Contralateral relapse after surgery for breast cancer: evaluation of follow-up paradigms.

BACKGROUND: Early treatment of breast cancer patients with loco-regional relapse or contralateral disease has been shown to improve survival. There is no current consensus on the optimal follow-up strategy. This study estimates the risk of isolated contralateral relapse (CR) after breast cancer surgery and its change over time, together with the efficacy of clinical examination, self-examination and mammography in the detection of CR. METHODS: Data from patients treated for early breast cancer at Guy's Hospital between 1990 and 1997 were collected and those with isolated contralateral recurrences were analysed. Life table analysis was performed and CR, CR-free and cumulative CR rates were calculated. Correlations were evaluated using Pearson's correlation coefficient. RESULTS: One thousand one hundred and forty-three women were included in the study and 23 patients had isolated CR. The median probability of CR was a constant 0.24% per year. Only one recurrence was found clinically at follow up, while the majority was detected through mammography and self-palpation. CONCLUSIONS: The risk of CR is low and constant with time. Contralateral mammography is useful and can detect the vast majority of contralateral recurrences. These findings may have practical implications especially on the planning of postmastectomy follow up.

ZEN and the art of breast health maintenance.

Zearalenone (ZEN) is a non-steroidal mycoestrogen that widely contaminates agricultural products. ZEN and its derivatives share similar molecular mechanisms and activity with estrogens and interact with ERα and ERß leading to changes in the reproductive system in both animals and humans. The reduced form of ZEN, α-ZEA ralenol, has been used as an anabolic agent for animals and also proposed as hormonal replacement therapy in postmenopausal women. Furthermore, both zearelanol ZEN and derivatives have been patented as oral contraceptives. ZEN has been widely used in the United States since 1969 to improve fattening rates in cattle by increasing growth rate and feed conversion efficiency. Evidence of human harm from this practice is provided by observations of central precocious puberty. As a result, this practice has been banned by the European Union. As ZEN has been associated with breast enlargement in humans, it has been included in many bust-enhancing dietary supplements but epidemiological evidence is lacking with regard to breast cancer risk. Extensive work with human breast cancer cell lines has shown estrogenic stimulation in those possessing ER but a reduction in DMBA-induced breast cancers in rodents given ZEN. Protein disulfide isomerase provides a molecular biomarker of dietary exposure to ZEN and its derivatives allowing the detection and control of harmful food intake. The interaction of ZEN with anti-estrogens, anticancer agents and antioxidants requires further investigation.

The three-surgeon technique for liver tissue dissection: towards real bloodless hepatectomy.

PURPOSE: Bleeding during hepatectomy remains a major cause of mortality despite recent developments in surgical and anaesthetic techniques. To date there is no single surgical device that combines speed, efficient haemostasis and safety for the adjacent vital structures during parenchymal division. This article presents the Three Surgeon Technique (3ST), a novel method of parenchymal dissection for major hepatectomies and compare it with our standard radiofrequency ablation (RFA) - assisted technique. METHODS: 77 patients who underwent major liver resection were divided into two groups: 38 of them (group A) underwent 41 RFA-assisted liver resections and 39 (group B) underwent 41 hepatectomies with the 3ST. The data for the 3ST were prospectively collected and compared to the already collated RFA patient group. RESULTS: Blood transfusion was necessary in 28 and 13 patients in group A and B respectively (p=0.016), with an average of 1.7 and 0.6 units of red blood cells (p<0.001). The Pringle maneuver was not required with the 3ST. The mean time of parenchymal dissection was 90.49 and 77.52 min in group A and B, respectively (p=0.007). CONCLUSION: The 3ST is a novel, reliable and safe alternative to the stand alone RFA-assisted technique. It is a faster procedure, and requires less blood units transfusion.

Digital infrared thermal imaging (DITI) of breast lesions: sensitivity and specificity of detection of primary breast cancers.

