Radial scars and complex sclerosing lesions on core needle biopsy of the breast: upgrade rates and long-term outcomes.

PURPOSE: Radial scars and complex sclerosing lesions of the breast are part of a group of "indeterminate" breast lesions, which are excised due to risk of coexistent carcinoma. The aim of this study was to assess rate of upgrade of these lesions to invasive and in situ carcinoma and to quantify the risk of development of subsequent cancer in women diagnosed with these lesions. METHODS: A retrospective review of a prospectively maintained breast screening database was performed. All patients with radial scar identified at either core biopsy or final excision biopsy between January 2006 and July 2012 were identified. Full pathological reports for both core biopsy and final excision biopsy were reviewed. Patient outcomes were followed for a mean of 117.1 months. RESULTS: Of 451 B3 biopsies performed at our screening unit, 95 (22%) were found to have a radial scar or complex sclerosing lesion (CSL) on core needle biopsy. Within this group, 77 had no atypia on CNB, with 7 (9%) upgraded to invasive/in situ carcinoma on final excision. Of nine with definite atypia on CNB, 3 (33%) were upgraded. In those patients without atypia or malignancy on final excision, 7.5% developed cancer during 10-year follow-up. CONCLUSION: Patients with radial scar with atypia have a higher risk of upgrade to malignancy. Further research is needed to identify which patients may safely avoid excision of radial scar. Patients with a diagnosis of radial scar on CNB are at increased subsequent risk of breast cancer and may benefit from additional screening.

Health-related quality of life following breast reconstruction compared to total mastectomy and breast-conserving surgery among breast cancer survivors: a systematic review and meta-analysis.

The present review evaluated health-related quality of life (HR-QoL) outcomes in surgical breast cancer survivors who received breast reconstruction (BR), breast-conservation surgery (BCS) or mastectomy (M), and whether HR-QoL domains across generic and disease/surgery-specific questionnaires are compatible. Six electronic databases were searched for appropriate observational studies. Standardized scores for different HR-QoL domains in the BR, BCS, and M treatment groups were extracted from each study for the purpose of a meta-analysis. Using Stata version 14.0, a random-effects meta-analysis model was adopted for each outcome variable to estimate the effect size, 95% CI-confidence intervals, and statistical significance. Sixteen of the 18 eligible studies with BR (n = 1474) and BCS (n = 2612) or M (n = 1458) groups were included in the meta-analysis. The BR group exhibited a better physical health (k = 12; 0.1, 95% CI 0.04, 0.24) and body image (k = 12; 0.50, 95% CI 0.10, 0.89) than the M group. However, the two groups exhibited comparable social health (k = 13; 0.1, 95% CI -0.07, 0.37), emotional health (k = 13; -0.08, 95% CI - 0.41, 0.25), global health (k = 7; 0.1, 95% CI - 0.01, 0.27), and sexual health (k =11; 0.2, 95% CI - 0.02,0.57). There was no clear evidence of the superiority of BR to BCS for all the six domains. These results suggest that HR-QoL outcomes in BR and BCS groups are better than the M group. Therefore, women opting for BR or BCS are likely to report fairly better HR-QoL outcomes than M. However, due to the significant heterogeneity observed in most BR versus BCS outcomes, developing a unified questionnaire incorporating both breast/surgery-specific and generic HR-QoL domains is warranted.

Breast cancer detection among Irish BRCA1 & BRCA2 mutation carriers: a population-based study.

