Although the gastrointestinal tract is a fairly frequent site of melanoma metastases, reports of small bowel intussusception caused by melanoma are very rare. We report the case of a 77-year-old man ...who was admitted to our hospital with epigastric pain, melena and anaemia. After clinical examination, laboratory evaluation and radiological work-up the diagnosis of a jejunal intussusception was made. Exploratory laparoscopy revealed a large tumour arising from the jejunum, approximately 20 cm distal to the angle of Treitz. Small bowel resection with an end-to-end anastomosis was performed. Histological examination showed an intestinal melanoma. There are different theories concerning the origin of malignant melanoma in the small bowel. Although the small and large intestines normally contain no melanocytes, these cells have occasionally been found in the alimentary and respiratory tracts and even in lymph nodes, which supports the theory of a primary origin of melanoma at these sites. Since this was a solitary intestinal lesion and there was no history of cutaneous melanoma, we conclude that this could be an example of a very rare primary melanoma of the small intestine.
We present two cases of desmoid tumour of the anterior abdominal wall in young women in whom the defect after radical excision could not be closed without using prosthesis. The first case warranted ...the use of a composite mesh, the second a polypropylene prosthesis. In both cases primary closure of the skin was possible. Both women are doing fine with no sign of relapse or incisional hernia.
The Human Epidermal growth factor Receptor 2 (HER2) has been established as a key player in the development of certain human tumors. ToGA trial has demonstrated that the addition of the monoclonal ...antibody blocking HER2 receptor, trastuzumab (Herceptin®), to chemotherapy significantly improves overall survival of patients with HER2-positive advanced or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction. Therefore, it is essential that pathologists guarantee an accurate testing of HER2 status in these tumours. Following the international recommendations and the Belgian criteria for reimbursement of trastuzumab, a consortium of expert pathologists (Belgian Working Group Molecular Pathology) proposes an adaptation of the international guidelines in order to develop strategies for optimal performance, interpretation and reporting assays.
A case of intrapulmonary primitive neuro-ectodermal tumour (PNET) without thoracic wall involvement is presented in a 33-year-old man. PNET of the thoracopulmonary region, also called Askin tumour, ...is a rare undifferentiated sarcoma usually involving the thoracic wall. Primary intrapulmonary PNET without parietal pleura or thoracic wall involvement is very rare. The correlation between anatomo-pathological aspects and clinical imaging is emphasized, which is discussed in the light of the most recent literature.
Studies with I
125-labeled low-density lipoproteins (LDLs) have shown the presence of high-affinity LDL receptors on insulin-producing β cells but not on neighboring α cells. By using gold-labeled ...lipoproteins, we demonstrate receptor-mediated endocytosis of LDLs and very low-density lipoproteins in rat and human β cells. Specific for human β cells is the fusion of LDL-containing endocytotic vesicles with lipid-storing vesicles (LSVs. diameter, 0.6–3.6 μm), which are absent in rodent β cells. LSVs also occur in human pancreatic α and duct cells, but these sequester little gold-labeled LDL. In humans <25 years old, LSVs occupy 1% of the cytoplasmic surface area in β, α, and duct cells. In humans >50 years old, LSV surface area in β cells (11 ± 2% of cytoplasmic surface area) is fourfold higher than in α and duct cells and 10-fold higher than in β cells at younger ages (
P < 0.001); the mean LSV diameter in these β cells (1.8 ± 0.04 μm) is larger than at younger ages (1.1 ± 0.2 μm;
P < 0.005). Oil red O staining on pancreatic sections confirms that neutral lipids accumulate in β cells of older donors. We conclude that human β cells can incorporate LDL and very low-density lipoprotein material in LSVs. The marked increase in the LSV area of aging human β cells raises the question whether it is caused by prolonged exposure to high lipoprotein levels such as occurs in Western populations and whether it is causally related to the higher risk for type 2 diabetes with aging.
