The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture.

The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system.

Adrenal insufficiency is a contraindication for omalizumab therapy in mast cell activation disease: risk for serum sickness.

Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab therapy may be more likely to cause serum sickness than previously thought. In patients with regular adrenal function, serum sickness can occur after 3 to 10 days which resolves after the antigen and circulating immune complexes are cleared. If the symptoms do not resolve within a week, injection of 20 to 40 mg of prednisolone on two consecutive days could be given. However, in MCAD patients whose adrenal cortical function is completely suppressed by exogenous glucocorticoid therapy, there is a high risk that serum sickness will be masked by the MCAD and evolve in a severe form with pronounced damage of organs and tissues, potentially leading to death. Therefore, before the application of the first omalizumab dose, it is important to ensure that the function of the adrenal cortex is not significantly limited so that any occurring type III allergy can be self-limiting.

Lymphatic Interventions for Treatment of Chylothorax.

PURPOSE: To determine effectiveness of lymphatic interventional procedures for treatment of chylothorax. MATERIAL AND METHODS: Analysis of interventions performed from 2001 to 2014. RESULTS: In 21 patients with therapy resistant chylothorax a lymphatic radiological intervention was attempted, which could be performed in 19 cases: 17 thoracic duct embolizations (15 transabdominal, one transzervical and one retrograde transvenous procedure), 2 percutaneous destructions of lymphatic vessels, one CT-guided injection of ethanol next to a duplicated thoracic duct. Fourteen of seventeen (82.3 %) of the technically successful embolizations lead to clinical cure. This encluded three patients with prior unsuccessful surgical thoracic duct ligation. Also the injection of ethanol was clinically effective. Complications were a bile peritonitis requiring operation, and one clinical deterioration of unknown cause. CONCLUSION: Interventional lymphatic procedures allow for effective treatment in many cases of chylothorax, and should be considered early during treatment. KEY POINTS: • Thoracic duct embolization is an effective treatment method for chylothorax. • If embolization is impossible, percutaneous lymphatic destruction or injection of sclerosants/tissue adhesive next to the thoracic duct may be tried.

Caecal intussusceptions in horses: a New Zealand perspective.

OBJECTIVE: To establish the prevalence of intussusceptions involving the caecum in a population of horses admitted to a university hospital for colic. DESIGN: Retrospective clinical study METHODS: Medical records of all horses admitted to the Massey University Veterinary Teaching Hospital between 1991 and 2004 were examined for information of those horses diagnosed with an intussusception involving the caecum. RESULTS: A total of 135 horses were admitted for colic surgery during the study period and 61 horses had a diagnosis of ileocaecal (37), caecocaecal (5) or caecocolic intussusception (19) made either at surgery or necropsy. Of the horses with ileocaecal intussusception, 32 had an incomplete hand-sewn ileocaecostomy without reduction and 29 survived to discharge. All the horses with caecocaecal intussusceptions were diagnosed preoperatively via rectal examination and/or transabdominal ultrasound: 2 were euthanased at surgery and 3 survived to discharge. In the 19 horses with caecocolic intussusceptions, manually reduction at surgery was performed in 6 and 5 of them survived to discharge. A typhlectomy was performed via a colotomy in 6 horses, 3 of which survived to discharge. CONCLUSIONS: The high prevalence of intussusceptions involving the caecum seen at this referral centre may indicate a higher prevalence in New Zealand than is reported elsewhere in the world. CLINICAL RELEVANCE: Intussusceptions involving the caecum should be considered as a differential diagnosis in horses presenting with chronic low-grade colic. Transabdominal ultrasound is useful for identifying caecocaecal and caecocolic intussusceptions. Hand-sewn side-to-side incomplete ileocaecostomy is a quick, effective and safe method of surgical treatment of ileocaecal intussusceptions.

Prostate cancer tissue is masked by bicalutamide: a case report.

Prostate cancer is the most common malignant tumor in men. Recently, a slightly decreased frequency of margin positivity following neoadjuvant bicalutamide treatment due to tumor shrinkage was reported. Trials investigating other anti-androgens in the past also reported lower frequencies of surgical margin positivity, but patients outcome has not improved. In this case, local recurrence was confirmed by needle biopsy in a patient five years following radical prostatectomy for prostate adenocarcinoma. After therapy with 50 mg bicalutamide for a month, the tumour was resected. Despite of detailed histological work-up and immunohistochemistry cancer suspicious lesions were not found. We think that bicalutamide may be capable of masking prostate cancer cells.

