Image-based response assessment during immunotherapy in skin cancer.

Immune-checkpoint inhibitors and further immunotherapeutic treatment strategies have significantly extended therapy options for melanoma and other skin cancer entities over the last decade. In the context of a broader application of immunotherapeutic approaches, sufficient ways to monitor the course of the disease during therapy are required. Immunotherapies are based on different ways of modulating the immune system. This leads to complex clinical response patterns including pseudoprogression and others, requiring an adaptation of conventional diagnostic imaging tools or the introduction of novel technologies. In this review, current non-invasive imaging approaches for response assessment during immunotherapies in skin cancers as well as their limitations are discussed. To overcome present hurdles, promising alternatives to better address novel imaging features during immunotherapy are depicted giving an outlook on what can be expected in the future.

Radiologic predictors for failure of non-operative management of complicated diverticulitis: a single-centre cohort study.

PURPOSE: Modern non-operative management of diverticulitis consists of a complex therapeutic regimen and is successful in most cases even of complicated diverticulitis. Still, a certain proportion of patients requires urgent surgery due to failure of the conservative approach. This study aims to identify predictors for failure of conservative treatment of complicated diverticulitis with the need for subsequent urgent resection during the acute episode. METHODS: A single-centre retrospective cohort study was performed at our tertiary centre including cases of acute complicated diverticulitis (characterized by localized abscess formation and/or pericolic air) between 2007 and 2019 that were treated guideline-conform by multimodal conservative treatment. Radiologic characteristics of disease in CT scans upon admission were analysed by uni- and multivariable logistic regression to determine predictors for resection within 30 days after onset of the conservative therapy approach. RESULTS: A total of 669 cases of acute diverticulitis were identified, of which 141 patients met the inclusion criteria. Overall, 13% (n = 19) of patients were operated within 30 days despite initial conservative management. Multivariable logistic regression identified length of inflamed bowel greater than 7 cm (p < 0.011) and abscess formations >1 cm (p < 0.001) as significant risk factors for failure of conservative treatment. CONCLUSION: Patients with length of inflamed bowel >7 cm or abscess formation >1 cm have increased risk for failure of conservative treatment of acute episodes of diverticulitis with contained perforations with subsequent need for urgent surgery. Therefore, conservative treatment of those patients should be monitored with special caution.

[Disseminated tuberculosis mimicking metastatic gastric cancer - a case report]. / Disseminierte Tuberkulose imitiert metastasiertes Magenkarzinom ­ ein Fallbericht.

Increasing numbers of active tuberculosis in Germany were recorded in the last years. Thus, also extrapulmonary manifestations of tuberculosis gain clinical significance as differential diagnoses, especially when a metastatic tumor disease is suspected. We report the case of a 77-year-old male patient who presented with unilateral leg pain and B symptoms. Further investigations revealed an osteolytic mass in the sacrum as well as CT-morphological findings consistent with metastatic gastric cancer. However, transgastric biopsies showed necrotising granuloma with giant cells leading to molecular and cultural detection of Mycobacterium tuberculosis instead of suspected neoplastic tissue. A nine-month treatment regimen for suspected disseminated tuberculosis with bone involvement was initiated according to national guidelines. Clinical and radiological follow up examinations after treatment completion showed complete remission.

Short-term and long-term outcome of radiological-guided insertion of central venous access port devices implanted at the forearm: a retrospective monocenter analysis in 1704 patients.

OBJECTIVES: The objectives are to analyze the technical success rate as well as the short-term and long-term complications of totally implantable venous access ports (TIVAPs) at the forearm. METHODS: Retrospective analysis of 1,704 consecutively implanted TIVAPs was performed. Primary endpoints were defined as technical success rate, clinical outcome, device service interval, and rates of major complications. Minor complications not requiring port explantation were defined as secondary endpoints. RESULTS: The technical success rate was 99.2 % with no major complications. During follow-up, a total of 643,200 catheter-days were documented, the mean device service interval was 380.6 days/patient. A total of 243 complications (14.4 %) in 226 patients were observed (0.4/1000 catheter-days), in 140 patients (8.3 %) the port device had to be explanted. Disconnection between the port device and the catheter (1.6 %) was more frequent than fracture (0.8 %) and leakage (0.6 %) of the catheter, which occurred more frequently when the catheter was inserted via the cephalic versus the brachial vein. CONCLUSION: TIVAP implantation at the forearm is a simple and safe procedure with a low rate of early and late complications.

