Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Percutaneous endoscopic gastrostomy (PEG), although a standard method for long-time enteral nutrition, still leaves uncertainty about details in indication, technique and complications. Based on own experiences (approximately 1000 PEG's and 170 EPJ's in the last 10 years) these topics are discussed. As new indications the PEG for decompression in chronic intestinal obstruction and the questionable relative contraindications ascites, peritoneal carcinosis and Morbus Crohn are discussed. The common thread-pull through-technique is recommended in a slightly modified variation, according to direct puncture techniques of small intestine: the cannulas inserted in the intestine are fixed by an endoscopic alligator forceps, thus facilitating precise puncture and raising safety for the patient due to avoidance of dislocation. As complications local infections, implantation metastases and the buried bumper syndrome have to be mentioned and avoided. Alternative methods for PEG and different exchange systems for more comfort for the patients are discussed finally.
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PMID:[Percutaneous endoscopic gastrostomy (PEG)]. 1207 Oct 92

We report 12 cases, complicating Crohn's disease by cancer origin. 8 patients who had chronic anorectal fistula, developed mucinous adenocarcinoma, 4 patients colorectal cancer. Features like early onset of disease, duration of disease for more than 10 years, chronic (pan-)colitis with high inflammatory activity and persistence of chronic fistulas and stenosis seem to trigger malignant transformation. Submucosal growth, overlap-syndromes with Crohn's disease and absence of sufficient clinical control of stenosis or fistula lead to advanced tumour stages at time of diagnosis combined with poor prognosis. Within four years after diagnosis 7 of 10 patients died related to metastatic disease or local recurrence. Absence of sufficient possibilities for clinical control indicates radical and early surgical resection of both endoscopically not surveilable stenosis and longstanding anorectal fistulas.
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PMID:[Cancer and Crohn's disease]. 1229 80

Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment of this disease. We present a review of currently available clinical data to assist the practicing oncologist in the treatment of these patients. Approximately 5,300 new cases and 1,100 deaths from small bowel adenocarcinoma are reported annually in the United States. Increased incidence is seen in patients with Crohn's disease, hereditary nonpolyposis colorectal cancer, and familial adenomatouspolyposis. Factors associated with poor prognosis are age > 75 years, lack of surgical resection, advanced stage, and tumor arising in the duodenum. The median survival of patients with localized, locally advanced, and metastatic disease is 50.1, 22.2, and 8.6 months, respectively. Few data exist on the use of (neo)adjuvant or palliative chemo(radio)therapy in this setting. Fluorouracil (5-FU)based chemotherapy, as a single agent or in combination with others, has been used in most case series. Duodenal adenocarcinoma accounts for more than 50% of all cases of small bowel adenocarcinoma. Resectability is the key prognostic factor, along with age, performance status, tumor location, and presence of distant metastasis. Although the activity of 5-FU-based regimens has been documented, the assessment of clinical benefit is hindered by the lack of prospective, randomized data.
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PMID:Management of small bowel adenocarcinoma. 1243 6

