Neurogenic Unilateral Leg Edema.

This case report describes neurogenic unilateral leg edema that was a consequence of chronic regional pain syndrome induced by an S1 radiculopathy.

Unilateral axillary adenopathy following COVID-19 vaccination: a multimodality pictorial illustration and review of current guidelines.

We present a multimodality pictorial review of axillary lymphadenopathy in patients recently vaccinated against COVID-19. As the mass vaccination programme continues to be rolled out worldwide in an effort to combat the pandemic, it is important that radiologists consider recent COVID-19 vaccination in the differential diagnosis of unilateral axillary lymphadenopathy and are aware of typical appearances across all imaging methods. We review current guidelines on the management of unilateral axillary lymphadenopathy in the context of recent COVID-19 vaccination.

A novel technique to repair a transverse sacral fracture in a previously fused lumbosacral spondylolisthesis.

BACKGROUND: Transverse fractures of the sacrum are rare, and surgical treatment for these fractures ranges from conservative to challenging. Transverse stress fractures of the sacrum after placement of lumbar-to-sacral instrumentation have been previously described. We report a new technique to repair a transverse Type-2 Roy-Camille fracture with spondylolisthesis of S1 over S2 in a previously fused instrumented high-grade L4-L5, L5-S1 spondylolisthesis. CASE DESCRIPTION: A 64-year-old female who previously had an L4-L5, L5-S1 fusion for spondylolisthesis presented with excruciating lower back pain and radiculopathy for over 6 months. She was found to have an S1-S2 transverse fracture caused by previous implantation of pedicle screws. She underwent repositioning of several failed right lumbar and sacral screws and then had bilateral S1-S2 screws placed directly across the fracture line. The patient had an unremarkable postoperative course. She discontinued most of her pain medications within 6 weeks postoperatively. In the months following surgery, she reported only minimal lower back pain and no radiculopathy with the last appointment 5 years postoperatively. CONCLUSIONS: We describe a novel technique to reduce an iatrogenic transverse type-2 Roy-Camille fracture at S1-S2 in a previously instrumented high-grade L4-L5, L5-S1 spondylolisthesis. The patient's fracture achieved adequate reduction and fusion with symptomatic relief.

Hybrid Biosynthetic Autograft Extender for Use in Posterior Lumbar Interbody Fusion: Safety and Clinical Effectiveness.

Autologous iliac crest bone graft is the preferred option for spinal fusion, but the morbidity associated with bone harvest and the need for graft augmentation in more demanding cases necessitates combining local bone with bone substitutes. The purpose of this study was to document the clinical effectiveness and safety of a novel hybrid biosynthetic scaffold material consisting of poly(D,L-lactide-co-glycolide) (PLGA, 75:25) combined by lyophilization with unmodified high molecular weight hyaluronic acid (10-12% wt:wt) as an extender for a broad range of spinal fusion procedures. We retrospectively evaluated all patients undergoing single- and multi-level posterior lumbar interbody fusion at an academic medical center over a 3-year period. A total of 108 patients underwent 109 procedures (245 individual vertebral levels). Patient-related outcomes included pain measured on a Visual Analog Scale. Radiographic outcomes were assessed at 6 weeks, 3-6 months, and 1 year postoperatively. Radiographic fusion or progression of fusion was documented in 221 of 236 index levels (93.6%) at a mean (±SD) time to fusion of 10.2+4.1 months. Single and multi-level fusions were not associated with significantly different success rates. Mean pain scores (+SD) for all patients improved from 6.8+2.5 at baseline to 3.6+2.9 at approximately 12 months. Improvements in VAS were greatest in patients undergoing one- or two-level fusion, with patients undergoing multi-level fusion demonstrating lesser but still statistically significant improvements. Overall, stable fusion was observed in 64.8% of vertebral levels; partial fusion was demonstrated in 28.8% of vertebral levels. Only 15 of 236 levels (6.4%) were non-fused at final follow-up.

