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Molecular markers for human colon cancer in stool and blood identified by RT-PCR.

There is a need for sensitive and specific diagnostic and prognostic molecular markers which can monitor early patterns of gene expression in non-invasive exfoliated colonocytes shed in the stool, and aggression in carcinoma cells in blood of resected colorectal cancer patients. RNA-based detection methods are more comprehensive than either DNA- or protein-based methods. By routinely and systematically being able to perform quantitative gene expression studies on non-invasive samples using carefully selected tumor-specific colon cancer genes, we can quantitatively and accurately monitor changes at various stages in the neoplastic process, allowing for surgical and/or other therapies, and thus, decrease mortality from colorectal cancer.

Adenocarcinoma↗

Advances in understanding the biology and genetics of acute myelocytic leukemia.

Acute myelocytic leukemia (AML) is a malignant neoplasm of hematopoietic cells characterized by an abnormal proliferation of myeloid precursor cells, decreased rate of self-destruction and an arrest in cellular differentiation. The leukemic cells have an abnormal survival advantage. Thus, the bone marrow and peripheral blood are characterized by leukocytosis with a predominance of immature cells, primarily blasts. As the immature cells accumulate in the bone marrow, they replace the normal myelocytic cells, megakaryocytes, and erythrocytic cells. This leads to a loss of normal bone marrow function and associated complications of bleeding, anemia, and infection. The incidence of AML increases with age, peaking in the sixth decade of life. In the United States, there are about 10,000 new cases of AML and 7,000 deaths in those with an AML diagnosis per year. Current molecular studies of AML demonstrate that it is a heterogeneous disorder of the myeloid cell lineage. This paper will discuss the most recent understanding and research of the cellular origin of AML and associated common genetic mutations that fuel the neoplastic process. Also discussed are how these advances have impacted the classification, selection of therapy, and definition of complete remission in AML. Promyelocytic leukemia will be discussed in detail as this AML subtype reveals how our understanding of the biology and genetics of the disease has led to targeted therapy that results in a cure in up to 80% of patients.

Cytogenetics↗

[Graves ophthalmopathy with coexisting tumor of the right orbit and hyperprolactinemia--case report].

Ophthalmopathy is a typical manifestation of Graves disease. Although most commonly ophthalmopathy affects both eyes, sometimes it is localized in only one orbit; neoplastic process must be considered then. The coexistence of a tumor of the orbital area and Graves ophthalmopathy is extremely rare. We present a case of a 42-years-old female with bilateral Graves ophthalmopathy, and a coexisting tumor of the right orbit. Magnetic resonance imaging of the orbits revealed a thickening of both rectus inferior extraocular muscles typical for Graves ophthalmopathy. An irregular low-signal mass was observed at the apex of the right orbit; it did not compress the optic nerve. The mass enhanced with gadolinium contrast, with its largest length of 4 cm, height of 2.5 cm, and the largest transverse diameter of 3 cm. It extended along the right trigeminal nerve into the right cavernous sinus, sella turcica, compressed the optic chiasm and penetrated into the right orbital inferior fissure. The tumor infiltrated the dura matter, and surrounded the intracranial part of the right optic nerve but did not cause its compression. Secondary amenorrhoea was present in this patient, probably due to hyperprolactinemia caused by the tumor (the plasma prolactin 1652 ulU/ml, RR 70.00-510.00). The patient was treated with radioiodine for hyperthyroidism and referred to neurosurgeons. Stereotactic therapy and surgery were considered in her case.

Adult↗

Malacoplakia of the pelvis. Report of a case with cytologic and ultrastructural findings obtained by fine needle aspiration.

Malacoplakia is a rare granulomatous, inflammatory disease usually diagnosed on a biopsy specimen. Only five cases have been diagnosed by FNA, most of them in the prostate. We report the cytologic and ultrastructural findings in fine needle aspirates of pelvic malacoplakia. The main characteristic of the smears was a richly inflammatory background with abundant, foamy histiocytes containing Michaelis-Gutmann bodies. The results indicate that fine needle aspiration is useful in diagnosing this disease, excluding a neoplastic process and performing follow-up.

