Pancreas-related persisting sequelae in ALL survivors with a history of asparaginase-associated pancreatitis: A part of the ALL-STAR study.

OBJECTIVES: Asparaginase-associated pancreatitis (AAP) occurs in up to 18% of patients treated for acute lymphoblastic leukemia (ALL); however, long-term sequelae are largely unexplored. We aimed to explore pancreatic sequelae among ALL survivors with and without AAP. METHODS: We investigated pancreatic sequelae in a national cohort of ALL survivors, aged 1-45 years at ALL diagnosis treated according to the NOPHO-ALL2008 protocol and included sex- and age-matched community controls. RESULTS: We included 368 survivors (median follow-up 6.9 years), including 47 survivors with AAP and 369 controls. The p-lipase and p-pancreas-type amylase levels were lower in AAP survivors compared with both non-AAP survivors (Medians: 23 U/L [IQR 14-32] and 18 U/L [IQR 10-25] versus 29 [IQR 24-35] and 22 [17-28], p < .001 and p = .002) and community controls (28 U/L [IQR 22-33] and 21 U/L [IQR 17-26], both p < .006). Fecal-elastase was more frequently reduced in AAP survivors compared with non-AAP survivors (7/31 vs. 4/144, p = .001). Persisting pancreatic sequelae were found in 15/47 of AAP survivors and 20/323 of non-AAP survivors (p < .001), including diabetes mellitus in 2/39 of AAP survivors and 2/273 of non-AAP survivors. CONCLUSIONS: ALL survivors with AAP are at increased risk of persisting pancreatic dysfunction and require special attention during follow-up.

Ensuring competence in ultrasound-guided procedures-a validity study of a newly developed assessment tool.

OBJECTIVES: To investigate the validity of the Interventional Ultrasound Skills Evaluation (IUSE) tool for assessment of procedural competence in ultrasound-guided procedures in a clinical environment, including a pass/fail score. METHODS: Novices and experienced radiologists were recruited from four hospitals and were observed and assessed while performing ultrasound-guided procedures. Performances were assessed using the IUSE tool by two independent raters. Validity evidence was gathered in accordance with Messick's framework: response process was ensured by standardisation of written rater instructions. Internal structure was explored using Cronbach's alpha for internal consistency reliability; inter-rater reliability was calculated as Pearson's r independently across all ratings, and test-retest reliability was reported using Cronbach's alpha. Relationship to other variables was investigated by comparing performances of the participants in each group. Consequences evidence was explored by calculating a pass/fail standard using the contrasting groups method. RESULTS: Six novices and twelve experienced radiologists were enrolled. The IUSE tool had high internal consistency (Cronbach's alpha = 0.96, high inter-rater reliability (Pearson's r = 0.95), and high test-retest reliability (Cronbach's alpha = 0.98), and the mean score was 33.28 for novices and 59.25 for experienced with a highly significant difference (p value < 0.001). The pass/fail score was set at 55 resulting in no false positives or false negatives. CONCLUSIONS: Validity evidence from multiple sources supports the use of the IUSE tool for assessment of competence in ultrasound-guided procedures in a clinical environment and its use in high-stakes assessment such as certification. A credible pass/fail criterion was established to inform decision-making. KEY POINTS: • A multi-site validity investigation established that the Interventional Ultrasound Skills Evaluation (IUSE) tool can be used to assess procedural competence in ultrasound-guided procedures. • Validity evidence was gathered according to Messick's framework validity from the following sources: response process, internal structure, relationship to other variables, and consequences evidence. • The IUSE tool can be used for both formative and summative assessment, and a credible pass/fail score was established to help inform decision-making such as certification.

National, clinical cohort study of late effects among survivors of acute lymphoblastic leukaemia: the ALL-STAR study protocol.

