Aesthetic breast surgery: putting in context-a narrative review.

OBJECTIVE: This review article summarises the latest evidence for commonly undertaken procedures in aesthetic breast surgery with a focus on key principles of breast augmentation, reduction, and mastopexy. The paper also outlines various approaches and controversies as well as complications such as breast implant associated anaplastic large cell lymphoma (BIA-ALCL) and breast implant illness (BII) which are increasingly being recognised and becoming a challenge to manage. BACKGROUND: Changing trends of aesthetic breast surgery over the decades has warranted a continuous evolution of this field. The ability to deliver safe and appropriate care is dependent upon sound reconstructive principles and proper training. The lack of uniformity in either is a cause of concern. The impact of social media and changing perception of body image can also no longer be overlooked in the field of aesthetics and reconstruction. METHODS: Review of literature including recent journals, textbook chapters, online databases like PubMed, and current government and surgical society guidelines. CONCLUSIONS: Breast reconstruction is based on sound surgical principles and it is imperative to follow these for the practice of this speciality. There are two important issues that revolve around this aspect of surgery. First relates to the urgent need to invest time and effort in improving regulations and outcomes in the cosmetic surgery industry. Second, it is crucial to promote and prioritize the development and training in this field as the principles of aesthetic breast surgery underpins oncoplastic breast surgery for management of cancer.

Oncoplastic breast-conserving surgery for women with primary breast cancer.

