Evaluation of long-term outcome following therapeutic mammaplasty: the effect of wound complication on initiation of adjuvant therapy and subsequent oncological outcome.

INTRODUCTION: Therapeutic mammaplasty (TM) facilitates large tumour resection while maintaining optimal aesthetic outcome. It carries higher wound complication risks, which may delay adjuvant therapy initiation. Whether this delay affects oncological outcome requires evaluation. METHODS: Data were collected for consecutive patients receiving TM at the Leeds breast unit (2009-2017). A prospectively maintained database was used to determine tumour characteristics, wound complication rates, receipt of adjuvant therapy and breast cancer recurrence or death. RESULTS: In total 112 patients (median age of 54 years) underwent 114 TM procedures. The most common histological subtypes were invasive ductal carcinoma (61.4%), invasive lobular carcinoma (13.2%) and ductal carcinoma in situ (13.2%). Of the patients, 88.2% had oestrogen receptor-positive cancer and 14% had human epidermal growth factor receptor-positive cancer; 26.3% had multifocal cancer. The median tumour size was 30mm. The median Nottingham Prognostic Index was 4.2. The local recurrence rate was 3.5% (median follow-up of 8.6 years). The 5- and 10-year disease-free survival (DFS) was 88.5% and 83.5%, and the equivalent overall survival (OS) rates were 94% and 83.5%. Wound complication rate was 23.6% (n=27), the commonest being wound infection (11.4%; n=13) and T-junction wound breakdown (10.5%; n=12). The median time to adjuvant therapy was 72 days (interquartile range [IQR] 56-90) for patients with wound complications, and 51 days (IQR 42-58) for those without. However, this delay did not affect DFS or OS (log-rank test; p=0.58 and p=0.94, respectively). This was confirmed on Cox regression analysis. CONCLUSION: Our study finding demonstrates that although wound complications after TM leads to a modest delay to adjuvant therapy, the long-term oncological outcomes were comparable with those in patients without wound complications.

'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.

Impact of family history risk assessment on surgical decisions and imaging surveillance at breast cancer diagnosis.

INTRODUCTION: In June 2013, the National Institute for Health and Care Excellence (NICE) published guidance on the management of women with a family history (FH) of breast cancer (BC) and a personal diagnosis of BC. When diagnosed with BC, pressure of timely treatment takes priority and there is potential for a significant FH to be overlooked. This can affect treatment options and follow-up imaging (FUI) surveillance. METHODS: The practice in our breast unit was compared with the NICE guidance with regard to arranging appropriate FUI and referral to the genetics team for women diagnosed with BC with a FH of BC. Data were obtained retrospectively on 200 women with BC, identified from the breast multidisciplinary team meetings from January to March 2014. Initial audit showed poor compliance with recording of FH. A standardised history taking proforma was produced for clinic use. A re-audit was conducted on a further 200 women between May and July 2016. RESULTS: In the initial audit, FH was taken in 151 women (76%) compared with 174 women (87%) in the re-audit. Thirty-seven women (25%) were thought to be of moderate risk (MR) or high risk (HR) based on FH in the first audit. Re-audit identified 35 women (20%) with MR or HR FH. Under half (43%) of the women of HR were referred to the genetics team initially; this increased to 70% in the second audit. While almost half (46%) of the women with MR or HR had inappropriate FUI in the initial audit, this fell to 11% in the re-audit. CONCLUSIONS: A proportion of women diagnosed with BC would fall into the MR or HR categories as defined in the NICE FH guidance. Inadequate recording of FH could result in inadequate FUI surveillance and in some cases missing the opportunity for a genetic referral to assess suitability for gene testing.

Evaluation of the usage and influence of groin ultrasound in primary and secondary healthcare settings.

AIM: Groin ultrasound scan (USS) is used to aid the diagnosis of inguinal hernias. Our radiology department offers access to image symptomatic patients for general practitioners (GPs) as well as surgeons. We examined the utilisation of groin USS in primary and secondary healthcare settings, and investigated its influence on proceeding to surgery. METHODS: A retrospective data analysis was performed for patients seen in the surgical outpatient clinics (January 2010-January 2011). Clinical, radiological, and surgical findings were compared. RESULTS: 267 USS were performed by musculoskeletal radiology specialists; patients were referred for USS by GPs in 98 cases (36.7 %), compared to 169 cases (63.3 %) where the referral for USS was organised by surgeons. Clinical examination by surgeons detected inguinal hernias in 105 groins (39.3 %), and USS detected inguinal hernias in 154 groins (57.7 %). Of 162/267 (60.7 %) cases where clinical examination was negative, 98/162 (60.4 %) also had a negative USS; only five of these patients (5.1 %) underwent surgery. In the 64/162 (39.6 %) cases where only the USS findings were positive, 19/64 underwent surgery (29.7 %). When hernia was detected on both USS and clinical examination (n = 90), 68/90 underwent surgery (75.6 %). For patients who underwent surgery, sensitivity for hernia detection was 80 % for clinical examination versus 96.3 % for USS. CONCLUSION: Groin USS is highly sensitive, and patients could be referred for USS by GPs when clinical examination findings are equivocal or negative. If USS is also negative, patients may be managed conservatively in primary care setting if they remain asymptomatic. Positive clinical examination findings appear to have a greater influence in the decision to treat surgically.

