Mastectomy margins for ductal carcinoma-in-situ (DCIS): 18 Years of follow-up.

BACKGROUND: In patients undergoing mastectomy for ductal carcinoma in situ (DCIS), the significance of a positive or close (<2 mm) margin and associated recurrence risk is unclear. The study sought to evaluate risk of recurrence in relation to the mastectomy surgical margin. METHODS: A single institution retrospective review of patients with DCIS who underwent mastectomy between 2000 and 2010 was performed. Patient demographics, tumor biology, margin status and adjuvant therapy were recorded. The incidence of local recurrence (LR), distant metastasis were analyzed. RESULTS: A total of 282 patients with DCIS were identified. Overall, 12.3% of patients had a pathological positive/close margin (n = 9 tumor on ink and n = 36 <2 mm). Adjuvant radiation was administered to 11 patients with a positive or close margin. At a median follow-up of 12 years, LR was 3.4% (n = 10). None of the patients with LR had a positive or close margin. Additionally, none of the patients who received radiation developed LR. CONCLUSION: Risk of recurrence after mastectomy for DCIS is low and appears to be unrelated to margin status or the use of radiation therapy.

Hereditary Endocrine Tumor Registries.

Context: Endocrine neoplasia syndromes are phenotypically complex, and there is a misconception that they are universally rare. Genetic alterations are increasingly recognized; however, true prevalence is unknown. The purpose of a clinical registry is to monitor the quality of health care delivered to a specified group of patients through the collection, analysis, and reporting of relevant health-related information. This leads to improved clinical practice, decision-making, patient satisfaction, and outcome. Objective: This review aims to identify, compare, and contrast active registries worldwide that capture data relevant to hereditary endocrine tumors (HETs). Methods: Clinical registries were identified using a systematic approach from publications (Ovid MEDLINE, EMBASE) peer consultation, clinical trials, and web searches. Inclusion criteria were hereditary endocrine tumors, clinical registries, and English language. Exclusion criteria were institutional audits, absence of clinical data, or inactivity. Details surrounding general characteristics, funding, data fields, collection periods, and entry methods were collated. Results: Fifteen registries specific for HET were shortlisted with 136 affiliated peer-reviewed manuscripts. Conclusion: There are few clinical registries specific to HET. Most of these are European, and the data collected are highly variable. Further research into their effectiveness is warranted. We note the absence of an Australian registry for all HET, which would provide potential health and economic gains. This review presents a unique opportunity to harmonize registry data for HET locally and further afield.

Hereditary Endocrine Tumors and Associated Syndromes: A Narrative Review for Endocrinologists and Endocrine Surgeons.

OBJECTIVE: Hereditary endocrine tumors (HET) were among the first group of tumors where predisposition syndromes were recognized. The utility of genetic awareness is having the capacity to treat at an earlier stage, screen for other manifestations and initiate family cascade testing. The aim of this narrative review is to describe the most common hereditary syndromes associated with frequently encountered endocrine tumors, with an emphasis on screening and surveillance. METHODS: A MEDLINE search of articles for relevance to endocrine tumors and hereditary syndromes was performed. RESULTS: The most common hereditary syndromes associated with frequently encountered endocrine tumors are described in terms of prevalence, genotype, phenotype, penetrance of malignancy, surgical management, screening, and surveillance. CONCLUSION: Medical practitioners involved in the care of patients with endocrine tumors should have an index of suspicion for an underlying hereditary syndrome. Interdisciplinary care is integral to successful, long-term management of such patients and affected family members.

Need for Completion Thyroidectomy in Patients Undergoing Lobectomy for Indeterminate and High-Risk Nodules: Impact of Intra-Operative Findings and Final Pathology.