BACKGROUND: Oncoplastic breast-conserving surgery (O-BCS) involves removing the tumour in the breast and using plastic surgery techniques to reconstruct the breast. The adequacy of published evidence on the safety and efficacy of O-BCS for the treatment of breast cancer compared to other surgical options for breast cancer is still debatable. It is estimated that the local recurrence rate is similar to standard breast-conserving surgery (S-BCS) and also mastectomy, but the aesthetic and patient-reported outcomes may be improved with oncoplastic techniques. OBJECTIVES: Our primary objective was to assess oncological control outcomes following O-BCS compared with other surgical options for women with breast cancer. Our secondary objective was to assess surgical complications, recall rates, need for further surgery to achieve adequate oncological resection, patient satisfaction through patient-reported outcomes, and cosmetic outcomes through objective measures or clinician-reported outcomes. SEARCH METHODS: We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via OVID), Embase (via OVID), the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov on 7 August 2020. We did not apply any language restrictions. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and non-randomised comparative studies (cohort and case-control studies). Studies evaluated any O-BCS technique, including volume displacement techniques and partial breast volume replacement techniques compared to any other surgical treatment (partial resection or mastectomy) for the treatment of breast cancer. DATA COLLECTION AND ANALYSIS: Four review authors performed data extraction and resolved disagreements. We used ROBINS-I to assess the risk of bias by outcome. We performed descriptive data analysis and meta-analysis and evaluated the quality of the evidence using GRADE criteria. The outcomes included local recurrence, breast cancer-specific disease-free survival, re-excision rates, complications, recall rates, and patient-reported outcome measures. MAIN RESULTS: We included 78 non-randomised cohort studies evaluating 178,813 women. Overall, we assessed the risk of bias per outcome as being at serious risk of bias due to confounding; where studies adjusted for confounding, we deemed these at moderate risk. Comparison 1: oncoplastic breast-conserving surgery (O-BCS) versus standard-BCS (S-BCS) The evidence in the review found that O-BCS when compared to S-BCS, may make little or no difference to local recurrence; either when measured as local recurrence-free survival (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.61 to 1.34; 4 studies, 7600 participants; very low-certainty evidence) or local recurrence rate (HR 1.33, 95% CI 0.96 to 1.83; 4 studies, 2433 participants; low-certainty evidence), but the evidence is very uncertain due to most studies not controlling for confounding clinicopathological factors. O-BCS compared to S-BCS may make little to no difference to disease-free survival (HR 1.06, 95% CI 0.89 to 1.26; 7 studies, 5532 participants; low-certainty evidence). O-BCS may reduce the rate of re-excisions needed for oncological resection (risk ratio (RR) 0.76, 95% CI 0.69 to 0.85; 38 studies, 13,341 participants; very low-certainty evidence), but the evidence is very uncertain. O-BCS may increase the number of women who have at least one complication (RR 1.19, 95% CI 1.10 to 1.27; 20 studies, 118,005 participants; very low-certainty evidence) and increase the recall to biopsy rate (RR 2.39, 95% CI 1.67 to 3.42; 6 studies, 715 participants; low-certainty evidence). Meta-analysis was not possible when assessing patient-reported outcomes or cosmetic evaluation; in general, O-BCS reported a similar or more favourable result, however, the evidence is very uncertain due to risk of bias in the measurement methods. Comparison 2: oncoplastic breast-conserving surgery (O-BCS) versus mastectomy alone O-BCS may increase local recurrence-free survival compared to mastectomy but the evidence is very uncertain (HR 0.55, 95% CI 0.34 to 0.91; 2 studies, 4713 participants; very low-certainty evidence). The evidence is very uncertain about the effect of O-BCS on disease-free survival as there were only data from one study. O-BCS may reduce complications compared to mastectomy, but the evidence is very uncertain due to high risk of bias mainly resulting from confounding (RR 0.75, 95% CI 0.67 to 0.83; 4 studies, 4839 participants; very low-certainty evidence). Data on patient-reported outcome measures came from single studies; it was not possible to meta-analyse the data. Comparison 3: oncoplastic breast-conserving surgery (O-BCS) versus mastectomy with reconstruction O-BCS may make little or no difference to local recurrence-free survival (HR 1.37, 95% CI 0.72 to 2.62; 1 study, 3785 participants; very low-certainty evidence) or disease-free survival (HR 0.45, 95% CI 0.09 to 2.22; 1 study, 317 participants; very low-certainty evidence) when compared to mastectomy with reconstruction, but the evidence is very uncertain. O-BCS may reduce the complication rate compared to mastectomy with reconstruction (RR 0.49, 95% CI 0.45 to 0.54; 5 studies, 4973 participants; very low-certainty evidence) but the evidence is very uncertain due to high risk of bias from confounding and inconsistency of results. The evidence is very uncertain for patient-reported outcome measures and cosmetic evaluation. AUTHORS' CONCLUSIONS: The evidence is very uncertain regarding oncological outcomes following O-BCS compared to S-BCS, though O-BCS has not been shown to be inferior. O-BCS may result in less need for a second re-excision surgery but may result in more complications and a greater recall rate than S-BCS. It seems that O-BCS may give better patient satisfaction and surgeon rating for the look of the breast, but the evidence for this is of poor quality, and due to lack of numerical data, it was not possible to pool the results of different studies. It seems O-BCS results in fewer complications compared with surgeries involving mastectomy. Based on this review, no certain conclusions can be made to help inform policymakers. The surgical decision for what operation to proceed with should be made jointly between clinician and patient after an appropriate discussion about the risks and benefits of O-BCS personalised to the patient, taking into account clinicopathological factors. This review highlighted the deficiency of well-conducted studies to evaluate efficacy, safety and patient-reported outcomes following O-BCS.

Effect of Immediate Implant-Based Breast Reconstruction After Mastectomy With and Without Acellular Dermal Matrix Among Women With Breast Cancer: A Randomized Clinical Trial.

