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PubMed2006

The role of epigenetic alterations in pancreatic cancer.

The past several years have witnessed an explosive increase in our knowledge about epigenetic features in human cancers. It has become apparent that pancreatic cancer is an epigenetic disease, as it is a genetic disease, characterized by widespread and profound alterations in DNA methylation. The introduction of genome-wide screening techniques has accelerated the discovery of a growing list of genes with abnormal methylation patterns in pancreatic cancer, and some of these epigenetic events play a role in the neoplastic process. The detection and quantification of DNA methylation alterations in pancreatic juice is likely a promising tool for the diagnosis of pancreatic cancer. The potential reversibility of epigenetic changes in genes involved in tumor progression makes them attractive therapeutic targets, but the efficacy of epigenetic therapies in pancreatic cancer, such as the use of DNA methylation inhibitors, remains undetermined. In this review, we briefly summarize recent research findings in the field of pancreatic cancer epigenetics and discuss their biological and clinical implications.

Cell Cycle Proteins↗

PubMed2006

Inflammatory pseudotumor of the cavernous sinus and skull base.

Inflammatory pseudotumor is a non-neoplastic process of unknown etiology characterized by a proliferation of connective tissue with an inflammatory infiltrate. Intracranial inflammatory pseudotumors classically involve the cavernous sinus but can also occur in the supratentorial or infratentorial compartments and spinal canal. Symptoms are dependent on location, and, when present in the cavernous sinus, typically include cranial nerve palsies of those nerves in the cavernous sinus. These lesions are rapidly responsive to steroid therapy. Surgery is typically indicated for biopsy only, but complete resection may be justified for lesions outside the cavernous sinus.

Adult↗

PubMed2005

Characteristic appearance of large subcutaneous gouty tophi in magnetic resonance imaging.

The development of multiple large tophi in patients with gout is rare. We report magnetic resonance (MR) and histological features of large subcutaneous tophi in a 32-year-old male patient with no known arthritis. His subcutaneous lesions were confused with a neoplastic process, evaluated by MR imaging, and surgically excised after biopsy. The honeycomb-like appearance on the gadolinium-enhanced images may reflect the characteristic multilobular structure of the tophi composed of avascular urate deposits and surrounding vascularized granulation tissue.

Journal Article↗

PubMed2005

Nicorandil and idiopathic anal ulceration.

PURPOSE: Several reports have implicated nicorandil as a reversible cause of anal ulceration. We have recently commenced a specialist clinic for patients presenting with severe anal ulceration to assess treatment in this difficult group. Recognition of this association may avoid unnecessary surgery. METHODS: Twenty-six patients treated with nicorandil had severe painful anal ulceration. Examination under anesthesia was required to biopsy the lesions to exclude neoplasia or inflammatory bowel disease. In total, three patients had proximal diverting stomas without subsequent ulcer resolution, two had perineal debridement with one requiring subsequent skin grafting, and one had an abdominoperineal excision for unremitting pain. RESULTS: The association of perianal ulceration with nicorandil became apparent only in the latter part of this series. Ten ulcers successfully re-epithelialized when nicorandil was stopped. Nine patients reported anal pain relief and partial healing on clinical examination at two months but failed to show subsequent complete resolution. One patient agreed to nicorandil cessation and reported symptomatic anal pain relief at two weeks but subsequently developed unstable angina requiring hospital admission. Nicorandil was recommenced with anal pain relapse. CONCLUSIONS: Failure to recognize nicorandil as an etiologic factor in the development of anal ulceration, when other potential underlying well-recognized inflammatory or neoplastic processes have been excluded, may lead to unnecessary surgical intervention in a group of high-risk patients. One of our patients had a potentially avoidable abdominoperineal resection. Pharmaceutical manipulation with alternative antiangina medication may induce healing. Pharmacologic manipulation should be coordinated with a physician to minimize precipitation of unstable angina.

Aged↗

PubMedDate not supplied

Improved methods for extracting RNA from exfoliated human colonocytes in stool and RT-PCR analysis.