INTRODUCTION: Current guidelines increasingly suggest the use of thyroid lobectomy for indeterminate (Bethesda 3 and 4) and high-risk (Bethesda 5 and 6) thyroid nodules; however, the clinical reality is often very different. MATERIALS AND METHODS: The aim of this study was to determine the rate of completion thyroidectomy (CTx) for indeterminate and high-risk thyroid nodules which are pre-operatively classified as suitable for unilateral resection (lobe eligible) based on current guidelines. Seven hundred consecutive patients with thyroid nodules and FNA cytology over four years (2015-2018) were reviewed. RESULTS: Distribution of the dominant nodules by Bethesda was: non-diagnostic 3.9%, benign 28.1%, atypia of unknown significance 19.0%, follicular neoplasm 23.6%, suspicious for malignancy 6.1% and malignancy 19.3%. Of 298 indeterminate nodules, 68.8% (205/298) had relative but independent indications for a total thyroidectomy (TTx) and the remainder were candidates for lobectomy. For these lobe eligible patients, the overall risk of ultimately needing a TTx was 19.4% (18/93), comprising 4.3% (4/93) from intra-operative findings and 15.7% (14/89) from final pathology. Similarly, of 170 high-risk nodules, 63.5% (108/170) had upfront indications for a TTx and the remaining 62 nodules were lobe eligible. Of the patients taken to the operating room for a lobectomy, 21.0% (13/62) were upgraded to a TTx intra-operatively and 26.5% (13/49) post-operatively. The lobe success rate for indeterminate nodules was 25.2% and for high-risk nodules was 21.2%. The rate of CTx, or the proportion of patients needing a second operation was 15.7% (14/89) and 26.5% (13/49), respectively. CONCLUSIONS: In counselling a patient for surgery, the risk of needing a more radical initial procedure or second surgery needs to be accurately explained. There are three points of care that can influence operative strategy, pre-operatively by way of high-risk clinical factors, intra-operatively via anatomical findings and post-operatively in response to unrecognized pathological features. Additionally, the patient's personal value judgment and level of risk aversion should be taken into consideration.

RECEIVER OPERATING CHARACTERISTIC ANALYSIS OF INTRAOPERATIVE PARATHYROID HORMONE MONITORING TO DETERMINE OPTIMUM SENSITIVITY AND SPECIFICITY: ANALYSIS OF 896 CASES.

Objective: While intraoperative parathyroid hormone (IOPTH) monitoring with a ≥50% drop commonly guides the extent of exploration for primary hyperparathyroidism (pHPT), receiver operating characteristic (ROC) analysis has not been performed to determine whether other criteria yield better sensitivity and specificity. The aim of this study was to identify the optimum percent change of IOPTH following removal of the abnormal parathyroid pathology, in order to predict biochemical cure. Secondary aims were to identify patient subgroups with increased area under the ROC curve (AUC) and the need for moderated criteria. Methods: A retrospective review was performed on patients undergoing primary parathyroid surgery for sporadic pHPT between 1999 and 2010 at a tertiary center for endocrine surgery. Eight hundred and ninety-six patients with primary hyperparathyroidism were included. Multigland disease (MGD) was defined as the intraoperative detection of more than 1 enlarged hypercellular gland or persistent disease after single gland excision. ROC analysis was used to determine the value with the best performance at predicting MGD, following bilateral exploration. Results: MGD was diagnosed in 174 patients (19.4%). ROC analysis demonstrated an AUC of 0.69. An IOPTH drop of 72% was the point of optimal discrimination with a sensitivity of 55% and specificity of 76% for predicting MGD. Subgroup analysis by preoperative calcium, preoperative PTH, localization studies, or pre- and post-excision IOPTH, did not identify any factors associated with an improved AUC. Conclusion: To our knowledge, this is the first study to use ROC analysis in a large patient cohort. An IOPTH drop of 72% was found to have optimal discriminating ability. We failed to identify a subset of patients for whom there was substantial improvement in the AUC, sensitivity, or specificity. Abbreviations: AUC = area under the ROC curve; BE = bilateral neck exploration; FE = focal parathyroid exploration; IOPTH = intraoperative parathyroid hormone; MGD = multigland disease; MIBI = Tc99m-sestamibi I-123 subtraction single-photon emission computed tomography/computed tomography; pHPT = primary hyperparathyroidism; ROC = receiver operating characteristic; SGD = single gland disease; US = surgeon-performed neck ultrasound.

Fluorescence techniques in adrenal surgery.

This chapter describes the use of fluorescence via indocyanine green (ICG) in minimally invasive adrenal surgery (laparoscopic and robotic). ICG is a non-toxic dye that can aid identification of vascular structures and parenchymal tissue planes in real time. The primary utility of ICG fluorescence in adrenal surgery is to help delineate the margins of resection, to guide a more precise operation. In particular, for patients with bilateral adrenal disease or a heredity associated with high risk of recurrence (e.g., VHL, MEN2a) this may facilitate subtotal adrenal resection (e.g., cortical sparing adrenalectomy), obviating the incidence of iatrogenic adrenal insufficiency and its numerous sequelae including lifelong hormone supplementation, osteoporosis and risk of Addisonian crisis.

Near-infrared imaging in re-operative parathyroid surgery: first description of autofluorescence from cryopreserved parathyroid glands.

