The spectrum of male breast disease at Charlotte Maxeke Johannesburg Academic Hospital - a 3-year retrospective review.

BACKGROUND: The spectrum of male breast disease (MBD) and its relative proportions is not well documented. This study aims to describe the demographics, clinical, radiological and histopathological characteristics of the spectrum of MBD managed at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). METHODS: This is a retrospective, descriptive study of all male patients diagnosed with MBD at CMJAH between 1 January 2016 and 31 December 2018. Patients' data were extracted from the Breast Imaging Department, CMJAH Breast Clinic and the National Health Laboratory Services patients' records. Data collected included patients' demographics, clinical presentation, radiological findings and histopathological diagnosis, where available. The collected data were captured using REDCap™ and were analysed using Statistica 13 and SAS version 9.2. P-value of 0.05 was used for statistical significance. RESULTS: Of the 269 males imaged, 244 (91%) had a diagnosed breast condition, 90% of which were benign. Gynaecomastia accounted for 85% of all breast disease diagnosed. Patients who presented with benign breast disease were significantly younger than those with malignant breast disease, with a mean age of 45.59 years vs 58.29 years (p = 0.0007). Seventyone per cent of patients had a known HIV status with 39% being HIV positive. There was a significant association between patients with HIV and benign breast disease (p = 0.0129). CONCLUSION: Gynaecomastia is the most common MBD seen at CMJAH. There was a significant association between HIV and benign breast disease. This association should be explored further with respect to the direct effects of the virus and to those of the antiretroviral medication.

Unusual histopathologies of the appendix.

INTRODUCTION: Appendicitis is the most common surgical emergency. Most commonly it is a result of luminal occlusion that leads to ischaemia and eventually to perforation with resultant localised or diffuse peritonitis. Unusual causes have been documented including viral infections, parasites, tuberculosis and neoplasms. These conditions are important to recognise, as they may need additional specific management. This study endeavours to identify the incidence and type of unusual histopathology of appendicitis. METHOD: A retrospective review of histopathological reports of appendix specimens obtained during appendectomies done between January 2012 and December 2014 in the three academic hospitals of Johannesburg - Chris Hani Baragwanath Academic Hospital (CHBAH), Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), and Helen Joseph Hospital (HJH). All specimens were examined by pathologists of the National Health Laboratory Services (NHLS). RESULTS: A total of 2 408 histopathology results were obtained from the NHLS. 164 specimens were excluded because they were part of colonic resection for unrelated conditions. Of the 2 244 specimens included, 8.1% were normal, 52.7% showed acute appendicitis and 30.1% showed complicated appendicitis. Unusual pathology comprised 5.3% (119/2 244). The median age of all patients was 25.6 years (0-88yrs) and the gender distribution was 61.9% males and 38.1% females. The most common unusual causes were parasites (37%), mainly schistosomiasis (24.3%), followed by neoplasm (20%) and fibrous obliteration (14.2%). CONCLUSION: All appendectomy specimens must be submitted to the pathologist for histological diagnosis. It is important that the result be checked before the patient is discharged as further specific treatment may be indicated.

A prospective study of receptor profiles in breast cancer and the ipsilateral axillary lymph node metastases measured simultaneously in treatment naïve cases.

BACKGROUND: The heterogeneity of receptor profiles in breast cancer is well known. The differing receptor profiles of primary breast cancer and nodal metastases have been investigated and found to range between 10-50% depending on the hormone receptor tested. A study comparing the hormone status of primary breast cancers and the synchronous ipsilateral involved sentinel lymph node has not been performed in a South African population. METHOD: This is a prospective study where two specialist radiologists performed the simultaneous core needle biopsies of the primary breast cancer and the clinically positive axillary nodes. All receptor status analysis was conducted by one specialist histopathologist. RESULTS: Of 141 patients who gave written informed consent for this study, 29 were excluded; 112 patients met the inclusion criteria. Anonymised demographics of age, clinical stage, HIV status and metastatic screening were recorded. The simultaneous biopsies and receptor measurements identified 10 patients with discordant receptor status in the positive axillary lymph nodes. In each case, the receptor profile of the axillary lymphatic metastases was more aggressive than that of the primary tumour. The luminal A subtype had a significantly greater risk of discordance than other subtypes (p = 0.02). CONCLUSION: Core needle biopsy and receptor analysis should be considered on the positive axillary nodes in breast cancer patients. Adjuvant treatment should be targeted to the receptor profile of the lymph node metastases.