Biopsy, Needle↗

Cytogenetic characteristics of patients with signs and symptoms of myelodysplastic syndromes in the State of Pará, Brazil.

The myelodysplastic syndromes (MDS) are clonal hematopoietic diseases characterized by medullary dysplasia, cytopenias, and frequent evolution to acute myeloid leukemia. In 1982, the French-American-British (FAB) group proposed a classification for the MDS, based on morphological characteristics of peripheral blood and of the bone marrow. Later, cytogenetics proved to be a useful tool for the refinement of prognosis, through the use of the International Prognosis Score System (IPSS), as well as through evidence of clonality. Recently, the World Health Organization (WHO) proposed a new classification for the MDS, based on significant modifications of the FAB proposal, with the inclusion of chromosome analysis. A cytogenetic analysis was made of 17 patients with symptoms of MDS in the State of Para, based on WHO recommendations, and application of the IPSS. Good metaphases were obtained for 13 patients; 12 had a normal karyotype and only one had a clonal abnormality, del(3)(p25). The genes related to neoplastic processes that have been mapped to 3p are: XPC in 3p25.1 and FANCD2 and VHL in 3p25-26. Four patients had classic symptoms of MDS; in the rest the possibility of MDS was excluded or several months of observation before diagnosis were recommended. Among those with MDS, it was not possible to apply IPSS and WHO recommendations, because fundamental data were lacking, specifically the medullary blast and ring sideroblast counts. We advocate the implementation of routine cytogenetic analyses for the study of MDS, especially in patients with moderate hematopoietic dysplasia.

Adolescent↗

[Malignant angioendotheliomatosis as a rare cause of cerebrovascular insufficiency].

Malignant angioendotheliomatosis, so called intravascular malignant lymphomatosis or angiotropic lymphoma, was found in cerebral hemispheres, spinal cord and nerve roots of a 50-year-old woman who died 4 months after onset of neurological symptoms. The pathological findings were characterised by neoplastic cells within the lumina and wall of small vessels as well as by multiple infarcts in the CNS. Vascular occlusions were caused by tumor cells and secondary changes of the wall. Positive reactions of Common Leucocyte Antigen and B-cell-markers support the idea of a lymphoid origin for the tumor cells. The differentiation to the angiocentric lymphoma as a T-cell tumor and the obscure pathogenesis of this neoplastic process must be clarified in the future.

B-Lymphocytes↗

[Second neoplasm in a 13-year-old boy complicated by Crohn's disease. Case report].

UNLABELLED: Genetic abnormalities and immune system disorders resulting from them are the causes of neoplastic diseases as well as inflammatory bowel disease, including Crohn's disease. However, the rearrangement of genes may not only be the cause of neoplasms but also the result of oncolytic treatment used. One of the late treatment-related complications of neoplastic diseases is the development of a second neoplasm and possible disorders belonging to the group of inflammatory bowel diseases, for example Crohn's disease. The paper presents the case of a 13-year-old boy (K.G.) treated for a second neoplasm, complicated by Crohn's disease. The patient was diagnosed with acute lymphoblastic leukaemia -- middle risk group (ALL-MRG) at the age of 3, treated according to the BFM 87 Protocol (dexamethasone, prednisone, vincristine, daunoribicin, asparaginase, cyclophosphamide, cytarabine, mercaptopurine, methotrexate, thioguanine, doxorubicin), and complete remission was achieved. Eight years after the first line treatment the boy was diagnosed with the second neoplastic process -- pre-B acute lymphoblastic leukaemia (ALL-L2 pre-B common +). The ALLIC 2002 Protocol (dexamethasone, prednisone, vincristine, daunoribicin, asparaginase, cyclophosphamide, cytarabine, mercaptopurine. methotrexate, thioguanine, doxorubicin) was started. On day 71 of the therapy, during aplasia of blood marrow following chemotherapy, inflammation of the caecum was diagnosed and metronidazole was introduced. Once blood counts improved, the complaints decreased and with continued chemotherapy of Protocol M (mercaptopurine, methotrexate), completely subsided. The symptoms reappeared during the 2-week break before Protoco II. The physical examination revealed the presence of a hard, painless tumour (3 x 10 cm) in the right iliac fossa. Colonoscopy showed a cauliflower-like formation within the Mauchin's valve projecting to the caecum lumen. The histopathological evaluation of the sections demonstrated a typical picture of Crohn's disease. Crohn's disease of the ileum was diagnosed, the treatment with dexamethazone (according to Protocol II) was instituted which led to complete regression of the iliac lesions. Steroid therapy (prednisone) continued until the treatment supporting the remission according to Protocol ALLIC 2002 (mercaptopurine, methotrexate orally) was initiated. CONCLUSION: The differential diagnosis of complications accompanying neoplasms should consider the inflammatory bowel diseases; their atypical course may be masked by the treatment of the underlying disease.