Observations on the effects of Suppressor of Cytokine Signaling 7 (SOCS7) knockdown in breast cancer cells: their in vitro response to Insulin Like Growth Factor I (IGF-I).

PURPOSE: Suppressor of cytokine signaling 7 (SOCS7) is a member of the SOCS family and is known to interact with phospholipase Cγ-1 (PLCγ-1), one of the insulin-like growth factor-I (IGF-I) receptor downstream molecules. In this study, we sought to observe the effect of knocking down SOCS7 gene on breast cancer cells in vitro growth and migration and to elucidate whether this involves IGF-I-PLCγ1 route using the PLCγ-1 blocker U73122. METHODS: Suitable breast cancer cells (MCF7 and MDA-MB-231) were transfected with anti-SOCS7 ribozymal transgene, to create sub-lines with SOCS7 knockdown verified by RT-PCR. The growth and migration of the cells were evaluated in the presence or absence of IGF-I and PLCγ-1 inhibitor using growth assay, scratch-wound and electrical cell impedance sensing (ECIS) migration assays. RESULTS: IGF-I treatment produced more pronounced influence on MCF7 growth and migration and on MDA-MB-231 migration when SOCS7 gene was knocked down in both lines (p < 0.05). The absence of IGF-I-induced growth response in MDA-MB-231 could be due to the intrinsic characteristics of these cells. PLCγ-1 pharmacological inhibition during their in vitro migration seemed to only occur when SOCS7 gene was knocked down. CONCLUSIONS: To the best of our knowledge, this is the first report of the SOCS7 regulatory role in IGF-I induced in vitro functions in ER-positive and ER-negative breast cancer cells. IGF-I treatment and SOCS7 loss have synergistically resulted in increased growth and migration of MCF7 and in increased migration of MDA-MB-231 cells. The migratory effects could be due to a precise anti-PLCγ-1 role.

Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer.

The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.

The mRNA expression of DAP1 in human breast cancer: correlation with clinicopathological parameters.

UNLABELLED: This pilot study is the first to focus on the potential role of death-associated protein 1 (DAP1) in human breast cancer. MATERIALS AND METHODS: A total of 153 samples were studied. DAP1 transcription levels were determined using quantitative polymerase chain reaction (qPCR). Transcript levels within breast cancer specimens were compared to those of normal background tissues and correlated with clinicopathological data accumulated over a 10-year follow-up period. RESULTS: The expression of DAP1 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. NPI3, p=0.0026), and TNM stage (TNM1 vs. 4, p=0.0039). Lower DAP1 expression levels were significantly associated with local recurrence (p=0.02) and distant metastasis (p=0.001). CONCLUSION: This study demonstrates an inverse association between DAP1 mRNA levels and tumour stage and clinical outcome in breast cancer; thus, providing evidence that DAP1 plays a pro-apoptotic role in human breast cancer. The relationship between oncogenesis and the autophagy pathway merits further investigation.

Does post-mastectomy radiotherapy represent a contraindication to skin-sparing mastectomy and immediate reconstruction: an update.

The use of skin-sparing mastectomy (SSM) to facilitate breast reconstruction is increasing due to a wide acceptance of improved cosmetic outcomes and evidence of equivalence in oncologic outcomes. The rates of patients undergoing mastectomy for whom post-mastectomy radiotherapy (PMRT) will be recommended is increasing as evidence of decreased loco-regional recurrence and increased survival mounts. PMRT may adversely effect complication rates and cosmetic outcomes for patients undergoing immediate breast reconstruction and PMRT--although the evidence for this is methodologically flawed. This article summarises the above evidence and highlights a reconstructive algorithm that may be used to mitigate the possible deleterious effects of PMRT on results.

The mRNA expression of DAP3 in human breast cancer: correlation with clinicopathological parameters.