Perivascular epitheloid cell tumor (PEComa) mimicking retroperitoneal liposarcoma.

PEComas are a collection of generally rare tumors, defined by the World Health Organization as 'mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epitheloid cells'. We describe the case of retroperitoneal PEComa with a liposarcoma-like appearance on cross-sectional imaging, but distinctive immunohistochemistry revealing the correct diagnosis.

Acute hypophysitis and hypopituitarism in early syphilitic meningitis in a HIV-infected patient: a case report.

BACKGROUND: Sexually transmitted diseases and most notably syphilis-infections are rising amongst men who have sex with men. In HIV-co-infected patients, an accelerated clinical course of syphilis neurological involvement is known. CASE PRESENTATION: A 46 year old HIV-positive male patient came in to our emergency department in the late evening with acute fever, rapidly progressive cephalgia and photophobia. Palmar skin efflorescence was evocative of an active syphilis infection. A reactive Treponema pallidum particle agglutination (TPPA) assay with positive Treponema pallidum-specific IgG/IgM immunofluorescence as well as a highly reactive Veneral diseases research laboratory (VDRL) test confirmed the diagnosis. Liquor pleocytosis, liquor protein elevation and a highly positive VDRL test in cerebrospinal fluid (CSF) were interpreted in context of the clinical symptoms as neurosyphilitic manifestations within an early syphilis infection (stage II). Cranial nuclear magnetic resonance scans of the sella turcica, which were performed due to low thyroidea stimulation hormone (TSH) and thyroxin levels, showed signs of hypophysitis such as pituitary gland enlargement and inhomogeneous contrast enhancement. Advanced endocrine laboratory testing revealed hypopituitarism. Fourteen days of intravenous ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to complete disappearance of all clinical symptoms. Two months later, nuclear magnetic resonance scan showed normal pituitary size and that the syphilis serology had normalized. CONCLUSION: We report to the best of our knowledge the first case of a HIV-positive patient with acute hypophysitis and hypopituarism due to early neurosyphilis infection. Ceftriaxone treatment and levothyroxine- and hydrocortisone-substitution led to the disappearance of all clinical symptoms. We strongly recommend to exclude syphilis infection in every clinical situation unclear in HIV-patients, especially when additional risk factors are known.

The Role of RYR2 in Atrial Fibrillation.

Background. Atrial fibrillation (AF) is a common arrhythmia in elderly patients and is associated with increased risk of mortality. The pathogenesis of AF is complex and based on multiple genetic and environmental factors. Genome-wide association studies identified several loci in AF patients, indicating the complex genetic architecture of this disease. In rare cases, familial forms of AF have been described. Today, pathogenic variants in at least 11 different genes are associated with monogenic AF. Case presentation. The 37-year-old male patient presented to our emergency department with AF. At the age of 35, he had already been diagnosed with paroxysmal AF. Additionally, his 34-year-old brother had also been diagnosed with AF as well as nonobstructive hypertrophic cardiomyopathy. Moreover, the patient's father was diagnosed with AF in his twenties. Transthoracic echocardiography and cardiac MRI revealed a reduced systolic left ventricular ejection without any signs of hypertrophic cardiomyopathy. Genetic testing identified the heterozygous missense variants c.3371C > T, p.(Pro1124Leu) in RYR2 (NM_001035.3) and c.2524C > A, p.(Pro842Thr) in HCN4 (NM_005477.3) in the patient's and his brother's DNA. Discussion. This case of familial AF helps to strengthen the role of RYR2 as a disease gene in the context of AF. Although the variant in RYR2 needs to be classified formally as variant of unknown significance, we regard it as probably disease-causing due to the previously published data. As RYR2 has already been identified as a possible target for prevention and therapy of AF, the knowledge of variants in RYR2 might become even more crucial for individual molecular therapies in the future.