Importance: The use of acellular dermal matrix (ADM) in implant-based breast reconstructions (IBBRs) is established practice. Existing evidence validating ADMs proposed advantages, including improved cosmetics and more single-stage IBBRs, is lacking. Objective: To evaluate whether IBBR with ADM results in fewer reoperations and increased health-related quality of life (HRQoL) compared with conventional IBBR without ADM. Design, Setting, and Participants: This was an open-label, multicenter, randomized clinical trial of women with primary breast cancer who planned for mastectomy and immediate IBBR, with a 2-year follow-up for all participants. Participants were enrolled at 5 breast cancer units in Sweden and the United Kingdom between 2014 and May 2017. Exclusion criteria included previous radiotherapy and neo-adjuvant chemotherapy. Data were analyzed until August 2017. Interventions: Participants were allocated to immediate IBBR with or without ADM. Main Outcomes and Measures: The primary trial end point was number of reoperations at 2 years. HRQoL, a secondary end point, was measured as patient-reported outcome measures using 3 instruments from the European Organization for Research and Treatment of Cancer Quality of life Questionnaire. Results: From start of enrollment on April 24, 2014, to close of trial on May 10, 2017, a total of 135 women were enrolled (mean [SD] age, 50.4 [9.5] years); 64 were assigned to have an IBBR procedure with ADM and 65 to the control group who had IBBR without ADM. There was no statistically significant difference between groups for the primary outcome. Of 129 patients analyzed at 2-year follow-up, 44 of 64 (69%) had at least 1 surgical event in the ADM group vs 43 of 65 (66%) in the control group. In the ADM group, 31 patients (48%) had at least 1 reoperation on the ipsilateral side vs 35 (54%) in the control group. The overall number of reoperations on the ipsilateral side were 42 and 43 respectively. Within the follow-up time of 24 months, 9 patients (14%) in the ADM group had the implant removed compared with 7 (11%) in the control group. We found no significant mean differences in postoperative patient-reported HRQoL domains, including perception of body image (mean difference, 3; 99% CI, -11 to 17; P = .57) and satisfaction with cosmetic outcome (mean difference, 8; 99% CI, -6 to 20; P = .11). Conclusions and Relevance: Immediate IBBR with ADM did not yield fewer reoperations compared with conventional IBBR without ADM, nor was IBBR with ADM superior in terms of HRQoL or patient-reported cosmetic outcomes. Patients treated for breast cancer contemplating ADM-supported IBBR should be informed about the lack of evidence validating ADM's suggested benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT02061527.

A quality evaluation of the clinical practice guidelines on breast cancer using the RIGHT checklist.

BACKGROUND: Breast cancer is the most frequent type of cancer in women. The methodological quality of clinical practice guidelines (CPGs) on breast cancer has been shown to be heterogeneous. The aim of our study was to evaluate the quality of breast cancer CPGs published in years 2018-2020, using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. METHODS: We searched Medline (via PubMed), Chinese National Knowledge Infrastructure (CNKI), Wanfang and Chinese Biomedical Literature (CBM) as well as websites of guideline organizations for CPGs on breast cancer published between 2018 and 2020. We used the RIGHT checklist to evaluate the reporting quality of the included guidelines by assessing whether the CPGs adhered to each item of the checklist and calculated the proportions of appropriately reported RIGHT checklist items. We also presented the adherence reporting rates for each guideline and the mean rates for each of the seven domains of the RIGHT checklist. RESULTS: A total of 45 guidelines were included. Eighteen (40.0%) guidelines had an overall reporting rate below 50% and only three (6.7%) reported more than 80% of the items. The domains "Basic information" and "Background" had the highest reporting rates (75.9% and 62.5%, respectively). The mean reporting rates of the domains "Evidence", "Recommendation", "Review and quality assurance", "Funding and declaration and management of interests" and "Other information" were 42.7%, 53.0%, 33.3%, 45.0%, and 44.4%, respectively. CONCLUSIONS: The reporting quality varied among guidelines for breast cancer, showing the need for improvement in reporting the contents. Guideline developers should pay more attention to reporting the evidence, review and quality assurance, and funding and declaration and management of interests in future.

Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin.

BACKGROUND: Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy. METHODS: Thirty-six patients with untreated primary breast cancer were recruited to a window study and transcriptomic profiling of tumour samples carried out before and after metformin treatment. RESULTS: Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic level and there was a differential change in expression between two previously identified cohorts of patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation gene composite signature correlated with change in a proliferation gene signature. In vitro assays showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK activation. CONCLUSIONS: We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells with implications for patient selection and drug combinations. CLINICAL TRIAL REGISTRATION: NCT01266486.