Aggressive angiomyxoma of the prostate mimicking benign prostatic hyperplasia.

Aggressive angiomyxoma (AAM) is a locally invasive soft tissue tumor with a high risk of local recurrence but without metastatic spread. The mesenchymal tumor is relatively site-specific and has a peak incidence in females in their 2nd or 4th decade. Only few cases in males have been reported in the literature. We describe what we think is the first case of an aggressive angiomyxoma arising in the prostate presenting with classical symptoms of benign prostatic hyperplasia.

[Diagnostic imaging of vascular leiomyosarcomas]. / Bildgebende Diagnostik von vaskulären Leiomyosarkomen.

Primary vascular leiomyosarcomas are very rare tumors, with the venous variety most often arising from the inferior caval vein and the arterial variety from the pulmonary artery. The tumors show either an exclusive intra- or extravascular pattern or a mixed growth pattern. The clinical symptoms depend on tumor location, with intraluminal tumors of the inferior caval vein causing edema or a Budd-Chiari syndrome. Leiomyosarcomas of the pulmonary artery can mimic chronic central or recurrent peripheral pulmonary embolism. Contrast enhanced spiral CT with multiplanar reconstruction is the diagnostic method of choice when a vascular leiomyosarcoma is suspected. MRI with MR-angiography can be added. If a tumor of undetermined origin shows a broad contact with a vessel and/or an intraluminal component, possible primary vascular leiomyosarcoma should be included in the differential diagnosis.

Limitations and pitfalls of Couinaud's segmentation of the liver in transaxial Imaging.

The segmental anatomy of the human liver has become a matter of increasing interest to the radiologist, especially in view of the need for an accurate preoperative localization of focal hepatic lesions. In this review article first an overview of the different classical concepts for delineating segmental and subsegmental anatomy on US, transaxial CT, and MR images is given. Essentially, these procedures are based on Couinaud's concept of three vertical planes that divide the liver into four segments and of a transverse scissura that further subdivides the segments into two subsegments each. In a second part, the limitations of these methods are delineated and discussed with the conclusion that if exact preoperative localization of hepatic lesions is needed, tumor must be located relative to the avascular planes between the different portal territories.

FDG-PET findings of vertebral compression fractures in osteoporosis: preliminary results.

The aim of this study was to evaluate FDG-PET findings in patients with osteoporosis or preclinical osteoporosis and acute vertebral compression fractures in order to determine whether FDG-PET has a value for distinction of pathological from osteoporotic vertebral fractures. 17 patients with a spontaneous compression fracture of the spine were evaluated by bone scanning with Tc-99m HDP, positron emission tomography with fluorine-18 deoxyglucose (FDG-PET) and magnetic resonance imaging (MRI). Osteoporosis had been established in all cases by X-ray and osteodensitometry. PET and bone scan images were scored independently from 0 (no pathological uptake) to 4 (definitive pathological uptake) by two blinded nuclear medicine physicians. The results of the blinded scoring were compared to MRI findings which served as gold standard. In 13 out of 17 patients, MRI demonstrated a vertebral fracture generating from osteoporosis. In 12 of these 13 cases, PET scans were scored with 0 or 1 and categorized as true negative. Standard uptake values (SUV) ranged between 1.1 and 2.4. In one of the 13 patients, PET was interpreted false positive with an uptake score of 3 (SUV = 2.9). Of the 17 patients, MRI revealed a pathological fracture caused by spondylodiscitis in three patients and by plasmacytoma in one patient. In these patients, all PET scans were highly positive with a score of 3 and 4 and SUV values between 3.8 to 9.8. The bone scans of all 17 patients were positive with scores of 3 or 4 but a differentiation between osteoporotic and pathological fractures was not possible. Our preliminary results indicate that acute vertebral fractures that originated from osteoporosis or preclinical osteoporosis tend to have no pathologically increased FDG uptake. Since a high FDG uptake is characteristic for malignant and inflammatory processes, use of FDG-PET may have potential value for differentiation between osteoporotic and pathological vertebral fractures.

Umbilical evagination of the urinary bladder in a neonatal filly.