Whole-Body Imaging for the Primary Staging of Melanomas-A Single-Center Retrospective Study.

BACKGROUND: Melanoma staging at diagnosis predominantly depends on the tumor thickness. Sentinel lymph node biopsy (SLNB) is a common tool for primary staging. However, for tumors of >4 mm with ulceration, 3D whole-body imaging and, in particular, Fluor-18-Deoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT), is recommended beforehand. This study aimed to investigate the real-world data of whole-body imaging for initial melanoma staging and its impact on the subsequent diagnostic and therapeutic procedures. METHODS: In this retrospective single-center study, 94 patients receiving 18F-FDG-PET/CT and six patients with whole-body computed tomography (CT) scans were included. The clinical characteristics, imaging results, and histologic parameters of the primary tumors and metastases were analyzed. RESULTS: Besides the patients with primary tumors characterized as pT4b (63%), the patients with pT4a tumors and pT3 tumors close to 4 mm in tumor thickness also received initial whole-body imaging. In 42.6% of the patients undergoing 18F-FDG-PET/CT, the imaging results led to a change in the diagnostic or therapeutic procedure following on from this. In 29% of cases, sentinel lymph node biopsy was no longer necessary. The sensitivity and specificity of 18F-FDG-PET/CT were 66.0% and 93.0%, respectively. CONCLUSION: Whole-body imaging as a primary diagnostic tool is highly valuable and influences the subsequent diagnostic and therapeutic procedures in a considerable number of patients with a relatively high tumor thickness. It can help avoid the costs and invasiveness of redundant SLNB and simultaneously hasten the staging of patients at the time of diagnosis.

The influence of metastatic patterns and tumor load on therapeutic efficacy of immunotherapy in patients with metastatic melanoma as determined by quantitative PET-parameters using [ 18 F]-fluorodeoxyglucose PET/computed tomography.

The introduction of immunotherapy was a revolution in the treatment of metastatic melanoma. Nevertheless, there are only few clinical parameters to predict response to immunotherapy. The purpose of this study was to identify metastatic patterns that can predict response by using noninvasive 18 F-FDG PET/CT imaging. In 93 immunotherapy-treated patients, total metabolic tumor volume (MTV) was measured before and after treatment. The differences were compared to quantify therapy response. Patients were divided into seven subgroups regarding the affected organ systems. The results as well as clinical factors were evaluated in multivariate analyses. No subgroup of metastatic patterns had a significant difference in response rates, but with a trend towards poorer response regarding osseous and hepatic metastases. Osseous metastases presented with significant lower disease-specific survival (DSS) ( P = 0.001). Sole lymph node metastases were the only subgroup with MTV reduction and with significant higher DSS (57.6 months; P = 0.033). Patients, who ever developed brain metastases, showed a high progression of MTV of 201 ml ( P = 0.583) and poor DSS of 49.7 months ( P = 0.077). Lower numbers of affected organs indicated significantly higher DSS (hazard ratio, 1.346; P = 0.006). Osseous metastases represented a negative predictive factor for response to immunotherapy and survival. Cerebral metastases, especially when nonresponsive to immunotherapy, predicted poor survival and high increase of MTV. A high number of affected organ systems was identified as a negative factor for response and survival. Patients with only lymph node metastases showed a better response and survival.

Advanced hemodynamic monitoring before and after transjugular intrahepatic portosystemic shunt: implications for selection of patients--a prospective study.

