Dietary and non-dietary factors associated with iron status in a cohort of Danish adults followed for six years. Tissue damage in haemochromatosis: An analysis of the roles of iron and alcoholism. Effect of iron supplementation on the iron status of pregnant women: Consequences for newborns. Estimates of available iron in diets of individuals 1 year old and older in the Nationwide Food Consumption Survey. Lack of adverse side effects of oral ferrous sulfate therapy in 1-year-old infants. Heterozygosity for a hereditary hemochromatosis gene is associated with cardiovascular death in women. Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 months: Delayed maturation of auditory brainstem responses. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. The effect of food processing on phytate hydrolysis and availability of iron and zinc. Anemia vs iron deficiency: Increased risk of preterm delivery in a prospective study. Epidemiologic evidence of an association between body iron stores and risk of cancer. A vegetarian diet rich in soybean products compromises iron status in young students. Ascorbic acid prevents the dosedependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption. Physiological anemia of early development in the rat: Characterization of the iron-responsive component. Fe2+ uptake by mouse intestinal musosa in vivo and by isolated intestinal brush-border membrane vesicles. Competitive interaction of iron and zinc in the diet: Consequences for human nutrition. Studies on the bioavailability of zinc in humans: Effects of heme and nonheme iron on the absorption of zinc. Studies on the bioavailability of zinc in humans: Mechanism of the intestinal interaction of nonheme iron and zinc. Moderate elevation of body iron level and increased risk of cancer occurrence and death. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia. Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965. Effect of iron supplementation on serum ferritin levels during and after pregnancy. The effect of cysteinecontaining peptides released during meat digestion on iron absorption in humans. Tuntawiroon M, Sritongkul N, Brune M, Rossander-Hulten L, Pleehachinda R, Suwanik R, Hallberg L. Dose-dependent inhibitory effect of phenolic compounds in foods on nonheme-iron absorption in men. Body iron stores are associated with serum insulin and blood glucose concentrations. Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation: A prospective cohort study in men in eastern Finland. Plasma ferritin concentration: Their clinical significance and relevance to patient care. Body iron stores and mortality due to cancer and ischaemic heart disease: A 17-year follow-up study of elderly men and women. Calcium intake is weakly but consistently negatively associated with iron status in girls and women in six European countries. Effect of variations in fat and linoleic acid intake on the calcium, magnesium and iron balance of young men. The inhibitory effect of dietary calcium on iron bioavailability: A cause for concern?
Clinical accuracy also is much higher if patients are diagnosed in specialty clinics of tertiary care facilities (by movement disorder specialists). Stratifying on age, the prevalence estimates clearly increase with increasing age: 41 per 100,000 in individuals 40 to 49 years; 107 per 100,000 in individuals 50 to 59 years; 428 per 100,000 in individuals 60 to 69 years; 1,087 per 100,000 in individuals 70 to 79 years; and 1,903 per 100,000 in individuals over age 80 years (Pringsheim et al. Mutations associated with an autosomal recessive inheritance pattern have also been described; however, these disease genes are found in only a handful of familial cases worldwide. Two studies reviewed in Update 2008 examined the association specifically with chlorophenoxy acid and ester herbicides and found increased odds ratios (Brighina et al. In the Korean Veterans Health Study, 180,639 Korean veterans were followed for vital status and cause of death (Yi et al. Substantial research has gone into understanding the molecular mechanisms responsible for the toxicity, especially in connection with paraquat and rotenone (Blandini and Armentero, 2012; Di Monte et al. The injection of 2,4-D directly into the rat brain results in toxicity in the basal ganglia (Bortolozzi et al. In addition, a study of mice and 2,4D yielded no evidence of neurochemical damage to the dopaminergic system (Thiffault et al. Many other possi ble etiologic factors have been investigated (Breland and Currier, 1967; Gallagher and Sander, 1987; Hanisch et al. The association was even stronger after controlling for smoking and education in a multivariate model but quite imprecise. For 31 of 32 war-specific exposures, participants were asked whether they had ever been exposed, days exposed (not exposed, 5, 630, > 30), and whether they felt ill after exposure (not exposed, no, yes). A total of 616 medical recordconfirmed cases were followed from enrollment in the registry (20052010) until death or July 25, 2013, whichever came first. Estimates were adjusted for povertyincome ratio, education, race, age, sex, and smoking status. The women were evaluated for their physical function in 1996 (n = 154) and with neurocognitive tests in 2008 (n = 459). The manifestations of neuropathy can include a combination of sensory changes, weakness, and autonomic instability. Clinically, various forms of peripheral neuropathy can be characterized by the distribution of nerve abnormalities and their patterns of progression. Peripheral neuropathy resulting from toxic exposure usually affects nerve fibers in a symmetric pattern, beginning distally in the longest fibers (in the toes) and mov ing proximally (toward the spine). Sensory deficits begin at the toes, progress above the ankles, and only later affect the hands. Physiologically, various forms of peripheral neuropathy