Axillary lymph node dissection for patients with invasive breast cancer at Charlotte Maxeke and Chris Hani Baragwanath Academic Hospitals.

BACKGROUND: The extent of axillary surgery correlates with its morbidity and sentinel lymph node biopsy (SLNB) has become the standard of care in clinically node-negative (cN0) patients.This study aims to evaluate the application of SLNB and axillary lymph node dissection (ALND) and the associated risk factors for node-negative ALND in our units. METHODS: We included female patients with primary breast cancer who underwent axillary surgery in the breast units at Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital from March 2013 to March 2015. Univariate and multivariable logistic regression models were used to determine factors associated with pathological node-negative (pN0) ALND. RESULTS: 505 patients were included and 344 patients were staged clinically node-positive (68.1%), 161 (31.9%) were assessed as clinically node-negative and deemed eligible for SLNB. Sensitivity of clinical nodal staging was 85.9% with a positive predictive value of 76.5%. The majority of patients (313, 61.9%) underwent primary surgery while 192 (38.1%) underwent surgery after NACT. We performed 118 SLNBs and 387 ALNDs of which 97 were pathologically node-negative. Risk was not increased after NACT (OR 1.06, p = 0.790). We identified a significant risk in patients with triple-negative and HER-2 enriched subtypes compared to hormone receptor-positive patients (OR 3.05, 95% CI: 1.6-5.7, p = 0.001 and OR 2.25, 95% CI: 1.1-4.8, p = 0.035). CONCLUSION: The prevalence of pN0 ALND was 25.06%. In our cohort a significantly higher risk was found in hormone receptor-negative tumours. Preoperative nodal assessment needs to be optimised and include pathological confirmation. SLNB needs to be extended to patients after NACT despite resource-constraints.

"The profile of thyroid cancer in patients undergoing thyroidectomy at Chris Hani Baragwanath Academic Hospital.

BACKGROUND: The histological type of thyroid cancer in well-resourced countries is predominantly papillary. Follicular carcinoma is predisposed by iodine deficiency that was present the Black population of South Africa until salt iodination in 1995. The aim of this study was to analyse the profile of thyroid cancer in Black South Africans from January 2001 to December 2017 and to identify any temporal changes in thyroid cancer histological subtypes since salt iodination. METHOD: Histopathological reports of patients who underwent thyroidectomy for cancer at Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between January 2001 and December 2017 were retrospectively assessed. Data captured included name, age, gender, race, the date when the specimen was sent and the detailed histopathological report. RESULTS: Of the 143 thyroidectomies performed for malignancy, papillary thyroid cancer was the predominant type (65%) with a papillary to follicular thyroid cancer ratio of 4:1. Follicular, medullary and anaplastic cancers were 16.8%, 9.8% and 2.8% respectively. The reports were incomplete in 5 cases and there were 3 non-epithelial neoplasms. CONCLUSION: There is a gradual temporal increase in the frequency of resected papillary cancer over a 16 year period while follicular has remained static. These changes may be attributable to better salt iodination.

An overview of risk factors for recurrent breast cancer.

The multidisciplinary management of Breast Cancer (BC) has evolved over the past 50 years: the patient is offered a choice of surgical procedures with or without radiation therapy, cytotoxics and treatments targeting the nuclei of the cancer cells. This has resulted in a reduction of disease recurrence and a significant increase in 5-year survival. But these good results deteriorate over time and almost 20% women with early stage, oestrogen-receptor (ER) positive BC will suffer recurrent cancer at 10 years. The aim of this review is the identification of risk factors for the recurrence of BC, to examine pathogenic pathways leading to BC and to report on modifications to lifestyle, surgical procedures and treatment regimes which can reduce the recurrence of BC. Patient factors associated with increased risk included the extremes of age, ethnicity, genetic inheritance obesity and alcohol ingestion. Human Immunodeficiency Virus (HIV) was not identified as a cause of BC. Treatment-related factors included microscopically positive excision margins, delay in initiation of adjuvant chemoradiation and lack of compliance with endocrine therapy. Reclassifying BC according to molecular subgroups more accurately identifies patients at risk for recurrence and aids in the appropriate selection of therapy targeted to the primary and lymphatic metastases.

