Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection.

BACKGROUND: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. METHODS: DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. RESULTS: The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. CONCLUSIONS: Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users

Acceptability and appropriateness of a clinical pathway for managing anxiety and depression in cancer patients: a mixed methods study of staff perspectives.

BACKGROUND: Clinical pathways (CPs) can improve health outcomes, but to be sustainable, must be deemed acceptable and appropriate by staff. A CP for screening and management of anxiety and depression in cancer patients (the ADAPT CP) was implemented in 12 Australian oncology services for 12 months, within a cluster randomised controlled trial of core versus enhanced implementation strategies. This paper compares staff-perceived acceptability and appropriateness of the ADAPT CP across study arms. METHODS: Multi-disciplinary lead teams at each service tailored, planned, championed and implemented the CP. Staff at participating services, purposively selected for diversity, completed a survey and participated in an interview prior to implementation (T0), and at midpoint (6 months: T1) and end (12 months: T2) of implementation. Interviews were recorded, transcribed and thematically analysed. RESULTS: Seven metropolitan and 5 regional services participated. Questionnaires were completed by 106, 58 and 57 staff at T0, T1 and T2 respectively. Eighty-eight staff consented to be interviewed at T0, with 89 and 76 at T1 and T2 (response rates 70%, 66% and 57%, respectively). Acceptability/appropriateness, on the quantitative measure, was high at T0 (mean of 31/35) and remained at that level throughout the study, with no differences between staff from core versus enhanced services. Perceived burden was relatively low (mean of 11/20) with no change over time. Lowest scores and greatest variability pertained to perceived impact on workload, time and cost. Four major themes were identified: 1) Mental health is an important issue which ADAPT addresses; 2) ADAPT helps staff deliver best care, and reduces staff stress; 3) ADAPT is fit for purpose, for both cancer care services and patients; 4) ADAPT: a catalyst for change. Opposing viewpoints are outlined. CONCLUSIONS: This study demonstrated high staff-perceived acceptability and appropriateness of the ADAPT CP with regards to its focus, evidence-base, utility to staff and patients, and ability to create change. However, concerns remained regarding burden on staff and time commitment. Strategies from a policy and managerial level will likely be required to overcome the latter issues. TRIAL REGISTRATION: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN12617000411347. https://www.anzctr.org.au/

Efficacy and safety of high-dose chemotherapy as the first or subsequent salvage treatment line in patients with relapsed or refractory germ cell cancer: an international multicentric analysis

\ua9 2024 The Author(s)Background: In relapsed or refractory (RR) metastatic germ cell cancer (GCC), high-dose (HD) chemotherapy (CTX) plus autologous stem cell transplantation is considered the standard of care. Limited data exist regarding the efficacy of HD-CTX following conventionally dosed salvage regimens (CDRs). This analysis explores and contrasts the efficacy of HD-CTX as the first or subsequent salvage regimen. Patients and methods: Data were retrospectively collected to explore the efficacy of HD-CTX administered as the first (group A) or subsequent salvage CTX (group B) after a CDR. The primary endpoint was OS from the time of HD-CTX. Associations of survival, overall response rate (ORR), and toxicity with clinical characteristics were explored using stratified Kaplan–Meier and Cox regression models. Results: Overall, 283 patients with GCC were included from 11 international centers, with 159 patients (56%) in group A and 124 patients (44%) in group B. The first salvage treatment was administered between 1998 and 2022, with a median follow-up of 27.0 [standard deviation (SD) 46.2] months for group A and 17.0 (SD 48.5) months for group B. The median OS from HD-CTX treatment initiation was not reached in group A, compared with 25 months in group B (P = 0.00027), associated with 2- and 5-year OS rates of 74% and 63% (group A) versus 53% and 37% (group B), respectively. When administered as the first salvage treatment, HD-CTX was associated with a higher ORR (79% versus 60%; P = 0.013) and lower nonhematologic grade ≥3 toxicity rate (78% versus 97%; P < 0.001). Concerning risk factor analysis for the total cohort, the International Prognostic Factors Study Group score was the only independent predictor of OS in multivariable analysis (P = 0.006). Conclusions: When administered as the initial salvage treatment or after CDR, HD-CTX exhibits curative potential for patients with RR GCC. The efficacy and safety outcomes were more favorable when HD-CTX was conducted as the first salvage treatment line

Effect of core versus enhanced implementation strategies on adherence to a clinical pathway for managing anxiety and depression in cancer patients in routine care: a cluster randomised controlled trial.

