Although pathologists have recognized the classic forms of lobular neoplasia for decades, our understanding of this disease has changed markedly since its first description. The term lobular neoplasia encompasses a spectrum of entities ranging from atypical lobular hyperplasia to more recently recognized lobular carcinoma in situ (LCIS) variants including LCIS with necrosis and pleomorphic LCIS. Along with an expanded definition
Helena Hwang; Megan E. Sullivan; Barbara Susnik
This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles.
The theoretical and practical reasons for replacing the terms "cervical dysplasia" and "cervical carcinoma in situ" by the single diagnostic entity of "cervical intraepithelial neoplasia" are reviewed and the advantages and drawbacks of this newer terminology discussed. The histological characteristics and cytological features of the various grades of cervical intraepithelial neoplasia are described and the differential diagnosis of this lesion is considered. Images
Buckley, C H; Butler, E B; Fox, H
... Almost everyone with type 2A disease develops medullary thyroid cancer (see Thyroid Gland Disorders: Medullary cancer ). About 50% ... endocrine neoplasia type 2B can consist of medullary thyroid cancer, pheochromocytomas, and growths around nerves (neuromas). Some people ...
\\u000a Several genetic syndromes are associated with multiple endocrine tumors. In this chapter, we focus on Multiple Endocrine Neoplasia\\u000a (MEN) types 2 and 1. Von Hippel Lindau and Neurofibromatosis will be discussed in other sections.
Yariv J. Houvras; Gilbert H. Daniels
HPV infections of the lower genital tract are associated with the increasing incidence of vulvar intraepithelial neoplasia. The new classification divides vulvar intraepithelial neoplasia according to its incidence into two groups: usual and differentiated type. The usual type occurs mainly in young women and is associated with HPV infection, the differentiated type is HPV-negative and occurs in older women. The diagnosis is based on biopsy from a suspicious lesion. The standard treatment involves surgical excision. Topical treatment is now being preferred in young women in order to preserve appearance of the genitalia and sexual function. The high risk of recurrence is the reason for strict monitoring of patients after treatment completion. PMID:21542276
Miklos, P; Babala, P; Klacko, M; Masák, L; Ondrus, D
The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue.
Anal intraepithelial lesions are caused by chronic infection with oncogenic types of human papillomavirus. Their incidence and prevalence are increasing, especially among patients with HIV infection. Their natural history is not well known, but high-grade intraepithelial lesions seem to have an important risk to progress to squamous cell carcinoma. Their treatment can be achieved by many ways (surgery, coagulation, imiquimod, etc.) but there is a high rate of recurrent lesions. Pretherapeutic evaluation should benefit from high-resolution anoscopy. Periodic physical examination and anal cytology may probably be interesting for screening the disease among patients with risk factors. Vaccine against oncogenic types of papillomavirus may prevent the development of anal intraepithelial neoplasia. PMID:23122632
de Parades, Vincent; Fathallah, Nadia; Barret, Maximilien; Zeitoun, Jean-David; Lemarchand, Nicolas; Molinié, Vincent; Weiss, Laurence
International consensus meetings in Padova and Vienna have attempted to rationalise the grading and classification of gastrointestinal epithelial neoplasia (GEN). With its minor adjustments, the Vienna classification of GEN seeks to be more closely in tune with patient management and it is hoped that it is not seen as fiddling around with terms but as a genuine contribution to patient
M F Dixon
The inflammation caused by Trypanosoma cruzi produces irritation and cell proliferation and may contribute to the development of cancer. The objective was to determine the occurrence of gynecologic neoplasia (GN) and demographic characteristics in patients with Chagas disease (CD). We used protocols of 671 autopsies between 1976 and 2008. The patients were divided into 3 groups: with GN and CD,
Venina Marcela Dominical; Camila Lourencini Cavellani; Laura Penna Rocha; Rosana Rosa Miranda Corręa; Gilberto de Araújo Pereira; Vicente de Paula Antunes Teixeira
PURPOSE: Dietary fiber has been implicated in colorectal neoplasia, despite conflicting evidence. This is a review of the currently available data on the role of dietary fiber in colorectal carcinogenesis. METHODS: A literature search was conducted using the MEDLINE database. All case-control, longitudinal, and randomized, controlled studies published in English between 1988 and 2000 were identified, as were animal model
Shomik Sengupta; Joe J. Tjandra; Peter R. Gibson
Opinion statement Multiple endocrine neoplasia type I is a rare autosomal dominant disorder with many endocrine and nonendocrine manifestations.\\u000a Hyperparathyroidism, islet cell tumors, and pituitary tumors are diagnosed most commonly in these patients. There is controversy\\u000a regarding treatment of the different manifestations and screening modalities of this disorder because no large series has\\u000a determined the best therapeutic approach. Our institution advocates
Rasa Zarnegar; Laurent Brunaud; Orlo H. Clark
Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocíticas crónicas o juveniles, y la LMC atípica.
Analysis of epidemiological, cohort and randomized studies of antihypertensive drugs containing reports of development of malignant neoplasms shows that long term use of some antihypertensive drugs while preventing cardiovascular complications has been associated with increased risk of malignancies. Most convincing evidence exists for association between the use of diuretics and renal cancer. Association between the use of reserpine and breast cancer in women, between atenolol and some types of cancer in elderly men also can not be ruled out. There is no proof of existence of either negative or positive correlation between malignant neoplasia and long-term use of calcium antagonists, angiotensin converting enzyme inhibitors or angiotensin receptor blockers. PMID:12494152
Preobrazhenski?, D V; Sidorenko, B A; Stetsenko, T M; Kiktev, V G
BACKGROUNDUse of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions.AIMTo develop common worldwide terminology for gastrointestinal epithelial neoplasia.METHODSThirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between
R J Schlemper; R H Riddell; Y Kato; F Borchard; H S Cooper; S M Dawsey; M F Dixon; C M Fenoglio-Preiser; J-F Fléjou; K Geboes; T Hattori; T Hirota; M Itabashi; M Iwafuchi; A Iwashita; Y I Kim; T Kirchner; M Klimpfinger; M Koike; G Y Lauwers; K J Lewin; G Oberhuber; F Offner; A B Price; C A Rubio; M Shimizu; T Shimoda; P Sipponen; E Solcia; M Stolte; H Watanabe; H Yamabe
Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are major genetic disorders carrying a high risk of endocrine tumor development. The mutated genes were identified in 1993 (MEN2-RET) and 1997 (MEN1), enabling genetic testing and functional studies. Genetic analysis has led to new clinical and therapeutic strategies for MEN1/2 patients, and has improved our understanding of the pathways underlying the development of such tumors, which occur in an autosomal dominant manner and with high penetrance. The MEN1 gene encodes menin, a protein involved in many cell functions, such as transcription, genome stability, cell cycling and apoptosis. The MEN1 gene has 10 exons, and its exhaustive analysis in MEN1 patients helps guide their management. MEN2 is related to activating missense mutations in the RET protooncogene, which encodes a tyrosine kinase receptor (TKR). RET activation occurs upon autodimerization induced by the binding of specific ligands belonging to glial cell-derived neurotrophic factor-like family (GFL) proteins, regulated by coreceptors. The position of missense mutations--in the extracellular or intracellular TK domains--influences the aggressiveness of the most frequent malignancy, medullary thyroid carcinoma, establishing a genotype-phenotype correlation. We also briefly describe the genetic basis of three other inherited states predisposing individuals to endocrine tumors, namely Carney's syndrome, hyperparathyroidism type 2 (HRPT2) and familial isolated pituitary adenoma (FIPA), which are related to inactivating mutations in the PRKAR1-alpha, HRPT2 and AIP genes, respectively. PMID:20669561
Multiple endocrine neoplasia type 1 (MEN1) is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors. Some patients may also develop carcinoid tumors, adrenocortical tumors, facial angiofibromas, collagenomas, and lipomas. MEN1 is an autosomal-dominant disorder, due to mutations in the tumor suppressor gene MEN1, which encodes a 610 amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. Patients with MEN1 have a decreased life-expectancy and the outcomes of current treatments, which are generally similar to that for the respective tumors occurring in non-MEN1 patients, are not as successful because of multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases. The prognosis for MEN1 patients might be improved by pre-symptomatic tumor detection and undertaking treatment specific for MEN1-tumors. Thus, it is recommended that MEN1 patients and their families should be cared for by multi-disciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors. PMID:23565397
Thakker, R V
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant tumor syndrome characterized by the occurrence of tumors in multiple endocrine tissues and nonendocrine tissues. The three main endocrine tissues most frequently affected by tumors are parathyroid (95%), enteropancreatic neuroendocrine (50%) and anterior pituitary (40%). Tumors are caused by a heterozygous germline-inactivating mutation in the MEN1 gene (1st hit) followed by somatic inactivating mutation or loss of the normal copy of the gene (2nd hit), leading to complete loss of function of the encoded protein menin. Most of the disease features and tumors are recapitulated in mouse models with heterozygous germline loss of the Men1 gene. Also, tissue-specific tumors are observed in mouse models with homozygous somatic loss of the Men1 gene specifically in MEN1-associated endocrine tissues. Hence, mouse models could serve as possible surrogates for studying MEN1 and related states. To gain insights into MEN1 pathophysiology, menin-interacting partners and pathways have been identified to investigate its tumor suppressor and other functions. Also, the 3D crystal structure of menin has been deciphered which could be useful to reveal the relevance of MEN1 gene mutations and menin's interactions. This chapter covers clinical, genetic and basic findings about the MEN1 syndrome, MEN1 gene and its product protein menin. PMID:23652667
Agarwal, Sunita K
Multiple endocrine neoplasia type 1 (MEN1) is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors. Some patients may also develop carcinoid tumors, adrenocortical tumors, facial angiofibromas, collagenomas, and lipomas. MEN1 is an autosomal-dominant disorder, due to mutations in the tumor suppressor gene MEN1, which encodes a 610 amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. Patients with MEN1 have a decreased life-expectancy and the outcomes of current treatments, which are generally similar to that for the respective tumors occurring in non-MEN1 patients, are not as successful because of multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases. The prognosis for MEN1 patients might be improved by pre-symptomatic tumor detection and undertaking treatment specific for MEN1-tumors. Thus, it is recommended that MEN1 patients and their families should be cared for by multi-disciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors.
Thakker, R. V.
Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics. PMID:23267125
Frega, Antonio; Sopracordevole, Francesco; Assorgi, Chiara; Lombardi, Danila; DE Sanctis, Vitaliana; Catalano, Angelica; Matteucci, Eleonora; Milazzo, Giusi Natalia; Ricciardi, Enzo; Moscarini, Massimo
Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called "3 P's": parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia. PMID:22584699
Diaz, René E; Wohllk, Nelson
Efficacia e sicurezza della terapia con ventilazione a pressione positiva non invasiva nell'edema polmonare acuto Efficacy and safety of pressure support noninvasive positive pressure ventilation therapy in acute cardiogenic pulmonary edema
Efficacy and safety of pressure support noninvasive positive pressure ventilation therapy in acute cardiogenic pulmonary edema. F.M. Sarullo, G. D'Alfonso, I. Brusca, P. De Michele, A. Taormina, P. Di Pasquale, A. Castello. Background. Non-invasive positive pressure ventila- tion (NIPPV) is an effective treatment for acute respirato- ry failure in patients with chronic obstructive pulmonary disease. We assessed the efficacy and
Filippo Maria Sarullo; Giovanni D'Alfonso; Ignazio Brusca; Piero De Michele; Andrea Taormina; Pietro Di Pasquale; Antonio Castello
This pilot study investigated the prevalence and distribution of human papillomavirus (HPV) type in vulvar lesions in women with a history of vulvar intraepithelial neoplasia. Fifty-two specimens were collected. Uncommon HPV subtypes were found among the specimens, which may have implications for HPV vaccination coverage. PMID:22300742
Likes, Wendy; Bloom, Leonard
We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on ApcMin-induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-azadeoxycytidine, reduced the average number of intestinal
Peter W Laird; Laurie Jackson-Grusby; Amin Fazeli; Stephanie L Dickinson; W Edward Jung; En Li; Robert A Weinberg; Rudolf Jaenisch
The risk of patients with Hirschsprung's disease later developing multiple endocrine neoplasia remains a matter of concern. The multiple endocrine neoplasia 2–Hirschsprung's disease association has been shown to cosegregate in Hirschsprung's disease patients with both short- and long-segment aganglionosis, although patients with long-segment aganglionosis a to carry the greatest risk. The Hirschsprung's disease–medullary thyroid carcinoma relationship also appears to be bi-directional, and activation or suppression of the rearranged during transfection gene appeared to vary over succeeding generations within the same family. Rearranged during transfection gene variations are associated with both conditions. The cosegregation of Hirschsprung's disease and multiple endocrine neoplasia 2 is particularly interesting as it involves both “switch off” and “switch on” of the rearranged during transfection proto-oncogene in the same patient. This cosegregation mostly relates to the cysteine-rich area on RET-620 (the “Janus gene”). The mechanism whereby rearranged during transfection influences gene activation in multiple endocrine neoplasia 2 is complex, but genetic variations impair the rearranged during transfection tyrosine kinase response to tyrosine kinase activation, thus appearing to dictate downstream signaling cascade responses. Better understanding of the RET-620 relationship allows for a more cost-effective method of identifying those at risk by focusing rearranged during transfection gene testing to this specific area as a “hot spot”. The clinical awareness of possible medullary thyroid carcinoma has led to timely intervention and early treatment of this chemo- and radioresistant tumor with poor prognosis. Establishment of “risk” by genetic testing has become a classic model of molecular medicine being integrated into patient care and offering rearranged during transfection-directed prophylactic surgical management. In addition, novel approaches to treatment based on this genetic knowledge have already shown early promise in randomized clinical trials.
Moore, Sam W.; Zaahl, Monique
. Hyperparathyroidism occurs sporadically, in association with multiple endocrine neoplasia (MEN) types I and II,\\u000a or rarely as familial hyperparathyroidism (FHPT) without other manifestations. We analyzed our experience in 16 FHPT patients\\u000a from 14 families treated between 1934 and 1991 and reviewed 51 other FHPT patients reported in the literature to determine\\u000a the clinical course of these patients. Among our
Shih-Ming Huang; Quan-Yang Duh; John Shaver; Allan E. Siperstein; Jean-Louis Kraimps; Orlo H. Clark
Adenomatous neoplasia or glandular tumours in the ear are very rare to occur. We are reporting two patients who presented\\u000a with polypoid mass in external auditory canal of whom one patient was diagnosed to have ceruminous adenoma of external auditory\\u000a canal and the other adenomatous carcinoma of middle ear based on histopathology findings of biopsied specimen. Review of available\\u000a literature
Madhira Srivalli; Hamid Abdul Qaiyum; Prayaga N. Srinivas Moorthy; Kolloju Srikanth
The term lobular neoplasia (LN) includes lobular carcinoma in situ (LCIS) and atypical lobular neoplasia (ALH). It is generally considered to be a risk lesion and a non-obligatory precursor for the subsequent development of an invasive carcinoma in the ipsilateral or contralateral breast. LN has also been termed lobular intraepithelial neoplasia (LIN). A grading system (LIN 1-LIN 3) has been suggested as a tool for a more precise estimation of the individual risk. When LN is the most significant finding in a core biopsy, the probability of a higher grade lesion is about 17% in the follow-up surgical biopsy, justifying follow-up surgery in the majority of cases. A higher risk of progression is attributed to LIN 3 (pleomorphic LN, extensive LN, and signet ring cell LN) compared to LIN 1 or LIN 2. These special forms of LN may have an unusual presentation clinically or histologically. Using immunohistology, LN are characterized by the loss of E-cadherin, low proliferative activity and by positive hormone receptor status. The molecular characteristics of LN are similar to those of invasive lobular carcinomas, indicating the nature of LN as a precursor lesion. PMID:16896673
Sinn, H P; Helmchen, B; Aulmann, S
Colon cancer screening is arguably the most important activity performed by gastroenterologists. Recent decreases in rates of death from colorectal cancer indicate that screening methods such as colonoscopy have a positive impact. There is still room for improvement, however, particularly in prevention of right-sided colon cancer. Practice issues, such as making colonoscopy more comfortable, safer, and less costly, are keys to continued success in cancer prevention. Colonoscopy techniques, technologies, and quality control measures have advanced to improve detection, classification, and removal of early neoplasias. In particular, slow, careful inspection of the colon by gastroenterologists who have been trained in lesion recognition has improved rates of detection of polypoid and flat neoplasias. Image enhancement methods such as chromoendoscopy have greatly improved neoplasia detection in patients with chronic colitis, but are not widely used because they are perceived as inconvenient. More convenient methods, such as "digital" chromoendoscopy, show promise but have had mixed results. Ultra-high magnification systems, including optical magnification and confocal endomicroscopy, can be used during the colonoscopy examination to evaluate small polyps, allowing physicians to make immediate diagnoses and decisions about whether to remove polyps. In patients with inflammatory bowel disease, improved imaging techniques could eliminate the needs for analysis of randomly selected biopsy samples and resection of all (neoplastic and non-neoplastic) polyps. It is important to maintain high standards of quality for colonoscopy examination, detection, and removal of high-risk lesions, as well as to make colon cancer screening more widely accepted and affordable for the entire at-risk population. PMID:20420951
Wallace, Michael B; Kiesslich, Ralf
Background Recent evidence suggests that noninvasive precursor lesions, classified as pancreatic intraepithelial neoplasia (PanIN), can\\u000a progress to invasive pancreatic cancer. This review will discuss the major genetic alterations in PanIN lesions.\\u000a \\u000a \\u000a \\u000a Methods A comprehensive review of the literature was performed in order to find studies on the molecular profile of human PanIN lesions.\\u000a In addition, recent publications on genetically engineered mouse models
Georg Feldmann; Robert Beaty; Ralph H. Hruban; Anirban Maitra
Early epidemiological studies of cervical neoplasia suggested a causal relation with sexual activity and human papillomaviruses (HPVs) have emerged as prime suspects as venerally transmitted carcinogens. HPVs fall into two broad camps: low risk types, associated with cervical condylomas and CIN 1; and high risk types (mostly 16 and 18), found in 50-80% of CIN 2 and CIN 3 lesions, and 90% of cancers. This association with cancer is very strong, with odds ratios of > 15 (often much higher) in case-control studies that are methodologically sound. An infrequently detected third group of intermediate risk type HPVs is associated with all grades of CIN and occasionally with cancers. HPVs have also been detected in a wide range of asymptomatic controls, indicating that other events are required for development of neoplasia such as viral persistence and/or altered expression of viral genes, often following integration of the viral genome. This leaves the two major viral oncogenes, E6 and E7, directly coupled to viral enhancers and promoters, allowing their continued expression after integration. High risk HPV E7 proteins bind and inactivate the Rb protein, whereas E6 proteins bind p53 and direct its rapid degradation. A range of putative cofactors has been implicated in progression: HLA type, immunosuppression, sex steroid hormones, and smoking; most of these cofactors appear to influence progression to CIN 3. The natural history includes progression to CIN 3 in 10% of CIN 1 and 20% of CIN 2 cases, whereas at least 12% of CIN 3 cases progress to invasive carcinoma. Cervical glandular intraepithelial neoplasia (CGIN) often coexists with squamous CIN, and the premalignant potential of high grade CGIN is not in doubt, but the natural history of low grade CGIN remains uncertain. A high proportion of CGIN lesions and adenocarcinomas are HPV positive, and HPV18 has been implicated more in glandular than in squamous lesions. A strong clinical case for the application of HPV typing of cells recovered from cervical scrapes can be made; however, a rigorous cost-benefit analysis of introducing HPV typing into the cervical screening programme is required. Prophylactic and therapeutic HPV vaccines are under development. This article reviews the aetiology, pathogenesis, and pathology of cervical neoplasia, emphasising the role of HPVs.
Arends, M J; Buckley, C H; Wells, M
High-grade prostatic intraepithelial neoplasia (HGPIN) has been established as a precursor to prostatic adenocarcinoma. HGPIN shares many morphological, genetic, and molecular signatures with prostate cancer. Its predictive value for the development of future adenocarcinoma during the prostate-specific antigen screening era has decreased, mostly owing to the increase in prostate biopsy cores. Nevertheless, a literature review supports that large-volume HGPIN and multiple cores of involvement at the initial biopsy should prompt a repeat biopsy of the prostate within 1 year. No treatment is recommended for HGPIN to slow its progression to cancer.
Miocinovic, Ranko; Magi Galluzzi, Cristina; Klein, Eric A
This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phe- nylethanolamine N-methyltransferase (PNMT), the enzyme that con- verts norepinephrine to epinephrine. Signs and symptoms of
GRAEME EISENHOFER; MCCLELLAN M. WALTHER; THANH-TRUC HUYNH; SHENG-TING LI; STEFAN R. BORNSTEIN; ALEXANDER VORTMEYER; MASSIMO MANNELLI; DAVID S. GOLDSTEIN; W. MARSTON LINEHAN; JACQUES W. M. LENDERS; KAREL PACAK
Objectives GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Methods Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. Results There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). Conclusions GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression.
Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N. Volkan
In a group of 22 women with cervical intraepithelial neoplasia and carcinoma of the cervix uteri and in a control group of 37 healthy women, a number of anamnestic and objective data about factors influencing these women and about consequences of such influence were analysed. Statistically significant differences between patients and controls were found in the character of work performed (physical vs. intellectual, p = 0.0312), the presence of stressing factors at the workplace (p = 0.02), a higher number of consumed meals per day in the control group (p = 0.0009), daily consumption of beer in a higher percentage of patients (p = 0.0015), the frequency of sexual intercourse in the last 2-3 months before the diagnosis of disease or examination (higher in controls, p = 0.0164) and subjective rating of sexual life in the fourth decade (better rating in controls, p = 0.0005). No differences were found between patients and controls in the number of sexual partners, the presence of antibodies against HSV-2 and other factors. According to data presented and data in the literature, external environment, some of the characteristics of sexual life and particularly infection with certain types of papillomaviruses have a certain influence on the development of cervical neoplasias. PMID:7757347
Strauss, J; Suchánek, A; Krcmár, M; Roth, Z; Kanka, J; Vonka, V
Renal neoplasia is described in coypus (Myocastor coypus) from a feral population of the species in East Anglia. A population control campaign was started in 1962, and in 1981 this became an eradication scheme. From 1976 onwards, a research programme included the postmortem examination of 9400 wild caught and captive coypus. During the period 1980-91, 15 cases (0.16%) of renal neoplasia were detected. The tumours were found in both sexes between estimated ages of 25 months and 13 years with no significant sex prevalence. There was no clear evidence that renal tumours were more common in older animals. Tumours were most common in captive coypus and were bilateral in approximately half of the animals. In all cases, the tumours were of epithelial type resembling adenomata and adenocarcinomata of other animals. Most were clearly benign, and, although some showed evidence of malignancy, no unequivocal evidence of metastasis was established. The prevalence of renal tumours in this series is greater than that recorded in previous published surveys of coypus and other rodents. This may relate to the origin of the coypus population, differences in age structure in animals examined, and the varied conditions under which the rodents lived. Aetiological factors remain undetermined. PMID:10489271
Keymer, I F; Wells, G A; Ainsworth, H L
The association between cervical neoplasia and certain HLA phenotypes observed in different studies has not been consistent. By serological typing, the association between HLA antigens, cervical carcinoma and cervical intraepithelial neoplasia (CIN) was studied in a group of 172 and 116 patients, respectively. We demonstrated an increased frequency of B63 in patients with HPV types other than HPV 16 or 18, and B55 in patients that were negative for all HPV types. The association between cervical carcinoma and DQ3, described in various populations, was not observed in the present study. However, we confirmed other previously observed associations between cervical cancer and class II antigens, i.e., a positive correlation with DR15 irrespective of the HPV status, with DR3 in patients harboring HPV types other than HPV 16 or 18, and with DR11 among HPV 16 positive patients. In contrast, a negative correlation between DR13 and HPV positive cervical cancer was observed which suggests protection of this antigen against HPV-associated cervical cancer. A slight increase of DR15 and DQ4 antigens was observed in CIN patients, suggesting that these specific HLA antigens may be important in determining the risk of CIN. PMID:10363725
Krul, E J; Schipper, R F; Schreuder, G M; Fleuren, G J; Kenter, G G; Melief, C J
Neoplasia is characterised by abnormal regulation of the cell cycle. Cyclin D1 is a protein derived from the PRAD1, CCND1 or bcl-1 gene on chromosome 11q13, which is involved in both normal regulation of the cell cycle and neoplasia. In the G1 (resting) phase of the cell cycle, cyclin D1 together with its cyclin dependent kinase (cdk) partner, is responsible for transition to the S (DNA synthesis) phase by phosphorylating the product of the retinoblastoma gene (pRB), which then releases transcription factors important in the initiation of DNA replication. Amplification of the CCND1 gene or overexpression of the cyclin D1 protein releases a cell from its normal controls and causes transformation to a malignant phenotype. Analysis of these changes provides important diagnostic information in mantle cell (and related) lymphomas, and is of prognostic value in many cancers. Knowledge of cyclin D1's role in malignancy at the various sites, provides a basis on which future treatment directed against this molecule can proceed.
Donnellan, R; Chetty, R
Epidemiologic and biochemical evidence suggest that smoking is an independent risk factor for cervical neoplasia; however, only two studies have adjusted by the potential confounding effect of human papillomavirus (HPV). To determine the association between self-reported current cigarette smoking and cervical intraepithelial neoplasia (CIN), we conducted a case-control study that controlled for HPV infection and other reported risk factors. The
Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, the authors had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked
M. L. Brandi; A. Falchetti; F. Tonelli; G. Weber; A. Svensson; C. Larsson; R. Castello; L. Furlani; S. Scappaticci; M. Fraccaro
For the last five millennia we have been dealing with the annoyance of verrucas. Anogenital human papillomavirus (HPV) infection is the most common sexually transmitted disease in the United States and is increasing in incidence. As in other gastrointestinal conditions, HPV infection can lead to a stepwise transition from normal cells to dysplastic cells and then to invasive anal cancer. Knowledge of the natural history of HPV infection, risk factors, diagnostic tools, and therapeutic methods gives us the tools to adequately prevent, evaluate, treat, and counsel our patients. In this review, the authors detail the diagnosis, management, and treatment of anal condyloma and anal intraepithelial neoplasia with a focus on prevention, early detection, and treatment using current data and technology.
Echenique, Ignacio; Phillips, Benjamin R.
Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia.
Wen, Victoria W.; MacKenzie, Karen L.
Clinically significant prostate cancer usually occurs in men who are 65 and older although precursor lesions are known to exist many years prior to cancer diagnosis. Histopathological changes referred to as Prostatic Intraepithelial Neoplasia (PIN) are co...
A. P. Kumar
Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386
Wen, Victoria W; Mackenzie, Karen L
The pathological, cytological, and clinical features of vulvar intraepithelial neoplasia (VIN) are described. The rate of progression of VIN III to an invasive carcinoma is very low and spontaneous regression can occur. These features prevent the drawing of a direct analogy between vulvar and cervical intraepithelial neoplasia. The concept of microinvasive carcinoma of the vulva is discussed, and it is concluded that no satisfactory definition of this entity has been achieved. Images
Buckley, C H; Butler, E B; Fox, H
Multiple endocrine neoplasia type 1 (MEN1) is inherited in an autosomal dominant fashion and predisposes to the development of hyperplastic or neoplastic changes in the parathyroid and pituitary glands and the endocrine pancreas, along with numerous other characteristic tumors and features. The management of each entity differs to some degree from their sporadic counterparts, while the lack of a genotype-phenotype correlation requires lifelong clinical, biochemical and radiological screening for the development of new tumors. While the syndrome itself is relatively rare (a prevalence of 1-10/100?000), it is likely that health-care practitioners from numerous specialities will occasionally encounter a patient with MEN1 and therefore a basic knowledge of the syndrome is important. In addition, many of the associated tumors are seen commonly in sporadic form, and a judicious policy is therefore required in deciding how thoroughly patients who develop these tumors should be screened for MEN1. The current literature on MEN1 is reviewed and key learning points are suggested for the clinician. PMID:23279763
Carroll, Richard W
Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (?oct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of ?oct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the ?oct are different between normal vulvar tissue and VIN lesions (p<0.0001). Moreover, no correlation is found between the epidermal layer thickness and ?oct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue.
Wessels, Ronni; de Bruin, Daniel M.; Faber, Dirk J.; van Boven, Hester H.; Vincent, Andrew D.; van Leeuwen, Ton G.; van Beurden, Marc; Ruers, Theo J. M.
The enterochromaffin-like (ECL) cell in the oxyntic mucosa has a key role in the regulation of gastric secretion since it synthesizes and releases the histamine regulating the acid secretion from the parietal cell. Gastrin is the main regulator of the ECL cell function and growth. Long-term hypergastrinemia induces ECL cell hyperplasia, and if continued, neoplasia. ECL cell carcinoids occur in man after long-term hypergastrinemia in conditions like pernicious anemia and gastrinoma. There is also accumulating evidence that a proportion of gastric carcinomas of the diffuse type is derived from the ECL cell. Furthermore, the ECL cell may, by producing substances with angiogenic effects (histamine and basic fibroblast growth factor), be particularly prone to develop malignant tumors. Although the general opinion is that gastrin itself has a direct effect on the oxyntic mucosal stem cell, it cannot be excluded that the general trophic effect of gastrin on the oxyntic mucosa is mediated by histamine or other substances from the ECL cell, and that the ECL cell, therefore, could play a role also in the tumorigenesis/carcinogenesis of gastric carcinomas of intestinal type.
Waldum, H. L.; Brenna, E.; Sandvik, A. K.
The aim of this study was to detect numerical chromosomal aberrations that may be involved in the progression of cervical intraepithelial neoplasia (CIN) toward cervical carcinoma. Therefore, cervical lesions (five CIN 1, seven CIN 2, six CIN 3, six invasive carcinomas, and six normal samples) were studied by in situ hybridization (ISH) on serial 3-microm-thick paraffin tissue sections, using a panel of eight centromeric DNA probes for chromosomes 1, 3, 6, 7, 8, 11, 17, and X. An estimation of the percentage of dysplastic epithelium with abnormal ISH signals per nucleus was made. Chromosome aneusomy could be detected in all persisting and high-grade CIN lesions and invasive carcinomas. In most cases, when one of the chromosomes showed aneusomy then all studied chromosomes showed numerical changes. Interestingly, the abnormal ISH signals were found only in a varying part of the morphologically dysplastic epithelium, the remainder showing no such changes. In aneuploid regions of the CIN 1 lesions the mean chromosome index for all chromosomes was 1.97+/-0.03 with a range of 1.92 to 2.00. The chromosome index ratios of chromosomes 1, 7, and X showed a significant positive correlation with CIN grade (r > or = 0.74; P < or = 0.006). It is concluded that chromosome aneusomy of chromosomes 1, 7, and X may be involved in the progression of CIN lesions. Images Figure 1 Figure 2
Bulten, J.; Poddighe, P. J.; Robben, J. C.; Gemmink, J. H.; de Wilde, P. C.; Hanselaar, A. G.
Background Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions. Methods Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008). Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend. Results We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4%) that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%). Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2%) as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p < 0.03) of a higher frequency of invasive carcinomas that were concomitant with lobular carcinoma in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular hyperplasia cases. Conclusions Our findings confirm a frequent association between lobular neoplasia and columnar cell lesions, the majority of which lacked atypia. We also observed a greater frequency of invasive carcinoma, more commonly invasive lobular carcinoma, associated with more developed forms of lobular neoplasia (lobular carcinoma in situ).