can be character ized by the results of electrodiagnostic testing to indicate which neural structures are affected. The clinical manifestations of most symmetric axonal neuropa thies are similar except for variations in the rates of progression and in whether pain is prominent. No specific signature distinguishes a toxicant-related neuropathy from one induced by other causes. Peripheral neuropathy also occurs commonly as a complication of diabetes; its reported prevalence in people who have chronic diabetes is up to 50%. Such outcomes would include earlyonset peripheral neuropathy and porphyria cutanea tarda. In a primary analysis, the investigators had in cluded diabetes as a potential confounder in the statistical model. In a secondary analysis, the subjects who had conditions that were known to be associated with neuropathy were excluded, and the subjects who had diabetes were enumerated. In both analyses, there were strong and significant associations between serum di oxin concentrations and possible and probable neuropathy, and significant trends were found with increasing concentrations of dioxin. No evidence of an increased incidence of neuropathy or of a doseresponse relationship was found for either group when stratified by high versus low hemoglobin A1C level that suggested a concentrationdependent risk of neuropathy. However, this study was limited by the small sample size and a lack of information regarding the duration of diabetes. The normal activity of those target processes is important for maintaining synaptic connections between nerve cells and for supporting the mechanisms involved in axon regeneration during recovery from peripheral neuropathy.
Ureteroscopic visualization of the tumor is desirable, and tissue biopsy through the ureteroscope may be performed if feasible. Staging of tumors of the renal pelvis and ureter is not influenced by the presence of any concomitant bladder tumors that may be identified, although it may not be possible to identify the true source of the primary tumor in the presence of metastases if both upper- and lower-tract tumors are present. In that situation, the tumor of highest grade and/or stage is most likely to have contributed to the nodal or metastatic spread. Pathologic staging depends on histologic determination of the extent of invasion by the primary tumor. Treatment frequently requires resection of the entire kidney, ureter, and a cuff of bladder surrounding the ureteral orifice. T3 (for renal pelvis only, top of diagram): tumor invades beyond muscularis into peripelvic fat or the renal parenchyma. T3 (for ureter only, bottom of diagram): tumor invades beyond muscularis into periureteric fat. Renal Pelvis and Ureter 493 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. Data taken from the National Cancer Data Base (Commission on Cancer of the American College of Surgeons and the American Cancer Society) for the years 2000 to 2002. Transitional cell carcinoma of the renal pelvis and ureter: prognostic relevance of nuclear deoxyribonucleic acid ploidy studied by slide cytometry: an 8-year survival time study. Upper tract recurrences following radical cystectomy: an analysis of prognostic factors, recurrence pattern and stage at presentation. Transitional cell carcinoma of the upper urinary tract: evaluation of prognostic factors by histopathology and flow cytometric analysis. Ureteropyeloscopic diagnosis and treatment of upper urinary tract urothelial malignancies. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Risk factors for the development of bladder cancer after upper tract urothelial cancer. Upper urinary tract tumors developing after treatment of superficial bladder cancer: 7-year follow-up of 591 consecutive patients. Nucleolar organizer regions: a new prognostic factor for upper tract urothelial cancer. Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups. Limitations of computed tomography in the preoperative staging of upper tract urothelial carcinoma. Predisposing factors include smoking, exposure to chemicals such as phenacetin and dyes, and schistosomiasis. It has also been suggested that the incidence of this disease correlates inversely with fluid intake. Bladder cancer can present as a low or high-grade papillary lesion, as a high-grade in situ lesion that can occupy large areas of the mucosal surface, or as an infiltrative cancer that invades the bladder wall and progresses into the perivesical tissues, regional lymph nodes and can thereafter metastasize. Noninvasive papillary lesions have a relatively low risk for progression to invasive disease; however, this risk is dependent on the grade of the lesion. High-grade papillary and in situ lesions may be associated with a malignant course, including invasion of the bladder wall and the subsequent development of regional and/or distant metastases. The most common histologic variant is urothelial (transitional cell) carcinoma, although this may exhibit features of glandular or squamous differentiation. In less than 10% of cases, pure adenocarcinoma or squamous carcinoma of the bladder may occur, and less frequently, sarcoma, lymphoma, small cell anaplastic carcinoma, pheochromocytoma, or choriocarcinoma. Distant spread is most commonly to retroperitoneal lymph nodes, lung, bone, and liver. Primary tumor assessment includes bimanual examination under anesthesia before and after endoscopic surgery (biopsy or transurethral resection) and histologic verification of the presence or absence of tumor when indicated. Bimanual examination following endoscopic surgery is an indicator of clinical stage. The finding of bladder wall thickening, a mobile mass, or a fixed mass suggests the presence of T3 and/or T4 disease, respectively. Appropriate imaging techniques for extravesical extension of the primary tumor and lymph node evaluation should be incorporated into clinical staging.