The role of Ki-67 in breast cancer.

The proliferative marker, Ki-67, is a human nuclear antigen, and forms an integral part of cell division in both normal and malignant tissue. Since the hallmark of cancer is uncontrolled and relentless cell proliferation, the Ki-67 proliferative index is increasingly used to assess and manage breast cancer. The value of Ki-67 as a prognostic indicator, a guide to the selection of therapy, and a method of measuring response to ongoing treatment, is examined in this review.

Sentinel lymph node biopsy in breast cancer - a learning curve : general surgery

The strongest predictor of recurrence versus survival in women with breast cancer is the presence or absence of lymph node metastases.1 Regional nodal status can be accurately predicted by identification and examination of the sentinel lymph node (SLN). If the SLN shows no evidence of tumour it is over 90certain that the remaining regional lymph nodes are negative.2 The use of sentinel lymph node direction (SLND) in early breast cancer can spare patients with node-negative disease the adverse effects of complete axillary lymph node dissection (ALND). In this study; an initial experience of 30 women with early stage breast cancer and clinically negative nodes who underwent SLN mapping followed by ALND is presented. The success and failure of vital blue dye and lymphoscintigraphic technique to identify the SLN are examined. Features of the breast cancers which can result in false-negative results are discussed. Based on this initial experience with SLN biopsy recommendations are made which may help to shorten the learning curve for this technique

Fractionated high dose rate intraluminal brachytherapy in palliation of advanced esophageal cancer.

PURPOSE: To optimize the dose of fractionated brachytherapy for palliation of advanced esophageal cancer. METHODS AND MATERIALS: One hundred and seventy-two patients with advanced esophageal cancer were randomized to receive 12 Gy/2 fractions (group A); 16 Gy/2 fractions (group B), and 18 Gy/3 fractions (group C) by high dose rate intraluminal brachytherapy (HDRILBT). Treatment was given weekly and dose prescribed at 1 cm from the source axis. Patients were followed up monthly and assessed for dysphagia relief and development of complications. RESULTS: Twenty-two patients died before completing treatment due to advanced disease and poor general condition. The overall survival was 19.4% at the end of 12 months for the whole group (A--9.8%, B--22.46%, C--35.32%; p > 0.05). The dysphagia-free survival was 28.9% at 12 months for the whole group (A--10.8%, B--25.43%, C--38.95%; p > 0.05). Forty-three patients developed fibrotic strictures needing dilatation (A--5 of 35, B--15 of 60, C--23 of 55; p = 0.032). Twenty-seven patients had persistent luminal disease (A--11, B--6, C--10), 15 of which progressed to fistulae (A--7, B--2, C--6; p = 0.032). There was no effect of age, sex, race, histology, performance status, previous dilation, presenting dysphagia score, presenting weight, grade, tumor length, and stage on overall survival, dysphagia-free, and complication-free survival (p > 0.05). On a multivariate analysis, brachytherapy dose (p = 0.002) and tumor length (p = 0.0209) were found to have a significant effect on overall survival; brachytherapy dose was the only factor that had an impact on local tumor control (p = 0.0005), while tumor length was the only factor that had an effect on dysphagia-free survival (p = 0.0475). When compared to other forms of palliation currently available (bypass surgery, laser, chemotherapy, intubation, external radiotherapy), fractionated brachytherapy gave the best results with a median survival of 6.2 months. CONCLUSIONS: Fractionated brachytherapy is the best modality for palliation of advanced esophageal cancer. It offers the best palliation to patient when compared to all other modalities currently available. The optimal brachytherapy dose ranges between 16 Gy in two fractions and 18 Gy in three fractions given a week apart.

Internal jugular vein thrombosis following functional neck dissection.