This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case recurred and one developed invasive cancer. PMID:23599160
Woo, Sook-Bin; Cashman, Emma C; Lerman, Mark A
Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few reports have documented invasive SCC or SCC in situ (intraepithelial neoplasia, IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC, in some organs. However, case series of pigmented SCC or IEN of the esophagus have not yet been reported. This is the first study to analyze the incidence and clinicopathological features of pigmented SCC or IEN of the esophagus. We reviewed 18 surgically-resected and 122 endoscopically-resected esophageal specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed in this series, and all of them were located in the middle to lower third of the esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous epithelium around the IEN. The incidence of pigmented IEN was 2.5% of all endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive SCC was detected in both endoscopically-resected and surgically-resected specimens. The mechanism of pigmentation of esophageal IEN is unknown. However, production of melanocyte chemotactic factors by tumor cells has been demonstrated in pigmented SCC of the oral mucosa. Moreover, two of 3 cases of pigmented IEN in the present series had melanocytosis in the non-neoplastic squamous epithelium, and melanocytosis is thought to be associated with chronic esophagitis, therefore, it has been hypothesized that various stimuli can cause pigmentation in squamous epithelium. Additional studies are needed to clarify the mechanism of pigmentation in squamous IEN of the esophagus.
Ishida, Mitsuaki; Mochizuki, Yosuke; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Okabe, Hidetoshi
We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.
Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl? clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl? clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl? clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl? clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl? clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of “cells-of-origin” in epithelial cancers, namely their propensity for switch to primitive cell states.
Khan, Sumbul J.; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P.; Harsh, Sneh; Pandey, Ravi K.; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip
Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl(-) clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl(-) clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl(-) clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl(-) clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl(-) clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of "cells-of-origin" in epithelial cancers, namely their propensity for switch to primitive cell states. PMID:23708122
Khan, Sumbul J; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P; Harsh, Sneh; Pandey, Ravi K; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip
Objectives. To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism.Methods. Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who
Daniel S Engeler; Paul O Hösli; Hubert John; Fridolin Bannwart; Tullio Sulser; Mahul B Amin; Philipp U Heitz; Seife Hailemariam
Summary Conjunctival intraepithelial neoplasia (CIN) are considered to be the third most common ocular tumour and the most common tumour of the ocular surface. Due to their malignant potential, they must be carefully differentially and promptly treated. A recurrence rate of approximately 30% leads to the need for monitoring of patients even after successful treatment. This article presents several cases
Andrew Jaworski; James S. Wolffsohn; Genevieve A. Napper
Lobular neoplasia has been traditionally recognized as a marker of increased risk for subsequent breast carcinoma development; however, molecular studies suggest that it also behaves in a non-obligate precursor manner. We do not know, as yet, how to identify the subgroup of cases that is most likely to progress, but the epidemiological data would indicate that this progression occurs after
Frances P O'Malley
Lobular neoplasia has been traditionally recognized as a marker of increased risk for subsequent breast carcinoma development; however, molecular studies suggest that it also behaves in a non-obligate precursor manner. We do not know, as yet, how to identify the subgroup of cases that is most likely to progress, but the epidemiological data would indicate that this progression occurs after a long period of time. Thus, the current approach of conservative management of these lesions when identified in excision specimens is justified. Recently, several variants of lobular carcinoma in situ (LCIS), most notably pleomorphic LCIS, have been recognized and these can be difficult to differentiate from ductal carcinoma in situ. Application of strict diagnostic criteria and the judicial use of immunohistochemistry, particularly E-cadherin, can be helpful in this differential diagnosis. Another challenging issue is the management of lobular neoplasia when diagnosed on core biopsy. This controversial issue will be discussed in detail. The goals of this review are (1) to describe the morphological criteria used to diagnose the spectrum of lobular neoplastic lesions, including atypical lobular hyperplasia, LCIS and variants of LCIS; (2) to discuss the data exploring the biological potential of lobular neoplasia from an epidemiological and molecular viewpoint; and (3) to outline the recommendations for management of lobular neoplasia when encountered in core biopsies. PMID:20436498
O'Malley, Frances P
background Veterans Affairs (VA) Cooperative Study 380 showed that some advanced colorectal neoplasias (i.e., adenomas at least 1 cm in diameter, villous adenomas, adenomas with high-grade dysplasia, or cancer) in men would be missed with the use of flexible sig- moidoscopy but detected by colonoscopy. In a tandem study, we examined the yield of screening colonoscopy in women. methods To
Philip Schoenfeld; Brooks Cash; Andrew Flood; Richard Dobhan; John Eastone; Walter Coyle; James W. Kikendall; Hyungjin Myra Kim; David G. Weiss; Theresa Emory; Arthur Schatzkin; David Lieberman
Attention is focusing on testing and developing computer aided detection (CAD) systems to reliably highlight flat polyps and cancers to the reporting radiologist during CT colonography. This review will discuss the clinical relevance of flat colonic neoplasia, describe some of the challenges facing CAD detection algorithms, and review the current CAD literature on this topic. PMID:18511995
Taylor, Stuart A; Suzuki, Noriko; Beddoe, Gareth; Halligan, Steve
Sonographically detected testicular microlithiasis is an uncommon condition, which in recent years has been demonstrated with increased prevalence in patients with testicular tumors. We report a case of a 31-year old man with left testicular carcinoma and right intratubular germ cell neoplasia diagnosed by biopsy of the right testis at the time of left radical orchiectomy. In this case, preoperative
Brett L. Parra; Dennis D. Venable; Enrique Gonzalez; James A. Eastham
Evidence regarding a causal relationship between bacterial vaginosis and cervical intraepithelial neoplasia has so far been incomplete and conflicting. To determine whether bacterial vaginosis is associated with cervical intraepithelial neoplasia a retrospective study was conducted at the Genitourinary Medicine Clinic at Southlands Hospital, Shoreham-by-Sea, UK. Three hundred patients who presented to the clinic with a first diagnosis of genital warts in the absence of other sexually transmitted diseases were recruited. Results of cervical cytology and where abnormal, histology on colposcopically directed punch biopsies were collected. Bacterial vaginosis was diagnosed by the detection of clue cells on Gram-staining of a high vaginal swab, positive amine test, vaginal pH above 4.5 and the presence of characteristic vaginal discharge. Odds ratio showed an increased prevalence of cervical intraepithelial neoplasia associated with bacterial vaginosis. The results suggest that a prospective cross sectional study should be performed to formally test the hypothesis that bacterial vaginosis predisposes to cervical intraepithelial neoplasia. PMID:15512183
Uthayakumar, S; Boyle, D C; Barton, S E; Nayagam, A T; Smith, J R
A hyperspectral imaging system using a liquid-crystal tunable filter (LCTF) was constructed for the purpose of in vivo optical imaging of oral neoplasia. The system operates in fluorescence mode and has the dual capability of capturing high quality widefield images and detecting fluorescence emission spectra from arbitrary locations within the captured field of view (FOV). The system was calibrated and
Darren Roblyer; Cristina Kurachi; Ann M. Gillenwater; Rebecca Richards-Kortum
Cervical carcinoma and cervical intra-epithelial neoplasia (CIN) are likely to be associated with all sexually transmitted diseases (STDs). To help discover which (if any) of the recognised STDs might actually cause these conditions, a key question is whether one particular such association is much stronger than the others. The present study is therefore only of women newly attending an STD
S Franceschi; R Doll; J Gallwey; C La Vecchia; R Peto; A I Spriggs
Whilst there is strong evidence that human papillomavirus (HPV) is the principal aetiological agent in cervical neoplasia, some other sexually transmitted agents may either contribute or protect against cervical carcinogenesis, such as the herpes virus family (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) or Chlamydia trachomatis (CT). Epidemiological studies suggest that HSV may have a role in
Wael I Al-Daraji; John HF Smith
Six multiple endocrine neoplasia (MEN) syndromes have received a level of attention that might seem disproportionate to their low prevalence. The attention has been given because their hormonal excesses cause striking metabolic expressions and because they might clarify pathways disrupted in more common tumours. The recent discovery of the main gene in each MEN syndrome has furthered our understanding of
Stephen J. Marx
Methods of delivering an agent in a tissue-specific manner, by targeting annexin A1, a derivative of annexin A1, or a binding partner of annexin A1, are described. The methods can be used for detecting, imaging and/or treating neoplasia, angiogenesis or n...
J. E. Schnitzer P. Oh
A retrospective study of neoplasia in reptiles held at the Philadelphia Zoological Garden was conducted. A total of 3,684 original necropsy reports for the period 1901-2002 were reviewed and revealed 86 cases of neoplasia. Original glass slides or re-cuts from paraffin-embedded tissue blocks were examined for confirmation of the original diagnosis. At necropsy, a total of six neoplasms were identified in six of 490 chelonians (1.2%), 22 neoplasms in 19 of 736 lizards (3.0%), and 58 neoplasms in 53 of 1,835 snakes (2.9%). An additional 12 neoplasms were found in biopsies of one turtle and 10 snakes. In the chelonians, all the neoplasms were seen in turtles, four of six tumors were malignant (66%) and no organ predilection was noted. For lizards, the liver was the most commonly affected organ, with 7 of 22 primary neoplasms (31%). Multiple tumor types were identified in three lizards (15%), metastasis occurred in five cases (25%), and malignant tumors were identified in 16 cases (73%). In snakes, the liver was most frequently affected by neoplasia at necropsy, with 13 of 58 primary neoplasms (22%); multiple types of neoplasm were identified in five cases (10%) and metastasis in six (9%); and 42 tumors (80%) were diagnosed as malignant. When biopsies were included for snakes, however, the skin was the most commonly affected organ, with 17 of 69 neoplasms (24%). One of five lizards (20%) and four of six snakes (66%) with metastasis also had a second primary neoplasm. Since 1967, the incidence of lizard neoplasia has increased from 0.7% to 5.9%, and snake neoplasia has increased from 2.6% to 9.3%. PMID:17312806
Sykes, John M; Trupkiewicz, John G
Background The consistent association between obesity and colorectal cancer is thought to be explained by metabolic disturbances common, but not exclusive, to the obese. Methods We assessed the relation between metachronous neoplasia and the components of metabolic syndrome (MetS) as defined by the National Cholesterol Education Program’s Adult Treatment Panel III in 2,392 participants of two previously conducted chemoprevention trials. Waist circumference, fasting plasma glucose, trigylcerides, high-density lipoprotein, and systolic and diastolic blood pressure were measured at baseline. Results MetS classification was associated with increased odds of metachronous neoplasia among women [odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.01–1.85] but not among men (OR, 0.99; 95% CI, 0.81–1.21). High waist circumference in men (OR, 1.41; 95% CI, 1.15–1.72) and women (OR, 1.41; 95% CI, 1.05–1.90) and elevated fasting glucose in women (OR, 1.46; 95% CI, 1.09–1.96), as defined by Adult Treatment Panel III cutpoints, were associated with increased odds, whereas none of the other criteria were independently associated with metachronous neoplasia. When each trait was evaluated using quartiles, elevated glucose among women and large waist circumference among men were significantly associated with metachronous lesions. Exploratory analysis of waist circumference and fasting glucose suggested an interaction, where only the combination of large waist circumference and elevated glucose conferred significant increased odds of metachronous neoplasia among both men (OR, 1.36; 95% CI, 1.04–1.78; Pinteraction = 0.08) and women (OR, 1.83; 95% CI, 1.26–2.67; Pinteraction = 0.12). Conclusions These results suggest that, of the specific components of MetS, those that capture impaired glucose uptake increased the odds of metachronous neoplasia.
Ashbeck, Erin L.; Jacobs, Elizabeth T.; Martinez, Maria Elena; Gerner, Eugene W.; Lance, Peter; Thompson, Patricia A.
There are approximately one million new cases of colorectal cancer (CRC) per year worldwide, with substantial associated morbidity and mortality. The long natural history of colorectal neoplasia affords the opportunity to use preventive measures to improve survival in this disease. Currently screening for adenomatous polyps and early-stage cancers is the best methodology for improving survival. The increasing knowledge of CRC pathogenesis and its natural history is allowing the development of new tools to identify patients who will benefit most from colon cancer screening and the defining of appropriate surveillance intervals. The guidelines for screening for colorectal neoplasia have recently been substantially revised by several organizations based on developing technologies and a growing body of data on the efficacy of CRC screening.
Composite tumors of the adrenal medulla are rare and have been reported in both the presence and the absence of phacomatosis. Composite pheochromocytoma of the adrenal gland in multiple endocrine neoplasia 2B has not been reported so far. We report a case of a 27-year-old woman with marfanoid habitus and numerous mucosal neuromas of the oral cavity and the eyelids. Clinical investigations revealed a left adrenal medullary tumor and bilateral thyroid nodules. Histologic examination confirmed the presence of typical pheochromocytoma with large areas of ganglioneuroma and multifocal medullary carcinoma with cervical lymph nodes metastases. Our report is the first to describe composite pheochromocytoma with multiple endocrine neoplasia 2B; this report underlines the diversity of neoplasms that could be encountered in this disease and the complex mechanisms involved in its pathogenesis. PMID:18706367
Charfi, Slim; Ayadi, Lobna; Ellouze, Sameh; Ghorbel, Raoudha; Khabir, Abdelmajid; Gouiaa, Naourez; Bahri, Ibticem; Fakhfakh, Ines; Makni, Salwa; Sellami-Boudawra, Tahya
Multiple endocrine neoplasia (MEN) refers to the synchronous or metachronous development of tumours in two or more endocrine organs. MEN 2B is associated with medullary thyroid carcinoma and phaeochromocytoma along with classic morphological features such as marfanoid habitus and mucosal neuromas. Dominantly inherited germline mutations involving the REarranged during Transfection (RET) proto-oncogene are responsible. Affected patients usually present in childhood with thyroid mass or gastrointestinal symptoms. We describe the case of a 28-year-old man who presented to us with metastatic medullary thyroid carcinoma. He lacked the classic marfanoid habitus, but had mucosal neuromas and thickened corneal nerves. Whole-body metaiodobenzyl guanidine scan (MIBG) showed tracer uptake in adrenal and thyroid-confirming phaeochromocytoma and medullary thyroid carcinoma. This case exemplifies the late presentation of multiple endocrine neoplasia 2B and emphasises the need to screen all cases of medullary thyroid carcinoma for phaeochromocytoma. PMID:23645647
Balachandran, Karthik; Kamalanathan, Sadishkumar; Gopalakrishnan, S; Murugananadham, K
Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, the authors had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development. 28 refs., 2 figs.
Brandi, M.L.; Falchetti, A.; Tonelli, F. (Univ. of Florence (Italy)); Weber, G.; Svensson, A.; Larsson, C. (Karolinska Hospital, Stockholm (Sweden)); Castello, R.; Furlani, L.; Scappaticci, S.; Fraccaro, M.
A hyperspectral imaging system using a liquid-crystal tunable filter (LCTF) was constructed for the purpose of in vivo optical imaging of oral neoplasia. The system operates in fluorescence mode and has the dual capability of capturing high quality widefield images and detecting fluorescence emission spectra from arbitrary locations within the captured field of view (FOV). The system was calibrated and evaluated for spectral resolution and accuracy. In vivo hyperspectral images were obtained from two normal volunteers and two patients with confirmed oral malignancy. Normal volunteer measurements revealed differences in intensity and lineshape of spectra between different anatomic locations, but intensity and lineshape were similar between different measurement sites from the same anatomic location. Measurements from normal and neoplastic areas of two patients with previously confirmed oral neoplasia showed differences in intensity, lineshape, and location of peak intensity. We have demonstrated that this system can provide both high quality widefield images, and spectral information at chosen locations within the field of view.
Roblyer, Darren; Kurachi, Cristina; Gillenwater, Ann M.; Richards-Kortum, Rebecca
Anal cancer is a rare malignancy of the distal gastrointestinal tract, often associated with human papillomavirus, the most common sexually transmitted infection worldwide. Currently available screening methods for anal intraepithelial neoplasia, a precursor for anal cancer, combine anal Papanicolaou cytology and high resolution anoscopy with biopsy of suspicious lesions. Significant barriers to establishing anal cancer screening programmes include the small number of healthcare professionals performing high resolution anoscopy and the lack of data showing that anal cancer screening can reduce morbidity and mortality related to anal carcinoma. Despite several controversies surrounding anal cancer screening, the rising incidence of this disease in some groups supports routine screening programmes in high-risk populations, especially in HIV-positive men who have sex with men. This review outlines the epidemiology of anal intraepithelial neoplasia and anal cancer and summarizes issues related to the introduction of anal cancer screening programmes. PMID:23970583
Smyczek, Petra; Singh, Ameeta E; Romanowski, Barbara
AIMS: To determine the pattern of c-myc oncogene expression in anal squamous neoplasia and to determine if this could be used as a marker of disease progression. METHODS: The presence and localisation of the c-myc gene product p62 in archival specimens of anal squamous epithelium, normal and neoplastic, was examined using immunohistochemical staining with the monoclonal antibody Myc1-6E10. Ten normal
O A Ogunbiyi; J H Scholefield; K Rogers; F Sharp; J H Smith; S V Polacarz
Epidemiological and virological evidence suggests that invasive squamous cell carcinoma (SCC) of the vulva is etiologically heterogeneous and that basaloid or warty SCC (BWSCC) and vulvar intraepithelial neoplasia (VIN) are linked to human papillomavirus (HPV) infections while keratinizing SCC (KSCC) is a non-HPV-associated malignancy. In the present study, HPV-specific antibodies in sera of patients with BWSCC, VIN, and KSCC and
Yeping Sun; Allan Hildesheim; Louise A. Brinton; Philip C. Nasca; Cornelia L. Trimble; Robert J. Kurman; Raphael P. Viscidi; Keerti V. Shah
Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was
Tse-Ching Chen; Yasuni Nakanuma; Yoh Zen; Miin-Fu Chen; Yi-Yin Jan; Ta-Sen Yeh; Cheng Tang-Chiu; Tseng-Tong Kuo; Jun-ichi Kamiya; Koji Oda; Michinari Hamaguchi; Yoshiyuki Ohno; Ling-Ling Hsieh; Yuji Nimura
The role of human papillomaviruses (HPVs) in the development of genital neoplasias has been well documented1-5. The genomes of two HPV types, HPV16 and HPV18, have been found to be associated with about 70% of invasive carcinomas of the uterine cervix2,4,6. As, under non-stringent hybridization conditions, HPV DNA sequences have been detected in about 90% of cervical carcinomas4,6, it seems
Sylvie Beaudenon; Dina Kremsdorf; Odile Croissant; Stefania Jablonska; Simon Wain-Hobson; Gérard Orth
This case report describes for the first time a case of pure testicular carcinoid preaortic lymph node metastases in a 25 year old patient with carcinoid syndrome. The simultaneous occurrence of intratubular germ cell neoplasia in the surrounding testicular tissue was identified by OCT4 and placental-like alkaline phosphatase positivity. This confirmed that the tumour had a germ cell origin in the testis, rather than being a metastasis from an extragenital carcinoid.
Merino, J; Zuluaga, A; Gutierrez-Tejero, F; del Mar Serrano, M; Ciani, S; Nogales, F F
Mutation of LKB1 is the key molecular event underlying Peutz-Jeghers syndrome, a dominantly inherited condition characterized by a predisposition to a range of malignancies, including those of the reproductive system. We report here the use of a Cre-LoxP strategy to directly address the role of Lkb1 in prostate neoplasia. Recombination of a LoxP-flanked Lkb1 allele within all four murine prostate
Helen B. Pearson; Afshan McCarthy; Christopher M. P. Collins; Alan Ashworth; Alan R. Clarke
Summary A routine biopsy of the contralateral testis obtained during orchiectomy for embryonal carcinoma in a 26-year-old patient was negative for testicular intraepithelial neoplasia (TIN; carcinoma in situ of the testis). However, a rebiopsy that was taken because of unexplained elevation of a-fetoprotein 15 months later proved to be positive for TIN. Six previously reported cases of false-negative testicular biopsies
K-P Dieckmann; F. Kaup; V. Loy
Intestinal neoplasia (adenomas and carcinomas) can possibly be prevented by a diet rich in vegetables and fruits, treatment\\u000a with aspirin and other nonsteroidal antiinflammatory drugs, and early colonoscopic removal of adenomas. Ballast, fiber, and\\u000a secondary plant products could play a major role in colon cancer prevention. Recently there has been much experimental work\\u000a in vitro and in vivo about flavonoids
Harald P. Hoensch; Wilhelm Kirch
Background The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). Methods We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG2a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508). Results p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7). Conclusion Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence.
Terry, Mary Beth; Neugut, Alfred I; Mansukhani, Mahesh; Waye, Jerome; Harpaz, Noam; Hibshoosh, Hanina
Multiple endocrine neoplasias (MEN) are autosomal dominant disorders characterized by the occurrence of tumors in at least two endocrine glands. Two types of MEN syndromes have long been known: MEN type 1 (MEN1) and MEN type 2 (MEN2), associated with a different spectrum of affected organs. MEN1 and MEN2 are caused by germline mutations in the MEN1 tumor suppressor gene
Ilaria Marinoni; Natalia S. Pellegata
Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1-related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.
Lourenco, Delmar M; Coutinho, Flavia L.; Toledo, Rodrigo A.; Goncalves, Tatiana Denck; Montenegro, Fabio L. M.; Toledo, Sergio P. A.
Human papillomavirus (HPV) is a common sexually transmitted pathogen. Although most anogenital HPV infections resolve within several years, persistent infection may lead to neoplasia of the cervix, vagina, vulva, anus, and penis, and also genital warts. High-risk HPV types 16 and 18 are known to cause approximately 70% of all cervical cancers, and low-risk HPV types 6 and 11 are the main causes of genital warts. Prophylactic HPV vaccines have the potential to block the acquisition of HPV and hence subsequent development of anogenital neoplasia. Results from several clinical trials have demonstrated that the HPV L1 virus-like-particle vaccines are safe and highly immunogenic. These trials have documented a 100% vaccine efficacy in prevention of persistent HPV infection and, more important, of HPV-associated anogenital neoplasia in per-protocol analyses. Widespread vaccination of sexually naďve preadolescent children could substantially reduce the morbidity and mortality associated with anogenital malignancies. Furthermore, such a primary prevention program would also reduce healthcare costs. PMID:16729555
Ferris, Daron G
The Authors report the case of a 60-year-old man, V.A., a smoker with type II diabetes and cholelithiasis. One month after the onset of symptoms in March 1995, his clinical picture led us to suspect a pancreatic adenocarcinoma. Only 110 days after the initial discovery of a high CA 19-9, following the failure of numerous techniques and the solution of various problems of differential diagnosis, the first unclear X-ray image of a suspected pancreatic neoplasia was obtained. A new computed tomography scan and a further increase in CA 19-9 later confirmed the diagnosis. Duodenopancreatectomy with splenectomy for adenocarcinoma was performed. The thread connecting 150 days of clinical history is CA 19-9, which acted as an ideal marker. It enabled a clinical "rarity" (pancreatic neoplasia in its initial stages) to be diagnosed and it increased as the neoplasia developed. After surgical removal of the tumor, the marker is now returning to normal levels and will be used to monitor the post-operative phase, when any increase in level could mean a recrudescence of the disease. PMID:8799421
Boldrini, E; Cristani, A; Cioni, G; Roccato, S; De Santis, M; Bonilauri, S; Berselli, T; Melotti, G
In contrast with solid tumors, most of which are invasive ductal adenocarcinoma with dismal prognosis, cystic lesions of the pancreas are often either benign or low-grade indolent neoplasia. Those that are mucinous, namely, intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), constitute the most important category, not only because they are the most common, but more importantly because they have well-established malignant potential, representing an adenomacarcinoma sequence. While many are innocuous adenomas--in particular, those that are small and less complex, and in the case of IPMN, those that are branch-duct type are more commonly benign, some harbor or progress into in situ or invasive carcinomas. For this reason, pancreatic cysts with mucinous differentiation ought to be evaluated carefully, preferably by experts familiar with subtle evidences of malignancy in these tumors. In the past few years, the definition of IPMNs and MCNs has become more refined. The presence of ovarian-type stroma has now almost become a requirement for the diagnosis of MCN, and when defined as such, MCN is seen almost exclusively in women of perimenopausal age group as thick-walled multilocular cystic mass in the tail of the pancreas in contrast with IPMN which afflicts an elder population, both genders in almost equal numbers, and occur predominantly in the head of the organ. While mucinous lesions have well-established pre-malignant properties, most of the entities that fall into the nonmucinous true cyst category such as serous tumors, lymphoepithelial cysts, congenital cysts, and squamoid cyst of ducts have virtually no malignant potential. In contrast, the rare cystic tumors that occur as a result of degenerative/necrotic changes in otherwise solid neoplasia such as the rare cystic ductal adenocarcinomas, cystic endocrine neoplasia, and most importantly, solid-pseudopapillary tumor (SPT) in which cystic change is so common that it used to be incorporated into its name ("solid-cystic," "papillary-cystic") are malignant neoplasia, albeit variable degrees of aggressiveness. SPT holds a distinctive place among pancreatic neoplasia because of its highly peculiar characteristics, undetermined cell lineage, occurrence almost exclusively in young females, association with beta-catenin pathway, and also by being a very low-grade curable malignancy. In conclusion, cystic lesions in the pancreas constitute a biologically and pathologically diverse category most (but not all) of which are either benign or treatable diseases; however, a substantial subset, especially mucinous ones, has malignant potential that requires careful analysis. PMID:17957438
Adsay, N Volkan
Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer. Previous studies indicated that photodynamic therapy (PDT) represents an effective treatment modality in CIN. In 28 patients with CIN 1 - 3, 1 - 2 cycles of PDT were conducted using hexaminolevulinate (HAL) or methylaminolevulinate (MAL) and a special light delivery system. After 6 months, biopsies were obtained to assess response. The overall response rate for complete or partial response was 65%. Photodynamic therapy using new ALA esters is effective and may offer unique advantages in the therapy of CIN.
Soergel, Philipp; Staboulidou, Ismini; Hertel, Herrmann; Schippert, Cordula; Hillemanns, Peter
Vulvar intraepithelial neoplasia (VIN) is the currently accepted generic designation for the spectrum of vulvar lesions with the histologic features of squamous dysplasia and squamous cell carcinoma in situ. Although several classifications of VIN have been espoused in the past 20 years, VIN can be readily classified into two principal clinicopathologic types: classic (bowenoid) VIN and simplex (differentiated) VIN. This manuscript summarizes the historical development and current status of our knowledge about VIN. Information on the clinical and pathologic aspects are detailed and illustrated, as are considerations of differential diagnosis. PMID:11192069
Hart, W R
A need exists to characterize the various grades of cervical intrapithelial neoplasia (CIN), and attempt to differentiate between high- and low-grade lesions, that may have different behavioral and progressive potentials. The identification of patients with high- or low-grade CIN is useful, as it may allow identification of those patients that have true cancer precursors. Fifty patients referred for colposcopy with abnormal cytology were studied. Univariate analysis identified three factors as important predictors of histologic grade; the colposcopic opinion, lesion surface area and the index cytology (P < 0.005). Colposcopic opinion was associated with the index cytology (P < 0.01) and the lesion surface area (P < 0.005). Only the colposcopic opinion and the index cytologic smear appeared in the final model using a stepwise logistic regression analysis, indicating their independent prognostic importance in prediction of grade of abnormality in cervical intraepithelial neoplasia. The study demonstrates the value of colposcopic training and experience being necessary prior to utilizing excisional treatment methods if overtreatment is to be avoided. PMID:11578346
Shafi, M.I.; Dunn, J.A.; Finn, C.B.; Kehoe, S.; Buxton, E.J.; Jordan, J.A.; Luesley, D.M.
Lobular neoplasia of the breast represents a group of related malignancies with clinical implications ranging from risk lesions [atypical lobular hyperplasia and lobular carcinoma in situ (LCIS)] through to aggressive invasive lesions, notably invasive pleomorphic lobular carcinoma. The diversity in lobular carcinoma is evident at the morphological level, at the molecular marker level and in cytogenetic profiles. Research in these areas is already changing the face of the disease group, for example suggesting that some lobular and ductal carcinomas are closely related and even that one of the lobular group, the tubulo-lobular carcinomas, should, in fact, be regarded as a ductal cancer. More research is required to understand the long-term pathogenic implications of a diagnosis of in situ lobular neoplasia, particularly pleomorphic LCIS, and to understand the genetics behind the well-recognized high risk of bilateral disease. For invasive carcinoma, molecular studies will allow refinement of therapy and the possibility of novel targeted therapies, for example directed against fibroblast growth factor receptor 1. PMID:18171417
Hanby, A M; Hughes, T A
No adequate means exist to identify the minority of ulcerative colitis (UC) patients destined to undergo neoplastic progression. Recognition of this subset would advance UC cancer surveillance by focusing the available management options onto the highest risk patients. Three different assays of genomic alterations in nondysplastic UC biopsies show promise for distinguishing patients with neoplasia (UC progressors) from those without (UC nonprogressors), including assays of telomere length, anaphase bridges, and chromosomal fluorescence in situ hybridization. Expanding the number of patients and testing of assays simultaneously in the same biopsy further validated their utility. A panel approach also improved testing outcome. A total of 14 UC progressors was readily separable from 15 UC nonprogressors and 6 normal controls. Chromosomal entropy (ie, the extent of alteration diversity) proved to be the most useful test. By receiver-operating characteristic analysis, mean chromosomal entropy in 28 patients over all four chromosomes yielded 100% sensitivity and 92% specificity for distinguishing progressors from nonprogressors with optimum choice of threshold. Moreover, separation was achieved using only nondysplastic and predominantly rectal (82.8%) biopsies that were remote from neoplasia, suggesting that full colonoscopy with extensive biopsies might be avoided for the majority of UC patients, the nonprogressors. These data further strengthen the concept that genomic biomarkers can distinguish UC progressors from nonprogressors and improve cancer surveillance in UC.
Bronner, Mary P.; O'Sullivan, Jacintha N.; Rabinovitch, Peter S.; Crispin, David A.; Chen, Lu; Emond, Mary J.; Rubin, Cyrus E.; Brentnall, Teresa A.