Increasing the incidence of drain-free day-case mastectomies with the use of a fibrin tissue sealant; data from a single surgical center in the United Kingdom.

Day-case mastectomy surgery provides benefits to both patients and hospitals. Key barriers are the use of a drain and the risk of postoperative seroma formation. We introduced the use of a tissue sealant (Artiss) into the surgical site (post-mastectomy without immediate reconstruction and postaxillary clearance) and evaluated its effect on our practice, particularly day-case rates. A prospective audit of 177 patients who underwent a simple mastectomy with or without axillary surgery, or axillary node clearance with or without breast-conserving surgery was conducted at a single surgical center in the UK between November 2015 and November 2016. Artiss was used in all operations and, where appropriate, the drain was omitted to facilitate day-case surgery. The clinical outcomes were compared between patients undergoing different operations and duration of hospital stay. There was no statistically significant difference between day-case patients and inpatients in seroma aspiration rates (24.5% and 21.7%, respectively; P = 0.381) or other complications (22.4% and 16.1%, respectively; P = 0.106). The day-case mastectomy rate increased from 3.9% in the first quarter to 45.5% in the final quarter, which was a significant increase reaching well beyond the national target. The use of Artiss enabled us to increase the drain-free day-case surgery rates over a 1-year period, exceeding the 30% target recommended by the British Association of Day Surgery. We did not observe any increase in patient morbidity, and the change was cost-effective. We have now implemented the routine use of Artiss in women undergoing simple mastectomy with or without axillary surgery and stand-alone axillary node clearances as part of enhanced recovery clinical pathways.

The Results of Surveillance Imaging After Breast Conservation Surgery and Partial Breast Reconstruction With Chest Wall Perforator Flaps; A Qualitative Analysis Compared With Standard Breast-Conserving Surgery for Breast Cancer.

INTRODUCTION: Partial breast reconstruction (PBR) using chest wall perforator flaps (CWPF) allows for excision of tumors in the outer quadrant of the breast in women with small to moderate non-ptotic breasts resulting in a good aesthetic outcome. There are limited data available in the literature regarding long-term follow-up and the effect of CWPF on subsequent surveillance mammographic interpretation and recall rates. A retrospective audit with qualitative analysis of initial mammograms was performed to assess this. PATIENTS AND METHODS: This retrospective analysis of a prospectively maintained database included all consecutive patients who underwent either PBR with CWPF or wide local excision (WLE) between January 2013 and December 2014 by a single surgeon in a tertiary referral center. Qualitative analysis of the postoperative mammograms was performed after review by 2 blinded radiologists. RESULTS: Thirty-six patients were included in the study, 18 in each arm. The CWPF group was younger and had larger tumor size anticipated on preoperative imaging, which correlated with larger specimens excised. Both groups were comparable with respect to tumor pathological characteristics. Comparing the first postoperative mammograms, both groups were similar in features reported such as calcifications, fat necrosis, volume loss, and radiotherapy changes. During the follow-up period (median 4 years), 138 surveillance mammograms were performed. One patient was recalled for further imaging in the CWPF group. There was no significant difference in the need for diagnostic imaging and biopsy between the groups. CONCLUSION: Patients who underwent PBR using CWPF had similar features on postoperative surveillance mammograms compared with that post WLE.

Implant Based Breast Reconstruction With Acellular Dermal Matrix: Safety Data From an Open-label, Multicenter, Randomized, Controlled Trial in the Setting of Breast Cancer Treatment.

