Implications of Highly Penetrant Genetic Variants on Breast Surgery.

It seems the most probable beneficiaries from the molecular era are those harboring hereditary genetic variants, which are responsible for 5% to 10% of all breast cancer diagnoses. There are several key implications of such variants on clinical practice, from expedited anticipation of primary cancer diagnoses, which can have their risk mitigated by risk reduction surgery, to pragmatism surrounding the management of male breast cancer patients. This communication discusses the implications of highly penetrant (or pathogenic) hereditary variants in contemporary breast surgery practice.

Opioid prescribing after breast surgery: A systematic review of guidelines.

BACKGROUND: Despite advances in opioid-sparing analgesia, opioid prescribing in breast surgery remains suboptimal. Besides delayed rehabilitation, excess post-operative opioids may contribute significantly to opioid dependence. This systematic review of guidelines evaluates current opioid-prescribing recommendations after breast surgery to identify trends in prescribing. Additionally, it compares recommendations on different non-opioid and non-pharmacological adjuncts. METHODS: Electronic databases were searched systematically using terms "breast surgery", "analgesia", "opioid" and "guidelines". The grey literature was used to supplement the search. All articles that provided guidance on opioid prescribing in breast surgery were included. Quality of the guidelines were assessed using the AGREE II tool. Recommendations pertaining to opioid prescribing, analgesic adjuncts and non-pharmacological interventions were summarised and reported with descriptive statistics. RESULT: Eight guidelines pertaining to mastectomies, breast conserving surgery and breast reconstructions were included in this review. Although an opioid-sparing approach was unanimous, there were conflicting recommendations on opioid doses. Opioid requirements were stratified by procedure in 3 guidelines, and by patient risk factors in 2 guidelines. There was significant variability in the recommended multimodal adjuncts. Notably, non-pharmacological interventions such as patient education were infrequently included in guidelines. CONCLUSION: There is a lack of high-quality guidance on opioid prescribing after breast surgery. The optimum approach for personalised opioid prescribing remains unknown. Significant variability between guidelines provide little actionable interventions for prescribers. This could be driven by the paucity in evidence supporting a single efficacious analgesic regimen for patients undergoing breast surgery. Future guidelines should also regularly incorporate non-pharmacological adjuncts to reduce opioid prescribing.

Impact of Acute Surgical Assessment Unit Dedicated Ultrasound Access at a Tertiary Care Hospital.

Background Delayed diagnosis, unnecessary hospital admissions and extended length of stay are the problems associated with inappropriate access to radiological investigations. The acute surgical assessment unit (ASAU) in Limerick has two dedicated ultrasound scan (USS) slots daily to overcome this problem. The aim of the current study was to investigate the clinical impact on patient care and the cost-effectiveness of such an ASAU USS access. Methods A retrospective review of all patients who underwent USS investigation in the ASAU between May and September 2017 was conducted. Demographic, referral source, presenting complaint, and clinical outcome data were obtained from the ASAU Log. USS data was obtained from the National Integrated Medical System (NIMIS). The Integrated Patient Management System (IPMS) and Therefore Case Manager, Therefore 2014(12.0.2) was utilized to check for any discharged ASAU patient re-presenting to the emergency department (ED) within 30 days.  Results A total of 102 patients underwent USS investigation during the study period. The most common presenting complaint was epigastric or right upper quadrant pain (55.8%). Eighty-six patients underwent USS on the same day and the majority (51%) were discharged home with appropriate outpatient follow-up. Approximately 26,000 Euros were saved over four months. Post-discharge ED visits in the ASAU discharged group was zero in the 30 days.  Conclusion The ASAU USS dedicated slots in University Hospital Limerick has had a significant positive impact on patient diagnostics, surgical admissions rates and streamlining resource allocation. Having dedicated slots for radiological investigations in the ASAU should become standard of care across all healthcare jurisdictions.

Delayed gastropleural fistula: a rare cause of a persistent pleural effusion after blunt force trauma.

