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)

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

Due to the development of more effective medications, those infected with HIV are living longer. Consequently, more tumors and infections have been added to the AIDS-defining criteria in the last decade. Our aim was to review the occurrence and clinical course of colorectal (CR) malignancies in HIV infected/AIDS patients from a single institution. A retrospective review of HIV/AIDS patients with colorectal malignant tumors was undertaken. We included adult patients, with ELISA and Western blot test positive for HIV, and primary malignant tumors located in the colon or rectum. Malignant neoplasms of the anus were excluded for the purposes of this study. Twelve patients (9 males and 3 females), mean age 41 years, were identified with the following neoplasm: 6 adenocarcinomas (ACA), 5 non-Hodgkin lymphomas (NHL), and 1 small-cell carcinoma. Intravenous drug abuse was the main risk factor for HIV. No patient had identified risk factors for colorectal neoplasm. Five out of six patients with ACA had metastatic disease at the time of diagnosis. One patient with stage II ACA developed early liver metastases after colonic resection. Seven out of 12 patients underwent surgery. Six (85.7%) of these sustained postoperative complications, primarily wound infection. The overall survival in our series was dismal, averaging 20 months. For NHL average survival was 29 months, and 12 months for CR-ACA. This is the largest series of cases of colorectal cancer in the HIV/AIDS patient population published in the English language and the largest number of colorectal ACA reported in this unique population. Early in our experience, tumors frequently found in immunoincompetent patients were detected (NHL). More recently, we have only treated patients with colorectal ACA; none of them had no risk factors for colorectal cancer (family history, IBD, FAP, HNPCC). These patients developed tumors at earlier ages and were diagnosed at an advanced stage. Therefore, these tumors may be associated with the grade of immunosuppression induced during the course of the HIV infection and with a tumorigenic effect of the HIV on the colonic epithelium. Consequently, a high index of suspicion when evaluating chronic abdominal complaints in such patients is warranted. The use of the new antiretroviral therapy regimens should be further evaluated to know its impact in the survival.
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PMID:Colorectal malignancies in HIV-positive patients. 1462 61

Gastrointestinal (GI) tumors continue to be major causes of cancer-related mortality, in part, reflecting metastases that escape detection by histopathology. Moreover, although approximately 10% of carcinomas arise from unknown locations, these tumors frequently originate in the GI tract. Guanylyl cyclase C (GC-C) is a receptor selectively expressed by intestinal epithelial cells whose persistent expression by colorectal carcinomas and ectopic expression by adenocarcinomas of the upper GI tract suggest its use as a marker for GI malignancies. Here, expression of GC-C protein, identified by immunohistochemistry, was examined in tissues and tumors arising from the human GI tract. Guanylyl cyclase C protein was expressed by epithelial cells from the duodenum to the rectum, but not by those in normal esophagus and stomach. Expression was retained in tubular adenomas, inflammatory bowel disease, premalignant lesions, and in primary and metastatic adenocarcinomas from the colon, including metastases to lymph nodes and liver. Moreover, GC-C was ectopically expressed in all cases of dysplasia and adenocarcinomas arising from intestinal metaplasia in esophagus and stomach. Thus, GC-C appears to be an immunohistochemical marker for identifying adenocarcinomas of unknown origin, metastases in patients undergoing staging for GI adenocarcinomas, and intestinal metaplasia, dysplasia, and tumors arising therein in the upper GI tract.
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PMID:Guanylyl cyclase C is a marker of intestinal metaplasia, dysplasia, and adenocarcinoma of the gastrointestinal tract. 1575 94

The diagnosis and management of prostate cancer is hampered by the absence of markers capable of identifying patients with metastatic disease. In order to identify potential new markers for prostate cancer, we compared gene expression signatures of matched androgen-dependent and hormone refractory prostate cancer xenografts. One candidate gene overexpressed in a hormone refractory xenograft was homologous to the regenerating protein gene family, a group of secreted proteins expressed in the gastrointestinal tract and overexpressed in inflammatory bowel disease and cancer. This gene, Reg IV, was confirmed to be differentially expressed in the LAPC-9 hormone refractory xenograft. Consistent with its up-regulation in a hormone refractory xenograft, it is expressed in several prostate tumors after neoadjuvant hormone ablation therapy. As predicted by its sequence homology, it is secreted from transiently transfected cells. It is also expressed strongly in a majority of hormone refractory metastases represented on two high-density tissue microarrays. In comparison, it is not expressed by any normal prostate specimens and only at low levels in approximately 40% of primary tumors. These data support Reg IV as a candidate marker for hormone refractory metastatic prostate cancer.
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PMID:Reg IV: a promising marker of hormone refractory metastatic prostate cancer. 1578 72

