The effect of non-immersive virtual reality radiographic positioning simulation on first-year radiography students' image evaluation performance.

INTRODUCTION: Optimal radiographic image quality is critical because it affects the accuracy of the reporter's interpretation. Radiographers have an ethical obligation to obtain quality diagnostic images while protecting patients from unnecessary radiation, including minimizing rejected and repeated images. Repeated imaging due to positioning errors have increased in recent years. METHODS: This study evaluated the effectiveness of non-immersive virtual reality (VR) simulation on first-year students' evaluation of positioning errors on resultant knee and lumbar spine images. Crossover intervention design was used to deliver radiographic image evaluation instruction through traditional lecture and guided simulation using non-immersive VR to 33 first-year radiography students at a single academic institution located across four geographic program locations. Pre- and post-test knowledge assessments examined participants' ability to recognize positioning errors on multiple-choice and essay questions. RESULTS: Raw mean scores increased on multiple choice questions across the entire cohort for the knee (M = 0.82, SD = 3.38) and lumbar spine (M = 2.91, SD = 3.69) but there was no significant difference in performance by instructional method (p = 0.60). Essay questions reported very minimal to no raw mean score increases for the knee (M = 0.27, SD = 2.78) and lumbar spine (M = 0.00, SD = 2.55), with no significant difference in performance by instructional method (p = 0.72). CONCLUSION: Guided simulation instruction was shown to be as effective as traditional lecture. Results also suggest that novice learners better recognize image evaluation errors and corrections from a list of options but have not yet achieved the level of competence needed to independently evaluate radiographic images for diagnostic criteria. IMPLICATIONS FOR PRACTICE: Non-immersive VR simulation is an effective tool for image evaluation instruction. VR increases access to authentic image evaluation practice by providing a simulated resultant image based off the students' applied positioning skills.

Fibroblast activation protein-α expression in fibroblasts is common in the tumor microenvironment of colorectal cancer and may serve as a therapeutic target.

Background: Colorectal cancer (CRC) is still one of the leading causes of cancer death worldwide, emphasizing the need for further diagnostic and therapeutic approaches. Cancer invasion and metastasis are affected by the tumor microenvironment (TME), with cancer-associated fibroblasts (CAF) being the predominant cellular component. An important marker for CAF is fibroblast activation protein-α (FAP) which has been evaluated as therapeutic target for, e.g., radioligand therapy. The aim of this study was to examine CRC regarding the FAP expression as a candidate for targeted therapy. Methods: 67 CRC, 24 adenomas, 18 tissue samples of inflammation sites and 28 non-neoplastic, non-inflammatory tissue samples of colonic mucosa were evaluated for immunohistochemical FAP expression of CAF in tissue microarrays. The results were correlated with clinicopathological data, tumor biology and concurrent expression of additional immunohistochemical parameters. Results: 53/67 (79%) CRC and 6/18 (33%) inflammatory tissue specimens showed expression of FAP. However, FAP was only present in 1/24 (4%) adenomas and absent in normal mucosa (0/28). Thus, FAP expression in CRC was significantly higher than in the other investigated groups. Within the CRC cohort, expression of FAP did not correlate with tumor stage, grading or the MSI status. However, it was observed that tumors exhibiting high immunohistochemical expression of Ki-67, CD3, p53, and ß-Catenin showed a significantly higher incidence of FAP expression. Conclusion: In the crosstalk between tumor cells and TME, CAF play a key role in carcinogenesis and metastatic spread. Expression of FAP was detectable in the majority of CRC but nearly absent in precursor lesions and non-neoplastic, non-inflammatory tissue. This finding indicates that FAP has the potential to emerge as a target for new diagnostic and therapeutic concepts in CRC. Additionally, the association between FAP expression and other immunohistochemical parameters displays the interaction between different components of the TME and demands further investigation.

A prognostic systemic inflammation score (SIS) in patients with advanced intrahepatic cholangiocarcinoma.