A gastropleural fistula (GPF) is a rare pathological connection between the stomach and pleural cavity. Diagnosis and treatment are frequently delayed due to the lack of specific clinical, laboratory and radiological findings. We describe a case of a 53-year-old gentleman who presented to our institution with respiratory sepsis and a massive haemopneumothorax on imaging. Uniquely, he was discharged a week prior after a splenectomy for a traumatic fall. Gut flora in the pleural fluid and a subsequent positive dye test suggested an aero-digestive connection. Repeat imaging revealed a fistula between stomach and the left pleural cavity through a ruptured diaphragm. He underwent an open sleeve gastrectomy and primary repair of the diaphragm. This is the first GPF in literature presenting in such a fashion. Although rare, a persistent effusion with a history of blunt thoracoabdominal trauma may herald a GPF, which, if not diagnosed promptly, may result in significant morbidity.

Expression of Annexin A2 Promotes Cancer Progression in Estrogen Receptor Negative Breast Cancers.

When breast cancer progresses to a metastatic stage, survival rates decline rapidly and it is considered incurable. Thus, deciphering the critical mechanisms of metastasis is of vital importance to develop new treatment options. We hypothesize that studying the proteins that are newly synthesized during the metastatic processes of migration and invasion will greatly enhance our understanding of breast cancer progression. We conducted a mass spectrometry screen following bioorthogonal noncanonical amino acid tagging to elucidate changes in the nascent proteome that occur during epidermal growth factor stimulation in migrating and invading cells. Annexin A2 was identified in this screen and subsequent examination of breast cancer cell lines revealed that Annexin A2 is specifically upregulated in estrogen receptor negative (ER-) cell lines. Furthermore, siRNA knockdown showed that Annexin A2 expression promotes the proliferation, wound healing and directional migration of breast cancer cells. In patients, Annexin A2 expression is increased in ER- breast cancer subtypes. Additionally, high Annexin A2 expression confers a higher probability of distant metastasis specifically for ER- patients. This work establishes a pivotal role of Annexin A2 in breast cancer progression and identifies Annexin A2 as a potential therapeutic target for the more aggressive and harder to treat ER- subtype.

Patient experience in a surgical assessment unit following a closed-loop audit using a Kaizen Lean system.

BACKGROUND: The Acute Surgical Assessment Unit (ASAU) in University Hospital Limerick (UHL) has provided a solution to overcrowding and long waiting times since centralization of emergency services to UHL. Recognising the importance of its evolving role, the ASAU in UHL has recently undergone a major revamp to ease the pressure in the overcrowded emergency department (ED). This included a new purpose state-of-the-art-built unit and equipment, improved staffing levels and use of a Kaizen Lean system to identify key area of delays and inefficiency with subsequent implementation of suggestions derived after Kaizen Lean. Patient satisfaction reporting was analysed in the older building and subsequently in the new site post Kaizen Lean to complete a closed-loop audit. The aim of the study was to examine patient satisfaction response rates with the ASAU prior to and following Kaizen Lean implementation and transfer to a new purpose-built unit. METHODS: The survey comprised of two phases. In phase 1, 100 questionnaires were distributed to patients in ASAU (older building, pre-Kaizen Lean). In phase 2, the survey was repeated (100 patients) after Kaizen Lean implementation and transfer to the new state-of-the-art unit. Questionnaire design was based on WHO strategy on responsiveness measurement guidelines and was tailored to a population of surgical patients. Results were analysed using IBM SPSS, version 21 and Excel 2013. RESULTS: Two hundred questionnaires were analysed. Implementation of suggestions derived post Kaizen Lean translated into improved resource usage with reduced waiting time to be seen by nurses and doctors. Patients had better awareness about their treatment plan and planned next steps in the management. Satisfaction across different domains, perceptions of privacy and overall treatment were also improved. CONCLUSIONS: A Kaizen Lean approach improved the transition of an ASAU to a new purpose-built unit and further improved overall patient satisfaction with services of the ASAU.

Axillary ultrasound-guided core biopsy in breast cancer: identifying higher nodal burden and more aggressive clinicopathological characteristics.