One possible explanation for this discrepancy is that the currently accepted dose factor massively underestimates the effect of strontium. The mortality rate even increased between the end of the first week and the end of the first year of life by 26 percent. Jens Scheer in Bremen, had looked into infant mortality within the first seven days of life. In the southern areas of the Federal Republic, particularly in Bavaria and Baden-Wьrttemberg, where the highest amounts of radiation had been detected, considerably more deaths were registered amongst newborns than in those (northern) areas, where there had been less radioactive fallout. The extrapolation had, however, omitted to take sufficient account of previous changes in infant mortality brought about by fallout from atmospheric nuclear weapons tests. A paper, published in 1997 by Alfred Kцrblein61 and Helmut Kьchenhoff, came to the conclusion that there was a significant increase in perinatal mortality in the whole of Germany following Chernobyl. Analysis of monthly death rates showed an increase in perinatal mortality seven months after the exposure of pregnant women to radioactive caesium was calculated to have been at its highest. Alfred Kцrblein (Munich Institute for the Environment) had already drawn the wrath of the establishment upon himself by disrespectfully and carefully reading the renowned studies from the Cancer Registry in Mainz (Director: Prof. Jцrg Michaelis) on cancer incidence in the vicinity of German nuclear power plants and coming to very different results than Michaelis and the Minister for the Environment at the time, Angela Merkel. The resoluteness of Kцrblein and the coherence of his arguments have played a great part in prompting a new analysis of cancer incidence in the vicinity of German nuclear power plants. On the basis of stillbirth statistics from other European countries, Scherb and Weigelt even consider it possible that this figure underestimates the effect (see below). Since Chernobyl there has also been an increase in perinatal mortality in southern Germany. This showed that, in the more heavily contaminated southern part of Germany, there were two increases in the incidence rate of early neonatal mortality, once in early summer 1986 and once in winter 1986/87. In southern Bavaria, more badly hit by Chernobyl fallout than northern Bavaria, the birth rate in February 1987 showed an 11 percent significant (p=0. According to this model, it follows that, for the years 1986 to 1992, there were about 3,200 stillbirths (r1,300=2V) more than had been expected. This is an average of about 460 additional stillbirths per annum in this period of time and group of countries. A Finnish study showed a distinctive increase in premature births of children who had been conceived in the first four months after Chernobyl in the areas with the highest dose rates and ground contamination with caesium-137. But Scherb and Weigelt still believe, albeit for different reasons, that the stillbirth statistics published in February 2001 by Auvinen and colleagues provide them with consistent and usable data for the years 1977 to 1992. Backed by this data, Scherb and Weigelt analysed the trend in stillbirths in Finland from 1977 to 1994. The effect was approximately twice as strong as in Sweden and about two thirds of the effect in Hungary. Alfred Kцrblein calculated that for the period 1987 to 1992 an additional 1,209 (95 % confidence interval: 875 to 1,556)75 infants had died. Brьske-Hohlfeld: European stillbirth proportions before and after the Chernobyl accident; International Journal of Epidemiology 1999; 28:932-940. Weigelt: Spatial-temporal change-point regression models for European perinatal data; European Radiation Research 2000, 30th Annual Meeting of the European Society for Radiation Biology, Warzawa, August 27-31, 2000. Brьske-Hohlfeld: Regression Analysis of Time Trends in Perinatal Mortality in Germany 1980-1993; Environmental Health Perspectives Vol. Weigelt: Spatial-temporal logistic regression of the cesium contamination and the time trend in annual stillbirth proportions on a district level in Bavaria, 1980 to 1993; in: Friedl, H. There are, however, a number of unsettling indications: x x in Poland there were considerably less live births in 1986 compared to previous years. He came to the conclusion that in May 1986, 23 percent of early pregnancies in Greece were terminated. No one wants to talk about this and we have no knowledge of accurate data on these abortions. For us, these appallingly high numbers of aborted embryos count as victims of Chernobyl. Ever since discovering the mutagenicity of ionising radiation in animal experiments, damaging radiation genetic effects in humans have also been repeatedly considered and examined.