BACKGROUND: Optimal strategies to facilitate implementation of evidence-based clinical pathways are unclear. We evaluated two implementation strategies (Core versus Enhanced) to facilitate implementation of a clinical pathway for the management of anxiety and depression in cancer patients (the ADAPT CP). METHODS: Twelve cancer services in NSW Australia were cluster randomised, stratified by service size, to the Core versus Enhanced implementation strategy. Each strategy was in place for 12 months, facilitating uptake of the ADAPT CP (the intervention being implemented). The Core strategy included a lead team with champions, staff training and awareness campaigns prior to implementation, plus access to feedback reports and telephone or online support during implementation. The Enhanced strategy included all Core supports plus monthly lead team meetings, and proactive, ongoing advice on managing barriers, staff training and awareness campaigns throughout implementation. All patients at participating sites were offered the ADAPT CP as part of routine care, and if agreeable, completed screening measures. They were allocated a severity step for anxiety/depression from one (minimal) to five (severe) and recommended management appropriate to their severity step. Multi-level mixed-effect regression analyses examined the effect of Core versus Enhanced implementation strategy on adherence to the ADAPT CP (binary primary outcome: adherent ≥ 70% of key ADAPT CP components achieved versus non-adherent < 70%), with continuous adherence as a secondary outcome. Interaction between study arm and anxiety/depression severity step was also explored. RESULTS: Of 1280 registered patients, 696 (54%) completed at least one screening. As patients were encouraged to re-screen, there were in total 1323 screening events (883 in Core and 440 in Enhanced services). The main effect of implementation strategy on adherence was non-significant in both binary and continuous analyses. Anxiety/depression step was significant, with adherence being higher for step 1 than for other steps (p = 0.001, OR = 0.05, 95% CI 0.02-0.10). The interaction between study arm and anxiety/depression step was significant (p = 0.02) in the continuous adherence analysis only: adherence was significantly higher (by 7.6% points (95% CI 0.08-15.1%) for step 3 in the Enhanced arm (p = .048) and trending to significance for step 4. DISCUSSION: These results support ongoing implementation effort for the first year of implementation to ensure successful uptake of new clinical pathways in over-burdened clinical services. TRIAL REGISTRATION: ANZCTR Registration: ACTRN12617000411347 (Trial registered 22/03/2017; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372486&isReview=true )

Comparison of implementation strategies to influence adherence to the clinical pathway for screening, assessment and management of anxiety and depression in adult cancer patients (ADAPT CP): Study protocol of a cluster randomised controlled trial

© 2018 The Author(s). Background: Health service change is difficult to achieve. One strategy to facilitate such change is the clinical pathway, a guide for clinicians containing a defined set of evidence-based interventions for a specific condition. However, optimal strategies for implementing clinical pathways are not well understood. Building on a strong evidence-base, the Psycho-Oncology Co-operative Research Group (PoCoG) in Australia developed an evidence and consensus-based clinical pathway for screening, assessing and managing cancer-related anxiety and depression (ADAPT CP) and web-based resources to support it - staff training, patient education, cognitive-behavioural therapy and a management system (ADAPT Portal). The ADAPT Portal manages patient screening and prompts staff to follow the recommendations of the ADAPT CP. This study compares the clinical and cost effectiveness of two implementation strategies (varying in resource intensiveness), designed to encourage adherence to the ADAPT CP over a 12-month period. Methods: This cluster randomised controlled trial will recruit 12 cancer service sites, stratified by size (large versus small), and randomised at site level to a standard (Core) versus supported (Enhanced) implementation strategy. After a 3-month period of site engagement, staff training and site tailoring of the ADAPT CP and Portal, each site will "Go-live", implementing the ADAPT CP for 12 months. During the implementation phase, all eligible patients will be introduced to the ADAPT CP as routine care. Patient participants will be registered on the ADAPT Portal to complete screening for anxiety and depression. Staff will be responsible for responding to prompts to follow the ADAPT CP. The primary outcome will be adherence to the ADAPT CP. Secondary outcomes include staff attitudes to and experiences of following the ADAPT CP, using the ADAPT Portal and being exposed to ADAPT implementation strategies, collected using quantitative and qualitative methods. Data will be collected at T0 (baseline, after site engagement), T1 (6 months post Go-live) and T2 (12 months post Go-live). Discussion: This will be the first cluster randomised trial to establish optimal levels of implementation effort and associated costs to achieve successful uptake of a clinical pathway within cancer care. Trial registration: The study was registered prospectively with the ANZCTR on 22/3/2017. Trial ID ACTRN1261700041134

Primary pancreatic lymphoma – pancreatic tumours that are potentially curable without resection, a retrospective review of four cases

BACKGROUND: Primary pancreatic lymphomas (PPL) are rare tumours of the pancreas. Symptoms, imaging and tumour markers can mimic pancreatic adenocarcinoma, but they are much more amenable to treatment. Treatment for PPL remains controversial, particularly the role of surgical resection. METHODS: Four cases of primary pancreatic lymphoma were identified at Prince of Wales Hospital, Sydney, Australia. A literature review of cases of PPL reported between 1985 and 2005 was conducted, and outcomes were contrasted. RESULTS: All four patients presented with upper abdominal symptoms associated with weight loss. One case was diagnosed without surgery. No patients underwent pancreatectomy. All patients were treated with chemotherapy and radiotherapy, and two of four patients received rituximab. One patient died at 32 months. Three patients are disease free at 15, 25 and 64 months, one after successful retreatment. Literature review identified a further 103 patients in 11 case series. Outcomes in our series and other series of chemotherapy and radiotherapy compared favourably to surgical series. CONCLUSION: Biopsy of all pancreatic masses is essential, to exclude potentially curable conditions such as PPL, and can be performed without laparotomy. Combined multimodality treatment, utilising chemotherapy and radiotherapy, without surgical resection is advocated but a cooperative prospective study would lead to further improvement in treatment outcomes