Epithelial ovarian cancer is associated with high mortality due to diagnosis at later stages associated with peritoneal involvement. Several trials have evaluated the effect of intraperitoneal ...treatment. In this preclinical study, we report the efficacy, pharmacokinetics and pharmacodynamics of intraperitoneal treatment with two approved nanomolecular formulations of paclitaxel (nab-PTX and mic-PTX) in a murine ovarian cancer xenograft model.
IC50 was determined in vitro on three ovarian cancer cell lines (OVCAR-3, SK-OV-3 and SK-OV-3-Luc IP1). EOC xenografts were achieved using a modified subperitoneal implantation technique. Drug treatment was initiated 2 weeks after engraftment, and tumor volume and survival were assessed. Pharmacokinetics and drug distribution effects were assessed using UHPLC-MS/MS and MALDI imaging mass spectrometry, respectively. Pharmacodynamic effects were analyzed using immunohistochemistry and transmission electron microscopy using standard protocols.
We demonstrated sub-micromolar IC
concentrations for both formulations on three EOC cancer cell lines in vitro. Furthermore, IP administration of nab-PTX or mic-PTX lead to more than 2-fold longer survival compared to a control treatment of IP saline administration (30 days in controls, 66 days in nab-PTX treated animals, and 76 days in mic-PTX animals, respectively). We observed higher tissue uptake of drug following nab-PTX administration when compared to mic-PTX, with highest uptake after 4 hours post-treatment, and confirmed this lower uptake of mic-PTX using HPLC on digested tumor samples. Furthermore, apoptosis was not increased in tumor implants up to 24h post-treatment.
Intraperitoneal administration of both nab-PTX and mic-PTX results in a significant anticancer efficacy and survival benefit in a mouse OC xenograft model.
Patients with metastatic colorectal cancer and KRAS mutation are unlikely to benefit from treatment with anti-EGFR antibodies, and testing for KRAS mutation in this setting is recommended. ...Pathologists have a crucial role in accurate testing for KRAS mutations, whether or not testing is performed in their own laboratory, as mutation analysis is performed on paraffin embedded tissue selected by the pathologists. The type of fixative used is a very important issue, as some fixatives do not allow molecular testing. Pathologists must select the most appropriate tumoral tissue block for KRAS mutation analysis and hence, must know the sensitivity of the KRAS mutation detection methodology utilized in their reference laboratory. It is essential that they select a tissue block that contains enough percentage of viable tumour cells, as false negative results will occur when the sample is contaminated with high levels of nontumour elements. Pathologists not only have to recognize the area of invasive carcinoma and distinguish it from non-invasive neoplastic components, but also have to estimate the percentage of necrotic debris and nontumoural elements. For tests that require a high percentage of tumour cells, macrodissection before extraction of nucleic acids is often indicated. The primary pathologists in addition are responsible for preparation of the pathology report for the tissue block on which the KRAS mutation analysis was performed and should transmit the results to the requesting clinician. Pathologists should participate in a multidisciplinary oncologic consult to achieve correct interpretation of the results e.g. in case of potential false negative results.
Studies on the pathogenesis of type 1 diabetes have mainly focused on the role of the immune system in the destruction of pancreatic beta-cells. Lack of data on the cellular and molecular events at ...the beta-cell level is caused by the inaccessibility of these cells during development of the disease. Indirect information has been collected from isolated rodent and human islet cell preparations that were exposed to cytotoxic conditions. This article reviews in vitro experiments that investigated the role of beta-cells in the process of beta-cell death. beta-Cells rapidly die in necrosis because of toxic levels of oxidizing radicals or of nitric oxide; they progressively become apoptotic after prolonged culture at low glucose or with proinflammatory cytokines. Their susceptibility to necrosis or apoptosis varies with their functional state and thus with the environmental conditions. A change in cellular phenotype can alter its recognition of potentially cytotoxic agents and its defense mechanisms against cell death. These observations support the view that beta-cells are not necessarily passive victims of a cytotoxic process but can actively participate in a process of beta-cell death. Their role will be influenced by neighboring non-beta-cells, which can make the islet internal milieu more protective or toxic for the beta-cells. We consider duct cells as potentially important contributors to this local process.
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