BACKGROUND: High-risk breast cancer screening for BRCA1/2 mutation carriers with clinical breast exam, mammography and MRI has reported sensitivity of 100 %, but BRCA1/2 mutation carriers still present with interval cancers. AIMS: We investigated the presentation and screening patterns of an Irish cohort of BRCA1/2 mutation carriers with breast cancer. MATERIALS AND METHODS: BRCA1/2 mutation carriers with breast cancer were identified in this retrospective cohort study. Records were reviewed for BRCA1/2 mutation status, demographics, screening regimen, screening modality, stage and histology at diagnosis. RESULTS: Fifty-three cases of breast cancer were diagnosed between 1968 and 2010 among 60 Irish hereditary breast ovarian cancer (HBOC) families. In 50 of 53 women, the diagnosis of breast cancer predated the identification of BRCA1/2 mutations. Breast cancer detection method was identified in 47 % of patients (n = 25): 80 % (n = 20) by clinical breast exam (CBE), 12 % by mammography (n = 3), 8 % by MRI (n = 2). Fourteen women (26 %) developed a second breast cancer. Ten of these patients (71 %) were involved in regular screening; 50 % were detected by screening mammography, 20 % by MRI and 30 % by CBE alone. Six patients (43 %) had a change in morphology from first to second breast cancers. There was no change in hormone receptor status between first and second breast cancers. CONCLUSION: In this cohort of Irish BRCA1/2 mutation carriers, compliance with screening was inconsistent. There was a 30 % incidence of interval cancers occurring in women in high-risk screening. Preventive surgery may be a more effective risk reduction strategy for certain high-risk women.

Meta-analysis to determine the clinical impact of axillary lymph node dissection in the treatment of invasive breast cancer.

There are divergent opinions regarding the optimum surgical management of the axilla in patients with invasive breast cancer. Guidelines mandate axillary lymph node dissection (ALND) in the setting of positive sentinel lymph nodes. However, recent studies have questioned the true benefits of this procedure. Therefore, a meta-analysis of relevant randomized trials was performed in order to clarify the oncological benefit of axillary lymph node dissection. A comprehensive search of published randomized trials that compared patients with primary operable breast cancer with/without ALND was performed using MEDLINE, and available data were cross-referenced. Reviews of each study were conducted, and data were extracted. Primary outcomes were overall survival and recurrent axillary disease. A total of 7347 patients with operable primary breast cancer were identified from 8 randomised controlled trials comparing axillary recurrence in patients with or without ALND. Six of these trials provided data on overall survival on 6895 patients. Overall survival favours patients having ALND (OR = 1.22 (95% CI 1.03-1.44, p = 0.02). Similarly, patients undergoing ALND had increased recurrence-free survival (OR = 2.25 (95% CI 1.28-3.94, p = 0.0047). ALND appears to positively impact on overall and recurrence-free survival from breast cancer. These data highlight the enduring benefits of ALND in an era where adjuvant therapies are being promoted to manage regionally advanced/metastatic disease.

Surgical management of lobular carcinoma from a national screening program: a retrospective analysis.

OBJECTIVE: To compare the surgical outcomes of women diagnosed with invasive ductal and lobular carcinoma of the breast. BACKGROUND: The role of Breast Conserving Surgery (BCS) for invasive cancers of the breast is well established; however its role for invasive lobular carcinoma is less well defined. Concerns exist regarding the need for re-excision of margins and the eventual need for mastectomy in women with Invasive Lobular Carcinoma (ILC) compared with Ductal Carcinoma (IDC). In this study we compare the surgical results of these two groups examining BCS from a national breast cancer screening program. METHODS: Analysis of mammographically detected ILC and IDC tumours obtained from the national breast cancer screening program of the Republic of Ireland (BreastCheck) was performed. BreastCheck offers biannual screening mammograms to women throughout the Republic of Ireland between 50 and 65 years of age. We examined and pooled the data across 4 screening zones from 2005 to 2010. CONCLUSIONS: We observed similar success rates and trends in both the ILC and IDC groups where BCS was attempted. Patients selected for BCS with ILC were statistically more likely to have successful surgery compared with IDC as tumour size increased. There however was no statistical difference in a pooled analysis of successful treatment across all tumour sizes in comparing the two groups. We conclude that BCS is an appropriate and acceptable treatment option for women diagnosed with ILC.

Re-evaluating the role of axillary lymph node dissection in screen-detected breast cancer patients.

