50 research outputs found

    Long-term survival of a woman with well differentiated papillary mesothelioma of the peritoneum: a case report and review of the literature

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    <p>Abstract</p> <p>Introduction</p> <p>Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epitheloid mesothelioma, which is usually seen in young women. WDPMP is generally considered of low malignant potential, however the long-term nature of the tumor remains poorly defined.</p> <p>Case presentation</p> <p>We describe the long-term follow-up of a 60-year-old woman of West African descent who has survived 24 years with WDPMP after receiving extensive local and systemic adjuvant chemotherapy. Her clinical course has included three exploratory laparotomies with intraperitoneal and intravenous chemotherapy over two decades. Her course was complicated by anthracycline-induced cardiomyopathy, for which she underwent an orthotopic heart transplant. Our patient is alive with stable radiological evidence of peritoneal disease, and continues to suffer from chronic abdominal pain.</p> <p>Conclusion</p> <p>No consensus exists regarding optimal treatment strategies for WDPMP. However, given the low malignant potential of the tumor, careful consideration should be made before proceeding with aggressive interventions. Further, long-term follow-up reports are required to fully characterize this tumor.</p

    Wnt signalling in adenomas of familial adenomatous polyposis patients

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    BACKGROUND: Epigenetic silencing of Wnt antagonists and expression changes in genes associated with Wnt response pathways occur in early sporadic colorectal tumourigenesis, indicating that tumour cells are more sensitive to Wnt growth factors and respond differently. In this study, we have investigated whether similar changes occur in key markers of the Wnt response pathways in the genetic form of the disease, familial adenomatous polyposis (FAP). METHODS: We investigated epigenetic and expression changes using pyrosequencing and real-time RT-PCR in samples from seven patients without neoplasia, and matched normal and tumour tissues from 22 sporadic adenoma and 14 FAP patients. RESULTS: We found that 17 out of 24 (71%) FAP adenomas were hypermethylated at sFRP1, compared with 20 out of 22 (91%) of sporadic cases. This was reflected at the level of sFRP1 transcription, where 73% of FAP and 100% of sporadic cases were downregulated. Increased expression levels of c-myc and FZD3 were less common in FAP (35 and 46% respectively) than sporadic tumours (78 and 67% respectively). CONCLUSION: Overall, the changes in expression and methylation were comparable, although the degree of change was generally lower in the FAP adenomas. Molecular heterogeneity between multiple adenomas from individual FAP patients may reflect different developmental fates for these premalignant tumours

    Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation

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    Acetylcholine (ACh) has been shown to modulate neuronal differentiation during early development. Both muscarinic and nicotinic acetylcholine receptors (AChRs) regulate a wide variety of physiological responses, including apoptosis, cellular proliferation and neuronal differentiation. However, the intracellular mechanisms underlying these effects of AChR signaling are not fully understood. It is known that activation of AChRs increase cellular proliferation and neurogenesis and that regulation of intracellular calcium through AChRs may underlie the many functions of ACh. Intriguingly, activation of diverse signaling molecules such as Ras-mitogen-activated protein kinase, phosphatidylinositol 3-kinase-Akt, protein kinase C and c-Src is modulated by AChRs. Here we discuss the roles of ACh in neuronal differentiation, cell proliferation and apoptosis. We also discuss the pathways involved in these processes, as well as the effects of novel endogenous AChRs agonists and strategies to enhance neuronal-differentiation of stem and neural progenitor cells. Further understanding of the intracellular mechanisms underlying AChR signaling may provide insights for novel therapeutic strategies, as abnormal AChR activity is present in many diseases

    Quality-of-life outcomes in older patients with early-stage rectal cancer receiving organ-preserving treatment with hypofractionated short-course radiotherapy followed by transanal endoscopic microsurgery (TREC): non-randomised registry of patients unsuitable for total mesorectal excision

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    Background Older patients with early-stage rectal cancer are under-represented in clinical trials and, therefore, little high-quality data are available to guide treatment in this patient population. The TREC trial was a randomised, open-label feasibility study conducted at 21 centres across the UK that compared organ preservation through short-course radiotherapy (SCRT; 25 Gy in five fractions) plus transanal endoscopic microsurgery (TEM) with standard total mesorectal excision in adults with stage T1–2 rectal adenocarcinoma (maximum diameter ≤30 mm) and no lymph node involvement or metastasis. TREC incorporated a non-randomised registry offering organ preservation to patients who were considered unsuitable for total mesorectal excision by the local colorectal cancer multidisciplinary team. Organ preservation was achieved in 56 (92%) of 61 non-randomised registry patients with local recurrence-free survival of 91% (95% CI 84–99) at 3 years. Here, we report acute and long-term patient-reported outcomes from this non-randomised registry group. Methods Patients considered by the local colorectal cancer multidisciplinary team to be at high risk of complications from total mesorectal excision on the basis of frailty, comorbidities, and older age were included in a non-randomised registry to receive organ-preserving treatment. These patients were invited to complete questionnaires on patient-reported outcomes (the European Organisation for Research and Treatment of Cancer Quality of Life [EORTC-QLQ] questionnaire core module [QLQ-C30] and colorectal cancer module [QLQ-CR29], the Colorectal Functional Outcome [COREFO] questionnaire, and EuroQol-5 Dimensions-3 Level [EQ-5D-3L]) at baseline and at months 3, 6, 12, 24, and 36 postoperatively. To aid interpretation, data from patients in the non-randomised registry were compared with data from those patients in the TREC trial who had been randomly assigned to organ-preserving therapy, and an additional reference cohort of aged-matched controls from the UK general population. This study is registered with the ISRCTN registry, ISRCTN14422743, and is closed. Findings Between July 21, 2011, and July 15, 2015, 88 patients were enrolled onto the TREC study to undergo organ preservation, of whom 27 (31%) were randomly allocated to organ-preserving therapy and 61 (69%) were added to the non-randomised registry for organ-preserving therapy. Non-randomised patients were older than randomised patients (median age 74 years [IQR 67–80] vs 65 years [61–71]). Organ-preserving treatment was well tolerated among patients in the non-randomised registry, with mild worsening of fatigue; quality of life; physical, social, and role functioning; and bowel function 3 months postoperatively compared with baseline values. By 6–12 months, most scores had returned to baseline values, and were indistinguishable from data from the reference cohort. Only mild symptoms of faecal incontinence and urgency, equivalent to less than one episode per week, persisted at 36 months among patients in both groups. Interpretation The SCRT and TEM organ-preservation approach was well tolerated in older and frailer patients, showed good rates of organ preservation, and was associated with low rates of acute and long-term toxicity, with minimal effects on quality of life and functional status. Our findings support the adoption of this approach for patients considered to be at high risk from radical surgery. Funding Cancer Research UK