Neither intraepithelial nor intramucosal carcinomas of the large intestine are associated with risk for metastasis. Carcinoma in a polyp is classified according to the pT definitions adopted for colorectal carcinomas. For instance, carcinoma that is limited to the lamina propria is classified as pTis, whereas tumor that has invaded through the muscularis mucosae and entered the submucosa of the polyp head or stalk is classified as pT1. Tumor that has penetrated the visceral peritoneum as a result of direct extension through the wall and subserosa of the colon or proximal rectum is assigned to the pT4 category, as is tumor that directly invades or is histologically adherent to other organs or structures, whether or not it penetrates a serosal surface. For both colon and rectum, expanded data sets have shown different outcomes for tumors within the pT4 category based on extent of disease (see section "Prognostic Factors"; Tables 14. Therefore, T4 lesions have been subdivided into pT4a (tumor penetrates to the surface of the visceral peritoneum) and pT4b (tumor directly invades or is adherent to other organs or structures). Tumors that clinically appear adherent to another organ or structure should be resected en bloc as standard of practice. However, if on microscopic review the adhesion is secondary to inflammation and the carcinoma does not actually involve the adjacent structure or organ, then the lesion is classified as either pT3 or pT4a, as appropriate. Regional lymph nodes are classified as N1 or N2 according to the number involved by metastatic tumor. Involvement of 13 nodes by metastasis is pN1; involvement of 4 or more nodes by tumor metastasis is pN2. The number of nodes involved with metastasis influences outcome within both the N1 and the N2 groups (see section "Prognostic Features"; Tables 14. Accordingly pN1 has been subdivided into pN1a (metastasis in 1 regional lymph node) and pN1b (metastasis in 23 regional lymph nodes), and pN2 has been subdivided into pN2a (metastasis in 46 regional lymph nodes) and pN2b (metastasis in 7 or more regional lymph nodes). Such tumor deposits may represent discontinuous spread, venous invasion with extravascular spread (V1/2), or a totally replaced lymph node (N1/2). The absence of metastasis in any specific site or sites examined pathologically is not pM0. The designation of M0 should never be assigned by the pathologist, because M0 is a global designation referring to the absence of detectable metastasis anywhere in the body. Therefore, "pM0" would connote pathological documentation of the absence of distance metastasis throughout the body, a determination that could only be made at autopsy (and would be annotated as aM0). Although the data are not definitive, complete eradication of the tumor, as detected by pathologic examination of the resected specimen, may be associated with a better prognosis and, conversely, failure of the tumor to respond to neoadjuvant treatment appears to be an adverse prognostic factor. Therefore, specimens from patients receiving neoadjuvant chemoradiation should be thoroughly examined at the primary tumor site, in regional nodes and for peritumoral satellite nodules or deposits in the remainder of the specimen. Those patients with minimal or no residual disease after therapy may have a better prognosis than gross residual disease. Whereas a number of different grading systems for tumor regression have been advocated, a four-point tumor regression grade will be used to assess response that is similar to that of Ryan et al. Tumor regression grade Description No viable cancer cells Single cells or small groups of cancer cells Residual cancer outgrown by fibrosis Minimal or no tumor kill; extensive residual cancer Tumor regression grade 0 (Complete response) 1 (Moderate response) 2 (Minimal response) 3 (Poor response) is the surgically dissected nonperitonealized surface of the specimen. It corresponds to any aspect of the colorectum that is not covered by a serosal layer of mesothelial cells and must be dissected from the retroperitoneum or subperitoneum in order to remove the viscus. In contradistinction, serosalized surfaces of the colorectum are not dissected; they are naturally occurring anatomic structures and are not pathologic surgical margins. For proximal rectal or retroperitoneal colon cancers (ascending, descending, possibly cecum), surgically dissected margins will include those that lie in a retroperitoneal or subperitoneal location as described above (Figure 14. For segments of the colon that are entirely covered by a visceral peritoneum (transverse, sigmoid, possibly cecum), the only specimen margin that is surgically dissected is the mesenteric margin, unless the cancer is adherent to or invading an adjacent organ or structure. For rectal cancer, the quality of the surgical technique is likely a key factor in the success of surgical outcomes relative to local recurrence and possibly long-term survival. With this approach, all mesorectal soft tissues encasing the rectum, which includes the mesentery and all regional nodes, are removed intact. Rectal resection performed by less precise techniques may be associated with incomplete excision of the mesorectum. Job Name: - /381449t might otherwise be considered negative for metastasis by standard hematoxylin and eosin (H&E). The boundary between the rectum and anal canal most often has been equated with the dentate line, which is identified pathologically. However, with advances in sphincter-preservation surgery, defining the boundary between the rectum and the anus as the anorectal ring, which corresponds to the proximal border of the puborectalis muscle palpable on digital rectal examination, is more appropriate.