A critical evaluation of the electronic surgical logbook.

BACKGROUND: The Association of Surgeons of Great Britain and Ireland (ASGBI) devised the electronic surgical logbook (version 2.4) for higher trainees in General Surgery enabling trainees to compile a uniform data set of their operative and training experience. This is in use by higher surgical trainees (HST) in the United Kingdom. This logbook permits trainees to submit data centrally into a Regional Analysis Database (RAD). With the implementation of the European Working Time Directive (EWTD) there is need for reliable data to assess the effects of the directive on training. In order to draw meaningful conclusions from the database the quality of data needs to be validated. We critically analysed the RAD in the Yorkshire region for a one-year period. METHODS: The RAD from the ASGBI for the Yorkshire region was analysed. Data for the period 01/10/2002-30/09/2003 was identified and interrogated using Microsoft Excel (2000 version). The RAD was compared with information obtained from the Regional Surgical Advisor for Yorkshire with respect to hospitals, surgical consultants and HST's in the region during the study period. RESULTS: There were 13,755 operations entered for the study period. 579 corrections to the data had to be made (4.2%) and a further 1140 entries were deleted (8.2%). Following corrections and deletions 12,615 operative entries were available for analysis. Overall 12.5% of the data required either correction or exclusion from the database prior to analysis. CONCLUSION: The RAD has a large dataset useful to monitor and assess training. However, the quality of the data needs to be verified prior to use. Recommendations have been made to develop the ASGBI logbook, which would eventually translate to improved data reliability of the RAD.

Role of magnetic resonance imaging in the diagnosis and single-stage surgical resection of invasive lobular carcinoma of the breast.

BACKGROUND: Conventional imaging with mammography and ultrasonography has a low sensitivity for diagnosis and a tendency to underestimate the extent of invasive lobular carcinoma (ILC) of the breast. The aim was to determine whether magnetic resonance imaging (MRI) had any advantages for the characterization of ILC. METHODS: Twenty patients with histologically proven ILC underwent preoperative imaging with MRI. MRI was performed to aid detection of malignancy in six patients with a clinically suspicious presentation but normal or indeterminate imaging on mammography and ultrasonography. In 14 patients MRI was performed to determine tumour extent. RESULTS: MRI accurately identified malignancy in five of six patients with normal or indeterminate conventional imaging. In seven of 14 patients in whom MRI was performed to determine tumour extent, it provided significant additional information. These included four patients in whom conventional imaging grossly underestimated tumour size, two patients in whom MRI identified an unsuspected contralateral breast tumour and one patient in whom MRI predicted tumour invasion of the pectoral muscle. The correlation between tumour size on histological examination was better with MRI (r = 0.967) than with mammography (r = 0.663) and ultrasonography (r = 0.673). CONCLUSION: MRI can provide considerable additional information in the detection and characterization of ILC.

BCL10 in malignant lymphomas--an evaluation using fluorescence in situ hybridization.

BCL10 is a tumour suppressor gene originally cloned from a t(1;14)(p22;q32) breakpoint in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. Translocations involving this gene, though uncommon, are sometimes encountered in MALT lymphomas. This gene is thought to play an important role in the development of malignant lymphomas. Fluorescence in situ hybridization (FISH) was therefore undertaken on 22 cases of malignant lymphoma of varying histology to establish the incidence of rearrangements involving the BCL10 gene. Initially, one case with a novel t(1;2)(p22;p12) translocation involving the BCL10 gene was identified, in a marginal zone lymphoma of the MALT type, and was reported elsewhere. Seven other cases were subsequently identified with abnormalities in the 1p region, including a translocation with a breakpoint in the 1p22 region in a case of lymphoblastic lymphoma. However, none of these involved the BCL10 gene. Mutation analysis of BCL10 was then performed on 57 cases of malignant lymphoma, including 17 MALT lymphomas, by single-strand conformational polymorphism (SSCP) analysis of tumour DNA. Tissue was obtained for mutation analysis for 12 of the 22 cases analysed by FISH. Selected cases with SSCP band shifts were further studied by direct sequencing. Polymorphisms were identified in eight cases, but no mutations of pathogenic significance were identified. Further RT-PCR and mutation analysis was performed on cDNAs from 12 cases (four MALT, seven diffuse large B-cell lymphoma, one Hodgkin's disease) in which DNA analysis had already been completed. This included the MALT lymphoma with the t(1;2)(p22;p12) rearrangement. Again, no mutations were identified in the coding sequence. This study confirms that rearrangements of the BCL10 gene are uncommon in lymphoma (1/22) and may be limited tothe MALT subtype of non-Hodgkin's lymphomas. It was also found that breakpoints or rearrangements in the 1p22 region do not necessarily involve the BCL10 gene. Moreover, the absence of mutations at both the DNA (0/60) and the mRNA (0/12) level indicates that this gene is not frequently inactivated by mutation, in those tumours in which it is not involved in translocations. Our findings suggest that the BCL10 gene is unlikely to have a frequent or key role in general lymphomagenesis.