BACKGROUND: This pilot study is the first to focus on the potential role for death-associated protein 3 (DAP3) in human breast cancer. MATERIALS AND METHODS: A total of 153 samples were studied. The levels of transcription of DAP3 were determined using quantitative polymerase chain reaction (qPCR). Transcript levels within breast cancer specimens were compared to those of normal background tissues and correlated with clinicopathological data accumulated by over a 10-year follow-up period. RESULTS: The expression of DAP3 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. 3, p=0.036), TNM stage (TNM1 vs. 3, p=0.07), and tumour grade (grade 1 vs. 3, p=0.08). Lower DAP3 expression levels were significantly associated with local recurrence (p=0.013), distant metastasis (p=0.0057) and mortality (p=0.019). CONCLUSION: This study demonstrates an inverse association between DAP3 mRNA levels and tumour stage and clinical outcome in breast cancer, consistent with the pro-apoptosis function of DAP3. Further research is required in order to confirm our findings and clarify the mechanisms that regulate DAP3 expression in human breast cancer.

The impact of digital mammography on screening a young cohort of women for breast cancer in an urban specialist breast unit.

OBJECTIVE: To compare the diagnostic performance of full-field digital mammography (FFDM) with screen-film mammography (SFM) in a corporate screening programme including younger women. METHODS: Data were available on 14,946 screening episodes, 5010 FFDM and 9936 SFM. Formal analysis was by logistic regression, adjusting for age and calendar year. FFDM is compared with SFM with reference to cancer detection rates, cancers presenting as clustering microcalcifications, recall rates and PPV of recall. RESULTS: Overall detection rates were 6.4 cancers per thousand screens for FFDM and 2.8 per thousand for SFM (p < 0.001). In women aged 50+ cancer detection was significantly higher for FFDM at 8.6 per thousand vs. 4.0 per thousand, (p = 0.002). In women <50, cancer detection was also significantly higher for FFDM at 4.3 per thousand vs. 1.4 per thousand, (p = 0.02). Cancers detected as clustering microcalcifications increased from 0.4 per thousand with SFM to 2.0 per thousand with FFDM. Rates of assessment recall were higher for FFDM (7.3% vs. 5.0%, p < 0.001). FFDM provided a higher PPV for assessment recall, (32 cancers/364 recalls, 8.8%) than SFM, (28 cancers/493 recalls, 5.7%). CONCLUSIONS: Cancer detection rates were significantly higher for FFDM than for SFM, especially for women <50, and cancers detected as clustering microcalcifications.

Evidence for a tumour suppressor function of SETD2 in human breast cancer: a new hypothesis.

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. We previously demonstrated SETD2 to be a potential tumour suppressor gene in breast cancer. The aim of this study was to compare SETD2 expression in breast cancer with that in adjacent non-cancerous breast tissue (ANCT) in paired samples. A hypothesis is proposed that explains the mode of action of SETD2 as a tumour suppressor gene. MATERIALS AND METHODS: Paired samples of tumour and adjacent non-cancerous tissue (ANCT) from 25 patients were analysed. The levels of transcription of SETD2 were determined using quantitative polymerase chain reaction and normalized against cytokeratin 19. Immunohistochemical staining with appropriate antibodies against SETD2 protein was also performed in selected samples. RESULTS: Levels of SETD2 mRNA were significantly higher in ANCT when compared to those in tumour samples (p=0.01). Immunohistochemistry also demonstrated a higher protein expression in ANCT. CONCLUSION: This study offers further evidence that SETD2 behaves like a tumour suppressor gene. Our hypothesis links SETD2 mode of action with telomerase regulation through human telomerase reverse transcriptase (hTERT). Several studies have emphasised the importance of histone methylation of hTERT promotor in telomerase regulation. SETD2 function of histone methylation could be the missing link in this chain which could explain the potential tumour suppressor function of SETD2.

The evolving role of radiofrequency ablation therapy of breast lesions.