An 8-hour-old Standardbred filly was evaluated because of an enlarging umbilical mass and stranguria. It was suspected that the mass was the urinary bladder; this was confirmed on surgical exploration of the abdomen. Despite a normal umbilical ring, the bladder had descended and partially everted through its urachal communication with the umbilical stalk. Partial cystectomy and umbilical resection were performed and resulted in an excellent clinical outcome. Evagination of the urinary bladder via the umbilicus has rarely been described in human infants, and, to our knowledge, it has not been reported in the veterinary literature.

Radiological signs of osteitis around extramedullary metal implants. A radiographic-microbiological correlative analysis in rabbit tibiae after local inoculation of Staphylococcus aureus.

Radiographic changes in the early stages of osteomyelitis may be subtle and, especially after plate osteosynthesis, frequently missed. A previously described experimental model of local bacterial infection was used in an attempt to determine the reliability of specific changes on conventional radiographs for the diagnosis of osteitis after metal-plate implantation and subsequent inoculation of Staphylococcus aureus in rabbit tibiae. Roentgenograms of the treated limbs were evaluated, and seven radiographic parameters, to which numerical scores were assigned, were determined for each bone. Our results substantiate the conclusion that a radiographically verified periosteal reaction is a constant and early skeletal feature of acute osteomyelitis and has the strongest association to the microbiological results (P < 0.05), emphasising its high predictive value. Plate implantation does not notably impede the diagnosis of osteomyelitis. An association between the amount of inoculated bacteria and the extent of radiographic changes could be found. The results of this present study closely resemble those described in man and suggest that this model may be useful for future experimental investigations in determining a score judging the severity of osseous involvement in local bacterial infection after plate osteosynthesis.

Improving the detectability of focal liver lesions on T2-weighted MR images: ultrafast breath-hold or respiratory-triggered thin-section MRI?

The purpose of this study was to determine whether a respiratory-triggered (RT) T2-weighted turbo spin-echo (TSE) sequence with thin section can improve the detectability of focal liver lesions compared to a breath-hold (BH) T2-weighted TSE sequence. In 25 patients an RT TSE with 8-mm sections (8-TSE RT) and 5-mm sections (5-TSE RT) and a BH TSE sequence with 8-mm sections (8-TSE BH) were performed. Forty-one focal liver lesions (mean: 1.8 +/- 1.2 cm; 14 lesions < or =1 cm; 27 lesions >1 cm) were evaluated. The 5-TSE RT was significantly better in lesion detection compared to the 8-TSE BH sequence for all sizes of lesions (40/41 vs. 33/41; P = 0.014). For lesions >1 cm no relevant differences in the detection rate of the sequences were found (8-TSE RT, 26/27; 5-TSE RT, 26/27; 8-TSE BH, 25/27), for lesions < or =1 cm the 5-TSE RT provided significantly better sensitivity than the 8-TSE BH (14/14 vs. 8/14, P = 0.015). The results of this study suggest that lesion detection could be significantly improved by using an RT TSE sequence with thin sections compared with a BH TSE sequence.

[Diagnosis of intramural bile duct varicose veins ("pseudo-cholangiocarcinoma sign"]. / Zur Diagnostik der intramuralen Gallengangsvarikose ("pseudo-cholangiocarcinoma sign").

We report the case of a patient with portal hypertension and portal vein thrombosis who was admitted to hospital for evaluation prior to a scheduled portosystemic shunt operation. Ultrasound examination revealed dilatation of intrahepatic bile ducts and echogenic thickening of the walls of both right and left main bile ducts as well as the common bile duct, highly suspicious of a carcinoma. Further evaluation, however, showed a varicosis of the bile duct walls to be the cause of the thickening of the walls, the varicosis resulting from the long-standing cavernous transformation of the portal vein and the portal hypertension. This tumour-like thickening of the walls, caused by numerous tiny varicose veins, is also known as "Pseudo-cholangiocarcinoma sign" in the Anglo-American world.

Subchondral cystic lesions of the proximal extremity of the tibia in horses: 12 cases (1983-2000).

