Innovations for the future of breast surgery.

BACKGROUND: Future innovations in science and technology with an impact on multimodal breast cancer management from a surgical perspective are discussed in this narrative review. The work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England. METHODS: Expert opinion was sought around themes of surgical de-escalation, reduction in treatment morbidities, and improving the accuracy of breast-conserving surgery in terms of margin status. There was emphasis on how the primacy of surgical excision in an era of oncoplastic and reconstructive surgery is increasingly being challenged, with more effective systemic therapies that target residual disease burden, and permit response-adapted approaches to both breast and axillary surgery. RESULTS: Technologies for intraoperative margin assessment can potentially half re-excision rates after breast-conserving surgery, and sentinel lymph node biopsy will become a therapeutic procedure for many patients with node-positive disease treated either with surgery or chemotherapy as the primary modality. Genomic profiling of tumours can aid in the selection of patients for neoadjuvant and adjuvant therapies as well as prevention strategies. Molecular subtypes are predictive of response to induction therapies and reductive approaches to surgery in the breast or axilla. CONCLUSION: Treatments are increasingly being tailored and based on improved understanding of tumour biology and relevant biomarkers to determine absolute benefit and permit delivery of cost-effective healthcare. Patient involvement is crucial for breast cancer studies to ensure relevance and outcome measures that are objective, meaningful, and patient-centred.

This article describes how future innovations in science and technology influence the management of breast cancer from a surgical perspective. This work was undertaken in response to the Commission on the Future of Surgery project initiated by the Royal College of Surgeons of England.

Population-based study of the sensitivity of axillary ultrasound imaging in the preoperative staging of node-positive invasive lobular carcinoma of the breast.

BACKGROUND: Preoperative staging of the axilla is important to allow decisions regarding neoadjuvant treatment and the management of the axilla. Invasive lobular carcinoma metastases are difficult to detect because of the infiltrative pattern of the nodal spread. In this study the sensitivity of preoperative axillary staging between invasive lobular (ILC) and ductal (IDC) carcinoma was compared. METHODS: All women diagnosed with pure ILC or IDC in the West of Scotland in 2012-2014 were identified from a database maintained prospectively within the Managed Clinical Network. Pretreatment axillary ultrasound imaging (AUS), core biopsy and fine-needle aspiration cytology (FNAC) results were compared between ILC and IDC. RESULTS: Some 602 women with ILC and 4199 with IDC had undergone axillary surgery, of whom 209 and 1402 respectively had nodal metastases. Pretreatment AUS sensitivity was significantly lower in ILC than in IDC (32·1 versus 50·1 per cent respectively, P < 0·001; OR 0·47, 95 per cent c.i. 0·34 to 0·64). Core biopsy had equally high sensitivity of 86 per cent in both subtypes; however, FNAC was significantly less sensitive in both ILC (55 per cent; P = 0·003) and IDC (75·6 per cent; P = 0·006). Multivariable analysis revealed that cT3-4 status and symptomatic presentation were both significant in predicting nodal metastasis in patients with ILC and false-negative AUS findings (OR 3·77, 95 per cent c.i. 1·69 to 8·42, P = 0·001; and OR 1·92, 1·24 to 2·98, P = 0·003, respectively). CONCLUSION: AUS is inferior in detecting axillary node metastasis in ILC compared with IDC. Women with cT3-4 lobular carcinoma may benefit from ultrasound-guided axillary biopsy regardless of the ultrasonographic appearance of the nodes.

An International Multicenter Review of the Malignancy Rate of Excised Papillomatous Breast Lesions.