INTRODUCTION: The American College of Surgeons Oncology Group (ACOSOG), Z0011 trial, demonstrated that there was no therapeutic benefit from completion lymphadenectomy in early stage breast cancer patients with positive sentinel node (SLN) biopsy. Patients with asymptomatic screen-detected tumors may represent a subgroup where completion axillary dissection with its attendant morbidities is unacceptable. Therefore, the aim of this study was to evaluate the role of ALND in an asymptomatic screen-detected breast cancer cohort. METHODS: Patients were recruited from the national screening program which offers women (aged 50 to 65) biannual digital mammography. Over a 1 year period 519 screen-detected breast cancer patients were recruited of which 110 had a positive SLN. RESULTS: Of 519 patients in a national screening program that were clinically/radiologically identified as axillary node negative, 110 (21.2%) had a positive SLN. All 110 (T1 = 68, T2 = 42) patients proceeded to have an axillary clearance. 68 (59%) had T1 tumors and of these 40 (60%), despite a positive SLN, had no metastatic nodes on final pathological analysis of their axilla. In addition, 21 (50%) patients with T2 tumors had no metastatic nodes except for a positive SNB. Furthermore, only 6 (8.8%) of T1 tumors with a positive SLN had 4 or more metastatic axillary lymph nodes. CONCLUSION: 55.45% of patients with a screen-detected T1/T2 tumor had negative completion lymphadectomy. These findings compel us to re-evaluate the role of axillary dissection in the screen-detected asymptomatic breast cancer population to avoid unnecessary ALND with its attendant morbidities.

Radiotherapy and breast reconstruction: a meta-analysis.

The optimum sequencing of breast reconstruction (BR) in patients receiving postmastectomy radiation therapy (PMRT) is controversial. A comprehensive search of published studies that examined postoperative morbidity following immediate or delayed BR with combined radiotherapy was performed. Medical (MEDLINE & EMBASE) databases were searched and cross-referenced for appropriate studies where morbidity following BR was the primary outcome measured. A total of 1,105 patients were identified from 11 appropriately selected studies. Patients undergoing PMRT and BR are more likely to suffer morbidity compared with patients not receiving PMRT (OR = 4.2; 95% CI, 2.4-7.2 [no PMRT vs. PMRT]). Reconstruction technique was also examined with outcome when PMRT was delivered after BR, and this demonstrated that autologous reconstruction is associated with less morbidity in this setting (OR = 0.21; 95% CI, 0.1-0.4 [autologous vs. implant-based]). Delaying BR until after PMRT had no significant effect on outcome (OR = 0.87; 95% CI, 0.47-1.62 [delayed vs. immediate]). PMRT has a detrimental effect on BR outcome. These results suggest that where immediate reconstruction is undertaken with the necessity of PMRT, an autologous flap results in less morbidity when compared with implant-based reconstruction.

A comparative study of risk factors and prognostic features between symptomatic and screen detected breast cancer.

AIMS: To compare prognostic factors in screen detected breast cancer (SDBC) and symptomatically presenting breast cancer (SBC). METHODS: Data were examined on 100 SDBC and 100 SBC. Multiple clinical patient factors were assessed including histopathological features. Using the Gail model each patient's risk of developing breast cancer was calculated and these data were examined for differences between groups. RESULTS: There was no difference in the mean age of patient presentation or in the risk of breast cancer development between groups (2.2% vs. 2.2%, SDBC vs. SBC, actuarial risk of cancer at 5 years). SDBC patients had a significantly lower grade (1.95 vs. 2.44, SDBC vs. SBC, P<0.05), a smaller size of tumour (15.4mm vs. 29.3mm, SDBC vs. SBC, P<0.05) and a higher rate of oestrogen (94% vs. 81%, P<0.05) and progesterone (75% vs. 52%, P<0.05) receptor positivity. When compared using the Nottingham Prognostic Index, SDBC was associated with a better prognosis (r=-0.444, P<0.001). CONCLUSIONS: Though both groups have similar demographics and risk, SDBC patients appear to have more favourable prognostic features. This has implications for the application of systemic therapy in breast cancer and supports the observation that SDBC is a more indolent form of disease.

The clinical and pathological differences in prevalent round screen-detected and symptomatic invasive breast cancer.

