[Guideline-based diagnosis of pancreatitis]. / Leitliniengerechte Diagnostik der Pankreatitis.

BACKGROUND: There is currently no S3 guideline that contains statements on the diagnosis and treatment of acute, chronic and autoimmune pancreatitis in a single guideline. OBJECTIVES: This article presents the most relevant recommendations relating to radiological imaging from the new "S3 guideline for pancreatitis". MATERIALS AND METHODS: The guideline was developed by the DGVS (German Society for Digestive and Metabolic Diseases). After an online-based Delphi survey, the statements were discussed by an interdisciplinary expert team at a 3-day consensus conference and then agreed upon. The level of evidence scheme (version 2) of the Oxford Centre for Evidence-based Medicine was used. RESULTS: The new German "S3 guideline pancreatitis" comprises for the first time all entities of pancreatitis, acute, chronic and autoimmune pancreatitis and contains a large number of innovations with regard to diagnostic imaging and therapy. In addition to the evidence-based recommendations for diagnosis and therapy, a German-language glossary of the revised Atlanta classification on acute pancreatitis was adopted by consensus of the interdisciplinary guideline expert team. Furthermore, protocol recommendations for the performance of computed tomography (CT) are provided for the first time. In this article we introduce the key recommendations and innovations in the field of diagnostic radiologic imaging for acute, chronic and autoimmune pancreatitis. CONCLUSIONS: In the future, every radiologist should have deep knowledge of the recommended time intervals for radiological imaging in acute pancreatitis and know the German terms for the description of acute pancreatitis; furthermore they should be able to classify the morphologies to the appropriate stages.

[Portal vein thrombosis-treatment options]. / Pfortaderthrombosen ­ therapeutische Möglichkeiten.

Portal vein thrombosis is a rare disease that describes a thrombosis in the extrahepatic or intrahepatic portion of the portal vein. Chronic liver disease or malignancy of the liver itself is often already present. However, inflammation or malignancy of nearby organs can also cause portal vein thrombosis. In addition, portal vein thrombosis can also occur in patients who have no corresponding previous illness. With every newly diagnosed portal vein thrombosis, an interdisciplinary decision is necessary: radiological intervention for recanalization, solitary anticoagulant therapy or surgical procedures (e.g., shunt installation or liver transplantation) have to be discussed. It is necessary to contact an appropriate center for this. The therapeutic decision must include the portal vein thrombosis etiology and accompanying diseases of the patient.

Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status and primary tumor location: analysis of untreated RAS-wild-type mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109).

PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.

ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.

Prospective evaluation of CT-guided HDR brachytherapy as a local ablative treatment for renal masses: a single-arm pilot trial.

PURPOSE: In this pilot trial, we investigate the safety of CT-guided high-dose-rate brachytherapy (HDR-BT) as a local ablative treatment for renal masses not eligible for resection or nephrectomy. METHODS: We investigated renal function after irradiation by HDR-BT in 16 patients (11 male, 5 female, mean age 76 years) with 20 renal lesions (renal cell carcinoma n = 18; renal metastases n = 2). Two patients had previous contralateral nephrectomy and two had ipsilateral partial nephrectomy. Six lesions had a hilar localization with proximity to the renal pelvis and would have not been favorable for thermal ablation. Renal function loss was determined within 1 year after HDR-BT by renal scintigraphy and laboratory parameters. Further investigations included CT and MRI every 3 months to observe procedural safety and local tumor control. Renal function tests were analyzed by Wilcoxon's signed rank test with Bonferroni-Holm correction of p-values. Survival and local tumor control underwent a Kaplan-Meier estimation. RESULTS: Median follow-up was 22.5 months. One patient required permanent hemodialysis 32 months after repeated HDR-BT and contralateral radiofrequency ablation of multifocal renal cell carcinoma. No other patient developed a significant worsening in global renal function and no gastrointestinal or urogenital side effects were observed. Only one patient died of renal tumor progression. Local control rate was 95% including repeated HDR-BT of two recurrences. CONCLUSION: HDR-BT is a feasible and safe technique for the local ablation of renal masses. A phase II study is recruiting to evaluate the efficacy of this novel local ablative treatment in a larger study population.

Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy : Efficacy and outcome.

PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. RESULTS: The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. CONCLUSION: Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

[Contralateral hepatic hypertrophy following unilateral yttrium-90 radioembolization : Implications for liver surgery]. / Kontralaterale Leberhypertrophie nach einseitiger Yttrium-90-Radioembolisation : Implikationen für die Leberchirurgie.

