The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.

OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

MRI Features Can Predict 1p/19q Status in Intracranial Gliomas.

BACKGROUND AND PURPOSE: The 2016 revision of the World Health Organization Classification of Tumors of the Central Nervous System mandates codeletion of chromosomes 1p and 19q for the diagnosis of oligodendroglioma. We studied whether conventional MR imaging features could predict 1p/19q status. MATERIALS AND METHODS: Patients with previous 1p/19q testing were identified through pathology department records, typically performed on the basis of an oligodendroglial component on routine histology; 69 patients met the inclusion criteria. Preoperative imaging of patients with grade II or III gliomas was retrospectively assessed by 2 neuroradiologists, blinded to the 1p/19q status. Thirteen MR imaging features were first assessed in a small initial cohort (n = 10), after which the criteria were narrowed for the remaining patients as a validation cohort. RESULTS: There was 85% agreement between radiologists for the overall prediction of 1p/19q status in the validation cohort, with an accuracy of 84%. The presence of >50% T2-FLAIR mismatch and calcification was found to be the most useful for predicting 1p/19q status. The >50% T2-FLAIR mismatch variable was demonstrated in 14 tumors and had 100% specificity for identifying a noncodeleted tumor (P = .001), with 97% interobserver correlation. Calcification was visualized in 7 tumors, 6 of which were 1p/19q codeleted (specificity, 97%; P = .006), with 100% interobserver correlation. CONCLUSIONS: The presence of >50% T2-FLAIR mismatch is highly predictive of a noncodeleted tumor, while calcifications suggest a 1p/19q codeleted tumor. If formal 1p/19q testing is not possible, a combined MR imaging-histologic assessment may improve the diagnostic accuracy over histology alone.

Outcomes in emergency general surgery following the introduction of a consultant-led unit.

BACKGROUND: Patients presenting with emergency surgical conditions place significant demands on healthcare services globally. The need to improve emergency surgical care has led to establishment of consultant-led emergency surgery units. The aim of this study was to determine the effect of a changed model of service on outcomes. METHODS: A retrospective observational study of all consecutive emergency general surgical admissions in 2009-2012 was performed. A 2-year time frame before and after the establishment of the emergency general surgery (EGS) service was used to determine the number of admissions and operations, emergency department and hospital length of stay, as well as complication rates. RESULTS: The study included 7233 acute admissions. The EGS service managed 4468 patients (61·6 per cent increase) and performed 1804 operations (41·0 per cent increase). The most common diagnoses during the EGS period included acute appendicitis (532, 11·9 per cent), biliary disease (361, 8·1 per cent) and abdominal pain (561, 12·6 per cent). Appendicectomy (536, 29·7 per cent), cholecystectomy (239, 13·2 per cent) and laparotomy (226, 12·5 per cent) were the most commonly performed procedures. In the EGS period, time in the emergency department was reduced (from 8·0 to 6·0 h; P < 0·001), as was length of hospital stay (from 3·0 to 2·0 days; P < 0·001). The number of complications was reduced by 46·8 per cent, from 172 (6·2 per cent) to 147 (3·3 per cent) (P < 0·001), with a 53 per cent reduction in the number of deaths in the EGS period, from 29 (16·9 per cent) to seven (8 per cent) (P = 0·039). CONCLUSION: The establishment of a consultant-led emergency surgical service has been associated with improved provision of care, resulting in timely management and improved clinical outcomes.

Efficacy of thiopurines and adalimumab in preventing Crohn's disease recurrence in high-risk patients - a POCER study analysis.

BACKGROUND: Crohn's disease recurs in the majority of patients after intestinal resection. AIM: To compare the relative efficacy of thiopurines and anti-TNF therapy in patients at high risk of disease recurrence. METHODS: As part of a larger study comparing post-operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine-intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment. RESULTS: A total of 101 patients [50% male; median (IQR) age 36 (25-46) years] were included. There were no differences in disease history between thiopurine- and adalimumab-treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2-i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab-treated patients [intention-to-treat (ITT); P = 0.028] or 24 of 62 (39%) vs. 3 of 24 (13%) respectively [per-protocol analysis (PPA); P = 0.020]. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab). CONCLUSIONS: In Crohn's disease patients at high risk of post-operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.

Geographical variation in incidence of knee arthroscopy for patients with osteoarthritis: a population-based analysis of Victorian hospital separations data.