PURPOSE: To investigate immediate and short-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on cardiocirculatory, hepatic, and renal function and characterize predictors for TIPS outcome in terms of organ function after TIPS. MATERIALS AND METHODS: This prospective study was approved by the ethics committee at a university hospital and was conducted in a medical intensive care unit. Informed consent was obtained. Twenty patients with indication for TIPS were enrolled. Monitoring of hemodynamic and hepatic function (transpulmonary thermodilution, indocyanine green plasma disappearance rate [ICG-PDR]) was performed. Biochemical markers of organ function were obtained. Statistical analysis (Wilcoxon test, Spearman correlation, multivariate linear regression analysis, receiver operating characteristic [ROC] analysis) was performed. RESULTS: After TIPS, central venous pressure (median, 11 vs 15 cm H(2)O; P < .001), cardiac index (3.4 vs 3.8 L/min/m(2); P = .001), and global end-diastolic volume index (GEDVI) (726 vs 775 mL/m(2); P = .003) increased significantly. Portosystemic pressure gradient (28 vs 11 cm H(2)O; P < .001) and systemic vascular resistance index (1610 vs 1384 dyn · sec · cm(-5) · m(2); P = .015) decreased significantly. Creatinine (1.1 vs 1.1 mg/dL; P = .008) and blood urea nitrogen (BUN) (27 vs 21 mg/dL; P = .006) decreased significantly. Bilirubin (1.8 vs 2.2 mg/dL; P = .032) and international normalized ratio (1.4 vs 1.5; P = .022) increased significantly. ICG-PDR significantly deteriorated after TIPS (P = .006). Higher baseline creatinine was independently associated with a decrease in creatinine after TIPS (R = 0.816, P < .001). ROC analysis identified baseline BUN (P = .026, area under ROC curve [AUC] = 0.818), cystatin C (P = .033, AUC = 0.805), and creatinine (P = .052, AUC = 0.779) as predictors of a decrease in creatinine of 0.5 mg/dL or greater and/or 25% or greater. An increase in bilirubin of 1 mg/dL or greater 1 week after TIPS was significantly associated with high baseline BUN (P = .007, AUC = 0.893) and high central venous pressure (P = .040, AUC = 0.800). Lower baseline alanine aminotransferase (P = .002, AUC = 1.000) and cardiac power index · GEDVI (P = .005, AUC = 0.960) predicted favorable TIPS outcome (creatinine decrease of ≥ 0.2 mg/dL without model for end-stage liver disease score increase of more than one point). CONCLUSION: Patients with renal insufficiency, compensated hepatocellular function, decreased cardiac preload, and decreased cardiac performance benefit most from TIPS.

Detection, classification, and characterization of focal liver lesions: Value of diffusion-weighted MR imaging, gadoxetic acid-enhanced MR imaging and the combination of both methods.

AIM: To evaluate diffusion-weighted MR imaging (DWI), gadoxetic acid-enhanced MR imaging and the combination of both methods in the detection, classification, and characterization of focal liver lesions (FLL). METHODS: A total of 119 FLL (28 HCCs, 39 metastases, 15 FNHs, 11 adenomas, 13 hemangiomas, 13 cysts) were retrospectively analyzed in 36 patients. In those patients MR imaging of the liver comprising respiratory-triggered DWI (b values of 50, 300, and 600 s/mm(2)) and gadoxetic acid-enhanced MR imaging including image acquisition in the hepatocyte-selective phase (20 min post injection) had been performed. Three image sets were assigned and compared: DWI only (set A), gadoxetic acid-enhanced MR imaging only (set B), and both modalities in combination (set C). Two readers independently interpreted the images in random order. For each reader and image set, the area under the receiver operating characteristic curve (Az) and sensitivity in the detection of FLL was determined as well as the accuracy in the classification and characterization of FLL. RESULTS: There was no significant difference between the three image sets in the detection of FLL with regards to Az. However, when only lesions with a diameter of 10 mm or less were analyzed, the Az values of set C were significantly higher than those of sets A and B for both readers. For classifying and characterizing FLL both set B and C were significantly superior to set A. CONCLUSION: Adding DWI to gadoxetic acid-enhanced MR imaging significantly increases the accuracy in the detection of small FLL.

