Microvascular breast reconstruction and thromboembolic events in patients on hormone therapy: Audit of practice from a tertiary referral centre.

INTRODUCTION: Hormonal therapy with tamoxifen and aromatase inhibitors reduces breast cancer recurrence and mortality but represents a risk factor for thromboembolic events. Therefore, most surgeons discontinue hormonal agents before microvascular surgery and for a variable period thereafter. There are no guidelines regarding when therapy should be stopped (preoperatively) or when it should be resumed (post-operatively). We, therefore, audited our hospital practice with the objective of making recommendations for microvascular breast reconstruction patients. PATIENTS AND METHODS: A review was performed of all free flap breast reconstructions between 2014 and 2019. Patients were classified according to hormone medication status at operation. Timings of drug cessation and recommencement were recorded. Thrombotic events, namely flap microvascular thrombosis, deep vein thrombosis, superficial vein thrombosis and pulmonary embolism, were compared. RESULTS: A total of 240 patients had 275 free flaps over five years with 36 receiving hormone therapy within one month prior to surgery, which was discontinued 8.5 days (range: 0-28 days) before surgery. Intraoperative microvascular thromboses (HT 2.0%, NHT 0%, and p = 0.869) and post-operative microvascular complications/flap re-explorations (HT 6.6%, NHT 0%, and p = 0.234) were comparable between the two groups. Systemic venous thromboembolic events were also similar (HT 8.3%, NHT 6.1%, and p = 0.893). Age, BMI, smoking status and preoperative chemotherapy did not influence the incidence of thrombotic complications. CONCLUSION: Hormone therapy did not significantly increase the risk of thromboembolic events. Despite the widespread practice of withholding it for 2 weeks prior to reconstructive surgery, this study does not support such practice being beneficial in terms of thromboembolic events and flap viability. Large-scale trials are needed to establish definitive protocols.

International multidisciplinary expert panel consensus on breast reconstruction and radiotherapy.

BACKGROUND: Conflicting evidence challenges clinical decision-making when breast reconstruction is considered in the context of radiotherapy. Current literature was evaluated and key statements on topical issues were generated and discussed by an expert panel at the International Oncoplastic Breast Surgery Meeting in Milan 2017. METHODS: Studies on radiotherapy and breast reconstruction (1985 to September 2017) were screened using MEDLINE, Embase and CENTRAL. The literature review yielded 30 controversial key questions. A set of key statements was derived and the highest levels of clinical evidence (LoE) for each of these were summarized. Nineteen panellists convened for dedicated discussions at the International Oncoplastic Breast Surgery Meeting to express agreement, disagreement or abstention for the generated key statements. RESULTS: The literature review identified 1522 peer-reviewed publications. A list of 22 key statements was produced, with the highest LoE recorded for each statement. These ranged from II to IV, with most statements (11 of 22, 50 per cent) supported by LoE III. There was full consensus for nine (41 per cent) of the 22 key statements, and more than 75 per cent agreement was reached for half (11 of 22). CONCLUSION: Poor evidence exists on which to base patient-informed consent. Low-quality studies are conflicting with wide-ranging treatment options, precluding expert consensus regarding optimal type and timing of breast reconstruction in the context of radiotherapy. There is a need for high-quality evidence from prospective registries and randomized trials in this field.

ANTECEDENTES: El hecho de que la evidencia disponible sea conflictiva supone un reto para la toma de decisiones a la hora de considerar la reconstrucción mamaria en el contexto de radioterapia (radiotherapy, RT). En el seno de un panel de expertos reunidos durante el International Oncoplastic Breast Surgery Meeting celebrado en Milán en 2017, se revisó la literatura disponible y se generaron y discutieron los aspectos más relevantes. MÉTODOS: Se hizo una búsqueda bibliográfica de los estudios de RT y reconstrucción mamaria (1985-septiembre de 2017) en las bases MEDLINE, EMBASE y CENTRAL. La revisión de la literatura permitió identificar 30 cuestiones clave controvertidas. A partir de ellas, se construyeron una serie de afirmaciones, para las que se obtuvo el mayor nivel de evidencia (levels of clinical evidence, LoE) posible. El acuerdo, desacuerdo o abstención respecto a las cuestiones propuestas fueron el resultado de las discusiones de 19 expertos reunidos durante el International Oncoplastic Breast Surgery Meeting. RESULTADOS: Se identificaron 1.522 artículos publicados en revistas con peer review. Se elaboró una lista de 22 afirmaciones clave y se anotó el LoE más alto obtenido para cada una de ellas. El grado de variabilidad fue de II a IV, pero la mayoría de las afirmaciones (54,5%) obtuvieron un LoE III. Hubo un consenso total en el 41% (9/22) de las afirmaciones, mientras que se obtuvo más de un 75% de acuerdo en la mitad de las afirmaciones (11/22). CONCLUSIÓN: La evidencia en la que basar el consentimiento informado en estos pacientes es escasa. Se trata de estudios de baja calidad con gran variedad de opciones terapéuticas, que dificultan el consenso de los expertos acerca del tipo y momento óptimo para la reconstrucción mamaria en el contexto de RT. Para obtener datos de mayor calidad se precisan estudios prospectivos y ensayos clínicos en este campo.