BACKGROUND: The potential for radiofrequency ablation (RFA) therapy is an area of increasing interest in the context of breast conserving therapy for breast cancer. This non surgical technique potentially provides a non invasive, cosmetically pleasing result that is preferable to surgeon and patient. MATERIALS AND METHODS: A literature review was carried out facilitated by PubMed and Medline databases. Cross referencing of the obtained articles was used to identify other relevant studies. A total of 17 studies were reviewed. RESULTS: RFA is emerging as a promising treatment for breast cancer. Pilot and phase II studies have shown RFA to be effective at ablation with few complications or adverse effects experienced by patients. However, complete ablation of tumours is still not achieved in all patients. CONCLUSION: RFA represents a promising therapeutic modality for breast lesions. However, there is a clear need for further research and refinement of the procedure before it can be offered as a therapeutic alternative to surgical excision for operable breast cancer.

Surgical excision for B3 breast lesions diagnosed by vacuum-assisted core biopsy.

UNLABELLED: The aim of this retrospective study was to assess whether open surgical excision is required following a B3 diagnosis on 11-gauge vacuum-assisted core biopsy (VACB) of radiologically indeterminate breast lesions. PATIENTS AND METHODS: Twenty-four women with a histological diagnosis of the B3 category on VACB of radiologically indeterminate breast lesions were identified over a 3-year period. The VACB procedure was performed under stereotactic (n=21), ultrasound (n=2) or magnetic resonance imaging (MRI) (n=1) guidance using the Suros system. Nineteen patients underwent open surgical excision. The remaining 5 patients who had 'complete' removal of the radiological abnormality using VACB under ultrasound (n=2, papilloma) or stereotactic (n=4, atypical ductal hyperplasia) guidance were followed up clinically and radiologically. RESULTS: The median patient age was 49 years. The disease status in three patients was upgraded to ductal carcinoma in situ at open surgical excision. The VACB showed atypical lobular hyperplasia in these 3 patients, associated with microcalcification (n=2) or mass lesion (n=1). No single case of upgrading to invasive breast cancer was identified in our series. The remaining patients (16 out of 19) had a benign biopsy. The upgrade to malignancy was significantly associated with the presence of atypical lobular hyperplasia, a BI-RADS category of 4 and incomplete removal of the radiological abnormality by VACB. After a mean follow-up of 18 months, no malignancy was detected in the 5 patients who did not undergo open surgical biopsy. CONCLUSION: Open surgical excision is strongly recommended for atypical lobular hyperplasia identified in VACB specimens. VACB can be a safe alternative to surgery in the treatment of B3 lesions in selected cases, providing thorough multidisciplinary discussion has taken place.

Evidence of a tumour suppressor function for DLEC1 in human breast cancer.

UNLABELLED: DLEC1 (deleted in lung and oesophageal cancer), located on 3p22.3, is a candidate tumour suppressor gene in lung, esophageal, and renal cancer. The aim of this study was determine whether the mRNA expression levels of DLEC1 were consistent with a tumour suppressive function. MATERIALS AND METHODS: A total of 153 samples were analysed. The levels of transcription of DLEC1 were determined using quantitative PCR and normalised against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues. RESULTS: Levels of transcription were lower [corrected] in tumour samples compared to adjacent non cancerous tissue (ANCT) samples but this was not statistically significant (median 0.167 vs. 0.03; p=0.138). DLEC1 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for >10 years (p=0.041). DISCUSSION: These findings are consistent with a possible tumour suppressor function of DLEC1 in breast cancer.

Herceptin and breast cancer: an overview for surgeons.