PURPOSE: Systemic-inflammatory response parameters (SIR) are known prognostic markers in different tumour entities, but have not been evaluated in patients with iCCA treated with systemic chemotherapy. Therefore, we evaluated the impact of different SIR markers on the clinical course of patients with advanced iCCA treated at our center. METHODS: SIR markers were retrospectively evaluated in 219 patients with iCCA at the West-German-Cancer-Center Essen from 2014 to 2019. Markers included neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), CRP, and the modified Glasgow-Prognostic-Score (mGPS), which were correlated with clinico-pathological findings, response to chemotherapy (ORR), progression-free (PFS) and overall survival (OS) using Kaplan-Meier analyses, and Cox proportional models. RESULTS: Median overall survival (OS) of the entire cohort was 14.8 months (95% CI 11.2-24.4). Median disease-free survival (DFS) in 81 patients undergoing resection was 12.3 months (95% CI 9.7-23.1). The median OS from start of palliative CTX (OSpall) was 10.9 months (95% 9.4-14.6). A combined Systemic Inflammatory Score (SIS) comprising all evaluated SIR markers correlated significantly with ORR, PFS, and OSpall. Patients with a high SIS (≥ 2) vs. SIS 0 had a significantly inferior OSpall (HR 8.7 95% CI 3.71-20.38, p < 0.001). Multivariate analysis including known prognostic markers (ECOG, CA19-9, LDH, and N- and M-status) identified the SIS as an independent prognostic factor. CONCLUSIONS: Inflammatory markers associate with inferior survival outcomes in patients with iCCA. A simple SIS may guide treatment decisions in patients treated with systemic chemotherapy.

[Hemithyroidectomy or total thyroidectomy for low-risk papillary thyroid cancer? : Surgical criteria for primary and secondary choice of treatment in an interdisciplinary treatment concept]. / Hemithyreoidektomie oder totale Thyreoidektomie beim papillären Niedrigrisikokarzinom der Schilddrüse? : Chirurgische Kriterien der primären und sekundären Therapiewahl im interdisziplinären Behandlungskonzept.

The increase in small intrathyroid papillary thyroid cancer (PTC) observed worldwide over the past two decades, with no increase in cancer-specific mortality, has challenged the previous concept of total thyroidectomy as a one-size-fits-all panacea. After exclusion of papillary microcarcinomas, a systematic review of 20 clinical studies published since 2002, which compared hemithyroidectomy (HT) to total thyroidectomy (TT), found comparable long-term oncological outcomes for low-risk papillary thyroid cancer (LRPTC) 1-4 cm in diameter, whereas postoperative complication rates were markedly lower for HT. To refine individual treatment plans, HT should be combined with ipsilateral central lymph node dissection and intraoperative frozen section analysis for staging. Based on recent evidence from studies and in consideration of individual risk factors, patients with LRPTC can be offered the concept of HT as an alternative to the standard TT. A prerequisite for the treatment selection and decision is a comprehensive patient clarification of the possible advantages and disadvantages of both approaches.

Multimodal survival prediction in advanced pancreatic cancer using machine learning.

BACKGROUND: Existing risk scores appear insufficient to assess the individual survival risk of patients with advanced pancreatic ductal adenocarcinoma (PDAC) and do not take advantage of the variety of parameters that are collected during clinical care. METHODS: In this retrospective study, we built a random survival forest model from clinical data of 203 patients with advanced PDAC. The parameters were assessed before initiation of systemic treatment and included age, CA19-9, C-reactive protein, metastatic status, neutrophil-to-lymphocyte ratio and total serum protein level. Separate models including imaging and molecular parameters were built for subgroups. RESULTS: Over the entire cohort, a model based on clinical parameters achieved a c-index of 0.71. Our approach outperformed the American Joint Committee on Cancer (AJCC) staging system and the modified Glasgow Prognostic Score (mGPS) in the identification of high- and low-risk subgroups. Inclusion of the KRAS p.G12D mutational status could further improve the prediction, whereas radiomics data of the primary tumor only showed little benefit. In an external validation cohort of PDAC patients with liver metastases, our model achieved a c-index of 0.67 (mGPS: 0.59). CONCLUSIONS: The combination of multimodal data and machine-learning algorithms holds potential for personalized prognostication in advanced PDAC already at diagnosis.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