AIM: To determine the sensitivity and specificity of digital infrared thermal imaging (DITI) in a series of women who underwent surgical excision or core biopsy of benign and malignant breast lesions presenting through the symptomatic clinic. MATERIALS AND METHODS: DITI was evaluated in 63 symptomatic patients attending a one-stop diagnostic breast clinic. RESULTS: Thermography had 90 true-negative, 16 false-positive, 15 false-negative and 5 true-positive results. The sensitivity was 25%, specificity 85%, positive predictive value 24%, and negative predictive value 86%. CONCLUSION: Despite being non-invasive and painless, because of the low sensitivity for breast cancer, DITI is not indicated for the primary evaluation of symptomatic patients nor should it be used on a routine basis as a screening test for breast cancer.

The effects of mild hypothermia on coagulation tests and haemodynamic variables in anaesthetized rabbits.

OBJECTIVE: Hypothermia has been associated with coagulation defects. The purpose of this experimental study was to investigate the effect of mild hypothermia on clinically used coagulation tests and on haemodynamic variables. METHODS: Nine New Zealand rabbits were subjected to mild core hypothermia by administration of general anaesthesia and exposure to room temperature of 22 degrees C for 60 minutes. Blood samples were obtained at normothermia and mild hypothermia for measurement of prothrombin time, activated partial thromboplastin time, fibrinogen levels, platelet count and haemoglobin concentration. Hypothermic values were compared to the normothermic values. Additionally, the progressive temperature drop and haemodynamic changes (blood pressure, heart rate) were recorded. RESULTS: Core temperature decreased significantly over time changing from 39.4 +/- 0.27 to 36.6 +/- 0.28 degrees C (p = 0.0001). Prothrombin time and activated partial thromboplastin time increased [corrected] at hypothermia, but the changes were not statistically significant (p = 0.203 and p = 0.109, respectively). Platelet count, fibrinogen levels and haemoglobin concentration decreased significantly (p = 0.0001, p = 0.03 and p = 0.027) but remained within normal limits. Mean arterial pressure and heart rate declined significantly over time (p = 0.0001 and p = 0.0001, respectively). CONCLUSION: The results of this study suggest that short term mild hypothermia may affect the coagulation mechanism to a clinically nonsignificant extent, while haemodynamic responses are significantly suppressed.

What can be done about hot flushes after treatment for breast cancer?

Breast cancer survivors frequently experience severe hot flushes as a result of their treatment. This can adversely affect their quality of life, compliance with treatment and overall survival. To relieve vasomotor symptoms, a variety of drugs have been used including clonidine, gabapentin, selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Stellate ganglion block (SGB) has recently emerged as a new technique against hot flushes and preliminary studies report encouraging efficacy with minimal complications. Other approaches include various alternative treatments and, in a few cases, hormone replacement therapy (HRT). All randomized, controlled studies of drugs, hormone treatments and alternative therapies for vasomotor symptoms have been reviewed and efficacy and safety noted. Side-effects of current medical treatments frequently outweigh the benefits--leading many patients to discontinue the medications. Statistically significant differences between placebo and test agent may not translate into a meaningful subjective benefit. Desvenlafaxine looks promising as does SGB, despite its invasive nature. The favorable safety profile of SGB is confirmed through the long experience of SGB performed for other medical purposes. The majority of non-HRT treatments for hot flushes are little better than placebo but early results from randomized trials of desvenlafaxine and pilot studies of SGB suggest that it is worthwhile to test their efficacy specifically in breast cancer survivors.

Nipple-sparing skin-reducing mastectomy with reconstruction for large ptotic breasts.

BACKGROUND: Breast reconstruction is routinely used to alleviate the psychological adverse effects of mastectomy. Nipple preservation further improves the cosmetic result, and causes less trauma on the body surface. Nipple-sparing mastectomy, however, comes with challenges, especially in the case of large, ptotic breasts to the degree that large-sized breasts have conventionally been a contraindication for nipple preservation. In this report, we describe a novel technique for nipple preservation in immediate reconstruction of large, ptotic breasts. METHODS: From 2013 to 2018, 24 patients (30 breasts) with large, ptotic breasts were treated with mastectomy and immediate reconstruction with nipple preservation. Median BMI was 28 and 8 patients were smokers. The technique involves the de-epithelialisation of a large area of the breast skin, the mastectomy through a lateral full-thickness incision within the de-epithelialised area, imbrication of the de-epithelialised skin, lifting of the nipple to a higher position and finally closure of wound. RESULTS: There were no full, 4 partial nipple necroses and 3 re-operations were done under local anaesthetic to correct partial peripheral necrosis of the areola. Six patients needed seroma aspiration and 4 presented with cellulitis. No implants were lost and there were no delays to adjuvant treatment. CONCLUSIONS: The proposed technique has significant advantages and may be ideal when large skin reductions are necessary in immediate breast reconstruction with nipple preservation. The low complication rate makes the method ideal when adjuvant treatment is to follow and/or patients are of high risk for surgical complications.

