Demographics and deprivation in obstetric brachial plexus palsy: a retrospective cohort study.

The present study analyses the relationships between deprivation and obstetric brachial plexus palsy (OBPP). A retrospective observational study was conducted of infants with OBPP seen between 2008 and 2020 (n = 321). The index of multiple deprivation (IMD) was used to assign an IMD rank to patients based on birth postcode and the relationship with OBPP was analysed, including deprivation, gestational diabetes, age at referral and at first assessment. Quintile-based analysis demonstrated over-representation of patients from more deprived neighbourhoods (n = 109, 39%) living in the top 20% most deprived neighbourhoods. A total of 48 (15%) mothers had diabetes and 98 (31%) infants underwent surgical brachial plexus exploration (a marker of disease severity). Neither diabetes, age at referral nor age at first assessment were associated with IMD score. This suggests that neighbourhood deprivation is associated with OBPP, though the mechanisms are unclear. Further studies in this area may enable targeted health intervention for more deprived maternal and infant groups.Level of evidence: III.

Receipt of mastectomy and adjuvant radiotherapy following breast conserving surgery (BCS) in New Zealand women with BCS-eligible breast cancer, 2010-2015: an observational study focusing on ethnic differences.

BACKGROUND: Women with early breast cancer who meet guideline-based criteria should be offered breast conserving surgery (BCS) with adjuvant radiotherapy as an alternative to mastectomy. New Zealand (NZ) has documented ethnic disparities in screening access and in breast cancer treatment pathways. This study aimed to determine whether, among BCS-eligible women, rates of receipt of mastectomy or radiotherapy differed by ethnicity and other factors. METHODS: The study assessed management of women with early breast cancer (ductal carcinoma in situ [DCIS] and invasive stages I-IIIA) registered between 2010 and 2015, extracted from the recently consolidated New Zealand Breast Cancer Registry (now Te Rehita Mate Utaetae NZBCF National Breast Cancer Register). Specific criteria were applied to determine women eligible for BCS. Uni- and multivariable analyses were undertaken to examine differences by demographic and clinicopathological factors with a primary focus on ethnicity (Maori, Pacific, Asian, and Other; the latter is defined as NZ European, Other European, and Middle Eastern Latin American and African). RESULTS: Overall 22.2% of 5520 BCS-eligible women were treated with mastectomy, and 91.1% of 3807 women who undertook BCS received adjuvant radiotherapy (93.5% for invasive cancer, and 78.3% for DCIS). Asian ethnicity was associated with a higher mastectomy rate in the invasive cancer group (OR 2.18; 95%CI 1.72-2.75), compared to Other ethnicity, along with older age, symptomatic diagnosis, advanced stage, larger tumour, HER2-positive, and hormone receptor-negative groups. Pacific ethnicity was associated with a lower adjuvant radiotherapy rate, compared to Other ethnicity, in both invasive and DCIS groups, along with older age, symptomatic diagnosis, and lower grade tumour in the invasive group. Both mastectomy and adjuvant radiotherapy rates decreased over time. For those who did not receive radiotherapy, non-referral by a clinician was the most common documented reason (8%), followed by patient decline after being referred (5%). CONCLUSION: Rates of radiotherapy use are high by international standards. Further research is required to understand differences by ethnicity in both rates of mastectomy and lower rates of radiotherapy after BCS for Pacific women, and the reasons for non-referral by clinicians.

Wound complications following surgery to the lymph nodes: A protocol for a systematic review and meta-analysis.

BACKGROUND: Malignancies that spread to the lymph nodes may be identified through surgical biopsy, and treatment of metastatic disease may be through lymph node dissection. These surgeries, however, may be associated with significant adverse outcomes, particularly wound complications, the true incidence of which remains unknown. Multiple studies have reported their individual rates of complications in isolation. The aim of this study will be to systematically evaluate data that presents the incidence of wound complications in patients undergoing these surgeries. METHODS: We have designed and registered a protocol for a systematic review and meta-analysis of studies presenting incidence data. We will search MEDLINE, EMBASE and CENTRAL for relevant articles. Meta-analysis will be undertaken to synthesise an overall incidence of surgical site infection, wound dehiscence, haematoma and seroma. Subgroup analyses will investigate the effects of anatomical location, primary malignancy and study design on pooled incidence. Risk of bias will be evaluated for each included study using bespoke tools matched to the study design. DISCUSSION: The results of this study will provide the incidence of wound complications and secondary complications following lymph node surgery. This will directly impact upon the consent process, and may influence the nature of future research studies aimed at reducing post-operative complications.