The potential benefits of breast cancer screening include the detection of cancers at a more favourable stage, however, cancers detected during the prevalent round of screening may differ from true screen-detected cancers. These differences are poorly defined. This study prospectively assessed all women between 50 and 64 years of age undergoing curative surgery for breast cancer, both screen-detected and symptomatic, in one screening centre during the prevalent round of the national breast cancer-screening programme. Four hundred and thirty seven patients (364 screen-detected and 73 symptomatic patients) underwent surgery for breast cancer. Symptomatic breast cancers were of a higher grade (p < 0.0001; Chi2) and less likely to be oestrogen receptor positive (49% versus 88%; p < 0.0001; Fisher's exact test); however there was no difference in size of tumour or axillary nodal positivity. This study suggests that tumours detected by screening during the prevalent round of a screening programme are of a more prognostically favourable type than symptomatic breast cancers in the same age group.

PET CT imaging in patients undergoing sentinel node biopsy for melanoma.

AIMS: Sentinel lymph node biopsy (SLNB) has been adopted in the surgical treatment of melanoma to reduce morbidity and enhance staging. Positron emission tomography with computerised tomography (PET/CT) has been utilised in the staging of patients with malignancy though the role of this imaging modality in early stage melanoma is unclear. This study examined the preoperative value of PET/CT in patients undergoing SLNB for malignant melanoma. METHODS: Patients presenting with primary melanoma without evidence of either locoregional or systemic metastasis were considered candidates for SLNB. Selected patients underwent preoperative PET/CT followed by definitive surgical therapy including SLNB with regional lymphadenectomy, where indicated. RESULTS: During a 12-month period 83 patients were identified as having undergone SLNB for melanoma, of which 37 (45%) had preoperative PET/CT. Mean melanoma thickness 1.9 mm and 2.4 mm (PET/CT vs. no PET/CT, p>0.05). 13 (15.6%) patients were found to have lymphatic metastasis at SLNB; nine of these patients underwent PET/CT, only two of these scans were suggestive of lymphatic metastasis (positive predictive value 24%, negative predictive value 76%). PET/CT revealed no unheralded metastatic disease but did identify a second occult malignancy in 4 (10.8%) patients undergoing therapy for melanoma. CONCLUSIONS: The results of this study do not support the use of PET/CT in patients undergoing SLNB for melanoma. SLNB appears to be a more sensitive staging modality in the detection of lymphatic metastasis; however PET/CT may have a future role as a screening tool for malignancy.

A characterization of anaerobic colonization and associated mucosal adaptations in the undiseased ileal pouch.

INTRODUCTION: The resolution of pouchitis with metronidazole points to an anaerobic aetiology. Pouchitis is mainly seen in patients with ulcerative colitis pouches (UCP). We have recently found that sulphate reducing bacteria (SRB), a species of strict anaerobe, colonize UCP exclusively. Herein, we aimed to correlate levels of different bacterial species (including SRB) with mucosal inflammation and morphology. METHODS: Following ethical approval, fresh faecal samples and mucosal biopsies were taken from 9 patients with UCP and 5 patients with familial adenomatous polyposis pouches (FAPP). For the purposes of comparison, faecal samples and mucosal biopsies were also taken from the stomas of 7 of the 9 patients with UC (UCS). Colonization by four types of strict anaerobes (SRB, Clostridium perfringens, Bifidobacteria and Bacteroides) as well as by three types of facultative anaerobes (Enterococci, Coliforms and Lactobacilli) was evaluated. Inflammatory scores and mucosal morphology were assessed histologically in a blinded fashion by a pathologist. RESULTS: In general, strict anaerobes predominated over facultative in the UCP (P = 0.041). SRB were present in UCP exclusively. Even after exclusion of SRB from total bacterial counts, strict anaerobes still predominated. In the UCS, facultative anaerobes predominated. Strict and facultative anaerobes were present at similar levels in the FAPP. Enterococci were present at significantly reduced levels in the UCP when compared with the UCS (P = 0.031). When levels of SRB and other anaerobic species were individually correlated with mucosal inflammation and morphology, no trends were observed. CONCLUSION: We have previously identified that SRB exclusively colonize UCP. In addition we have now identified a novel increase in the strict/facultative anaerobic ratio within the UCP compared to UCS. These stark differences in bacterial colonization, however, appear to have limited impact on mucosal inflammation or morphology.