Myocarditis or inherited disease? - The multifaceted presentation of arrhythmogenic cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is now usually referred to as arrhythmogenic cardiomyopathy (ACM) because of the possible left and biventricular affection. In recent years, it has been shown that early-stage ACM, especially in women carrying a disease-causing variant in the DSP gene, may present with clinical signs of myocarditis. CASE PRESENTATION: The female patient was diagnosed with myocarditis based on arrhythmia and findings on magnetic resonance imaging at the age of 24 years. An additional performed myocardial biopsy confirmed a lymphocytic inflammatory reaction. Subsequently, the patient experienced cardiac arrest because of ventricular fibrillation and was resuscitated. As a result, she received an implantable cardioverter defibrillator, and repeated ablations of recurrent ventricular tachycardia were performed. After four years, molecular genetic testing identified the heterozygous, likely pathogenic nonsense variant c.4789G > T, p.(Glu1597*) in DSP (NM_004415.4). Based on this finding, ACM could be diagnosed, and a heart transplantation was performed only a few months later because of rapid disease progression. DISCUSSION: Truncating variants in DSP have been associated with fulminant progression of arrhythmia. However, the currently used ARVC task force criteria are inadequate to detect DSP-associated ACM with left dominant presentation. Moreover, the initial diagnosis of myocarditis may distract from a more extensive search for other causes. Consequently, in cases of recurrent or unusually prolonged myocarditis, especially if present without detected pathogens, molecular genetic testing should be considered.

Whole-body MRI including diffusion-weighted imaging (DWI) for patients with recurring prostate cancer: technical feasibility and assessment of lesion conspicuity in DWI.

PURPOSE: To evaluate the principal methodological aspects of whole-body magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) with background suppression using a time-optimized protocol for restaging of prostate cancer patients in a technical feasibility study. MATERIALS AND METHODS: Seventeen patients underwent MRI at 1.5T from the base of the skull to the proximal thigh using axial T1-weighted (T1w), T2w short-tau inversion recovery (STIR), and DWI (b-values: 50 and 500 s/mm(2)) and sagittal T1w and T2w STIR of the spine. Apparent diffusion coefficient (ADC) values of liver, spleen, kidney, muscle, and bone were measured. Image quality in DWI was assessed by using a scale from 0-9. Contrast-to-noise ratios (CNRs) of lymph node and bone metastases were determined in T1w, T2w STIR, and DWI. Bone metastases were further subclassified according to their Hounsfield units (HU) in computed tomography (CT). RESULTS: Mean acquisition and mean room times were 66:20 and 75:21 minutes, respectively. ADC values of normal organs showed good concordance with reported data. Good to excellent image quality was observed for DWI (mean scores 7.41-8.00) with the exception of the neck (mean score 4.76). CNR of DWI (b-value 50 s/mm(2) ) for lymph node metastases was clearly superior compared to all other sequences. For bone metastases T1w performed significantly better for sclerotic lesions (HU > 600), DWI (b-value 50 s/mm(2) ) for nonsclerotic lesion (HU < 300). CONCLUSION: In patients with recurrent prostate cancer a whole-body MR protocol including DWI is technically robust. Due to the high CNR of DWI compared to T1w and T2w STIR, detection of malignant lesions should be facilitated by DWI, except for sclerotic bone metastases.

Comparison of diffusion-weighted MR imaging and multidetector-row CT in the detection of liver metastases in patients operated for pancreatic cancer.

AIM: The purpose of this study is to determine the value of diffusion-weighted MR imaging (DWI) in the detection of liver metastases in patients with pancreatic tumors when compared to multidetector-row CT (MDCT). METHODS: DWI and MDCT were performed in 31 consecutive patients with newly diagnosed, potentially resectable pancreatic tumors. CT images were obtained in the arterial and the portal venous phase. For DWI, a respiratory-triggered single-shot echo-planar imaging sequence (b values: 0, 300, and 600 s/mm(2)) was acquired. Images were analyzed in consensus by two radiologists blinded to the clinical data. Imaging results were correlated with intraoperative surgical and ultrasound findings as well as with results of histopathologic analysis and imaging follow-up. RESULTS: Sensitivity and specificity in detecting liver metastases were 53.3% and 77.8% for MDCT and 86.7% and 97.5% for DWI, respectively. In our study population DWI would have changed the therapeutic management in 4 out of 31 patients (12.9%) when compared to MDCT. CONCLUSION: In the present pilot study, DWI performed significantly better than MDCT in the detection of liver metastases in patients with pancreatic tumors. Therefore, DWI may help to optimize therapeutic management in those patients in the future.