This report describes multiple endocrine neoplasia in a dog, which is a rare hereditary disorder characterized by the presence of two or more neoplasms of different endocrine tissues within a patient. A 14 yr old dog was evaluated for polyuria/polydipsia, polyphagia, and abdominal enlargement. Adrenal-dependent hyperadrenocorticism with concomitant left thyroid enlargement and a presumed abdominal metastatic lesion were diagnosed by an adrenocorticotropic hormone stimulation test, ultrasonography, and computed tomography. Trilostane therapy was initiated and resolved the clinical signs for 2 yr at which time the dog presented with left testicular enlargement. The dog was euthanized and was diagnosed with adrenocortical carcinoma, thyroid carcinoma, an abdominal mass compatible with a metastatic lymph node, and bilateral interstitial cell testicular adenomas. To the authors' knowledge, this is the first report to describe the concomitant association of these types of endocrine neoplasms in a dog. The concomitant presence of these neoplasms could represent a potential variant of multiple endocrine neoplasia; however, the presence of the interstitial cell testicular adenomas may have only been an incidental finding. If any of these tumors are diagnosed, veterinarians should perform a thorough clinical assessment to evaluate for the presence of additional endocrine neoplasms or hyperplasia. PMID:22267170
Proverbio, Daniela; Spada, Eva; Perego, Roberta; Grieco, Valeria; Lodi, Matteo; Di Giancamillo, Mauro; Ferro, Elisabetta
Twenty two patients referred to a district colposcopy clinic because of an abnormal cervical cytology report or a suspicious cervix and found to have a cervical epithelial abnormality were studied. The techniques of cytology, histology, immunohistochemistry, and DNA-DNA hybridisation were used to detect infection by human papillomavirus. Using an indirect immunoalkaline phosphatase technique human papillomavirus antigen was found in biopsy specimens from six of the 22 patients and DNA of papillomavirus type 6 in biopsy specimens from 13 of these women, including four out of six whose histological diagnosis was cervical intraepithelial neoplasia grade 3. In eight cases where cytological, colposcopical, and histological investigations all indicated the presence of wart virus infection, papillomavirus type 6 DNA was found in seven. Papillomavirus type 6 DNA was found in more than half of the proved cases of cervical intraepithelial neoplasia. The presence of this viral DNA in women with no cervical abnormality is to be studied. Images FIG 1 FIG 2 FIG 3 FIG 4 (a) FIG 4 (b)
McCance, D J; Walker, P G; Dyson, J L; Coleman, D V; Singer, A
Cyclooxygenase-2 (COX-2) has been implicated in the development of gastrointestinal malignancies. The aim of the present study was to determine COX-2 expression/activity throughout stages of experimental and human pancreatic neoplasia. COX-2 immunohistochemistry was performed in pancreata of hamsters subjected to the carcinogen N-nitrosobis-(2-oxopropyl)amine (BOP) and in human pancreatic tumors. COX-2 activity was determined by prostaglandin E2 assay in tumor versus matched normal pancreatic tissues. The activity of the COX inhibitor sulindac was tested in the PC-1 hamster pancreatic cancer model. COX-2 expression was elevated in all pancreatic intraepithelial neoplasias (PanINs) and adenocarcinomas. In BOP-treated hamsters, there were significant progressive elevations in COX-2 expression throughout pancreatic tumorigenesis. In human samples, peak COX-2 expression occurred in PanIN2 lesions and remained moderately elevated in PanIN3 and adenocarcinoma tissues. COX-2 activity was significantly elevated in hamster and human pancreatic cancers compared to pair-matched normal pancreas. Furthermore, hamster pancreatic tumor engraftment/formation in the PC-1 hamster pancreatic cancer model was reduced 4.9-fold by oral administration of sulindac. Increased COX-2 expression is an early event in pancreatic carcinogeneses. The BOP-induced hamster carcinogenesis model is a representative model used to study the role of COX-2 in well-differentiated pancreatic tumorigenesis. COX inhibitors may have a role in preventing tumor engraftment/formation. PMID:16820089
Crowell, Pamela L; Schmidt, C Max; Yip-Schneider, Michele T; Savage, Jesse J; Hertzler, Dean A; Cummings, William O
The prognosis of oesophageal neoplasia is dependent on the stage of the disease at the time of detection. Early lesions have an excellent prognosis in contrast to more advanced stages that usually have a dismal prognosis. Therefore, the early detection of these lesions is of the utmost importance. In recent years, several new techniques have been introduced to improve the endoscopic detection of early lesions. The most important improvement, in general, has been the introduction of high-resolution/high-definition endoscopy into daily clinical practice. The value of superimposing techniques such as chromoendoscopy, narrow band imaging and computed virtual chromoendoscopy onto high-resolution/high-definition endoscopy will have to be proven in randomised cross-over trials comparing these techniques with standard techniques. Important future adjuncts to white-light endoscopy serving as 'red-flag' techniques for the detection of early neoplasia may be broad field functional imaging techniques such as video autofluorescence endoscopy. In addition, real-time histopathology during endoscopy has become possible with endocytoscopy and confocal endomicroscopy. The clinical value of these techniques needs to be ascertained in the coming years. PMID:18656825
Curvers, W L; Kiesslich, R; Bergman, J J G H M
The distinction between lobular neoplasia and infiltrating lobular carcinoma from ductal neoplasia and infiltrating duct carcinoma with equivocal histologic features may present a challenge as this distinction has important therapeutic implications. Although E-cadherin staining has been of value in helping to make this determination, the variability of the E-cadherin staining pattern and the immunohistochemistry techniques can be problematic in clinical
Young J Choi; Marguerite M Pinto; Liming Hao; Ali K Riba
OBJECTIVES:Stool testing is a well established method of screening for colorectal neoplasia. Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood. In this large, prospective study, we assessed fecal calprotectin (a leukocyte-derived protein) as a screening biomarker for colorectal neoplasia. Fecal calprotectin was directly compared to fecal hemoglobin (Hb) and colonoscopy as the existing criterion
Paul J. Limburg; Mary E. Devens; Jonathan J. Harrington; Nancy N. Diehl; Douglas W. Mahoney; David A. Ahlquist
The existence of cervical neoplasia in women with human immunodeficiency virus (HIV) represents one of the most serious challenges in the oncologic care of immunosup- pressed patients. While the development of most cancers in the immunosuppressed patient can be attributed solely to immune deficiency, the relationship between squamous cell neoplasia of the cervix and HIV is quite unique because of
Background: Most patients from typical multiple endocrine neoplasia type 1 (MEN 1) kindreds harbor mutations in the MEN-1 gene, MEN1. We hypothesized that some patients with atypical endocrine neoplasia would also have mutations in MEN1. Methods: DNA sequencing analysis of mutations in the coding region of MEN1 was performed with genomic DNA obtained from peripheral blood lymphocytes in a total
Alan P. B. Dackiw; Gilbert J. Cote; Jason B. Fleming; Pamela N. Schultz; Pamela Stanford; Rena Vassilopoulou-Sellin; Douglas B. Evans; Robert F. Gagel; Jeffrey E. Lee
Introduction. Our objective was to determine if prothymosin-?, a marker for gastric metaplasia previously identified in a Helicobacter-induced gastric metaplasia and neoplasia mouse model, shows significant up regulation in human gastric metaplasia and neoplasia compared to the normal gastric mucosa. Methods. Seven tissue microarrays containing a total of 594 cores from 132 patients with gastric cancer were obtained. Each core
C. M. Leys; S. Nomura; E. Montogomery; J. R. Goldenring
This audit was set up to investigate Plastic Surgeons' perception of minimum standards of reporting of skin neoplasia at the time of publication of the Royal College of Pathologists' guidelines. Eight histopathology case reports of skin neoplasia were formulated; four had the minimum information required and four had vital information omitted. Surgeons were asked to evaluate and suggest management. Marks
Y. S Lau; S. K Suvarna; L Kangesu; A Mosahebi
Objective.Vulvar intraepithelial neoplasia (VIN) is a premalignant disease of the lower genital tract. The increased occurrence of high-risk human papillomavirus (HPV) infection seems to be associated with the increasing frequency of VIN. Integration of HPV DNA into host chromosome has been hypothesized to be a critical step in the carcinogenesis of cervical neoplasia resulting in altered expression of two viral
Peter Hillemanns; Xiuli Wang
Primary hyperparathyroidism is a common endocrinological disorder. In rare circumstances, it is associated with familial syndromes, such as multiple endocrine neoplasia type 1. This syndrome is caused by a germline mutation in the multiple endocrine neoplasia type 1 gene encoding the tumor-suppressor protein menin. Usually, primary hyperparathyroidism is the initial clinical expression in carriers of multiple endocrine neoplasia type 1 mutations, occurring in more than 90% of patients and appearing at a young age (20–25 years). Multiple endocrine neoplasia type 1/primary hyperparathyroidism is generally accompanied by multiglandular disease, clinically manifesting with hypercalcemia, although it can remain asymptomatic for a long time and consequently not always be recognized early. Surgery is the recommended treatment. The goal of this short review is to discuss the timing of surgery in patients when primary hyperparathyroidism is associated with multiple endocrine neoplasia type 1.
Giusti, Francesca; Tonelli, Francesco; Brandi, Maria Luisa
Primary hyperparathyroidism is a common endocrinological disorder. In rare circumstances, it is associated with familial syndromes, such as multiple endocrine neoplasia type 1. This syndrome is caused by a germline mutation in the multiple endocrine neoplasia type 1 gene encoding the tumor-suppressor protein menin. Usually, primary hyperparathyroidism is the initial clinical expression in carriers of multiple endocrine neoplasia type 1 mutations, occurring in more than 90% of patients and appearing at a young age (20-25 years). Multiple endocrine neoplasia type 1/primary hyperparathyroidism is generally accompanied by multiglandular disease, clinically manifesting with hypercalcemia, although it can remain asymptomatic for a long time and consequently not always be recognized early. Surgery is the recommended treatment. The goal of this short review is to discuss the timing of surgery in patients when primary hyperparathyroidism is associated with multiple endocrine neoplasia type 1. PMID:22584719
Giusti, Francesca; Tonelli, Francesco; Brandi, Maria Luisa
Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as
B. T. TEH; S. KYTOLA; F. FARNEBO; L. BERGMAN; F. K. WONG; G. WEBER; N. HAYWARD; C. LARSSON; B. SKOGSEID; A. BECKERS; C. PHELAN; M. EDWARDS; M. EPSTEIN; F. ALFORD; D. HURLEY; S. GRIMMOND; G. SILINS; M. WALTERS; C. STEWART; J. CARDINAL; S. KHODAEI; F. PARENTE; L. TRANEBJĆRG; R. JORDE; J. MENON; A. KHIR; T. T. TAN; S. P. CHAN; A. ZAINI; B. A. K. KHALID; K. SANDELIN; N. THOMPSON; L. BRANDI; M. WARTH; J. LEISTI; D. CAMERON; J. J. SHEPHERD; K. OBERG; M. NORDENSKJOLD; P. SALMELA
Vulvar intraepithelial neoplasia (VIN) is a precursor to invasive vulvar carcinoma. The two major types of VIN, usual and differentiated, differ in epidemiology, pathogenesis, clinical manifestations, pathology, and malignant potential. Usual VIN commonly occurs in younger women. It is associated with human papillomavirus and tends to have multifocal and multicentric involvement. Differentiated VIN is frequently associated with benign vulvar dermatoses such as lichen sclerosus and lichen simplex chronicus. It occurs in older women and typically is unifocal and unicentric. Clinicians must have a high suspicion for VIN, which is diagnosed by biopsy. Surgical excision has been the standard treatment in order to prevent progression to invasive disease. The objectives of treatment have expanded to include preservation of normal vulvar function and anatomy. Therefore, management options are being investigated, including topical therapy, laser excision and vaporization, and photodynamic therapy. All can be effective in both eliminating disease and maintaining relatively normal-appearing and functioning anatomy. PMID:20868402
Lai, Kimberly W; Mercurio, Mary Gail
Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. The term VIN is used to denote high-grade squamous lesions and is subdivided into usual-type VIN (including warty, basaloid, and mixed VIN) and differentiated VIN. Usual-type VIN is commonly associated with carcinogenic genotypes of human papillomavirus (HPV) and other HPV persistence risk factors, such as cigarette smoking and immunocompromised status, whereas differentiated VIN usually is not associated with HPV and is more often associated with vulvar dermatologic conditions, such as lichen sclerosus. Biopsy is indicated for any pigmented vulvar lesion. Treatment is indicated for all cases of VIN. When occult invasion is not a concern, VIN can be treated with surgical therapy, laser ablation, or medical therapy. After resolution, women should be monitored at 6 and 12 months and annually thereafter. PMID:22015906
Diagnostic x-ray examinations as a potential risk for neoplasia were investigated in a prospective study of 55,908 women who participated in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. The x-ray exposure histories of 145 mothers whose children developed neoplasms and 290 matched controls were examined. Of the childhood neoplasms, 40 were malignant and 105 were benign. Generally, the data were consistent with increased risk of malignant neoplasms among children of women exposed to x-rays before and during pregnancy, with a somewhat higher relative risk estimate for preconception exposure. No significant association of x-ray exposure and benign neoplasms was detected.
Shiono, P.H. (Univ. of Hawaii, Manoa); Chung, C.S.; Myrianthopoulos, N.C.
Gestational trophoblastic neoplasia (GTN) describes a heterogeneous group of interrelated lesions that arise from abnormal proliferation of placental trophoblasts. GTN lesions are histologically distinct, malignant lesions that include invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). GTN tumors are generally highly responsive to chemotherapy. Early stage GTN disease is often cured with single-agent chemotherapy. In contrast, advanced stage disease requires multiagent combination chemotherapeutic regimens to achieve a cure. Various adjuvant surgical procedures can be helpful to treat women with GTN. Patients require careful followup after completing treatment and recurrent disease should be aggressively managed. Women with a history of GTN are at increased risk of subsequent GTN, hence future pregnancies require careful monitoring to ensure normal gestational development. This article will review the workup, management and followup of women with all stages of GTN as well as with recurrent disease.
May, Taymaa; Goldstein, Donald P.; Berkowitz, Ross S.
The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.
McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.
Previous research has produced conflicting results regarding the association of bacterial vaginosis (BV) and cervical intraepithelial neoplasia (CIN). These studies have been weakened in their conclusions mainly by failure to adequately control for the presence of sexually transmitted infections (STIs). One proposed mechanism suggesting that carcinogenic nitrosamines acting either independently or via human papilloma virus (HPV) has not been fully tested previously. We undertook a prospective, case-controlled, cross-sectional study where the presence of STIs, in particular human papillomavirus (HPV) which is known to be associated with the development of CIN, was controlled for. Women with BV were not found to have CIN more frequently than women with normal vaginal flora and the quantities of nitrosamines produced by women with BV did not differ significantly from women without BV. We thus found that BV is not associated with CIN. PMID:12657117
Boyle, D C M; Barton, S E; Uthayakumar, S; Hay, P E; Pollock, J W; Steer, P J; Smith, J R
We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.
Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa
Combination laser conization was performed for the treatment of cervical intraepithelial neoplasia (CIN) in 473 patients, who were followed for a mean period of 70 months. In 16 cases (3.4%) CIN was demonstrated during follow up, and in 10 cases (2.1%) within the first year after treatment. The grade of CIN in the cone specimen was of no predictive value to recurrence. When excisional margins were involved recurrence was observed in 8.7% of cases, compared to 2.3% when margins were uninvolved. The risk of recurrence was significantly higher in patients with involvement of the endocervical cone margin. The only case of invasive disease during follow-up was observed more than 2 years after conization; cone biopsy was without involved margins. The results clearly demonstrate the method to be effective and justify an expectant management of all patients after conization by this method. PMID:8063246
Andersen, E S; Pedersen, B; Nielsen, K
Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1). This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.
Piecha, Grzegorz; Chudek, Jerzy; Wiecek, Andrzej
Objectives High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined. Methods The placebo arms of two large, multinational, clinical trials of an HPV6/11/16/18 vaccine were combined. A total of 8441 healthy women aged 15–26?years underwent cervicovaginal cytology (Papanicolaou (Pap) testing) sampling and C trachomatis testing at day 1 and every 12?months thereafter for up to 4?years. Protocol-specified guidelines were used to triage participants with Pap abnormalities to colposcopy and definitive therapy. The main outcome measured was CIN. Results At baseline, 2629 (31.1%) tested positive for hrHPV DNA and 354 (4.2%) tested positive for C trachomatis. Among those with HPV16/18 infection (n=965; 11.4%) or without HPV16/18 infection (n=7382, 87.5%), the hazard ratios (HRs) associated with development of any CIN grade 2 according to baseline C trachomatis status were 1.82 (95% CI: 1.06 to 3.14) and 1.74 (95% CI 1.05 to 2.90), respectively. The results were comparable when only the 12 most common hrHPV infections were considered, but the excess risk disappeared when the outcome was expanded to include CIN grade 3 or worse. Conclusion Further studies based on larger cohorts with longitudinal follow-up in relation to the C trachomatis acquisition and a thorough evaluation of temporal relationships of infections with hrHPV types, C trachomatis and cervical neoplasia are needed to demonstrate whether and how in some situations C trachomatis sets the stage for cervical carcinogenesis. Trial registration NCT00092521 and NCT00092534.
Ault, Kevin A; Lyytikainen, Erika; Dillner, Joakim; Garland, Suzanne M; Ferris, Daron G; Koutsky, Laura A; Sings, Heather L; Lu, Shuang; Haupt, Richard M; Paavonen, Jorma
Although the oral cavity is easily accessible to inspection, patients with oral cancer most often present at a late stage, leading to high morbidity and mortality. Autofluorescence imaging has emerged as a promising technology to aid clinicians in screening for oral neoplasia and as an aid to resection, but current approaches rely on subjective interpretation. We present a new method to objectively delineate neoplastic oral mucosa using autofluorescence imaging. Autofluorescence images were obtained from 56 patients with oral lesions and 11 normal volunteers. From these images, 276 measurements from 159 unique regions of interest (ROI) sites corresponding to normal and confirmed neoplastic areas were identified. Data from ROIs in the first 46 subjects was used to develop a simple classification algorithm based on the ratio of red-to-green fluorescence; performance of this algorithm was then validated using data from the ROIs in the last 21 subjects. This algorithm was applied to patient images to create visual disease-probability maps across the field of view. Histologic sections of resected tissue were used to validate the disease-probability maps. The best discrimination between neoplastic and non-neoplastic areas was obtained at 405 nm excitation; normal tissue could be discriminated from dysplasia and invasive cancer with a 95.9% sensitivity and 96.2% specificity in the training set and with a 100% sensitivity and 91.4% specificity in the validation set. Disease probability maps qualitatively agreed with both clinical impression and histology. Autofluorescence imaging coupled with objective image analysis provided a sensitive and non-invasive tool for the detection oral neoplasia.
Roblyer, Darren; Kurachi, Cristina; Stepanek, Vanda; Williams, Michelle D.; El-Naggar, Adel K.; Lee, J. Jack; Gillenwater, Ann M.; Richards-Kortum, Rebecca
Since 1985, pathologists at Cornell University have investigated the causes of lesions in freshwater fish throughout New York waters in order to clarify possible impairment of fish health by environmental contaminants. Fishermen and biologists alerted us to several relatively protected reservoirs and ponds in which we have found no evidence of elevated levels of anthropogenic environmental contaminants but in which up to 100% of brown bullheads exhibited skin neoplasia. Complete necropsies and histologic study revealed that over 30% of mature brown bullheads from some of these sites had benign or malignant hepatocellular or biliary liver neoplasia. Up to 50% of brown bullheads had benign or malignant liver neoplasia in other relatively unpolluted waters with no evidence of skin neoplasia in bullheads. Multiple samplings of brown bullheads from several of these sites have revealed puzzling variability in the prevalence of skin, liver, and other neoplasia in these fish populations. The cause of these striking epizootics of neoplasia in brown bullheads in unpolluted waters in New York State remains unclear. We hypothesize that natural carcinogens such as N-nitroso compounds formed in aquatic sediments or radon from geologic formations may contribute to epizootic fish neoplasia in New York waters. PMID:8772257
Spitsbergen, J M; Wolfe, M J
Intraepithelial neoplasia is of critical importance to the cancer che- moprevention field because it is a target condition for which drugs must be sought that will prevent its development or stop its progression. The term \\
Charles W. Boone; Gary J. Kelloff; Vernon E. Steele
PurposeTo report a case of conjunctival-corneal intraepithelial neoplasia (CCIN) in an elderly African American patient treated with topical mitomycin C and the subsequent complication of limbal stem cell deficiency.
Blonie W. Dudney; Monika A. Malecha
The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological–pathological review\\u000a of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in\\u000a situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive\\u000a carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and
S. Menon; G. J. R. Porter; A. J. Evans; I. O. Ellis; C. W. Elston; Z. Hodi; A. H. S. Lee
In patients with ulcerative colitis, epidemiolĂłgica! work has suggested an association between low folate status and an increased risk of colonie neoplasia. The aim of the present study was to determine if experimen tal folate deficiency increases the likelihood of developing neoplasia in rats treated with the carcinogen dimethylhydrazine. Weanling male Sprague-Dawley rats were fed with an amino acid-defined diet
Marilia L. Cravo; Joel B. Mason; Martha Hutchinson; Donald Smith; Jacob Selhub; Irwin H. Rosenberg
A review of the perioperative morbidity and mortality and long-term survival in elderly and high-risk patients with colorectal neoplasia was undertaken. Elderly high-risk patients with localized disease were compared with those with advanced disease. Over a five-year period, 82 high-risk (at least one major organ system disease), or elderly (age ?70 years) patients underwent an operation for colorectal neoplasia. Overall,
Stephen D. Fitzgerald; Walter E. Longo; Gayle L. Daniel; Anthony M. Vernava III
Cervical condyloma and cervical intraepithelial neoplasia are related to human papillomavirus infections, some of which may be involved in the etiology of cancer of the uterine cervix. This case-control study was designed to assess the relation of age at first sexual intercourse, number of sexual partners, and cigarette smoking to the risk of cervical condyloma and cervical intraepithelial neoplasia. Cases and controls were premenopausal women under age 50 years who had been referred for examination at the Colposcopy Clinic of Saint-Sacrement Hospital in Quebec from 1982 to 1985. These were 136 cases of histologically confirmed cervical condyloma and 247 cases of cervical intraepithelial neoplasia. The 137 controls were women without anogenital condyloma, dysplasia, or carcinoma. Information on personal characteristics and exposures of subjects was obtained by interview. Associations observed with age at first intercourse were different for condyloma and cervical intraepithelial neoplasia. Relative risk of condyloma varied little with age at first intercourse. In contrast, relative risk of cervical intraepithelial neoplasia increased as age at first intercourse decreased. For the two types of lesions, relative risk was elevated among women with more than one sexual partner and increased steadily with increasing number of cigarettes smoked per day. The association with cigarette smoking was, however, somewhat stronger for cervical intraepithelial neoplasia. PMID:3394700
Brisson, J; Roy, M; Fortier, M; Bouchard, C; Meisels, A
The disappearance rate (k) of i.v. glucose was measured in cachectic and non-cachectic cancer patients and tumour-free controls. The respective k values were found to be 1.06 +/- 0.27 (mean +/- s.d.), 1.64 +/- 0.34 and 1.63 +/- 0.23. Of the other parameters measured, only plasma albumin level was found to vary significantly amongst the 3 categories, the mean level being the lowest in cachectic cancer patients. The means of total plasma protein, fasting blood glucose and plasma liver enzyme concentrations were similar in the 3 groups. Glucagon, a potent insulin secretogogue, failed to augment the fasting insulin level in cachectic but did so in non-cachectic cancer patients. Taken together, the findings suggest that the reduced glucose tolerance in patients with neoplasia is due to impairment of insulin release exhibited predominantly by ill-nourished advanced cancer patients having a moderate to sever degree of hypoalbuminemia.
Jasani, B.; Donaldson, L. J.; Ratcliffe, J. G.; Sokhi, G. S.
Cervical Intraepithelial Neoplasia (CIN) is a precursor to invasive cervical cancer, which annually accounts for about 3700 deaths in the United States and about 274,000 worldwide. Early detection of CIN is important to reduce the fatalities due to cervical cancer. While the Pap smear is the most common screening procedure for CIN, it has been proven to have a low sensitivity, requiring multiple tests to confirm an abnormality and making its implementation impractical in resource-poor regions. Colposcopy and cervicography are two diagnostic procedures available to trained physicians for non-invasive detection of CIN. However, many regions suffer from lack of skilled personnel who can precisely diagnose the bio-markers due to CIN. Automatic detection of CIN deals with the precise, objective and non-invasive identification and isolation of these bio-markers, such as the Acetowhite (AW) region, mosaicism and punctations, due to CIN. In this paper, we study and compare three different approaches, based on Mathematical Morphology (MM), Deterministic Annealing (DA) and Gaussian Mixture Models (GMM), respectively, to segment the AW region of the cervix. The techniques are compared with respect to their complexity and execution times. The paper also presents an adaptive approach to detect and remove Specular Reflections (SR). Finally, algorithms based on MM and matched filtering are presented for the precise segmentation of mosaicism and punctations from AW regions containing the respective abnormalities.
Srinivasan, Yeshwanth; Yang, Shuyu; Nutter, Brian; Mitra, Sunanda; Phillips, Benny; Long, Rodney
In multiplex endocrine neoplasia type 1, hyperparathyroidism, pancreas tumor and pituitary tumor are generally combined. The authors report two patients with this syndrome, in whom overproduction of parathormone and gastrin was detected, and parathyroid adenomas were detected by parathyroid scintigraphy. Pancreatic adenomas were discovered with somatostatin receptor scintigraphy or magnetic resonance imaging. Hyperprolactinaemia without pituitary tumor in the first case, and prolactinoma in the second case, as well as nonfunctioning adrenal adenomas in both cases were also observed. After several unsuccessful surgical interventions a long-term octreotide (Sandostatin, Novartis) treatment was started; in the first patient subcutaneous injection was given for 6 months, then the treatment was continued with the long-acting intramuscular preparation (Sandostatin LAR, Novartis). The second patient received long-acting octreotide from the beginning of medical therapy. The authors intended to obtain data about the effects of this therapy on all overproduced hormones. In the first case, a 6-months treatment with subcutaneous octreotide surprisingly resulted not only in a decrease of serum gastrin, but also in that of parathormone level. In the second case, serum gastrin was normalized, but parathormone did not change. The levels of prolactin and adrenocortical hormones were not affected. At present, the two patients are without any symptoms of their disease. PMID:12063865
Valkusz, Zsuzsanna; Gáspár, László; Julesz, János; Pávics, László
A strong positive relationship between dietary intake of eggs and risk of colorectal cancer has been observed in a number of epidemiological surveys. In this study we investigated the relationship between egg consumption and intermediate biomarkers of crypt cell proliferation in the colon and rectum of 75 patients who had adenomatous polyps or no evidence of bowel disease. Biopsies of normal flat mucosa were obtained at colonoscopy, and microdissected crypts were used to measure crypt length, frequency of mitosis per crypt and spatial distribution of mitoses within the crypt. There was no significant difference in the consumption of eggs by patients with adenomatous polyps (n = 53) and those without (n = 22). There was no significant positive correlation between frequency of egg consumption and any of the parameters of crypt cell proliferation in the group as a whole, nor when the patients with polyps were analysed separately. This study provides no biological evidence of any relationship between egg consumption and abnormal cell proliferation among patients at relatively high risk of colorectal neoplasia. PMID:7496330
Matthew, J A; Johnson, I T
The histologic features of 21 parathyroid glands obtained from 16 Mayo Clinic patients aged 2 to 52 years who had multiple endocrine neoplasia type 2b (MEN 2b) were evaluated. The findings were correlated with the patients' ages and with the serum concentrations of calcium (15 patients), phosphorus (14 patients), and immunoreactive parathyroid hormone (iPTH) (11 patients), and with the response of serum iPTH to calcium infusion (6 patients). We also studied the histologic features of 13 parathyroid glands obtained from 8 patients not seen at the Mayo Clinic with MEN 2b. The microscopic appearance of the glands was normal in patients under the age of 17; with increased age, the glands did not exhibit normal involution, and an appearance consistent with mild chief-cell hyperplasia was evident. This abnormality was not associated with clinical or laboratory manifestations of hyperparathyroidism. We presently believe that parathyroidectomy for the disorder is not justified. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5
Carney, J. A.; Roth, S. I.; Heath, H.; Sizemore, G. W.; Hayles, A. B.
Anal Intraepithelial Neoplasia (AIN) is an increasingly common condition for which the best treatment has not been well established. Traditional management was based on a 'watch and wait' strategy, but as the natural history of AIN and its progression to anal cancer is becoming better understood, more active treatment strategies are warranted. A best evidence topic in surgery was written according to a structured protocol to address the question whether treatment is indicated in patients with AIN. A total of 169 papers were identified using the defined search criteria. This included only one randomised controlled trial. Case series were therefore also included to help answer the question. The details of the papers were tabulated including relevant outcomes and study weaknesses. We conclude that treatment of high grade AIN, particularly in high risk groups is recommended to try to avoid progression to anal cancer. Treatment options that have shown some benefit include topical use of imiquimod cream or ablation directed by high resolution anoscopy. PMID:23643642
Orchard, M; Roman, A; Parvaiz, A C
We previously reported that normal human keratinocytes controlled neoplastic progression of tumor cells at an early stage of transformation in stratified squamous epithelium. We now studied if cells at a more advanced stage of transformation were also subject to such microenvironmental control. To accomplish this, 3D human tissues that mimic intraepithelial neoplasia were fabricated by mixing genetically marked (beta-gal), early-stage (II-4 cells) or advanced-stage (SCC13) transformed keratinocytes with normal keratinocytes, and tumor cell fate and phenotype were monitored in organotypic culture and after surface transplantation to nude mice. In vivo, SCC13 cells evaded local growth suppression to undergo connective tissue invasion at significantly lower tumor cell volumes (12:1, 50:1 normal:tumor cells) than II-4 cells. This behavior was explained by the growth suppression of II-4 cells, while advanced-stage tumor cells escaped this control and continued to undergo clonal expansion in mixed cultures to form large, intraepithelial tumor clusters. These communities of tumor cells underwent autonomous growth that was associated with altered expression of markers of differentiation (keratin 1) and cell-cell communication (connexin-43). Furthermore, significantly greater numbers of SCC13 cells expanded into a basal position after low-calcium stripping of suprabasal cells of mixed cultures compared to II-4 cells, suggesting that expansion of these cells enabled tumor cell invasion after transplantation. These findings demonstrated that early tumor development in human stratified squamous epithelium required escape from microenvironmental growth control that was dependent on the transformation stage of intraepithelial tumor cells during the premalignant stage of cancer progression. PMID:15856457
Zhang, Weitian; Vaccariello, Michael A; Wang, Youai; Alt-Holland, Addy; Fusenig, Norbert E; Garlick, Jonathan A
Objective The aim of this study was to determine whether the presence of bacterial vaginosis (BV) is associated with cervical intraepithelial neoplasia (CIN) and human papilloma virus (HPV) infection. Methods A total of 588 women who had abnormal Pap smears and had finally undergone loop electrosurgical excision procedure (LEEP) in our institute from September 2002 to May 2006 were selected. The screening tests for BV were done in 552 of the 588, and BV was diagnosed if three of the following four findings were satisfied: presence of abnormal discharge, vaginal pH>4.5, presence of clue cells, positive amine or whiff test. Five hundred and five patients had HPV typing tests by the HPV DNA chip. Forty two patients diagnosed with invasive cancer were excluded from this study. CIN was subdivided into low-grade CIN (CIN I) and high-grade CIN (CIN II/III) groups. Results There was no statistically significant difference in patient characteristics between BV-present and BV-absent group. The incidence of CIN was significantly higher in the BV-present group (p=0.043), however, no statistical significance of BV on CIN was observed on multivariate analysis. HPV infection showed no significant relationship with BV. BV with or without HPV infection did not influence the incidence of CIN, regardless of the severity. Conclusion There was significant correlation between BV and the presence of CIN, regardless of the severity of CIN. In addition, there was no significant association between the presence of BV and HPV infection.
Nam, Ka Hyun; Kim, Soo Rim; Kim, Sang Wun; Kim, Jae Wook; Lee, Mi Kyung; Nam, Eun Ji; Jung, Yong Wook
Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic inflammatory response. Successful treatment requires adherence to a regime that is uncomfortable at best and at worst painful. Topical treatments can be successful in motivated adherent patients willing to accept these side effects.