The role of sentinel lymph node biopsy in ductal carcinoma in situ.

AIM: To review the role of sentinel lymph node (SLN) biopsy in the surgical management of patients with ductal carcinoma in situ (DCIS). METHODS: A search was conducted of Medline and the National Library of Medicine to identify key articles concerning DCIS, SLN biopsy (SLNB) and axillary dissection. Further relevant articles were obtained from the references cited in the literature. RESULTS: Up to 20% of patients with a core biopsy diagnosis of DCIS will be later up-staged based on an invasive component identified on the excision specimen. Quality assurance in breast screening programmes requires minimally invasive pre-operative diagnosis and also axillary sampling in the case of documented invasive disease. As an effective and validated procedure, SLNB represents a paradigm shift in the surgical management of the axilla for patients with invasive breast cancer. It remains undefined which, if any, subgroups of patients with DCIS should undergo SLNB. CONCLUSION: Axillary lymphadenectomy is an overtreatment for patients with DCIS. Performing a SLNB during the initial procedure may avoid a second operation in some DCIS patients who are diagnosed with occult invasive disease at their definitive operation. When predictors of hidden invasive disease are clarified by further study, SLNB may be used in the management of selected high-risk DCIS patients.

Major upper gastrointestinal surgery is associated with an antigen-dependent proinflammatory T cell response.

BACKGROUND: T cells play a central role in the immune response to injury. Oesophageal and pancreatic resections are associated with significant risk of systemic inflammatory response syndrome and sepsis. This study involved a detailed analysis of T cell function in a consecutive cohort of patients undergoing such surgery. METHODS: Twenty-five patients undergoing major oncological upper gastrointestinal surgery were investigated for T cell expression of Fas and the activation markers CD69 and CD25, as well as interleukin (IL) 2, IL-10 and interferon (IFN) gamma responses to stimulation with staphylococcal enterotoxin B (SEB). T cell activation in healthy volunteer peripheral blood mononuclear cells was studied in co-culture with patients' serum, either alone or with cytotoxic T lymphocyte-associated antigen (CTLA) 4, an inhibitor of antigen presentation. RESULTS: T cells expressed significantly raised levels of CD69 and CD25 after surgery, but no change in Fas expression was evident. There was a significant increase in the production of IL-2 after surgery without a concomitant increase in IFN-gamma or IL-10 in response to SEB. Postoperative serum activated healthy volunteer T cells, a response that was inhibited (P = 0.053) by co-incubation with CTLA-4. CONCLUSION: Major surgery results in pan-T cell activation via a serum-mediated antigenic mechanism that is independent of Fas expression. Postoperative T cells are primed for an augmented proinflammatory response to superantigen, sustained for at least 1 week, implicating the adaptive immune system in the development of the postoperative systemic immunoinflammatory state.

Minimally invasive parathyroidectomy with operative ultrasound localization of the adenoma.

BACKGROUND: Minimally invasive parathyroidectomy is the procedure of choice for primary hyperparathyroidism due to parathyroid adenoma. Adequate perioperative adenoma localization is essential for this operation. We describe a technique using ultrasound to perform minimally invasive parathyroidectomy. METHODS: 99mTc sestamibi scanning was performed on patients with primary hyperparathyroidism to localize parathyroid adenomas; no intraoperative gamma probe was used. We also performed pre- and intraoperative ultrasound scanning to localize these adenomas. RESULTS: All patients underwent successful localization and removal of their parathyroid adenomas. At follow-up, all patients were well, with calcium within normal limits. CONCLUSION: The use of intraoperative ultrasound facilitates minimally invasive parathyroidectomy and may obviate the need for intraoperative 99mTc sestamibi scanning.