Adolescent↗

The role of macrophages in angiogenesis. Comparison between HIV+ and HIV- populations with anal dysplasia and anal cancer.

BACKGROUND: While macrophages (CD68+) have been associated with angiogenesis in some inflammatory and neoplastic processes by increasing the release of vascular endothelial growth factor (VEGF), their role in anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma has not been established. This study records macrophage infiltration in anal pre-invasive and invasive lesions in HIV+ and HIV- populations, and determines their relationship with angiogenesis. MATERIALS AND METHODS: Sixty patients (31 HIV+) with AIN and anal SCC were studied. Paraffin sections were stained for CD68, VEGF and von Willebrand factor. The density of CD68 cells, the expression of VEGF and angiogenesis were quantified, and compared amongst groups and between HIV+ and HIV- populations. RESULTS: All three parameters increased linearly as the lesions became more dysplastic, in HIV+ and HIV- groups. The CD68 count was statistically lower in HIV+ (p<0.005) compared with HIV- groups, while the differences in VEGF expression and in angiogenesis were not significant between HIV+ and HIV- populations. CONCLUSION: There was a significant decrease of macrophage infiltrate in the HIV+ group. The relative increase in VEGF expression and angiogenesis in the face of lower macrophage infiltration in HIV+ patients may be explained either by a greater release of angiogenic factors by macrophages, or by VEGF expression not being solely dependent on macrophage activation.

Anal Canal↗

[Alpha-fetoprotein immunotherapy as a stage of combined treatment of cancer patients].

The paper discusses the preliminary findings on alpha-feto-protein (AFP) treatment of 58 patients with stage III-IV malignancies of different localizations. No influence on neoplastic processes was registered in poorly differentiated cell tumors, nor were any immunological mechanisms of antitumor action triggered on. However, in moderately- and well-differentiated cell tumors, several foci of acute immune inflammation were induced. It is suggested that AFP is responsible for tumor cell apoptosis by freeing antigenic determinants from shielding antibodies via elimination of < > of tumor growth.

Apoptosis↗

Integrins adhesion molecules and some of their ligands in laryngeal cancer.

In this review data regarding the regular expression and distribution of integrins adhesion molecules as well as some of their ligands in cases of squamous cell carcinoma of the larynx (LSCC) are discussed. Cancer of the larynx is one of the most common malignancies of the head and neck. Upon neoplastic transformation several alterations of the integrins adhesion molecules and extracellular matrix (ECM) components are observed, i.e. the loss of the normal architecture especially depolarization of some integrins, like alpha6beta4, alpha3beta1, alpha2beta1 as well as the presence of alpha6beta1 integrin in neoplastic epithelium. Furthermore, the upregulation of alpha5beta1 integrin is a negative prognostic factor. In cases of laryngeal cancer, disorganization of the basal membrane components (laminins 1 and 5, type IV collagen, tenascin, fibronectin isoforms) which represent integrins ligands, is found. This is due to partial or complete destruction of the basal membrane, thus, permitting extravasation and migration of cancer cells. These phenomena are observed in a greater degree in tumors showing poor prognosis. It seems that damage of these adhesion complexes is important in the neoplastic process. So, further studies are necessary to establish the importance of these markers to early larynx cancer diagnosis and reach the decision on appropriate therapeutic strategies in the management of those patients.