Weis, Stephen E
Pancreatic ductal adenocarcinoma (PDAC) is an almost lethal disease. Thus, it is important to better understand its genetic progression from normal cells through precancerous lesions pancreatic intraepithelial neoplasia (PanIN) to invasive pancreatic cancer. Carriers of a germline mutation in BRCA2 have an increased risk of developing PDAC when compared with the general population. The purpose of our study was to examine the role of BRCA2 dysfuction in the progression of PDAC. Here we generated a novel in vitro model of pancreatic carcinogenesis. Cancerous PanIN-BR1 cells were established by stable transduction with lentiviral-mediated BRCA2 RNA interference in PanIN cell isolated from mice with oncogenic KrasG12D. Our data showed that silencing of BRCA2 promoted cell proliferation, migration and invasion in vitro. The tumorigenic potential of PanIN-BR1 were assessed by xenograft tumor formation in BALB/c nude mice. The expression of PCNA , Snail and Slug in the tumor xenografts was detected by immunohistochemistry. The staining for PCNA, Snail and Slug in PanIN-BR1-formed xenograft tissue was significantly more intense than PanIN-formed xenograft tissue. Microarray assay was also performed. Based on gene expression profiling and further validation by real-time PCR and Western Blot, we found that the expression of Cyclinb2, Cyclina2, Twist1, Wisp1 and Cxcr4 revealed a significant increase in the PanIN-BR1 cells, however, the expression of p15, p16 and Wisp2 showed a significant decrease in the PanIN-BR1 cells, compared to the PanIN cells. Collectively, these data reported here demonstrate that BRCA2 may be a promising therapeutic targets for PDAC progression. PMID:22934697
Wang, Qi; Liu, Hongrui; Liu, Tingting; Shu, Shizhen; Jiang, He; Cheng, Shidan; Yuan, Yaozong; Yang, Weiguo; Wang, Lifu
OBJECTIVES.: The purpose of our prospective cohort study was to determine whether cervical intraepithelial neoplasia (CIN) 1 regresses, persists, or progresses during pregnancy. Eighty-four primigravid patients, ages 16 to 32 years old (mean 26), with no history of abnormal Pap smear, had abnormal Pap test results during their prenatal care between August 1995 and December 1998. The initial Pap results on these patients were: 57 (67.8%) atypical squamous cells of undetermined significance; 21 (25%) low-grade squamous intraepithelial lesions (LSIL); and 6 (7.2%) high-grade squamous intraepithelial lesions. Colposcopy and directed biopsies performed showed: 21(25%) normal; 6 (7.2%) acute cervicitis; 9 (10.7%) chronic cervicitis; 39 (46.4%) CIN 1; 7 (8.3%) CIN 2; and 2 (2.4%) CIN 3. RESULTS.: Thirty-nine patients with LSIL were seen for follow-up colposcopy and biopsy in the second and third trimesters of pregnancy and postpartum. Twenty-eight patients (71.8%) had a repeat normal (regression) as follows: 2 (7.1%) in the second trimester, 4 (14.3%) in the third trimester, and 22 (78.6%) postpartum. Three patients (7.7%) had progression. Eight patients (20.5%) had persistent CIN 1. CONCLUSIONS.: Our study found that more than 70% of CIN 1 was associated with pregnancy regression in primigravidas. Our study suggests the need for postpartum follow-up of all the patients diagnosed with CIN 1 during pregnancy. The follow-up should include a Pap smear. Patients without regression of LSIL by Pap smear at the postpartum visit should be thoroughly investigated and treated. PMID:17051041
Ventolini, Gary; Samlowski, Ralph
Focus is on some evidence of a possible relationship between the repeated involvement of the ovarian surface epithelium in the process of ovulation and the frequency of the development of the common ovarian neoplasms from this epithelium. Data about comparative ovarian oncology have been accumulating, and 3 noteworthy features have been revealed: 1) practically all tumor types encountered in the human ovary may be seen in the mammalian ovary; 2) ovarian tumors in other mammals are apparently much rarer than in human beings; and 3) this rarity is largely because of the infrequency of epithelial neoplasms derived from the ovarian surface epithelium--the cystadenoma and the adenocarcinoma. In women these account for the majority of all ovarian neoplasms and for the great majority of ovarian malignant neoplasms. Another situation has been revealed in the domestic fowl, with its frequent egg production. Adenocarcinoma of the ovary is the most common epithelial neoplasm in the entire body. The relation to egg production was demonstrated in an experiment where adenocarcinomas were induced in the ovaries of 17 out of 19 hens by maintaining them throughout life in a stable environment with 12 hours of fluorescent lighting daily. Egg production rapidly reached a maximum; it then declined over 3 years, with no seasonal rest periods. No tumors appeared in control hens kept under normal lighting conditions with seasonal variations. The surface epithelium of the ovary does not appear to play any active role in the adult processes of reproduction. The few electron microscopic studies available suggest a simple mesothelial function. The process of ovulation involves repeated minor trauma to the covering epithelium as well as repeated exposure of the ovarian surface to the estrogen rich viscous follicular fluid. Epidemiological data in human beings may be suggestive of a possible relationship between the process of ovulation and the development of the common ovarian neoplasm. In the absence of ovulation, ovarian neoplasms of surface epithelial origin are very rare, but germ cell and mesenchymal tumors occasionally arise. In patients denied the ovarian physiological rest periods afforded by pregnancies, a higher incidence of ovarian cancer has been reported. The hypothesis that the extravagant and mostly purposeless ovulations in the human female may have a contributing role in neoplasia of the surface epithelium of the ovary requires additional consideration. PMID:4104488
Fathalla, M F
Carney Complex (CNC) and Multiple Endocrine Neoplasia type 1 (MEN1) are forms of multiple endocrine neoplasia of dominant autosomal inheritance. Diagnosis of CNC occurs when two major criteria (lentiginoses, primary pigmented nodular adrenocortical disease, cardiac and cutaneous myxomas, acromegaly, testicular neoplasias, thyroid cancer) are observed and/or a major criterion associated with a supplementary criterion (affected relative, PRKAR1A gene mutation) occurs. On the other hand, diagnosis for MEN1 occurs through detection of two or more tumors located at the pituitary gland, parathyroid and/or pancreatic cells. The present case describes a 55 year-old male patient, diagnosed with acromegaly, primary hyperparathyroidism and papillary thyroid cancer, exhibiting components that meet the diagnostic criteria of both conditions described. Despite the occurrence of only one sporadic association or the acromegaly per se being responsible for the papillary cancer, new molecular mechanisms may not be ruled out. PMID:19169494
Nunes, Vania S; Chang, Cláudia V; Mazeto, Gláucia M F S; Marques, Mariângela E A; Castro, Ana Valéria B; Nogueira, Célia R
This article addresses nonseptic diseases associated with the hoof complex, namely keratoma, white line disease, canker, and neoplasia. Keratoma is an uncommon cause of lameness, which may be surgically removed. White line disease, a keratolytic process on the solar surface of the hoof, is treated with therapeutic farriery and resection of the hoof wall when appropriate. Equine canker is an infectious process that results in development of a chronic hypertrophy of the horn-producing tissues. Neoplasia involving the equine foot is rare, and melanoma is the most common type of neoplasm reported. PMID:22981198
Redding, W Rich; O'Grady, Stephen E
We considered the possibility that herpetic recurrences and herpes virus associated neoplasia are mutually exclusive disorders because they are expressions of different herpes virus-host relationships. We assumed that the human body copes with orofacial and genital herpes infections in the same manner. In our retrospective study, the relative risk of a history of fever blisters for cervical neoplasia was estimated to be 0.49, with 0.34 and 0.69 as the limits of the 95% confidence interval. It is suggested that recurrent herpes labialis is presumably a determinant of an effective immune response in general. PMID:3176912
Burger, M P; Wilterdink, J B
A family with multiple endocrine neoplasia, type II living in southeastern Ontario is described. Twenty individuals are known to have had medullary carcinoma of the thyroid, pheochromocytoma or both, the diagnosis of multiple endocrine neoplasia. type II is strongly suspected in five other individuals in the earlier generations. In this family the diseases seems to be transmitted by an autosomal dominant gene. A screening program set up for the family in 1977 has in 2 years identified four asymptomatic individuals (three with medullary carcinoma of the thyroid and one with this carcinoma and a pheochromocytoma). The family background, clinical picture, treatment and some of the problems of the screening program are described.
Partington, M W; Ghent, W R; Sears, E V; Simpson, N E
Background Prior work has related elevated life stress to greater risk of cervical neoplasia in women with human immunodeficiency virus\\u000a (HIV) and human papillomavirus (HPV).\\u000a \\u000a \\u000a \\u000a Purpose This study investigated associations between depressive symptoms and cervical neoplasia in HIV+ HPV+ women. Participants were\\u000a 58 HIV+ HPV+ women.\\u000a \\u000a \\u000a \\u000a Method Participants underwent colposcopy, including HPV screening, Papanicolaou smear, and cervical biopsy to determine study eligibility.\\u000a Eligible
Stacy M. Dodd; Deidre B. Pereira; Ilona Marion; Michele Andrasik; Rachel Rose; Trudi Simon; Mary Ann Fletcher; Joseph Lucci; Kevin Maher; Mary Jo O’Sullivan; JoNell Efantis-Potter; Michael H. Antoni
Studies on the etiology of hematopoietic neoplasia (HN) in soft-shell clams, Mya arenaria, have been inconclusive. Petroleum-derived hydrocarbons, polychlorinated-biphenyls and a virus have all been implicated as causative agents. The isolation of 100 nm virus-like particles from neoplastic clams proved conclusively that the causative agent is a retrovirus. The virus can induce a neoplasia in non-neoplastic clams and similar virus particles can be re-isolated and induce neoplasia. The activities of the RT are temperature dependent, found at 6[degrees]C, but not at 25[degrees]C and 37[degrees]C. The incidence rate for neoplasia in Narragansett Bay, Rhode Island was 7.7% and for combined other locations, 3.7% (26/699). HN was present in clams throughout the year at varying levels. The highest incidence occurred in October (11.5%); the lowest incidence in April (1.2%) and June (2.5%). The outcome of the disease depends on the water temperature and degree of severity of neoplasia in the clams. Death rate was greatest when water temperature was at 15[degrees]C (100%). High severity clams had the highest death rate (100%). Chronicity of persistent neoplasia occurred more at 10[degrees]C (19%) than at 6[degrees]C (15%) or 15[degrees]C (0%). Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. Neoplasia causes metabolic alteration in clams. Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. The time to remission was longer at 6[degrees]C than 10[degrees]C. Neoplasia causes metabolic alteration in clams. This shown by a significant increase in uric acid, asparatate transminase and triglycerides and a decrease in urea in the hemolymph. The cell membrane of neoplastic hemocytes also shows differences in their binding pattern to lectin than the normal hemocytes, indicating a change in cell surface glycoprotein probably induced by the retrovirus.
The terms ductal and lobular intraepithelial neoplasia (DIN and LIN) were introduced by Tavossoli 15 years ago, who proposed they should replace, respectively, ductal and lobular carcinoma in situ (DCIS and LCIS). This proposal has been slowly gaining ground. We argue that DCIS and LCIS should now be definitively abandoned. Bringing together 'in situ' and other entities into the simpler and more logical DIN/LIN framework--as has been done with intraepithelial neoplasias of cervix, vagina, vulva, prostate, and pancreas--would eliminate the artificial and illogical distinctions between 'not cancers' (e.g. flat epithelial atypia, atypical ductal hyperplasia--now classified as low grade DIN) and 'cancers' (e.g. DCIS--now considered medium-high grade DIN). Elimination of the term 'carcinoma' from entities that cannot metastasize will reduce confusion among health professionals and patients, and contribute to reducing the risk of overtreatment, as well as reducing adverse psychological reactions in patients. PMID:23643807
Galimberti, Viviana; Monti, Simonetta; Mastropasqua, Mauro Giuseppe
OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25% of all cases of thymic carcinoids. In patients with MEN1, this is an insidious tumor not associated with Cushing's or carcinoid syndrome. Local invasion, recurrence, and distant metastasis are common, with no known effective treatment. We propose that CT or MRI of the chest, as well as octreoscanning, should be considered as part of clinical screening in patients with MEN1. We also propose performing prophylactic thymectomy during subtotal or total parathyroidectomy on patients with MEN1 to reduce the risks of thymic carcinoid and recurrence of hyperparathyroidism. Its male predominance, the absence of LOH in the MEN1 region, clustering in close relatives, and the presence of different MEN1 mutations in these families suggest the involvement of modifying genes in addition to the MEN1 gene. A putative tumor suppressor gene in 1p may be involved. Images Figure 1. Figure 2. Figure 3.
Teh, B T; Zedenius, J; Kytola, S; Skogseid, B; Trotter, J; Choplin, H; Twigg, S; Farnebo, F; Giraud, S; Cameron, D; Robinson, B; Calender, A; Larsson, C; Salmela, P
Various risk factors were investigated in 167 cervical intra-epithelial neoplasia (CIN) case and control pairs in Japan. CIN cases showed evidence of nine known risk factors including smoking and sexual behaviour. However, after adjustment for papillomavirus infection, the highest determinant, the only remaining risk factors were: being married, early age at first pregnancy and multiparity. © 1999 Cancer Research Campaign
Yoshikawa, H; Nagata, C; Noda, K; Nozawa, S; Yajima, A; Sekiya, S; Sugimori, H; Hirai, Y; Kanazawa, K; Sugase, M; Shimizu, H; Kawana, T
Although cigarette smoking has been identified as a cofactor for cervical neoplasia, it is not clear whether smoking exerts an early or late effect on the evolution of human papillomavirus (HPV)-related lesions. A case- control study of Washington State women who presented for routine gynecologic care from 1997 to 2001 was conducted. All women underwent cytologic testing and HPV DNA
Tiffany G. Harris; Shalini L. Kulasingam; Nancy B. Kiviat; Constance Mao; S. Nicholas Agoff; Qinghua Feng; Laura A. Koutsky
The management of a core biopsy diagnosis of lobular neoplasia is controversial. Detailed radiological-pathological review of 47 patients with cores showing classical lobular neoplasia was performed (patients with pleomorphic lobular carcinoma in situ (LCIS) or associated risk lesions were considered separately). Immediate surgical excision in 25 patients showed invasive carcinoma in 7, ductal carcinoma in situ (DCIS) in 1 and pleomorphic LCIS in 1; radiological-pathological review showed that the core biopsy missed a mass in 5, missed calcification in 2 and that calcification appeared adequately sampled in 2. Nineteen patients had follow-up of at least 2 years. Four patients developed malignancy at the site of the core biopsy (invasive carcinoma in three, DCIS in one); one carcinoma was mammographically occult, one patient had dense original mammograms and two had calcifications apparently adequately sampled by the core. In conclusion, most carcinomas identified at the site of core biopsy showing lobular neoplasia were the result of the core missing the radiological lesion, emphasising the importance of multidisciplinary review and investigation of any discordance. Some carcinomas were found after apparently adequate core biopsy, raising the question of whether excision biopsy should be considered after all core biopsy diagnoses of lobular neoplasia. PMID:18389278
Menon, S; Porter, G J R; Evans, A J; Ellis, I O; Elston, C W; Hodi, Z; Lee, A H S
Ulcerative colitis (UC) is an inflammatory disease of the colon that is associated with increased risk of colorectal cancer associated with genomic instability. We have previously demonstrated that genomic instability is present in UC patients with colonic neoplasia, and hypothesized that the chromosomal alterations may be taking place in regions that are susceptible to mutation or that provide a growth
Ru Chen; Mary P. Bronner; David A. Crispin; Peter S. Rabinovitch; Teresa A. Brentnall
Objectives. The aim of this study was twofold: first, to determine the feasibility of photodynamic therapy (PDT) of vulvar intraepithelial neoplasia III (VIN III) using topically applied 5-aminolevulinic acid (ALA) for photosensitization, and second, to compare PDT results with those of laser evaporation and local excision.Methods. Fifteen patients with VIN III had 10 g of 10% ALA gel applied to
Mathias K. Fehr; René Hornung; Viola A. Schwarz; René Simeon; Urs Haller; Pius Wyss
ObjectivesSurgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We
Ram Athavale; R. Naik; K. A. Godfrey; P. Cross; M. H. Hatem; A. de Barros Lopes
Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominantly inherited cancer syndrome characterized by medullary carcinoma of the thyroid, phaeochromocytoma and hyperparathyroidism. Almost all gene carriers can be detected by screening tests before the age of 40 (ref. 1), but the nature and location of the predisposing gene are unknown. Simpson et al.2 recently reported preliminary evidence for linkage
C. G. P. Mathew; K. S. Chin; D. F. Easton; K. Thorpe; C. Carter; G. I. Liou; S.-L. Fong; C. D. B. Bridges; H. Haak; A. C. Nieuwenhuijzen Kruseman; S. Schifter; H. H. Hansen; H. Telenius; M. Telenius-Berg; B. A. J. Ponder
High-grade prostatic intraepithelial neoplasia (HGPIN) is a precursor to inva- sive prostate cancer observed as an isolated entity in a growing subset of men undergoing prostate biopsy. The presence of HGPIN predicts an increased risk of 1) coexisting occult prostate cancer at baseline and 2) delayed progression to prostate cancer. As such, men with HGPIN represent a population at high
Samir S. Taneja
In a retrospective study of cervical neoplasia, the relative risk estimate (with 95% confidence limits) of a first pregnancy before 22 years of age was 2.6 (1.41;5.12), with regard to the herpes simplex virus (HSV) infection 6 (2.05;23.81) and with regard to the cytomegalovirus (CMV) infection 2 (1.07;3.85). There was no relation between gravidity and cervical neoplasia. After eliminating the confounding effect of the HSV and the CMV infection, the relative risk for cervical neoplasia of a first pregnancy before 22 years of age was estimated to be 2.17 (1.24; 3.80). There was no evidence of a tumor-promoting role of low age at first pregnancy in the possible neoplastic outcome of the HSV and CMV infections. The association between low age at first pregnancy and cervical neoplasia presumably results from the association between a low age at first pregnancy and the occurrence of a causal infectious agent other than HSV and CMV. PMID:2854937
Burger, M P; Wilterdink, J B
Objective: To compare three screening tests for cervical neoplasia. Method: Women (6301) were screened simultaneously with cytology, cervicography and the acetic acid test (AAT). Biopsies were taken from the acetowhite lesions and every fifth seemingly normal cervix. Positive cases (both at screening and histology) were referred for colposcopy. The histology results served as the golden standard. Results: Cytology was positive
H. S. Cronjé; B. F. Cooreman; E. Beyer; R. H. Bam; B. D. Middlecote; P. D. J. Divall
The aim of this study was to evaluate the diagnostic potential, treatment efficacy, specimen adequacy, and acute complication rate associated with electrosurgical excision procedure (EEP) of the cervix for the management of cervical intraepithelial neoplasia (CIN). Analysis was performed retrospectively on 153 consecutive patients who underwent EEP under colposcopic guidance. Patients with negative endocervical curettage (ECC), adequate colposcopy, and biopsy-proven
Thomas J. Herzog; Sybilann Williams; Lisa M. Adler; Janet S. Rader; Richard T. Kubiniec; H. Marvin Camel; David G. Mutch
Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterized by the development of tumours of the parathyroid, anterior pituitary and pancreatic islets, etc. Heterozygous germ line mutations of MEN1 gene are responsible for the onset of MEN1. We investigated the probands and 31 family members from eight unrelated Chinese families associated with MEN1 and identified four novel
Xiao-Hua Jiang; Jie-Li Lu; Bin Cui; Yong-Ju Zhao; Wei-qing Wang; Jian-Min Liu; Wen-Qiang Fang; Ya-Nan Cao; Yan Ge; Chang-xian Zhang; Huguette Casse; Xiao-Ying Li; Guang Ning
Purpose. Pseudoepitheliomatous hyperplasia at the limbus can mimic an ocular surface squamous neoplasia. It is an uncommon manifestation of vernal keratoconjunctivitis and has been reported previously in limbal VKC. It, however, has not been reported as a manifestation in the palpebral form of the disease and needs to be kept in the differential diagnosis of a limbal mass lesion in vernal keratoconjunctivitis. Case Report. We report the case of a 24 year old male patient having palpebral VKC and presenting with a papillomatous limbal mass with focal areas of keratinization mimicking an ocular surface squamous neoplasia. An excision biopsy was performed, and the specimen sent for histopathologywhich revealed features of pseudoepitheliomatous hyperplasia with no evidence of dysplasia or malignant transformation. The subepithelium revealed a dense plasma-rich inflammation. Discussion. We report this relatively uncommon presentation of limbal pseudoepitheliomatous hyperplasia mimicking an ocular surface squamous neoplasia in palpebral vernal keratoconjunctivitis. Wide excision as is required for an ocular surface neoplasia may thus be avoided if this entity is recognized in vernal keratoconjunctivitis.
Jain, Arun K.; Thapa, Bikram
Multiple endrocrine neoplasia (MEN) type 1 is characterized by mainly a triad of pancreatic, pituitary and parathyroid involvement. This is a case report of a 41-year-old male in whom recognition of collagenoma and gingival papule led to the identification of MEN type 1. Often the recognition of such dermatological manifestations help in the presymptomatic diagnosis of complex syndromes.
Simi, SM; Narayanan, Beena; Nandakumar, G
Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1) correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2) avoid persistent hypoparathyroidism; and 3) facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1) subtotal parathyroidectomy with removal of at least 3–3˝ glands; and 2) total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1) the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2) the surgeon's experience; 3) the timing of surgery; 4) the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay) of the curative potential of the surgical procedure; and, 5) the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.
Tonelli, Francesco; Giudici, Francesco; Cavalli, Tiziana; Brandi, Maria Luisa
Significant differences in colon cancer incidence worldwide have led to the hypothesis that this variation can be explained largely by environmental, notably dietary influences. Although a positive correlation between dietary fat intake and incidence is suggested from some human epidemiological and rodent carcinogenesis studies, a direct association remains contentious. Using a spontaneous mouse tumor model of multiple intestinal neoplasia, we
Harpreet S. Wasan; Marco Novelli; Julie Bee; Walter F. Bodmer
Objective: To identify genetic changes, other than the MEN1 gene, that might be involved in the tumorigenesis and progression of multiple endocrine neoplasia type 1 (MEN1)-related tumours. Methods: We used comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) to study tumours from various sites in a patient with MEN1. Results: Gain of genetic material was not found. Frequent losses
Soili Kytola; Markus J Makinen; Marketta Kahkonen; Bin Tean Teh; Jaakko Leisti; Pasi Salmela
BACKGROUND: The highest rates of cervical cancer are found in developing countries. Frontline monitoring has reduced these rates in developed countries and present day screening programs primarily identify precancerous lesions termed cervical intraepithelial neoplasias (CIN). CIN lesions described as mild dysplasia (CIN I) are likely to spontaneously regress while CIN III lesions (severe dysplasia) are likely to progress if untreated.
Ashleen Shadeo; Raj Chari; Kim M Lonergan; Andrea Pusic; Dianne Miller; Tom Ehlen; Dirk Van Niekerk; Jasenka Matisic; Rebecca Richards-Kortum; Michele Follen; Martial Guillaud; Wan L Lam; Calum MacAulay
Background: Some experts maintain that (1) >90% of patients with multiple endocrine neoplasia type 1 (MEN1) are first seen with hyperparathyroidism (HPTH) so that routine screening for other features is unnecessary and (2) MEN1 has ?94% penetrance by age 50 years. Methods: We constructed a regional registry of patients with or at risk for MEN1 and examined phenotypic profiles in
Sally E. Carty; Audrey K. Helm; Janet A. Amico; Martha R. Clarke; Thomas P. Foley; Charles G. Watson; John J. Mulvihill
Recently it has become possible to identify persons who have multiple endocrine neoplasia (MEN) syndrome types 2A and 2B based on the presence of missense mutations in the RET protooncogene. Kindred members who have inherited these syndromes can be identified before clinical or biochemical evidence of medullary thyroid carcinoma (MTC) develops, the malignancy that occurs in all affected patients. It
Michael A Skinner; Mary K DeBenedetti; Jeffrey F Moley; Jeffrey A Norton; Samuel A Wells
The present investigation extends the validation of the Female Sexual Function Index (FSFI; Rosen et al., 2000) to include women with vulvar excisions for vulvar intraepithelial neoplasia (VIN). No instrument previously has been validated in this population. We administered the instrument to 43 women (n = 43) with VIN treated with vulvar excision and age-matched healthy controls (n = 43).
Wendy M. Likes; Cheryl Stegbauer; Donna Hathaway; Candice Brown; Todd Tillmanns
BACKGROUND: Ocular surface squamous neoplasia (OSSN) is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined. RESULTS: Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were
Kenneth O Simbiri; Masanao Murakami; Michael Feldman; Andrew P Steenhoff; Oathokwa Nkomazana; Gregory Bisson; Erle S Robertson
Menin is a protein encoded by the gene mutated in multiple endocrine neoplasia type 1 (MEN1) characterized by multiple endocrine tumors of the parathyroid glands, pancreatic islets and the anterior pituitary, especially prolactinoma. In this study, we examined the effects of menin on human prolactin (hPRL) expression. In rat pituitary GH3 cells stably expressing menin, both PRL gene expression\\/ secretion
H Namihira; M Sato; K Murao; W M Cao; S Matsubara; H Imachi; M Niimi; H Dobashi; T Ishida
The First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia, in July 2005. The conference covered regional issues relating to infection with the human papillomavirus—epidemiology, virology, and immunology, testing, screening, and prevention strategies—as well as cervical cancer screening and its management.
Faro, Edited by Sebastian
Objective. Cervical infection with human papillomavirus (HPV) results in a more permissive environment for malignant transformation. In squamous epithelia the Langerhans' cell (LC) is responsible for antigen presentation. Studies that use S-100 immunostaining demonstrate low LCs in cervical intraepithelial neoplasia (CIN) while those that use other methods have shown normal numbers of LCs. This observation led us to postulate that
Joseph P. Connor; Karen Ferrer; John P. Kane; Jeffrey M. Goldberg
Aim: To describe the use of a new spatulated cryoprobe in treatment of conjunctival neoplasia. Methods: A new cryoprobe design was submitted to Mira, Inc resulting in new hand held probes capable of producing homogeneous freezing over large surface areas. The active surface of the small, medium, and large spatulated probes are 8.5 mm2, 25.2 mm2, and 70 mm2. End freezing reduces the possibility of inadvertent freezing of adjacent tissues (outside the targeted zone). In this series, the probes were employed to treat patients with squamous and melanocytic conjunctival neoplasia. Results: 12 consecutive patients with malignant conjunctival neoplasia were treated with these new cryotherapy probes. Techniques of probe construction and clinical use are described. Cryoburns of the cornea, sclera, and conjunctiva were formed and recorded by digital photography. Ophthalmic examinations before and after surgery demonstrated that no acute intraocular or adnexal complications occurred. No loss of visual acuity could be attributed to this use of the cryoprobes. Conclusion: “Finger-tip” cryoprobes were used to treat malignant conjunctival neoplasia (squamous and melanocytic). Probe design allowed for uniform freezing over large surface areas. This cryoprobe design appears to be ideal for treatment of conjunctival tumours.
Finger, P T
The aims of this study were to review the diagnostic pathway of women with smears reported as 'glandular neoplasia' and to outline the management, colposcopy findings, treatment and final histological diagnosis in these women. The design was a retrospective review. A total of 114 women were identified over a 5-year period from the cytology database at the Royal Liverpool University Hospital Cytology Department, whose hospital case notes were available for review. Methods included a review of the case notes for the demographic details, indication for smear, colposcopic findings, investigation and/or treatment procedures, histology, final diagnosis and current disease status. Of 114 smears reported as 'glandular neoplasia', 67 were reported as consistent with cervical glandular intra-epithelial neoplasia (CGIN), six with endocervical adenocarcinoma, 36 with endometrial adenocarcinoma and five with other glandular neoplastic abnormalities. The average age was 46.5 years. 79 (69.3%) smears were routine call/recall and 36 (30.7%) women were symptomatic. The positive predictive value (PPV) for a significant histological abnormality in the CGIN smear group was 80.6% (23.9% invasive carcinomas, 43.3% CGIN and 13.4% CIN) and the PPV of an 'endometrial adenocarcinoma' smear was 86.1%. Smears indicating glandular neoplasia are associated with a high probability of clinically significant lesions, the PPV of a CGIN smear being over 80%. Immediate referral for colposcopy and assessment by an experienced colposcopist is recommended. PMID:15324445
Kirwan, J M; Herrington, C S; Smith, P A; Turnbull, L S; Herod, J J O
Germ-line mutations of the APC gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominantly inherited disease in humans. Patients with FAP develop multiple benign colorectal tumors. Recently, a mouse lineage that exhibits an autosomal dominantly inherited predisposition to multiple intestinal neoplasia (Min) was described. Linkage analysis showed that the murine homolog of the APC gene (mApc) was tightly
Li-Kuo Su; Kenneth W. Kinzler; Bert Vogelstein; Antonette C. Preisinger; Amy Rapaich Moser; Cindy Luongo; Karen A. Gould; William F. Dove
The aim of our study was to assess the frequency and location of apoptotic bodies (ABs) in haematoxylin and eosin-stained sections of prostatic intra-epithelial neoplasia (PIN) and then to compare the patterns with those in benign prostatic hyperplasia (BPH) and prostatic invasive adenocarcinoma (PAC). ABs were identified in all epithelial cell layers of the ducts, acini and tumour islands, as
Rodolfo Montironi; Cristina Magi Galluzzi; Marina Scarpelli; Ioannis Giannulis; Lucilla Diamanti
High-grade prostatic intraepithelial neoplasia (HGPIN) is a premalignant lesion associated with increased risk of coexistent cancer or delayed progression to carcinoma. Extended biopsy schemes have improved the ability to rule out concurrent cancers, increased the detection of isolated HGPIN and removed the routine necessity for immediate repeat biopsy. As the natural history of HGPIN is poorly defined, and no non-invasive
G Godoy; S S Taneja
THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALO METHANES (THMs) IN THE DRINKING WATER Christopher Sistrunk and Tony DeAngelo, North Carolina Central University and US Environmental Protection Agency The THMs are the most widely distributed and the most co...
OBJECTIVE: To evaluate the utility of human papillomavirus detection in identifying women with abnormal Papanicolaou smears who can be safely followed up with cytologic study only, we conducted a study to determine the sensitivity, specificity, and negative and positive predictive values of a Food and Drug Administration–approved human papillomavirus test kit for detection of cervical intraepithelial neoplasia in colposcopically directed
Raymond H. Kaufman; Ervin Adam; Joseph Icenogle; Herschel Lawson; Nancy Lee; K. O. Reeves; John Irwin; Terry Simon; Robert Uhler; Carol Entman; William C. Reeves
Multiple intestinal neoplasia (Min) mice are a good model for the investigation of the effects of dietary alterations in a genetic model for intestinal cancer. Previ- ous studies have shown that selenium-enriched broccoli is protective against chemically induced colon cancer sus- ceptibility. This study investigated whether selenium-en- riched broccoli would be protective against intestinal can- cer susceptibility in Min mice.
Cindy D. Davis; Huawei Zeng; John W. Finley
Background & Aims:Colorectal cancer is one of the leading causes of cancer death. Most colorectal cancers are believed to develop from colorectal adenomas. We examined the effect of the selective cyclooxygenase-2 inhibitors rofecoxib and celecoxib, nonselective nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen on colorectal neoplasia (colorectal cancer, colorectal adenoma, or both).
Elham Rahme; Alan N. Barkun; Youssef Toubouti; Marc Bardou
A woman received radiation therapy to the adenoids for benign disease at the age of 10 years and subsequently developed an adenocarcinoma of the middle ear, a parathyroid adenoma, and a papillary carcinoma of the thyroid gland in adulthood. This appears to be the first such case on record. The literature of neoplasia after head and neck irradiation is briefly reviewed.
Sirota, D.K.; Eden, A.R.; Biller, H.F.
Background Werner syndrome (WS) is an autosomal recessive genetic instability and progeroid (‘premature aging’) syndrome which is associated with an elevated risk of cancer. Objectives Our study objectives were to characterize the spectrum of neoplasia in WS using a well-documented study population, and to estimate the type-specific risk of neoplasia in WS relative to the general population. Methods We obtained case reports of neoplasms in WS patients through examining previous case series and reviews of WS, as well as through database searching in PubMed, Google Scholar, and J-EAST, a search engine for articles from Japan. We defined the spectrum (types and sites) of neoplasia in WS using all case reports, and were able to determine neoplasm type-specific risk in Japan WS patients by calculating standardized incidence and proportionate incidence ratios (SIR and SPIR, respectively) relative to Osaka Japan prefecture incidence rates. Results We used a newly assembled study population of 189 WS patients with 248 neoplasms to define the spectrum of neoplasia in WS. The most frequent neoplasms in WS patients, representing 2/3 of all reports, were thyroid neoplasms, malignant melanoma, meningioma, soft tissue sarcomas, leukemia and pre-leukemic conditions of the bone marrow, and primary bone neoplasms. Cancer risk defined by SIRs was significantly elevated in Japan-resident WS patients for the six most frequent neoplasms except leukemia, ranging from 53.5-fold for melanoma of the skin (95% CI: 24.5, 101.6) to 8.9 (95% CI: 4.9, 15.0) for thyroid neoplasms. Cancer risk as defined by SPIR was also significantly elevated for the most common malignancies except leukemia. Conclusions WS confers a strong predisposition to several specific types of neoplasia. These results serve as a guide for WS clinical care, and for additional analyses to define the mechanistic basis for cancer in WS and the general population.