Identification of parathyroid glands is one of the primary tenets in endocrine surgery. Multiple localizing techniques have been described and are in use in routine practice. More recently near-infra red imaging has been gaining popularity and is used for identification in real time. Parathyroid glands are unique in that they fluoresce when excited by near-infrared light, without the use of a biomarker. This is called autofluorescence (AF). In this case report we describe the presence of persistent AF by thawed parathyroid glands which have previously been cryopreserved. We confirm that the mechanism behind AF involves an intrinsic primary fluorophore, unique to parathyroid glands.

CRYOPRESERVATION OF PARATHYROID TISSUE: A WHITE PAPER ON ESTABLISHING A LOCAL SERVICE.

Objective: Preservation of parathyroid function is one of the primary tenets of endocrine surgery. For patients with thyroid disease, an inadvertently compromised parathyroid gland is routinely autotransplanted into the neck at the time of surgery. By contrast, for patients with parathyroid disease secondary to hyperplasia, the timing of auto-transplantation needs to be further considered in order to balance the risks between persistent disease and permanent hypocalcemia. Cryopreservation preserves cellular function and permits the storage of parathyroid tissue for potential re-implantation at a later date in patients who develop hypoparathyroidism. Methods: In this paper, we review the process of cryopreservation, with particular emphasis on the regulatory issues involved in establishing a local service, tissue processing, billing and reimbursements, outcome (functionality), and complications. Results: A detailed description of the technique as performed at our institution is described and illustrated. Conclusion: Cryopreservation affords surgical insurance against the disastrous sequelae of permanent hypoparathyroidism. Our techniques are easy to adopt with only a modest initial investment of time and money, particularly for institutions that already cryopreserve other tissue types. Abbreviations: PTH = parathyroid hormone; RMPI = Roswell Park Memorial Institute; RPMI-SSS = RPMI-serum substitute supplement.

CALCIUM CREATININE CLEARANCE RATIO IS NOT HELPFUL IN DIFFERENTIATING PRIMARY HYPERPARATHYROIDISM FROM FAMILIAL HERPERCALCEMIC HYPOCALCIURIA: A STUDY OF 1000 PATIENTS.

OBJECTIVE: With increasing recognition of more subtle presentations of primary hyperparathyroidism (pHPT), laboratory values are frequently seen in a range that would be expected for patients who have familial hypercalcemic hypocalciuria (FHH). Calcium creatinine clearance ratio (CCCR) has been advocated as a diagnostic tool to differentiate between these two disorders. However, it is limited by an indeterminate range (0.01-0.02). The aim of this study is to assess the relevance of CCCR in a modern series of patients with surgically managed pHPT. METHODS: We performed a retrospective cohort study of 1000 patients who underwent parathyroid surgery for pHPT over eleven years. CCCR was evaluated by degree of biochemical derangement, single versus multiple gland disease and interfering medications. RESULTS: Patient demographics and resected histopathology were typical for a current series of patients with pHPT. In retrospect, none of the patients were suspected to have FHH post operatively. CCCR was less than 0.01 for 19.0%, between 0.01-0.02 for 43.7% and greater than 0.02 in 37.3%. Distribution of CCCR for patients free from interfering medications and different histological subtypes were the same. One third of the cohort had mild calcium elevations, more typical for FHH. Of these, almost two thirds had a CCCR in a range suspect for FHH (<0.02). CONCLUSION: To our knowledge this is the largest series to evaluate the validity of CCCR for patients with surgically confirmed pPHT. The utility of CCCR in screening for FHH is limited, as 63% of modern patients with confirmed pHPT have low values.

Women are more than twice as likely to die from burns as men in Australia and New Zealand: an unexpected finding of the Burns Evaluation And Mortality (BEAM) Study.

While the risk of death after nonthermal trauma and sepsis may be higher for men, sex differences in outcome after burns are inconsistently reported. The Burns Evaluation And Mortality Study examined the outcomes of all patients admitted after thermal injury to the intensive care unit (ICU) at 8 of 9 burn referral centers in Australia and New Zealand between January 1, 2005, and December 31, 2011. There were 348 women and 1367 men treated for acute burns. Women were older, had more extensive burns, and higher severity of illness scores. Women spent longer in hospital and in ICU than men. Mortality among women was higher than in men (21% vs 8.3%, P<.001). Trends toward a survival disadvantage for women were seen across all ages, at all levels of severity of illness, at every proportion of body surface area burnt, and across all centers. After adjusting for confounding factors, women had more than double the risk of death compared with men (odds ratio, 2.35; 95% confidence interval, 1.38-4.01; P=.002). Our study conclusively shows worse outcomes for women with burns admitted to ICUs in Australia and New Zealand. Further research is required to determine why this is happening.