Animals↗

[10 years survival of patient with lung cancer and cerebral metastasis].

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.

Adenocarcinoma↗

Pleuropericarditis and pericardial tamponade associated with inflammatory bowel disease.

Extraintestinal manifestations have been described with inflammatory bowel disease (IBD). Cardiac involvement in IBD is rare and may present as pericardial effusion, myopericarditis and conduction defects. Here we present a case of IBD with asymptomatic pericardial tamponade. A 37-year-old African-American man with ulcerative colitis with history of previous colectomy with ileorectal anastomosis was hospitalized for resection of the stricture of ileorectal anastomosis. The patient was afebrile with stable vitals and modest jugular venous distension, but no pulsus paradoxus. Cardiopulmonary examination was normal. A CT scan done to evaluate rise in liver function tests following removal of stricture showed a large 3.1 cm pericardial effusion. A transthoracic 2-D echocardiogram showed a moderate-sized posterior pericardial effusion limiting left ventricular filling. Central venous pressure was 18 mm Hg and the patient underwent drainage of 300 ml of old bloody pericardial effusion. Pericardial biopsy showed organizing fibrinohemorrhagic chronically inflamed pericardium without granuloma or neoplastic process. Serologies for EBV, Coxsackie virus and hepatitides were negative. Drug-related pericarditis seems less likely as the patient was not on sulfasalazine, and ANA, dsDNA and rheumatoid factor titers were negative. The patient was diagnosed to have pericardial tamponade associated with IBD.

Adult↗

[Imaging of median sternotomy complications].

Median sternotomy is the surgical technique of chosen for cardiac surgery. Although the complications after median sternotomy are not so frequent, these are associated to elevated mortality. The complications can interest the presternal compartment, the sternal compartment or the retrosternal compartment. Even if the clinical diagnosis of infection is not difficult for the clinician, it is nearly impossible to establish the depth of the infection. Multislice CT, thanks to the possibility to obtain thin layers and three-dimensional multiplanar reconstructions and Volume Rendering, turns out extremely useful for being able to demonstrate the extension and the depth of the infection. Of fundamental importance it is the elaboration of the images, executed on workstation, with which multiplanar reformatted and Volume Rendering images are obtained. The CT turns out useful moreover like guide for the execution of interventional procedures such as aspiration of material for bacteriological characterization or eventual positioning of a catheter for abscess drainage. The Magnetic Resonance, thanks to its high resolution of contrast and to its multiplanarity, finds one of its elective applications in the study of the flogistic and neoplastic processes of the soft tissues. A great limit of the MR is the possible generation of artifacts due to sternal suture.

Cardiac Surgical Procedures↗

[Rare case of papillary cystic carcinoma of ectopic thyroid gland in glossothyroid ductus].

The neck midline cyst is the most common congenital malformation in the neck area. In described case of 33 years women the diagnosis was established on clinical examination, the results of USG and the aspiration biopsy. The tumor was surgically excited and the microscopy examination revealed papillary cystic carcinoma of ectopic thyroid gland in glossothyroid ductus. In the every case of neck tumor we have to consider neoplastic process.

Adult↗

Appraisal of anti-idiotypic antibodies in the treatment of solid tumors in humans.

Anti-idiotypic antibodies may be valuable in the induction of antitumor immunity in two ways--they can serve as a ready source of antigen when the appropriate TAA is difficult or impossible to purify. More importantly, regulatory anti-idiotypic antibodies can activate specific T-helper cells, bringing all the components of cellular immunity to bear on neoplastic process. Although the results in studies in animals have demonstrated resistance to tumor challenge after immunization with anti-idiotypic antibodies, studies of humans with advanced malignancies have failed to produce substantial clinical results. Nevertheless, immunization with anti-idiotypic antibodies has influenced some tumors. These studies represent important, initial steps toward understanding the immune network and modulating it in favor of the host, against human tumors. As a continued understanding of the immune network evolves and strategies for activating and suppressing specific immune responses are developed, it should be possible to design vaccines for specific uses. Although current anti-idiotypic vaccines do not seem promising for the treatment of established solid tumors in humans, we can look with anticipation to studies of polyvalent vaccines for the prevention of carcinoma in high risk groups.