OBJECTIVE: To determine clinical and radiographic features of subchondral cystic lesions (SCL) of the proximal extremity of the tibia in horses that could be used to classify these lesions as being related to osteochondrosis or osteoarthritis and to evaluate results of surgical debridement. DESIGN: Retrospective study. ANIMALS: 12 horses with 14 SCL. PROCEDURE: Medical records and radiographs obtained before and after treatment were reviewed. RESULTS: In 6 young horses (8 lesions), SCL were considered to be related to osteochondrosis; all involved the lateral tibial condyle. The remaining 6 horses were mature and had radiographic evidence of osteoarthritis in addition to SCL. Arthroscopic debridement was performed in 4 horses in which lesions were considered to be a result of osteochondrosis and in 3 horses with osteoarthritis. Three horses in which SCL were considered to be a result of osteochondrosis performed athletically after debridement. Two horses with moderate osteoarthritis returned to work after arthroscopic debridement but at a lower level of athletic performance. One horse with SCL related to osteochondrosis responded to medical treatment and went on to race. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that arthroscopic debridement of SCL is feasible in horses in which lesions involve the cranial portion of the lateral or medial tibial condyle, and that treated horses may be able to perform athletically.

[CT angiography hemodynamically relevant to renal artery stenosis. Evaluation of AXIAL, MPR, MIP and SSD reconstruction procedures under standard investigation conditions]. / CT-Angiographie hämodynamisch relevanter Nierenarterienstenosen. Evaluation der Rekonstruktionsverfahren AXIAL, MPR, MIP und SSD unter standardisierten Untersuchungsbedingungen.

PURPOSE: To evaluate the various reconstruction methods of helical-CT angiography for the assessment of hemodynamically relevant renal artery stenoses in comparison to i.a. DSA. METHODS: In 76 renal arteries the reconstruction modalities AXIAL, MRP, MIP and SSD of helical-CT angiography were compared with the results of i.a. DSA for the determination of the grade and location of the stenosis. RESULTS: The highest accuracy of stenosis grading was 76% with AXIAL reconstruction. In 8% of the cases grading of the stenosis was not evaluable by the AXIAL reconstruction. In these cases, a higher sensitivity in the detection of hemodynamically relevant stenoses (> grade II, > 50%) was achieved with the reconstruction mode MPR (96%) than with MIP (92%). In 51% of the cases the reconstruction mode SSD was not suitable for any diagnosis of renal artery stenosis because of overlying calcified plaques. CONCLUSIONS: The evidence of hemodynamically relevant stenosis in helical-CT angiography in comparison to i.a. DSA succeeds most reliable by using the reconstruction modality AXIAL in combination with MPR. The MIP reconstruction provides information about the anatomy of the renal arteries within one image.

Infantile fibromatosis of the neck with intracranial involvement: MR and CT findings.

CT and MR imaging studies were performed in a 3-year-old boy with infantile fibromatosis arising from the infratemporal fossa and extending into the middle cranial fossa. On CT scans, the lesion was hyperattenuating (44-49 Hounsfield units [HU]), enhancing significantly after application of contrast material (63-66 HU). The MR images showed a multilobulated lesion of heterogeneous signal intensity. The tumor was markedly hypointense on T2-weighted images and slightly hypointense on T1-weighted images relative to brain tissue, iso- or slightly hyperintense relative to tongue muscle on both T2- and T1-weighted images, and enhanced strongly after administration of gadopentetate dimeglumine.

Surgery for portal hypertension and transjugular intrahepatic portosystemic shunts in Germany: results of a national survey. / Portosystemische Shuntchirurgie und transjugulärer intrahepatischer Stent (TIPS) in Deutschland. Ergebnisse einer Umfrage.

A national survey was conducted to determine the role of portosystemic shunt surgery and transjugular intrahepatic portosystemic shunt (TIPS) in Germany. A questionnaire was mailed to 1324 surgical units at 1273 hospitals, and 941 responses (74%) were received. Interventional endoscopy for variceal bleeding is carried out predominantly (73%) in medical departments. From 1992 to 1997 the annual number of surgical shunts dropped from 253 to 120, whereas the respective numbers of TIPS increased from 202 to 920. In this 6-year period a total of 1042 shunts and 3575 TIPS were reported by 109 and 64 centers, respectively. TIPS was applied mainly in university hospitals (88.9%), whereas shunt surgery was more broadly used in non-university hospitals (58.8%). Clearly, prospective randomized comparisons of TIPS and surgical shunts are needed to reveal which treatment is best in patients with variceal bleeding stratified for mortality risk and stage of liver disease. However, the decreasing number and experience with shunt surgery may impede such studies. Probably, liver transplant centers which currently do only 41.2% of shunt procedures are most familiar with surgery in portal hypertension and are therefore most appropriate to maintain quality and expertise in this palliative and demanding branch of surgery.