INTRODUCTION: More than 90% of patients diagnosed with childhood acute lymphoblastic leukaemia (ALL) today will survive. However, half of the survivors are expected to experience therapy-related chronic or late occurring adverse effects, reducing quality of life. Insight into underlying risk trajectories is warranted. The aim of this study is to establish a Nordic, national childhood ALL survivor cohort, to be investigated for the total somatic and psychosocial treatment-related burden as well as associated risk factors, allowing subsequent linkage to nation-wide public health registers. METHODS AND ANALYSIS: This population-based observational cohort study includes clinical follow-up of a retrospective childhood ALL survivor cohort (n=475), treated according to a common Nordic ALL protocol during 2008-2018 in Denmark. The study includes matched controls. Primary endpoints are the cumulative incidence and cumulative burden of 197 health conditions, assessed through self-report and proxy-report questionnaires, medical chart validation, and clinical examinations. Secondary endpoints include organ-specific outcome, including cardiovascular and pulmonary function, physical performance, neuropathy, metabolic disturbances, hepatic and pancreatic function, bone health, oral and dental health, kidney function, puberty and fertility, fatigue, and psychosocial outcome. Therapy exposure, acute toxicities, and host genome variants are explored as risk factors. ETHICS AND DISSEMINATION: The study is approved by the Regional Ethics Committee for the Capital Region in Denmark (H-18035090/H-20006359) and by the Danish Data Protection Agency (VD-2018-519). Results will be published in peer-reviewed journals and are expected to guide interventions that will ameliorate the burden of therapy without compromising the chance of cure.

Can Strain Elastography Predict Malignancy of Soft Tissue Tumors in a Tertiary Sarcoma Center?

This study aims to investigate the ability of ultrasound strain elastography as an adjunct to predict malignancy in soft tissue tumors suspect of sarcoma or metastasis in a tertiary reference center for sarcoma. A total of 137 patients were included prospectively. Patients were referred on the basis of clinical or radiological suspicion of malignant soft tissue tumor. All patients had previously undergone diagnostic imaging (MRI, CT or PET-CT). After recording strain elastography cine loops, ultrasound guided biopsy was performed. Three investigators, who were blinded to final diagnosis, reviewed all elastograms retrospectively. For each elastogram, a qualitative, visual 5-point score was decided in consensus and a strain ratio was calculated. Final pathology obtained from biopsy or tumor resection served as gold standard. Eighty-one tumors were benign, and 56 were malignant. t-tests showed a significant difference in mean visual score between benign and malignant tumors. There was no significant difference in mean strain ratio between the two groups. Strain elastography may be a valuable adjunct to conventional B-mode ultrasound, perhaps primarily in primary care, when considering whether to refer to a sarcoma center or to biopsy, although biopsies cannot reliably be ruled out based on the current data.

Targeted ultrasound and fine-needle aspiration cytology for sentinel node diagnostics in early-stage melanoma: a validation study.

Ultrasound-guided fine-needle aspiration cytology (US-FNAC) is used to evaluate the involvement of lymph nodes in various malignant diseases. Its value in detecting sentinel lymph node (SN) metastasis preoperatively in melanoma patients is controversial and is the subject of this study. In this prospective validation study, 91 consecutive patients with melanoma clinical stage I (n=64) and II (n=27) were examined with US-FNAC before SN biopsy from 2012 to 2014 at a tertiary center. All patients underwent lymphoscintigraphy before the US-FNAC. Lymph nodes that showed any of the Berlin morphologic criteria on ultrasonography were examined using FNAC. The median Breslow thickness of the melanomas was 1.22 mm (range: 0.47-11.5 mm). Twenty-two percent of the patients had metastases in their SNs, 90% of which were smaller than 2 mm in largest diameter. The percentages of metastases with a size more than 1 mm were 50 and 29%, respectively, in the true-positive and false-negative US groups. The sensitivity, specificity, positive predictive value, and negative predictive value for overall US examination were 30, 81, 24, and 83%, respectively. None of the FNACs contained conclusive malignant cells. The specificity of the FNAC was 76%. Our results show that US-FNAC was not a useful diagnostic tool in our setting as it did not add significantly to the staging and management of patients with mainly thin cutaneous melanomas, perhaps because of the often small size of the SN metastases. It may be useful in the early diagnosis of lymph node metastases in a subgroup of melanoma patients with larger metastases.