BACKGROUND: Papillary lesions of the breast are a relatively rare, but heterogeneous group ranging from benign to atypical and malignant. Debate exists regarding the optimal management of these lesions. In the absence of more accurate risk-stratification models, traditional management guidelines recommend surgical excision, despite the majority of lesions proving benign. This study sought to determine the rate of malignancy in excised breast papillomas and to elucidate whether there exists a population in which surgical excision may be unnecessary. METHODS: A multicenter international retrospective review of core biopsy diagnosed breast papillomas and papillary lesions was performed between 2009 and 2013, following institutional ethical approval. Patient demographics, histopathological, and radiological findings were recorded. All data was tabulated, and statistical analysis performed using Stata. RESULTS: A total of 238 patients were included in the final analysis. The age profile of those with benign pathology was significantly younger than those with malignant pathology (p < 0.001). Atypia on core needle biopsy was significantly associated with a final pathological diagnosis of malignancy (OR = 2.73). The upgrade rate from benign core needle biopsy to malignancy on the final pathological sample was 14.4 %; however, only 3.7 % had invasive cancer. CONCLUSIONS: This international dataset is one of the largest in the published literature relating to breast papillomas. The overall risk of malignancy is significantly associated with older age and the presence of atypia on core needle biopsy. It may be possible to stratify higher-risk patients according to age and core needle biopsy findings, thereby avoiding surgery on low-risk patients.

Routine four-quadrant cavity shaving at the time of wide local excision for breast cancer reduces re-excision rate.

INTRODUCTION: Breast conservation therapy (BCT) has been shown to have comparable long-term survival outcomes when compared with mastectomy. Clearance of excision margin is one of the mainstays of the surgical treatment, which if not achieved at the first operation of BCT results in the need for subsequent surgery. METHODS: This study evaluated the impact of routinely taken cavity shavings on re-excision rates. This retrospective two-centre study describes the use of routine four-quadrant cavity shaving in 449 patients with consecutively treated with wide local excision for invasive cancer or ductal carcinoma in situ. RESULTS: The overall incomplete excision rate was 10.6%. Routine cavity shaving prevented the need for re-excision in 84 patients (18.7%) and identified the need for further re-excision in 33 patients (7.3%). Median time from surgery to radiotherapy was 50 days (range 13-209) for non-re-excised patients versus 78 days (range 47-260) for re-excised patients (p<0.001). Median time to chemotherapy (n=75) was 44 days (range 14-106) for non-re-excised patients versus 56 days (range 35-116) for re-excised patients (p=0.017). CONCLUSIONS: This study demonstrates that routine cavity shaving decreases re-excision rate in patients treated with wide local excision and prevents delays to adjuvant treatment due to incomplete excision.

'PartBreCon' study. A UK multicentre retrospective cohort study to assess outcomes following PARTial BREast reCONstruction with chest wall perforator flaps.

BACKGROUND: Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. METHODS: STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. RESULTS: Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). CONCLUSIONS: This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.

Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients. METHODS: A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage. RESULTS: Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence). CONCLUSION: Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage.

A systematic review of oncoplastic volume replacement breast surgery: oncological safety and cosmetic outcome.

INTRODUCTION: Oncoplastic breast conserving surgery allows higher volume excision to achieve oncological safety with minimal aesthetic compromise. The primary outcome of this study was to assess the oncological safety in the setting of volume replacement oncoplastic breast conserving surgery. The secondary objective was to assess cosmetic outcome. METHODS: A systematic literature review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to explore the oncological safety of oncoplastic breast conserving surgery, with particular focus on volume replacement. Resection margin rates, re-excision rates, conversion to mastectomy rates, local and distant disease recurrence, volume replacement techniques, cosmetic outcomes and patient-reported outcome measures were assessed. FINDINGS: The search criteria identified 155 articles, of which 40 met the inclusion criteria. These studies included 2,497 patients with a mean age of 47.8 years (range 38.4-59.6 years), a body mass index of 24.3kg/m2 (22.1-28.0kg/m2), with a mean follow-up of 37.1 months (6-125 months). A variety of volume replacement techniques were used, most commonly latissimus dorsi and chest wall perforator flaps. Whole mean pathological tumour size was 29.7mm (17-65mm) and mean specimen weight was 123.6g (46.5-220g). Mean re-excision rate was 7.2% and completion mastectomy rate was 2.3%. Locoregional and distant recurrence rate was 2.5% (0-8.1%) and 3.1% (0-14.6%), respectively. There were a variety of patient-reported outcome measures employed, with overall good to excellent outcomes. CONCLUSIONS: This review demonstrates that volume replacement oncoplastic breast conserving surgery is a safe option in terms of re-excision, completion mastectomy rates, and local and distant recurrence. Available patient-related outcome measures and cosmetic assessment tend towards better outcomes compared with wide local excision and mastectomy. However, data are significantly limited, with a paucity of high-level evidence, and it is therefore necessary to be cautious regarding the strength and interpretation of data in this review. Further prospective studies are required on this subject.