There is a periductal neural component, which is frequently involved by cholangiocarcinomas. Mass forming intrahepatic cholangiocarcinoma shows a radial growth pattern invading into the adjacent liver parenchyma with well-demarcated gross margins. Compared with primary hepatocellular carcinoma, regional lymph node metastases are more commonly associated with intrahepatic cholangiocarcinoma. The lymph node drainage patterns from the intrahepatic bile ducts demonstrate laterality. Tumors in the left lateral bisegment (segment 23) of the liver may preferentially drain to lymph nodes along the lesser curvature of the stomach and subsequently to the celiac nodal basin. In contrast, intrahepatic cholangiocarcinomas of the right liver (segment 58) may primarily drain to hilar lymph nodes and subsequently to caval and periaortic lymph nodes. For right liver (segment 58) intrahepatic cholangiocarcinomas, the regional lymph nodes include the hilar (common bile duct, hepatic artery, portal vein, and cystic duct) periduodenal and peripancreatic lymph nodes. For left liver (segment 24) intrahepatic cholangiocarcinomas, regional lymph nodes include hilar, and gastrohepatic lymph nodes. For intrahepatic cholangiocarcinomas, disease spread to the celiac and/or periaortic and caval lymph nodes are considered distant metastases (M1). Intrahepatic cholangiocarcinomas usually metastasize to other intrahepatic locations (classified in the T category as multiple tumors) and to the peritoneum, and subsequently, to the lungs and pleura (classified in the M category as distant metastasis). The T classification of invasive intrahepatic cholangiocarcinoma is determined by the number of tumors present (solitary vs. Liver diagram differentiating intrahepatic bile ducts (open lumens) from extrahepatic bile ducts (across lumens) and mass forming tumor growth pattern (A) from periductal infiltrating growth pattern (B). The definition of the term "multiple tumors" includes satellitosis, multifocal tumors, and intrahepatic metastasis. Vascular invasion includes both major vessel invasion [defined as invasion of the branches of the main portal vein (right or left portal vein) or as invasion of one or more of the three hepatic veins (right, middle, or left)] and microscopic invasion of smaller intraparenchymal vascular structures identified on histopathologic examination. Direct invasion of adjacent organs, including colon, duodenum, stomach, common bile duct, portal lymph nodes, abdominal wall, and diaphragm is considered T3 disease, not as distant metastasis. Extraregional nodal involvement and other distant metastatic sites are classified as M1 disease. For patients treated with surgical resection, the main predictors of poor outcome include regional lymph node involvement and incomplete resection. Other important prognostic factors include the finding of satellitosis or multiple intrahepatic tumors, vascular invasion, and periductal infiltrating tumor growth pattern. Validation of T1, T2, T3, and N1 categories is based on multivariate analyses of outcome and survival data of single institution and multi-institution studies of patients with intrahepatic cholangiocarcinoma. Clinical staging depends on imaging procedures designed to demonstrate the tumor growth pattern of intrahepatic cholangiocarcinoma, the number of intrahepatic masses, and the presence or absence of vascular invasion. Surgical exploration is carried out if imaging shows that a complete resection is possible and that hepatic reserve is sufficient for a safe resection. Radiographic assessment for the presence or absence of distant metastases prior to surgical exploration is warranted. Complete pathologic staging consists of evaluation of the primary tumor, including tumor number, involvement of local regional lymph nodes, and the presence or absence of vascular invasion. Solitary tumors with no vascular invasion and no lymph node involvement or metastasis are classified as T1. Tumors that perforate the visceral peritoneum, with or without invasion of extrahepatic structures are classified as T3. The pathologic definition of the periductal infiltrating type is the finding of a diffuse longitudinal growth pattern along the intrahepatic bile ducts on both gross and microscopic examination. T4 includes the diffuse periductal infiltrating tumors and the mixed mass forming and periductal infiltrating tumors. Stage I tumors are defined as T1 without regional lymph node metastasis (pN0, cN0). T1: Solitary tumor without vascular invasion; T2: Solitary tumor with vascular invasion or multiple tumors; T3: Tumor perforating the visceral peritoneum or involving the local extra hepatic structures by direct invasion. Intrahepatic Bile Ducts 203 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. These include the following: Intrahepatic cholangiocarcinoma Mass forming tumor growth pattern Periductal infiltrating tumor growth pattern Mixed mass forming and periductal infiltrating growth pattern Mixed Hepatocellular this staging classification does not apply to primary sarcomas of the liver stroma or to liver metastases from other sites.