Lauper, Julia M.; Krause, Alison; Vaughan, Thomas L.; Monnat, Raymond J.
Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence excitation wavelengths are useful for the detection of neoplasia. 42 hamsters were treated with DMBA to induce carcinogenesis, and 20 control animals were treated only with mineral oil. Fluorescence excitation emission matrices were measured from the cheek pouches of the hamsters weekly. Results showed increased fluorescence near 350-370 nm and 410 nm excitation and decreased fluorescence near 450-470 nm excitation with neoplasia. The optimal diagnostic excitation wavelengths identified using this model - 350-370 nm excitation and 400-450 nm excitation - are similar to those identified for detection of human oral cavity neoplasia.
Coghlan, Lezlee; Utzinger, Urs; Drezek, Rebekah A.; Heintzelmann, Doug; Zuluaga, Andres F.; Brookner, Carrie; Richards-Kortum, Rebecca R.; Gimenez-Conti, Irma; Follen, Michele
Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases. PMID:23803756
Doll, Kemi M; Soper, John T
Japanese-style fermented soy sauce (shoyu) contains anticarcinogenic activity. ICR mice were fed a semi-purified diet containing shoyu. 2 wks later a regimen consisting of 2 doses (p.o.) of benzo(a)pyrene per wk for 4 wks was begun, to initiate forestomach neoplasia. 23 wks later the animals were sacrificed, forestomach neoplasms counted and histologically confirmed. Shoyu produced a significant dose-dependent reduction in neoplasms, which appeared maximal when shoyu was present at 20% of the diet. Exposure to nitrite neither enhanced nor diminished the anticarcinogenic effect. Shoyu was found to contain antioxidant activity which may be related to the observed anticarcinogenic effect. Surprisingly mouse forestomach ornithine decarboxylase (ODC) activity was induced by shoyu, due in part to high sodium chloride content. Since ODC induction appears to be an early and possibly obligatory event in tumor promotion, the inhibition of neoplasia by shoyu probably occurs at a later step.
Benjamin, H.; Storkson, J.M.; Nagahara, A.; Pariza, M.W. (Univ. of Wisconsin, Madison (United States))
Endoscopic mucosal resection has expanded the role of the gastroenterologist in the management of esophageal neoplasia from screening and diagnosis to staging and endoscopic treatment. Its rise to prominence is a reflection of the long identified need to obtain histological information regarding depth of invasion and neoplastic margins during therapy that previously could not be achieved with ablative techniques. The resultant improvement in diagnosis and staging has allowed for better selection of patients for endoscopic therapy who may be spared invasive surgery. The clinical indications, endoscopic techniques, outcomes and complications in the management of esophageal neoplasia are reviewed in this manuscript. Training requirements to achieve proficiency in EMR as well as potential quality measures to assess competence are also proposed in this review.
Namasivayam, Vikneswaran; Wang, Kenneth K.; Prasad, Ganapathy A
In 202 women with koilocytotic atypia in cervical smears, 136 had predominantly small condylomata of the uterine cervix, and 66 had cervical intraepithelial neoplasia (CIN) of varying degree either with koilocytosis of the neoplasia or associated with condylomata. Koilocytosis correlated well with the histological diagnosis of condylomata, but occasionally it obscured the cytological evidence of CIN. Human papilloma virus particles were found in the cells of condylomata in 10 cases and in those of CIN II with koilocytosis in two cases of 21 examined ultrastructurally. There was evidence that the condyloma of the uterine cervix is a well-defined morphological entity and also that cytopathie changes similar to those seen in condylomata are present in some cases of CIN. Images
Pilotti, S; Rilke, F; De Palo, G; Della Torre, G; Alasio, L
19 (34%) of 56 Jamaicans with lympho-proliferative neoplasia had antibody to the human T-cell leukaemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukaemia. Of 16 consecutive patients presenting with NHL, 11 (69%) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukaemia/lymphoma. HTLV-associated leukaemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica. PMID:6134957
Blattner, W A; Gibbs, W N; Saxinger, C; Robert-Guroff, M; Clark, J; Lofters, W; Hanchard, B; Campbell, M; Gallo, R C
ONE OF THE RISK FACTORS FOR HUMAN PAPILLOMAVIRUS (HPV) INFECTION and subsequent lower genital tract neoplasias and cancers is im- paired cell-mediated immunity. HIV-positive women with severe immunosuppression are 5 times more likely than HIV-negative wo- men to have lower genital tract neoplasias. A corresponding in- crease in the risk of invasive vulvar and anal cancers, but not of cer-
Alex Ferenczy; François Coutlée; Eduardo Franco; Catherine Hankins
Background and aims Majority of cases of anal squamous cell carcinoma are human papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia (AIN). This study was conducted to examine methods which may enable the routine diagnosis of HPV-induced changes in the anal rim and the consequences of such detection especially in view of a more sensitive diagnosis of AIN. Results were
A. D. Varnai; M. Bollmann; H. Griefingholt; N. Speich; C. Schmitt; R. Bollmann; Dorothee Decker
Testicular germ cell cancer is aetiologically linked to genital malformations and male infertility and is most probably caused by a disruption of embryonic programming and gonadal development during fetal life. In some cases, germ cell neoplasia is associ- ated with a relative reduction of Y chromosomal material (e.g. 45,X\\/46,XY) or other abnormalities of the Y chromosome. The euchromatic long arm
Lone Frydelund-Larsen; Peter H. Vogt; Henrik Leffers; Alexandra Schadwinkel; Gedske Daugaard; Niels E. Skakkebaek; Ewa Rajpert-De Meyts
AimsTo evaluate the risk of having occult ductal carcinoma in situ or invasive carcinoma in the region of a focus of lobular (in situ) neoplasia (LN) diagnosed on needle core biopsy (NCB) of breast.MethodsAll cases of LN diagnosed on NCB of breast over 10 years (2000–2009 inclusive) were reviewed. The clinical presentation, radiological appearances and final pathological diagnosis on open
Colin A Purdie; Denis McLean; Elizabeth Stormonth; E Jane Macaskill; Jean B McCullough; Sharon L Edwards; Douglas C Brown; Lee B Jordan
Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been de- scribed. We report characterization of the seven Italian cases inwhichthisassociationoccurredamongaseriesof221MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the
P. Ferolla; A. Falchetti; P. Filosso; P. Tomassetti; G. Tamburrano; N. Avenia; G. Daddi; F. Puma; R. Ribacchi; F. Santeusanio; G. Angeletti; M. L. Brandi
High-grade prostatic intra-epithelial neoplasia (HGPIN) occurs a decade earlier in men of African descent in the US and Brazil, compared to white men. Prostate cancer incidence and mortality is worse in the African-American than in US white men. Sub-Saharan Africa was thought to be a low incidence area. This disparity has been attributed to lifestyle factors such as diet. We
F F Angwafo; A Zaher; R Befidi-Mengue; A Wonkam; I Takougang; I Powell; G Murphy
Sebaceous neoplasia comprises a spectrum ranging from benign to malignant. Proper histological identification is important for treatment, prognosis and potential association with the Muir–Torre syndrome (MTS). Our increased understanding of the significance and pathogenesis of these tumours has led to improved risk stratification, screening recommendations, and treatment of patients with an initial presentation of a sebaceous tumour. This review focuses on the diagnostic and histological features of sebaceous lesions, the MTS, and recent insights into the molecular pathogenesis of sebaceous tumorigenesis.
Shalin, Sara C; Lyle, Stephen; Calonje, Eduardo; Lazar, Alexander J F
Background Alcohol is a significant risk factor for development of hepatocellular carcinoma (HCC). To date, no rodent model has demonstrated formation of hepatic neoplasia in the setting of chronic alcohol consumption alone. Methods We investigated whether rats selectively bred for high alcohol preference (P rats), allowed free access to water, or water and 10% (v/v) alcohol for 6, 12 or 18 months, develop hepatic neoplasia. Results At necropsy, liver tumor incidence and multiplicity were significantly increased in 18-month alcohol-consuming versus water-consuming P rats. These data were confirmed histologically by glutathione-S-transferase pi-class (GSTp) staining. Phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK) staining was also increased in the sinusoidal lining cells within livers of alcohol-consuming versus water only P rats. In addition, cytochrome p450IIE1 (CYP2E1) mRNA, protein expression/activity, and intrahepatic oxidative stress were significantly increased in alcohol-consuming P rat livers versus water only. In contrast, acetaldehyde dehydrogenase expression decreased in alcohol-consuming versus water only P rats. No significant difference in alcohol dehydrogenase expression was detected. Conclusions These data demonstrate that chronic alcohol consumption is associated with hepatic neoplasia, MAPK/ERK activation, increased CYP2E1 activity, and intrahepatic oxidative stress in P rats. Since these rats are well-characterized as a model of alcoholism, these findings identify a novel rodent model of alcohol or “alcoholism”-induced liver neoplasia.
Yip-Schneider, Michele T.; Doyle, Courtney J.; McKillop, Iain H.; Wentz, Sabrina C.; Brandon-Warner, Elizabeth; Matos, Jesus M.; Sandrasegaran, Kumaresan; Saxena, Romil; Hennig, Matthew E.; Wu, Huangbing; Waters, Joshua A.; Klein, Patrick J.; Froehlich, Janice C.; Schmidt, C. Max
Objectives. Conflicting findings have been reported regarding the relationship between prostatic intraepithelial neoplasia (PIN) and serum prostate-specific antigen (PSA) concentration. This study evaluates whether high-grade PIN significantly raises serum PSA concentration.Methods. We evaluated 194 totally embedded whole-mounted radical prostatectomy specimens removed for clinically localized prostate cancer. No patient received preoperative therapy. In each specimen, the volume of high-grade PIN and
Erik E. Alexander; Junqi Qian; Peter C. Wollan; Robert P. Myers; David G. Bostwick
OBJECTIVE:To investigate whether human papillomavirus (HPV) testing could be used in the follow-up after large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN).METHODS:We performed a retrospective study of 41 women who developed subsequent CIN after LLETZ (group A) and 82 women without CIN for a minimum of 5 years after LLETZ (group B). The first post-treatment
Evangelos Paraskevaidis; George Koliopoulos; Yannis Alamanos; Vasiliki Malamou-Mitsi; Evangelos D Lolis; Henry C Kitchener
Aim: To assess presentation and outcome of pancreaticoduodenal endocrine tumors (PDETs) in a single center series of multiple endocrine neoplasia type 1 (MEN1) patients. Methods: Retrospective analysis of prospectively collected data of MEN1 patients observed at the University of Verona. Results: Thirty-one MEN1 patients had PDETs, including 16 nonfunctioning (NF), 6 insulinomas and 9 Zollinger-Ellison syndrome (ZES). In 16 of
Maria Vittoria Davě; Letizia Boninsegna; Luca Dalle Carbonare; Marco Toaiari; Paola Capelli; Aldo Scarpa; Giuseppe Francia; Massimo Falconi
Introduction Pancreatic endocrine tumors (PETs) occur in at least 50% of patients with multiple endocrine neoplasia type 1 (MEN1) and are\\u000a the leading cause of disease-specific mortality. However, the timing and extent of surgery for MEN1-related PETs is controversial\\u000a owing to the indolent tumor growth seen in most patients and the desire to avoid complications associated with insulin dependence.\\u000a To help
Maria A. Kouvaraki; Suzanne E. Shapiro; Gilbert J. Cote; Jeffrey E. Lee; James C. Yao; Steven G. Waguespack; Robert F. Gagel; Douglas B. Evans; Nancy D. Perrier
Aims: Germline mutated RET proto-oncogene, causing multiple endocrine neoplasia (MEN)-2a syndrome is the indication for prophylactic total thyroidectomy. Literature regarding the risk and the extent of early surgical intervention is scarce and the optimum age for surgery is still controversial. To optimize management in these young children we evaluate our experience and results.Patients and methods: From 1990 to 2001 preventive
T. Kahraman; J. W. B. de Groot; C. Rouwe; R. M. W. Hofstra; Th. P. Links; R. H. Sijmons; J. Th. M. Plukker
. Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) type IIa is rare, occurring in 20% to 30%\\u000a of the patients. The aim of this study was to evaluate clinical findings, surgical therapy, and outcome for 56 patients affected\\u000a by PHPT among 249 MEN-IIa patients collected from 84 families assembled by the Groupe d’Etude des Tumeurs á Calcitonine (GETC,\\u000a French
Jean-Louis Kraimps; Anne Denizot; Bruno Carnaille; Jean-François Henry; Charles Proye; François Bacourt; Emile Sarfati; Jean-Louis Dupond; Brigitte Maes; Jean-Paul Travagli; Andrée Boneu; Patrick Roger; Chantal Houdent; Jacques Barbier; Elisabeth Modigliani
Mussels of the genus Mytilus are widely used in environmental monitoring. They can develop a leukaemia-like disease, haemic neoplasia, which could be induced, in part, by environmental stressors. The molluscan p53 tumor suppressor gene family was previously shown to be involved in haemic neoplasia at the protein level. The purpose of this study was the quantification of molluscan p53-like isoforms at the mRNA level in mussels with haemic neoplasia compared to normal controls. The three isoforms monitored were a p53-like, a TAp63/73-like containing an intact transactivation (TA) domain, and an NH(2)-terminally truncated p63/73 isoform termed DeltaNp63/p73-like that lacks the full TA domain. Using a comprehensive data set of 62 individual Mytilus trossulus and reverse transcription real-time PCR, we found that both the p53 and the DeltaNp63/73 isoforms were up-regulated in neoplastic haemocytes compared to normal haemocytes (p<0.0001). In contrast, the mRNA levels of the non-truncated isoform TAp63/73 did not change significantly in mussels with the disease at alpha=0.01 (p=0.0141), in contrast to previous findings at the protein level. Correlations in mRNA levels between the truncated isoform and the full-length isoforms in normal haemocytes were lost in neoplastic haemocytes. The increase in mRNA concentration of the truncated DeltaNp63/73 isoform in molluscan haemic neoplasia is similar to observations in many human cancers and cell lines and underlines the phylogenetically ancient oncogenic role of this isoform. PMID:18653229
Muttray, Annette F; Schulte, Patricia M; Baldwin, Susan A
There is no guideline defining the optimal time from a positive screening fecal occult blood test to follow-up colonoscopy.\\u000a We reviewed records of 231 consecutive primary care patients who received a colonoscopy within 18 months of a positive fecal\\u000a occult blood test. We examined the relationship between time to colonoscopy and risk of neoplasia on colonoscopy using a logistic\\u000a regression analysis
Ziad F. Gellad; Daniel Almirall; Dawn Provenzale; Deborah A. Fisher
Neoplastic adnexal disease represents one of the most frequently encountered and therapeutically challenging ophthalmic problems of horses. This paper reviews current concepts in equine periocular neoplasia. Specifically, a literature-based review of the aetiopathogenesis of the most common tumours to affect the equine eyelid (squamous cell carcinoma, sarcoid, melanoma and lymphosarcoma) is provided. Current and emerging treatment modalities, including photodynamic therapy, are reviewed. PMID:20939161
Giuliano, E A
. Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly\\u000a inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening\\u000a after
Ina Kopp; Detlef Bartsch; Anja Wild; Thomas Schilling; Christoph Nies; Anders Bergenfelz; Harald Rieder; Babette Simon; Matthias Rothmund
Esophageal squamous cell carcinoma is occasionally associated with malignancies located in other regions of the alimentary tract, as well as in the head, neck, and upper respiratory tract. The stomach is most commonly used for reconstruction of the alimentary tract after esophagectomy for esophageal cancer. When synchronous tumors are located in the stomach, it is often unsuitable for use in esophageal reconstruction. In such cases, an invasive procedure involving anastomosis between the esophagus and the colon must be performed. However, this procedure is associated with a high incidence of mortality and morbidity. Seven patients with synchronous esophageal cancer and gastric epithelial neoplasia were encountered. First, endoscopic submucosal dissection (ESD) was performed for the gastric epithelial neoplasia. Then, following successful ESD, Ivor-Lewis esophagectomy for esophageal cancer was planned 1 to 2 weeks later. A total of 11 gastric epithelial lesions were found in seven patients. En bloc resection by ESD was possible in all 11 lesions and histologically complete resection was achieved in all 11 lesions. Follow-up endoscopy was done 1-2 weeks after ESD; six patients with well-healing ulcers underwent esophagectomy the next day (8 or 15 days after ESD). In one patient with a poorly healed ulcer, a second follow-up endoscopy was done 1 week later and then esophagectomy was performed the next day (22 days after ESD). Post-surgical complications related to ESD, such as bleeding or mediastinal leak, were not seen in any of the seven patients. In patients with synchronous esophageal cancer and gastric epithelial neoplasia, ESD for gastric epithelial neoplasia followed by Ivor-Lewis esophagectomy 1 to 2 weeks later is an effective choice of treatment. PMID:23237403
H I; Kim, G H; Park, D Y; Kim, Y D; Lee, B E; Ryu, D Y; Kim, D U; Song, G A
The role of the PEA3 subfamily of Ets transcription factors in breast neoplasia is controversial. Although overexpression of PEA3 (E1AF\\/ETV4), and of the related factors ERM (ETV5) and ER81 (ETV1), have been observed in human and mouse breast tumors, PEA3 factors have also been ascribed a tumor suppressor function. Here, we utilized the MMTV\\/Wnt1 mouse strain to further interrogate the
Rebecca Baker; Claire V. Kent; Rachel A. Silbermann; John A. Hassell; Lawrence J. T. Young; Louise R. Howe; Mikhail V. Blagosklonny
AIMS--To investigate the effect of combination endocrine treatment (CET) or luteinising hormone releasing hormone agonist and flutamide on non-neoplastic prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. METHODS--The morphology, including the mitotic activity, of 12 radical prostatectomies from patients with prostatic adenocarcinoma pretreated for three months with CET was evaluated in haematoxylin and eosin stained sections and compared with an untreated
R Montironi; C Magi-Galluzzi; G Muzzonigro; E Prete; M Polito; G Fabris
BACKGROUND: Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. METHODS: In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects
John Burn; D. Timothy Bishop; Jukka-Pekka Mecklin; Finlay Macrae; Gabriela Möslein; Sylviane Olschwang; Marie-Luise Bisgaard; Raj Ramesar; Diana Eccles; Eamonn R. Maher; Lucio Bertario; Heikki J. Jarvinen; Annika Lindblom; D. Gareth Evans; Jan Lubinski; Patrick J. Morrison; Judy W. C. Ho; Hans F. A. Vasen; Lucy Side; Huw J. W. Thomas; Rodney J. Scott; Malcolm Dunlop; Gail Barker; Faye Elliott; Jeremy R. Jass; Ricardo Fodde; Henry T. Lynch; John C. Mathers
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by tumors of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid tumors, often at a young age. Causal to the syndrome are germline mutations of the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has enabled presymptomatic diagnosis and
Koen MA Dreijerink; Jo WM Höppener; HT Marc Timmers; Cornelis JM Lips
Abstract Objective. Autofluorescence imaging (AFI) systems may allow better visualization of colorectal neoplasia than conventional methods. However, this is difficult to demonstrate objectively. Recently, a second-generation AFI system with a noise-reduction algorithm was developed. We aimed to objectively evaluate the visualization of colorectal neoplasia by using a second-generation AFI system and software to calculate the color-contrast index. Material and methods. We retrospectively reviewed 53 consecutive colorectal neoplasias examined using the second-generation AFI system. Color-contrast indices between the colorectal lesions and the surrounding normal mucosa in the WLI, AFI and NBI images were calculated. The WLI, AFI, NBI and CE images were also evaluated by endoscopists using questionnaire-based visualization scores. Results. The color-contrast index seen in the AFI images (33.74 ± 9.20) was significantly higher than that in either the WLI (11.14 ± 6.14) or NBI images (11.72 ± 7.12). There was no significant difference between the color-contrast indices of the WLI and NBI images. The mean AFI image visualization score (6.7 ± 1.8) was significantly higher than that of WLI (6.0 ± 1.7), and tended to be higher than that of the NBI images (6.1 ± 1.6) when assessed by less-experienced endoscopists. Conclusions. This study objectively demonstrates that compared to WLI and NBI, the second-generation AFI system enables superior visualization of colorectal neoplasms. The visualization scores were higher for the AFI images when evaluated by less-experienced endoscopists. These results indicate that the second-generation AFI system may aid less-experienced endoscopists in the detection of colorectal neoplasia. PMID:24011375
Ide, Daisuke; Tamai, Naoto; Inomata, Hiroko; Ohya, Tomohiko R; Aihara, Hiroyuki; Saito, Syoichi; Kato, Tomohiro; Tajiri, Hisao
OBJECTIVES Proton pump inhibitors (PPIs) are frequently prescribed to patients with Barrett’ s esophagus (BE), but in a subset, they can induce significant hypergastrinemia. Elevated levels of gastrin have been associated with tumorigenic effects in a number of gastrointestinal cancers. We decided to investigate the association between serum gastrin levels and dysplasia in BE. METHODS We performed a cross-sectional study and enrolled patients with BE without dysplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (AC), as well as gastroesophageal reflux disease controls, all chronically taking PPIs. Fasting serum gastrin was measured, and data were collected on patient characteristics, medication use, and the highest degree of BE neoplasia. RESULTS A total of 95 patients were enrolled. The mean age was 64.7 (±10.0) years, and 70.5 % were male. The median serum gastrin level was 40 pM. There was no significant difference in gastrin levels with increased degrees of BE neoplasia (overall P = 0.68). In multivariable analysis, the highest quartile of gastrin was associated with significantly increased odds of advanced neoplasia (HGD or AC) (odds ratio (OR): 5.46, 95 % confidence interval (CI): 1.20–24.8). CONCLUSIONS In BE patients taking PPIs, an elevated serum gastrin is associated with a history of HGD or AC. Prospective studies are needed to determine whether patients with nondysplastic BE and elevated serum gastrin are at increased risk for neoplastic progression.
Wang, Judy S.; Varro, Andrea; Lightdale, Charles J.; Lertkowit, Nantaporn; Slack, Kristen N.; Fingerhood, Michael L.; Tsai, Wei Yann; Wang, Timothy C.; Abrams, Julian A.
Synchronous colorectal neoplasias are defined as 2 or more primary tumors identified in the same patient and at the same time. The most voluminous synchronous cancer is called "first primitive" or "index" cancer. The aim of this work is to describe our experience of minimally invasive approach in patients with synchronous colorectal neoplasias. Since January 2001 till December 2009, 557 patients underwent colectomy for colorectal cancer at the Department of General and Emergency Surgery of the University of Perugia; 128 were right colon cancers, 195 were left colon cancers while 234 patients were affected by rectal cancers. We performed 224 laparoscopic colectomies (112 right, 67 left colectomies and 45 anterior resections of rectum), 91 Transanal Endoscopic Microsurgical Excisions (TEM) and 53 Trans Anal Excisions (TAE). In the same observation period 6 patients, 4 males and 2 females, were diagnosed with synchronous colorectal neoplasias. Minimal invasive treatment of colorectal cancer offers the opportunity to treat two different neoplastic lesions at the same time, with a shorter post-operative hospitalization and minor complications. According to our experience, laparoscopy and TEM may ease the treatment of synchronous diseases with a lower morbidity rate.
In situ hybridization (ISH) was performed on paraffin-embedded tissues to detect multiple high-risk human papillomavirus (HPV) subtypes in 27 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma (CA) specimens. These results were compared with those of HPV detection by HPV-PCR genotyping and p16 immunohistochemistry in the same specimens. Of the 27 cases, 17 (63%) showed HPV-DNA by HPV-ISH, including 3 metastatic lesions. HPV-DNA was detected in 18 cases (67%) by PCR. The concordance rate between HPV-ISH and HPV-PCR genotyping was 74% with moderate agreement (Kappa value, 0.41). HPV-16 was identified in 5 cases, HPV-18 in 2 cases, and HPV-45 in 1 case. Combining the results of HPV-ISH and HPV-PCR/genotyping, 22 cases (81.5%) were considered HPV positive. Immunohistochemical staining of p16 indicated that 25 (93%) cases were positive; however, 4 of these cases were HPV-negative by both PCR and ISH. Combining HPV-ISH and HPV-PCR/genotyping techniques demonstrated a high sensitivity of HPV detection in FFPE tissues from cervical glandular neoplasias. In contrast, p16 immunohistochemistry seemed to have a low specificity for determining HPV status in cervical glandular neoplasia. HPV-ISH is useful for recognizing the distribution of HPV in AIS and CA tissues and visualizing signal patterns, and may be a useful tool to confirm the cervical origin of neoplasias and metastatic lesions.
Sheng, Zhang; Minato, Hiroshi; Sasagawa, Toshiyuki; Nakada, Satoko; Kinoshita, Eriko; Kurose, Nozomu; Nojima, Takayuki; Makinoda, Satoru
To elucidate mechanisms of cancer progression, we generated inducible human neoplasia in 3-dimensionally intact epithelial tissue. Gene expression profiling of both epithelia and stroma at specific time points during tumor progression revealed sequential enrichment of genes mediating discrete biologic functions in each tissue compartment. A core cancer progression signature was distilled using the increased signaling specificity of downstream oncogene effectors and subjected to network modeling. Network topology predicted that tumor development depends upon specific ECM-interacting network hubs. Blockade of one such hub, the ?1 integrin subunit, disrupted network gene expression and attenuated tumorigenesis in vivo. Thus, integrating network modeling and temporal gene expression analysis of inducible human neoplasia provides an approach to prioritize and characterize genes functioning in cancer progression. Significance Investigating tumor progression in patient samples is complicated by etiologic heterogeneity, genetic instability, and an overabundance of precursor lesions that fail to progress. These complexities obscure construction of a dynamic picture of progression from normal tissue to invasive cancer. Here, we generate inducible human neoplasia driven by conditionally active Ras and characterize the sequence of gene expression programs engaged in epithelial tumor tissue and adjacent stroma during carcinogenesis. We show that tumor-intrinsic gene expression can be refined by sufficient downstream oncogene effectors and apply a generalizable network modeling strategy to prioritize targets based upon local interconnectivity. This analysis highlights the importance of tumor-stroma interaction during tumorigenesis and identifies ? integrin as a potential oncotherapeutic that distinguishes normal and neoplastic tissue.
Reuter, Jason A.; Ortiz-Urda, Susana; Kretz, Markus; Garcia, John; Scholl, Florence A.; Pasmooij, Anna M.G.; Cassarino, David; Chang, Howard Y.; Khavari, Paul A.
The infection with human papillomavirus (HPV) has been described as a risk factor for squamous cell carcinoma of the conjunctiva (SCCC), although the evidence is conflicting. To assess the relation between HPV infection and intraepithelial neoplasia or SCCC, we evaluated archived material from biopsies of the conjunctiva performed at the Maputo Central Hospital (Mozambique) in patients with suspected eye cancer. The quality of DNA was assessed by PCR using ?-globin-specific primers. A total of 22 consecutive biopsies (intraepithelial neoplasia, SCCC, and benign conditions) positive for ?-globin were further tested for HPV infection by PCR using the general primers GP5+/GP6+ and CPI/CPII. In addition, PCR with type-specific primers HPV 16 and HPV 18 was performed. Nineteen biopsies corresponded to intraepithelial neoplasia (two low-grade and nine high-grade) or SCCC (n=8), from which 11 (57.9%) tested positive for HPV infection; nine were positive for CPI/CPII, including one case also positive for GP5+/GP6+ and HPV 18, and the remaining two tested positive only for HPV 16. HPV DNA was not detected in any of the three biopsies of benign conditions. These results suggest a stronger association between infection with cutaneous HPV and SCCC than for mucosal HPV. However, further research is required to clarify the relation between HPV and SCCC as well as to understand the potential of the HPV vaccine currently available for cervical cancer to prevent SCCC. PMID:23752127
Carrilho, Carla; Gouveia, Patrícia; Yokohama, Hideki; Lopes, José M; Lunet, Nuno; Ferro, Josefo; Ismail, Mamudo; Walboomers, Jan; Sobrinho-Simőes, Manuel; David, Leonor
Optical spectroscopy has been shown to be an effective method for detecting neoplasia. Guided Therapeutics has developed LightTouch, a non invasive device that uses a combination of reflectance and fluorescence spectroscopy for identifying early cancer of the human cervix. The combination of the multispectral information from the two spectroscopic modalities has been shown to be an effective method to screen for cervical cancer. There has however been a relative paucity of work in identifying the individual spectral components that contribute to the measured fluorescence and reflectance spectra. This work aims to identify the constituent source spectra and their concentrations. We used non-negative matrix factorization (NNMF) numerical methods to decompose the mixed multispectral data into the constituent spectra and their corresponding concentrations. NNMF is an iterative approach that factorizes the measured data into non-negative factors. The factors are chosen to minimize the root-mean-squared residual error. NNMF has shown promise for feature extraction and identification in the fields of text mining and spectral data analysis. Since both the constituent source spectra and their corresponding concentrations are assumed to be non-negative by nature NNMF is a reasonable approach to deconvolve the measured multispectral data. Supervised learning methods were then used to determine which of the constituent spectra sources best predict the amount of neoplasia. The constituent spectra sources found to best predict neoplasia were then compared with spectra of known biological chromophores.
Baker, Kevin C.; Bambot, Shabbir
Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case 'a priori'. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients. PMID:23542137
Di Bisceglie, Cataldo; Bertagna, Angela; Composto, Emanuela R; Lanfranco, Fabio; Baldi, Matteo; Motta, Giovanna; Barberis, Anna M; Napolitano, Emanuela; Castellano, Elena; Manieri, Chiara
Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters (follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B levels) were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case ‘a priori'. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients.