Randomized clinical trial on the effect of fibrin sealant on latissimus dorsi donor-site seroma formation after breast reconstruction.

BACKGROUND: Latissimus dorsi (LD) flap procedures comprise 50 per cent of breast reconstructions in the UK. They are frequently complicated by seroma formation. Fibrin sealants may reduce seroma volumes at the donor site. The aim was to investigate the effect of fibrin sealant (Tisseel(®)) on total seroma volumes from the breast, axilla and back (donor site) after LD breast reconstruction. Secondary outcomes were specific back seroma volumes together with incidence and severity of wound complications. METHODS: Consecutive women undergoing implant-assisted or extended autologous LD flap reconstruction were randomized to either standard care or application of fibrin sealant to the donor-site chest wall. All participants were blinded for the study duration but assessors were only partially blinded. Non-parametric methods were used for analysis. RESULTS: A total of 107 women were included (sealant 54, control 53). Overall back seroma volumes were high, with no significant differences between control and sealant groups over 3 months. Fibrin sealant failed to reduce in situ back drainage volumes in the 10 days after surgery, and did not affect the rate or volume of seromas following drain removal. CONCLUSION: This randomized study, which was powered for size effect, failed to show any benefit from fibrin sealant in minimizing back seromas after LD procedures.

A feasibility study (ICG-10) of indocyanine green (ICG) fluorescence mapping for sentinel lymph node detection in early breast cancer.

BACKGROUND: There is now increasing evidence to support the use of indocyanine green (ICG) for sentinel lymph node (SLN) detection in early breast cancer. The primary objective of this feasibility study (ICG-10) was to determine the sensitivity and safety of ICG fluorescence imaging in sentinel lymph node identification when combined with blue dye and radiocolloid. METHODS: One hundred women with clinically node negative breast cancer (95 unilateral; 5 bilateral) had sentinel lymph node (SLN) biopsy using blue dye, radioisotope and ICG. One patient was excluded from analysis and sensitivity, or detection rate, of ICG alone, and in combination with blue dye and/or radioisotope, was calculated for the remaining 104 procedures in 99 patients. RESULTS: Transcutaneous fluorescent lymphography was visible in all 104 procedures. All 202 true SLNs, defined as blue and/or radioactive, were also fluorescent with ICG. Detection rates were: ICG alone 100%, ICG & blue dye 95.0%, ICG & radioisotope 77.2%, ICG & blue dye & radioisotope 73.1%. Metastases were found in 25 of 201 SLNs (12.4%) and all positive nodes were fluorescent, blue and radioactive. The procedural node positivity rate was 17.3%. CONCLUSION: The results of this study confirm the high sensitivity of ICG fluorescence for SLN detection in early breast cancer. The combination of ICG and blue dye had the highest nodal sensitivity at 95.0% defining a dual approach to SLN biopsy that avoids the need for radioisotope.

Ultrasound of the axilla: where to look for the sentinel lymph node.

AIMS: The aim of this paper is to guide the radiologist to the most likely location of the sentinel lymph node (SLN). MATERIALS AND METHODS: Patients with invasive breast cancer underwent axillary ultrasound examination. The position and morphological appearances of the lymph nodes were noted and core biopsy (CB) was performed of the largest or most suspicious node. Those patients whose biopsy revealed no evidence of malignancy proceeded to a surgical sentinel lymph node (SLN) biopsy (SLNB) looking for histopathological evidence of previous CB. RESULTS: Of 121 patients who underwent axillary ultrasound and CB no malignancy was identified in 73, all of whom subsequently underwent SLNB. Histological evidence of CB in the SLN was identified in 47 (64%) patients. The position of all the lymph nodes identified on ultrasound and the 47 patients whose SLNs were identified were drawn on composite diagrams of the axilla. Of the 36 nodes identified as sentinel whose position relative to other nodes could be determined, 29 (81%) represented the lowest node identified in the axilla, four (11%) were the second lowest, and three (8%) were the third lowest node. None of the four patients whose CB was from the fourth lowest node had the CB site identified at subsequent SLNB. CONCLUSION: Ultrasound of the axilla should be carried out in a systematic fashion focusing on level I nodes paying particular attention to the lowest one or two lymph nodes.

Use of ultrasound-guided axillary node core biopsy in staging of early breast cancer.