INTRODUCTION: HER-2 over-expression is implicated in the pathogenesis of breast cancer and represents a key marker and determinant of patient outcome. Trastuzumab/Herceptin (TZ) is a recombinant humanised monoclonal antibody which targets HER-2. Introduction into clinical practice has significantly improved the natural history of HER-2 over-expressing tumors and has altered the standard of care for these women. This article reviews the established and emerging roles of TZ in the management of breast cancer (BC). METHODS: Literature review facilitated by Medline and PubMed databases. FINDINGS: The clinical utility of TZ was first established in the management of HER-2 over-expressing metastatic breast cancer (MBC), with improvements recognised in both the quality and quantity of life. Prospective randomized controlled trials have consistently demonstrated the efficacy of TZ for early breast cancer (EBC) in the adjuvant setting with significant improvements in disease free and overall survival. Emerging roles for TZ include neo-adjuvant therapy and the treatment of progressive disease. TZ is well tolerated and safe, however, associated cardiac dysfunction remains a significant clinical concern. CONCLUSION: HER-2 status is critically important in the management algorithm for BC and should be determined in all cases. Quality assurance of laboratory testing is of paramount importance. TZ has an established role in the management of HER-2 positive MBC and EBC in conjunction with conventional chemotherapy. Appropriate patient selection and monitoring for cardiac dysfunction are required.

The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters.

BACKGROUND: SET domain containing protein 2 (SETD2) is a histone methyltransferase that is involved in transcriptional elongation. There is evidence that SETD2 interacts with p53 and selectively regulates its downstream genes. Therefore, it could be implicated in the process of carcinogenesis. Furthermore, this gene is located on the short arm of chromosome 3p and we previously demonstrated that the 3p21.31 region of chromosome 3 was associated with permanent growth arrest of breast cancer cells. This region includes closely related genes namely: MYL3, CCDC12, KIF9, KLHL18 and SETD2. Based on the biological function of these genes, SETD2 is the most likely gene to play a tumour suppressor role and explain our previous findings. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of SETD2 were consistent with a tumour suppressive function in breast cancer. This is the first study in the literature to examine the direct relationship between SETD2 and breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of SETD2 were determined using quantitative PCR and normalized against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analyzed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of SETD2 mRNA were significantly lower in malignant samples (p = 0.0345) and decreased with increasing tumour stage. SETD2 expression levels were significantly lower in samples from patients who developed metastasis, local recurrence, or died of breast cancer when compared to those who were disease free for > 10 years (p = 0.041). CONCLUSION: This study demonstrates a compelling trend for SETD2 transcription levels to be lower in cancerous tissues and in patients who developed progressive disease. These findings are consistent with a possible tumour suppressor function of this gene in breast cancer.

Evidence of a tumour suppressive function of E2F1 gene in human breast cancer.

BACKGROUND: The E2F family of transcription factors are key regulators of genes involved in cell cycle progression, cell fate determination, DNA damage repair and apoptosis. E2F1 is unique in that it contributes both to the control of cellular proliferation and cellular death. Furthermore, unlike other E2Fs, E2F1 responds to various cellular stresses. This study aimed to examine the level of mRNA expression of E2F1 gene in normal and malignant breast tissue and correlate the level of expression to tumour stage. MATERIALS AND METHODS: One hundred and twenty-seven breast cancer tissue and 33 normal tissues were analyzed. Levels of transcription of E2F1 were determined using real-time quantitative PCR, normalized against CK19. Levels of expression were analyzed against TNM stage, nodal involvement, tumour grade and distant metastasis. RESULTS: The levels of E2F1 mRNA were lower in malignant tissues. They declined further with increasing TNM stage. This became statistically significant when TNM stages 3 and 4 were compared to TNM stages 1 and 2 disease (TNM1 vs. TNM3 p = 0.032; TNM1 vs. TNM4 p = 0.032; TNM2 vs. TNM3 p = .019; TNM2 vs. TNM4 p = 0.021). The levels of E2F1 also fell with increasing tumour grade, when comparing grade 2 and 3 with grade 1, however, the differences were not statistically significant. CONCLUSION: These results are highly suggestive of the role of E2F1 as a tumour suppressive gene in human breast cancer.