Gestational gigantomastia complicated by pseudo-angiomatous stromal hyperplasia - a multidisciplinary management approach.

SUMMARY: Gestational gigantomastia is a rare condition typified by disproportionate bilateral breast enlargement in pregnant women, resulting in skin thinning, ulceration, and bleeding. Less than sixty cases have been documented worldwide, and only one other in South Africa. Pseudo-angiomatous stromal hyperplasia (PASH) is a rare benign proliferation of stromal tissue in a tumorous or diffuse pattern. This, to the best of our knowledge, is the first published case, a 27-year-old human immunodeficiency virus (HIV) positive woman, to present with both conditions concurrently. Medical management with cabergoline was initiated and, seven months post-delivery, a novel Goldilocks mastectomy was performed with acceptable outcomes.

Review: Endometrial function in pregnancy establishment in cattle.

The endometrium is fundamentally required for successful pregnancy in ruminants and species where the posthatching conceptus undergoes a protracted elongation and peri-implantation phase of pregnancy. Moreover, there are substantial waves of pregnancy loss during this pre- and peri-implantation period of pregnancy the precise source of which has not been clearly defined i.e., the maternal uterine contribution to this loss. Understanding the molecular interactions required for successful pregnancy in cattle will allow us to intervene to support pregnancy success during this vulnerable window. The endometrium contributes to most key developmental milestones of pregnancy establishment, including (1) contributing to the regulation of the oestrus cycle, (2) nourishing the preimplantation conceptus, (3) responding to the conceptus to create a more receptive microenvironment, (4) providing essential biophysical support, and (5) signalling and producing factors which affect the mother systemically. This review will summarise what we currently know about conceptus-maternal interactions as well as identify the gaps in our knowledge that could be filled with newer in vitro model approaches. These include the use of microfluidics, organ-on-a-chip devices, and bioinformatic approaches. This will help maximise food production efficiency (both meat and dairy) and decrease the environmental burden, while enhancing our understanding of the fundamental processes required for successful implantation in cattle.

Retroperitoneoscopic adrenalectomy - introducing a new surgical technique in South Africa.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy (PRA) is purported to be superior to the laparoscopic transperitoneal approach (LA) in patients with a select spectrum of benign adrenal pathologies. Advantages attributed to the technique include minimal blood loss, shortened operative times, and decreased postoperative pain, explained anatomically by the direct access to the adrenal gland. Reduced workspace is a limitation. METHODS: A retrospective review of 22 consecutive PRAs performed in a single centre between 1 September 2016 and 30 October 2020 is presented. Two experienced laparoscopic surgeons operated on all patients after acquiring the technique at international centres. Suitable candidates were carefully pre-selected. Non-benign pathology, high vascularity, body mass index (BMI) ≥ 45 kg/m2 and anatomical concerns on prior computed tomography (CT) imaging were exclusion criteria. RESULTS: Twenty-two PRAs were performed for a spectrum of benign adrenal pathologies. Twenty-one surgeries (95%) were completed. A single case of pheochromocytoma required conversion. The procedure was safe, a minor postoperative complication (pneumaturia) occurred in one case, and the mortality rate was 0%. Median operative time (80 minutes) is comparable to other reported series in the literature, with a modest linear descending tendency noted over the study period. Underlying pathology influenced operative times. Pheochromocytomas proved to be most challenging and required careful preoperative evaluation. CONCLUSION: The PRA procedures performed at Tygerberg Academic Hospital were safe and reproducible in a select group of cases with benign adrenal pathology. Endocrine surgeons proficient with laparoscopic techniques should be encouraged to use the PRA approach when encountering adrenal neoplasms that fit the criteria.

A comparison of invasive lobular carcinoma with other invasive breast cancers at Tygerberg Academic Hospital.