Diagnostic accuracy of magnetic resonance imaging for nerve injury in obstetric brachial plexus injury: protocol for systematic review and meta-analysis.

BACKGROUND: Early and accurate clinical diagnosis of the extent of obstetric brachial plexus injury (OBPI) is challenging. The current gold standard for delineating the nerve injury is surgical exploration, and synchronous reconstruction is performed if indicated. Magnetic resonance imaging (MRI) is a non-invasive method of assessing the anatomy and severity of nerve injury in OBPI but the diagnostic accuracy is unclear. The primary objective of this review is to determine the diagnostic accuracy of MRI in comparison to surgical brachial plexus exploration for detecting root avulsion in children under 5 with OBPI. The secondary objectives are to determine its' diagnostic accuracy for detecting nerve abnormality and detecting pseudomeningocele(s) in this group. METHODS: This review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).We will include studies reporting the accuracy of MRI (index test) compared to surgical exploration (reference standard) in detecting any of the three target conditions (root avulsion, any nerve abnormality and pseudomeningocele) in children under five with OBPI. Case reports and studies where the number of true positives, false positives, true negatives and false negatives cannot be derived will be excluded. We plan to search PubMed, Embase and CENTRAL for relevant studies from database inception to 15 June 2022. We will also search grey literature (medRxiv, bioRxiv and Google Scholar) and perform forward and backward citation chasing. Screening and full-text assessment of eligibility will be conducted by two independent reviewers, who will then both extract the relevant data. The QUADAS-2 tool will be used to assess methodological quality and risk of bias of included studies by two reviewers independently. The following test characteristics for the target conditions will be extracted: true positives, false positives, true negatives and false negatives. Estimates of sensitivity and specificity with 95% confidence intervals will be shown in forest plots for each study. If appropriate, summary sensitivities and specificities for target conditions will be obtained via meta-analyses using a bivariate model. DISCUSSION: This study will aim to clarify the diagnostic accuracy of MRI for detecting nerve injury in OBPI and define its clinical role. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021267629.

Provision and standards of care for treatment and follow-up of patients with Autoimmune Hepatitis (AIH).

Background: Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals. Methods: Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool. Results: Hospitals (14 university hospitals (UHs), 14 district general hospitals (DGHs)) had median (range) of 8 (3-23) gastroenterologists; including 3 (0-10) hepatologists. Eight hospitals (29%, all DGHs) had no hepatologist. In individual hospital departments, there were 50% (18-100) of all consultants managing AIH: in DGH's 92% (20-100) vs 46% (17-100) in UHs. Specialist nurses managed AIH in only 18%. Seventeen (61%) hospitals had a histopathologist with a liver interest, these were more likely to find rosettes than those without (172/795 vs 50/368; p<0.001).Of 999 steroid-treated patients with ≥12 months follow-up, 25% received steroids for <12 months. After 1 year of treatment, 82% of patients achieved normal serum alanine aminotransaminase (ALT); this was higher in UHs than DGHs. Three-monthly liver blood tests were inadequately recorded in 26%. Of potentially eligible patients with liver decompensation, transplantation was apparently not considered in 5% (n=7). The same standards were attained in different types of hospital. Conclusion: Management of AIH in UK hospitals is often shared between most gastroenterologists. Blood test monitoring and treatment duration are not always in line with recommendations. Some eligible patients with decompensation are not discussed with transplant teams. Care might be improved by expanding specialist input and management by fewer designated consultants.

Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

BACKGROUND: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. METHODS: Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed. RESULTS: In 1267 patients with AIH, followed-up for 3.8(0-15) years, 5- and 10-year death/transplant rates were 7.1+0.8% and 10.1+1.3% (all-cause) and 4.0+0.6% and 5.9+1% (liver-related) respectively. Baseline parameters independently associated with death/transplantation for all-causes were: older age, vascular/respiratory co-morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver-related: the last four of these and peak bilirubin All-cause and liver-related death/transplantation was independently associated with: non-treatment with corticosteroids, non-treatment with a steroid-sparing agent (SSA), non-treatment of asymptomatic or non-cirrhotic patients and initial dose of Prednisolone >35mg/0.5mg/kg/day (all-cause only), but not with type of steroid (Prednisolone versus Budesonide) or steroid duration beyond 12-months. Subsequent all-cause and liver-death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3-months, but not with failure to normalise levels over 12-months. CONCLUSIONS: We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non-cirrhotic sub-groups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12-months and patients attaining normal ALT within 12-months versus not.

Maintaining cancer services during the COVID-19 pandemic: the Aotearoa New Zealand experience.

COVID-19 caused significant disruption to cancer services around the world. The health system in Aotearoa New Zealand has fared better than many other regions, with the country being successful, so far, in avoiding sustained community transmission. However, there was a significant initial disruption to services across the cancer continuum, resulting in a decrease in the number of new diagnoses of cancer in March and April 2020. Te Aho o Te Kahu, Aotearoa New Zealand's national Cancer Control Agency, coordinated a nationwide response to minimise the impact of COVID-19 on people with cancer. The response, outlined in this paper, included rapid clinical governance, a strong equity focus, development of national clinical guidance, utilising new ways of delivering care, identifying and addressing systems issues and close monitoring and reporting of the impact on cancer services. Diagnostic procedures and new cancer registrations increased in the months following the national lockdown, and the cumulative number of cancer registrations in 2020 surpassed the number of registrations in 2019 by the end of September. Cancer treatment services - surgery, medical oncology, radiation oncology and haematology - continued during the national COVID-19 lockdown in March and April 2020 and continued to be delivered at pre-COVID-19 volumes in the months since. We are cautiously optimistic that, in general, the COVID-19 pandemic does not appear to have increased inequities in cancer diagnosis and treatment for Maori in Aotearoa New Zealand.

PET-CT for staging pT4b melanomas prior to sentinel lymph node biopsy: a 5-year review.

In this centre, patients with pT4b cutaneous melanoma are staged using 18F-FDG PET-computed tomography (PET-CT) prior to considering sentinel lymph node biopsy (SLNB). The objective was to assess the utility of PET-CT in terms of rates of detection of metastases leading to changes in planned treatment and if performing PET-CT was associated with a delay in surgical management. In this single-centre retrospective cohort study, 88 consecutive patients with pT4b melanoma were identified from February 2014 to May 2019. Data were collected from clinical records. Of the 88 patients, 76 patients underwent PET-CT and 16/76 (21%) of these demonstrated metastatic/potentially metastatic disease. In total 16/76 (21%) patients had positive findings on PET-CT, and of these 14 (18%) had alterations to their clinical care. Performing PET-CT did not significantly delay time to wide local excision (PET-CT median 74 days (range 16-220) vs. no PET-CT median 55 days (range 36-143) P = 0.56) or SLNB (PET-CT median 67 days (range 16-206) vs. no PET-CT median 124 days (range 45-203) P = 0.66). Of the 29 patients undergoing SLNB who had negative PET-CT findings, 12/29 (41%) demonstrated microscopic metastatic disease. At the median follow-up of 1.75 years, 28 patients (34%) had died. Median survival was not reached. Performing staging PET-CT prior to SLNB in patients with pT4b melanoma can reveal metastases in over a fifth of patients, leading to alteration in management without treatment delay. Due to the low sensitivity of PET-CT for small metastases, SLNB remains important for definitive staging.

The impact of the COVID-19 pandemic on cancer diagnosis and service access in New Zealand-a country pursuing COVID-19 elimination.