Twenty-five patients on whom 27 functional neck dissections were performed for upper aerodigestive tract squamous carcinoma were prospectively investigated to determine the frequency of venous thrombosis on the side of the neck dissection. Retrograde venography, performed within 1 month postoperatively, was used to determine the status of the internal jugular vein. Nineteen veins were patent at venography, but ipsilateral occlusion was demonstrated in 8. In 5 of the 8 patients, venous thrombosis followed major wound sepsis or fistula formation. No causes for the remaining 3 cases of internal jugular vein thromboses were identified. Possible mechanisms for "spontaneous" internal jugular vein occlusion following functional neck dissection are endothelial trauma, reduction in venous flow during anesthesia, and the altered coagulability profile of some cancer patients. The finding that functional neck dissection does not always maintain patency of the internal jugular vein is especially important when surgical treatment to the opposite side of the neck is planned, as the surgeon may be faced with an unexpectedly complicated postoperative course.

Tumour kinetics in breast cancer.

In vivo bromodeoxyuridine was used to measure the 'bromo' labelling index (LI,%), the duration of the S-phase (Ts, hours) and the potential tumour doubling time (Tpot, days) in women with stages I-IV breast cancer. These were studied in relation to lymph node status, tumour size, histological grade, oestrogen receptor status (ER), ploidy and S-phase fraction (SPF). In our patients, a LI of 10%, a Tpot of 2 days or an SPF of 9-10.5% predicted aggressive breast cancer. The LI was significantly higher (5%) in ER-negative than in ER-positive (2%) tumours (P = 0.03). There was a trend towards increased DNA synthesis in cancers with an SPF over 10% (P = 0.08). ER-negative breast cancers over 2 cm in diameter had shorter median Tpots of 5.3 days (P = 0.02) and 8 days (P = 0.05) compared with smaller, ER-positive tumours. A trend towards faster growth rates was seen in lymph node-positive, high-SPF (> 10%) breast cancers. Tumour kinetics may have additional prognostic value in the selection of node-negative patients for adjuvant therapy.

Risk factors for complications after thyroid surgery.

Data on 60 patients who underwent thyroid surgery were retrospectively reviewed. The clinicopathological data were compared with the occurrence of the complications of recurrent laryngeal nerve palsy, hypocalcaemia and laryngeal oedema. Age, pressure symptoms and types of pathology were not associated with complications. Large glands and radiological evidence of a compressed trachea were statistically significant risk factors for postoperative complications.

Primary malignant melanoma of the oesophagus. Report of a case with flow cytometric DNA analysis.

Primary malignant melanoma is a very rare tumour of the oesophagus, and although this is the first case reported in a black patient in South Africa, the clinical, radiographic and histopathological features were characteristic of this malignancy. Primary oesophageal melanoma is a highly lethal tumour--fewer than 2% of patients are surviving 5 years after diagnosis. Flow cytometric DNA analysis of the resected specimen in this case revealed two populations of malignant cells, one of which had grossly abnormal DNA. Existence of two clones of malignant melanoma cells supports the observations that this tumour is biologically aggressive, radioresistant and almost always incurable.

Pancreatic leiomyosarcoma. A case report.

The pancreas is an unusual site for leiomyosarcoma. Only 12 such cases have previously been reported. A case of pancreatic leiomyosarcoma in a 68-year-old man is presented and the diagnostic dilemma and management of such a tumour are discussed.

Phaeochromocytoma. A report of 10 patients.

A spectrum of presentation of phaeochromocytoma in black South Africans is described. Ten patients were reviewed over a 9-year period. Sweating, headache, and palpitations were prominent symptoms in 9 patients; postural dizziness occurred in 5; gastro-intestinal symptoms in 7; diabetes in 3; and hypertension in all. One patient developed a phaeochromocytoma crisis, characterised by hypotension and pulmonary oedema, before operation. One woman presented in pregnancy. Urinary vanillylmandelic acid was elevated in 9 out of 10 subjects tested; plasma catecholamines were elevated in 6 out of 6 tested. Computed tomography detected 7 adrenal tumours and 3 paragangliomas. All patients were stabilised pre-operatively with alpha- and/or beta-receptor blockers. Intraoperative pressor crises were controlled with sodium nitroprusside, phentolamine, or magnesium sulphate infusions. At operation all tumours appeared benign, each was successfully removed, and the diagnosis confirmed on histological examination. There was no operative mortality. Two patients had residual hypertension. This study highlights the various challenges presented by this catecholamine-producing tumour.

