The pancreas is a large, retroperitoneal organ situated immediately behind the posterior wall of the lesser sac, in the floor of the supracolic compartment of the abdominal cavity. Although principally an exocrine gland, the pancreas also performs crucially important endocrine functions. The exocrine pancreas secretes digestive enzymes. These are produced by the pancreatic acini and released into an elaborate ductal system which eventually opens into the second part of the duodenum. The endocrine component of the pancreas is represented by the islets of Langerhans that are present diffusely in the pancreatic substance. The islets are microscopic collections of cells whose secretions include pro-insulin and glucagon; hormones of vital importance in carbohydrate metabolism. Its deep location and its close topographical relationship to several vital structures make pancreatic surgery both challenging and hazardous. A sound appreciation of the topographical, vascular and ductal anatomy of the pancreas is fundamental to the successful surgical management of pancreatic cancers, congenital malformations of the pancreas and various surgical complications of acute pancreatitis.The spleen is the largest lymphoid organ in the body. It is situated deep in the left hypochondrium, wedged between the gastric fundus, left hemidiaphragm and left kidney. Trauma, lymphoid neoplasia, gastric cancers, portal hypertension and idiopathic thrombocytopenia may necessitate splenectomy. A sound knowledge of the surgical and functional anatomy of the spleen is essential if splenectomy is to be performed safely and effectively. 相似文献
Langerhans cell histiocytosis (LCH) remains a poorly understood disorder with heterogeneous clinical presentations characterized by focal or disseminated lesions that contain excessive CD1a+ langerin+ cells with dendritic cell features known as “LCH cells.” Two of the major questions investigated over the past century have been (i) the origin of LCH cells and (ii) whether LCH is primarily an immune dysregulatory disorder or a neoplasm. Current opinion is that LCH cells are likely to arise from hematopoietic precursor cells, although the stage of derailment and site of transformation remain unclear and may vary in patients with different extent of disease. Over the years, evidence has provided the view that LCH is a neoplasm. The demonstration of clonality of LCH cells, insufficient evidence alone for neoplasia, is now bolstered by finding driver somatic mutations in BRAF in up to 55% of patients with LCH, and activation of the RAS‐RAF‐MEK‐ERK (where MEK and ERK are mitogen‐activated protein kinase and extracellular signal‐regulated kinase, respectively) pathway in nearly 100% of patients with LCH. Herein, we review the evidence that recurrent genetic abnormalities characterized by activating oncogenic mutations should satisfy prerequisites for LCH to be called a neoplasm. As a consequence, recurrent episodes of LCH should be considered relapsed disease rather than disease reactivation. Mapping the complete genetic landscape of this intriguing disease will provide additional support for the conclusion that LCH is a neoplasm and is likely to provide more potential opportunities for molecularly targeted therapies. 相似文献
Transplantation of islets into the liver confers several site‐specific challenges, including a delayed vascularization and prevailing hypoxia. The greater omentum has in several experimental studies been suggested as an alternative implantation site for clinical use, but there has been no direct functional comparison to the liver. In this experimental study in mice, we characterized the engraftment of mouse and human islets in the omentum and compared engraftment and functional outcome with those in the intraportal site. The vascularization and innervation of the islets transplanted into the omentum were restored within the first month by paralleled ingrowth of capillaries and nerves. The hypoxic conditions in the islets early posttransplantation were transient and restricted to the first days. Newly formed blood vessels were fully functional, and the blood perfusion and oxygenation of the islets became similar to that of endogenous islets. Furthermore, islet grafts in the omentum showed at 1 month posttransplantation functional superiority to intraportally transplanted grafts. We conclude that in contrast to the liver the omentum provides excellent engraftment conditions for transplanted islets. Future studies in humans will be of great interest to investigate the capability of this site to also harbor larger grafts without interfering with islet functionality. 相似文献
Although many adults retain good hearing as they age, hearing loss associated with ageing is common among elderly persons. There are a number of pathophysiolological processes underlying age-related changes to functional components in the inner ear. Genetic factors determine the ageing process but are under the influence of intrinsic and environmental factors. It is difficult to distinguish changes of normal ageing from those of other contributing factors. The effects of age-related deafness can have significant physical, functional and mental health consequences. Although a deficit in hearing can be corrected to some degree by a hearing aid or other appropriate amplification devices, hearing-related rehabilitative needs are much more than simply amplifying external sound. Only by better understanding the process of ageing and its effect on the auditory function can we better accommodate elderly people in our day-to-day interactions. We review here the structure and function of the inner ear, pathophysiology associated with age-related hearing loss (ARHL), heritability, allelism and modifier genes of ARHL, and evaluate the genetic analyses for identification of genetic factors that are involved. 相似文献
Introduction: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasia driven by activation mutations alongside the MAPK pathway. Its broad spectrum of clinical manifestations and diverse course and clinical outcome, make interpretation of trial data difficult. Use of different stratification systems further complicates comparison among trials.
Areas covered: This review summarizes the published data derived from prospective clinical trials from Phase II onwards. PubMed was searched using combinations of the keywords ‘Langerhans cell histiocytosis’, ‘histiocytosis X’, ‘pediatric’, ‘children’, ‘treatment’, and ‘therapy’. Only full-length papers published in English and German were included in the review.
Expert opinion: Mortality in multisystem LCH is restricted to patients with involvement of risk organs (hematopoiesis, liver and spleen) at diagnosis, and is particularly high (up to 60–70%) if systemic therapy fails to control the disease. For the rest of the cohort, mortality is almost negligible, and the main challenges are disease relapses and related permanent consequences (encountered in up to 50% of the survivors). While systemic therapy has clearly improved survival of patients with most severe disease form, its role in providing sustained disease control and preventing permanent consequences in patients with ‘low risk’ disease is less clear. 相似文献
Potential roles of inherited and environmental risk factors in pathogenesis of Langerhans cell histiocytosis (LCH), a myeloid neoplastic disorder, are undefined. We therefore evaluated the role of parental and perinatal factors on the risk of this childhood cancer.
Methods
Information on LCH cases (n = 162) for the period 1995–2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on year of birth at a ratio of 10:1 for the same period. Variables evaluated included parental age, race/ethnicity, size for gestational age, and birth order. Logistic regression was used to generate an adjusted odds ratio (aOR) and 95% confidence interval (CI) testing the association between each factor and LCH.
Results
Few perinatal or parental factors were associated with LCH risk, with the exception of race/ethnicity. Mothers of Hispanic ethnicity were more likely to have children who developed LCH compared to non-Hispanic whites (aOR: 1.51; 95% CI: 1.02–2.25). This risk increased when both parents were Hispanic (aOR: 1.80; 95% CI: 1.13–2.87). Non-Hispanic black mothers were suggested as less likely to give birth to offspring who developed LCH compared to non-Hispanic whites (aOR: 0.50; 95% CI: 0.24–1.02).
Conclusions
LCH is characterized by somatic mutations in MAPK pathway genes in myeloid precursors. Increased risk for LCH in children of Hispanic parents suggests potential impact of inherited factors on LCH pathogenesis. 相似文献