BACKGROUND: The COVID-19 pandemic has disrupted cancer services globally. New Zealand has pursued an elimination strategy to COVID-19, reducing (but not eliminating) this disruption. Early in the pandemic, our national Cancer Control Agency (Te Aho o Te Kahu) began monitoring and reporting on service access to inform national and regional decision-making. In this manuscript we use high-quality, national-level data to describe changes in cancer registrations, diagnosis and treatment over the course of New Zealand's response to COVID-19. METHODS: Data were sourced (2018-2020) from national collections, including cancer registrations, inpatient hospitalisations and outpatient events. Cancer registrations, diagnostic testing (gastrointestinal endoscopy), surgery (colorectal, lung and prostate surgeries), medical oncology access (first specialist appointments [FSAs] and intravenous chemotherapy attendances) and radiation oncology access (FSAs and megavoltage attendances) were extracted. Descriptive analyses of count data were performed, stratified by ethnicity (Indigenous Maori, Pacific Island, non-Maori/non-Pacific). FINDINGS: Compared to 2018-2019, there was a 40% decline in cancer registrations during New Zealand's national shutdown in March-April 2020, increasing back to pre-shutdown levels over subsequent months. While there was a sharp decline in endoscopies, pre-shutdown volumes were achieved again by August. The impact on cancer surgery and medical oncology has been minimal, but there has been an 8% year-to-date decrease in radiation therapy attendances. With the exception of lung cancer, there is no evidence that existing inequities in service access between ethnic groups have been exacerbated by COVID-19. INTERPRETATION: The impact of COVID-19 on cancer care in New Zealand has been largely mitigated. The New Zealand experience may provide other agencies or organisations with a sense of the impact of the COVID-19 pandemic on cancer services within a country that has actively pursued elimination of COVID-19. FUNDING: Data were provided by New Zealand's Ministry of Health, and analyses completed by Te Aho o Te Kahu staff.

The surgical management of cutaneous abscesses: A UK cross-sectional survey.

AIM: Cutaneous abscesses are one of the most common acute general surgery presentations. This study aimed to understand the current practice in the management of cutaneous abscesses in the United Kingdom (UK), once the decision has been made that acute surgical incision and drainage (I&D) is required. METHOD: General surgeons from across the UK were surveyed on their opinions on the optimum management of cutaneous abscesses. Outcomes measured included anaesthesia, incision technique, antibiotic administration, departmental abscess pathways, and post-drainage management. A combination of Likert scales, multiple-choice questions, and short answer questions were used. Comparisons were made of Likert scales between regions using a two-sample independent t-test. The survey was peer reviewed and distributed through the Association of Coloproctology of Great Britain and Ireland (ACPGBI) network between April and June 2018. RESULTS: Sixty-one responses were collected from surgeons throughout the UK. Of these respondents, 69% indicated that cutaneous abscesses would always or usually require a General Anaesthetic (GA) for treatment, and 82% indicated that abscesses were at least sometimes not treated until the next day due to a lack of resources. While 79% of surgeons stated that pus swabs are always or are usually taken, 44% of respondents never or rarely chased the results. The main indications for giving antibiotics were sepsis/systemically unwell patients, and cellulitis. 31% of responding centres had an abscess management protocol, and 82% of respondents confirmed that they would always pack the abscess wound post-operatively. CONCLUSION: 'Incision and drainage' is currently the most widely used technique for the surgical management of cutaneous abscess. However, this study demonstrates the significant variability in the use of anaesthesia, antibiotics, packing and the use of protocols to guide and streamline patient management.

Managing haematology and oncology patients during the COVID-19 pandemic: interim consensus guidance.

INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consider causes in addition to COVID-19, including other infections and therapy-related pneumonitis. For suspected or confirmed COVID-19, discuss temporary cessation of cancer therapy with a relevant specialist. Provide information on COVID-19 for patients and carers. Adopt measures within cancer centres to reduce risk of nosocomial SARS-CoV-2 acquisition; support population-wide social distancing; reduce demand on acute services; ensure adequate staffing; and provide culturally safe care. Measures should be equitable, transparent and proportionate to the COVID-19 threat. Consider the risks and benefits of modifying cancer therapies due to COVID-19. Communicate treatment modifications, and review once health service capacity allows. Consider potential impacts of COVID-19 on the blood supply and availability of stem cell donors. Discuss and document goals of care, and involve palliative care services in contingency planning. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This interim consensus guidance provides a framework for clinicians managing patients with cancer during the COVID-19 pandemic. In view of the rapidly changing situation, clinicians must also monitor national, state, local and institutional policies, which will take precedence. ENDORSED BY: Australasian Leukaemia and Lymphoma Group; Australasian Lung Cancer Trials Group; Australian and New Zealand Children's Haematology/Oncology Group; Australia and New Zealand Society of Palliative Medicine; Australasian Society for Infectious Diseases; Bone Marrow Transplantation Society of Australia and New Zealand; Cancer Council Australia; Cancer Nurses Society of Australia; Cancer Society of New Zealand; Clinical Oncology Society of Australia; Haematology Society of Australia and New Zealand; National Centre for Infections in Cancer; New Zealand Cancer Control Agency; New Zealand Society for Oncology; and Palliative Care Australia.

Improving management of comorbidity in patients with colorectal cancer using comprehensive medical assessment: a pilot study.

BACKGROUND: Screening for and active management of comorbidity soon after cancer diagnosis shows promise in altering cancer treatment and outcomes for comorbid patients. Prior to a large multi-centre study, piloting of the intervention (comprehensive medical assessment) was undertaken to investigate the feasibility of the comorbidity screening tools and proposed outcome measures, and the feasibility, acceptability and potential effect of the intervention. METHODS: In this pilot intervention study, 72 patients of all ages (36 observation/36 intervention) with newly diagnosed or recently relapsed colorectal adenocarcinoma were enrolled and underwent comorbidity screening and risk stratification. Intervention patients meeting pre-specified comorbidity criteria were referred for intervention, a comprehensive medical assessment carried out by geriatricians. Each intervention was individually tailored but included assessment and management of comorbidity, polypharmacy, mental health particularly depression, functional status and psychosocial issues. Recruitment and referral to intervention were tracked, verbal and written feedback were gathered from staff, and semi-structured telephone interviews were conducted with 13 patients to assess screening tool and intervention feasibility and acceptability. Interviews were transcribed and analysed thematically. Patients were followed for 6-12 months after recruitment to assess feasibility of proposed outcome measures (chemotherapy uptake and completion rates, grade 3-5 treatment toxicity, attendance at hospital emergency clinic, and unplanned hospitalisations) and descriptive data on outcomes collated. RESULTS: Of the 29 intervention patients eligible for the intervention, 21 received it with feedback indicating that the intervention was acceptable. Those in the intervention group were less likely to be on 3+ medications, to have been admitted to hospital in previous 12 months, or to have limitations in daily activities. Collection of data to measure proposed outcomes was feasible with 55% (6/11) of intervention patients completing chemotherapy as planned compared to none (of 14) of the control group. No differences were seen in other outcome measures. Overall the study was feasible with modification, but the intervention was difficult to integrate into clinical pathways. CONCLUSIONS: This study generated valuable results that will be used to guide modification of the study and its approaches prior to progressing to a larger-scale study. TRIAL REGISTRATION: Retrospective, 26 August 2019, ACTRN12619001192178.

Interprofessional Education for Cancer Care.

BACKGROUND: Cancer care is typically delivered by a range of health professionals, and is frequently a uniprofessional pre-registration clinical placement. A workplace-based, 6-hour interprofessional education (IPE) pilot on cancer care, led by clinical tutors, was undertaken in a New Zealand hospital, accompanied by an external evaluation. The pilot involved a cohort of 21 dietetic, medicine, pharmacy, physiotherapy and radiation therapy students. The aim of the evaluation was to determine student and tutor reactions to IPE, and any changes in perceptions and attitudes. METHODS: The evaluation used focus groups to collect data: two student groups and one tutor group. Focus groups were audio-recorded, transcribed; the content was coded and then analysed. RESULTS: Both students and tutors reported benefits from having IPE in the workplace environment, with cancer care seen as a suitable topic. Students reported a better understanding of professional roles, skills and the provision of collaborative care, and suggested other professions should be included in future IPE. Patient selection needed to be better tailored for physiotherapy students to ensure uniform relevance. As a result of competing demands, tutors found that they needed an 18-month lead time to establish the IPE programme. Tutors felt that the programme had gone relatively smoothly and that they had benefitted from forming closer interpersonal relationships, but noted considerable unanticipated and unremunerated preparation time. DISCUSSION: This short workplace-based IPE programme elicited a positive student and tutor response, but highlighted the need for improvements: broadening the topic area, targeted patient selection, including more professions and providing administrative support for tutors. Cancer care was generally seen as a suitable topic.

Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK.

BACKGROUND & AIMS: There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals. METHODS: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103). RESULTS: Of 1267 patients (80% women, 91% Caucasian, age (median(range)) 55(8-86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking Nitrofurantoin and 0.7% Khat. Twenty-one percent had clinical decompensation and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was ≥1 year in 19% and was longer in jaundiced vs non-jaundiced patients. HBV and HCV serology were undocumented in 4%, serum immunoglobulins in 31% and autoantibodies in 11%-27%. When documented, ≥1 antibody was present in 83%. LKM-1-positive and autoantibody-negative patients had more severe disease. Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University Hospitals compared to District General Hospitals, were more likely to report histological features of AIH. CONCLUSIONS: This cohort from across the UK is older than other multicentre AIH cohorts. One-fifth had decompensation or MELD >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one-third and rosettes and emperipolesis were infrequently reported.

Early Molecular Stratification of High-risk Primary Biliary Cholangitis.

High-risk primary biliary cholangitis (PBC), defined by inadequate response at one year to Ursodeoxycholic acid (UDCA), is associated with disease progression and liver transplantation. Stratifying high-risk patients early would facilitate improved approaches to care. Using long-term follow-up data to define risk at presentation, 6 high-risk PBC patients and 8 low-risk patients were identified from biopsy, transplant and biochemical archival records. Formalin-fixed paraffin-embedded (FFPE) liver biopsies taken at presentation were graded (Scheuer and Nakanuma scoring) and gene expression analysed using the NanoString® nCounter PanCancer Immunity 770-gene panel. Principle component analysis (PCA) demonstrated discrete gene expression clustering between controls and high- and low-risk PBC. High-risk PBC was characterised by up-regulation of genes linked to T-cell activation and apoptosis, INF-γ signalling and leukocyte migration and down-regulation of those linked to the complement pathway. CDKN1a, up-regulated in high-risk PBC, correlated with significantly increased expression of its gene product, the senescence marker p21WAF1/Cip, by biliary epithelial cells. Our findings suggest high- and low-risk PBC are biologically different from disease outset and senescence an early feature in high-risk disease. Identification of a high-risk 'signal' early from standard FFPE tissue sections has clear clinical utility allowing for patient stratification and second-line therapeutic intervention.

Effect of statin and aspirin use on toxicity and pathological complete response rate of neo-adjuvant chemoradiation for rectal cancer.

AIM: To retrospectively evaluate the potential impact of statin and aspirin use on acute toxicity and pathological complete response (pCR) rate in rectal cancer patients receiving neo-adjuvant long-course radiation therapy (LCRT) with concurrent chemotherapy. METHODS: A retrospective review was performed of all patients undergoing neo-adjuvant LCRT for rectal adenocarcinoma at the Regional Cancer Treatment Service between 1 September 2007 and 1 June 2011. Data obtained include demographic details; date and radiological TNM stage at diagnosis; medication taken at time of RT; toxicity during LCRT; and surgical histology to determine if a pCR was obtained following LCRT. RESULTS: Neo-adjuvant LCRT was administered to 142 patients for rectal cancer during this period; concurrent chemotherapy was omitted in 13 due to significant comorbidities. TNM stage was 2 or 3 radiologically at diagnosis in 127 (89.4%) of patients. At the time of LCRT, 23% were taking a statin and 25% were taking aspirin. Of 135 assessable patients, 34 (13%) achieved a pCR at surgery. On logistic regression, pCR was not significantly associated with the use of chemotherapy, statins, aspirin, other NSAIDs, T-stage or N-stage. There was no significant correlation between statin or aspirin use with bladder or rectal toxicity. Actuarial time to maximum rectal toxicity was not different in statin users or nonusers. CONCLUSION: In contrast to other larger retrospective series, this study did not find improvements in toxicity or pCR rate through statin or aspirin use in rectal cancer patients undergoing LCRT. Their potential benefits in this setting would be best studied prospectively in a large randomized trial.

