Multi-Modal Mass Spectrometric Imaging of Uveal Melanoma

Matrix assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI), was used to obtain images of lipids and metabolite distribution in formalin fixed and embedded in paraffin (FFPE) whole eye sections containing primary uveal melanomas (UM). Using this technique, it was possible to obtain images of lysophosphatidylcholine (LPC) type lipid distribution that highlighted the tumour regions. Laser ablation inductively coupled plasma mass spectrometry images (LA-ICP-MS) performed on UM sections showed increases in copper within the tumour periphery and intratumoural zinc in tissue from patients with poor prognosis. These preliminary data indicate that multi-modal MSI has the potential to provide insights into the role of trace metals and cancer metastasis.

Hepatic Resection Following Selective Internal Radiation Therapy for Colorectal Cancer Metastases in the FOXFIRE Clinical Trial: Clinical Outcomes and Distribution of Microspheres

The FOXFIRE (5-Fluorouracil, OXaliplatin and Folinic acid ± Interventional Radio-Embolisation) clinical trial combined systemic chemotherapy (OxMdG: Oxaliplatin, 5-fluorouracil and folic acid) with Selective Internal Radiation Therapy (SIRT or radio-embolisation) using yttrium-90 resin microspheres in the first-line management for liver-dominant metastatic colorectal cancer (CRC). We report clinical outcomes for patients having hepatic resection after this novel combination therapy and an exploratory analysis of histopathology. Multi-Disciplinary Teams deemed all patients inoperable before trial registration and reassessed them during protocol therapy. Proportions were compared using Chi-squared tests and survival using Cox models. FOXFIRE randomised 182 participants to chemotherapy alone and 182 to chemotherapy with SIRT. There was no statistically significant difference in the resection rate between groups: Chemotherapy alone was 18%, (n = 33); SIRT combination was 21% (n = 38) (p = 0.508). There was no statistically significant difference between groups in the rate of liver surgery, nor in survival from time of resection (hazard ratio (HR) = 1.55; 95% confidence interval (CI) = 0.83–2.89). In the subgroup studied for histopathology, microsphere density was highest at the tumour periphery. Patients treated with SIRT plus chemotherapy displayed lower values of viable tumour in comparison to those treated with chemotherapy alone (p < 0.05). This study promotes the feasibility of hepatic resection following SIRT. Resin microspheres appear to preferentially distribute at the tumour periphery and may enhance tumour regression.

Epidemiological and morphological analysis of feline injection site sarcomas

Feline injection site sarcomas (FISS) are malignant neoplasms of mesenchymal origin which arise in sites of injections in cats. The prevalence is estimated between 1 in 1000 and 1 in 10 000 vaccinations in the United Kingdom. The aim of this study was to estimate the incidence of FISS in Poland and to analyse clinical aspects and histological and cytological features of injection site sarcomas. In our study the prevalence of FISS was 0.16% (16 FISS on 10.000 of cats) in feline patients in one of a veterinary surgery which conducts the general practice and 85 on 10.000 cats in a practice focused on veterinary oncology. The most typical microscopic features of FISS found in the present analysis were: the presence of perilesional scarring and inflammation, aggregates of lymphocytes at the tumour periphery, moderate but usually marked cellular pleomorphism and intralesional necrosis. The most typical cytologic features of FISS found in present study were: the presence of neutrophils, marked cellular pleomorphism, the presence of lymphocytes and macrophages, the presence of extremely large nuclei in the neoplastic cells, and high sample cellularity.

Absence of extramural venous invasion is an excellent predictor of metastasis-free survival in colorectal carcinoma stage II—a study using tangential tissue sectioning

AimsExtramural venous invasion (EVI) is an important predictor of haematogenous metastasis in colorectal cancer (CRC). However, remarkable discrepancies in incidence rates indicate major problems regarding EVI assessment. The present prospective study applies tangential vessel preparation to CRC resection specimens and correlates results of EVI with metachronous haematogenous metastatic (MHM) spread.MethodsStage II CRC diagnosed at the Institute of Pathology, University Teaching Hospital Feldkirch, Austria over a period of 30 months were analysed and tangential sectioning of the pericolonic tissue was performed. Confirmation, or exclusion of MHM, as assessed by computerised tomography, sonography or biopsy, was recorded.ResultsIn 50/79 (63%) cases EVI was detected. In 13/50 (26%), MHM developed. Of the 29/79 (37%) patients without EVI, only one (3.5%) developed MHM. Statistically, the rate of MHM for patients with EVI was independent of adjuvant chemotherapy.ConclusionsTangential sectioning of the tumour periphery in CRC stage II yields a high rate of histologically evaluable extramural veins and permits proper assessment of EVI. Absence of EVI is significantly associated with metastasis-free survival, a finding of potential therapeutic value. On the other hand, one-third of the patients with EVI and circumferential tumour growth develop MHM, a setting in which the option for adjuvant chemotherapy should be considered. This study emphasises the importance of tangential sectioning of the invasive tumour front in CRC compared with the recommended perpendicular technique. The sensitivity and specificity of this method regarding MHM are characterised.

Focus on the Tumour Periphery in MRI Evaluation of Soft Tissue Sarcoma: Infiltrative Growth Signifies Poor Prognosis

Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas (STS) has been shown to be of prognostic importance and preoperative risk stratification could individualize neoadjuvant treatment.Patients and methods. We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The findings were correlated to histopathology and to outcome.Results. The MRI-based peripheral tumour growth pattern was classified as pushing in 34 tumours, focally infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in two-thirds of the microscopically infiltrative tumours. Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of metastases (P=.01) and a 3.7 times higher risk of local recurrence (P=.02).Discussion. Based on this observation we suggest that MRI evaluation of STS should focus on the peripheral tumour growth pattern since it adds prognostic information of value for decisions on neoadjuvant therapies.

Microvascular Architecture of Hepatic Metastases in a Mouse Model

Development of effective treatment for hepatic metastases can be initiated by a better understanding of tumour vasculature and blood supply. This study was designed to characterise the microvascular architecture of hepatic metastases and observe the source of contributory blood supply from the host. Metastases were induced in mice by an intrasplenic injection of colon carcinoma cells (106 cells/ml.) Vascularization of tumours was studied over a three week period by scanning electron microscopy of microvascular corrosion casts. Metastatic liver involvement was observed initially within a week post induction, as areas approximately 100 μm in diameter not perfused by the casting resin. On histology these spaces corresponded to tumour cell aggregates. The following weeks highlighted the angiogenesis phase of these tumours as they received a vascular supply from adjacent hepatic sinusoids. Direct sinusoidal supply of metastases was maintained throughout tumour growth. At the tumour periphery most sinusoids were compressed to form a sheath demarcating the tumour from the hepatic vasculature. No direct supply from the hepatic artery or the portal vein was observed. Dilated vessels termed vascular lakes dominated the complex microvascular architecture of the tumours, most tapering as they traversed towards the periphery. Four vascular branching patterns could be identified as true loops, bifurcations and trifurcations, spirals and capillary networks. The most significant observation in this study was the direct sinusoidal supply of metastases, together with the vascular lakes and the peripheral sinusoidal sheaths of the tumour microculature.