Large-scale mass wasting in the western Indian Ocean constrains onset of East African rifting

Faulting and earthquakes occur extensively along the flanks of the East African Rift System, including an offshore branch in the western Indian Ocean, resulting in remobilization of sediment in the form of landslides. To date, constraints on the occurrence of submarine landslides at margin scale are lacking, leaving unanswered a link between rifting and slope instability. Here, we show the first overview of landslide deposits in the post-Eocene stratigraphy of the Tanzania margin and we present the discovery of one of the biggest landslides on Earth: the Mafia mega-slide. The emplacement of multiple landslides, including the Mafia mega-slide, during the early-mid Miocene is coeval with cratonic rifting in Tanzania, indicating that plateau uplift and rifting in East Africa triggered large and potentially tsunamigenic landslides likely through earthquake activity and enhanced sediment supply. This study is a first step to evaluate the risk associated with submarine landslides in the region

Accurate isolation and detection of circulating tumor cells using enrichment-free multiparametric high resolution imaging

IntroductionThe reliable and accurate detection of rare circulating tumor cells (CTCs) from cancer patient blood samples promises advantages in both research and clinical applications. Numerous CTC detection methods have been explored that rely on either the physical properties of CTCs such as density, size, charge, and/or their antigen expression profiles. Multiple factors can influence CTC recovery including blood processing method and time to processing. This study aimed to examine the accuracy and sensitivity of an enrichment-free method of isolating leukocytes (AccuCyte® system) followed by immunofluorescence staining and high-resolution imaging (CyteFinder® instrument) to detect CTCs.MethodHealthy human blood samples, spiked with cancer cells from cancer cell lines, as well as blood samples obtained from 4 subjects diagnosed with cancer (2 pancreatic, 1 thyroid, and 1 small cell lung) were processed using the AccuCyte-CyteFinder system to assess recovery rate, accuracy, and reliability over a range of processing times.ResultsThe AccuCyte-CyteFinder system was highly accurate (95.0%) at identifying cancer cells in spiked-in samples (in 7.5 mL of blood), even at low spiked-in numbers of 5 cells with high sensitivity (90%). The AccuCyte-CyteFinder recovery rate (90.9%) was significantly higher compared to recovery rates obtained by density gradient centrifugation (20.0%) and red blood cell lysis (52.0%). Reliable and comparable recovery was observed in spiked-in samples and in clinical blood samples processed up to 72 hours post-collection. Reviewer analysis of images from spiked-in and clinical samples resulted in high concordance (R-squared value of 0.998 and 0.984 respectively).DiscussionThe AccuCyte-CyteFinder system is as an accurate, sensitive, and clinically practical method to detect and enumerate cancer cells. This system addresses some of the practical logistical challenges in incorporating CTCs as part of routine clinical care. This could facilitate the clinical use of CTCs in guiding precision, personalized medicine

Changes in psychosocial distress and the number and types of problems reported by patients with cancer when routine screening is integrated within cancer services

Background: The impact of patient-reported outcome measures on patient outcomes in longitudinal clinical studies is poorly understood. This observational study explored longitudinal changes in distress and problems reported by cancer patients screened and managed in accordance with a clinical pathway for anxiety and depression (ADAPT CP), implemented over 12 months. Methods: Patients reported distress using the Distress Thermometer and indicated reasons for distress using the 39-item Problem List across five domains: practical, social, emotional, spiritual/religious, and physical. Repeat screening occurred on average 3 monthly (quarterly). Results: Six hundred sixty patients from 10 participating services completed 1,256 screening events over 12 months, reporting 8,645 problems. On average, more emotional (27-34%) and physical (19-22%) issues were reported across all quarters than practical (7-9%) and social (8-9%) issues. Distress and emotional, physical, practical, and social problems reduced from initial to follow-up screens, although the decrease in emotional problems over time was not significantly different than that of the other problems. Worry, fatigue, sleep difficulties, health of family members, and insurance/finances were more persistent problems. Conclusions: Although distress and the change in the number of emotional concerns over time did not differ from other problems, rescreening is recommended within oncology settings to allow patients to indicate new or persistent problems and hospital staff to monitor and assess needs. Emotional concerns are high in oncology patients, suggesting the need for the prioritization of psychosocial care. These problems can persist over time due to their clinically challenging nature or because access to, or implementation of, evidence-based interventions are not yet widespread