In order to diagnose colon cancer at an earlier, more localized stage, there is a need to develop diagnostic markers (genes) which can detect early patterns of gene expression in exfoliated colonocytes shed in the stool during routine screening for this disease. An RNA-based detection is more pertinent than either a DNA-based or a protein-based method as a screening procedure, but it has not been widely used as a cancer screen because of the difficulty of handling and stabilizing the RNA molecule. We describe a method that permits extraction of intact nondegraded total RNA from human colonocytes in stool and from normal and malignant colon tissues (which were employed for comparison with stool). Because it utilizes commercially available kits, this method is simpler than other published methods and does not require isolation of messenger (m)RNA, thereby reducing the chances of contaminating the preparations with degrading nucleases, and even a small amount of isolated total RNA can be adequately reverse transcribed, making high-quality copy (c) DNA. This is followed by PCR (either qualitative end point or semiquantitative real-time) using colon cancer-specific gene primers. By routinely and systematically being able to perform quantitative gene expression measurements on noninvasive samples, the goal of this pilot work is to lay the groundwork for conducting a large clinical study to identify groups of selected genes whose expression is consistently altered at an early stage in the neoplastic process. Such work will permit noninvasive monitoring of at-risk patients through the analysis of their stool samples. Correct diagnosis will allow for surgical and/or other interventions before the tumor is well established and, thus, should decrease mortality from this preventable disease.

Adenocarcinoma↗

PubMed2005

CD117 expression in glial tumors.

C-kit is a proto-oncogene involved in normal growth and development and neoplastic processes, and its product, CD117, is a highly specific immunohistochemical diagnostic marker for gastrointestinal stromal tumors (GISTs). Because GISTs that express immunohistochemically-detectable CD117 respond dramatically to treatment with tyrosine kinase inhibitors, identification of central nervous system tumors that express CD117 might open new therapeutic approaches for treatment of brain tumors. Specimens from 52 glial tumors of various histologic types and grades were assayed for CD117 immunoreactivity, and about 75% of the tumors were positive for CD117 expression; all except a few exhibited strong cytoplasmic and membranous staining. The proportion of high grade tumors of all tumor types with detectable CD117 immunoreactivity was statistically significantly greater than low grade tumors, and glioblastoma and anaplastic oligodendroglioma showed the highest staining grade. These findings support further investigation into the possibility that CD117 has an important role in growth of glial tumors and that patients with brain tumors expressing CD117 might benefit from treatment with receptor tyrosine kinase inhibitors.

Biomarkers, Tumor↗

PubMed2005

Xanthoma of the urinary bladder.

Xanthomas of the urinary bladder are rare lesions of reactive nature. They present as yellow-white mucosal plaques that may be mistaken for a neoplastic process. A biopsy displays stromal accumulation of lipid macrophages without accompanying inflammatory component. This article presents a 78-year-old woman who had a tumour-suspect xanthoma of the urinary bladder occurring subsequent to several resections of non-invasive carcinomas.

Aged↗

PubMed2006

Current treatment in cardiac amyloidosis.

Involvement of the heart is a common finding in amyloidosis. The heart is usually infiltrated by amyloid fibrils in primary amyloidosis and age-related forms of amyloidosis, less commonly in transthyretin familial amyloidosis, and rarely in secondary amyloidosis. The most common clinical presentation is restrictive cardiomyopathy with right-sided heart failure. The second most frequent presentation is congestive heart failure due to systolic dysfunction, followed by arrhythmias and orthostatic hypotension. The diagnosis of amyloidosis requires tissue sample confirmation; at present, Congo red staining in polarized light is the diagnostic method of choice. The characterization of protein fibril type by immunohistochemistry or biochemistry is essential for patient prognosis and treatment. The therapeutic approach consists of specific treatment of amyloidosis and supportive treatment for cardiac-related symptoms. The treatment depends on the type of amyloidosis and the stage of disease. The mainstay of supportive treatment of cardiac failure is diuretic therapy. Primary amyloidosis treatment protocol includes melphalan and prednisone chemotherapy. Heart transplantation is only a palliative treatment. Stem cell transplantation is an emerging treatment alternative. Combination therapy of melphalan and stem cell transplantation has been shown to be a promising treatment strategy. Secondary amyloidosis requires aggressive treatment of the associated inflammatory and neoplastic process. Age-related (senile) amyloidosis benefits from supportive cardiac treatment when applicable. Transthyretin amyloidosis, the most common cardiac hereditary amyloidosis, is treated by liver or combined liver-heart transplantation. New therapies based on chemical and immunologic reaction with amyloid or its precursor are under intensive development.