Clinicians' views on introducing epidermal growth factor receptor testing in New Zealand.

AIM: Inequities exist in the outcomes of patients diagnosed with lung cancer in New Zealand, with Maori (the indigenous population) having significantly higher diagnosis rates and poorer survival. We investigated the feasibility of introducing epidermal growth factor receptor (EGFR) testing into New Zealand as one step to address these inequities. METHODS: An anonymous electronic questionnaire was distributed to clinicians from specialties involved in lung cancer management. Questions were grouped around topics including challenges in lung cancer management, EGFR testing, targeted therapy, costs and interest in the development of a national lung tissue bank. RESULTS: In total, 61 clinicians responded and noted that few of their non-small-cell lung cancer patients were tested for EGFR mutations. Most clinicians (84%) would prefer a centralized testing service and 95% would use an overseas laboratory if publicly funded; however 62% did not know or had no preference for test procedures. Under half (46%) had used tyrosine kinase inhibitors with only a small number of patients and 79% supported the development of a lung tissue bank. CONCLUSION: While most respondents had little experience with EGFR testing, clinicians supported its introduction into New Zealand. However, a number of potential issues, including cost, laboratory expertise and the need for improved access to first-line targeted therapies that could be used if tests were mutation positive were also identified. Respondents identified potential cultural sensitivities related to sending tissue samples abroad for genetic tests that would necessitate clinicians discussing this option with individual patients.

Early outcomes of active surveillance for localized prostate cancer.

OBJECTIVE: To describe the preliminary clinical outcomes of active surveillance (AS), a new strategy aiming to individualize the management of early prostate cancer by selecting only those men with significant cancers for curative therapy, and illustrate the contrast with a policy of watchful waiting (WW). PATIENTS AND METHODS: Eighty men with early prostate cancer began AS at the authors' institution between 1993 and 2002. Eligibility included histologically confirmed prostatic adenocarcinoma, fitness for radical treatment, clinical stage T1/T2, N0/X, M0/X, a prostate specific antigen (PSA) level of < or = 20 ng/mL, and a Gleason score of < or = 7. PSA was measured and a digital rectal examination conducted at 3-6 month intervals. The decision between continued monitoring or radical treatment was informed by the rate of rise of PSA, and was made according to the judgement of each patient and clinician. During the same period, 32 men with localized prostate cancer (any T stage, N0/X, M0/X, any PSA, Gleason score < or = 7) were managed by WW; hormonal treatment was indicated for symptomatic prostate cancer progression. The PSA doubling time (DT) was calculated using linear regression of ln(PSA) against time, using all pretreatment PSA values. RESULTS: At a median follow-up of 42 months, 64 (80%) of the 80 patients on AS remained under observation, 11 (14%) received radical treatment and five (6%) died from other causes. No patient developed evidence of metastatic disease, none started palliative hormone therapy, and there were no deaths from prostate cancer. Of the 11 patients who received radical treatment all remained biochemically controlled with no clinical evidence of recurrent disease. The median PSA DT while on AS was 12 years. Twenty (62%) of the 32 patients on WW remained on observation, eight (25%) received palliative hormonal therapy and four (12%) died, including one from prostate cancer. CONCLUSIONS: AS is feasible in selected men with early prostate cancer. The natural history of this disease often appears extremely indolent, and most men on AS will avoid radical treatment. There is a marked contrast between AS (with radical treatment for biochemical progression) and WW (with palliative treatment for symptomatic progression). Ongoing studies are seeking to optimize the AS protocol, and to compare the long-term outcomes with those of immediate radical treatment.