Ian C. Bennett

Intraoperative Ultrasound-Guided Excision of Nonpalpable Breast Lesions

The methods commonly used to guide surgical excision of impalpable breast lesions include preoperative placement of hookwires, carbon injections, and, more recently, radioisotope injections. However, all of these techniques have disadvantages, not the least of which is subjecting the patient to an additional stressful and often traumatic procedure preoperatively. The use of intraoperative ultrasound to guide the excision of sonographically visible impalpable lesions is a new technique that avoids the need for a preoperative localization procedure. This report describes one of the author’s (I.B.) personal series of ultrasound-guided breast excisions, collating data collected prospectively, and reviews the efficacy of this technique. Data in relation to 115 ultrasound guided breast excisions performed in 103 patients were reviewed. The technique of using a high-frequency real-time ultrasound probe intraoperatively to localize and guide excision of breast abnormalities is described. There were no failed excisions, as confirmed by specimen sonography, pathology findings, and/or follow-up ultrasound. Breast malignancies comprised 42% of all excised lesions, and of these, adequate margins of excision were achieved at the first operation in 93% of cases. Direct ultrasound localization of the lesion at the time of surgery allowed optimal placement of the incision and eliminated delays in operating time because specimens did not have to be sent to the Radiology Department for confirmation of excision. Intraoperative ultrasound-guided excision is a safe and efficient technique in the management of impalpable, sonographically visible breast lesions, and early reports in the world literature support the findings of this series, which show it to have significant advantages over other current methods, particularly with respect to a reduction in patient anxiety and improved surgical resection margins.

Exploring the prevalence of ten polyomaviruses and two herpes viruses in breast cancer.

Several different viruses have been proposed to play a role in breast carcinogenesis. The aim of this study was to investigate the prevalence of a subset of viruses in breast cancer tissue. We investigated the prevalence of 12 DNA viruses: EBV and CMV from the Herpesviridae family and SV40, BKV, JCV, MCV, WUV, KIV, LPV, HPyV6, HPyV7, and TSV from the Polyomaviridae family in 54 fresh frozen breast tumour specimens. Relevant clinical data and basic lifestyle data were available for all patients. The tissue samples were DNA extracted and real-time PCR assays were used for viral detection. The highest prevalence, 10% (5/54), was found for EBV. MCV, HPyV6, and HPyV7 were detected in single patient samples (2% each), while WUV, KIV, JCV, BKV, LPV, SV40, TSV and CMV were not detected in the 54 breast cancer specimens analysed here. Further investigations are needed to elucidate the potential role of viruses, and particularly EBV, in breast carcinogenesis.

High prevalence of human papillomaviruses in fresh frozen breast cancer samples

While the etiology of breast cancer remains enigmatic, some recent reports have examined the role of human papillomavirus (HPV) in breast carcinogenesis. The purpose of this study was to determine the prevalence of HPV in breast cancer tissue using PCR analysis and sequencing. Fifty‐four (54) fresh frozen breast cancers samples that were removed from a cohort of breast cancer patients were analyzed. Samples were tested for HPV using comprehensive PCR primers, and in situ hybridization was performed on paraffin embedded tissue sections. Findings were correlated with clinical and pathological characteristics. The HPV DNA prevalence in the breast cancer samples was 50% (27/54) with sequence analysis indicating all cases to be positive for HPV‐18 type. While HPV patients were slightly younger, no correlation was noted for menopausal status or family history. HPV positive tumors were smaller with earlier T staging and demonstrated lesser nodal involvement compared to HPV negative cancers. In situ hybridization analyses proved negative. The high proportion of HPV positive breast cancers detected in this series using fresh frozen tissues cannot be dismissed, however the role of HPV in breast carcinogenesis remains unclear and may ultimately be ascertained by monitoring future breast cancer incidence amongst women vaccinated against high risk HPV types. J. Med. Virol. 83:2157–2163, 2011.

BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer

We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide‐induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro‐apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl‐2 protein family, which involves the positive regulation of anti‐apoptotic member Bcl‐2 and the negative regulation of pro‐apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl‐2/NF‐κB pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2‐mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer.

Leiomyoma of the Nipple

Abstract:  Leiomyoma is a rare, benign neoplasm of the nipple. We report the case of a patient with a leiomyoma arising from her left nipple who presented with persistent nipple pain and tenderness which led to the eventual complete excision of her left nipple and areola complex. The clinical characteristics, gross and microscopic pathologic findings, and management of this lesion are discussed. Surgical management should be tailored primarily to the control of symptoms. Clinicians should be aware that this is a rare, but potential cause of chronic persistent pain and swelling in the region of the nipple‐areola complex of the breast.