DLL3 (delta-like protein 3) expression correlates with stromal desmoplasia and lymph node metastases in medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) are rare and aggressive neuroendocrine tumors of the thyroid. About 70% of MTC are sporadic; approximately 50% of those harbor somatic RET mutation. DLL3 is widely expressed in many neuroendocrine tumors and has been evaluated as a potential therapeutic target. Since stromal desmoplasia in sporadic MTC has been identified as a reliable predictor of aggressive behavior and development of lymph node metastases, a possible correlation of DLL3 expression with the presence of stromal desmoplasia was of particular interest. 59 paraffin-embedded samples of sporadic MTC with (44 cases) and without (15 cases) stromal desmoplasia and known lymph node status were included. DLL3 expression was determined by immunohistochemistry; no expression (0%), low expression (1-49%) and high expression (≥50%) were correlated with clinicopathological data. The proportion of DLL3 positivity was significantly correlated with both stromal desmoplasia (P < 0.0001) and lymph node metastases (P < 0.0001). MTC without stromal desmoplasia consistently lack DLL3 expression. This is the first study to focus on MTC regarding DLL3 expression and the relationship to various factors. Our results demonstrate that expression of DLL3 in MTC represents a reliable surrogate marker for stromal desmoplasia and lymph node metastases and might be an indicator for aggressive clinical behavior. DLL3 expression in ≥50% of tumor cells virtually excludes MTC without stromal desmoplasia. DLL3 was discussed as a potential therapeutic target in malignant tumors of other locations with positive immunohistochemical reaction and might therefore be a new therapeutic option in MTC, as well.

Assessing professional competence in optometry - a review of the development and validity of the written component of the competency in optometry examination (COE).

BACKGROUND: Credentialing assessment for overseas-educated optometrists seeking registration in Australia and New Zealand is administered by the Optometry Council of Australia and New Zealand. The aim was to review the validation and outcomes of the written components of this exam to demonstrate credentialing meets entry-level competency standards. METHODS: The Competency in Optometry Examination consists of two written and two clinical parts. Part 1 of the written exam comprises multiple choice questions (MCQ) covering basic and clinical science, while Part 2 has 18 short answer questions (SAQ) examining diagnosis and management. Candidates must pass both written components to progress to the clinical exam. Validity was evaluated using Kane's framework for scoring (marking criteria, item analysis), generalization (blueprint), extrapolation (standard setting), and implications (outcome, including pass rates). A competency-based blueprint, the Optometry Australia Entry-level Competency Standards for Optometry 2014, guided question selection with the number of items weighted towards key competencies. A standard setting exercise, last conducted in 2017, was used to determine the minimum standard for both written exams. Item response theory (Rasch) was used to analyse exams, produce reliability metrics, apply consistent standards to the results, calibrate difficulty across exams, and score candidates. RESULTS: Data is reported on 12 administrations of the written examination since 2014. Of the 193 candidates who sat the exam over the study period, 133 (68.9%) passed and moved on to the practical component. Ninety-one (47.2%) passed both the MCQ and SAQ exams on their first attempt. The MCQ exam has displayed consistently high reliability (reliability index range 0.71 to 0.93, average 0.88) across all 12 administrations. Prior to September 2017 the SAQ had a set cutscore of 50%, and the difficulty of the exam was variable. Since the introduction of Rasch analysis to calibrate difficulty across exams, the reliability and power of the SAQ exam has been consistently high (separation index range 0.82 to 0.93, average 0.86). CONCLUSIONS: The findings from collective evidence support the validity of the written components (MCQ and SAQ) of the credentialing of the competency of overseas-educated optometrists in Australia and New Zealand.

Combined systemic inflammation score (SIS) correlates with prognosis in patients with advanced pancreatic cancer receiving palliative chemotherapy.