Systematic review of partial breast reconstruction with pedicled perforator artery flaps: Clinical, oncological and cosmetic outcomes.

The use of chest wall perforator flaps (CWPFs) following breast conservation surgery for breast cancer has become a useful tool in the armamentarium of the oncoplastic breast surgeon, however robust evidence for the technique is lacking. The aim of this study was to conduct a systematic review appraising the current evidence for the use of CWPFs, evaluating clinical, oncological and cosmetic outcomes. A PRISMA-compliant systematic review, with PROSPERO published protocol a priori and search of all relevant database and trial registries between 1990 to July 2020. Eleven studies amounting to 432 cases were reviewed and considered to be at high risk of bias due to small sample size, selective outcome reporting and selection bias. Heterogeneity due to lack of consensus of outcome measures prevented meaningful analysis. Fifty-two (12.3%) clinical complications were recorded: seroma (n = 9; 2.1%), fat necrosis (n = 9; 2.4%), haematoma (n = 8; 1.9%), infection (n = 9; 2.1%), and flap necrosis (n = 9; 2.1%). Thirty-four (10.8%) patients had an involved positive margin, 29 patients underwent re-excision (9.3%) and four underwent completion mastectomy (1.3%). One local recurrence and six distant recurrences were observed during a mean follow up of 21 months (1-49). A pooled patient cosmetic satisfaction descriptor of good or excellent was described in 93% of cases. CWPFs are a safe method of partial breast reconstruction following BCS. They are associated with a low complication rate, acceptable short-term oncological outcomes and satisfactory cosmetic outcome. There is a relative paucity in quality of data in this field and larger prospective studies are needed to investigate outcomes further.

The effect of postoperative complications on survival and recurrence after surgery for breast cancer: A systematic review and meta-analysis.

BACKGROUND: This systematic review investigated the impact of complications on long term outcomes for patients with primary invasive operable breast cancer. METHODS: A systematic review was performed using appropriate keywords, and meta-analysis using a random effects model completed. RESULTS: Ten retrospective cohort studies, including 37,657 patients were included. Five studies identified a relationship between wound complications, infection and pyrexia and recurrence or recurrence-free survival. Risk of recurrence, 1-year and 5-year recurrence-free survival and overall survival were related to complications, particularly for patients with poor Nottingham Prognostic Index. Five studies failed to demonstrate a relationship between complications and prognosis. Complication was found to significantly affect 5-year recurrence-free survival (HR 1.48 95 % CI 1.02-2.14, p = 0.04) but not recurrence (HR 2.39, 95 %CI 0.94-6.07, p = 0.07), with a high degree of heterogeneity amongst analysed studies (I2 = 95 %). DISCUSSION: Further research is needed to quantify the effects of postoperative complication on prognosis following surgery for breast cancer.

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.

Randomized clinical trial of techniques for closure of the pancreatic remnant following distal pancreatectomy.

BACKGROUND: Pancreatic fistula and intra-abdominal fluid collection are the commonest complications after distal pancreatectomy. Several techniques have been described to achieve perfect closure of the stump. METHODS: In this randomized clinical trial the stapler technique was compared with stapling combined with a seromuscular patch. Seventy patients who underwent distal pancreatectomy were randomized between January 2002 and December 2006 to either closure of the pancreatic stump by stapler (35 patients) or closure by stapler and covering with a seromuscular patch of jejunum (35). The primary endpoint was the rate of postoperative fistula and/or intra-abdominal fluid collections. RESULTS: The overall rate of these pancreas-related complications was higher in the stapling-alone group. However, rates of clinically relevant postoperative complications (grade B or C fistula and/or fluid collection requiring treatment) were comparable. The reintervention rate and median hospital stay were similar in both groups. CONCLUSION: Covering the stapled pancreatic remnants with a seromuscular patch is a simple method that decreased overall pancreas-related complications such as fistula. This technique did not affect clinically relevant outcomes as severe complications requiring treatment were similar with both techniques.