The aim of this study was to see how effective ultrasound-guided needle biopsy was at detecting lymph node involvement in patients with early breast cancer. Patients with newly diagnosed invasive breast cancer underwent axillary ultrasound (US) where lymph node size and morphology were noted. A core biopsy (CB) was undertaken of any node greater than 5 mm in longitudinal section. Patients with benign CBs proceeded to sentinel lymph node (SLN) biopsy, whereas those with malignancy underwent axillary lymph node dissection (ALND). US and CB findings were correlated with final surgical histology in all cases. One hundred and thirty-nine patients were examined, of whom 52.5% had lymph node metastases on final histology. One hundred and twenty-one patients (87%) underwent axillary node CB. The overall sensitivity of CB for detecting lymph node metastases was 53.4% (60.3% for macrometastases; 26.7% for micrometastases). The US morphological characteristics most strongly associated with malignancy were absence of a hilum and a cortical thickness greater than 4 mm. However, one third of patients with normal lymph node morphology had nodal metastases, and only 12% of these were diagnosed on CB. CB of axillary lymph nodes can diagnose a substantial number of patients with lymph node metastases, allowing these patients to proceed directly to ALND, avoiding unnecessary SLN biopsy.

Titanium clip placement to allow accurate tumour bed localisation following breast conserving surgery: audit on behalf of the IMPORT Trial Management Group.

INTRODUCTION: Accurate tumour bed (TB) localisation is a key requirement for the UK IMPORT (Intensity Modulated Partial Organ Radiotherapy) trial. We audited the value of titanium clips for TB localisation following breast conserving surgery (BCS) in breast radiotherapy (RT) planning. PATIENTS AND METHODS: At surgery, paired clips were positioned around the TB as follows: 1. Medial, lateral, superior and inferior: half-way between skin and fascia; 2. Posterior: at the pectoral fascia; 3. Anterior: close to the suture line. Thirty consecutive patients with clips inserted were audited at the time of RT planning. Audit standards were set as follows: (i) 5/6 pairs of clips identified on RT planning computed tomography (CT) scan - 100%; (ii) possible clip migration: <10%; (iii) TB localisation improved with clips: >50%. Inter- and intra-observer variability in clinician outlining of the TB was studied in a subset of 12 randomly selected patients to see if this impacted on positioning of radiotherapy field borders. RESULTS: Five or six pairs of clips were identified in all 30 cases. The TB could be successfully identified using CT seroma alone in only 8/30 (27%) patients. Clips were essential for the TB localisation of the other 22/30 (73%) patients. There was no evidence of clip migration. TB localisation led to modified RT field borders in 18/30 (60%) patients. Five of these patients had highly visible seromas, so the addition of clips modified field borders in 13/30 (43%) patients. Both inter- and intra-observer variability was reasonable and did not impact on positioning of radiotherapy field borders. CONCLUSION: Titanium clips provide an accurate and reliable method of TB localisation following BCS. We anticipate that the audit results will lead to clips being adopted as best practice by the Association of Breast Surgeons (ABS) at BASO (British Association of Surgical Oncology).

Ultrasound guided percutaneous axillary lymph node core biopsy: how often is the sentinel lymph node being biopsied?

Patients with breast cancer now frequently undergo axillary ultrasound and core biopsy (CB) in an attempt to reduce the number of unnecessary sentinel lymph node (SLN) biopsies. This study aimed to establish the frequency of successful targeting of the SLN by ultrasound guided biopsy. A total of 137 patients had axillary ultrasound of which 121 underwent CB. 73 (60%) patients proceeded to SLN after negative CB. All SLNs were examined for evidence of metastases and previous CB. Of the 73 patients, 51 had no evidence of malignancy in the SLN (true negative=70%). However nodal deposits were found in the remaining 22 patients, representing a false negative rate for CB of 30%. Overall histopathological evidence of previous CB was identified in 47 (64%) of 73 patients undergoing SLN biopsy. The reason for false negative findings in the 22 (30%) patients was failure to sample the sentinel lymph node in 10 (45%) and failure to sample the metastatic disease in the sentinel node in 11 (55%). This study suggests that both better methods of identifying the sentinel lymph node and more adequate sampling are required.

Skin-reducing mastectomy with breast reconstruction and sub-pectoral implants.