Multifocal and multicentric breast cancer, is it time to think again?

Multifocal multicentric breast cancer has traditionally been considered a contraindication to breast conserving surgery because of concerns regarding locoregional control and risk of disease recurrence. However, the evidence supporting this practice is limited. Increasingly, many breast surgeons are advocating breast conservation in selected cases. This short narrative review summarises current evidence on the role of surgery in multifocal multicentric breast cancer and shows that when technically feasible the option of breast conservation is oncologically safe.

Follow-up may not be beneficial after treatment of grade 1 breast cancer.

BACKGROUND: Identification of women treated for breast cancer who have a low risk of locoregional recurrence or contralateral breast cancer, and who can be discharged safely from follow-up, would lower costs without compromising prognosis. This study investigated the risk of locoregional recurrence and contralateral breast cancer in women treated for grade 1 breast cancer. METHODS: Some 1143 women who had surgery for breast cancer were followed, and the rate of locoregional recurrence or contralateral breast cancer was determined. The risk was compared to the tumour grade. RESULTS: At a mean follow-up of 9.1 years, 10-year estimates of the cumulative risk of locoregional recurrence or contralateral breast cancer for grade 1, 2 and 3 breast cancer were 0.03 (95 per cent confidence interval (c.i.) 0.01 to 0.08), 0.12 (0.09 to 0.15) and 0.16 (0.13 to 0.20) respectively. Grade 1 tumours had a risk of locoregional recurrence or contralateral breast cancer of 285 (95 per cent c.i. 93 to 670) per 100,000 person-years. CONCLUSION: Women treated for grade 1 breast cancer could be discharged from follow-up after completion of the primary treatment, without compromising their quality of care.

Autologous tissue immediate breast reconstruction: desired but oncologically safe?

BACKGROUND: There has been a dramatic increase in the incidence of immediate breast reconstruction after mastectomy for breast cancer over the past few decades and autologous tissue flaps are being used with increasing frequency. Concern has been expressed that these complex procedures may lead to a delay in the delivery of adjuvant therapy, which in turn may adversely affect recurrence and survival rates. Several publications have looked into the effect of immediate reconstruction on the timing of delivery of adjuvant therapy, but all types of immediate breast reconstruction (IBR) tend to be examined as a homogenous group. AIM: The aim of this review was to search current literature and look specifically at the effect of autologous tissue reconstructions on adjuvant therapy, and identify possible causes of delay. DISCUSSION: From the data analysed, it appears that there may be a delay in the delivery of adjuvant therapy associated with autologous tissue IBR, especially transverse rectus abdominis muscle (TRAM) flaps. The studies available, however, examine small numbers of patients, which makes proving statistical significance difficult. Moreover, there also appears to be no consensus on what constitutes a delay in the delivery of adjuvant therapy. From 3% to 72% of autologous tissue IBR patients seem to receive their adjuvant treatment with a delay, according to the guidelines of the respective centres. Moreover, the period of time until chemotherapy appears generally increased from 13% to 36% compared with mastectomy alone patients. The most common reasons for delay are wound and flap complications. CONCLUSION: At the moment, despite the increasing popularity of autologous IBR, these procedures have not proved their oncological safety. Further studies looking at the effect of IBR, especially TRAM flap reconstruction, are needed.

The role of digital breast tomosynthesis in breast cancer screening: a manufacturer- and metrics-specific analysis.