The presentation, management and outcome of inflammatory breast cancer cases in the UK: Data from a multi-centre retrospective review.

OBJECTIVES: Inflammatory Breast cancer (IBC) is a rare but aggressive form of breast cancer. Its incidence and behaviour in the UK is poorly characterised. We collected retrospective data from hospitals in the UK and Ireland to describe the presentation, pathology, treatment and clinical course of IBC in the UK. MATERIALS AND METHODS: Patients with IBC diagnosed between 1997-2014 at fourteen UK and Irish hospitals were identified from local breast unit databases. Patient characteristics, tumour pathology and stage, and details of surgical, systemic and radiotherapy treatment and follow-up data were collected from electronic patient records and medical notes. RESULT: This retrospective review identified 445 patients with IBC accounting for 0.4-1.8% of invasive breast cancer cases. Median follow-up was 4.2 years. 53.2% of tumours were grade 3, 56.2% were oestrogen receptor positive, 31.3% were HER2 positive and 25.1% were triple negative. 20.7% of patients had distant metastases at presentation. Despite trimodality treatment in 86.4%, 40.1% of stage III patients developed distant metastases. Five-year overall survival (OS) was 61.0% for stage III and 21.4% for stage IV patients. CONCLUSIONS: This is the largest series of UK IBC patients reported to date. It indicates a lower incidence than in American series, but confirms that IBC has a high risk of recurrence with poor survival despite contemporary multi-modality therapy. A national strategy is required to facilitate translational research into this aggressive disease.

Preventive strategies for septic complications of acute pancreatitis.

The diagram of the mortality of acute pancreatitis is characterized by two distinct peaks, in a similar manner to other generalized acute inflammatory responses. In the first phase, which is characterized by "hyper-inflammatory" mechanisms, death occurs due to overwhelming SIRS and subsequent multi-organ failure. The second peak of death is usually detected much later, at least two weeks after the onset of acute pancreatitis. Infection in necrotising pancreatitis is frequently observed in this so-called "compensatory antiinflammatory" phase. Since there has been no effective therapy evolved to prevent the activation of inflammatory and proteolytic cascades, the treatment of acute pancreatitis is merely symptomatic. Adequate fluid resuscitation and analgesia are the mainstays of treatment. In case of development of multi-organ failure, extensive medical and ventilatory supportive therapy is usually necessary. However, recent studies suggested certain methods might decrease the incidence of infection in pancreatic necrosis, which is usually due to bacterial translocation from the gut. Numerous attempts have been published in the literature to decrease the frequency of septic complications. Furthermore, the outcome of studies favouring antibiotic prophylaxis in acute pancreatitis were debatable. The development of multi-resistant strains of Gram-positive bacteria and Candida, due to long-term antibiotic use, is a strong argument against the indication of prophylactic antibiotic use. Recently, various clinical studies aimed to decrease bacterial translocation, including probiotic use and enteral feeding as part of the treatment. This paper provides a systematic review on data available in the evidence based literature on the use of antibiotics and the role of alternative and supportive therapy in the treatment of severe acute pancreatitis.

Oncoplastic breast conservation surgery is oncologically safe when compared to wide local excision and mastectomy.