OBJECTIVE: To evaluate clinical outcomes of using acellular dermal matrix (ADM) with implant based breast reconstructions (IBBRs) in a randomized controlled trial. SUMMARY BACKGROUND DATA: The use of ADMs in IBBRs is widespread, but link between ADM and complications remain a controversial topic. In view of reports concerning harm, we present 6-months safety data of ADM-assisted IBBR in the setting of breast cancer treatment. METHODS: An open-label, randomized, controlled trial recruiting patients from 4 centers in Sweden and 1 in UK. Eligible were women with breast cancer planned for mastectomy with immediate IBBR. Participants were randomly allocated to IBBR with or without ADM (Strattice, Branchburg, NJ), with stratification by center in blocks of 6. Main primary endpoint was number of unplanned reoperations at 24 months, and safety expressed as the incidence of adverse events with a 6-month follow-up time for all participants. Analysis were done per protocol using Fisher exact test for complications and reoperations. RESULTS: From start of enrolment on April 24, 2014, to close of trial on May 10, 2017, 135 women were enrolled, of whom 64 with ADM and 65 without ADM were included in the final analysis. Four patients (6%) in each group had reconstructive failure with implant loss, but IBBR with ADM exhibited a trend of more overall complications and reoperations (difference 0·16, 95% CI, -0·01 to 0·32, P = 0·070), and with higher risk of wound healing problems (P = 0·013). CONCLUSIONS: With 6-months follow-up for all participants, immediate IBBR with ADM carried a risk of implant loss equal to conventional IBBR without ADM, but was associated with more adverse outcomes requiring surgical intervention. Further investigation of risk factors and patient selection in a long-term follow-up is warranted.

Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer.

Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study integrating measurement of markers of systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics at paired time points to profile the bioactivity of metformin in primary breast cancer. We show metformin reduces the levels of mitochondrial metabolites, activates multiple mitochondrial metabolic pathways, and increases 18-FDG flux in tumors. Two tumor groups are identified with distinct metabolic responses, an OXPHOS transcriptional response (OTR) group for which there is an increase in OXPHOS gene transcription and an FDG response group with increased 18-FDG uptake. Increase in proliferation, as measured by a validated proliferation signature, suggested that patients in the OTR group were resistant to metformin treatment. We conclude that mitochondrial response to metformin in primary breast cancer may define anti-tumor effect.

Objective assessment of clinical, oncological and cosmetic outcomes following volume replacement in patients undergoing oncoplastic breast-conserving surgery: protocol for a systematic review.

INTRODUCTION: Oncoplastic breast surgery allows the excision of larger tumours without compromising cosmetic outcome and can be broadly divided into volume displacement and volume replacement techniques. Although oncoplastic surgery has rapidly gained acceptance and is now widely practised, evidence is still lacking especially in patients who underwent volume replacement techniques. As it is a relatively new technique that has been described in the literature in the recent years, a summary of evidence from this literature can help clinicians to understand the clinical, oncologicalandcosmetic outcomes of such procedures. METHODS AND ANALYSIS: All original studies including randomised controlled trials, cohort studies, case-control studies and case series involving more than 10 women undergoing partial breast reconstruction using a volume replacement technique will be included. The primary objective is to evaluate the clinical, oncological and cosmetic outcomes following volume replacement in patients undergoing oncoplastic breast-conserving surgery. The secondary objective is to review the patient-reported outcomes (PROMs) associated with oncoplastic breast surgery to help identify any unmet needs and to consider refining the existing PROMs to suit women undergoing volume replacement surgery.A comprehensive literature search, eligibility assessment and extraction of data will be conducted by two trained teams acting independently. Data will be extracted and stored in a database with standardised extraction fields to facilitate easy and consistent data entry. Heterogeneity will be assessed using the Cochrane tests. ETHICS AND DISSEMINATION: This systematic review requires no ethical approval. It will be published in a peer-reviewed journal, and it will also be presented at nationalandinternational conferences. PROSPERO REGISTRATION NUMBER: CRD42017075700; Pre-results.

Staged approach to partial breast reconstruction to avoid mastectomy in women with breast cancer.