Journal Article↗

PubMed1999

Pericardial Effusion and Tamponade.

Pericardial effusion may occur as a result of a variety of clinical conditions, including viral, bacterial, or fungal infections and inflammatory, postinflammatory, autoreactive, and neoplastic processes. More common causes of pericardial effusion and tamponade include malignancy, renal failure, viral and bacterial infectious processes, radiation, aortic dissection, and hypothyroidism. It can also occur after trauma or acute myocardial infarction (as in postpericardiotomy syndrome following cardiac or thoracic surgery) or as an idiopathic pericardial effusion. Although pericardial effusion is common in patients with connective tissue disease, cardiac tamponade is rare. Among medical patients, malignant disease is the most common cause of pericardial effusion with tamponade. Table 1 shows the causes of pericardial tamponade. The effusion fluid may be serous, suppurative, hemorrhagic, or serosanguineous. The pericardial fluid can be a transudate (typically occurring in patients with congestive heart failure) or an exudate. The latter type, which contains a high concentration of proteins and fibrin, can occur with any type of pericarditis, severe infections, or malignancy. Once the diagnosis of pericardial effusion has been made, it is important to determine whether the effusion is creating significant hemodynamic compromise. Asymptomatic patients without hemodynamic compromise, even with large pericardial effusions, do not need to be treated with pericardiocentesis unless there is a need for fluid analysis for diagnostic purposes (eg, in acute bacterial pericarditis, tuberculosis, and neoplasias). The diagnosis of pericardial effusion/tamponade relies on a strong clinical suspicion and is confirmed by echocardiography or other pericardial imaging modalities. Alternatively, when the diagnosis of cardiac tamponade is made, there is a need for emergency drainage of pericardial fluid by pericardiocentesis or surgery to relieve the hemodynamic compromise. Following pericardiocentesis, it is necessary to prevent recurrence of tamponade. Intrapericardial injection of sclerosing agents, surgical pericardiotomy, and percutaneous balloon pericardial window creation are techniques used to prevent reaccumulation of pericardial fluid and recurrence of cardiac tamponade.

Journal Article↗

PubMed2002

Barrett's Esophagus, a Complication of GERD.

The treatment of patients with Barrett's esophagus is similar to that of any patient with underlying gastroesophageal reflux disease (GERD). The treatment of reflux includes medical and surgical therapy. A key component of medical therapy is the use of a proton pump inhibitor to treat the underlying GERD. The major controversy is whether the end point of therapy should be the control of reflux symptoms or the control of esophageal pH. When controlling reflux symptoms with proton pump inhibitor therapy, it is important to eliminate all of the symptoms of reflux. An alternative to medical therapy is surgical fundoplication, which is currently performed laparoscopically. Fundoplication may be indicated when a patient has persistent regurgitation even while on proton pump inhibitor therapy. An individual patient also may choose fundoplication, preferring surgical intervention to taking medication long term on a daily basis. Patients with Barrett's esophagus also have the risk of the developing of adenocarcinoma of the esophagus. Therefore, there is an additional goal in the therapy for individuals with Barrett's to prevent progression to adenocarcinoma. The standard approach to the issue of the premalignant nature of Barrett's esophagus is surveillance endoscopy with biopsy in order to detect dysplasia, a cytologic and architectural histologic change. Dysplasia is the first step in the neoplastic process, an early stage offering the opportunity of intervention and longer-term survival.

Journal Article↗

PubMed1985

Nasopharyngeal carcinoma. Brief review.