The Burns Evaluation and Mortality Study (BEAMS): predicting deaths in Australian and New Zealand burn patients admitted to intensive care with burns.

BACKGROUND: An understanding of prognosis following burns is important. It alleviates patient and familial stress, provides a framework for better resource use, and facilitates benchmarking of performance between specialist centers. METHODS: Data were collected from eight tertiary referral burns centers in Australia and New Zealand. Our aim was to identify factors independently associated with mortality to develop a mortality prediction model, which accurately quantifies the risk of death among adults with burns who require intensive care. RESULTS: Between January 2005 and December 2011, 1,715 patients were admitted to intensive care unit with acute thermal burns. The mean (SD) age was 41.1 (18.0) years, and 20.3% (n = 348) were female. Median percentage of total body surface area was 17% (6-35%) and percent full-thickness surface area was 4% (0-20%). Inhalational injury was documented as present in 36.2%. Accidental injury was the most common etiology of burn (70.4%) and most frequently via a flame (68.3%). Overall hospital mortality was 10.9% (n = 187). Independent risk factors for death were age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.06-1.10; p < 0.001), percentage of full-thickness surface area (OR, 1.07; 95% CI 1.06-1.08; p < 0.001), and Acute Physiology and Chronic Health Evaluation II score excluding age (OR, 1.11; 95% CI, 1.07-1.15; p < 0.001) and female sex (OR, 3.35; 95% CI, 1.84-6.11; p = 0.001). There was no association between inhalational injury or deliberate self-harm and death, as well as etiology or type of burn. CONCLUSION: A highly discriminatory mortality prediction model was developed using logistic regression. Risk of death following major burns can be predicted from a combination of physiologic and burns specific parameters. Female sex is a highly significant risk factor.

Candida in burns: risk factors and outcomes.

Sepsis due to Candida is an uncommon but a significant cause of death in burns patients. Colonization is common, but consensus guidelines for prophylaxis and empirical therapy do not specifically include this cohort. Our aim was to define predictive factors for candidaemia in a burns unit, to guide protocols for prevention and early treatment. We conducted a 10-year review (July 1998-December 2007) of patients admitted to the Victorian Adult Burns Service, Melbourne, Australia. Of 1929 patients admitted with acute burn injury, 143 had Candida isolated at any site, most commonly Candida albicans. There were 12 episodes of candidaemia. Prior colonization was an important risk factor for candidaemia, and the risk increased substantially with the number of colonized sites; indeed 43% of patients colonized at more than three sites (and not on antifungals) developed candidaemia. Other risk factors were higher total burn surface area, higher full-thickness surface area, prolonged admission, number and duration of intensive care unit admissions, number of visits to the operating theatre, alcohol as a contributing factor to burn, prior treatment with total parenteral nutrition, or certain antibiotics (ceftriaxone, vancomycin, amikacin, co-trimoxazole). The attributable mortality of candidaemia was 15% (n = 2). Initiation of antifungal therapy was often delayed. Our results support early empirical antifungal therapy in septic burns patients who are colonized, before the results of cultures become known. The role of prophylactic antifungals is less clear, but should be strongly considered for patients colonized at multiple sites.

Mortality prediction and outcomes among burns patients from Australian and New Zealand intensive care units.

BACKGROUND: Acute Physiology and Chronic Health Evaluation (APACHE) III scores have been shown to correlate with outcomes for patients with burn injuries. It is unknown whether they can be used to compare outcomes between intensive care units that admit patients with burns in Australia and New Zealand. OBJECTIVE: To assess the APACHE III-j score as a predictor of mortality for burns patients and use it to compare riskadjusted outcomes between different ICUs. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of all patients listed in the Australian and New Zealand Intensive Care Society Adult Patient Database with a diagnosis of burns between 1 January 2001 and 30 June 2008. Logistic regression analysis was used to assess the relationship between APACHE III-j score and mortality, and to derive a predicted risk of death for each patient. Standardized mortality ratios for individual ICUs were calculated and outcome variation assessed. RESULTS: Data on 1618 patients were included in the analysis (mean age, 40.6 years; mortality, 13.2%). Increasing APACHE III-j scores were significantly associated with increasing likelihood of death (odds ratio, 1.05 [95%CI, 1.04-1.06]). The largest ICU and two small ICUs had risk-adjusted outcomes that were significantly better than the rest. Over the study period there was a decline in observed mortality accompanied by a parallel reduction in predicted risk of death. CONCLUSION: The APACHE III-j score is a good predictor of death among burns patients admitted to ICUs in Australia and New Zealand. It can be used to compare risk-adjusted outcomes between individual ICUs and over time.