AIM: Digital Breast Tomosynthesis (DBT), with or without Digital Mammography (DM) or Synthetic Mammography (SM), has been introduced or is under consideration for its introduction in breast cancer screening in several countries, as it has been shown that it has advantages over DM. Despite this there is no agreement on how to implement DBT in screening, and in many cases there is a lack of official guidance on the optimum usage of each commercially available system. The aim of this review is to carry out a manufacturer-specific summary of studies on the implementation of DBT in breast cancer screening. METHODS: An exhaustive literature review was undertaken to identify clinical observer studies that evaluated at least one of five common metrics: sensitivity, specificity, area under the curve (AUC) of the receiver-operating characteristics (ROC) analysis, recall rate and cancer detection rate. Four common DBT implementation methods were discussed in this review: (1) DBT, (2) DM with DBT, (3) 1-view DBT with or without 1-view DM or 2-view DM and (4) DBT with SM. RESULTS: A summary of 89 studies, selected from a database of 677 studies, on the assessment of the implementation of DBT in breast cancer screening is presented in tables and discussed in a manufacturer- and metric-specific approach. Much more studies were carried out using some DBT systems than others. For one implementation method of DBT by one manufacturer there is a shortage of studies, for another implementation there are conflicting results. In some cases, there is a strong agreement between studies, making the advantages and disadvantages of each system clear. CONCLUSION: The optimum implementation method of DBT in breast screening, in terms of diagnostic benefit and patient radiation dose, for one manufacturer does not necessarily apply to other manufacturers.

Radiofrequency ablation in the treatment of primary breast cancer: no surgical redundancies yet.

BACKGROUND/INTRODUCTION: Radiofrequency energy has emerged as a new tool for the local destruction of cancer by inducing thermal tissue necrosis in the target region. Radiofrequency ablation (RFA) has recently been used to treat breast cancer primaries, potentially offering all the advantages of minimally invasive techniques. METHODS/EVIDENCE: Nine published studies addressing the role of RFA in the treatment of breast cancer have been identified and analysed, in six, first-line RFA was followed by surgical removal and there were 12 failures in 108 ablations. Three further studies involved RFA without subsequent excision and in 1/60 there was a local relapse after 4 months (follow-up range: 15-29 months). DISCUSSION: Existing RFA techniques may not be able to destroy the whole of the malignant lesion, because of local conditions allowing cancer cells to survive within the target area or because electrodes cannot be accurately directed to the tumour site with ultrasound. Additionally, distant in-breast cancers can be missed on pre/intraoperative imaging. Histological information is unavailable after tissue destruction so that the opportunity to reassess tumour grade based on more extensive sampling is lost, but this can be improved by more extensive sampling with vacuum-assisted core biopsy. CONCLUSIONS: Before RFA can be safely used in the treatment of breast cancer primaries, several criteria need to be met. These include development of RFA devices and techniques, standardisation of the treatment protocol, including imaging and selection of patients, and establishment of a feasible post-treatment follow-up strategy.

Effect of harmonic scalpel on seroma formation following surgery for breast cancer: a prospective randomized study.

PURPOSE: With the escalating cost of healthcare provision, surgical techniques that could lead to shorter postoperative stay and reducing cost of health provision are welcomed. We report the results of a prospective randomized trial to investigate the role of harmonic scalpel (HS) in reducing postsurgical seroma formation, complications, pain and consequent cost in breast surgery. PATIENTS AND METHODS: Thirty-three procedures were carried out on 32 women. Patients were prospectively randomized to either HS or electrocautery (EC). The two cohorts were accordingly matched and postsurgical seroma volumes, complications and pain scores were documented. RESULTS: There were 16 procedures in the HS and 17 in the EC group. First 48 h drainage, total drained volume, aspirated volume, operative time, pain score, number of patients that developed seromas, number of clinic visits for aspiration, complications and required analgesia were comparable in the two groups. Multivariate analysis showed no significant correlation between the total amount of seroma drainage and the known risk factors (body mass index/BMI, size of the invasive tumor and number of positive nodes). CONCLUSION: No significant reduction in seroma formation or wound complications and pain could be found with the use of HS. We were unable to demonstrate any significant clinical advantages with the use of HS or cost benefit.

Pressure dressing in breast surgery: is this the solution for seroma formation?