Nasopharyngeal carcinoma has a well-defined geographic distribution, primarily affecting persons from southern China and Southeast Asia. Environmental factors are numerous and appear to have a secondary role, mainly in the promotion of the neoplastic process. Relationship with the Epstein-Barr virus is indicated by the identification of viral genome copies within the cells and by a persistent host antibody response with restricted specificity for nasopharyngeal malignancies. The World Health Organization has recently adopted a histologic classification categorized into three subtypes according to the degree of epithelial differentiation, keratinization, and stromal lymphocytic infiltration. The tumor expands locally to contiguous structures, spreads through the cervical lymphatics following the jugular chain, and eventually metastasizes to the skeleton and liver. Primary management consists of radiation therapy to cervicofacial fields and usually offers adequate palliation, with a five-year median survival of 67 percent for stage I and 17 percent for stage IV disease.

Antibodies, Viral↗

PubMed1989

An overview of the retinoids.

The retinoids, a group of compounds consisting of vitamin A and its derivatives, have been the subject of intense investigation over the past 30 years. These molecules have shown beneficial effects in the areas of acne, psoriasis, neoplastic processes and, most recently, reversal of extrinsically aged skin. Additional retinoids are currently under development. Adverse reactions to these drugs include mucocutaneous irritation, hyperlipidemia, and profound teratogenicity. Appropriate patient selection is imperative before beginning therapy with these medications. An overview of retinoid metabolism and the currently available compounds is presented. The newest class of retinoids, the arotinoids, is also discussed.

Abnormalities, Drug-Induced↗

PubMed1991

Value of lymph node biopsy in the treatment of patients with the human immunodeficiency virus.

The indications and value of lymph node biopsy in patients infected with the human immunodeficiency virus (HIV) are not clearly defined. We reviewed 29 consecutive lymph node biopsies performed on 24 patients with the HIV over a 4-year period. Indications for biopsy included: (1) new or worsening medical symptoms with no detectable etiology in patients with lymphadenopathy, (2) disproportionately larger or enlarging lymph node in patients with generalized adenopathy, and (3) exclusion of concomitant disease in patients with previously defined infectious or neoplastic processes. The biopsy samples exhibited a diversity of histologic appearances including atypical and reactive hyperplasia, malignancy, and infection. Nineteen biopsies (64%) resulted in the institution or alteration of treatment. The absolute number of T-helper cells prior to biopsy was significantly lower in patients with a diagnosis of malignancy or infection (p < 0.05), as well as in those who eventually died (p < 0.05). Four (14%) minor complications resulted from lymph node biopsy. Based on our results, we conclude that lymph node biopsy is indicated in the above three subsets of HIV-infected patients. Biopsy can be performed with minimal morbidity and significantly alters therapy in the majority of patients.

AIDS-Related Complex↗

PubMed1991

Bronchoalveolar carcinoma: factors affecting survival.

One hundred thirty-four consecutive patients (65 men and 69 women) underwent pulmonary resection for bronchoalveolar carcinoma. Mean age was 65 years. Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and wedge excision in 19. Only 10 patients had lymph node metastases (7.5%). The neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in stage II, 9 were in stage IIIa, and 1 was in stage IIIb. There were two operative deaths (1.5%). Thirty-nine complications occurred in 31 patients. Median follow-up was 5.1 years. Recurrent bronchoalveolar carcinoma developed in 45 patients. Five- and 10-year survival for patients in stage I was 75.2% and 62.0%, respectively. Survival for patients with T1 N0 M0 neoplasms was identical to expected survival and was 90.5% at 5 years, as compared with 55.4% for patients with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease, and 0.0% for patients with bilateral disease (p less than 0.0001). Other significant factors adversely affecting survival included the presence of signs and symptoms, diffuse malignant invasion, mucin-producing tumors, and the histological absence of scar. We conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases. Early aggressive pulmonary resection is safe and offers the potential for cure. The presence of bilateral cancer, however, is ominous.

Adenocarcinoma↗

PubMed1993

Hodgkin's disease and the malignant lymphomas.