One of the difficulties of an immediate breast reconstruction with a sub-pectoral tissue expander is fashioning the lower, medial end of the pouch because of the insertion of the fibres of the pectoral muscle into the ribs. This often requires delayed corrections to provide a good cosmetic result with fullness of the lower medial quadrant of the reconstructed breast. Skin-reducing mastectomy (SRM) is a technique that potentially resolves this cosmetic problem by creating a dermomuscular pouch with adequate volume in the lower-medial quadrant and, at the same time, provides satisfactory coverage of the silicone implant. Much of the surgical scarring lies in relatively concealed areas of the breast. The risk of complications is reduced by use of permanent expanders and achieving compatibility between the length of the skin flaps and that of the dermomuscular pouch. The indications for this technique are the same as those of a skin-sparing mastectomy. The procedure is particularly useful for women with large breasts and in cases of bilateral prophylactic mastectomy for women at increased risk of breast cancer. We report our experience with 18 skin-reducing mastectomies carried out in 10 women. One had a complication (5%) (haematoma and infection) and one had poor long-term cosmetic result (5%) (fibrosis of the lower pole of the reconstructed breast). SRM is, from an oncological perspective, a skin-sparing mastectomy (type IV) that provides a good cosmetic result by creating a dermomuscular pouch.

Management of the axilla in women with breast cancer.

There remain several outstanding questions relating to management of the axilla in women with early stage breast cancer. This paper summarises the outcome of a national debate aimed at discussing certain key issues including a) whether axillary dissection has any survival advantage b) is an axillary staging procedure always necessary c) what is the optimum method of staging the axilla and d) whether an axillary dissection is always necessary in cases of a positive sentinel node. Electronic voting was undertaken at the beginning and end of the debate and results are compared and presented herein.

A critique of the sentinel node concept.

The concept of "the sentinel node" is false. In the axilla, the lymphatic system usually first drains into a group of low axillary nodes (level 1). The validity, as a staging procedure, of a 4 node axillary sample was demonstrated 30 years ago by Prof. Sir Patrick Forrest. Sentinel node biopsy (SNB) should not become the standard of care for all breast cancer patients. All the various options (axillary sampling, SNB, axillary dissection or simply a watchful attitude) are acceptable and to be advised according to the patient's wishes and conditions and to the tumour characteristics. We would also propose the change of the terminology from SNB to "guided axilary sampling" (GAS).

Axillary staging in women with small invasive breast tumours.

AIMS: To identify a group of women with small breast cancers of favourable histological grade for whom observation alone may be an acceptable approach for management of the axilla. METHODS: In a retrospective analysis the incidence of nodal metastases was examined in a group of 355 consecutive patients over 55 years of age who underwent mastectomy or breast conserving surgery. All patients had either grade I (<20 mm) or grade II (<15 mm) oestrogen receptor positive tumours without lymphovascular invasion (LVI). In a related study on 173 clinically node negative patients, the rate of axillary recurrence was assessed in patients with small (<10 mm), non-high grade (I and II), ER-positive invasive ductal carcinomas without LVI. Axillary surgery was either omitted (135 patients) or delayed (38 patients) at the time of wide local excision or mastectomy. RESULTS: The overall incidence of positive nodes in this good prognostic group of patients was 13% (95% confidence interval 9.5-16.5). When the analysis was confined to grade I (< or =20 mm) and grade II (< or =10 mm) the overall incidence of nodal metastases was 10%. Rates of axillary recurrence at a median follow up of 49 months were only 1% when axillary surgery was omitted according to patient choice/departmental policy with no cases of uncontrolled axillary recurrence. CONCLUSION: The risk:benefit ratio for detection of node positive cases in a selected group of older patients does not justify any form of axillary procedure at the time of primary surgery.

Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy?

Contrast-enhanced (CE) MRI was used to monitor breast cancer response to neoadjuvant chemotherapy. Patients underwent CE MRI before and after therapy, together with conventional assessment methods (CAM). CE MRI was carried out at 1.5 T in the coronal plain with 3D sequences before and after bolus injection. An expert panel determined chemotherapy response using both CE MRI and CAM. Histopathological response in the surgical specimen was then used to determine the sensitivity and specificity of CE MRI and CAM. In total, 67 patients with 69 breast cancers were studied (mean age of 46 years). Tumour characteristics showed a high-risk tumour population: median size 49 mm: histopathological grade 3 (55%): oestrogen receptor (ER) negative (48%). Histopathological response was as follows: - complete pathological response (pCR) 17%; partial response (pPR) 68%; no response (NR) 15%. Sensitivity of CAM for pCR or pPR was 98% (CI 91-100%) and specificity was 50% (CI 19-81%). CE MRI sensitivity was 100% (CI 94-100%), and specificity was 80% (CI 44-97%). The absolute agreement between assessment methods and histopathology was marginally higher for CE MRI than CAM (81 vs 68%; P=0.09). In 71%, CE MRI increased diagnostic knowledge, although in 20% it was judged confusing or incorrect. The 2nd MRI study significantly increased diagnostic confidence, and in 19% could have changed the treatment plan. CE MRI persistently underestimated minimal residual disease. In conclusion, CE MRI of breast cancer proved more reliable for predicting histopathological response to neoadjuvant chemotherapy than conventional assessment methods.