Superior mesenteric artery aneurysms: a case report.

Aneurysms of the superior mesenteric artery (SMA) are rare, accounting for 8% of visceral artery aneurysms. Aneurysms at the site are very liable to rupture, irrespective of size, and may be difficult to manage even in the elective situation. The fact that 50-60% of SMA aneurysms are mycotic has important implications in the selection of the appropriate surgical procedure. In this paper we report a case of an SMA aneurysm diagnosed at the time of impending rupture and treated successfully. The aetiology, mode of presentation, diagnosis and management of SMA aneurysms are discussed.

Evaluation of the results of oesophagectomy for oesophageal cancer.

The long-term results of standard techniques of oesophagectomy were examined in 127 patients with squamous cell carcinoma of the oesophagus. A near-total oesophagectomy with a cervical anastomosis was performed in 93 patients and an oesophagogastrectomy with an intrathoracic anastomosis was carried out in 34 patients. One hundred and eight patients had a curative oesophagectomy and 19 patients had a palliative resection. Eight patients received radiotherapy to the tumour bed. There were 15 deaths in hospital and the overall 5-year survival rate including perioperative deaths was 13.2 per cent. Survival was adversely affected by incomplete excision of macroscopic tumour (P less than 0.001), positive regional lymph nodes (P less than 0.05) and distant lymphatic metastases (P less than 0.02). The 5-year survival rate of patients with tumour invasion beyond the oesophageal wall (T3) and negative nodes was 20 per cent. Postoperative irradiation had no effect on the survival of patients with gross residual tumour. Complete clearance of microscopic tumour was achieved in 50 per cent of patients with T3 tumours and this group did not benefit from adjuvant radiotherapy. Survival in patients undergoing curative oesophagectomy with residual microscopic tumour, however, was significantly improved by irradiation of the tumour bed (P less than 0.01). These results suggest that the survival of patients can be increased significantly by the excision of all gross tumour and by identification of those who will benefit from local radiotherapy.

Parotid haemangioma. A case report.

The presentation of a rare cavernous haemangioma of the parotid in a 17-year-old male is the twenty-first case in the English literature, and the first report in a black adult patient. The aetiology of this lesion is unknown and differs from that of the infantile capillary type. The pathognomonic signs of fluctuating size, discoloration and bruit are rare; the diagnostic hallmark in this case was spontaneous tumour regression. Doppler studies and arteriography may be valuable in diagnosis and management, in which surgical excision is the treatment of choice.

DNA ploidy in oesophageal cancer. A preliminary report.

Prognosis in oesophageal cancer is directly related to depth of invasion and lymph node metastases. However, without surgical exploration, assessment of the spread of oesophageal cancer is notoriously inaccurate and there is a need for another objective measurement of prognosis. In this study, the relationship of DNA-ploidy status to tumour length, histological appearance, extra-oesophageal spread and survival was examined in 42 patients with squamous oesophageal cancer. No correlation was found between DNA-ploidy status and tumour length or histological appearance. But the DNA-aneuploidy rate in cancers with extra-oesophageal spread was significantly greater than the rate in tumours localised to the oesophagus (P = 0.038). Short-term survival was poorer in patients with DNA-aneuploid cancers than in those with a DNA-diploid pattern. DNA analysis may prove to be a more accurate guide to prognosis in oesophageal cancer than either clinical or operative staging.

Insulinoma in a black South African. A case report.

A 69-year-old black woman with an insulinoma presented with recurrent episodes of sweating and confusion culminating in two episodes of hypoglycaemic coma. The diagnosis was confirmed by finding an inappropriately elevated serum insulin level in the presence of hypoglycaemia after a fast of 14 hours. Computed tomography revealed a large tumour in the head of the pancreas. Removal of the tumour necessitated partial resection of the head and body of the pancreas, which in turn necessitated certain repair and drainage procedures. Postoperative complications, while not insignificant, were acceptable. At 1-year follow-up the patient is well.