Diseases
Inhibition of 7, 12-dimethylbenzanthracene-induced rat mammary tumor growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Mutation ResearchGenetic Toxicology and Environmental Mutagenesis 521(12):165178. West Virginia Department of Health Vietnam-era veterans mortality study, preliminary report. Chemical predictors of wheeze among farmer pesticide applicators in the Agricultural Health Study. Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study. Lifetime pesticide use and telomere shortening among male pesticide applicators in the Agricultural Health Study. Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands. Relation of polymorphism of arsenic metabolism genes to arsenic methylation capacity and developmental delay in preschool children in Taiwan. Effects of 2,3,7,8tetrachlorodibenzo-p-dioxin on adipogenic differentiation and insulin-induced glucose uptake in 3T3-L1 cells. Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix metabolism and age-related macular degeneration-like pathology. Association between dioxin and diabetes mellitus in an endemic area of exposure in Taiwan: A population-based study. Association between blood dioxin level and chronic kidney disease in an endemic area of exposure. Effect of 2,3,7, 8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P450 1A1, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary. Plasma folate level, urinary arsenic methylation profiles, and urothelial carcinoma susceptibility. Mitochondrial-targeted aryl hydrocarbon receptor and the impact of 2,3,7,8-tetrachlorodibenzop-dioxin on cellular respiration and the mitochondrial proteome. Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice. Reduced expression of progesterone receptor-B in the endometrium of women with endometriosis and in cocultures of endometrial cells exposed to 2,3,7,8-tetrachlorodibenzop-dioxin. Characterizing exposure of veterans to Agent Orange and other herbicides used in Vietnam: Scientific considerations regarding a request for proposals for research. Veterans and Agent Orange: Herbicide/dioxin exposure and acute myelogenous leukemia in the children of Vietnam veterans. Veterans and Agent Orange: Length of presumptive period for association between exposure and respiratory cancer. Gulf War and health, volume 8: Update of health effects of serving in the Gulf War. Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes. Perinatal exposure to dioxins and dioxin-like compounds and infant growth and body mass index at seven years: A pooled analysis of three European birth cohorts. Cancer incidence in children and young adults did not increase relative to parental exposure to atomic bombs. Cancer incidence among pulp and paper workers exposed to organic chlorinated compounds formed during chlorine pulp bleaching. Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls. Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark. Aryl hydrocarbon receptor signaling modifies Toll-like receptor-regulated responses in human dendritic cells. The effect of a vegetarian versus conventional hypocaloric diet on serum concentrations of persistent organic pollutants in patients with type 2 diabetes. Dibenzodioxin and dibenzofuran congener levels in four groups of Vietnam veterans who did not handle Agent Orange.
Recommendations for intervention Healthy dietary intake should be encouraged, including sufficient calcium and vitamin D from foods or supplements. The underlying causes of under- or overweight should be addressed, including treatment of endocrine disorders. Related co-morbidities due to obesity should be prevented and treated, as discussed later in this chapter in the sections on abnormal glucose metabolism, lipid abnormalities, and metabolic syndrome. Of 40 patients, 20% had impaired glucose tolerance, 5% had diabetes, and 72% had higher than normal levels of insulin. Of 24 patients, 4% had diabetes, 17% had insulin resistance, and 29% had dyslipidemia (unhealthy levels of cholesterol and triglycerides). Of 17 females, more than 1 in 10 (12%) had delayed menarche, starting their periods later in life than their healthy peers. Of 24 patients, 17% had dyslipidemia (unhealthy cholesterol and triglyceride levels). Of 17 patients, 6% had impaired fasting blood sugar, 24% had low first-phase insulin release, 17% had increased first-phase insulin release and high fasting insulin, and 8% had impaired glucose tolerance. Chapter 7: Endocrine Disorders * Different studies used different biochemical criteria. Interestingly, insulin levels were low 10 to 45 minutes after an oral glucose test, suggesting slow initial insulin secretion, but became elevated 60 to 120 minutes after the test (4, 6). Good to Know the foods and drinks you consume are broken down into sugars-such as glucose-that enter your blood and fuel your body. Androgen treatment can significantly elevate both blood sugar and insulin levels (1). Chronic steroid therapy also predisposes patients to insulin resistance and high blood sugar, known as hyperglycemia (12-14). Patients can be screened for glucose tolerance by measuring blood sugar and insulin concentrations after fasting for 8 hours, and by measuring post-prandial blood sugar and insulin concentrations 2 hours after a meal. The danger of measuring only serum glucose values, or relying solely on fasting values, is that some patients may be overlooked-particularly those with impaired glucose tolerance whose blood sugar and insulin levels are normal after fasting but elevated 2 hours after a meal. In patients who have suspected endocrine abnormalities and possess risk factors such as overweight/obesity or hyperlipidemia, a more detailed evaluation is needed in consultation with an endocrinologist. A registered dietician can provide valuable guidance, particularly by helping the patient distinguish unhealthy "simple" carbohydrates (such