Neutropenia and its subsequent infectious complications represent the most common dose-limiting toxicity of cancer chemotherapy. Febrile neutropenia (FN) occurs with common chemotherapy regimens in 25 to 40% of treatment-naive patients, and its severity depends on the dose intensity of the chemotherapy regimen, the patient's prior history of either radiation therapy or use of cytotoxic treatment, and comorbidities. The occurrence of FN often causes subsequent chemotherapy delays or dose reductions. It may also lengthen hospital stay, increase monitoring, diagnostic and treatment costs, and reduce patient quality of life. A decade after their introduction, colony-stimulating factors (CSFs) such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are now an integral part of the prevention of potentially life-threatening FN; however, only G-CSF has US Food and Drug Administration approval for use in chemotherapy-induced neutropenia. These adjunctive agents accelerate formation of neutrophils from committed progenitors, thereby reducing the duration and severity of neutropenia. Important uses of CSFs in oncology are prevention of FN after chemotherapy, treatment of febrile neutropenic episodes and support following bone marrow transplantation, and collection of CSF-mobilised peripheral blood progenitor cells. G-CSF is used more frequently than GM-CSF for all of these indications because of fewer associated adverse effects. Clinical trials to date have not demonstrated a significant effect on overall survival or disease-free survival, which is most likely to be due to small sample size and lack of power to prove effect. However, they have demonstrated clinical utility in allowing the delivery of planned chemotherapy dose on schedule, an important clinical goal especially in curative tumour settings. The high cost of these agents limits their widespread use. Current American Society of Clinical Oncology guidelines recommend primary prophylaxis, or first cycle use, with CSFs being confined to patients with > or = 40% risk of FN, which may include elderly patients and other high-risk patients. In addition to the risk of FN, primary prophylaxis should also be considered if the patient has risk factors that place them in the Special Circumstances category. These risk factors may include decreased immune function in patients who are already at an increased risk of infection and pre-existing neutropenia due to disease, extensive prior chemotherapy, or previous irradiation to the pelvis or other areas containing large amounts of bone marrow. Future studies are needed to better define the patients most likely to benefit from CSF therapy, both for prophylaxis and as an adjunct to antibiotics for treatment of FN. Other potential uses include combination therapy with stem cell factors and other cytokines to boost progenitor cell development, maintaining dose intensity of salvage therapy in metastatic cancer patients, and application in patients with pneumonia, Crohn's fistulas, diabetic foot infections and a variety of other infectious conditions.
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PMID:Colony-stimulating factors for the management of neutropenia in cancer patients. 1247 91

Sarcoidosis remains a fascinating illness that almost always affects the respiratory tract but often involves many other organs as well. Although many patients seem to have only an intrathoracic illness, with perhaps one other site or organ involved, others can experience a severe multi-organ disease. The inciting stimulus, even if unknown, can elicit an immunologic host response-the non-caseating granuloma-in almost every organ. It is intriguing that this stimulus can be so widespread throughout the body, while the biology of the disease can be so variable. Many series of patients with sarcoidosis have reported the multiple organs involved and the clinical presentation. Our series of 67 patients (40 female, 27 male, mean age 38.7 years +/- 13.2 (SD) at time of diagnosis) generally mirrors the clinical pattern found in five comparison series that span the past 60 years. However, more emphasis is given in this series to associated medical conditions that can complicate the presentation of sarcoidosis, as well as to co-morbid illnesses that must be managed in addition to the patient's sarcoidosis. Although most patients had intrathoracic sarcoidosis diagnosed at initial evaluation (40%), many had other organs or bodily sites involved in addition (or subsequently) as the illness evolved. Confounding the initial patient evaluation were two factors: (1) the presence of an occupational respiratory exposure(s) (n = 25 or 37% of patients); (2) a previously diagnosed malignancy (n = 6 or 9%) that heightened the possibility of a primary malignancy presenting in the chest, or the reactivation of a prior malignancy (breast, thyroid, and lymphoma) that could metastasize to the lung. Symptoms present when a patient's diagnosis was established usually differentiated respiratory and/or abdominal organ involvement. Although respiratory symptoms could be absent (n = 18 or 27%) for many patients with incidental thoracic findings, most had typical ones, including exertional dyspnea. For patients with an abdominal presenting illness (n = 11 or 16%), nonspecific digestive and abdominal symptoms were experienced as well as arthralgias. Almost every patient had at least one important other illness that factored significantly into the management of their sarcoidosis. Older patients had more illnesses, such as cardiovascular illness, diabetes mellitus, neurologic problems, and functional gastrointestinal symptoms. Depression affected all ages and was probably underrecognized; more emphasis on this illness is needed. Obesity was associated with disordered sleep syndromes, but not invariably so, as half the subjects had a good body habitus. Thus, many of the other illnesses experienced by sarcoidosis patients are common problems that middle-aged people develop. However, digestive and gastroenterological symptoms seemed disproportionately frequent in this series. This is a component of multi-organ sarcoidosis that has not received extensive coverage in the literature. Approximately one-third of sarcoidosis patients had one of two very common problems-gastroesophageal reflux or irritable bowel syndrome. But these are common problems, and it is thus necessary to separate these symptoms from those associated with abdominal visceral involvement of sarcoidosis. Although liver and/or splenic involvement with sarcoidosis do not cause organ dysfunction or insufficiency, they can contribute to abdominal symptoms. Finally, it remains of interest whether inflammatory bowel disease-Crohn's disease in particular-is another organ manifestation of sarcoidosis, or is it unrelated?
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PMID:Sarcoidosis: impact of other illnesses on the presentation and management of multi-organ disease. 1248 22

