. It is concluded that implantable injection ports provide a safe and reliable method of prolonged venous access.

Granulomatous mastitis.

Granulomatous mastitis is a benign breast disease of importance, because it clinically resembles breast carcinoma. It occurs in women of child-bearing age, and is diagnosed histopathologically by finding inflammatory changes with granuloma formation confined to the lobules of the breast. A case of bilateral granulomatous mastitis appearing as metachronous lesions is described. The possible cause of the disease is discussed. Cultures of the involved tissue failed to grow any causative organism. Detailed immunological studies appeared to exclude an immunological cause.