BACKGROUND: Patients with sentinel lymph node (SLN) metastases may not require axillary lymph node dissection (ALND) but it remains unclear if patients with a positive ultrasound-guided axillary core biopsy (ACB) would satisfy such criteria. AIMS: The aim of this study was to assess if breast cancer patients with a positive pre-operative ACB have more aggressive tumour characteristics/higher axillary nodal burden compared to those with a positive SLN. METHODS: Data was extracted from a prospectively maintained breast cancer database between 2012 and 2015. Patients who underwent ALND after either positive ACB or SLN were included and tumour characteristics/nodal burden were compared. RESULTS: One hundred eighty patients underwent ALND, 125/180 after positive ACB and 55/180 after positive SLNB. Patients with positive ACB were more likely to undergo mastectomy (chi-square test; p = 0.03) and have higher tumour grades (Mann-Whitney test; p < 0.01) compared to the SLNB group. Median positive nodes excised during ALND were 2 (1-22) and 1 (1-11) for ACB and SLNB groups respectively (p < 0.001). Fifty-six patients received neoadjuvant chemotherapy (NCT). Of 72/125 patients in the ACB group not receiving NCT, the median number of positive nodes was 4 (range, 1-22). Ten patients within the ACB group satisfied ACOSOG Z011 criteria. CONCLUSION: Breast cancer patients with a positive ACB are more likely to have aggressive tumour characteristics and higher nodal burden compared to those identified as having axillary nodal disease on SLNB, which may affect surgical decision making.

Breast cancer and chronic pain: a mixed methods review.

BACKGROUND: More patients are surviving breast cancer; however, many complain of persistent pain, which significantly impacts on their lives. Studies have predominantly examined risk factors alone. This mixed methods study will systematically compare prospective and retrospective studies of chronic pain following breast cancer treatment. A wider scope than risk factors alone is included in a narrative review element. RESULTS: Common risk factors and themes were identified, and these were compared with some of the retrospective literature available. Several common themes arose in the literature such as common patient demographics, perioperative and postoperative management, treatment modalities and psychological factors. The variation in disease severity, treatment mode and symptom progression between participants in the studies made it difficult to draw conclusions from both the prospective and retrospective literature. CONCLUSION: Chronic pain is common after breast cancer. The literature has focused predominantly on risk factors for the development of chronic pain. It may be more beneficial to focus on chronic pain mechanisms and to consider the patient's narrative and experience of their illness and how this has impacted on the perception and intensity of persistent pain. A shared understanding between the patient and professional is likely to have more beneficial outcomes.

Deadly combination: Clostridium septicum and colorectal malignancy.

Gas gangrene is a life-threatening, necrotising soft tissue infection. Colorectal malignancy-associated Clostridiumsepticum is a rare cause of gas gangrene. This case outlines an initial presentation of colonic malignancy as gas gangrene from C.septicum infection.A 69-year-old man presented with abdominal pain, vomiting and constipation. Abdominal X-ray revealed dilated small bowel loops. Lactate was elevated. A diagnosis of small bowel obstruction was made. Subsequent CT revealed caecal thickening and subcutaneous emphysema overlying the left flank. Clinically, he became haemodynamically unstable. Examination revealed crepitus overlying the left flank in keeping with gas gangrene. The patient required immediate surgical debridement. Tissue specimens cultured C.septicum Following a complicated postoperative period, he was transferred to the plastic surgery team for further tissue debridement and reconstruction. A colonoscopy was later performed which was suspicious for malignancy. Colorectal multidisciplinary team discussion is awaited.

Extracellular matrix gene expression profiling using microfluidics for colorectal carcinoma stratification.

In cancer, biomarkers have many potential applications including generation of a differential diagnosis, prediction of response to treatment, and monitoring disease progression. Many molecular biomarkers have been put forward for different diseases but most of them do not possess the required specificity and sensitivity. A biomarker with a high sensitivity has a low specificity and vice versa. The inaccuracy of the biomarkers currently in use has led to a compelling need to identify more accurate markers with diagnostic and prognostic significance. The aim of the present study was to use a novel, droplet-based, microfluidic platform to evaluate the prognostic value of a panel of thirty-four genes that regulate the composition of extracellular matrices in colorectal carcinoma. Our method is a novel approach as it uses using continuous-flowing Polymerase Chain Reaction for the sensitive detection and accurate quantitation of gene expression. We identified a panel of relevant extracellular matrix genes whose expression levels were measured by real-time quantitative polymerase chain reaction using Taqman® reagents in twenty-four pairs of matched colorectal cancer tumour and associated normal tissue. Differential expression patterns occurred between the normal and malignant tissue and correlated with histopathological parameters and overall surgical staging. The findings demonstrate that a droplet-based microfluidic quantitative PCR system enables biomarker classification. It was further possible to sub-classify colorectal cancer based on extracellular matrix protein expressing groups which in turn correlated with prognosis.

A colonic duplication cyst causing bowel ischaemia in a 74-year-old lady.

