Volume-controlled vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery: a meta-analysis.

It is unknown whether there are any clinically relevant differences between volume-controlled (<30-50 ml/24h across trials) vs no/short-term drainage after axillary lymph node dissection in breast cancer surgery on outcomes such as seroma formation, wound infection or length of hospital stay. Randomised controlled trials comparing volume-controlled drainage vs no or short-term drainage after axillary lymph node dissection in breast cancer surgery were identified systematically using Pubmed, EMBASE and The Cochrane library. Trial data were reviewed and extracted independently by two reviewers in a standardised unblinded manner. Six randomised controlled trials which included a total of 561 patients fulfilled our inclusion criteria. Patients randomised to volume-controlled drainage were less likely to develop clinically relevant seromas compared to patients randomised to no/short-term drainage. There was, however, no difference in wound infections between patients treated with volume-controlled drainage and patients with no or short-term drainage. Patients randomised to volume-controlled drainage stayed significantly longer in hospital than patients randomised to no/short-term drainage. Based on available evidence, clinically relevant seromas occur more frequently in patients treated with no/short-term drainage. However, no/short-term drainage after axillary lymph node dissection does not lead to an increase in wound infections and is associated with shorter hospital stay.

A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer.

BACKGROUND: To reduce the risk of seroma after modified radical mastectomy in breast cancer patients, the use of suction axillary drainage is a standard procedure. The optimal time to remove the drain is not established. Whether the removal or preservation of the pectoral fascia influences the risk of seroma formation or loco-regional recurrence rate remains unclear. METHOD: The trial included 247 patients with breast cancer who underwent modified radical mastectomy in five Swedish hospitals 1993-1997. The median follow-up time was 6 years. One hundred and twenty-two and 125 patients, respectively, were randomised between removal versus preservation of the pectoral fascia. Of these 247 patients a total of 198 patients were also randomised to have the drain removed 24 h postoperatively or to keep the drain in until discharge had decreased to less than 40 ml/24 h. RESULTS: Early removal of the axillary drain was associated with significantly more seromas and a shorter average postoperative hospital stay. There were no differences between the two groups regarding the rate of wound infections and/or hematoma formation. Removal or preservation of the pectoral fascia did not influence the formation of seroma or the amount of peroperative bleeding. A trend towards an increased risk for chest wall recurrence was observed in patients with preserved pectoral fascia (16/125 compared with 8/122; hazard ratio=2.0, 95% confidence interval=0.9-4.7). CONCLUSION: Early removal of axillary drain shortened the duration of hospital stay without any increase in wound complications. However, it yielded a significantly higher incidence of seroma. Seroma formation and the chest wall recurrence rate was not significantly influenced by the preservation of the pectoral fascia or not.

Gelatinase A, membrane type 1 matrix metalloproteinase, and extracellular matrix metalloproteinase inducer mRNA expression: correlation with invasive growth of breast cancer.

Invasive breast cancer varies widely in biologic aggressiveness, from fairly indolent tumors to rapidly disseminating carcinomas. Matrix metalloproteinases have enzymatic activity and assist in tumor invasion by degrading basement membranes and extracellular matrix. The extracellular matrix metalloproteinase inducer EMMPRIN is thought to stimulate fibroblasts to produce the zymogen pro-gelatinase A. The membrane type 1-matrix metalloproteinase (MT1-MMP) is thought to assist in tumor invasion and metastasis by activating pro-gelatinase A, which shows enhanced expression in various tumors. Overexpression of gelatinase A has shown to correlate with a malignant phenotype in many tumor forms. The aim of the study was to investigate the mRNA expression pattern of MT1-MMP, gelatinase A, and EMMPRIN in breast tumors. Formalin-fixed paraffin-embedded breast tissue samples from 18 patients operated on with breast-conserving surgery for invasive breast carcinoma <20 mm between 1977 and 1985 were analyzed using the mRNA in situ hybridization technique. Most of the patients were node-negative (15/18) and underwent postoperative irradiation to the breast (16/18). The median age at diagnosis was 52 years (21-83 years). At the time of the study 11 patients were alive, 4 without recurrence; 7 patients had been operated for ipsilateral breast tumor recurrences, and 2 had distant metastases. The median follow-up was 112 months (102-193 months). Seven patients died of disseminated breast cancer; their median follow-up was 43 months (22-116 months). (35)S-labeled antisense and sense mRNA probes transcribed from linearized plasmids containing cDNA for the matrix metalloproteinases gelatinase A and MT1-MMP and the glycoprotein EMMPRIN were hybridized to 5 microm paraffin-embedded tissue sections. Several invasive carcinomas were surrounded by normal tissue and carcinoma in situ lesions. Gelatinase A, MT1-MMP, and EMMPRIN mRNA expression were detected in all of the carcinomas. The gelatinase A mRNA expression was mainly localized to stromal cells at moderate to high levels surrounding the invading carcinoma cells but was also seen in single cells at low levels in in situ lesions and in some normal glandular cells. MT1-MMP and EMMPRIN were expressed in all of the carcinomas and were mainly localized to tumor cells; but they were also seen to some extent in single cells at low levels in in situ lesions and in normal glandular cells. No differences in levels of expression for gelatinase A, MT1-MMP, or EMMPRIN were seen in patients who survived compared to patients who died from metastatic disease. The co-expression of gelatinase A, MT1-MMP, and EMMPRIN mRNA in invasive breast carcinoma supports the theory that these proteins interact and are important for the invasive phenotype in breast carcinoma. Hence EMMPRIN may be a central factor for stimulation of gelatinase A activation. Specific inhibition for individual MMP members could in the future be target-specific events in breast tumor progression. Inhibition of EMMPRIN could be such a target.

Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer.

INTRODUCTION: The aims of the study were to assess the outcome among patients with early breast cancer operated on with wide local excision who developed a subsequent ipsilateral breast tumor recurrence, and to identify risk factors for uncontrolled local disease. Uncontrolled local disease (ULD) was defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated with salvage treatment during the period of follow-up (2-18 years). PATIENTS AND METHODS: Eighty-five patients in a cohort of 759 patients, treated for invasive Stage I-II breast cancer with breast-conserving surgery 1976-1985 in Stockholm, with a subsequent ipsilateral breast tumor recurrence (IBTR) were reviewed retrospectively. The majority of the patients were premenopausal (58%), node negative (72%), and had received postoperative radiotherapy (79%). Median follow-up time following breast-conserving surgery was 13 (9-19) years. Multivariate Cox's hazard regression was used in the statistical analysis to identify prognostic factors for ULD. RESULTS: The majority (n = 61) of the IBTR's were located in the original tumor quadrant and showed the same histopathological features as the primary tumor. Salvage mastectomy (n = 65) or reexcision (n = 14) were performed in 79 (93%) of the patients. Twenty-one patients developed ULD. Five years following the diagnosis of IBTR the disease-free survival was 59%, the cumulative incidence for ULD was 24%, and for death in breast cancer 34%. In the cohort of 759 patients, patients who received radiotherapy following the primary breast-conserving surgery had 1% cumulative incidence of ULD following the diagnosis of IBTR compared to 4% among patients that received no postoperative radiotherapy. The cumulative incidence at 5 years of ULD following salvage mastectomy was 12% compared to 33% after salvage reexcision. Patients operated on with breast-conserving surgery with an original tumor size < 15 mm, who were treated with salvage mastectomy for IBTR, had in multivariate analysis the lowest relative risk for ULD. Adjuvant chemotherapy following IBTR treatment did not seem to improve local tumor control. Following the diagnosis of IBTR, 78% (n = 21) of the patients with ULD and/or regional recurrence (n = 27), died of a disseminated breast cancer in contrast to 10% (n = 6) among the remaining 58 patients. CONCLUSION: Uncontrolled local disease is an important outcome measure following breast-conserving surgery. In this cohort, salvage mastectomy provided a superior local control rate compared to salvage reexcision. A higher although not statistically significant rate of ULD was also seen in patients who had not received postoperative radiotherapy as part of their primary treatment.

A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group.

BACKGROUND: The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. METHODS: The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). RESULTS: At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed. CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%.

Myocardial infarction among women with early-stage breast cancer treated with conservative surgery and breast irradiation.

PURPOSE: To assess the possible impact of the irradiation on the risk of acute myocardial infarction among breast cancer patients treated with conservative surgery and postoperative radiation therapy. METHODS AND MATERIALS: The incidence of and mortality from acute myocardial infarction was assessed in a group of 684 women with early-stage breast cancer diagnosed during 1976-1987 who had been treated with breast conserving surgery plus postoperative radiation therapy given with tangential photon fields. In 94% of the patients the total dose was between 48-52 Gy given with 2 Gy daily fractions 5 days per week for a total treatment period of about 4 1/2-5 1/2 weeks. In 88% of the patients the target volume included the breast parenchyma alone. In the remaining patients regional nodal areas were also irradiated. A concurrent group of 4,996 breast cancer patients treated with mastectomy without postoperative radiation therapy was used as a reference. RESULTS: After a median follow-up of 9 years (range: 5-16 years) 12 conservatively treated patients (1.8%) had developed an acute myocardial infarction and 5 (0.7%) had died due to this disease. The age-adjusted relative hazard of acute myocardial infarction for the conservative group vs. the mastectomy group was 0.6 (95% C.I.: 0.4-1.2) and for death due to this disease 0.4 (0.2-1.1). The incidence of acute myocardial infarction among the conservatively treated women was similar irrespective of tumor laterality. CONCLUSIONS: There was no indication of an increased risk of acute myocardial infarction with the radiation therapy among the women treated with conservative surgery. However, due to the small number of events the study could not exclude the possibility that cardiac problems may arise in some patients with left-sided cancers who have their heart located anteriorly in the mediastinum. Individual, three-dimensional dose planning represents one method to identify such patients and is basic to technical changes aimed at decreasing the cardiac radiation dose volume.