BACKGROUND: Support for the oncological safety of oncoplastic breast conservation surgery (OBCS) is mostly based on evidence comparing recurrence rates after OBCS to wide local excision (WLE). However, OBCS is often indicated for larger cancers and oncological results should also be compared to patients treated with mastectomy. In this study we compared recurrence and survival following OBCS, mastectomy and WLE. METHODS: Patients treated with OBCS between 2009 and 2012 were identified from a prospectively maintained database. For comparison, consecutive patients treated with WLE or mastectomy with or without immediate reconstruction (Ms ± IR) over the same time period were identified. Histological variables of patients were compared using Fisher Exact or Chi squared tests, and recurrence and survival were compared using Kaplan-Meier and Cox regression survival analysis. RESULTS: 980 patients' data were analysed (OBCS: n = 104; WLE: n = 558; Ms ± IR: n = 318). Tumour size, grade, nodal status, ER, and PR expression of patients treated with OBCS were all significantly more adverse compared with patients treated with WLE (p < 0.001). These histological variables were similar in patients treated with Ms ± IR and OBCS. 5-year local recurrence rates were similar in all three groups (WLE: 3.4 per cent, OBCS: 2 per cent, Ms ± IR: 2.6 per cent; log rank = 0.973), while distant recurrence rates were higher after Ms ± IR and OBCS (Ms ± IR:13.1 per cent, OBCS:7.5 per cent, WLE:3.3 per cent; log rank: p < 0.001). CONCLUSION: OBCS is oncologically safe in patients even when histological results are similar to patients treated with Ms ± IR.

Lipoprotein (a) and plasminogen are immunochemically related.

Earlier studies demonstrated that lipoprotein (a), a lipoprotein of high atherogenicity, possesses proteolytic activity. In this report, we provide evidence that the lipoprotein (a)-specific antigen, apoprotein (a) is immunochemically related to plasminogen. This was demonstrated by polyclonal antisera from rabbit, sheep and horse, and with three monoclonal antibodies from mouse. Using immunospecific adsorbers against lipoprotein (a), all plasminogen could be adsorbed from lipoprotein (a)-positive and apparently lipoprotein (a)-negative plasma. As an additional similarity to plasminogen, lipoprotein (a) binds selectively to lysine-Sepharose, but with a somewhat lower affinity. In an assay system for measuring the fibrinolytic activity challenged with streptokinase, lipoprotein (a) prolonged strikingly the fibrinolysis time under certain experimental conditions.

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis.

BACKGROUND: Studies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (CPN), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. METHODS AND RESULTS: A total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, CPN, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and CPN but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and CPN did not correlate quantitatively; however, the relative risk of disease development was substantially increased in subjects with high antibody levels to both hHSP60 and CPN:, reaching an odds ratio of 82.0 (95% CI 10.6 to 625.0). CONCLUSIONS: High levels of antibodies to hHSP60 and CPN: are independent risk factors for coronary atherosclerosis, but their simultaneous presence substantially increases the risk for disease development.

Massive retroperitoneal ganglioneuroma presenting with small bowel obstruction 18 years following initial diagnosis.

BACKGROUND: Ganglioneuroma is a rare tumour of neural crest origin, which arises from maturation of a neuroblastoma. While previously considered to be non-functioning, they are now known to be frequently endocrinologically active. AIMS AND METHODS: We report a case of a massive retroperitoneal ganglioneuroma presenting with small bowel obstruction in an adult, 18 years after initial diagnosis. Urinary dopamine levels were elevated, but other catecholamines were within normal limits. This is the first report in the English-language literature of a retroperitoneal ganglioneuroma presenting with or causing intestinal obstruction. We also review the metabolic, radiological, and histological features of these tumours. Relevant publications were identified from a Medline search using the MeSH headings 'ganglioneuroma', 'retroperitoneal neoplasms' and 'intestinal obstruction', and also from the reference lists of retrieved articles. CONCLUSIONS: Ganglioneuroma can grow to a massive size and present in a varied manner. It should be included in the differential diagnosis of any large retroperitoneal or mediastinal mass, including those causing bowel obstruction.

How to compare the oncological safety of oncoplastic breast conservation surgery - To wide local excision or mastectomy?