Di Bisceglie, Cataldo; Bertagna, Angela; Composto, Emanuela R; Lanfranco, Fabio; Baldi, Matteo; Motta, Giovanna; Barberis, Anna M; Napolitano, Emanuela; Castellano, Elena; Manieri, Chiara
Growth plate chondrocytes undergo a coordinated differentiation process resulting in terminal differentiation and new bone formation. Enchondromas are pre-malignant, benign cartilaginous lesions that arise from growth plate chondrocytes that fail to undergo terminal differentiation. NOV (nephroblastoma overexpressed) is a member of the CCN family of proteins, which share a common multi-modular organization. While the role of NOV in chondrocyte development and cartilage neoplasia is not known, other CCN family members play a role in chondrocyte differentiation, or are differentially regulated in cartilage neoplasia. In embryonic murine growth plates, NOV was expressed in pre-hypertrophic and early hypertrophic chondrocytes. PTHrP treatment (which inhibits terminal differentiation) decreased NOV expression in murine femurs maintained in organ culture, and decreased the activity of a NOV reporter construct in vitro. Expression of the CCN family members NOV, CTGF, CYR61, and WISP-1 was examined in 15 chondrosarcomas of various grades and in three enchondromas. Expression of all of the family members was lower in the higher-grade tumours. As identification of the grade of cartilage neoplasia can sometimes be difficult using histology alone, the level of expression of CCN family members could be a useful adjunct in the determination of tumour grade. PMID:14648665
Yu, Chunying; Le, Anh-Thy; Yeger, Herman; Perbal, Bernard; Alman, Benjamin A
Epidemiologic and mechanistic evidence suggests that folate is involved in colorectal neoplasia. Some polymorphic genes involved in folate metabolism--methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta-synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS enhancer region and 3' untranslated region)--have been investigated in colorectal neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with reduced enzyme activity in vitro. For the other polymorphisms, functional data are limited and/or inconsistent. Genotype frequencies for all of the polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR 677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are associated with moderately reduced colorectal cancer risk. In four of five genotype-diet interaction studies, 677TT subjects who had higher folate levels (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT homozygote subjects with the highest alcohol intake had the highest cancer risk. Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent. There have been only one or two studies of the other polymorphisms; replication is needed. Overall, the roles of folate-pathway genes, folate, and related dietary factors in colorectal neoplasia are complex. Research priorities are suggested. PMID:14977639
Sharp, Linda; Little, Julian
The author reviews the immunophenotypic profiles displayed by the major clinicopathologic categories of T cell neoplasia, the immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia, and the contributions made by antigen receptor gene rearrangement analysis to the understanding of T cell neoplasia. Neoplasms belonging to distinct clinicopathologic categories of T cell neoplasia often exhibit characteristic immunophenotypic profiles. Approximately 80% of lymphoblastic lymphomas and 20% of acute lymphoblastic leukemias express phenotypes consistent with prethymic and intrathymic stages of T cell differentiation, including intranuclear terminal deoxynucleotidyl transferase. Cutaneous T cell lymphomas of mycosis fungoides type usually express pan-T cell antigens CD2, CD5, and CD3, often lack the pan-T cell antigen CD7, and usually express the mature, peripheral helper subset phenotype, CD4+ CD8-. Cutaneous T cell lymphomas of nonmycosis fungoides type and peripheral T cell lymphomas often lack one or more pan-T cell antigens and, in addition, occasionally express the anomalous CD4+ CD8+ or CD4- CD8- phenotypes. T gamma-lymphoproliferative disease is divisable into two broad categories: those cases that are CD3 antigen positive and exhibit clonal T cell receptor beta chain (TCR-beta) gene rearrangements and those cases that are CD3 antigen negative and exhibit the TCR-beta gene germline configuration. Human T cell lymphotropic virus-I (HTLV-I) associated Japanese, Carribean, and sporadic adult T cell leukemia/lymphomas usually express pan-T cell antigens, the CD4+ CD8- phenotype, and various T cell-associated activation antigens, including the interleukin-2 receptor (CD25). Immunophenotypic criteria useful in the immunodiagnosis of T cell neoplasia include, in increasing order of utility, T cell predominance, T cell subset antigen restriction, anomalous T cell subset antigen expression, and deletion of one or more pan-T cell antigens. Only in exceptional circumstances do normal, non-neoplastic T cell populations express the CD4- CD8- or the CD4+ CD8+ phenotype and/or lack one or more pan-T cell antigens. T cell receptor beta chain gene rearrangement analysis represents an accurate, objective, and sensitive molecular genetic marker of T cell lineage and clonality that allows discrimination among non-T cell, polyclonal T cell and monoclonal T cell populations. Non-T cells exhibit the TCR-beta gene germline configuration.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 Figure 6 Figure 7
Knowles, D. M.
Although some molecular differences between flat-depressed neoplasias (FDNs) and protruding neoplasias (PNs) have been reported, it is uncertain if the BRAF mutations or the status of phosphorylated mitogen-activated protein kinase (p-MAPK) are different between theses two groups. We evaluated the incidence of BRAF and KRAS mutations, high-frequency microsatellite instability (MSI-H), and the immunohistochemical status of p-MAPK in the nonserrated neoplasias
K Konishi; M Takimoto; K Kaneko; R Makino; Y Hirayama; H Nozawa; T Kurahashi; Y Kumekawa; T Yamamoto; H Ito; N Yoshikawa; M Kusano; K Nakayama; B J Rembacken; H Ota; M Imawari
Differentiated vulvar intraepithelial neoplasia is a unique precursor to vulvar squamous cell carcinoma that is typically HPV-negative and frequently associated with nuclear p53 staining. These features imply a mode of pathogenesis involving somatic mutations. However, the genetic relationship of differentiated vulvar intraepithelial neoplasm and vulvar squamous cell carcinoma and the role of Tp53 mutations in this process have not been resolved. We analyzed 11 differentiated vulvar intraepithelial neoplasms and 6 associated vulvar squamous cell carcinomas. Sections were stained for p53 and p63 and DNA from multiple epithelial sites, representing normal control tissues (n=10), differentiated vulvar intraepithelial neoplasias (n=18), and vulvar squamous cell carcinomas (n=6), were obtained by laser capture microdissection, and sequenced for exons 2-11 of Tp53. Six of 10 cases contained at least one Tp53 mutation-positive differentiated vulvar intraepithelial neoplasia focus; 4 strongly p53 immuno-positive and 2 negative. Staining for p53 and p63 co-localized, targeting the immature epithelium, but surface epithelium was Tp53 mutation-positive. Four of five vulvar squamous cell carcinomas were Tp53 mutation-positive; two shared identical Tp53 mutation with adjacent differentiated vulvar intraepithelial neoplasia. Disparate foci of differentiated vulvar intraepithelial neoplasia often showed different mutations consistent with multiple neoplastic clones. Differentiated vulvar intraepithelial neoplasia is, with few exceptions, associated with Tp53 mutations and will be p53 immunopositive when missense mutations (versus some nonsense and all deletion mutations) are present. Multiple Tp53 mutations in different sites supports the presence of multiple independent genetic events, but shared Tp53 mutations in both differentiated vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma support a genetic relationship between the two. The confinement of p53 staining to immature cell nuclei is consistent with maturation-dependent degradation of mutant p53 protein. PMID:20062014
Pinto, Alvaro P; Miron, Alexander; Yassin, Yosuf; Monte, Nicolas; Woo, Terri Y C; Mehra, Karishma K; Medeiros, Fabiola; Crum, Christopher P
Pancellular dysplasia involving neuroendocrine cells has been shown to be comparatively rare but crucially implicated in the development of neuroendocrine tumors in ulcerative colitis (UC). We attempted to clarify the prevalence of chromogranin A expression as a marker of neuroendocrine differentiation in UC-associated neoplasia by immunohistochemical analyses of 26 lesions of low-grade dysplasia (LGD), 32 high-grade dysplasias (HGDs) and 27 invasive cancers (INVs), along with p53 expression. We additionally assessed the utility of these proteins for differential diagnosis between LGD and HGD. Chromogranin A was considered positive when immunoreactive cells were more than 5% of neoplastic lesions, and the positivity tended to be higher in HGDs (57.7%) or INVs (46.7%) than LGDs (32.0%). Focal or diffuse nuclear staining for p53 was defined as positive. The positive rate for p53 was also higher in HGDs (59.4%; P = 0.037) or INVs (59.3%) than LGDs (30.8%). A similar trend was found in co-positivity for both proteins (HGDs, 30.7%/INVs, 26.7% versus LGDs, 12.0%). No positivity for both proteins was identified in the non-neoplastic mucosa. The combination of the two proteins improved the sensitivity (66.7%), specificity (80.0%), positive predictive value (72.7%) and negative predictive value (75.0%) for HGD as compared to p53 alone (sensitivity, 57.7%; specificity 68.0%; positive predictive value, 65.2%; negative predictive value, 60.7%). In conclusion, we show here that neuroendocrine differentiation is relatively common and represents an early event in the UC-neoplasia pathway in which p53 and chromogranin A are coordinately up-regulated. Immunohistochemical assessment of their expression might provide a useful adjunct tool for grading dysplasia in UC. PMID:24029705
Shigaki, Kotaro; Mitomi, Hiroyuki; Fujimori, Takahiro; Ichikawa, Kazuhito; Tomita, Shigeki; Imura, Johji; Fujii, Shigehiko; Itabashi, Michihiro; Kameoka, Shingo; Sahara, Rikisaburo; Takenoshita, Seiichi
The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These
N. T. Tin; N. D. Ty; L. T. Hung
|In this article, the author describes the format of the Con Test, an Australian television game show which followed the same general rules and game play as the UK show PokerFace. At the end of each round a contestant needs to decide whether or not he or she should fold. A contestant needs to know how likely it is that he or she is in last place.…
A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett's neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett's metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett's metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step ("red-flag" widefield plus confirmatory high-resolution imaging) protocols to be enhanced.
Thekkek, Nadhi; Pierce, Mark C.; Lee, Michelle H.; Polydorides, Alexandros D.; Flores, Raja M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.
Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.
Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin
Colposcopic examination of 335 women with cytologically detected human papillomavirus (HPV) revealed involvement of the cervix in 316 patients (94%), vagina in 276 (82%) and vulva in 148 (44%). A symptom complex of pruritus and superficial dyspareunia was found in 98 of the 148 patients with vulvar infection (66%). Histologic examination revealed HPV-associated vulvar intraepithelial neoplasia (VIN) in 11 of 148 biopsies (7.4%). Follow-up of the patients with HPV infection with or without VIN showed a spontaneous regression rate of 56% but also demonstrated progression to VIN 3 in two patients and to invasive carcinoma of the vulva in one. PMID:2841459
Planner, R S; Hobbs, J B
A diagnosis of mixed testicular neoplasia in a short beaked common dolphin Delphinus delphis involving a Sertoli cell tumor, an interstitial (Leydig) cell tumor and a seminoma is presented. Lymphatic spread of the Sertoli cell tumor to an adjacent retroperitoneal lymph node was observed. Testicular neoplasms have been infrequently reported in marine mammals. Demonstration of clinical signs and further health implications is extremely challenging when dealing with non accessible wildlife species, such as dolphins. However, metastatic potential for these neoplastic conditions should be considered. PMID:23324422
Díaz-Delgado, J; Espinosa de Los Monteros, A; Fernández-Maldonado, C; Arbelo, M; Quesada-Canales, O; Andrada, M; Fernández, A
Methotrexate was developed in 1949 as a synthetic folic acid analogue to compete with folic acid and thus interfere with cell replication. While initially developed as a potential treatment for acute lymphoblastic leukaemia, a serendipitous observation led to methotrexate's use to effect the dramatic cure of a case of advanced choriocarcinoma. This prompted the exploration for the potential of methotrexate to treat other conditions involving disordered trophoblastic tissue. Methotrexate has subsequently revolutionized the treatment of two pregnancy-related conditions—gestational trophoblastic neoplasia and ectopic pregnancy. This article reviews the development of modern treatment protocols that use methotrexate to medically treat these two important gynaecological conditions.
Skubisz, Monika M.; Tong, Stephen
Objective To estimate the prevalence, incidence, and clearance of abnormal vaginal cytology and vaginal intraepithelial neoplasia in human immunodeficiency virus (HIV)-seropositive women. Methods Pap tests were done semiannually for 335 HIV-seropositive and 75 HIV-seronegative women with prior hysterectomy in the prospective Women’s Interagency HIV Study cohort. Endpoints included abnormal Pap tests after hysterectomy and vaginal intraepithelial neoplasia regardless of hysterectomy. Results Over a median of 5.6 years of follow-up, vaginal Pap tests were abnormal at 1,076 (29%, 95% C.I. 25%, 33%) of 3,700 visits among HIV seropositive vs. 31 (4%, 95% C.I. 2%, 8%) of 763 visits among seronegative women (P < 0.001). Abnormal Pap tests included 641 atypical squamous cells of undetermined significance (ASC-US), 425 low-grade squamous intraepithelial lesions (LSIL), and 10 high-grade squamous intraepithelial lesions in HIV-seropositive women, and 28 ASC-US and three LSIL in HIV-seronegative women. The incidence of abnormal Pap tests after hysterectomy was 14/100 person-years among HIV-seropositive and 2/100 person-years among HIV-seronegative women (P < 0.001) and remained stable across time. The 5-year clearance rate of abnormal Pap tests was 34/100 person-years for HIV-seropositive and 116/100 person-years for HIV-seronegative women (P < 0.001). In multivariate regression models, women with lower CD4 counts were more likely to have and less likely to clear abnormal cytology when it occurred. The incidence of vaginal intraepithelial neoplasia 2+ was 0.2 and 0.01 per 100 person-years for HIV-seropositive and HIV-seronegative women (P = 0.001). Two HIV-seropositive women developed Stage II cancers, with remission after radiotherapy. Conclusion Vaginal Pap tests are often abnormal in HIV-seropositive women. Though more common than in HIV-seronegative women, vaginal intraepithelial neoplasia 2+ and especially vaginal cancers are infrequent.
Massad, L. Stewart; Xie, Xianhong; Greenblatt, Ruth M.; Minkoff, Howard; Sanchez-Keeland, Lorraine; Watts, D. Heather; Wright, Rodney L.; D'Souza, Gypsyamber; Merenstein, Daniel; Strickler, Howard
Background Multiple endocrine neoplasia 2B (MEN2B) has a classic childhood phenotypic presentation characterized by mucosal neuromas\\u000a and marfanoid habitus. However, the diagnosis of MEN2B is often delayed beyond childhood, at which time medullary thyroid\\u000a carcinoma (MTC) may be regionally advanced or metastatic. We examined the extent of this delay and its impact on the treatment\\u000a of MTC.\\u000a \\u000a \\u000a \\u000a Methods Patients in the MEN
Curtis J. Wray; Thereasa A. Rich; Steven G. Waguespack; Jeffrey E. Lee; Nancy D. Perrier; Douglas B. Evans
This report describes the clinical and cytogenetic analysis of a kindred with multiple endocrine neoplasia type 2 (MEN-2 or Sipple's syndrome) in two generations. Medullary thyroid carcinoma was present in five members either as a large or as an occult tumour. Phaeochromocytoma was demonstrated in one severely hypertensive relative and urine vanillylmandelic acid (VMA) was increased in one normotensive member. Serum parathormone (PTH) was normal in all but one normocalcaemic patient of this family who did not have a history of nephrolithiasis. Prometaphase banding failed to detect a 20p12.2 deletion or chromosome instability as observed in some MEN-2 families. Images
Zatterale, A; Stabile, M; Nunziata, V; Di Giovanni, G; Vecchione, R; Ventruto, V
Objective To describe the epidemiological features of a possible disease cluster of vulvar cancer and pre-cancers in Australian Indigenous\\u000a women living in the Northern Territory (NT) of Australia.\\u000a \\u000a \\u000a \\u000a Methods We identified NT-resident women with a confirmed histological diagnosis of vulvar cancer or high-grade vulvar intraepithelial\\u000a neoplasia (VIN) between 1 January 1996 and 31 December 2005.\\u000a \\u000a \\u000a \\u000a Results Seventy-one women were identified; 32 diagnosed with
John R. Condon; Alice R. Rumbold; Jane C. Thorn; Margaret M. O’Brien; Margaret J. Davy; Ibrahim Zardawi
lndole-3-carbinol, 3,3 -dundolylmethane, and Âˇndole-3- acetonitrile, three ĂŤndolesoccurring in edible cruciferous vegetables, have been studied for their effects on 7,12- dimethylbenz(a)anthracene-induced mammary tumor for mation in female Sprague-Dawley rats and on benzo(a)pyrene-induced neoplasia of the forestomach in female ICR\\/Ha mice. When given by p.o. intubation 20 hr prior to 7,12-dimethylbenz(a)anthracene administration, indole-3-carbinol and 3,3 -dundolylmethane had an inhibi tory effect
Lee W. Wattenberg; William D. Loub
Prostate cancer is the second leading cause of cancer related deaths in US men, largely because of metastasis, which is ultimately fatal. A better understanding of metastasis biology will lead to improved prognostication and therapeutics. We previously reported 11q13.1 gain was independently predictive of recurrence after radical prostatectomy. Multiple endocrine neoplasia I (MEN1) maps to this region of copy number gain in aggressive prostate tumors and was shown to be the only gene at this locus at increased expression in prostate cancer. Here, we demonstrate an oncogenic role for MEN1 in prostate cancer using a variety of independent assays.
Paris, PL; Sridharan, S; Hittelman, AB; Kobayashi, Y; Perner, S; Huang, G; Simko, J; Carroll, P; Rubin, MA; Collins, C
Multiple endocrine neoplasia type 2 (MEN2) is a rare familial syndrome caused by mutations in the RET protooncogene and it is transmitted as an autosomal dominant trait. The underlying problem for all the MEN syndromes is failure of a tumour suppressor gene. The genetic defect in MEN2 is on chromosome 10 (10q11.2) and has also been identified both for MEN2A and MEN2B. The reported patient is an 18-year-old girl presented with long-term diarrhea and enterocutaneous fistula. Her thyroid nodules, marfanoid habitus and bumpy lips, were also highly suggestive for MEN2B.
Shahnazari, Banafshe; Aghamaleki, Aria; Larijani, Bagher; Mohajeri Tehrani, Mohammad Reza; Rafati, Hasan; Babamahmoodi, Abdolreza
Mammary gland tumors in female dogs are an excellent model for the clinic-pathological, diagnostic and prognostic investigation of mammary neoplasias. Prognostic and predictive markers are effective in research and routine diagnosis. Interleukins play a fundamental role in cancer, with a particular function in tumor growth, invasion and metastatic potential. Interleukin-8 (IL-8) is known to possess tumorigenic and pro-angiogenic properties, and its overexpression is seen in a number of human tumors. IL-8 serum levels were determined and correlated with the clinic-pathological features and clinical evolution of mammary gland neoplasias in female dogs. IL-8 was measured by an immunoenzymatic assay in 30 female dogs with mammary neoplasias within a 12 month follow-up and in 50 control animals. The correlation between IL-8 concentration and clinical parameters was investigated. A statistically significant difference in the IL-8 serum levels was found in tumor-bearing dogs compared to the controls. In addition, when the individual parameters were evaluated, IL-8 content showed a positive correlation with the tumor progression, lymph node involvement, recurrence and death. Single and multivariate analyses showed associations between tumor recurrence, metastasis, high clinical staging and high IL-8, and also with the death risk. This was also consistent with the high IL-8 content in dogs showing tumor recurrence and metastasis. IL-8 superexpression has been detected in a number of human tumors, usually associated with a poor prognostic. Besides promoting angiogenesis, IL-8 is strongly related with the metastatic phenotype of mammary tumor cells. High IL-8 concentration was found in mammary gland cancer patients with advanced disease stages. Our results show that IL-8 can be used as a non-invasive prognostic marker for mammary gland cancer, and can be useful for the prediction of disease progression and recurrence in dogs with mammary neoplasias. The increased level of this cytokine acts as an independent prognostic marker of survival and the identification of animals with the poor prognostic. PMID:22405680
Gelaleti, Gabriela Bottaro; Jardim, Bruna Victorasso; Leonel, Camila; Moschetta, Marina Gobbe; Zuccari, Debora Ap Pires de Campos
Adenomatous polyposis coli gene (APC) polymorphisms may influence the risk for colorectal neoplasia. However, results thus far have been inconclusive. We performed a systematic literature search of the Medline, Embase, Cochrane Collaboration, and HuGE databases and reviewed the references of pertinent articles through May 2012. Odds ratios with 95% confidence intervals were used to estimate the association between 3 APC polymorphisms (D1822V, E1317Q, and I1307K) and colorectal neoplasia. In total, 40 studies from 1997 to 2010 were included in this meta-analysis, and individuals with the D1822V variant homozygote VV genotype had a slight decrease in the risk for colorectal neoplasia compared with the wild-type homozygote DD genotype (pooled odds ratio = 0.87, 95% confidence interval: 0.77, 0.99). There was a small association between the APC E1317Q polymorphism and a risk for colorectal neoplasia (variant vs. wild-type: pooled odds ratio = 1.41, 95% confidence interval: 1.14, 1.76), particularly for colorectal adenomas (variant vs. wild-type: odds ratio = 2.89, 95% confidence interval: 1.83, 4.56). Compared with those who carried the wild-type I1307K, Ashkenazi Jews who carried the I1307K variant were at a significantly increased risk for colorectal neoplasia, with a pooled odds ratio of 2.17 (95% confidence interval: 1.64, 2.86). Our study suggests that APC is a candidate gene for colorectal neoplasia susceptibility. PMID:23576677
Liang, Jing; Lin, Chunqing; Hu, Fulan; Wang, Fan; Zhu, Lin; Yao, Xiaoping; Wang, Yibaina; Zhao, Yashuang
Background Human papillomavirus (HPV) is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM) and HIV?+?groups. HIV?+?MSM in particular, have anal cancer incidences about three times that of the highest worldwide reported cervical cancer incidences. Discussion There has therefore traditionally been a lack of data from studies focused on heterosexual men and non-HIV?+?women. There is also less evidence reporting on the putative precursor lesion to anal cancer (AIN – anal intraepithelial neoplasia), when compared to cervical cancer and CIN (cervical intraepithelial neoplasia). This review summarises the available biological and epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and anal cancer amongst traditionally non-high risk groups. Summary There is strong evidence to conclude that high-grade AIN is a precursor to anal cancer, and some data on the progression of AIN to invasive cancer.
Lobular neoplasia is the new WHO terminology that encompasses the so-called lobular carcinoma in situ and atypical lobular hyperplasia. Besides the classical forms, particular variants have been described, which are mammographically detectable with distinct histologic patterns and behaviour. These variants are characterized by pleomorphic cells, necrosis with calcifications and may be associated to an invasive lobular carcinoma. Their clinical issue looks more like a preinvasive lesion than a marker of increased risk. Thus, their identification on biopsy requires a surgical reexcision. Hybrid forms, sharing a mixed lobular and ductal morphology and phenotype, have also been mentionned. Despite a lack of prognostic evaluation, it seems logical to recommend a subsequent surgical investigation when they are observed. Classical forms are usually managed by simple follow-up, although this attitude does not make a consensus among pathologists. Lobular neoplasia are not all indolent lesions and belong to an heterogeneous group that percutaneous guided biopsies have emphasized. They should be managed in a pluridisciplinar way and correctly diagnosed on percutaneous biopsies as well as surgical specimens. PMID:15932809
Bibeau, Frédéric; Borrelly, Cécile; Chateau, Marie-Christine; Saingra, Bernard; Lemanski, Claire; Masson, Bruno; Rouanet, Philippe; Gutowski, Marian
Nucleotide sequence variation in the noncoding region of the genome of human papillomavirus type 16 (HPV16) was determined by direct sequencing and single-strand conformation polymorphism analysis of DNA fragments amplified by PCR. Individuals of diverse sexual promiscuity and/or cervicopathology were studied. In a group of 14 healthy, monogamous HPV16-positive females, only two HPV16 sequence variants could be documented. Among 17 females and 3 males with multiple sex partners and living in the same geographical region, nine sequence variants were found, whereas among 7 patients with cervical neoplasia from another region, five variants were detected. Although numbers are limited, in the group of individuals at high risk of acquiring a sexually transmitted disease or with cervical neoplasia, a larger number of HPV16 sequence variants was encountered (two types among 14 individuals versus nine types among 20; Fisher's exact test, P = 0.07). Seven of the individuals were sampled repeatedly over time. For these persistently infected women, no differences in HPV16 sequences were detected, irrespective of promiscuity, and persistence of a single viral variant, spread over multiple anatomic sites, for more than 2 years could be demonstrated. This indicates that viral persistence may be a common feature and that successful superinfection with a new variant may be rare, despite a potentially high frequency of viral reinoculation.
van Belkum, A; Juffermans, L; Schrauwen, L; van Doornum, G; Burger, M; Quint, W
Women who have abnormal Papanicolaou test results may undergo colposcopy to determine the biopsy site for histologic evaluation. Traditional grading systems do not accurately assess lesion severity because colposcopic impression alone is unreliable for diagnosis. The likelihood of finding cervical intraepithelial neoplasia grade 2 or higher increases when two or more cervical biopsies are performed. Excisional and ablative methods have similar treatment outcomes for the eradication of cervical intraepithelial neoplasia. However, diagnostic excisional methods, including loop electrosurgical excision procedure and cold knife conization, are associated with an increased risk of adverse obstetric outcomes, such as preterm labor and low birth weight. Methods of endometrial assessment have a high sensitivity for detecting endometrial carcinoma and benign causes of uterine bleeding without unnecessary procedures. Endometrial biopsy can reliably detect carcinoma involving a large portion of the endometrium, but is suboptimal for diagnosing focal lesions. A 3- to 4-mm cutoff for endometrial thickness on transvaginal ultrasonography yields the highest sensitivity to exclude endometrial carcinoma in postmenopausal women. Saline infusion sonohysteroscopy can differentiate globally thickened endometrium amenable to endometrial biopsy from focal abnormalities best assessed by hysteroscopy. Hysteroscopy with directed biopsy is the most sensitive and specific method of diagnosing endometrial carcinoma, other than hysterectomy. PMID:23939565
Apgar, Barbara S; Kaufman, Amanda J; Bettcher, Catherine; Parker-Featherstone, Ebony
Recent discoveries in molecular lymphology, developmental biology, and tumor biology in the context of long-standing concepts and observations on development, growth, and neoplasia implicate overlapping pathways, processes, and clinical manifestations in developmental disorders and cancer metastasis. Highlighted in this review are some of what is known (and speculated) about the genes, proteins, and signaling pathways and processes involved in lymphatic/blood vascular development in comparison to those involved in cancer progression and spread. Clues and conundra from clinical disorders that mix these processes and mute them, including embryonic rests, multicentric nests of displaced cells, uncontrolled/invasive "benign" proliferation and lymphogenous/hematogenous "spread", represent a fine line between normal development and growth, dysplasia, benign and malignant neoplasia, and "metastasis". Improved understanding of these normal and pathologic processes and their underlying pathomechanisms, e.g., stem cell origin and bidirectional epithelial-mesenchymal transition, could lead to more successful approaches in classification, treatment, and even prevention of cancer and a whole host of other diseases. PMID:22798218
Witte, Marlys H; Dellinger, Michael T; Papendieck, Cristobal M; Boccardo, Francesco
Chromosomal instability (CIN) is a characteristic feature of cancer. In this review, we concentrate on mechanisms leading to CIN in myeloid neoplasia, i.e., myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The pathogenesis of myeloid neoplasia is complex and involves genetic and epigenetic alterations. Chromosome aberrations define specific subgroups and guide clinical decisions. Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. Indeed, disease progression is often driven by clonal evolution into complex karyotypes. Earlier studies have shown an association between telomere shortening and advanced MDS and underlined the important role of dysfunctional telomeres in the development of genetic instability and cancer. Several studies link chromosome rearrangements and aberrant DNA and histone methylation. Genes implicated in epigenetic control, like DNMT3A, ASXL1, EZH2 and TET2, have been discovered to be mutated in MDS. Moreover, gene-specific hypermethylation correlates highly significantly with the risk score according to the International Prognostic Scoring System. In AML, methylation profiling also revealed clustering dependent on the genetic status. Clearly, genetic instability and clonal evolution are driving forces for leukemic transformation. Understanding the mechanisms inducing CIN will be important for prevention and for novel approaches towards therapeutic interventions.
Vajen, Beate; Thomay, Kathrin; Schlegelberger, Brigitte
Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred. PMID:7959678
Teh, B T; Hii, S I; David, R; Parameswaran, V; Grimmond, S; Walters, M K; Tan, T T; Nancarrow, D J; Chan, S P; Mennon, J
Pancreatico-duodenal tumors are the second most common endocrinopathy in multiple endocrine neoplasia syndrome type 1, and have a pronounced effect on life expectancy as the principal cause of disease-related death. Previous discussions about surgical management have focused mainly on syndromes of hormone excess and, in particular, the management of multiple endocrine neoplasia syndrome type 1-related Zollinger–Ellison syndrome. Since hormonal syndromes tend to occur late and indicate the presence of metastases, screening with biochemical markers and endoscopic ultrasound is recommended for early detection of pancreatico-duodenal tumors, and with early surgery before metastases have developed. Surgery is recommended in patients with or without hormonal syndromes in the absence of disseminated liver metastases. The suggested operation includes distal 80% subtotal pancreatic resection together with enucleation of tumors in the head of the pancreas, and in cases with Zollinger–Ellison syndrome, excision of duodenal gastrinomas together with clearance of regional lymph node metastases. This strategy, with early and aggressive surgery before metastases have developed, is believed to reduce the risks for tumor recurrence and malignant progression.
Akerstrom, Goran; Stalberg, Peter; Hellman, Per
RAS is the most frequently mutated oncogene in human cancers. Despite decades of effort, anti-RAS therapies have remained elusive. Isoprenylcysteine carboxylmethyltransferase (ICMT) methylates RAS and other CaaX-containing proteins, but its potential as a target for cancer therapy has not been fully evaluated. We crossed a Pdx1-Cre;LSL-KrasG12D mouse, which is a model of pancreatic ductal adenocarcinoma (PDA), with a mouse harboring a floxed allele of Icmt. Surprisingly, we found that ICMT deficiency dramatically accelerated the development and progression of neoplasia. ICMT-deficient pancreatic ductal epithelial cells had a slight growth advantage and were resistant to premature senescence by a mechanism that involved suppression of cyclin-dependent kinase inhibitor 2A (p16INK4A) expression. ICMT deficiency precisely phenocopied Notch1 deficiency in the Pdx1-Cre;LSL-KrasG12D model by exacerbating pancreatic intraepithelial neoplasias, promoting facial papillomas, and derepressing Wnt signaling. Silencing ICMT in human osteosarcoma cells decreased Notch1 signaling in response to stimulation with cell-surface ligands. Additionally, targeted silencing of Ste14, the Drosophila homolog of Icmt, resulted in defects in wing development, consistent with Notch loss of function. Our data suggest that ICMT behaves like a tumor suppressor in PDA because it is required for Notch1 signaling.
Court, Helen; Amoyel, Marc; Hackman, Michael; Lee, Kyoung Eun; Xu, Ruliang; Miller, George; Bar-Sagi, Dafna; Bach, Erika A.; Bergo, Martin O.; Philips, Mark R.
Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type?I?gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.
Vannella, Lucy; Lahner, Edith; Annibale, Bruno
An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5?-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2–?Ct = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers.
Pedersen, Susanne K.; Brown, Glenn S.; Ho, Thu; Kassir, Zena; Moynihan, Audrey T.; Vizgoft, Emma K.; Dunne, Robert; Pimlott, Letitia; Young, Graeme P.; LaPointe, Lawrence C.; Molloy, Peter L.