BACKGROUND: The lateral chest wall perforator flaps (CWPF) offer an excellent option for partial breast reconstruction (PBR) in women undergoing breast conservation surgery (BCS) for laterally placed tumours in small to moderate non-ptotic breasts. METHODS: A total of 20 patients underwent PBR with lateral CWPF over the last 4 years, as two-stage approach. This approach was undertaken for patients with high tumour to breast ratio (>30% predicted resection) in an attempt to avoid mastectomy. The reconstruction was carried out 2-4 weeks after wide local excision in order to ensure clear margins prior to undertaking PBR. RESULTS: Twenty-three women were selected for attempt at BCS with 2-stage approach. Three patients had extensive disease so they were then counseled for mastectomy after the first surgery and 20 patients had successful BCS. Out of 20 patients, 13 were symptomatic and 7 were screen-detected with mean age of 49 years. The median tumour size on pre-op imaging was 43 mm (23-75 mm). A percentage of 50% women with unifocal cancers undergoing primary surgery had disease overestimated on pre-op imaging. The complication rate was low. Good to excellent aesthetic outcomes were reported in 90% cases. Patients reported high satisfaction scores. CONCLUSIONS: We recommend considering two-stage approach in selected women with high tumour-breast ratio to ensure successful BCS prior to PBR. This approach facilitates BCS and avoids mastectomy in borderline cases, particularly lobular cancers, DCIS, bifocal cancers and post neoadjuvant chemotherapy where pre-operative disease estimation could be challenging. Our small series has shown that this approach results in safe oncological surgery with good aesthetic outcomes in the selected group of women.

Modified Lower Pole Autologous Dermal Sling for Implant Reconstruction in Women Undergoing Immediate Breast Reconstruction after Mastectomy.

Background. Autologous dermal sling with wise pattern skin reducing mastectomy allows one-stage implant reconstruction in women with large and ptotic breasts needing mastectomy for cancer or risk reduction. However, this technique is not suitable for women who lack ptosis and also carries risk of T-junction breakdown. Method. We have performed one-stage nipple sparing mastectomies with implant reconstruction in 5 women (8 breasts) by modifying the autologous dermal sling approach. All these women had small to moderate breasts with no ptosis or pseudoptosis. Results. Three women had bilateral procedures, two underwent bilateral mastectomies simultaneously, and one had contralateral risk reduction surgery a year after the cancer side operation. All women underwent direct to implant reconstruction with implant volumes varying from 320 to 375 cc. There were no implant losses and only one required further surgery to excise the nipple for positive nipple shaves. A low complication rate was encountered in this series with good aesthetic outcome. Conclusion. The modified lower pole dermal sling allows direct to implant reconstruction in selected women with small to moderate sized breasts with minimal ptosis. The approach is safe and cost-effective and results in more natural reconstruction with preservation of nipple.

A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer.

BACKGROUND: Sequential biopsy of breast cancer is used to assess biomarker effects and drug efficacy. The preoperative "window of opportunity" setting is advantageous to test biomarker changes in response to therapeutic agents in previously untreated primary cancers. This study tested the consistency over time of paired, sequential biomarker measurements on primary, operable breast cancer in the absence of drug therapy. METHODS: Immunohistochemistry was performed for ER, PR and Ki67 on paired preoperative/operative tumor samples taken from untreated patients within 2 weeks of each other. Microarray analysis on mRNA extracted from formalin fixed paraffin embedded cores was performed using Affymetrix based arrays on paired core biopsies analysed using Ingenuity Pathway Analysis (IPA) and Gene Set Analysis (GSA). RESULTS: In 41 core/resection pairs, the recognised trend to lower ER, PR and Ki67 score on resected material was confirmed. Concordance for ER, PR and Ki67 without changing biomarker status (e.g. ER+ to ER-) was 90, 74 and 80 % respectively. However, in 23 paired core samples (diagnostic core v on table core), Ki67 using a cut off of 13.25 % was concordant in 22/23 (96 %) and differences in ER and PR immunohistochemistry by Allred or Quickscore between the pairs did not impact hormone receptor status. IPA and GSA demonstrated substantial gene expression changes between paired cores at the mRNA level, including reduced expression of ER pathway analysis on the second core, despite the absence of drug intervention. CONCLUSIONS: Sequential core biopsies of primary breast cancer (but not core versus resection) was consistent and is appropriate to assess the effects of drug therapy in vivo on ER, PR and Ki67 using immunohistochemistry. Conversely, studies utilising mRNA expression may require non-treatment controls to distinguish therapeutic from biopsy differences.