Colonic duplication cysts are rare congenital malformations that predominantly present before the age of 2 years. We report the case of a 74-year-old lady who presented with sudden onset abdominal pain. A computed tomography scan noted a calcified structure adjacent to abnormal loops of bowel. Intraoperative findings revealed an ischaemic loop of small bowel wrapped around a mass in the mesentery adjacent to the sigmoid colon. Final histology revealed a colonic duplication cyst. Colonic duplication cysts are rare entities that most commonly cause obstruction or perforation. We present the very rare case of a colonic duplication cyst causing bowel ischaemia in an elderly female.

Real-time cell analysis of the inhibitory effect of vitamin K2 on adhesion and proliferation of breast cancer cells.

Breast cancer is the most prevalent cancer type worldwide. Continued efforts to improve treatment strategies for patients with breast cancer will be instrumental in reducing the death rates associated with this disease. In particular, the triple-negative breast cancer subtype of breast cancer has no targeted therapy available so it is essential to continue to work on any potential therapies. Vitamin K (VK) is known for its essential role in the clotting cascade. The antitumor properties of VK derivatives have been reported in both hepatocellular carcinoma and glioblastoma. Our hypothesis was that menaquinone-4, the most common form of vitamin K2 (VK2), is an effective anticancer agent against breast cancer cell types. In this study, we used a novel impedance-based live cell monitoring platform (xCELLigence) to determine the effects of VK derivatives on the triple-negative breast cancer cell line, MDA-MB-231, and the HER2+ breast cancer cell line, MDA-MB-453. Cells were treated with varying concentrations of menaquinone-4 (VK2) previously reported to have an antiproliferative effect on human glioblastoma cells. After initial testing, these concentrations were adjusted to 100, 125, and 150 µmol/L. A significant dose-dependent, growth inhibitory effect was found when cells were treated at these concentrations. These effects were seen in both adhesion and proliferation phases and show a dramatic reduction in cell growth. Additional analysis of MDA-MB-231 cells treated with VK2 (100 µmol/L) in combination with a low-glucose nutrient media showed a further decrease in adhesion and viability. This is the first study of its kind showing the real-time effects of VK derivatives on breast cancer cells and suggests that dietary factors may be an important consideration for patients.

Colonic perforation in Behcet's syndrome.

A 17-year-old gentleman was admitted to our hospital for headache, the differential diagnosis of which included Behcet's syndrome (BS). He developed an acute abdomen and was found to have air under the diaphragm on erect chest X-ray. Subsequent laparotomy revealed multiple perforations throughout the colon. This report describes an unusual complication of Behcets syndrome occurring at the time of presentation and a review of the current literature of reported cases.

Current status of combined hormone replacement therapy in clinical practice.

Approximately 20 million women worldwide use hormone replacement therapy (HRT). Formerly, it was thought to confer beneficial cardiac protection and reduce osteoporosis in addition to relieving the symptoms of menopause. However, many recent trials have contradicted these beliefs. The risk of breast cancer associated with HRT use has been well documented but underestimated. Many recent trials have reported higher than expected breast cancer incidence rates, particularly associated with combined HRT. Although it was believed estrogen conferred cardiac protection and reduced the incidence of myocardial ischemic events and cerebrovascular accidents, the more recent literature indicates that this is not true and that HRT users have a higher risk of cardiac and cerebral events. The role of HRT in clinical practice has been redefined. It is no longer an acceptable form of treatment for most women. The evidence indicates that the use of long-term HRT is no longer clinically justifiable.

Vaginal herniation: case report and review of the literature.

OBJECTIVE: The purpose of this study was to discuss the treatment of a case of spontaneous intestinal herniation per vagina in a patient who had undergone previous transabdominal hysterectomy and to review the related literature. STUDY DESIGN: A computer-based search of the English literature from January 1900 to October 2004 with the use of the terms vaginal herniation, vaginal evisceration, and vaginal trauma/injury was performed. Causes, presentation, and treatment were discussed and compared with a recent case that was treated locally in our hospital. RESULTS: Vaginal evisceration was described in the literature as early as 1864; since then <100 cases have been reported in the literature. It is more common in menopausal women with previous hysterectomy pelvic or vaginal surgery. Vaginal trauma, as in rough coitus, instrumentation, obstetric injury, is a recognized cause in premenopausal women. CONCLUSION: Vaginal evisceration is a rare, distressing emergency that requires aggressive resuscitation and urgent surgical intervention.