Thyroid carcinoma is a common endocrine cancer with a favorable prognosis if subjected to timely treatment. However, the clinical identification of follicular thyroid carcinoma (FTC) among patients with benign thyroid nodules is still a challenge. Preoperative fine needle aspiration-based cytology cannot always differentiate follicular carcinomas from benign follicular neoplasias. Because current methods fail to improve preoperative diagnosis of thyroid nodules, new molecular-based diagnoses should be explored. We conducted a microarray-based study to reveal the genetic profiles unique to FTC and follicular adenomas (FAs), to identify the most parsimonious number of genes that could accurately differentiate between benign and malignant follicular thyroid neoplasia. We confirmed our data by quantitative RT-PCR and immunohistochemistry in two independent validation sets with a total of 114 samples. We were able to identify three genes, cyclin D2 (CCND2), protein convertase 2 (PCSK2), and prostate differentiation factor (PLAB), that allow the accurate molecular classification of FTC and FA. Two independent validation sets revealed that the combination of these three genes could differentiate FTC from FA with a sensitivity of 100%, specificity of 94.7%, and accuracy of 96.7%. In addition, our model allowed the identification of follicular variants of papillary thyroid carcinoma with an accuracy of 85.7%. Three-gene profiling of thyroid nodules can accurately predict the diagnosis of FTC and FA with high sensitivity and specificity, thus identifying promising targets for further investigation to ultimately improve preoperative diagnosis. PMID:15713710
Weber, Frank; Shen, Lei; Aldred, Micheala A; Morrison, Carl D; Frilling, Andrea; Saji, Motoyasu; Schuppert, Frank; Broelsch, Christoph E; Ringel, Matthew D; Eng, Charis
BACKGROUND: Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine
Sophia K Apple; Mahan Matin; Eric P Olsen; Neda A Moatamed
We combine system's biology approaches with in vivo optical molecular imaging of epithelial neoplasia for estimating disease-specific biological parameters. Molecular imaging measures and maps the dynamic optical effects, generated by the topical application of acetic acid diluted solution. The dynamic characteristics of the in vivo measured optical signal are governed by the epithelial transport effects of the biomarker. Nine biological parameters, both structural and functional, have been identified to be potentially correlated with the neoplasia growth and to be manifested to the measured data in a convoluted manner. A compartmental model of the cervical neoplastic epithelium has been developed, which predicts the dynamic optical effects in all possible parameter value combinations. We have performed global sensitivity analysis for the purpose of identifying the subset of the input parameters that are the key determinants of the model's output. Finally, we have for the first time shown that it is possible to estimate, from in vivo measured dynamic optical data, the following neoplasia related parameters: number of neoplastic layers, intracellular and extracellular space dimensions, functionality of tight junctions, and extracellular pH. These findings have been (in part) validated with optical data and biopsies obtained from 30 women with cervical neoplasia. PMID:23221799
Papoutsoglou, George S; Balas, Costas
INTRODUCTION: Although some have suggested that certain vitamins or calcium supplements may reduce adenoma recurrence, our own prior retrospective study found no such effects. The purpose of this case-control study was to further investigate whether regular vitamin or calcium supplement intake influenced the incidence of recurrent adenomatous polyps in patients with previous neoplasia who were undergoing follow-up colonoscopy. METHODS: This
Richard L. Whelan; Karen D. Horvath; Neil R. Gleason; Kenneth A. Forde; Michael D. Treat; Susan L. Teitelbaum; Andrea Bertram; Alfred I. Neugut
OBJECTIVES: Malignant transformation of Barrett's mucosa is associated with the accumulation of genetic alterations. Stepwise radical endoscopic resection of the Barrett's segment with early neoplasia is a promising new treatment resulting in complete re-epithelialization of the esophagus with neosquamous epithelium. It is unknown whether radical resection also eradicates genetic abnormalities. The aim of this study was to prospectively evaluate whether
Femke P. Peters; K. K. Krishnadath; Agnieszka M. Rygiel; Wouter L. Curvers; Wilda D. Rosmolen; P. Fockens; Fiebo J. W. ten Kate; Jantine W. P. M. van Baal; Jacques Bergman
Whereas considerable experimental evidence suggests chronic hypergastrinemia can increase the occurrence of colonic neoplasia, the risks in man remain unclear. Zollinger-Ellison syndrome (ZES) is associated with marked plasma elevation of all forms of gastrin and, because of its prolonged course, has been shown to be an excellent model disease to study the effects of chronic hypergastrinemia in man. To determine
Murray Orbuch; David J. Venzon; Irina A. Lubensky; Horst C. Weber; Fathia Gibril; Robert T. Jensen
One of the most controversial issues in breast pathology is whether lobular neoplasia (LN) is a risk factor or a precursor lesion of invasive lobular carcinoma (ILC). This is consequent to the fact that no conclusive data on the biology of LN exist. Molecular studies of LN and ILC are scanty, variable, and not consistent. Clonality of 12 cases of
Luca Morandi; Gianluca Marucci; Maria P. Foschini; Maria G. Cattani; Annalisa Pession; Cristina Riva; Vincenzo Eusebi
The use of loop electrosurgical conization (LEC) for the treatment of large high-grade cervical intraepithelial neoplasias (CINs) is often associated with a difficult procedure that results in accidental sample fragmentation, thermal damage and sometimes the presence of positive margins. This study aims to compare LEC that removes the cervical cone in two blocks (anterior and posterior cervical lips – LEC2)
Waldemar Augusto Rivoire; Heleusa Ione Monego; Ricardo dos Reis; Márcia Appel Binda; Valentino Magno; Eduardo Belmonte Tavares; Luciano Serpa Hammes; Edison Capp; Maria Isabel Edelweiss
The expression and location of proliferating cell nuclear antigen (PCNA) immunostaining in epithelial, endothelial and stromal nuclei were assessed in prostatic intra-epithelial neoplasia (PIN). It was then compared with patterns in benign lesions and in invasive adenocarcinomas of the prostate. The PCNA-positive nuclei showed homogeneous or granular types of staining, or a mixture of both, and a gradation in the
R. Montironi; C. Magi Galluzzi; L. Diamanti; I. Giannulis; E. Pisani; M. Scarpelli
Differentiated (simplex) vulvar intraepithelial neoplasia (VIN) is an uncommon variant of VIN characterized by highly differentiated morphology, making it a potential diagnostic pitfall. It may arise in the background of lichen sclerosus, and unlike most VIN, is not causally associated with human papilloma virus infection. It occurs in an older demographic and is thought to be the precursor of aggressive, invasive vulvar squamous cell carcinoma. For this reason, the timely and accurate diagnosis of this unusual lesion is crucial. The clinical and histologic features of a case of a 70-year-old woman with newly diagnosed differentiated (simplex) VIN arising in a background of long-standing lichen sclerosus is reported, and the historic aspects, current terminology, and diagnostic criteria of differentiated (simplex) VIN are reviewed. PMID:21522046
Taube, Janis M; Badger, Joanna; Kong, Christina S; Dadras, Soheil S
LXR (Liver X Receptors) act as “sensor” proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study shows that deletion of LXR in mouse fed a high-cholesterol diet recapitulates initial steps of PCa development. Elevation of circulating cholesterol in Lxr??-/- double knockout mice results in aberrant cholesterol ester accumulation and prostatic intra-epithelial neoplasia. This phenotype is linked to increased expression of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2), which results in the down-regulation of the tumor suppressors Msmb and Nkx3.1 through increased methylation of lysine 27 of histone H3 (H3K27) on their promoter regions. Altogether, our data provide a novel link between LXR, cholesterol homeostasis, and epigenetic control of tumor suppressor gene expression.
Pommier, Aurelien J. C.; Dufour, Julie; Alves, Georges; Viennois, Emilie; De Boussac, Hugues; Trousson, Amalia; Volle, David H.; Caira, Francoise; Val, Pierre; Arnaud, Philippe; Lobaccaro, Jean-Marc A.; Baron, Silvere
Malic enzyme and malate dehydrogenase (MDH) activities were radiometrically assayed in digitonin fractionated normal primary cultures (NPC), preneoplastic selected primary cultures (SPC) and tumor-derived primary cultures (TPC) of rat tracheal epithelial cells. Carcinogen-altered SPC and TPC selectively grow in the absence of pyruvate, which is required by NPC for survival. Mitochondrial-containing particulate fractions from TPC and especially SPC had markedly higher levels of NADP+-dependent malic enzyme than NPC in the presence or absence of pyruvate. This suggests that induction of mitochondrial malic enzyme activity occurs early in the progression of neoplasia. Malic enzyme activities in the soluble fractions from the various populations were not distinctly different. In contrast, particulate-bound MDH activity was higher in NPC and SPC than TPC in most cases, indicating a decrease in this enzyme late in tumorigenesis. PMID:4027954
Wasilenko, W J; Marchok, A C
We describe a 15-year-old boy who presented with a stroke. Brain MRI imaging showed thalamic and multiple cerebral infarcts. An echocardiogram revealed multiple atrial masses, which were resected. Histological examination confirmed multiple atrial myxomas. Further clinical examination of the patient revealed subtle buccal and peri-oral lentigenes. The diagnosis of Carney complex was made clinically. The patient was subsequently diagnosed with testicular seminomas and a cutaneous angiomyxoma. Genetic investigation revealed a pathological mutation in the PRKAR1A gene. We review the reported manifestations and presentations of Carney complex, along with current diagnostic guidelines. We emphasise the importance of recognising the cutaneous manifestations of this rare autosomal dominantly inherited neoplasia syndrome. PMID:19219454
Vandersteen, Anthony; Turnbull, Jess; Jan, Wajanat; Simpson, John; Lucas, Sebastian; Anderson, David; Lin, Jean-Pierre; Stratakis, Constantine; Pichert, Gabriella; Lim, Ming
Hematopoietic malignancies are the most commonly reported neoplasms in lizards, occurring sporadically as in other reptiles. An unusually high incidence of lymphoid neoplasia occurred in a collection of Egyptian spiny-tailed lizards (Uromastyx aegyptius) from 1993-2001. Eight of 15 lizards necropsied at the Louisville Zoological Garden (53%) had multicentric lymphoma. Immunohistochemistry was not useful in characterizing the lineage of normal or neoplastic lymphocytes. By light and electron microscopy (EM), the neoplasms had plasmacytoid morphologic features suggesting B-cell origin, although some tumors also had a primitive lymphoblast component. A concurrent leukemic blood profile was identified in seven of the cases (88%). All were adult animals and no sex predilection was observed. No exposure to exogenous carcinogens was observed. Some of the lizards were unrelated, so hereditary factors were unlikely. Although examination by EM and viral isolation performed on archived tissues and plasma failed to detect viruses, an infectious etiology still warrants consideration. PMID:17315465
Gyimesi, Zoltan S; Garner, Michael M; Burns, Roy B; Nichols, Donald K; Brannian, Roger E; Raymond, James T; Poonacha, Kockanda B; Kennedy, Melissa; Wojcieszyn, John W; Nordhausen, Robert
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome known to predispose subjects to endocrine neoplasms in a variety of tissues such as the parathyroid glands, pituitary gland, pancreas and gastrointestinal tract. We herein report a patient with a past history of pituitary adenoma, presenting with symptoms of chronic diarrhea for nearly one year and a sudden upper gastrointestinal hemorrhage as well as perforation without signs. Nodules in the duodenum and in the uncinate process and tail of pancreas and enlargement of the parathyroid glands were detected on preoperative imaging. Gastroscopy revealed significant ulceration and esophageal reflux diseases. The patient underwent subtotal parathyroidectomy and autotransplantation, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection and recovered well. The results observed in our patient suggest that perforation and bleeding of intestine might be symptoms of Zollinger-Ellison Syndrome in patients with MEN1. PMID:23482249
Lu, Ying-Ying; Zhu, Feng; Jing, Da-Dao; Wu, Xie-Ning; Lu, Lun-Gen; Zhou, Gen-Quan; Wang, Xing-Peng
Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome known to predispose subjects to endocrine neoplasms in a variety of tissues such as the parathyroid glands, pituitary gland, pancreas and gastrointestinal tract. We herein report a patient with a past history of pituitary adenoma, presenting with symptoms of chronic diarrhea for nearly one year and a sudden upper gastrointestinal hemorrhage as well as perforation without signs. Nodules in the duodenum and in the uncinate process and tail of pancreas and enlargement of the parathyroid glands were detected on preoperative imaging. Gastroscopy revealed significant ulceration and esophageal reflux diseases. The patient underwent subtotal parathyroidectomy and autotransplantation, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection and recovered well. The results observed in our patient suggest that perforation and bleeding of intestine might be symptoms of Zollinger-Ellison Syndrome in patients with MEN1.
Lu, Ying-Ying; Zhu, Feng; Jing, Da-Dao; Wu, Xie-Ning; Lu, Lun-Gen; Zhou, Gen-Quan; Wang, Xing-Peng
Gestational trophoblastic neoplasia (GTN) comprises a spectrum of disease from low-risk disease which can be cured with simple relatively non-toxic treatment, to extremely aggressive tumours which require specialized management. The prognostic variables in patients with GTN are different from those in other gynaecological malignancies, and the major adverse prognostic variables include long interval from antecedent pregnancy, high concentrations of the pregnancy hormone, human chorionic gonadotrophin, metastases in brain and liver and failure of prior treatment. Patients who relapse after their prior treatment can also be categorized into different risk groups. Salvage treatment can vary from single agent actinomycin D to combination chemotherapy and, in selected cases, surgery. With appropriate management, the majority of patients can achieve long-term remission and, in most cases, preserve fertility. The late side-effects of more intensive treatment are a small risk of inducing second tumours and also of bringing forward the age of menopause. PMID:14614889
Newlands, E S
Multiple endocrine neoplasia-1 (MEN1) is an autosomal dominant syndrome with classic triad of parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary adenomas. Other recognized manifestations include carcinoid, cutaneous or adrenocortical tumors. It is commonly presented with clinical features related to parathyroid, pancreas or pituitary lesions. Here, we have presented a case that had virilization and biochemical Cushing's syndrome due to adrenocortical carcinoma as presenting feature of MEN1. Cushing's syndrome in MEN1 is an extremely rare and usually late manifestation and most cases are due to corticotropin-producing pituitary adenomas. Although Cushing's syndrome generally develops years after the more typical manifestations of MEN1 appear, it may be the primary manifestation of MEN1 syndrome particularly when related to adrenal adenoma or carcinoma.
Kharb, Sandeep; Pandit, Aditi; Gundgurthi, Abhay; Garg, M. K.; Brar, K. S.; Kannan, N.; Bharwaj, Reena
The administration of cytotoxic therapy to patients with fragile X syndrome (FXS) presents several unique therapeutic challenges. The existence of fragile sites poses a theoretical risk of tumorigenesis and potentially increased treatment associated toxicity, however, controversy exists. We review the 42 previously reported cases of neoplasia in patients with FXS and report two novel neoplasms in patients treated with radiation therapy or combined chemoradiation. Our experience suggests that radiation therapy can be delivered safely in these patients without an expectation for increased acute/sub-acute normal tissue toxicity; however, treatment requires specialized facilities with the resources to deliver this care safely. Pediatr Blood Cancer 2013;60:E153-E156. © 2013 Wiley Periodicals, Inc. PMID:23873828
Farach, Andrew; Farach, Laura S; Paulino, Arnold C
Summary Stromal responses elicited by early stage neoplastic lesions can promote tumor growth. However, the molecular mechanisms that underlie the early recruitment of stromal cells to sites of neoplasia remain poorly understood. Here we demonstrate an oncogenic KrasG12D-dependent upregulation of GM-CSF in mouse pancreatic ductal epithelial cells (PDEC). An enhanced GM-CSF production is also observed in human PanIN lesions. KrasG12D-dependent production of GM-CSF in vivo is required for the recruitment of Gr1+CD11b+ myeloid cells. The suppression of GM-CSF production inhibits the in vivo growth of KrasG12D-PDECs and, consistent with the role of GM-CSF in Gr1+CD11b+ mobilization, this effect is mediated by CD8+ T cells. These results identify a pathway that links oncogenic activation to the evasion of anti-tumor immunity.
Pylayeva-Gupta, Yuliya; Lee, Kyoung Eun; Hajdu, Cristina H.; Miller, George; Bar-Sagi, Dafna
A 12-year-old girl with total limbal stem cell deficiency in the right eye following chemical burns underwent autologous cultivated limbal epithelium transplantation from the healthy left eye. Postoperatively at 6 weeks a mass at the limbus was noted, which increased in size and involved infero-nasal limbus extending over 5 mm on bulbar conjunctiva. It was a gelatinous, placoid freely movable mass with irregular surface, multiple intralesional cysts without feeder vessels or intrinsic vascularization and stained brilliantly with rose bengal. Histopathology following excision biopsy showed hyperplastic epithelium with stratified columnar cells and goblet cells. At the last follow-up, 6 months following cultivated limbal epithelium transplantation the ocular surface was stable without any recurrence of the lesion. We herein report a rare complication of epithelial hyperplasia presenting as leukoplakia following cultivated limbal epithelium transplantation mimicking ocular surface squamous neoplasia. PMID:17181623
Fatima, Anees; Matalia, Himanshu P; Vemuganti, Geeta K; Honavar, Santosh G; Sangwan, Virender S
We describe a 15-year-old boy who presented with a stroke. Brain MRI imaging showed thalamic and multiple cerebral infarcts. An echocardiogram revealed multiple atrial masses, which were resected. Histological examination confirmed multiple atrial myxomas. Further clinical examination of the patient revealed subtle buccal and peri-oral lentigenes. The diagnosis of Carney complex was made clinically. The patient was subsequently diagnosed with testicular seminomas and a cutaneous angiomyxoma. Genetic investigation revealed a pathological mutation in the PRKAR1A gene. We review the reported manifestations and presentations of Carney complex, along with current diagnostic guidelines. We emphasise the importance of recognising the cutaneous manifestations of this rare autosomal dominantly inherited neoplasia syndrome.
Vandersteen, Anthony; Turnbull, Jess; Jan, Wajanat; Simpson, John; Lucas, Sebastian; Anderson, David; Lin, Jean-Pierre; Stratakis, Constantine; Pichert, Gabriella; Lim, Ming
Human papillomavirus (HPV) infection was investigated by in situ hybridisation in histological sections from 38 women with abnormal Papanicolaou smears. 13 patients had condylomatous lesions without atypia, 15 cervical intraepithelial neoplasia (CIN) I, 4 CIN II, 3 CIN III and 2 carcinoma in situ (CIS). HPV DNA was detected in 29 cases (78%) (1 specimen was technically inadequate). HPV 16 and 18, and 31, 33 and 35 were both present (67%) in CIN III. HPV 6 and 11 were more frequent in CIN I (56%) and in condylomatous lesions (38%). 31% of the condylomatous lesions without atypia contained HPV 31, 33, and 35 and 31% of those with CIN I were infected with HPV 16 and 18. These data confirm the frequent association of HPV infection with cervical cancer and CIN, and indicate that in situ hybridisation can identify patients with specific types of HPV infection at risk for cervical cancer. PMID:1851023
Cardillo, M R; Marino, R; Pozzi, V
Multipotent stromal cells (MSCs) and their osteoblastic lineage cell (OBC) derivatives are part of the bone marrow (BM) niche and contribute to hematopoietic stem cell (HSC) maintenance. Here, we show that myeloproliferative neoplasia (MPN) progressively remodels the endosteal BM niche into a self-reinforcing leukemic niche that impairs normal hematopoiesis, favors leukemic stem cell (LSC) function, and contributes to BM fibrosis. We show that leukemic myeloid cells stimulate MSCs to overproduce functionally altered OBCs, which accumulate in the BM cavity as inflammatory myelofibrotic cells. We identify roles for thrombopoietin, CCL3, and direct cell-cell interactions in driving OBC expansion, and for changes in TGF-?, Notch, and inflammatory signaling in OBC remodeling. MPN-expanded OBCs, in turn, exhibit decreased expression of many HSC retention factors and severely compromised ability to maintain normal HSCs, but effectively support LSCs. Targeting this pathological interplay could represent a novel avenue for treatment of MPN-affected patients and prevention of myelofibrosis. PMID:23850243
Schepers, Koen; Pietras, Eric M; Reynaud, Damien; Flach, Johanna; Binnewies, Mikhail; Garg, Trit; Wagers, Amy J; Hsiao, Edward C; Passegué, Emmanuelle
The management of cervical intraepithelial neoplasia (CIN(2-3)) diagnosed during pregnancy was the subject of this study. Two hundred and eight pregnant women with an abnormal cytology were assessed in our unit over a 10-year period. The age of the patients ranged from 20 to 45 (mean 28) years. Seventy-eight of these women were histologically proven to have CIN(2-3). All patients were followed up every 8-10 weeks by cytology and colposcopy during pregnancy and reassessed 8-12 weeks postpartum. The disease persisted in 30 cases (38.4%), whereas in the remaining 48 cases it regressed to CIN(1). No case of invasive disease developed during the follow-up period in these pregnant patients. Conservative management of CIN(2-3) during pregnancy is acceptable, but close follow-up and colposcopic expertise are necessary. PMID:12566748
Vlahos, G; Rodolakis, A; Diakomanolis, E; Stefanidis, K; Haidopoulos, D; Abela, K; Georgountzos, V; Michalas, S
Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease. It is associated with a broad range of endocrine tumours, most frequently arising in the parathyroid glands, the pituitary and the pancreas. Most neuroendocrine tumours will be diagnosed in the pancreas as non-functioning neuroendocrine tumours or insulinomas. Forty-two percent of the patients will develop a gastrin-secreting neuroendocrine tumour, a gastrinoma. Gastrinomas in MEN-1 tend to be small, multiple and preferentially located in the duodenum. This paper will focus on the specific characteristics of gastrinomas in the setting of MEN-1 compared to sporadic gastrinomas. The developments in understanding the tumorigenesis of these tumours and the consequences for diagnosis and therapy will be discussed.
LXR (Liver X Receptors) act as "sensor" proteins that regulate cholesterol uptake, storage, and efflux. LXR signaling is known to influence proliferation of different cell types including human prostatic carcinoma (PCa) cell lines. This study shows that deletion of LXR in mouse fed a high-cholesterol diet recapitulates initial steps of PCa development. Elevation of circulating cholesterol in Lxr??-/- double knockout mice results in aberrant cholesterol ester accumulation and prostatic intra-epithelial neoplasia. This phenotype is linked to increased expression of the histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2), which results in the down-regulation of the tumor suppressors Msmb and Nkx3.1 through increased methylation of lysine 27 of histone H3 (H3K27) on their promoter regions. Altogether, our data provide a novel link between LXR, cholesterol homeostasis, and epigenetic control of tumor suppressor gene expression. PMID:23675307
Pommier, Aurélien J C; Dufour, Julie; Alves, Georges; Viennois, Emilie; De Boussac, Hugues; Trousson, Amalia; Volle, David H; Caira, Françoise; Val, Pierre; Arnaud, Philippe; Lobaccaro, Jean-Marc A; Baron, Silvčre
Pollution caused by the electromagnetic fields (EMFs) of radio frequencies (RF) generated by the telecommunication system is one of the greatest environmental problems of the twentieth century. The purpose of this research was to verify the existence of a spatial correlation between base station (BS) clusters and cases of deaths by neoplasia in the Belo Horizonte municipality, Minas Gerais state, Brazil, from 1996 to 2006 and to measure the human exposure levels to EMF where there is a major concentration of cellular telephone transmitter antennas. A descriptive spatial analysis of the BSs and the cases of death by neoplasia identified in the municipality was performed through an ecological-epidemiological approach, using georeferencing. The database employed in the survey was composed of three data banks: 1. death by neoplasia documented by the Health Municipal Department; 2. BSs documented in ANATEL ("Agęncia Nacional de Telecomunicaçőes": 'Telecommunications National Agency'); and 3. census and demographic city population data obtained from official archives provided by IBGE ("Instituto Brasileiro de Geografia e Estatística": 'Brazilian Institute of Geography and Statistics'). The results show that approximately 856 BSs were installed through December 2006. Most (39.60%) of the BSs were located in the "Centro-Sul" ('Central-Southern') region of the municipality. Between 1996 and 2006, 7191 deaths by neoplasia occurred and within an area of 500 m from the BS, the mortality rate was 34.76 per 10,000 inhabitants. Outside of this area, a decrease in the number of deaths by neoplasia occurred. The greatest accumulated incidence was 5.83 per 1000 in the Central-Southern region and the lowest incidence was 2.05 per 1000 in the Barreiro region. During the environmental monitoring, the largest accumulated electric field measured was 12.4 V/m and the smallest was 0.4 V/m. The largest density power was 40.78 ?W/cm(2), and the smallest was 0.04 ?W/cm(2). PMID:21741680
Dode, Adilza C; Leăo, Mônica M D; Tejo, Francisco de A F; Gomes, Antônio C R; Dode, Daiana C; Dode, Michael C; Moreira, Cristina W; Condessa, Vânia A; Albinatti, Cláudia; Caiaffa, Waleska T
There are no consensus guidelines for the management of lobular neoplasia diagnosed on core biopsy as the highest risk factor for cancer. This study aimed to assess the risk of upgrade (invasive carcinoma or ductal carcinoma in situ) at the site of the lobular neoplasia and any clinical, radiological or pathologic factors associated with the upgrade. We reviewed all cases with a diagnosis of lobular neoplasia on core biopsy from June 2006 to June 2011. Any cases with radio-pathologic discordance, coexistent lesion that required excision (atypical ductal hyperplasia, flat epithelial atypia, duct papilloma or radial scar) or non-classic variant of lobular carcinoma in situ (pleomorphic, mixed ductal and lobular, lobular carcinoma in situ with necrosis) were excluded from the study. Core biopsy indications included calcification in 35 (40%), non-mass like enhancement in 19 (22%), mass lesion in 31 (36%) and mass as well as calcification in two cases (2%). Follow-up excisions were studied for the presence of upgrade. The study cohort included 87 cases and showed an upgrade of 3.4% (95% confidence interval: 1-10%). Three cases showed an upgrade (one ductal carcinoma in situ and two invasive cancers). All upgraded cases were breast imaging-reporting and data system score ?4 and associated with atypical duct hyperplasia or in situ or invasive cancer in prior or concurrent biopsies in either breast. The number of cores and lobules involved, pagetoid duct involvement, presence of microcalcification in lobular neoplasia, needle gauge and number of cores obtained showed no correlation with the upgrade. Our results suggest that with radio-pathologic concordance and no prior biopsy proven risk for breast cancer, core biopsy finding of lobular neoplasia as the highest risk lesion can be appropriately and safely managed with clinical and radiologic follow-up as an alternative to surgical excision. PMID:23307062
Chaudhary, Shweta; Lawrence, Loretta; McGinty, Geraldine; Kostroff, Karen; Bhuiya, Tawfiqul
Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical examination. Samples were analysed for sMMP-9 concentration (enzyme-linked immuno-sorbant assay) and compared to final diagnoses. Logistic regression modelling determined independent factors associated with neoplasia. A total of 365 patients were recruited of whom 300 were analysed, including 46 normal controls. A total of 27 significant adenomas and 63 malignancies were identified. The median sMMP-9 concentration was 443ng?ml?1 (IQR: 219–782; mean: 546). Patients with neoplasia had significantly elevated sMMP-9 levels (P<0.001). Logistic regression modelling identified elevated log(sMMP-9) as the most significant predictor of neoplasia (?2=38.33, P<0.001). Other significant factors were age, sex, smoking history, abdominal pain and weight loss. The model accurately predicted neoplasia in 77.3% of cases. Sensitivity and specificity were 77.9 and 77.1%. sMMP-9 estimation can accurately stratify patient to low- or high-risk cohorts. Serum sampling is a potential means of avoiding unnecessary colonoscopy and reducing patient anxiety, iatrogenic morbidity and mortality, and cost.
Hurst, N G; Stocken, D D; Wilson, S; Keh, C; Wakelam, M J O; Ismail, T
The aim of this paper was to provide epidemiological evidence to support the notion that cervical intraepithelial neoplasia (CIN) without human papillomavirus (HPV) is a true entity. If a diagnosis of HPV-negative cervical neoplasia is erroneous, one would not expect there to be any differences in risk factors between HPV-positive and HPV-negative patients. Patients at a gynaecological outpatient clinic of a university hospital [a total of 265 consecutive women with dyskaryotic cervical smears who were subsequently diagnosed with CIN I (n=37), CIN II (n=48) or CIN III (n=180)] completed a structured questionnaire regarding smoking habits and sexual history. Analysis of an endocervical swab for Chlamydia trachomatis, analysis of a cervical scrape for HPV, and morphological examination of cervical biopsy specimens were also performed. HPV was found in 205 (77.4%) out of the 265 women. Univariate analysis showed that current age (P=0.02), current smoking behaviour (P=0.002) and the number of sexual partners (P=0.02) were significantly associated with the presence of HPV. Age at first sexual intercourse, a past history of venereal disease or genital warts, and current infection with Chlamydia trachomatis were not associated with the presence of HPV. Using multivariate logistic regression analysis, the number of sexual partners and current smoking behaviour showed an independent significant association with HPV. HPV-negative and HPV-positive CIN patients differ with respect to the risk factors for HPV. These findings suggest that HPV-negative CIN is a separate true entity.
Burger, M. P.; Hollema, H.; Pieters, W. J.; Schroder, F. P.; Quint, W. G.
Background & Aims Experimental evidence indicates that proton pump inhibitors (PPI), non-steroidal anti inflammatory drugs (NSAID)/aspirin and statins can protect patients with Barrett's esophagus (BE) from developing neoplasias. However, only limited data are available on chemoprevention in patients with BE. Methods A retrospective observational study was performed using data from patients with documented BE. Prescription information was collected from pharmacy records. Cox regression analyses were performed to examine the association between prescriptions for PPI, NSAID/aspirin or statins and the risk of developing esophageal dysplasia or adenocarcinoma during follow-up (from 1982 to 2005). Results We examined data from 344 patients diagnosed with BE (mean age 61 years, 90.4% Caucasian, 94.2% male). After BE diagnosis, 67.2% of the patients were prescribed PPI for a mean duration of 5.1 years; 49.1% were prescribed NSAID for a mean duration of 3.6 years and 25.3% were prescribed statins for a mean duration of 2.8 years. During 2,620 patient-years following BE diagnosis, high-grade dysplasia or esophageal adenocarcinoma developed in 33 patients. PPI treatment after BE diagnosis was associated with a reduced risk of high-grade dysplasia or cancer; this association persisted after adjustment for gender, age, and the length of BE at time of the diagnosis. NSAID and/or aspirin therapy were associated with a non-significant trend toward lower incidence of high-grade dysplasia or esophageal cancer. Conclusions PPI therapy reduces the risk of neoplasms in patients with BE. NSAID/aspirin appear to reduce cancer risk whereas statin use is not significantly associated with the risk of neoplasia in patients with BE.
Nguyen, Dang M.; El-Serag, Hashem B.; Henderson, Louise; Stein, Daniel; Bhattacharyya, Achyut; Sampliner, Richard
Lobular intraepithelial neoplasia Grade 3 (LIN3) is a recently recognized variant of intraepithelial lobular neoplasia (LIN) of the breast composed of either uniform, generally small cells with massive lobular distension, pleomorphic cells, signet-ring cells, or any cell type with necrosis. In contrast to classic forms of LIN, there is no consensus on therapeutic strategies for LIN3. In part this is due to the paucity of molecular data that could assist in defining the relationship of LIN3 to classic LIN and carcinomas. In this study we have employed array comparative genomic hybridization to determine the patterns of chromosomal aberrations in nine LIN3 lesions. By comparison to array CGH data of 13 classic LIN lesions, we demonstrate that classic LIN and LIN3 share several recurrent changes, in particular gains of 1q and losses of 16q. Both aberrations are known to appear early in tumorigenesis and to be associated with good prognosis. However, apart from this overlap, there were a number of karyotypic features that were observed exclusively in LIN3. Clearly, this lesion was characterized by a significantly higher number of DNA copy number changes (9 vs. 31 on average), a considerable complexity of chromosomal rearrangements with more than 16 breakpoints in one chromosome and overlapping high copy amplifications encompassing a number of known oncogenes. Our data suggest that, at the genetic level, LIN3 represents a highly advanced lesion with considerable resemblance to carcinomas and, therefore, might represent the transition state from an intraepithelial neoplasm to breast carcinoma. PMID:20155841
Boldt, Vivien; Stacher, Elvira; Halbwedl, Iris; Popper, Helmut; Hultschig, Claus; Moinfar, Farid; Ullmann, Reinhard; Tavassoli, Fattaneh A
Helicobacter pylori is responsible for most human stomach cancers. Gastric cancer also is overrepresented in populations consuming high-salt diets. Attempts to test the hypothesis that high salt promotes H. pylori carcinogenesis have been hindered by the lack of a wild-type mouse model. Based on pilot observations of unexpectedly early gastric adenocarcinoma in C57BL/6 x 129S6/SvEv (B6129) mice infected with Helicobacter felis, we conducted a study to characterize H. pylori infection in these mice and to determine whether high salt promotes tumorigenesis. Male and female mice were gavaged with H. pylori Sydney strain-1 or vehicle only and divided into four groups based on infection status and maintenance on a basal (0.25%) or high (7.5%) salt diet. In uninfected mice, the high-salt diet enhanced proliferation and marginally increased parietal cell mucous metaplasia with oxyntic atrophy. Lesions in H. pylori infected mice without regard to diet or gender were of equivalent severity and characterized by progressive gastritis, oxyntic atrophy, hyperplasia, intestinal metaplasia, and dysplasia. Infected mice on the high-salt diet exhibited a shift in antimicrobial humoral immunity from a Th1 to a Th2 pattern, accompanied by significantly higher colonization and a qualitative increase in infiltrating eosinophils. No mice developed anti-parietal cell antibodies suggestive of autoimmune gastritis. At 15 months of age infected mice in both dietary cohorts exhibited high-grade dysplasia consistent with gastric intraepithelial neoplasia. In summary, we report for the first time H. pylori-induced gastric intraepithelial neoplasia in a wild-type mouse model and show no additive effect of high-salt ingestion on tumor progression. PMID:16322215
Rogers, Arlin B; Taylor, Nancy S; Whary, Mark T; Stefanich, Erinn D; Wang, Timothy C; Fox, James G
Background Colorectal cancer (CRC) screening is recommended for average risk adults beginning at age 50. However, 7% of CRC occurs in persons younger than age 50, a group for which risk factors are not well defined. We sought to determine whether a retrospective case-control study could identify risk factors for sporadic CRC and advanced adenomatous polyps (together known as sporadic colorectal neoplasia [CRN]). Methods Using the cancer registry, medical records, and endoscopy and pathology reports from 6 local hospitals, we identified potentially eligible persons with CRN (cases) or controls who had no neoplasia on colonoscopy between 1/1/00 and 12/31/02. Consenting subjects completed a survey encompassing medical and family history, physical measures, lifestyle habits, and diet. Results Surveys were completed by 20 (15%) of 130 potentially eligible cases and by 54 (13%) of 408 potentially eligible controls. The following factors differed between cases and controls: living with a spouse/significant other (55% vs. 80%; P=0.034); prior pelvic irradiation (20% vs. 2%; P=0.019); having a first degree relative with CRC (25% vs. 7%; P=0.05); having had a prior sigmoidoscopy, colonoscopy, or barium enema (15% vs. 41%, P=0.038), and lightest weight since age 21 (155 lbs vs. 135 lbs; gender-adjusted P=0.049). Conclusions The low recruitment rate of this retrospective case-control study precludes its use for a larger, more definitive study. Several potential risk factors for advanced sporadic CRN were identified. It remains to be determined whether these factors represent an artifact of selection bias or true risk factors that may be used to stratify risk and target screening in persons under age 50.