Genetic events during the transformation of a tamoxifen-sensitive human breast cancer cell line into a drug-resistant clone.

Tamoxifen resistance is a serious clinical problem commonly encountered in the management of patients with breast cancer. The mechanisms leading to its development are unclear. Tamoxifen acts via multiple pathways and has diverse effects. Hence transformation from a tamoxifen-sensitive to a resistant phenotype could involve multiple genetic events. Knowledge of the genetic pathways leading to resistance may facilitate the development of novel therapeutic strategies. In this study, a variation of conventional comparative genomic hybridization (CGH) has been employed to detect genetic alterations associated with tamoxifen resistance. MCF-7, a tamoxifen-sensitive human breast cancer cells line, and its tamoxifen-resistant clone, CL-9 were used. Both cell lines showed extensive areas of concordance but consistent differences were seen with the acquisition of tamoxifen resistance. These differences included the amplification of 2p16.3 approximately p23.2, 2q21 approximately q34, 3p12.3 approximately p14.1, 3p22 approximately p26, 3q, 12q13.2 approximately q22, 13q12 approximately q14, 17q21.3 approximately q23, 20q11.2 approximately q13.1 and 21q11.2 approximately q21 as well as the deletion of 6p21.1, 6p23 approximately p25, 7q11.1 approximately q31, 7q35 approximately q36, 11p15, 11q24, 13q33, 17p, 18q12 approximately q21.1, 19p, 19q13.3, 22q13.1 approximately q13.2. These findings were supported by conventional cytogenetics and chromosome painting. The regions identified by CGH potentially harbor genes that could be important in the development of tamoxifen resistance.

Colorectal subspecialization in a DGH. The way forward!

AIMS: To audit all aspects of the diagnosis and management of colorectal cancers by a specialist unit within a District General Hospital (DGH). To compare the clinical effectiveness of the specialist service with the service prior to specialization and attempt to assess the feasibility of setting up such a service within the constraints imposed by a DGH. MATERIALS AND METHODS: Data for this study was collected prospectively over a 3-year period from July 1997 to June 2000 since the establishment of a specialist colorectal service. The results so obtained have been compared with the Trent and Wales audit of 1993 as well as with the guidelines issued by the Royal College of Surgeons of England and the Association of Colo-proctologists of Great Britain and Ireland. We have attempted to evaluate whether specialization has altered the outcome for patients with colorectal cancer. RESULTS: A total of 2181 patients were seen at the specialist colorectal clinic and 42% underwent immediate flexible sigmoidoscopy. A total of 241 colorectal cancers were diagnosed during this period by the specialist unit, of which the rapid access clinic had picked up 191 (a pick-up rate of 8.75%). The mean age of patients with colorectal cancer was 69.23 years and the median waiting time from referral to clinic and from referral to treatment was 9 days and 24 days, respectively. These compare favourably with the waiting times prior to specialization. 117 rectal cancers were diagnosed of whom 32 (32%) underwent APER. A selective approach to short course preoperative radiotherapy resulted in 24% of rectal cancer patients receiving this treatment. The CRM was positive in 14% of resected rectal cancers, all of whom had received preoperative radiotherapy. The percentage of patients with Dukes' stage A disease has risen from 11% in 1993 to 23% and the percentage of patients undergoing emergency surgery have fallen from 29% in 1993 to 8.2%. The rate of permanent stoma formation has also decreased from 52% to 32%. This audit has also confirmed that the guidelines for the management of colorectal cancers were all being met or exceeded. CONCLUSION: The study demonstrates that, even within the constraints of a DGH, a specialist service can result in earlier diagnosis, shorter waiting periods and judicious use of adjuvant treatment leading to improved clinical effectiveness. It is possible to deliver a high quality service, which meets, and in some areas, surpasses the minimum guidelines, provided there is an integrated multidisciplinary approach.

Novel translocation of the BCL10 gene in a case of mucosa associated lymphoid tissue lymphoma.

Interest has focused on a recently identified gene, BCL10, thought to play an important role in the genesis of extranodal, marginal zone (MALT) lymphomas. This gene belongs to a family containing caspase recruitment domains (CARD), that are involved in the apoptotic pathway. Translocations of the BCL10 gene to the immunoglobulin heavy chain locus at 14q32 have been described. We report herein a case of MALT lymphoma showing t(1; 2)(p22; p12). The translocation was shown to involve the BCL10 gene and the immunoglobulin kappa light chain locus by fluorescence in situ hybridization.