PURPOSE: Pressure dressing (PD) after modified radical mastectomy (MRM) for breast cancer is investigated here as an easy-to-apply method to reduce seroma formation and subsequent need for clinical care. PATIENTS AND METHODS: Two hundred mastectomized patients who were treated with PD on the skin flaps and the axilla immediately postoperatively (group A) were compared with a similar non-PD group (B). Surgical technique and perioperative care were the same. Drains were removed when drain output was reduced to 30 ml per day, or on postoperative day 8 regardless of output. RESULTS: Mean time with drains kept in situ was 4.9 and 5.5 days in group A and B, respectively. Five (2.5%) patients in group A and 16 (8%) in group B developed seromas after the removal of the drains. In total, 9 seroma needle aspirations were performed in group A and 26 in group B. Differences were statistically significant. CONCLUSION: Our findings are supportive of PD as an effective, cheap and easy-to-apply method for the reduction (a) of the time with drains in situ after MRM, (b) of the number of patients developing seromas and (c) of the seroma aspirations. This can potentially reduce further complications, needed medical care and cut expenditure.

Nestin and CD146 expression in metaplastic breast cancer: stem-cell therapy in need? Lessons reported from a male patient.

OBJECTIVE: Metaplastic breast carcinomas represent a rare subtype of breast cancer exhibiting aggressive clinical features. They appear as highly chemoresistant tumors, therefore showing poor outcome and high rates of local recurrence or distant metastasis. CASE REPORT: A 37-year-old greek man was referred to our hospital for evaluation of a locally advanced, ulcerated, fixed, irregular and hard in consistency mass covering his left breast and chest wall. Further work out with CT and biopsy of the tumor revealed a triple negative metaplastic breast cancer classified as cT4cN3cM1. The patient received first line chemotherapy and afterward a palliative resection of the tumor. The histology revealed the presence of a combined triple negative adenocarcinoma with a predominant metaplastic squamous carcinoma and a spindle cell (sarcomatoid) carcinoma of the breast. In the tissue sample stem cell markers, nestin and CD146 (MCAM) were expressed, enhancing the theory that cancer cells of this tumor could possibly harbor stem cell properties. The patient received several chemotherapy regimens but died 6 months after the initiation of treatment. CONCLUSIONS: Metaplastic breast cancer consists of cells with stem cell properties. New targeted therapies are warranted in the view of the tumor's high resistance to conventional chemotherapy. Targeting nestin and CD146 might be a promising therapy as they seem to be implicated in the EMT pathway.

Expanding ulnar artery aneurysm presenting with signs of threatened rupture.

The case of a 25-year-old man admitted with an ulnar artery aneurysm of the wrist is presented. The size of the aneurysm (1.5 x 2.7 cm) and progressive pain gave the impression of a threatened rupture. Radiologic examinations confirmed the existence of a non-thrombosed ulnar artery aneurysm with occlusion of the 4th and 5th digital arteries. During an urgent surgical exploration a pseudo-aneurysm was found and resected and the artery was repaired. Thrombolysis of the digital arteries was performed with a good result. The combination of a large-sized pseudo-aneurysm, lack of a history of penetrating trauma and presentation of threatened rupture are unique and not reported previously in the literature.

Comparison of myocardial perfusion imaging and cardiac troponin I in patients admitted to the emergency department with chest pain.

BACKGROUND: Identification of patients with acute coronary syndromes (ACS) among those who present to emergency departments with possible myocardial ischemia is difficult. Myocardial perfusion imaging with 99mTc sestamibi and measurement of serum cardiac troponin I (cTnI) both can identify patients with ACS. METHODS AND RESULTS: Patients considered at low to moderate risk for ACS underwent gated single-photon emission CT sestamibi imaging and serial myocardial marker measurements of creatine kinase-MB, total creatine kinase activity, and cTnI over 8 hours. Positive perfusion imaging was defined as a perfusion defect with associated abnormalities in wall motion or thickening. cTnI >/=2.0 ng/mL was considered abnormal. Among the 620 patients studied, 59 (9%) had myocardial infarction and 81 (13%) had significant coronary disease; of these patients, 58 underwent revascularization. Perfusion imaging was positive in 241 patients (39%), initial cTnI was positive in 37 (6%), and cTnI was >/=2.0 ng/mL in 74 (12%). Sensitivity for detecting myocardial infarction was not significantly different between perfusion imaging (92%) and cTnI (90%), and both were significantly higher than the initial cTnI (39%). Sensitivity for predicting revascularization or significant coronary disease was significantly higher for perfusion imaging than for serial cTnI, although specificity for all end points was significantly lower. Lowering the cutoff value of cTnI to 1.0 ng/mL did not significantly change the results. CONCLUSIONS: Early perfusion imaging and serial cTnI have comparable sensitivities for identifying myocardial infarction. Perfusion imaging identified more patients who underwent revascularization or who had significant coronary disease, but it had lower specificity. The 2 tests can provide complementary information for identifying patients at risk for ACS.