Colorectal carcinoma with microsatellite instability (MSI-H) has a characteristic clinicopathologic profile, typically forming right-sided, lymphocyte-rich tumors that are often mucinous. Mucinous histology in general has been linked to adverse prognosis in some studies, but not in others. MSI-H carcinoma, in contrast, has a better prognosis than microsatellite stable carcinoma in most studies. We assessed the relationship between MSI status, clinicopathologic features and outcome for 248 consecutive patients with resected mucinous carcinoma. All cases were reviewed to confirm mucinous histology. Immunohistochemical stains for DNA mismatch repair enzymes hMLH1, hMSH2 and hMSH6 were performed on a representative block from each case. Tumors lacking expression of a mismatch repair enzyme were designated MSI-H; all others were classified as microsatellite stable. Age, sex, tumor size, site, grade, stage, growth pattern, Crohn's-like reaction, vascular invasion and number of tumor-infiltrating lymphocytes were evaluated without knowledge of MSI status or patient outcome. 72 (29.3%) mucinous carcinomas were MSI-H. Compared to microsatellite stable mucinous cancers, they were more likely to be right-sided (83.3 vs 48.6%, P<0.001), have a Crohn's -like reaction (65.7 vs 29.8%, P<0.001) and have many tumor infiltrating lymphocytes (72.2 vs 20.8%, P<0.001). MSI-H mucinous cancers presented more often as localized disease (66.7 vs 38.1%, P<0.001) and less often with lymph node (26.4 vs 44.9%) or distant (4.2 vs 16.5%) metastases. In univariate analysis, MSI had a favorable effect on age-adjusted survival (hazard ratio 0.597, P=0.02). In multivariate analysis, age, grade, Crohn's-like reaction and stage were independent predictors of survival, but MSI status was not. In conclusion, MSI-H mucinous carcinomas are right-sided, low-stage tumors with Crohn's-like reaction and tumor-infiltrating lymphocytes. The outcome for MSI-H mucinous carcinoma is better than that of microsatellite-stable mucinous carcinoma, but MSI status is not an independent predictor of survival.
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PMID:Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival. 1501 35

In recent decades, surgical treatment of familial adenomatous polyposis, chronic ulcerative colitis, and muscle-invasive bladder cancer has undergone a revolution. Specifically, ileoanal reservoir and neobladder have become the new "gold standard" of definitive surgical therapy for these disorders. This article discusses issues in surgical construction, indications, contraindications, perioperative care concepts, and nursing and health professional implications related to these two procedures. These interventions include screening candidates for ileoanal reservoir or neobladder to rule out Crohn's disease or metastatic cancer and educating candidates for continent diversions about the proposed procedure(s) and associated events, potential complications, postoperative exercise, sexual health and function issues, and the benefits of support group participation so they can gain a realistic understanding of ultimate functional outcomes. Questions for future research are addressed.
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PMID:Continent diversions: the new gold standards of ileoanal reservoir and neobladder. 1536 31

The microsatellite instability (MSI) mutational pathway is critical to carcinogenesis in a small but significant proportion of colorectal cancers. While MSI is identified in most cancers in individuals with hereditary non-polyposis colorectal cancer, the majority of MSI tumors are found in individuals with sporadic disease. Colorectal cancers arising as a result of MSI have distinct clinicopathologic features distinguishing them from those with microsatellite stability. MSI colorectal cancers affect a larger percentage of women, are usually localized proximal to the splenic flexure, and have a higher incidence of synchronous and metachronous tumors. They are associated with a mucinous histology, tumor-infiltrating lymphocytes, a Crohn's-like inflammatory response, and a higher grade but lower stage. Overall survival is better in individuals with MSI. The benefit of chemotherapy in MSI colorectal cancers, with and without lymph node metastases, remains unclear.
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PMID:Clinicopathologic features in colorectal cancer patients with microsatellite instability. 1554 14