Animals↗

[Adrenal tuberculosis as a cause of primary adrenal insufficiency--case report].

Adrenal tuberculosis is relatively infrequent cause of primary adrenocortical insufficiency in developed countries. Adrenal involvement is most often the result of hematogenous spread of the pulmonary tuberculosis. Isolated adrenal tuberculosis, especially with enlargement of adrenal glands can cause diagnostic problems and requires differentiation from primary or secondary neoplastic disease. In this paper we present a case of 61-year-old man with several months history of adrenocortical insufficiency without signs of pulmonary tuberculosis. Computed tomography scan revealed asymmetrical mass-like enlargement in adrenal glands. Despite of consecutive investigations, the diagnosis remained uncertain. Because of the possibility of neoplastic process of unknown origin, the patient was qualified for surgical exploration during which both enlarged glands were removed. The diagnosis of tuberculosis was made on microscopic examination.

Addison Disease↗

Cytogenetic findings in adult greek myelodysplastic syndrome patients: predominance of single trisomy 8.

Myelodysplastic syndrome (MDS) is a clonal disorder of the pluripotent hematopoietic stem cells which is characterized by ineffective and dysplastic hematopoiesis. The pathogenesis of MDS is not well defined and it appears that multiple genetic changes are involved. Several studies have shown that certain chromosomal abnormalities may be influenced by environmental factors, while differences in the incidence of certain aberrations in different areas have also been reported. The aim of this study was to investigate the frequency and the type of chromosomal changes in Greek primary MDS patients. Single chromosomal abnormalities were focused on as possibly being primary changes implicated in the initiation of the neoplastic process. Using conventional cytogenetics, 239 MDS patients were studied and 63 cases were found with an abnormal karyotype (26.36%). Among the cytogenetically abnormal cases, 46 patients presented single chromosomal abnormalities (73.1%). These aberrations were according to frequency +8 (28.57), del(5q), -7/del(7q) and +14 (6.35 each), i(17q) and del(11(q13) (4.76 each), +11, -Y, i(1q), del(8q), del(18p) and t(X;11) (1.59% each). In conclusion, the incidence of chromosomal abnormalities in Greek MDS patients was lower than that reported in the literature. The most common single anomaly was trisomy 8, while a relatively high incidence of an isolated +14 was also observed. Notably, this is the first time an isolated i(1q) has been described in the literature.

Adult↗

[Immunologic response to (pre)neoplastic cervical lesions associated with human papillomavirus].

Etiopathogenic and epidemiological studies have demonstrated that viruses are etiologically linked to approximately 20% of all human malignancies worldwide. Human papillomavirus (HPV) is one of the best characterized viruses associated with human cancer diseases, especially in the uterine cervix. Although the role of HPV is well established in the cellular transformation and maintenance of the malignant phenotype of keratinocytes, the viral infection by itself is not sufficient for cancer development. The small number of infected individuals eventually developing cancer of the cervix and the long latency period between primary infections and cancer emergence suggest that additional environmental or host factors are involved in malignant progression. In this context, the local mucosal immunity might be expected to play a key role in the host defence against HPV infection and associated-(pre)cancerous lesions. The purpose of this work was to analyse the immune co-factors implicated in the initiation and promotion of the neoplastic process. We have shown that the transformation zone (TZ), where a substantial majority of cervical (pre)cancers develop, is characterized by intrinsic immune alterations which could explain why this region is at higher risk of developing cancer. We have also provided evidence that the viral infection of cervical keratinocytes contributes to the local immunodeficiency by inhibiting the production of soluble and membrane molecules important for the migration and function of antigen-presenting cells.

Female↗