The unanticipated finding of a subcutaneous swelling, typically an enlarged lymph node in the neck, is legitimate cause for concern. After excluding benign or reactive conditions, this sign should initiate a series of investigations to characterize the neoplasm and, in the case of a lymphoma, lead to prompt treatment aimed at cure. The classic description of such cervical adenopathy is that by Thomas Hodgkin, who clearly recorded both the clinical behavior and the macroscopic findings evident at dissection. Subsequent histologic study revealed the multinucleate giant cells that characterize the tumor that now bears his name and linked it to those of Greenfield, Sternberg, and Reed. Initial debate centered on whether this entity was inflammatory or malignant, with the issue further clouded by the frequent coexistence of tuberculosis. Although a number of features exist in favor of both concepts, current consensus places it among the neoplastic processes. Hodgkin's disease was separated from other malignant lymphomas as agreement on diagnostic criteria emerged. The next major step forward was the demonstration, first by Vera Peters and then by Henry Kaplan, that adequate doses of radiotherapy were curative when delivered to treatment fields that encompassed the tumor. A further milestone was the introduction by Vincent DeVita, Jr., and his colleagues of combination chemotherapy that was effective in late stage of disseminated disease. The established cornerstones of managing these patients are accurate diagnosis; precise anatomic staging, modified as appropriate by associated factors known to have prognostic value; and selection of irradiation, chemotherapy, or whatever combination will result in the best possible patient survival. However, success is not universal, and death due to resistant or relapsing disease is encountered all too frequently. It is here that the benefits of a multidisciplinary approach are evident, because a substantial level of expertise coupled with sound judgment is needed to salvage these individuals, often by means of investigational programs. Some of the latter are limited by profound myelosuppression, and safety may center on the use of cytokines in the form of interleukins and growth factors, with or without bone marrow transplantation. In such situations, benefit must be balanced against risks in well-structured clinical trials that embody informed consent. Herein lies one of the major goals for the next decade. The non-Hodgkin's lymphomas can conveniently be considered in two broad categories. Some follow an indolent clinical course, in which the lymph node retains a follicular pattern with small component cells, and others are aggressive tumors, in which primitive blasts have diffusely effaced the glandular architecture.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1976

Effect of aprotinin, EACA and heparin on growth and vasopeptide system of Murphy-Sturm lymphosarcoma.

The effect of aprotinin, EACA and heparin on the growth of the transplanted rodent Murphy-Sturm lymphosarcoma and on several components of the tumor kinin-forming enzyme system was studied. Therapy was administered for 15 days, 3 times daily, one day after tumor transplant. Tumor weights and biochemical parameters (prekallikrein, kininogen and kininase) were measured on the 8th, 10th, 12th and 15th day of therapy. Both aprotinin and heparin significantly inhibited (p less than 0.01) tumor growth by the 15th day, compared to control, saline-administered animals. EACA did not affect the tumor growth rate at any time period. Tumor prekallikrein and kininogen levels were significantly higher (p less than 0.01) in the aprotinin-treated animals. Kininogen levels were higher in the EACA-treated tumors during the latter phase of growth. None of the agents affected the increase in tumor kininase activity that occured during the growth of the tumors. The tumor inhibition and biochemical data suggest the involvement of proteases in the neoplastic process.

Aminocaproates↗

PubMed1986

Pseudomyxoma peritonei associated with colloid carcinoma of the pancreas.

A case of pseudomyxoma peritonei associated with a mucin-rich, "colloid" adenocarcinoma of the pancreas is described. This previously unreported association was characterized by an extremely rapid clinical course, transerosal spread of the neoplastic process, and the consistent presence of intracytoplasmic lumina in all cells, an ultrastructural feature thought to characterize malignant lesions.

Adenocarcinoma, Mucinous↗

PubMed1989

The dilated pore of Winer--an overlooked cutaneous lesion of cats.

A retrospective study of 125 cutaneous cystic lesions in cats from 1978 to 1987 Revealed 14 examples of the dilated pore of Winer, a lesion previously described in man and in one cat. Histologically, this lesion appears as a flasklike cystic structure with a wide external opening and laminated keratinaceous content. The cyst is characterized by a thickened wall with numerous, closely apposed rete ridges, either at its base or throughout most of the circumference, with a thinner atrophic wall approaching the os. Clinically, the lesion is a hairless nodule or visible cutaneous defect containing either soft keratinaceous material or, more commonly, projections of horn-like material. In man, the lesion is believed to be either a hamartoma or a benign neoplastic process. Surgical excision is curative.

Animals↗