BACKGROUND: The second most common histological subtype of invasive breast carcinoma is invasive lobular carcinoma (ILC) occuring with a frequency 10-15% in Western countries and approximately 5%, in Africa, the Middle East and Asia (AMA). Combined hormone replacement therapy (CHRT) is a risk factor for the development of ILC which is infrequently diagnosed at our centre.This study aimed to investigate the incidence and clinicopathological characteristics of ILC as compared to invasive breast carcinoma of no special type (IBC-NST). METHODS: Clinical and pathological data on breast carcinoma patients attending the breast and endocrine unit at Tygerberg Academic Hospital since 2017 have been recorded on a Stellenbosch University REDCap® database. RESULTS: IBC-NST was the most frequent subtype diagnosed (83.9%) and ILC the second most common subtype (5.2%). Most ILCs were of luminal B intrinsic subtype, and the median size was slightly smaller than IBC-NST. There were significantly more grade 2 ILCs than IBC-NSTs (81.5% vs 50.9%). There was no statistical difference between stage and histological subtype. CONCLUSION: ILC has clinicopathological differences when compared to IBC-NST, although these were less pronounced in this study. The prevalence of ILC was similar to numbers reported in AMA. We hypothesise that there may be a discrepancy in the prevalence of ILC between public and private healthcare systems in South Africa, and that it may be due to differing trends in prescribing CHRT.

Impact of a multidisciplinary approach to ultrasound- guided thyroid fine-needle aspiration biopsy at Tygerberg Hospital, Cape Town, South Africa: A retrospective audit.

BACKGROUND: Thyroid nodules are common and mostly benign. Inadequate sampling generally occurs in 13 - 17% of thyroid fine-needle aspiration biopsies (FNABs), but the proportion was found to be as high as 45% on evaluating 100 ultrasound (US)-guided FNABs in a previous unpublished audit at Tygerberg Hospital, Cape Town, South Africa (SA). OBJECTIVES: Primary aim: To determine the diagnostic yield of US-guided thyroid biopsy after implementing changes to existing practices, involving the creation of a specialised clinic and applying protocols for referral and FNAB. Secondary aim: To compare the results with other centres in SA. METHODS: A retrospective audit of 178 thyroid biopsies was conducted. All US-guided thyroid biopsies performed in the specialised clinic between January 2017 and July 2018 were included. Data were analysed using descriptive statistics. RESULTS: The 178 nodules were biopsied in 159 patients. The mean age was 53.7 years, with a gender ratio of 9.6:1 (female/male). A reduction in non-diagnostic biopsies was noted compared with the historical cohort (45% v. 32.6%). Sixty-one nodules (34.3%) had previously been biopsied with inadequate cytology results. When repeat biopsies were excluded, only 16.2% (n=19) were classified as insufficient. CONCLUSIONS: These findings illustrate the importance of the multidisciplinary approach and standardisation of the US-guided biopsy procedure and the value of consistency and quality control in a health system. While nodular thyroid disease is common and FNAB is relatively simple, early referral to a central specialised unit to minimise the incidence of inadequate FNAB should be considered.

Symptomatic hepatothorax presenting 25 years after penetrating thoracoabdominal injury.

Hepatic herniation through the diaphragm is a rare finding. It generally occurs due to a congenital diaphragmatic abnormality or blunt trauma resulting in a diaphragmatic defect. Making the diagnosis is difficult, as there are few definitive clinical signs and chest radiograph (CXR) findings may be non-specific. To our knowledge, only a single case report exists of penetrating right diaphragm injury leading to hepatic herniation. A 42-year-old man presented to the emergency department of a regional hospital with hyperglycaemia and exertional dyspnoea. He was diagnosed with diabetes mellitus type 2. He gave a history of smoking for 15 pack-years, was negative for retroviral disease and had no history of pulmonary tuberculosis. He had no significant surgical history but reported being stabbed with a knife in 1995. The point of entry was below the level of the nipple in the right anterior axillary line. At the time, he was treated with an intercostal drain and discharged home. CXR showed a right-sided chest mass. We considered a differential diagnosis of pulmonary consolidation, diaphragm eventration or hepatothorax. Computerized tomography of the chest and abdomen demonstrated apparent intrathoracic extension of the right liver lobe and partial attenuation of the superior vena cava and right atrium due to a mass effect. The upper border of the liver abutted the aortic arch. Surgical treatment options were discussed. The patient declined surgery and will be followed up as an outpatient.