PURPOSE: The prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains dismal. New cytotoxic agents such as nab-paclitaxel and liposomal irinotecan (nal-Iri) have extended the armamentarium of therapeutic options in the last years. Nowadays, sequential therapeutic strategies with moderately toxic chemotherapeutic protocols can be administered to the patients. However, prognostic and predictive biomarkers are still missing to identify those patients, which profit most from a "continuum of care" concept rather than receiving intensive first-line protocols such as FOLFIRINOX. To this end, we retrospectively evaluated the impact of the systemic inflammation as one essential hallmark of cancer in patients with advanced PDAC treated with sequential systemic. METHODS: A cohort of 193 PDAC patients treated at our center from January 2005 to August 2011 were retrospectively evaluated for the following systemic inflammatory response (SIR) markers: neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) C-reactive protein (CRP), and the modified Glasgow Prognostic Score (mGPS). SIR markers were correlated with clinico-pathological findings, response to chemotherapy and overall survival (OS) using Kaplan-Meier curves and Cox proportional models. RESULTS: All evaluated SIR markers were significantly associated with OS in patients with metastatic disease but not in patients with locally advanced PDAC. Interestingly, all SIR markers were only prognostic in patients not receiving antibiotics as surrogate marker for systemic bacterial infections. Based on the evaluated SIR markers, we propose a new Systemic Inflammation Score (SIS), which significantly correlated with reduced OS (HR: 3.418 (1.802-6.488, p < 0.001)) and the likelihood of receiving further-line systemic therapies (p = 0.028). CONCLUSION: Routinely assessed SIR biomarkers have potential to support therapeutic decision making in patients with metastatic PDAC.

[Pathology and molecular profile of differentiated thyroid carcinoma]. / Pathologie und molekulares Profil differenzierter Schilddrüsenkarzinome.

The clinical term of differentiated thyroid carcinoma (DTC) includes follicular (FTC) and papillary thyroid carcinomas (PTC). In diagnostic thyroid pathology, however, the term differentiated carcinoma (NOS) is used only very rarely for tumors with morphological features of both FTC and PTC. The current World Health Organization (WHO) classification of thyroid tumors introduced the entity of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). As a result, the diagnostic criteria for PTC had to be adjusted (compulsory histological demonstration of invasion and/or papillae), which also significantly limited the diagnostic potential of a fine needle biopsy (FNB) of the thyroid. The FTC is now divided into three distinct subgroups. Moreover, the WHO classification also established the diagnostic criteria of poorly differentiated thyroid carcinoma (PDTC), which has to be distinguished from both differentiated carcinomas and benign adenomas. This article also summarizes the current diagnostic status of molecular pathological analyses of thyroid tumors.

Immunohistochemical Profile and 47-Gene Next-Generation Sequencing (NGS) Solid Tumor Panel Analysis of a Series of 13 Strumal Carcinoids.

Strumal carcinoid is an extraordinary rare tumor of the ovary consisting of thyroid tissue intermixed with neuroendocrine tumor component. The cellular origin of strumal carcinoids has been an area of debate. There is also little data on detailed immunohistochemical and molecular characteristics of these neoplasms. For this reason, this series investigated the characteristics of a series of 13 strumal carcinoids using immunohistochemical markers and a 47-gene next-generation sequencing (NGS) solid tumor panel analysis. Both cellular components showed thyroglobulin expression in all tumors. TTF-1 expression was noted in both cellular components of 11 cases. Chromogranin A was positive in both components of most tumors (n = 12, 92.3% in the neuroendocrine component and n = 10, 76.9% in the thyroid follicular component). Synaptophysin stained the neuroendocrine component of all cases, and it was also identified in the follicular thyroid component of a single case. All tumors were negative for CDX2 and calcitonin. ISLET1 was positive in the neuroendocrine component of 8 cases (6.5%). With the exception of one case, all tumors were positive for SSTR2a. The tumors were associated with a low Ki67 labeling index. All cases were microsatellite stable and no pathogenic mutations were identified using a 47-gene NGS solid tumor analysis. This series underscored that strumal carcinoids are distinct neuroendocrine tumors. The synchronous expression for thyroid follicular epithelial and neuroendocrine differentiation biomarkers may suggest a precursor cell origin displaying mixed-amphicrine differentiation. While strumal carcinoids can be diagnosed by their typical morphology and immunohistochemical profile, frequent SSTR expression may serve as a potential theranostic biomarker in the management of affected patients. In addition, the absence of common driver mutations in the NGS solid tumor panel may suggest that these neoplasms seem to be genetically unrelated to follicular epithelial-derived thyroid tumors and potentially different than other commonly identified well-differentiated neuroendocrine neoplasms. Therefore, further studies focusing on molecular characteristics of this entity are still needed.

Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

[Ectopic thyroid tissue in the adrenal gland : A case report and review of the literature]. / Ektopes Schilddrüsengewebe in der Nebenniere : Ein Fallbericht in Zusammenschau mit der Literatur.

We present a case of ectopic thyroid tissue in the adrenal gland and discuss the findings with regard to the literature. Ectopic thyroid tissue below the diaphragm is rare and the mechanism of development is poorly understood. From a differential diagnostic point of view, it is important to exclude metastatic spread from a thyroid primary.

[Pheochromocytomatosis after adrenalectomy: metastasis or cell seeding?] / Phäochromozytomatose nach Adrenalektomie: Metastasierung oder Zellverschleppung?

Pheochromocytomatosis is defined as a multifocal cell dissemination limited to the operatively opened space with no signs of distant metastasis. After primary adrenalectomy due to a pheochromocytoma this is a rare and underrecognized manifestation of a tumor recurrence. Between 2010 and 2019 a total of 5 patients with the presentation of pheochromocytomatosis were treated in this center. Clinical and survival data were compared to 12 patients with a metastasized pheochromocytoma. Patients presenting with pheochromocytomatosis showed a better but not significant overall survival (136.8 vs. 107 months). Furthermore, patients with pheochromocytomatosis presented more often with a noradrenaline secretion type. Tumor recurrence in the pheochromocytomatosis group occurred on average 69.2 months after the initial diagnosis and was therefore much later than in patients with distant metastases from a pheochromocytoma (39 months, p = 0.13). This article outlines this special manifestation of recurrence of a pheochromocytoma based on this patient collective. Besides technical operative aspects there appears to be evidence for tumor-specific factors that promote the development of pheochromocytomatosis. Importantly, it seems that all patients with a pheochromocytoma should receive lifelong aftercare and that patients should be closely monitored during the first 5 years after surgery.

[Symptomatic hyponatremia in a 43-year-old woman after a skiing accident with head injuries]. / Symptomatische Hyponatriämie bei einer 43-Jährigen nach Skiunfall mit Kopftrauma.

This article reports the case of a 43-year-old woman who presented to the emergency room with headache and paresthesia after a fall on the head while skiing. She had clinical signs of volume depletion and blood test showed severe hyponatremia. Cerebral imaging was unremarkable. The diagnosis of cerebral salt-wasting syndrome (CSWS) was made, which is defined by the presence of extracellular volume depletion due to a tubular defect in renal sodium transport in patients with normal adrenal and thyroid function. The disease is mostly secondary to a neurological disease or head trauma. The patient rapidly improved after volume therapy and treatment with mineralocorticoids. The differentiation of CSWS from the syndrome of inappropriate antidiuretic hormone (SIADH) secretion can be challenging but the distinction is important because treatment options are very different.

Neurophysiological evidence of impaired attention and working memory in untreated hematologic cancer patients.

OBJECTIVE: Neuroimaging studies of hematologic cancer patients report altered activity in dorsal attention and central executive networks. To determine the consequences of these altered brain networks, we evaluated neurophysiological correlates of attention and working memory in hematologic cancer patients prior to initiating treatment. METHODS: Hematologic cancer patients (19-80 years) were excluded for premorbid cognitive impairment, prior non-hematologic cancer diagnosis, and prior chemotherapy. Attention was manipulated by presenting an irrelevant spatial cue prior to visual search displays. Working memory was manipulated by presenting irrelevant distractors within memory displays. Electroencephalogram was recorded during task performance. RESULTS: Patients (n = 28) and controls (n = 15) were balanced on age, gender, and education. Spatial cues evoked larger N2pc amplitudes, a correlate of spatial attention, in patients than controls (p < .05; Cohen's d > 0.7). Memory distractors evoked larger contralateral delay activity amplitudes, a correlate of working memory load, in patients (p = .028; Cohen's d = 1.1) but not controls (p = .64). CONCLUSIONS: Prior to initiating treatment, hematologic cancer patients demonstrated poor control over spatial attention and working memory, consistent with altered dorsal attention and central executive network activity. SIGNIFICANCE: Hematologic cancer patients may be at a higher risk for selecting, processing, and storing distracting information that would compete with more immediate goal-related behaviors.