Comprehensive bowel examination results from the combined use of T2-weighted single-shot and breath hold T1-weighted gradient echo, minus/plus fat suppression, and gadolinium-enhanced 3D gradient echo (3D VIBE, T1 FAME, 3D THRIVE). Gadolinium-enhanced imaging should be performed dynamically, but the venous 60- to 90-second delayed phase images with fat suppression are generally the most valuable. Removal of fat signal for detection of enhancing normal and abnormal structures is critical. Newly available True-FISP (FIESTA, BFFE) sequences obtained in the 2D form can be very helpful in delineation of bowel wall pathology and overall bowel anatomy, particularly when combined with a water-based intraluminal distending agent. Advantages include rapid acquisition, high signal-to-noise, and motion insensitivity. Generalized protocol for comprehensive evaluation of the entire abdomen and pelvis can be used for the following bowel indications: type and severity of inflammatory bowel disease (IBD); identifying enteric abscesses and fistulae; preoperative staging of malignant neoplasms, including rectal carcinoma; differentiating postoperative and radiation therapy changes from recurrent carcinoma; follow-up evaluation of metastases response to localized ablative or systemic chemotherapy. For improved visualization of bowel wall in dedicated examinations, bowel distension should be achieved using either orally or rectally delivered contrast agents to produce either bright or dark lumen. We have found 2D True-FISP without fat suppression superior to 3D True-FISP and to single-shot echo-train sequences to provide a T2-weighted image of bowel morphology. Strengths include: performed without fat suppression results in the very dark bowel wall being sandwiched between intermediate high signal fat adjacent to bowel serosa, and very high lumen signal from water-distending agent; 2D True-FISP provides motion insensitivity that is lost if 3D is used; True-FISP produces better edge sharpness than single-shot echo-train, higher contrast, and resists flow void artifacts commonly seen with single-shot echo-train imaging combined with a water distending agent. Drawbacks of this technique include: artifacts related to extreme sensitivity to field inhomogeneity, including air-soft tissue interfaces at the patient skin surface, and from retained bowel gas; retained bowel gas is dark against dark bowel wall, impairing bowel wall assessment; and True-FISP does not provide sensitivity for edema, which is superior on single-shot echo-train imaging. Small/large bowel indications for MRI include: inflammatory bowel disease, infectious disease including abscess evaluation or for appendicitis, inflammatory conditions including ischemia, and partial obstruction, malnutrition, and neoplasm search.
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PMID:Magnetic resonance imaging of the gastrointestinal tract. 1631 98

Each year in the UK, around 16,000 people die from colorectal cancer. At disease presentation, around 55% of people have advanced cancer that has spread to lymph nodes, metastasised to other organs or is so locally advanced that surgery is unlikely to be curative (Dukes' stage C or D). Overall 5-year survival for colorectal cancer in the UK is around 47-51% (compared to 64% in the USA), but only 7% at most in those presenting with metastatic disease. These facts underlie the current introduction of national bowel screening programmes in the UK. Here we assess the role of screening of the general population in reducing mortality from colorectal cancer. We do not consider the screening arrangements needed for high-risk populations, including those with inflammatory bowel disease or a strong family history of colorectal cancer.
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PMID:Population screening for colorectal cancer. 1700 66

A 35-year-old female received right hemicolectomy for a poorly differentiated adenocarcinoma of the ascending colon with lymph node metastasis (1/28) in February 1997. CEA was 1.68 ng/microl prior to colectomy. Adjuvant chemotherapy with weekly 5-FU and leucovorin intravenously was started following surgery and discontinued after 17 doses in May 1997. She received bilateral salpingo-ophorecctomy for metastatic cancer in August 1999. Intravenous chemotherapy was resumed with weekly 5-FU and leucovorin intravenously in August 1999. CEA was 93.8 ng/microl in November 1999. Intravenous chemotherapy was discontinued after 20 doses and oral chemotherapy with futraful and leucovorin was started in January 2000. CEA was found to be 240.3 ng/microl in December 1999 and then elevated to 1521.3 ng/microl in June 2001, which was 10 months after resection of metastatic ovarian cancer. No metastatic lesions could be detected, however, with image studies. The CEA decreased to 396.6 ng/microl three months later. Futraful was switched to uracil-tegafur (UFUR) in September 2001. The CEA for the patient ranged from 68.5 to 298.9 ng/microl for the following 5 years without aggressive chemotherapy. No evidence of recurrence could be demonstrated by imaging studies. The patient is not a smoker and denied exposure to a smoking environment. She was also not known to have persistent infections, inflammatory bowel disease, pancreatitis, cirrhosis of the liver, or any benign tumors. The current case suggested that: (i) elevation of CEA is not necessarily well correlated with presence of metastatic colon cancer; (ii) some patients may live with elevated CEA for years without evidence of recurrence or metastasis; (iii) aggressive chemotherapy may not be necessary in patients with only elevated CEA.
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PMID:Unusual elevation of CEA in a patient with history of colon cancer. 1706 Apr 6