Colorectal carcinomas (CRCs) with high microsatellite instability (MSI-H) share clinicopathological features distinctly different from their microsatellite stable (MSS) counterparts. Unlike MSS cancers, MSI-H CRCs occur predominantly in the right-sided colon and are often characterised by a strong lymphocyte infiltration. A poor differentiation pattern is found in most MSI-H CRCs, even though patients with MSI-H carcinomas seem to have a significantly longer survival after surgical resection. To clarify which factors contribute to the obvious paradoxon of a more favourable prognosis of MSI tumours, several clinical and histopathological features as well as the microsatellite status were evaluated in 120 colorectal cancer cases fulfilling clinical criteria (Bethesda) indicative for familial colorectal cancer. Microsatellite instability status and lymphocyte infiltration were related to tumour stage and patients' follow-up. Statistical analysis confirmed well-known relations, such as enhanced lymphocyte infiltration accompanied by Crohn's like reaction (CLR) in MSI-H cancers (CLR+ in 27 out of 47 MSI-H vs 14 out of 71 MSS CRCs, P<0.001). However, after stratification for depth of local invasion and penetration of the primary tumour, T3 tumours displaying MSI had a significantly lower rate of distant metastases (M1 in four out of 35 MSI-H vs 20 out of 41 MSS CRCs, P<0.001). A similar tendency was observed for CLR-positive CRCs (M1 in six out of 29 CLR+ vs 17 out of 45 CLR- CRCs, P=0.13). In a logistic regression model, the MSI-H phenotype and the presence of CLR were independent predictors of a low UICC stage (P=0.006 and 0.04, respectively). These data, together with the recent definition of highly immunogenic neo-antigens expressed in MSI-H tumour cells, suggest that MSI-H CRCs elicit a protective host response that may prevent metastasis formation.
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PMID:Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases. 1585 45

The expression of CCL20 (MIP-3alpha), which chemoattracts leukocytes to sites of inflammation, has been shown in intestinal epithelial cells (IEC). Aim of this study was to analyze the role of the CCL20 receptor CCR6 in IEC and colorectal cancer (CRC) cells. Expression of CCR6 and CCL20 was analyzed by RT-PCR and immunohistochemistry. Signaling was investigated by Western blotting, proliferation by MTS assays and chemotactic cell migration by wounding assays. The effect of CCL20 on Fas-induced apoptosis was determined by flow cytometry. CCR6 and its ligand CCL20 are expressed in IEC. Moreover, CRC and CRC metastases express CCR6, which is upregulated during IEC differentiation. Stimulation of IEC with CCL20 and proinflammatory stimuli (TNF-alpha, IL-1beta, LPS) significantly upregulates CCL20 mRNA expression. CCL20 expression was significantly increased in inflamed colonic lesions in Crohn's disease and correlated significantly with the IL-8 mRNA expression in these lesions (r = 0.71) but was downregulated in CRC metastases. CCL20 activated Akt, ERK-1/2, and SAPK/JNK MAP kinases and increased IL-8 protein expression. The CCL20 mediated activation of these pathways resulted in a 2.6-fold increase of cell migration (P = 0.001) and in a significant increase of cell proliferation (P < 0.05) but did not influence Fas-induced apoptosis. In conclusion, IEC and CRC express CCL20 and its receptor CCR6. CCL20 expression is increased in intestinal inflammation, while CCR6 is upregulated during cell differentiation. CCR6 mediated signals result in increased IEC migration and proliferation suggesting an important role in intestinal homeostasis and intestinal inflammation by mediating chemotaxis of IEC but also in mediating migration of CRC cells.
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PMID:Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells. 1621 92


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