as candy) from healthier "complex" carbohydrates (such as whole grain breads). Insulin or oral medications should be tailored to the cause of diabetes, just as in the general population, with the goal of improving blood sugar control without causing low blood sugar, or hypoglycemia. Some practitioners recommend treatment with short-acting insulin at mealtime, to help the body process carbohydrates, if post-prandial blood sugar is consistently higher than 180 mg/dL. A combination of long-acting and short-acting insulin may be required for adequate blood sugar control. The duration of therapy may vary depending on the duration, dose, and type of transplant medications used-particularly for corticosteroids, tacrolimus, sirolimus, or similar medications. Of these patients, about half (55%) had unhealthy levels of cholesterol and triglycerides, a condition known as dyslipidemia. An abnormal lipid profile was observed in nearly half (40%) of patients with hyperglycemia or insulin resistance. Half of the 24 children tested had at least one metabolic abnormality, including 4 children with insulin resistance, 1 with diabetes, and 7 with dyslipidemia (2). This combination of test results is consistent with mild hypothyroidism, or low thyroid activity. Thyroid evaluation Thyroid function should be evaluated by obtaining an early morning. Recommendations for treating hypothyroidism Hypothyroidism should be treated promptly, particularly in children younger than 3 years of age. In central hypothyroidism, therapy should aim to raise free T4 levels to just above the middle of the normal range. Children grew significantly better on thyroid hormone than on placebo, and parents felt that their children had better energy levels during the thyroid hormone phase (5). Therapy should be discontinued immediately if routine hematological examination reveals clonal hematopoietic stem cell proliferation. Levels are lowest when you fall asleep, highest just after you wake, and gradually decline until the following night. Furthermore, 5 of 6 male patients had cryptorchidism, in which one or both testicles fail to descend, and 4 of 6 male 161 Fanconi Anemia: Guidelines for Diagnosis and Management patients had microphallus (an abnormally small penis).
These include Hepatocellular carcinoma Fibrolamellar variant of hepatocellular carcinoma 194 American Joint Committee on Cancer · 2010 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. Job Name: - /381449t Hepatocellular carcinoma is by far the more common of the two types of primary carcinoma of the liver. The staging classification does not apply to primary sarcomas or metastatic tumors, and no longer applies to tumors of the bile ducts (cholangiocarcinomas including mixed hepatocholangiocarcinoma), which are now considered in a separate, new staging system (see Chap. The histologic type and subtype should be recorded, since they may provide prognostic information. Underlying liver disease but not tumor factors predict long-term survival after hepatic resection of hepatocellular carcinoma. Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumor. Pathological aspects of hepatocellular carcinoma: a critical review of prognostic factors. Prognostic histologic indicators of curatively resected hepatocellular carcinomas: a multi-institutional analysis of 425 patients with definition of a histologic prognostic index. Prognostic value and clinical relevance of the 6th edition 2002 American Joint Committee on Cancer staging system in patients with resectable hepatocellular carcinoma. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Tumor size predicts vascular invasion and histologic grade: implications for expanding the criteria for hepatic transplantation. Hepatectomy for hepatocellular carcinoma with major portal or hepatic vein invasion: results of a multicenter study. Significance of resection margin in hepatectomy for hepatocellular carcinoma: a critical reappraisal. Prognostic evaluation of the new American Joint Committee on Cancer/ International Union Against Cancer staging system for hepatocellular carcinoma: analysis of 112 cirrhotic patients resected for hepatocellular carcinoma. Clinical significance of microscopic tumor venous invasion in patients with resectable hepatocellular carcinoma. Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s). Factors affecting long-term outcome after hepatic resection for hepatocellular carcinoma. Outcomes of liver transplantation in 490 patients with hepatocellular carcinoma: validation of a uniform staging after surgical treatment. Hepatocellular carcinoma, tumors of the perihilar bile duct, and gallbladder carcinomas are classified separately. Tumors of intrahepatic bile duct origin represent 1520% of all primary liver malignancies. The tumors of the bile ducts can be anatomically subdivided into three categories including intrahepatic, perihilar, and distal cholangiocarcinoma. The proportion of cholangiocarcinoma that is accounted for by intrahepatic tumors is approximately 20%. Clinically, these intrahepatic tumors can be difficult to differentiate from metastatic adenocarcinomas from other primary sites. The etiologic factors that predispose to the development of intrahepatic cholangiocarcinoma include primary sclerosing cholangitis, hepatobiliary parasitosis, intrahepatic lithiasis, and chronic viral hepatitis. The incidence of intrahepatic cholangiocarcinoma is age-dependent, with a progressive increase in cases starting in the sixth decade of life and peaking in the ninth decade. Although less common than either hepatocellular carcinoma or hilar bile duct Intrahepatic Bile Ducts 201 In order to view this proof accurately, the Overprint Preview Option must be set to Always in Acrobat Professional or Adobe Reader. Job Name: - /381449t cancer, the incidence of intrahepatic cholangiocarcinoma is increasing.