Breast conserving surgery for invasive breast cancer: risk factors for ipsilateral breast tumor recurrences.

To identify risk factors associated with an increased risk for ipsilateral breast tumor recurrence following breast-conserving surgery, a cohort of 759 women with T1-T2 tumors were studied. The majority of the patients (88%) had received postoperative radiation therapy to the breast. Median follow-up time was 10 (range: 6-17) years. There was a 1-1.5% yearly increase in ipsilateral breast tumor recurrences. For women < 50 ys the cumulative recurrence rate at 10 years was 18% and for women > or = 50 ys, 9%. Node positive women had a cumulative breast recurrence rate of 25% versus 10% for node negative women. Ten years postoperatively, irradiated patients had a cumulative recurrence rate of 11% versus 26% when no irradiation was given. The beneficial effect of radiotherapy was substantial during the first four postoperative years. The relative risk for an ipsilateral breast tumor recurrence during this period was 4.5 times higher than for non-irradiated patients. However, the protective effect of radiotherapy decreased with time. After ten years the relative risk of ipsilateral breast tumor recurrence was the same among irradiated and non-irradiated patients although the number of events during this period was low. Univariate analysis showed that seven factors were significantly associated with an increased risk of ipsilateral breast tumor recurrence, namely age < 50 ys, increasing tumor size, uncertain microscopic margins, axillary lymph node metastases, no postoperative tamoxifen treatment, premenopausal status, and no postoperative radiotherapy. Three factors remained independently significant after multivariate analysis: age < 50 ys, no postoperative radiation therapy, and positive lymph nodes. In conclusion, radiotherapy reduced the breast recurrence rate, but the effect decreased with time. Node-negative women > or = 50 were a low risk-group for ipsilateral breast tumor recurrence, with a cumulative risk at 10 years of 9% without radiation therapy and 5% with breast irradiation.

Mammographic features, predictors of early ipsilateral breast tumour recurrences?

Mammograms from 69 patients with Stage I/II breast cancer, operated on using breast-conserving surgery between 1987-1990 were blindly re-evaluated in order to predict retrospectively ipsilateral breast tumour recurrences. The study cohort was divided into two groups of 34 and 35 patients. Each group was matched according to age, the time at risk and to presence or absence of an ipsilateral breast tumour recurrence. The mammographic reinterpretation was performed by two radiologists that correctly predicted an ipsilateral breast tumour recurrence in 81%. Mammographic characteristics, such as diffuse microcalcifications, multifocality, solitary densities, especially of stellate type near the nipple and/or spicula in the vicinity of the retroareolar region were more often associated with an ipsilateral breast tumour recurrence. Data from this limited series suggest that certain mammographic features seem to correlate with the ability of the tumour to recur locally. Hence, mammography can play a prognostic role in deciding the treatment of choice in operable breast cancer.

Cardiac function in primary hyperparathyroidism before and after operation. An echocardiographic study.

OBJECTIVE: To identify possible causes for the increased cardiovascular morbidity and mortality seen in patients with primary hyperparathyroidism. DESIGN: Prospective, blind study. SETTING: University hospital, Sweden. SUBJECTS: 44 Patients with primary hyperparathyroidism and 23 (sex and age matched) control patients with atoxic nodular goitres. INTERVENTIONS: Exploration of the neck with removal of pathological parathyroid glands or thyroid resection. Echocardiography before, and one year after, the operation. MAIN OUTCOME MEASURES: Blood pressure and echocardiographic findings. RESULTS: Hyperparathyroid patients had higher blood pressure and greater left atrial diameter than control patients preoperatively. They also had a significantly lower E:A ratio (mitral flow velocity pattern) than the controls (p = 0.02) indicating a disturbance in early diastolic filling of the left ventricle. The E:A ratio correlated negatively with the systolic blood pressure. 19 of the hyperparathyroid patients (43%) had cardiac calcifications as did 14 (61%) of the controls. Most of calcifications were located in the aortic and mitral valves; only a few patients had calcifications in the myocardium. No significant changes had occurred one year after parathyroidectomy, except for a reduction in systolic blood pressure, in the hyperparathyroid patients. CONCLUSION: Echocardiographic investigation of patients with primary hyperparathyroidism shows early signs of left ventricular dysfunction that may be of clinical importance.

Sarcoma botryoides of the extrahepatic bile ducts. A light- and electron microscopic study of a case.

The clinical, light- and electron microscopic features of a sarcoma botryoides of the common bile duct of a 2 1/2-year-old boy are reported. Despite the absence of cross-striation under the light microscope, many tumour cells were found to contain abundant thin and thick filaments arranged in a sarcomere-like pattern at the electron-microscopic examination of originally paraffin-embedded material. Ultrastructural examination of embryonal rhabdomyosarcoma may be of value for a definite diagnosis also when only formalin-fixed and paraffin-embedded material is available.