Ability of troponin I to predict cardiac events in patients admitted from the emergency department.

OBJECTIVES: We sought to determine the predictive ability of troponin I (TnI) in a heterogeneous group of patients with chest pain admitted from the emergency department (ED) for exclusion of myocardial infarction (MI). BACKGROUND: Previous studies in high-risk patients demonstrated that troponin elevations are associated with increased cardiac events. Little information is available on its predictive ability in more heterogeneous, lower risk patients. METHODS: Consecutive patients admitted from the ED for possible MI underwent serial myocardial marker sampling of TnI and creatine kinase, CK-MB over an 8-h period. Patients with ST segment elevation were excluded. End points included MI, death, significant complications (e.g., cardiac or respiratory arrest, intra-aortic balloon pump, pulmonary artery catheter or pacemaker placement, revascularization or inotropic infusion) and significant disease. RESULTS: Events occurred in 513 (27%) of the 1,929 patients evaluated: MI in 175 (9.1%) and death in 34 (1.8%); an additional 248 patients (13%) without MI had complications, and 323 (17%) without MI had significant disease. Sensitivity of TnI for MI was high (96%). Patients without MI who were TnI-positive were more likely to have complications (43% vs. 12%) or significant disease (41% vs. 17%) as compared with those who were TnI-negative; however, the sensitivity of TnI for these two end points was low (14% and 21%, respectively). Predictive values were unchanged after excluding patients with ischemic electrocardiograms. CONCLUSIONS: Troponin I had a high sensitivity for MI when used as part of a rapid rule-in protocol; however, the sensitivity for other end points was low. Use of TnI alone failed to identify the majority of patients who had either significant disease or complications.

Value of acute rest sestamibi perfusion imaging for evaluation of patients admitted to the emergency department with chest pain.

OBJECTIVES: This study sought to determine the ability of early perfusion imaging using technetium-99m sestamibi to predict adverse cardiac outcomes in patients who present to the emergency department with possible cardiac ischemia and nondiagnostic electrocardiograms (ECGs). BACKGROUND: Evaluation of patients presenting to the emergency department with possible acute coronary syndromes and nondiagnostic ECGs is problematic. Accurate risk stratification is necessary to prevent serious adverse outcomes. Initial results suggest that early perfusion imaging using technetium-99m sestamibi enables reliable risk stratification. METHODS: Patients presenting to the emergency department with a low to moderate probability of acute coronary syndromes underwent rapid sestamibi injection with gated single-photon emission computed tomographic imaging. Studies showing perfusion defects with associated wall motion abnormalities were considered positive. RESULTS: A total of 532 consecutive patients underwent serial myocardial marker analysis and rest perfusion imaging. Of these patients, perfusion imaging was positive in 171 (32%). Positive perfusion imaging was the only multivariate predictor of myocardial infarction (MI) (p < 0.0001, odds ratio [OR] 33, 95% confidence interval [CI] 7.7 to 141) and was the most important independent predictor of MI or revascularization (p < 0.0001, OR 14, 95% CI 7.3 to 25), followed by diabetes (p < 0.01, OR 2.8, 95% CI 1.5 to 5.1), typical angina (p = 0.01, OR 2.1, 95% CI 1.2 to 3.7) and male gender (p = 0.03, OR 1.9, 95% CI 1.1 to 3.5). The sensitivity of positive perfusion imaging for MI was 93% (95% CI 77% to 98%), and for MI or revascularization it was 81% (95% CI 71% to 88%), with negative predictive values of 99% (95% CI 98% to 100%) and 95% (95% CI 92% to 97%), respectively. CONCLUSIONS: Positive rest perfusion imaging accurately identified patients at high risk for adverse cardiac outcomes, whereas negative perfusion imaging identified a low risk patient group. Early perfusion imaging allows for rapid and accurate risk stratification of emergency department patients with possible cardiac ischemia and nondiagnostic ECGs.