Indeed, a thyroid bud is formed in Tbx1-/- mice but does not develop properly beyond this stage, leading to a hypoplastic single-lobed gland located close to the midline (Fagman et al. Although the molecular mechanism underlying this phenotype is not clear, studies suggest that vasculature might be involved. Accordingly, thyroid bilobation occurs initially along the third pharyngeal arch arteries (Fagman et al. However, careful imaging shows that thyroid budding is delayed in Tbx1 mutants such that contact with the aortic sac never takes place, possibly owing to diminished numbers of Tbx1+ mesenchymal cells that might otherwise promote detachment and migration of the primordium (Fagman et al. Thyroid hypoplasia in Tbx1-deficient mice is therefore likely to be due to a primary loss of vessel contact anatomically, which in turn might impact access to growth signals that promote bilateral expansion of the primordium along embryonic vessels at a later stage. Thyroid bilobation defects have also been reported for mice deficient for Frs2a, which encodes a docking protein in the Fgf receptor signaling pathway that also diminishes growth of the mesenchyme surrounding the thyroid primordium (Kameda et al. It is likely that the thyroid phenotype in Frs2a mutants depends, at least in part, on impaired regulation of thyroid development by Tbx1-Fgf8. Blood vessel-mediated control of thyroid morphogenesis the importance of embryonic large vessels for thyroid development was first demonstrated in Shh-/- mice in which the thyroid in late embryos is hypoplastic, resembling the clinical malformation hemiagenesis (Fagman et al. Subsequent tomographic analyses revealed abnormal pharyngeal arch artery development leading to asymmetrically positioned carotid arteries and ipsilateral deviation of the thyroid rudiment in Shh null mutants (Alt et al. Notably, segments of the carotids, which are eventually located just lateral to the thyroid lobes. Together, this suggests that symmetric arch arteries define thyroid positioning in an intermediate stage of thyroid development and that this process is Shh dependent (Alt et al. Fgf8 promotes mouse thyroid morphogenesis in at least three distinct stages of development: recruitment of Nkx2-1+ progenitors to the thyroid placode (top), detachment and migration of the thyroid bud (middle), and transverse elongation of the thyroid primordium after its descent (bottom). These effects are governed by Tbx1 transcriptional activity, which might be triggered by Shh derived from the pharyngeal endoderm. Thyroid morphogenesis is also linked to blood vessel development (as highlighted in the bottom panel). Netrin might be involved in the effector mechanism that links these developmental processes. This is similar to the situation observed during the development of the pancreas, in which repression of Shh specifically in the dorsal anlage is necessary for fate determination of pancreatic progenitors (Hebrok et al. By contrast, the endoderm territory destined to a thyroid fate does not increase if Shh is globally deleted (Parlato et al. It is also worth noting that Foxe1 expression in the pharyngeal endoderm adjacent to the thyroid anlage requires Shh, whereas thyroidal Foxe1 does not (Parlato et al. This indicates that Shh has no direct role in Foxe1-mediated migration of the thyroid primordium. Surprisingly, lineage tracing of Shh+ progeny indicates that no thyroid progenitors express Shh (Westerlund et al. It is therefore likely that Shh influences thyroid development indirectly by shaping the 2132 pharyngeal apparatus and its vasculature. In zebrafish, live imaging employing the mCherry red fluorescent reporter has elegantly illustrated the coordinated development of the thyroid and the vasculature emerging from the apical pole of the heart (Opitz et al. In this study, mCherry was targeted to the thyroid through the thyroglobulin reporter and thus the cells detected were about or had already started to form follicles. This suggests that, in zebrafish, it is the differentiated thyroid cells rather than progenitors residing in the pharyngeal endoderm that interact with endothelial cells. In the mouse, by contrast, thyroid-vessel interactions occur in two distinct phases: first, precursor cells associate with the aortic sac and pharyngeal arch arteries as the undifferentiated primordium buds, migrates and lobulates (Fagman et al. A trivial explanation, supported by the asymmetric, ipsilateral colocation of the thyroid and carotid arteries in Shh-deficient mice (Fagman et al. Direct evidence of guidance by embryonic vessels has indeed been provided for the zebrafish thyroid by live imaging (Opitz et al. More recent studies in zebrafish infer an important role for netrin 1 expressed in pharyngeal arch mesenchyme in the conjoined development of thyroid and vasculature (Opitz et al. Netrins are members of the laminin superfamily that possess both chemoattractant and chemorepellent functions in embryonic development (Lai Wing Sun et al.
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