Assessment of the delayed repair of uncomplicated inguinal hernias in infants.

BACKGROUND: Potential strangulation of infant inguinal hernias is the main indication for their urgent repair. Lack of theatre time delays repair and prolongs hospitalisation. We report a series of patients with uncomplicated hernias who were discharged home to have their elective surgery at a later stage and assessed the outcomes of this approach. METHODS: A retrospective audit was performed of all infants with an inguinal hernia from January 2010 to June 2015. Incomplete records and infants operated after their first birthday were excluded. Two groups were identified; immediate surgery for infants with uncomplicated hernias, and delayed surgery for infants with uncomplicated hernias. Incarceration/strangulation rates in the interim period were documented for the delayed group, and comparison made between the groups regarding perioperative and anaesthetic complications and length of postoperative hospital stay. RESULTS: The mean time delay between diagnosis and repair was 8.78 weeks. None of the hernias in the delay group strangulated while awaiting repair. There was no significant difference in the perioperative complications between the two groups. Out of the 70 cases in the immediate repair group, there was 7 (10%) surgical and 4 (5.7%) anaesthetic complications. The delayed group (169 infants) had 8 (4.7%) surgical and 6 (3.6%) anaesthetic complications. The incarceration rate after being discharged home was 4.1%. This group of infants had no anaesthetic or surgical complications. Length of hospital stay postoperatively was 1.43 days in the immediate group and 1.3 in the delayed group (p = .485). CONCLUSION: Delayed repair, up to 2 months later, for uncomplicated infant hernia carries a small risk of incarceration but does not increase the rate of strangulation or other complications.

Gastrointestinal infections caused by consumption of raw drinking milk in England & Wales, 1992-2017.

Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003-2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.

Lymph node harvest in breast cancer patients with and without preoperative scintigraphy

Background: Sentinel lymph node biopsy (SLNB) is the standard of care for women with node negative breast cancer. Tc99 nanocolloid is a popular tracer, facilitating preoperative lymphoscintigraphy to identify sentinel nodes. This study compares the number of sentinel lymph nodes identified at the time of surgery in women who had lymphoscintigraphy with those who did not.Method: All women with primary breast cancer undergoing a SLNB from 2003­2017 who were node negative and did not have neoadjuvant chemotherapy were retrospectively reviewed in this study.Results: 576 women who had Tc99 preoperative injection were included in the study. Three hundred patients (Group 1) underwent lymphoscintigraphy preoperatively and 276 (Group 2) had no lymphoscintigraphy. The mean age at diagnosis for Groups 1 and 2 were 56 and 58 years, respectively. Both groups were also found to be similar in terms of histological subtype, tumour location, size, and HER2- and Estrogen receptor (ER) status. The surgery for the breast primary was similar in groups 1 and 2. While both groups had a median number of 2 nodes identified, the mean number of nodes identified for Group 2 (2.12) was 10% higher than for Group 1 (1.92) (p = 0.0026).Conclusion: This is the largest series to show that a preoperative lymphoscintigram (scan) can safely be omitted when performing a SLNB. As newer tracers are being used (e.g. Iron Oxide), it is important to know that accuracy of SLNB is not compromised by omission of a scan

A survey of staffing levels in paediatric diabetes services throughout the UK.

AIMS: To assess staffing levels of healthcare professionals involved in the care of children and young people with diabetes in the UK. METHODS: A web-based questionnaire was distributed to lead consultant paediatricians from all paediatric diabetes services in the UK between October and December 2014. Data on staffing levels and other aspects of diabetes services were collected and differences between the four nations of the UK and across the 10 English diabetes networks were explored. RESULTS: Some 175 services (93%) caring for 29 711 children and young people aged ≤ 24 years with diabetes participated in the survey. Northern Ireland and Wales had the lowest ratio of total staff to patient population. Nursing caseloads per one whole-time equivalent (WTE) nurse ranged from 71 patients in England to 110 patients in Northern Ireland with only 52% of the UK services meeting the Royal College of Nursing recommended nurse-to-patient ratio of > 1 : 70. Scotland and Northern Ireland had the highest ratio of consultants and fully trained doctors per 1000 patients (3.5 WTE). Overall, 17% of consultants had a Certificate of Completion of Training in Endocrinology and Diabetes. Some 44% of dietitians were able to adjust insulin dose. Only 43% of services provided 24-h access to advice from the diabetes team and 82% of services had access to a psychologist. Staffing levels adjusted for volume were not directly related to glycaemic performance of services in England and Wales. CONCLUSIONS: Wide variations in staffing levels existed across the four nations of the UK and important gaps were present in key areas.