Hand-assisted laparoscopic adrenalectomy: An alternative minimal invasive surgical technique for the adrenal gland

Background:  Presently the surgical approach to the adrenal gland is in a state of flux. While the traditional approach to the adrenal gland has been the open transabdominal technique, more recently laparoscopic approaches, particularly via the transabdominal route, have increasingly been utilized. However, laparoscopic intervention for the adrenal gland can be problematic in certain circumstances, particularly for large adrenal masses and in instances of adrenal malignancies.

Use of the harmonic scalpel in thyroidectomy

Thyroidectomy is a surgical procedure that requires meticulous dissection, safe anatomical exposure and effective haemostasis. Use of the harmonic scalpel in thyroidectomy may assist in achieving these goals, particularly in respect to enabling efficient haemostatic coagulation and division of small vessels. This report demonstrates the results of utilizing the harmonic scalpel in a series of 88 prospective thyroidectomies in patients under the care of two surgeons over a 2‐year period recording a number of parameters, including operative times and post‐operative complications. These data were compared with a retrospective cohort of 57 patients who underwent thyroidectomies by the same two surgeons prior to the introduction of the harmonic scalpel. The results of this study show that the use of the harmonic scalpel decreased surgical operating time by 20 min (22.5%) for a hemithyroidectomy and 13.5 min (12%) for a total thyroidectomy. Harmonic scalpel use was not associated with an increased complication rate and has been demonstrated to be a very efficient and safe tool in assisting with the conduct of a thyroidectomy.

Confirmation of a susceptibility locus on chromosome 13 in Australian breast cancer families

Two major genes determining predisposition to breast cancer, termed BRCA1 and BRCA2, have been mapped to the long arms of chromosomes 17 and 13, respectively. Each locus is believed to account for approximately 40% of cases of familial breast cancer. We used linkage and haplotype analysis with simple tandem repeat polymorphisms at chromosomal bands 17q21 and 13q12 to determine the contribution of the BRCA1 and BRCA2 genes to predisposition to breast cancer in four Australian breast cancer kindreds, one of which had two male cousins with breast cancer. Surprisingly all families segregated a haplotype of markers on 13q and showed positive lod scores supporting linkage to BRCA2. In addition, haplotype analysis identified an informative recombination between D13S260 and D13S171 in one affected individual, which refines the localisation of BRCA2 to between D13S260 and D13S267; a distance of 2–3 cM. Tumours of the stomach and cervix, as well as melanoma and leukaemia/lymphoma also occur in these pedigrees but the numbers are too low to determine whether they may be significantly associated with BRCA2 carrier status. Our results confirm the existence of BRCA2 on the long arm of chromosome 13 and support previous findings that this locus is likely to confer risk in families with affected males. Furthermore, our observations suggest that the BRCA2 gene may also contribute to the development of other neoplasms.

No association between HPV positive breast cancer and expression of human papilloma viral transcripts

Infectious agents are thought to be responsible for approximately 16% of cancers worldwide, however there are mixed reports in the literature as to the prevalence and potential pathogenicity of viruses in breast cancer. Furthermore, most studies to date have focused primarily on viral DNA rather than the expression of viral transcripts. We screened a large cohort of fresh frozen breast cancer and normal breast tissue specimens collected from patients in Australia for the presence of human papilloma virus (HPV) DNA, with an overall prevalence of HPV of 16% and 10% in malignant and non-malignant tissue respectively. Samples that were positive for HPV DNA by nested PCR were screened by RNA-sequencing for the presence of transcripts of viral origin, using three different bioinformatic pipelines. We did not find any evidence for HPV or other viral transcripts in HPV DNA positive samples. In addition, we also screened publicly available breast RNA-seq data sets for the presence of viral transcripts and did not find any evidence for the expression of viral transcripts (HPV or otherwise) in other data sets. This data suggests that transcription of viral genomes is unlikely to be a significant factor in breast cancer pathogenesis.

Intraoperative ultrasonography-guided excision of nonpalpable breast lesions

BackgroundThe use of intraoperative ultrasonography (US) to localize and guide excision of nonpalpable breast lesions has advantages over other techniques. It avoids the need for additional resources and minimizes patient morbidity.Methods and resultsThe technique of surgeon-performed US-guided excision as described in this report is straightforward and safe, easily reproducible, and suitable for teaching.ConclusionsThe US-guided breast excision technique is predictable and accurate, minimizes costs, and is advocated as an appropriate method for US-visible lesions requiring surgical excision. With appropriate training, breast surgeons can easily acquire the necessary skills to incorporate the use of US in their surgical practice.