Treatment of intestinal tuberculosis with small bowel perforation: a case report.

BACKGROUND: Diagnosis of intestinal tuberculosis poses a dilemma to physicians due to nonspecific symptoms like abdominal pain, fever, nausea, and a change in bowel habit. In particular, the distinction between inflammatory bowel disease and intestinal tuberculosis remains challenging. CASE PRESENTATION: A 27-year-old man from Colombia presented with fever, night sweats, and progressive lower abdominal pain. Computed tomography revealed a thickening of the bowel wall with a mesenterial lymphadenopathy, ascites ,and a pleural tumor mass. Histology of intestinal and pleural biopsy specimens showed a granulomatous inflammation. Although microscopy and polymerase chain reaction (PCR) for Mycobacterium tuberculosis (MTB) were negative, empirical MTB treatment was initiated on suspicion. Due to a massive post-stenotic atrophied intestinal bowel, MTB medications were administered parenterally in the initial phase of treatment to guarantee adequate systemic resorption. The complicated and critical further course included an intra-abdominal abscess and bowel perforation requiring a split stoma, before the patient could be discharged in good condition after 3 months of in-hospital care. CONCLUSIONS: This case highlights the clinical complexity and diagnostic challenges of intestinal MTB infection. A multidisciplinary team of physicians should be sensitized to a timely diagnosis of this disease, which often mimics inflammation similar to inflammatory bowel disease, other infections, or malignancies. In our case, radiological findings, histological results, and migratory background underpinned the suspected diagnosis and allowed early initiation of tuberculostatic treatment.

Diagnosis of hepatic metastasis: comparison of respiration-triggered diffusion-weighted echo-planar MRI and five t2-weighted turbo spin-echo sequences.

OBJECTIVE: The purpose of this study was to compare the value of respiration-triggered diffusion-weighted (DW) single-shot echo-planar MRI (EPI) and five variants of T2-weighted turbo spin-echo (TSE) sequences in the diagnosis of hepatic metastasis. MATERIALS AND METHODS: Fifty-two patients with extrahepatic primary malignant tumors underwent 1.5-T MRI that included DW EPI and the following variants of T2-weighted TSE techniques: breath-hold fat-suppressed HASTE, breath-hold fat-supressed TSE, respiration-triggered fat-suppressed TSE, breath-hold STIR, and respiration-triggered STIR. Images were reviewed independently by two blinded observers who used a 5-point confidence scale to identify lesions. Results were correlated with surgical and histopathologic findings and follow-up imaging findings. The accuracy of each technique was measured with free-response receiver operating characteristic analysis. RESULTS: A total of 118 hepatic metastatic lesions (mean diameter, 12.8 mm; range, 3-84 mm) were evaluated. Accuracy values were higher (p < 0.001) with DW EPI (0.91-0.92) than with the T2-weighted TSE techniques (0.47-0.67). Imaging with the HASTE sequence (0.47-0.52) was less accurate (p < 0.05) than imaging with the breath-hold TSE, breath-hold STIR, respiration-triggered TSE, and respiration-triggered STIR sequences (0.59-0.67). Sensitivity was higher (p < 0.001) with DW EPI (0.88-0.91) than with T2-weighted TSE techniques (0.45-0.62). For small (< or = 10 mm) metastatic lesions only, the differences in sensitivity between DW EPI (0.85) and T2-weighted TSE techniques (0.26-0.44) were even more pronounced. CONCLUSION: DW EPI was more sensitive and more accurate than imaging with T2-weighted TSE techniques. Because of the black-blood effect on vessels and low susceptibility to motion artifacts, DW EPI was particularly useful for the detection of small (< or = 10 mm) metastatic lesions.