BACKGROUND/AIM: To evaluate the frequency and geographical variation in knee arthroscopy for adults (>25 years) with a concomitant diagnosis of osteoarthritis. METHODS: This was a retrospective cohort study of hospital separations involving an elective knee arthroscopy in public and private hospitals in Victoria, Australia. Participants included patients receiving knee arthroscopies with a diagnosis code indicating osteoarthritis (OA) from 1 July 2008 to 30 June 2009. Records were excluded if the patient was under 25 years or their arthroscopy involved a ligament reconstruction. Crude rates per 100 000 population and negative binomial regression offset by total knee arthroscopy volume were used to analyse differences by region. RESULTS: There were 9620 arthroscopic procedures meeting the inclusion criteria. There were 5500 (57.2%) admissions where the principal diagnosis was knee OA (gonarthrosis) and 3510 (36.5%) where the principal diagnosis indicated a mechanical derangement and there was a primary or associated diagnosis of OA. When we examined the incidence rate ratios (IRR) by region, after adjustment for relevant factors and accounting for the total knee arthroscopy volume within each region, we identified significant variation in knee arthroscopy rates for patients with OA. The region with the highest adjusted IRR was Barwon South Western (IRR: 1.26, 95% confidence interval (CI): 1.16-1.36) and the region with lowest adjusted incidence rate ratio was the Gippsland region (IRR: 0.89, 95% CI: 0.80-0.98). CONCLUSIONS: We identified considerable geographical variation in arthroscopies for people with OA across Victoria. Further investigation is needed to understand whether this variation is a reflection of differences in OA prevalence, clinical decision-making or access.

Epidemiology of hepatitis B-associated hepatocellular carcinoma in Victoria.

BACKGROUND: Chronic hepatitis B (HBV) and cirrhosis are major risk factors for hepatocellular carcinoma (HCC). The proportion and characteristics of cases with cirrhosis are not well documented. AIM: Our aim was to compare demographic, viral and tumour characteristics of HBV-associated HCC in an Australian cohort, in patients with and without cirrhosis. METHODS: Existing HCC databases at six Melbourne teaching hospitals were reviewed for cases associated with HBV. Patient demographics, HBV viral characteristics, presence of cirrhosis, serum alpha-fetoprotein and tumour size were assessed. Mode of diagnosis was recorded through surveillance or symptoms, and treatment was either palliative, percutaneous or surgical. RESULTS: We identified 197 cases of HBV-related HCC. The mean age was 57.9 ± 12.9 years; 83% were male, and 55.3% and 35.3% were of Asian and European descent respectively. Of 168 patient with available data, 146 (87%) had cirrhosis versus 22 (13%) without. Patients with cirrhosis tended to be older (median 60 vs 52 years, P = 0.078). Asian patients were more likely to have HCC without cirrhosis than Europeans (17% vs 6%, P = 0.04). There were no other differences identified between cirrhotic and non-cirrhotic patients. Thirty-four per cent of patients had tumours greater than 5 cm at diagnosis, and 47% were diagnosed after presenting with symptoms. Twelve patients with HBV-HCC were outside current screening guidelines. CONCLUSION: Most patients in Melbourne with HBV-associated HCC have cirrhosis. HCC characteristics in non-cirrhotic and cirrhotic patients were similar. The large number of patients detected through symptoms and with large tumours reinforces the need for vigilance in screening.

Primary angiitis of the central nervous system: experience of a Victorian tertiary-referral hospital.

BACKGROUND: Primary angiitis of the central nervous system is a rare condition, which is often difficult to diagnose and is associated with significant morbidity and mortality. There is no standardised treatment protocol or randomised clinical trial evidence to guide management. AIM: To describe the clinical features, diagnostic modalities, treatment and outcomes in an Australian hospital population-based series of primary cerebral angiitis. METHODS: Data were collected via retrospective medical record review of patients with primary angiitis of the central nervous system for the period 1 July 1998 to 30 June 2009, using previously published diagnostic criteria. Eligible patient records were identified in two ways; from routinely collected hospital episode data, coded using the ICD-10-AM coding standard and by review of cerebral biopsy data. RESULTS: Ten of 12 included patients had a positive cerebral biopsy, with two patients diagnosed by angiography. Mean age at diagnosis was 47.2 years (range 18-73 years), with a female predominance of 5:1. Headache was the most common symptom experienced. Seventy per cent of the biopsy specimens showed a lymphocytic vasculitis. All patients received treatment with either steroids alone or a combination of steroids and cyclophosphamide, the latter treatment being initiated for those with a higher modified Rankin score of disability. Nine (75%) responded to treatment. There was one in-hospital death, and two patients had no documented response to treatment. CONCLUSION: This study presents the first Australian case series data of primary cerebral angiitis. Better understanding of management and outcomes of this rare condition would be gained through multicentre studies.