Hypercholesterolaemia screening in Type 1 diabetes: a difference of opinion.

AIM: To assess cholesterol screening of children with Type 1 diabetes by diabetes professionals using a survey of current practice, given that National Institute of Health and Care Excellence guidelines on childhood Type 1 diabetes do not recommend cholesterol screening, yet the National Paediatric Diabetes Audit has an annual cholesterol measure (> 12 years) as a key outcome indicator. METHODS: An online survey was sent to 280 members of the Association of Children's Diabetes Clinicians to assess cholesterol screening practice in children. RESULTS: A total of 87 diabetes professionals (31%) responded. The results showed that 94% of respondents measured cholesterol, 33% did this annually on all children, and 7% measured fasting cholesterol. A total of 63% used no guidelines to decide treatment or further investigation. The definition of 'high' cholesterol varied from > 4.5 to > 8 mmol/l, with 40% giving no response or specific level. Only 14% of clinicians had started statin therapy in their diabetes clinic in the previous 5 years. CONCLUSION: Whilst the majority of diabetes professionals measured cholesterol in children with Type 1 diabetes, there was marked variability in sampling, in children screened and in action taken if levels were considered abnormal. It is debatable whether cholesterol measures should be undertaken, certainly more than once, and whether cholesterol level should feature as a key outcome in the national audit in future.

Diabetic ketoacidosis in an adolescent and young adult population in the UK in 2014: a national survey comparison of management in paediatric and adult settings.

AIMS: To assess the management of diabetic ketoacidosis in young people, which differs in the UK between paediatric and adult services, and to evaluate outcomes and extent to which national guidelines are used. METHODS: A standardized questionnaire was sent to all paediatric and adult diabetes services in England, requesting details of all diabetic ketoacidosis admissions in young people aged > 14 years in paediatric services ('paediatric' patients), and in young adults up to the age of 22 years in adult services ('adult' patients). RESULTS: A total of 64 adult patients aged ≤ 22 years (mean age 19.2 years) were reported, of whom seven were aged between 10 and 16 years. A total of 71 paediatric patients were reported [mean (range) age 14.9 (11-18) years]. We found that 85% of paediatric and 69% of adult patients were treated according to national guidelines, 99% of paediatric and 89% of adult patients were treated with 0.9% saline and fixed-rate insulin infusions and 16% of adult patients received an insulin bolus. Insulin treatment was initiated later in paediatric patients than in adult patients (100 vs 39 min; P < 0.001). In 23% of adult patients and 8.8% of paediatric patients, potassium levels were < 3.5 mmol/l (P < 0.005). The lowest mean potassium levels were 3.8 mmol/l in paediatric and 3.5 mmol/l in adult patients (P < 0.005). Hypoglycaemia occurred in 42.3% of paediatric and 36% of adult patients. Time to resolution was similar in paediatric and adult patients (16.0 vs 18.2 h), as was duration of hospital stay (2.35 vs 2.53 days). CONCLUSIONS: Young people were treated according to national guidelines, but the quality of monitoring was variable in both paediatric and adult settings. The incidence of hypoglycaemia and hypokalaemia was unacceptably high.

A multi-country Salmonella Enteritidis phage type 14b outbreak associated with eggs from a German producer: 'near real-time' application of whole genome sequencing and food chain investigations, United Kingdom, May to September 2014.