BACKGROUND: Comparative studies suggest that patients treated with oncoplastic breast conservation surgery (OBCS) have similar pathology to patients treated with wide local excision (WLE). However, patients treated with OBCS have never been compared to patients treated with mastectomy. The aim of this study was to identify which control group was comparable to patients undergoing OBCS. METHODS: Commonly reported histopathological variables of patients treated with OBCS, WLE or mastectomy ± immediate reconstruction (Ms ± IR) were compared using Fisher Exact or Chi squared tests. RESULTS: 1000 patients' data were analysed (OBCS: n = 119; WLE: n = 600; Ms ± IR: n = 281). Tumour size was significantly bigger after OBCS than WLE (p < 0.001), but similar to Ms ± IR (p = 0.138). Tumour grade was higher after OBCS than WLE (p < 0.001), but similar to Ms ± IR (p = 0.497). More axillary nodes were involved in patients with OBCS than WLE (p < 0.001), but comparable to Ms ± IR (p = 0.175). ER and PR expressions were lower after OBCS compared to WLE (p = 0.007, p = 0.009), but identical to Ms ± IR (p = 1, p = 0.904 respectively). Differences in application of systemic (neo)adjuvant therapy followed the above trend. CONCLUSION: Striking similarities found between OBCS and mastectomy patients' histopathological results are in sharp contrast with previously published data. This study suggests that oncological outcomes following OBCS should be compared to mastectomy besides WLE.

Frequencies of certain complement protein alleles and serum levels of anti-heat-shock protein antibodies in cerebrovascular diseases.

BACKGROUND AND PURPOSE: A strong correlation exists between the intensity of atherosclerotic alterations in different arteries. Marked differences exist, however, in the age and sex distribution and risk factors for coronary heart disease (CHD) and cerebrovascular disease (CVD). We therefore performed genetic and immunologic studies in patients with CVD. METHODS: We studied 292 patients with CVD (stroke or transient ischemic attack) and as control either 198 healthy blood donors and 485 healthy elderly (aged >60 years) people (genetic study) or 94 blood donors aged 45 to 60 years and 49 healthy elderly (aged >60 years) people (anti-heat-shock protein [hsp] measurements). Allele frequencies of 3 genes (C4A, C4B, and C3) encoding proteins of the complement system were determined by electrophoresis and immunofixation. Serum concentration of autoantibodies against 60-kDa heat-shock protein (anti-hsp60) was measured by the enzyme-linked immunosorbent assay method. RESULTS: Marked differences were observed between CVD patients and controls in the genetic studies. In the CVD patients aged >60 years, the frequency (11.3%) of the deficient allele of the C4B gene (C4B*Q0) was significantly (P:=0.0003) higher than that of the healthy controls (5.4%). By contrast, in the group aged 45 to 60 years, the frequency of the C4B*Q0 allele was lower in patients than in controls. Serum concentration of anti-hsp60 in the CVD patients did not differ from control values. CONCLUSIONS: In previous studies C4B*Q0 frequency was reported to be higher in CHD patients aged 45 to 60 years than in aged-matched controls. Moreover, high anti-hsp60 levels were found in CHD patients. These findings contrast with our present report of lower frequency of C4B*Q0 in CVD patients. Therefore, genetic and immunologic factors may at least partly explain the differences between the natural history and risk factors of CHD and CVD.

Frequency of the R3500Q mutation of the apolipoprotein B-100 gene in a sample screened clinically for familial hypercholesterolemia in Hungary.

Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) cause early onset of coronary heart diseases (CHD). According to the recommendations of the international MEDPED program, we tried to find FH cases. We analyzed 73 FH probands and their 304 first-degree relatives. A total of 39 probands were found from the 21000 subjects screened (1:538) from family doctors' registers recording all citizens, while the remaining 34 were derived from screened patients from lipid clinics. In our FH probands, four cases of FDB (R3500Q mutation) were diagnosed with allele-specific PCR, and the mutation was also detectable in five cases out of seven living family members. In the remaining 69 FH families, 156 people were diagnosed clinically with FH, and 31.8% of the males (against 13% of the not clinically diagnosed FH males, P<0.01), and 32.4% of the females (against 13.5% of the not clinically diagnosed FH females, P<0.01) suffered from early onset CHD. The plasma total cholesterol level of the FDB patients, especially in the younger patients, was very close to normal values. Therefore, the FDB patients seem to be under-represented in this type of survey. Because FDB is one of the independent causes of early onset CHD, the R3500Q mutation should be considered in families with a high frequency of cardiovascular diseases.