Prognostic factors in the elderly: a profile and outcomes study of a community palliative care service.

Our ageing population creates challenges for palliative care, including accuracy of prognostication. This study highlights this by profiling the outcomes of an Australian, community-based palliative service over 6 months with collection of epidemiological, comorbidity and physical function data. Most patients had cancer, comorbidities and died during the study. Low scores on the Australian-modified Karnofsky Performance Scale and the presence of congestive cardiac failure were predictive of shorter survival.

Type 2 diabetes does not worsen prognosis in hepatocellular carcinoma.

INTRODUCTION: Type 2 diabetes (T2DM) is associated with liver inflammation and carcinogenesis. The prevalence of T2DM among patients with liver cirrhosis and hepatocellular carcinoma is increasing. However, the effect of T2DM on the natural history of hepatocellular carcinoma is not known. AIM: To examine the effect of T2DM on hepatocellular carcinoma (HCC) survival in treated and untreated disease. METHODS: Retrospective analysis was performed on HCC cases diagnosed during 2000-2005, and prospectively during 2006-August 2007. Demographics, HCC staging, response to treatment, and survival were collected. A comparison was made between patients with T2DM and without T2DM. RESULTS: One hundred and thirty-five patients were recruited in total; 58 (43%) had T2DM. Seventy (37 diabetic) patients were treated with percutaneous radiological therapies, with 168 treatments given. Treatment was determined by AASLD guidelines and patient tolerance, there was no randomisation. There was no significant difference in survival between diabetic and nondiabetic patients. There was a nonsignificant trend towards greater survival in diabetic patients (overall median survival diabetics 21 mths vs nondiabetics 5 mths, P=0.355). CONCLUSIONS: T2DM does not negatively impact on the natural history of treated or untreated HCC.

A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients.

Fluconazole antifungal prophylaxis is standard care in allogeneic hematopoietic stem cell transplant (HSCT) recipients, but this drug lacks anti-Aspergillus activity, the primary cause of invasive fungal infection (IFI) in many transplantation centers. We performed a randomized trial to compare itraconazole vs fluconazole, for prevention of IFIs in patients with acute leukemia (AL) and HSCT recipients. One hundred and ninety-five patients were randomly assigned to either fluconazole or itraconazole antifungal prophylaxis, after stratification into high-risk and low-risk groups. Antifungal prophylaxis was started at the beginning of chemotherapy and continued until resolution of neutropenia, or until amphotericin B treatment was started. IFI occurred in 11 (11%) of itraconazole, and in 12 (12%) fluconazole recipients. Invasive candidiasis (IC) developed in two (2%) itraconazole and one (1%) fluconazole recipients, while invasive aspergillosis (IA) developed in nine (9%) itraconazole and 11(11%) fluconazole recipients. There was no difference in the incidence of total IFI, IC and IA between the two study arms. However, there was a nonsignificant trend towards reduced mortality among patients who developed IA while receiving itraconazole prophylaxis (3/9=33% vs 8/11=73%, P=0.095).

[Possibilities of present-day research methods in the diagnosis of precancerous changes in the mucous membrane and "minor" endophytic gastric cancer]. / Vozmozhnosti sovremennykh metodov issledovaniia v diagnostike predrakovykh izmenenii slizistoi obolochki i "malogo" éndofitnogo raka zheludka.

Complex x-ray, endoscopic and morphologic examinations of the stomach carried out in 1250 patients revealed 152 cases with precancer mucosal changes (epithelial dysplasia, intestinal metaplasia). X-ray and endoscopic signs are described which permit suspect precancer changes in the gastric mucosa and "minor" endophytic cancer. Dysplasia progress was observed in 15.5% of cases, no progress in 21.1%. The diagnosis of such conditions should be complex. High-risk groups should be formed with due consideration for both the morphologic criterion and the x-ray and endoscopic signs of gastric wall involvement.