    Distribution of heavy metals in the eggs and hatchlings of olive ridley sea turtle, Lepidochelys olivacea, from Gahirmatha, Orissa

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    371-372Shell and yolk-albumen of fresh eggs, hatched egg shells and newly emerged hatchlings of olive ridley sea turtle, Lepidochelys olivacea, along with eight nesting beach sand samples showed higher iron, zinc and lead concentrations than cobalt, chromium, copper and nickel. Beach sand samples recorded higher values of all metals than the egg components. Newly emerged hatchlings also recorded higher values than the fresh eggs. Embryos might have accumulated these metals from the nesting beach during incubation

    Calcium metabolism in olive ridley turtle eggs during embryonic development

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    Analyses of calcium, magnesium, sulphur, potassium and phosphorus content of the eggshell, yolk-albumen and embryos of olive ridley turtle, Lepidochelys olivacea, have been carried out at various stages of embryonic development. Calcium is the major inorganic constituent in the egg (shell and yolk-albumen) and embryos. Other elements are present either in trace or in minute trace amounts. The egg contents (yolk and albumen) provide only 40% of the embryonic calcium requirement of the hatchling. The remaining 60% is provided by the eggshell. The eggshell also undergoes a similar reduction in its calcium content from laying to hatching. Elements other than calcium present in the yolk-albumen are sufficient for normal embryonic development. The movement of calcium from the eggshell to the embryo starts at about the 40th day of development at 29.5°C. Birds, turtles and crocodiles use their eggshell as the secondary source of embryonic calcium requirement. This dependence on the eggshell varies in different groups which is highest in birds and lowest in crocodiles

    Ultrastructure and characteristics of eggshells of the olive ridley turtle (Lepidochelys olivacea) from Gahirmatha, India

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    The structure of a chelonian eggshell is of prime importance for the developing embryo. It acts as a protective covering as well as mediator in the exchange of heat and water. The fresh eggshell of the olive ridley (Lepidochelys olivacea) turtle displays a variety of structural forms in their aragonite framework. Its netted substrate, loose texture and poorly organised crystallites favour the easy exchange of air and water during its development. The shell consists mostly of calcium in carbonate form and K, Mg, Fe, Ni, Pb, Zn, Co, Cr, Cu, Mn and Cd in traces. Ba and Sr in traces are also a feature of the thermal analysis graph. Phosphorus was not detected in the shell and its absence eliminates an earlier suggestion of it being a key factor in the development of aragonite crystals in the inorganic structure of marine turtle eggshells. Its combustion characteristics, which have not been previously reported, are recorded

    Oligometastatic deposits of prostate cancer found within the sigmoid pericolic fat that was resected for colonic adenocarcinoma: a case report.

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    BACKGROUND Prostate cancer may rarely metastasize to the colon and colonic lymph nodes, and local treatment of oligometastatic deposits may improve oncological outcomes. Immunohistochemical stains are used to determine the most likely source of metastatic deposits when they are seen within surgical specimens. The aim of this case report is to illustrate how such techniques were used to identify unexpected prostatic metastases within the pericolic fat of a sigmoid colon resection specimen following elective curative surgery for colorectal cancer. To our knowledge, this is the first report of complete excision of oligometastatic deposits of prostate cancer found incidentally within the specimen of another cancer. CASE REPORT An 89-year-old Caucasian man underwent sigmoid colectomy for an obstructing colorectal cancer in the sigmoid colon with some mesenteric lymphadenopathy. He had previously received radical radiotherapy for prostate cancer 10 years earlier. When the specimen was examined by the histopathologist, it was noted that the pericolic fat adjacent to the colorectal adenocarcinoma contained some metastatic deposits. Positive immunohistochemical staining for prostate-specific antigen and prostate-specific acid phosphatase with negative staining for CDX2 and CK20 revealed these to be prostatic metastases rather than colonic. Since these were completely excised, and there were no other metastases, this represented a serendipitous, curative excision of oligometastatic deposits of an additional cancer to the one that was being treated. CONCLUSIONS This case illustrates how immunohistochemical staining may be used to distinguish the source of metastatic deposits based on the likelihood of primary tumor from a careful and thorough patient history
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