We report an outbreak of Salmonella Enteritidis phage type 14b (PT14b) in the United Kingdom (UK) between May and September 2014 where Public Health England launched an investigation to identify the source of infection and implement control measures. During the same period, outbreaks caused by a Salmonella Enteritidis strain with a specific multilocus variable-number tandem repeat analysis (MLVA) profile occurred in other European Union Member States. Isolates from a number of persons affected by the UK outbreak, who had initially been tested by MLVA also shared this particular profile. Cases were defined as any person infected with S. Enteritidis PT14b, resident in England or Wales and without history of travel outside of this geographical area during the incubation period, reported from 1 June 2014 onwards, with a MLVA profile of 2­11­9-7­4-3­2-8­9 or a single locus variant thereof. In total, 287 cases met the definition. Food traceback investigations in the UK and other affected European countries linked the outbreaks to chicken eggs from a German company. We undertook whole genome sequencing of isolates from UK and European cases, implicated UK premises, and German eggs: isolates were highly similar. Combined with food traceback information, this confirmed that the UK outbreak was also linked to a German producer.

The challenges of managing breast cancer in the developing world - a perspective from sub-Saharan Africa.

Communicable diseases are the major cause of mortality in lower-income countries. Consequently, local and international resources are channelled mainly into addressing the impact of these conditions. HIV, however, is being successfully treated, people are living longer,and disease patterns are changing. As populations age, the incidence of cancer inevitably increases. The World Health Organization has predicted a dramatic increase in global cancer cases during the next 15 years, the majority of which will occur in low- and middle-income countries. Cancer treatment is expensive and complex and in the developing world 5% of global cancer funds are spent on 70% of cancer cases. This paper reviews the challenges of managing breast cancer in the developing world, using sub-Saharan Africa as a model.

Identifying targets to reduce the incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in the UK.

BACKGROUND: Diabetic ketoacidosis (DKA) is the leading cause of mortality in childhood diabetes, and at diagnosis might represent delayed presentation. The extent and reasons for delays are unclear, but identifying and targeting factors associated with DKA could reduce this incidence. OBJECTIVE: To compare the patient pathway before diagnosis of type 1 diabetes mellitus (T1DM) in children presenting with DKA and non-acidotic hyperglycaemia. DESIGN, SETTING AND PATIENTS: Over a 3-month period, children newly diagnosed with T1DM were identified on admission to UK hospitals. Parents and medical teams completed a questionnaire about events before diagnosis. RESULTS: Data were available for 261 children (54% male), median age 10.3y (range 0.8-16.6 y). 25% presented with DKA, but more commonly in children <2y (80% vs 23%, p<0.001). Fewer children with DKA reported polyuria (76% vs 86%) or polydipsia (86% vs 94%) (both p<0.05), but more reported fatigue (74% vs 52%) and weight loss (75% vs 54%) (both p<0.01). 24% of children had multiple healthcare professional (HCP) contacts, and these children had lower pH on admission. 46% of children with a delayed presentation to secondary care had non-urgent investigations. 64% of parents had considered a diagnosis of diabetes, and these children were less likely to present with DKA (13% vs 47%, p<0.001). CONCLUSIONS: Multiple HCP contacts increased risk of presentation in DKA, whereas, parental awareness of diabetes was protective. Improved public and health professional education targeting non-classical symptoms, awareness of diabetes in under 2 y, and point-of-care testing could reduce DKA at diagnosis of diabetes.

Wigner-Poisson statistics of topological transitions in a Josephson junction.

The phase-dependent bound states (Andreev levels) of a Josephson junction can cross at the Fermi level if the superconducting ground state switches between even and odd fermion parity. The level crossing is topologically protected, in the absence of time-reversal and spin-rotation symmetry, irrespective of whether the superconductor itself is topologically trivial or not. We develop a statistical theory of these topological transitions in an N-mode quantum-dot Josephson junction by associating the Andreev level crossings with the real eigenvalues of a random non-Hermitian matrix. The number of topological transitions in a 2π phase interval scales as √[N], and their spacing distribution is a hybrid of the Wigner and Poisson distributions of random-matrix theory.