High CCND1 amplification identifies a group of poor prognosis women with estrogen receptor positive breast cancer.

CCND1 encodes for the cyclin D1 protein involved in G1/S cell cycle transition. In breast cancer the mechanism of CCND1 amplification, relationship between cyclin D1 protein expression and the key clinical markers estrogen receptor (ER) and HER2 requires elucidation. Tissue microarrays of primary invasive breast cancer from 93 women were evaluated for CCND1 amplification by fluorescent in-situ hybridization and cyclin D1 protein overexpression by immunohistochemistry. CCND1 amplification was identified in 27/93 (30%) cancers and 59/93 (63%) cancers had overexpression of cyclin D1. CCND1 amplification was significantly associated with cyclin D1 protein overexpression (p < 0.001; Fisher's exact test) and both CCND1 amplification and cyclin D1 protein expression with oestrogen receptor (ER) expression (p = 0.003 and p < 0.001; Fishers exact test). Neither CCND1 amplification nor cyclinD1 expression was associated with tumor size, pathological node status or HER2 amplification, but high CCND1 amplification (Copy Number Gain (CNG) > or = 8) was associated with high tumor grade (p = 0.005; chi square 7.915, 2 df) and worse prognosis by Nottingham Prognostic Index (p = 0.001; 2 sample t-test). High CCND1 amplification (CNG > or = 8) may identify a subset of patients with poor prognosis ER-positive breast cancers who should be considered for additional therapy.

Medicolegal costs of bile duct injuries incurred during laparoscopic cholecystectomy.

BACKGROUND: When laparoscopic cholecystectomy (LC) is performed successfully, recovery is faster than after open cholecystectomy. However, LC results in higher incidences of biliary, bowel and vascular injury. METHODS: We performed a retrospective review of LC-related claims reported to the National Health Service Litigation Authority (NHSLA) during 2000-2005. The data were analysed from a medicolegal perspective to assess the effects of type of injury and delay in recognition on litigation costs. RESULTS: A total of 208 claims following laparoscopic procedures in general surgery were reported to NHSLA during 2000-2005, of which 133 (64%) were related to LC. Bile duct injury (BDI) accounted for the majority of claims (72%); bowel injury and 'others' accounted for 9% and 19%, respectively. Only 20% of BDIs were recognized during surgery; the majority were missed and diagnosed later. Claims related to LC resulted in payments totalling 6 m pound sterling, of which 4.3 m pound sterling was paid out for BDIs. The average cost was higher for patients who suffered a delay in diagnosis, as was the chance of a successful claim. CONCLUSIONS: Bile duct injury incurred during LC remains a serious hazard for patients. The resulting complications have led to litigation that has caused a huge financial drain on the health care system. Delayed recognition appears to correlate with more costly litigation.

Alveolar capillary dysplasia presenting as pneumothorax: a case report and review of literature.

Alveolar capillary dysplasia, although rare, is a universally fatal form of persistent pulmonary hypertension of the newborn. We report a case of a newborn male baby who developed respiratory distress and pneumothorax 11 h after an uncomplicated delivery. He deteriorated despite full ventilatory support and extracorporeal membrane oxygenation (ECMO). Open lung biopsy provided a diagnosis of alveolar capillary dysplasia and decision was made to withdraw treatment.

Cyclin D1 and breast cancer.

Cyclin D1 is one of the frequently overexpressed proteins and one of the commonly amplified genes in breast cancer. This article reviews the roles of cyclin D1 in cell-cycle regulation (normal and abnormal), mammary gland development and carcinogenesis and the relationship to oestrogen in breast tissues. It concludes by presenting the clinical, prognostic and therapeutic implications of our current knowledge of cyclin D1 in breast cancer.