Stomal varices secondary to portal hypertension are a rare but potentially fatal cause of hemorrhage. Management, determined by the site of the bleeding, centers on preventing additional bleeds and may include providing local pressure, applying silver nitrate, injection sclerotherapy, suture ligation of the bleeding point, and/or the placement of transjugular intrahepatic portosystemic shunts and refashioning the stoma. Two patients (60- and 69-year-old women) had panproctocolectomy for inflammatory bowel disease and presented at the authors' hospital with bleeding from the ileostomy 1 and 19 years, respectively, following the creation of their stomas. A third patient (a 72-year-old man) bled from an end colostomy following an abdominoperineal resection for Duke's C rectal adenocarcinoma performed 3 years previous. All three patients had recurrent admissions for stomal bleeding and stomal varices secondary to portal hypertension and were initially treated with local measures (pressure, silver nitrate, and suture ligation). Two had undergone revision of their stomas prior to current treatment. One patient responded to local treatment but later died due to liver failure, one stopped bleeding after transjugular portosystemic shunt placement, and one died from metastatic cancer. Clinicians should maintain a high index of suspicion of stomal varices in patients with underlying liver disease who present with recurrent stomal bleeds and provide appropriate treatment to stop active bleeding and reduce portal venous pressure.
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PMID:Stomal varices: a rare cause of stomal hemorrhage. A report of three cases. 1772 9

Invasive colorectal carcinomas (CRCs) with invasion confined to the lamina propria (LP) [intramucosal carcinoma (IMC)] lack access to lymphatics and therefore have no potential for metastases and local intervention (usually polypectomy) should be adequate treatment. For this reason, they are classified as "Tis" in the TNM system. It is believed that carcinomas invading the submucosa with unfavorable histology (tumors at/near the margin, and/or vascular invasion, and/or poor differentiation) require additional intervention after polypectomy, whereas those with favorable histology can be safely treated endoscopically. However, there are few data on poorly differentiated (PD) carcinomas showing invasion confined to the LP. Polypectomy is theoretically curative but in practice this has not been well demonstrated. Thus, the clinicopathologic features of 15 cases of PD CRCs with invasion limited to the LP on initial biopsies were studied to determine the best course of management for this rare subset of carcinomas. A computer search and histologic review of cases seen at Johns Hopkins Hospital was performed. Fifteen cases of PD CRC with invasion limited to the LP were identified. The clinicopathologic features of these tumors were reviewed. All 15 cases showed PD IMC with single cells infiltrating only the LP. Patients were 38 to 79 years (median, 62) of age with a male predominance (M:F=4:1). Three cases had signet ring cell differentiation, 1 had focal small cell features, and another had focal squamous differentiation. Fourteen of the cases were associated with background adenomas or adenomalike lesions including: 7 involving tubulovillous or villous adenomas, 6 involving tubular adenomas, 1 involving dysplasia associated with chronic inflammatory bowel disease. Nine of the lesions had surrounding high-grade dysplasia. One case showed no background dysplasia or adenoma. One patient was lost to follow-up and the remaining 14 were followed for 1 to 96 months (mean, 21.3 mo; median, 13 mo). Seven patients had no residual disease on follow-up colonoscopy, and no resection was performed. The remaining 7 patients were treated with partial colectomy (6) or low anterior resection (1), and of these, 5 had no infiltrating carcinoma and negative lymph nodes. One patient had a separate large colorectal (T3) carcinoma with 8/10 positive regional lymph nodes; the IMC seen on biopsy was presumably a metastasis as it was unassociated with an in situ component. Finally, the resected rectum from which an IMC had been previously detected had no residual invasive carcinoma, but the anal skin was involved by Paget disease. Thus, of the 15 cases of PD CRCs limited to the LP, 1 was a metastasis from a separate CRC and another had associated Paget disease of the anal skin. As such, even in the setting of PD carcinomas, no metastatic disease was seen arising from any of the cases that were confirmed as early primary lesions. These preliminary findings suggest that patients with isolated intramucosal PD CRCs may be managed endoscopically.
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PMID:Poorly differentiated colorectal carcinoma with invasion restricted to lamina propria (intramucosal carcinoma): a follow-up study of 15 cases. 1872 39

Colonic adenocarcinoma frequently complicates inflammatory bowel disease of the colon, but small bowel adenocarcinoma (SBA) is a rare complication of Crohn's disease (CD). We present two patients with SBA in CD and review the literature with regards to CD-related SBA. A 45-year-old male with a 17-year history of ileal CD presented with obstructive symptoms but no radiographic evidence of a mass. After laparoscopic ileocolectomy and repair of incidental ileosigmoid fistula, pathology showed a T3N0 adenocarcinoma within the ileal CD. Two years after his resection he was without evidence of disease. A 59-year-old male with a 15-year history of CD presented with an acute exacerbation. Small bowel follow through demonstrated a long ileal stricture for which he underwent an ileocolic resection. Postoperative pathology confirmed a T3N1 CD-related SBA. He died from metastatic cancer 3 months later. Review of the literature identified 154 cases of SBA complicating CD with several distinguishing features from de novo SBA. Patients with SBA and CD are, as a group, younger and more likely to be male. SBA is rarely diagnosed preoperatively in these patients, and has a poor prognosis due to its advanced stage at diagnosis.
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PMID:Small bowel adenocarcinoma complicating Crohn's disease: case series and review of the literature. 1809 59


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