BACKGROUND: Preservation of an adequate future liver remnant (FLR) is the principal limitation to liver surgery in patients with primary or secondary liver malignancies. Hence, methods to increase the volume of the FLR in preparation for liver resection are gaining in importance. OBJECTIVE: In addition to the traditional methods for induction of FLR hypertrophy, such as portal vein embolization (PVE) or portal vein ligation (PVL) with or without parenchymal dissection (ALPPS, in situ split), radioembolization (RE) using yttrium-90 microspheres also leads to a volume increase of non-embolized liver parenchyma. This review outlines its potential role as an alternative procedure for induction of liver hypertrophy. MATERIAL AND METHODS: Synopsis and critical discussion of the available literature on the mechanisms of induction of liver hypertrophy, the advantages and drawbacks of the traditional methods, and current research on volume changes associated with RE as well as their implications for possible clinical use in preparation for liver surgery. RESULTS: Both PVE and PVL can achieve a substantial contralateral volume gain of up to 70 %. The development of contralateral hypertrophy can be accelerated by dissecting the liver parenchyma along the intended plane of resection in addition to PVL (in situ split). Compared to these methods, RE achieves less contralateral liver hypertrophy; however, this effect should not be disregarded as RE provides effective treatment of ipsilateral liver tumors along with induction of hypertrophy and may be associated with a reduced risk of tumor progression compared to PVE and PVL. CONCLUSION: The available data suggest that RE can complement the armamentarium of methods for induction of FLR hypertrophy in specific situations. Further studies are needed to establish its definitive role for this indication and are in preparation.

Renal Sympathetic Denervation by CT-Guided Ethanol Injection: A Phase II Pilot Trial of a Novel Technique.

OBJECTIVES: CT-guided ethanol-mediated renal sympathetic denervation in treatment of therapy-resistant hypertension was performed to assess patient safety and collect preliminary data on treatment efficacy. MATERIALS AND METHODS: Eleven patients with therapy-resistant hypertension (blood pressure of >160 mmHg despite three different antihypertensive drugs including a diuretic) and following screening for secondary causes were enrolled in a phase II single arm open label pilot trial of CT-guided neurolysis of sympathetic renal innervation. Primary endpoint was safety, and secondary endpoint was a decrease of the mean office as well as 24-h systolic blood pressure in follow-up. Follow-up visits at 4 weeks, 3, and 6 months included 24-h blood pressure assessments, office blood pressure, laboratory values, as well as full clinical and quality of life assessments. RESULTS: No toxicities ≥3° occurred. Three patients exhibited worsened kidney function in follow-up analyses. When accounting all patients, office systolic blood pressure decreased significantly at all follow-up visits (maximal mean decrease -41.2 mmHg at 3 months). The mean 24-h systolic blood pressure values decreased significantly at 3 months, but not at 6 months (mean: -9.7 and -6.3 mmHg, respectively). Exclusion of five patients who had failed catheter-based endovascular denervation and/or were incompliant for antihypertensive drug intake revealed a more pronounced decrease of 24-h systolic blood pressure (mean: -18.3 and -15.2 mmHg at 3 and 6 months, p = 0.03 and 0.06). CONCLUSION: CT-guided sympathetic denervation proved to be safe and applicable under various anatomical conditions with more renal arteries and such of small diameter.

Tumor cell uptake of 99mTc-labeled 1-thio-ß-D-glucose and 5-thio-D-glucose in comparison with 2-deoxy-2-[18F]fluoro-D-glucose in vitro: kinetics, dependencies, blockage and cell compartment of accumulation.

PURPOSE: This study was conducted to investigate the capacity of (99m)Tc-labeled 1-thio-ß-D-glucose ((99m)Tc-1-TG) and 5-thio-D-glucose ((99m)Tc-5-TG) to act as a marker for glucose metabolism in tumor cells in vitro. PROCEDURES: We investigated the cellular uptake of (99m)Tc-1-TG, (99m)Tc-5-TG, and 2-deoxy-2-[(18)F]fluoro-D-glucose((18)F-FDG) in a human colorectal carcinoma and human lung adenocarcinoma cell line (HCT-116, A549) at different time points and varying glucose/insulin concentrations and under transporter blockage by cytochalasin-B and phloretin. Cell compartment analysis was performed. RESULTS: A significant uptake and time dependency thereof, a significant uptake dependency on glucose and insulin and a significant uptake inhibition by cytochalasin-B for (99m)Tc-1-TG and (99m)Tc-5-TG, was shown. Albeit substantial, the uptake was less pronounced in (99m)Tc-1-TG and (99m)Tc-5-TG compared with (18)F-FDG. (99m)Tc-1-TG and (99m)Tc-5-TG showed a higher accumulation in the cell membranes compared with (18)F-FDG. CONCLUSION: Tc-1-TG and (99m)Tc-5-TG showed an uptake in vitro with glucose analog characteristics but with membranous accumulation. Tumor imaging should be investigated in an animal model.

[Interventional radiological procedures in the therapy for colorectal liver metastases]. / Radiologisch-interventionelle Verfahren zur Therapie von kolorektalen Lebermetastasen.

Microtherapeutic procedures performed by interventional radiologists pose a viable alternative or additive to systemic chemotherapy for local tumour control in cases of non-operable (for technical, functional, and comorbidity reasons or at the patient's wish) liver metastases. A main focus includes local therapies such as radiofrequency ablation and interstitial brachytherapy which are performed under ultrasound, CT or MRI guidance to achieve a thermal or radiogenic ablation of the malignancy. Although highly effective, these procedures are limited to oligonodular manifestations. For disseminated metastases, locoregional techniques like the yttrium-90 radioembolisation have become established. Here, the active principle in the form of radioactively labelled microspheres is introduced into the liver through an arterial catheter under angiographic guidance. The present article focuses on metastases of colorectal cancer as the most frequent tumour entity encountered in interventional radiotherapy.

Evaluation of functional MR-urography in complex obstructive uropathy of infants: comparison to the conventional diagnostic algorithm--a pilot study.

OBJECTIVES: To analyze the impact of functional magnetic resonance urography (fMRU) on the therapeutic management in infants with complex obstructive uropathy (OU) compared to the conventional diagnostic algorithm [CDA, ultrasound, radioisotope nephrography (RN)]. METHODS: Retrospective analysis on 10 consecutive infants [female, n=3; male, n=7; age, 10.7 (2-17) months] with OU. Patients were examined according to CDA. If CDA revealed inconclusive results, fMRU was performed additionally. Split kidney function was assessed by RN [single kidney function (SKF)] and fMRU [volumetric differential renal function (vDRF)]. Findings were presented to an interdisciplinary truth-panel in a 2-step decision process (with and without fMRU). Clinical decision was determined. RESULTS: CDA indicated surgical intervention in 8 patients and conservative treatment in 2. Information by fMRU changed treatment strategy in 3 patients and led to the modification of the initially chosen surgical approach in 8 cases. The comparison of SKF and vDRF was not possible in 1 patient, whereas concordance was observed in 7 patients. SKF and vDRF differed >5% in 2 patients. CONCLUSIONS: fMRU has potential to improve therapeutic management of OU in infants. If surgical treatment is advised, the morphological information by fMRU has to be emphasized. Regarding kidney function estimation preliminary results are encouraging.

MRI versus bone scintigraphy. Evaluation for diagnosis and grading of stress injuries.

AIM: This study was set up to determine the value of magnetic resonance imaging (MRI) and bone scintigraphy (BS) for the diagnosis of stress injuries in athletes, and furthermore to assess reliability and prediction of healing time. PATIENTS, METHODS: Imaging data was analyzed retrospectively from 28 athletes who had received MRI and BS examinations for suspected stress injuries. MRI- and BS-data were rated by three specialists each in a blinded read, using a 5-point score (i.e. 0-4: inconspicuous to high-grade stress fracture). An interdisciplinary expert truth-panel set the reference standard. Standard statistical parameters, Fleiss' kappa (κ), and group comparisons were calculated. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for detection of stress injuries were 71.4%, 85.7%, 78.6%, 83.3% and, 75.0%, for MRI and 92.9%, 73.8%, 83.3%, 78.0% and, 91.2% for BS, respectively. Interobserver reliability for the diagnosis of a stress injury was κ = 0.9 for BS and κ = 0.85 for MRI. Mean healing times of mild (grades 1 and 2) and severe (grades 3 and 4) stress injuries were 88 days (d) versus 142d for BS and 57d versus 116d for MRI. No significant difference in healing time could be shown. CONCLUSIONS: MRI and BS reliably detect stress injuries. MRI is to be recommended as the primary imaging modality due to its potential for assessment of differential diagnoses and the lack of radiation exposure, the value of BS lies in the exclusion of stress fractures after inconclusive MRI examinations.

Biochemical interactions in the wnt pathway.

The wnt signal transduction pathway is involved in many differentiation events during embryonic development and can lead to tumor formation after aberrant activation of its components. The cytoplasmic component beta-catenin is central to the transmission of wnt signals to the nucleus: in the absence of wnts beta-catenin is constitutively degraded in proteasomes, whereas in the presence of wnts beta-catenin is stabilized and associates with HMG box transcription factors of the LEF/TCF family. In tumors, beta-catenin degradation is blocked by mutations of the tumor suppressor gene APC (adenomatous polyposis coli), or of beta-catenin itself. As a consequence, constitutive TCF/beta-catenin complexes are formed and activate oncogenic target genes. This review discusses the mechanisms that silence the pathway in cells that do not receive a wnt signal and goes on to describe the regulatory steps involved in the activation of the pathway.

Leukaemia inhibitory factor stimulates proliferation of prospermatogonial stem cells.

The effect of leukaemia inhibitory factor (LIF) on the proliferation of prospermatogonial stem cells was tested in vitro. Pieces of 3-day-old rat testis were cultured in the presence of a range of doses of LIF alone or in combination with 1 ng mL(-1) seminiferous growth factor (SGF). Stimulation of the proliferative activity of quiescent prospermatogonia was detected immunocytochemically with a cell proliferation kit. After 24 h culture, LIF significantly increased the percentage of labelled prospermatogonia, with the peak of activity at 20 pg mL(-1). The combination of LIF and SGF resulted in a decrease in DNA synthetic activity of the germ cells. Hence, LIF and SGF play a role in local regulation at the onset of spermatogenesis in the rat testis.