Imperiale, Thomas F.; Kahi, Charles J.; Stuart, Jennifer S.; Qi, Rong; Born, Lawrence J.; Glowinski, Elizabeth A.; Rex, Douglas K.
Objective Bacterial vaginosis (BV), the most common vaginal disorder among women of reproductive age, has been suggested as co-factor in the development of cervical cancer. Previous studies examining the relationship between BV and cervical intra-epithelial neoplasia (CIN) provided inconsistent and conflicting results. The aim of this study is to clarify the association between these two conditions. Methods A systematic review and meta-analysis were conducted to summarize published literature on the association between BV and cervical pre-cancerous lesions. An extensive search of electronic databases Medline (Pubmed) and Web of Science was performed. The key words ‘bacterial vaginosis’ and ‘bacterial infections and vaginitis’ were used in combination with ‘cervical intraepithelial neoplasia’, ‘squamous intraepithelial lesions’, ‘cervical lesions’, ‘cervical dysplasia’, and ‘cervical screening’. Eligible studies required a clear description of diagnostic methods used for detecting both BV and cervical pre-cancerous lesions. Publications were included if they either reported odds ratios (OR) and corresponding 95% confidence intervals (CI) representing the magnitude of association between these two conditions, or presented data that allowed calculation of the OR. Results Out of 329 articles, 17 cross-sectional and 2 incidence studies were selected. In addition, two studies conducted in The Netherlands, using the national KOPAC system, were retained. After testing for heterogeneity and publication bias, meta-analysis and meta-regression were performed, using a random effects model. Although heterogeneity among studies was high (?2?=?164.7, p<0.01, I2?=?88.5), a positive association between BV and cervical pre-cancerous lesions was found, with an overall estimated odds ratio of 1.51 (95% CI, 1.24–1.83). Meta-regression analysis could not detect a significant difference between studies based on BV diagnosis, CIN diagnosis or study population. Conclusions Although most studies were cross-sectional and heterogeneity was high, this meta-analysis confirms a connection between BV and CIN.
Gillet, Evy; Meys, Joris F. A.; Verstraelen, Hans; Verhelst, Rita; De Sutter, Philippe; Temmerman, Marleen; Broeck, Davy Vanden
The Pim proteins are a family of highly homologous protein serine/threonine kinases that have been found to be overexpressed in cancer. Elevated levels of Pim1 kinase were first discovered in human leukemia and lymphomas. However, more recently Pim1 was found to be increased in solid tumors, including pancreatic and prostate cancers, and has been proposed as a prognostic marker. Although the Pim kinases have been identified as oncogenes in transgenic models, they have weak transforming abilities on their own. However, they have been shown to greatly enhance the ability of other genes or chemical carcinogens to induce tumors. To explore the role of Pim1 in prostate cancer, we generated conditional Pim1 transgenic mice, expressed Pim1 in prostate epithelium, and analyzed the contribution of PIM1 to neoplastic initiation and progression. Accordingly, we explored the effect of PIM1 overexpression in 3 different settings: upon hormone treatment, during aging, and in combination with the absence of one Pten allele. We have found that Pim1 overexpression increased the severity of mouse prostate intraepithelial neoplasias (mPIN) moderately in all three settings. Furthermore, Pim1 overexpression, in combination with the hormone treatment, increased inflammation surrounding target tissues leading to pyelonephritis in transgenic animals. Analysis of senescence induced in these prostatic lesions showed that the lesions induced in the presence of inflammation exhibited different behavior than those induced in the absence of inflammation. While high grade prostate preneoplastic lesions, mPIN grades III and IV, in the presence of inflammation did not show any senescence markers and demonstrated high levels of Ki67 staining, untreated animals without inflammation showed senescence markers and had low levels of Ki67 staining in similar high grade lesions. Our data suggest that Pim1 might contribute to progression rather than initiation in prostate neoplasia.
Narlik-Grassow, Maja; Blanco-Aparicio, Carmen; Cecilia, Yolanda; Perez, Marco; Munoz-Galvan, Sandra; Canamero, Marta; Carnero, Amancio
AIM: To evaluate the efficacy and safety of grasper type scissors (GTS) for endoscopic submucosal dissection (ESD) of gastric epithelial neoplasia. METHODS: The study was performed by 4 endoscopists in 4 institutions affiliated to The Catholic University of Korea. ESD was performed in 76 consecutive patients with gastric epithelial neoplasia by using the GTS (37 patients) or the hook knife plus coagrasper (HKC) (39 patients). The complete resection rate, complication rate, total time elapsed and elapsed time per square centimeter of the dissected specimen were analyzed between the GTS and HKC group. RESULTS: The mean age of the GTS group was 62.3 ± 11.4 years and mean age of the HKC group was 65.6 ± 10.1 years. Differentiated adenocarcinoma was found in 32.4% in the GTS group and 33.3% in the HKC group. The procedures were performed without interruption in every case in both groups. The en bloc resection rates of both groups were 100%. The total time elapsed during the procedure was 44.54 ± 21.72 min in the GTS group and 43.77 ± 21.84 min in the HKC group (P = 0.88) and the time elapsed per square centimeter of the resected lesion was 7.53 ± 6.35 min/cm2 in the GTS group and 6.92 ± 5.93 min/cm2 in the HKC group (P = 0.66). The overall complication rate was not significantly different between the two groups. CONCLUSION: GTS is a safe and effective device for ESD compared with HKC. ESD can be performed with GTS alone, which can reduce the costs for ESD.
Chung, Woo-Chul; Kim, Byung-Wook; Lim, Chul-Hyun; Kim, Tae-Ho; Park, Jae-Myung; Kim, Joon-Sung
Background & objectives: Developing a feasible and sustainable model of cervical cancer screening in developing countries continues to be a challenge because of lack of facilities and awareness in the population and poor compliance with screening and treatment. This study was aimed to evaluate a single visit approach (SVA) for the management of cervical intraepithelial neoplasia (CIN) using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) along with loop electrosurgical excision procedure (LEEP) in women attending Gynaecology OPD in a tertiary care hospital in north India. Methods: In this hospital-based study, 450 women receiving opportunistic screening by conventional Pap cytology were also screened by VIA and VILI. VIA/VILI positive cases underwent same-day colposcopy and biopsy of all lesions. If the modified Reid score was >3, the patient underwent LEEP at the same visit. Results: Of the 450 women screened, 86 (19.1%) and 92 (20.5%) women were VIA and VILI positive, respectively. Detection rates of VIA, VILI and cytology findings at ASCUS threshold were 33.3, 35.5 and 24.4 per 1000, women, respectively to detect a lesion >CIN1. For detection of CIN2+ lesion, detection rates of VIA, VILI and cytology were 20, 22.2 and 22.2 per 1000 women, respectively. Sixteen patients with Reid score >3 underwent the See-and-treat protocol. The overtreatment rate was 12.5 per cent and the efficacy of LEEP was 81.3 per cent. There were no major complications. Interpretation & conclusions: The sensitivity of VIA/VILI was comparable to cytology. A single visit approach using visual screening methods at community level by trained paramedical personnel followed by a combination of ablative and excisional therapy can help to decrease the incidence of cervical neoplasia.
Singla, Shilpa; Mathur, Sandeep; Kriplani, Alka; Agarwal, Nutan; Garg, Pradeep; Bhatla, Neerja
Mutations of the MEN1 tumour suppressor gene predispose patients to the development of multiple endocrine neoplasia type 1 (MEN1) syndrome, which is characterized by multiple endocrine tumours, including prolactinomas. The recent findings of the interaction between menin, encoded by the MEN1 gene, and the oestrogen receptor, as well as the observation of rare cases of mammary carcinomas in our heterozygous Men1 mutant mice, led us to investigate a putative tumour suppressor function of the Men1 gene in mouse mammary cells by disrupting the gene in luminal epithelial cells. A significantly higher incidence of mammary intraepithelial neoplasia (MIN) was observed in mutant WapCre-Men1(F/F) mice (51.5%) than in WapCre-Men1(+/+) (0%) or Men1(F/F) (7.1%) control mice. The majority of MIN observed in the mutant mice displayed complete menin inactivation. Because of the leakage of WapCre transgene expression, prolactinomas were observed in 83.3% of mutant mice, leading to premature death. As there was no correlation between MIN development and elevated serum prolactin levels, and phospho-STAT5 expression was decreased in mammary lesions, the increased incidence of MIN lesions was most likely due to Men1 disruption rather than to prolactinoma development. Interestingly, in MIN lesions, we found a decrease in membrane-associated E-cadherin and beta-catenin expression, the latter of which is a menin partner. Finally, reduced menin expression was found in a large proportion of two independent cohorts of patients with breast carcinomas. Taken together, the current work indicates a role of Men1 inactivation in the development of mammary pre-cancerous lesions in mice and a potential role in human mammary cancer. PMID:23180448
Seigne, Christelle; Auret, Magdalena; Treilleux, Isabelle; Bonnavion, Rémy; Assade, Fouzia; Carreira, Christine; Goddard-Léon, Sophie; Lavergne, Emilie; Chabaud, Sylvie; Garcia, Amandine; Mazoyer, Sylvie; Lu, Jieli; Bachelot, Thomas; Frappart, Lucien; Zhang, Chang Xian
Human papillomavirus (HPV) infection strongly correlates with the development of anal intraepithelial neoplasias and carcinomas; however, few studies have characterized the distribution of the specific subtypes of the virus in the varying grades of dysplasia. This report characterizes the distribution of HPV 16/18 in surgical specimens with anal intraepithelial neoplasia (AIN) I-III and histological variants of anal carcinoma. A total of 111 anal surgical specimens with no dysplasia (10), AIN I-III (53), and anal carcinomas (48) were evaluated for the presence of high-risk HPV infection and subtyped by nested PCR or the Invader Assay. High-risk virus types were detected in progressively greater number of anal intraepithelial lesions from 56% in low grade to 88% in high grade. Type 16 was the prevalent subtype and was noted in 28% of low grade and 68% of high-grade lesions. Moderate dysplasias showed type 16 in 20%, a prevalence similar to that in low-grade lesions. The non-16/18 subtypes of the virus predominated and were present in 50% of the cases. Most (89%) squamous carcinomas were associated with high-risk viruses, 68% with type 16, a prevalence similar to that noted in high-grade dysplasia. Non-16/18 subtypes were encountered more frequently in squamous carcinomas from immunodeficient individuals (57% cases) as compared with immunocompetent individuals (18% cases). The similarity in the prevalence of type 16 in high-grade dysplasia and squamous carcinomas suggests that anal intraepithelial lesion III is the true precursor of squamous carcinoma and warrants aggressive management. Anal intraepithelial lesions II showed a virus distribution that was similar to low-grade dysplasia. In addition, a subset of these that were associated with type 16 or 18 showed progression, whereas those associated with non-16/18 subtypes regressed, thereby raising the possibility of conservative management for these lesions. PMID:19838162
Wong, Anna K; Chan, Raymond C; Aggarwal, Nidhi; Singh, Manoj K; Nichols, W Stephen; Bose, Shikha
Background In the Padova International Classification, gastric precancerous lesions are labelled as “indefinite for non?invasive neoplasia” (Indef?NiN) cytohistological alterations mimicking non?invasive neoplasia (NiN), but lacking all the attributes required for a definite NiN categorisation. Aim To apply a panel of immunohistochemical (IHC) markers of cell proliferation (Mib1), intestinal differentiation (Cdx2), apoptosis (pro?caspase 3) and cell immortalisation (hTERT) to compare the IHC profiles of a series of precancerous lesions arising in gastric intestinalised (ie, IM?positive) glands. Materials and methods By applying the histological criteria consistently provided by both the Padova Classification and the World Health Organization International Agency, 112 consecutive cases were considered: intestinal metaplasia (IM; n?=?54), Indef?NiN in IM?positive gastric glands (n?=?28) and low?grade (LG) NiN (n?=?30). In each histological category, the expression of the marker was separately scored in superficial, proliferative and coil compartments. Results In all glandular compartments, Mib1, Cdx2, hTERT and pro?caspase 3 were consistently more expressed in LG?NiN than in either IM or Indef?NiN lesions (analysis of variance: p<0.001). Significant ORs (calculated by ordinal logistic regression analysis for each glandular compartment) associated IM, Indef?NiN and LG?NiN with the expression of the considered markers. Conclusions A consistent overexpression (unrestricted to the proliferative zone) of IHC markers of cell proliferation, intestinal differentiation, decreased apoptosis and cell immortalisation differentiates LG?NiN from both (simple) IM and Indef?NiN (arising in IM). An increased proliferative activity in the proliferative zone discriminates Indef?NiN lesions (ie, hyperproliferative IM) from IM. Such divergent IHC profiles may provide a rationale for scheduling follow?up protocols more properly tailored on the patient's risk for cancer.
Mauro Cassaro; Rugge, Massimo; Tieppo, Chiara; Giacomelli, Luciano; Velo, Daniela; Nitti, Donato
Objective.To evaluate the efficacy of a single prophylactic dose of actinomycin D (Act-D) in the reduction of postmolar gestational trophoblastic neoplasia (GTN) in adolescents with high-risk hydatidiform mole (Hr-HM).
E. M. H. Uberti; M. C. F. Diestel; F. E. Guimarăes; G. De Nápoli; H. Schmid
Objectives The primary objective of this study was to evaluate the benefit of using a new fluorescence-reflectance imaging system, Onco-LIFE, for the detection and localization of intraepitheal neoplasia and early invasive squamous cell carcinoma. A secondary objective was to evaluate the potential use of quantitative image analysis with this device for objective classification of abnormal sites. Design This study was a prospective, multicenter, comparative, single arm trial. Subjects for this study were aged 45 to 75 years and either current or past smokers of more than 20 pack-years with airflow obstruction, forced expiratory volume in 1 second/forced vital capacity less than 75%, suspected to have lung cancer based on either sputum atypia, abnormal chest roentgenogram/chest computed tomography, or patients with previous curatively treated lung or head and neck cancer within 2 years. Materials and Methods The primary endpoint of the study was to determine the relative sensitivity of white light bronchoscopy (WLB) plus autofluorescence-reflectance bronchoscopy compared with WLB alone. Bronchoscopy with Onco-LIFE was carried out in two stages. The first stage was performed under white light and mucosal lesions were visually classified. Mucosal lesions were classified using the same scheme in the second stage when viewed with Onco-LIFE in the fluorescence-reflectance mode. All regions classified as suspicious for moderate dysplasia or worse were biopsied, plus at least one nonsuspicious region for control. Specimens were evaluated by the site pathologist and then sent to a reference pathologist, each blinded to the endoscopic findings. Positive lesions were defined as those with moderate/severe dysplasia, carcinoma in situ (CIS), or invasive carcinoma. A positive patient was defined as having at least one lesion of moderate/severe dysplasia, CIS, or invasive carcinoma. Onco-LIFE was also used to quantify the fluorescence-reflectance response (based on the proportion of reflected red light to green fluorescence) for each suspected lesion before biopsy. Results There were 115 men and 55 women with median age of 62 years. Seven hundred seventy-six biopsy specimens were included. Seventy-six were classified as positive (moderate dysplasia or worse) by pathology. The relative sensitivity on a per-lesion basis of WLB + FLB versus WLB was 1.50 (95% confidence interval [CI], 1.26–1.89). The relative sensitivity on a per-patient basis was 1.33 (95% CI, 1.13–1.70). The relative sensitivity to detect intraepithelial neoplasia (moderate/severe dysplasia or CIS) was 4.29 (95% CI, 2.00–16.00) and 3.50 (95% CI, 1.63–12.00) on a per-lesion and per-patient basis, respectively. For a quantified fluorescence reflectance response value of more than or equal to 0.40, a sensitivity and specificity of 51% and 80%, respectively, could be achieved for detection of moderate/severe dsyplasia, CIS, and microinvasive cancer. Conclusions Using autofluorescence-reflectance bronchoscopy as an adjunct to WLB with the Onco-LIFE system improves the detection and localization of intraepitheal neoplasia and invasive carcinoma compared with WLB alone. The use of quantitative image analysis to minimize interobserver variation in grading of abnormal sites should be explored further in future prospective clinical trial.
Edell, Eric; Lam, Stephen; Pass, Harvey; Miller, York E.; Sutedja, Thomas; Kennedy, Timothy; Loewen, Gregory; Keith, Robert L.
Optical coherence microscopy (0CM) is a new optical imaging technology that can provide detailed images of tissue architecture and cellular morphology of living tissue. The technique combines the sub-cellular resolution of high numerical aperture (NA) con...
A. L. Clark A. Gillenwater R. Alizadeh-Naderi A. K. El- Naggar R. Richards-Kortum
Text Version... 160°F Pavo, Pollo 165°F CARNE FRESCAS DE RES, CERDO, TERNERA, CORDERO 145°F con 3 minutos de descanso CARNE DE AVE ... More results from www.fda.gov/downloads/food/foodborneillnesscontaminants
Aim—To investigate the correlation between immunohistochemical and biochemical steroid receptor analyses by measurement of oestrogen, progesterone, and androgen receptor status in ovarian neoplasia. Methods—Tissue samples were obtained from 27 ovarian neoplasms, including two borderline tumours. Immunohistochemical staining of the tissue slides was scored semiquantitatively, incorporating the intensity and percentage of positive staining (histoscore). Tumours with a histoscore of 10 or more were considered steroid receptor positive. The epithelial and stromal fractions of the tumours were analysed separately. To study the uniformity of receptor expression throughout a tumour, up to four samples were analysed. Results—Immunohistochemical histoscores of the oestrogen receptor in the epithelial fractions were significantly correlated with the biochemical oestrogen receptor values (r = 0.408). Androgen receptor status in the epithelial fraction was correlated with that in the stromal fraction (r = 0.741), while androgen receptor histoscores in the epithelial fraction correlated with the biochemical assay values (r = 0.463). On biochemical analysis, 17 of the 27 ovarian tumours were oestrogen receptor positive and seven were progesterone receptor positive. On immunohistochemical analysis, eight tumours were oestrogen receptor positive and two were progesterone receptor positive. Biochemical analysis showed that 14 of the 26 tumours were slightly androgen receptor positive (10–50 fmol/mg protein), while all the others were negative. On immunohistochemical analysis, seven of the 26 tumours were androgen receptor positive. When two or more specimens from one tumour were analysed, marked differences in steroid status were found, especially in progesterone receptor and androgen receptor expression. Some parts of a tumour were steroid receptor positive, while other parts were negative owing to heterogeneity of expression. Conclusions—Immunohistochemical and biochemical analysis of steroid receptors in ovarian tumours correlated weakly or not at all. Heterogeneity of expression within a tumour and the presence of progesterone and androgen receptors in the stromal fraction partly accounted for this observation. Biochemical and immunohistochemical androgen receptor status was much lower than in previous reports. Key Words: steroid receptors • ovarian neoplasia • immunohistochemical analysis • biochemical analysis
van Doorn, H. C; Burger, C.; van der Valk, P.; Bonfrer, H.
The expression of glycoconjugates specific to Jack fruit lectin (JFL) was studied in the exfoliated squamous cells of different grades of intraepithelial and invasive neoplasia of the uterine cervix. It was observed that while normal cells showed almost negative binding, the lectin binding percentage of squamous cells significantly increased with increasing atypia of the epithelium. Correlation analysis between different groups revealed that mild lectin binding in cells had a negative correlation and intense binding had a positive correlation with various stages of tumor progression. These results indicate that the number of cells with aberrant expression of glycoconjugates increases as neoplastic transformation advances. The percentage of labeled and unlabeled cells also shows a continuous transition from low to severe grades of cervical intraepithelial neoplasia and invasive carcinomas. The present study therefore shows that JFL may be used as a probe for further elaboration of detection and grading of precancerous and cancerous lesions of the uterine cervix. PMID:7924807
Pillai, K R; Remani, P; Kannan, S; Mathew, A; Sujathan, K; Vijayakumar, T; Nair, M K
BACKGROUND: Prevalence of high risk (HR) human papillomavirus (HPV) types in the states of San Luis Potosí (SLP) and Guanajuato (Gto), Mexico, was determined by restriction fragment length-polymorphism (RFLP) analysis on the E6 ~250 bp (E6-250) HR-HPV products amplified from cervical scrapings of 442 women with cervical intraepithelial neoplasia and invasive carcinoma (280 from SLP and 192 from Gto). Fresh
Rubén López-Revilla; Luz A Martínez-Contreras; Mireya Sánchez-Garza
MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the
Lois M. Mulligan; John B. J. Kwok; Catherine S. Healey; Mark J. Elsdon; Charis Eng; Emily Gardner; Donald R. Love; Sara E. Mole; Julie K. Moore; Laura Papi; Margaret A. Ponder; Hakan Telenius; Alan Tunnacliffe; Bruce A. J. Ponder
Diagnosis of corneal intraepithelial neoplasia was missed in a patient who presented with recurrent large epithelial defects\\u000a with pannus. The patient was eventually diagnosed and successfully treated with topical mitomycin C. Mitomycin C may be preferable\\u000a to surgery in lesions with extensive corneal involvement. Impression cytology should be used for early diagnosis in suspicious\\u000a lesions.
Nikhil S. Gokhale
Summary Evidencesare reviewedthat show that Herpesvirus saimirĂ of squirrel monkeys can serve as a model in studying the role of Epstein-Barr virus in certain human neoplasia. Both the in vivoand in vitro experiments with Herpesvirus saimirĂ provide approaches by which the comparisons and further experimentation could enhance biological, pathological, immunological, chemotherapeutic, and preventative ap proaches in the involvement of a
D. V. Ablashr; G. R. Pearson
Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical
N G Hurst; D D Stocken; S Wilson; C Keh; M J O Wakelam; T Ismail
Although genital human papillomavirus (HPV) infection is well established as the etiologic agent for cervical intra- epithelial neoplasia (CIN), little is known about the cofactors involved in the development of high-grade lesions or the progression of low-grade to high-grade lesions. In our study of HPV-infected women with CIN (163 CIN I, 51 CIN II and 44 CIN III), women with
Gloria Y. F. Ho; Anna S. Kadish; Robert D. Burk; Jayasri Basu; Prabhudas R. Palan; Magdy Mikhail; Seymour L. Romney
A 46-year-old Caucasian heterosexual male was referred to a dedicated AIN clinic from colorectal multidisciplinary meeting (MDM) with AIN 3 following complete resection of anal squamous cell carcinoma (SCC). On further questioning, he revealed that he also had a lesion on his penis. Histology of the penile lesion demonstrated full thickness penile intraepithelial neoplasia (PIN 3). This case illustrates the importance of thorough genital examination in patients found to have one genital pathology. PMID:22581960
Buba, A; Howard, M; Stockford, G; Farrands, P; Richardson, D
Hexose uptake during the progression of neoplasia in rat tracheal epithelial cells was studied by measuring the uptake of 2-deoxy(ÂłH)glucose (2-dGlc) in nontumorigenic (C-18) and tumorigenic (T-8, 1000-WT) rat tracheal epithelial cell lines with varying degrees of cell association as well as in: (a) normal primary cell cultures (NPC) derived from explants of nonexposed tracheas; (b) selected primary cell cultures
W. J. Wasilenko; A. C. Marchok
OBJECTIVES:Several large population studies assessing the yield of average risk screening colonoscopy have evaluated Veterans Affairs (VA) populations. It remains uncertain how generalizable these findings are to men in the general population. The aim of this study was to define the prevalence of advanced neoplasia in male patients undergoing screening colonoscopy in diverse practice settings.METHODS:The Clinical Outcomes Research Initiative (CORI)
Gavin C. Harewood; David A. Lieberman
BackgroundPrevalence estimates of cervical intraepithelial neoplasia (CIN) among HIV-infected women in India have been based on cervical cytology, which may have underestimated true disease burden. We sought to better establish prevalence estimates and evaluate risk factors of CIN among HIV-infected women in Pune, India using colposcopy and histopathology as diagnostic tools.MethodologyPreviously unscreened, non-pregnant HIV-infected women underwent cervical cancer screening evaluation
Vikrant V. Sahasrabuddhe; Ramesh A. Bhosale; Smita N. Joshi; Anita N. Kavatkar; Chandraprabha A. Nagwanshi; Rohini S. Kelkar; Cathy A. Jenkins; Bryan E. Shepherd; Seema Sahay; Arun R. Risbud; Sten H. Vermund; Sanjay M. Mehendale; Landon Myer
Background: Missense germ-line mutations in the RET protooncogene are associated with multiple endocrine neoplasia type 2A (MEN 2A). Detection of these mutant alleles in kindred members predicts disease inheritance and provides the basis for preventative thyroidectomy. Methods: A polymerase chain reaction (PCR)-based genetic test for the 19 known RET mutations was designed to study 132 members of 7 kindreds with
Samuel A. Wells; David D. Chi; Koji Toshima; Louis P. Dehner; Cheryl M. Coffin; S. Bruce Dowton; Jennifer L. Ivanovich; Mary K. DeBenedettl; William G. Dilley; Jeffrey F. Moley; Jeffrey A. Norton; Helen Donis-Keller
The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent surgery for benign prostatic hyperplasia\\u000a (BPH) before and after the Chernobyl nuclear accident was studied. BPH samples were obtained by adenomectomy from 45 patients\\u000a operated in 1984 before the accident (Group I), and 47 patients from the low contaminated Kiev City (Group II) and 76 from\\u000a high contaminated area
Alexander F Vosianov; Alina M Romanenko; Larisa B Zabarko; Béla Szende; Ching Y Wang; Steven Landas; Gabriel P Haas
Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2-3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6-7 months of age. Well differentiated adenocarcinomas
John Digiovanni; Kaoru Kiguchi; Anita Frijhoff; Eric Wilker; David K. Bol; Linda Beltrán; Samantha Moats; Angel Ramirez; José Jorcano; Claudio Conti
ABSTRACT. Breast cancer management could be improved by developing real-time imaging tools to assess tissue architecture without extensive processing. We sought to determine whether confocal fluorescence microscopy (CFM) provides sufficient information to identify neoplasia in breast tissue. Breast tissue specimens were imaged following proflavine application. Regions of interest (ROIs) were selected in histologic slides and in the corresponding region on confocal images, and then divided into sets for training and validation. Readers reviewed images in the training set and evaluated images in the validation set for the presence of neoplasia. Accuracy was assessed using histologic diagnosis as the gold standard. Seventy tissue specimens from 31 patients were imaged; 235 ROIs were identified and diagnosed as neoplastic or non-neoplastic. A training set was assembled using 23 matched ROIs; 49 matched ROIs were assembled into a validation set. Neoplasia was identified in histologic images: 93% sensitivity, 97% specificity [area under the curve (AUC=0.987)] and in confocal images: 93% sensitivity 93% specificity (AUC=0.957). CFM produced images of architectural features in breast tissue comparable with conventional histology, while requiring little processing. Potential applications include assessment of excised tissue margins and evaluation of tissue adequacy for bio-banking and genomic studies. PMID:24165742
Dobbs, Jessica L; Ding, Hao; Benveniste, Ana Paula; Kuerer, Henry M; Krishnamurthy, Savitri; Yang, Wei; Richards-Kortum, Rebecca
Transgenic mice expressing human insulin-like growth factor 1 (IGF-1) in basal epithelial cells of prostate have been characterized. Transgene expression led to activation of the IGF-1 receptor and spontaneous tumorigenesis in prostate epithelium. Hyperplasia was evident in these mice by 2–3 months of age. Atypical hyperplasias and prostatic intraepithelial neoplasia were evident by 6–7 months of age. Well differentiated adenocarcinomas appeared in mice 6 months or older. Less differentiated tumors, diagnosed as small cell carcinomas, were also observed in two of the older mice. Both lobes of the mouse prostate gland (dorsolateral and ventral) presented preneoplastic and neoplastic changes. The incidence of tumors in mice ?6 months of age (38 mice total) was 50%. The development of neoplasia in these transgenic mice appeared to follow a stepwise progression through early preneoplastic changes that ultimately culminated in frank neoplasia. These mice offer an animal model for prostate cancer that will allow study of the stepwise development of this disease and the mechanism(s) whereby IGF-1 mediates this process.
DiGiovanni, John; Kiguchi, Kaoru; Frijhoff, Anita; Wilker, Eric; Bol, David K.; Beltran, Linda; Moats, Samantha; Ramirez, Angel; Jorcano, Jose; Conti, Claudio
EGLN1 and EGLN3 are members of the egg-laying-defective 9 (EglN) prolyl-hydroxylases which during normoxia catalyse hydroxylation of the hypoxia-inducible factor (HIF)-1alpha, thereby promoting its ubiquitination by a complex containing the von Hippel-Lindau (VHL) tumour suppressor. EGLN3 also has pro-apoptotic activity in some cell types. Analyses of a well-characterised series of cases of plasma cell dyscrasias, including multiple myeloma (MM), Waldenström's macroglobulinaemia (WM) and monoclonal gammopathy of undetermined significance (MGUS) surprisingly demonstrated that the CpG island of EGLN3, and not EGLN1, is frequently methylated in these disorders. Multiple myeloma patients with a methylated EGLN3 promoter showed trends towards an increased risk of death, bone lytic lesions, anaemia, advanced stage of disease and the presence of extramedullary disease. Those individuals with methylation in the EGLN3 CpG island also had significantly lower albumin levels. These data suggest that the prolyl-hydroxylases may be a novel class of potential tumour suppressors in plasma cell neoplasia that warrant further investigation with regard to their potential utility as biomarkers. Moreover, we observed that EGLN3 is also methylated at high frequency in B-cell lymphoma subtypes, implying that loss of EGLN3 is an important epigenetic event not only in plasma cell neoplasias but also in B-cell neoplasias. PMID:19737309
Hatzimichael, Eleftheria; Dasoula, Aggeliki; Shah, Reshma; Syed, Nelofer; Papoudou-Bai, Alexandra; Coley, Helen M; Dranitsaris, George; Bourantas, Konstantinos L; Stebbing, Justin; Crook, Tim
A new genotyping-based DNA assay (Digene LQ(®)) was developed recently. The primary aim was to assess the distribution of HPV types using this new assay in atypical squamous cells of undeterminate significance (ASCUS). The secondary aim was to correlate the HPV types with the severity of the disease. The study population comprised 376 ASCUS women. The women were all Hybrid Capture II (HCII) positive and were admitted in three European referral gynecology clinics between 2007 and 2010. A colposcopy with histological examination was performed in all these patients. HPV 16 was typed in 40 % of patients, HPV 18 in 7 %, and HPV 31 in 17 %, and 18 % of patients had mixed genotypes. Patients aged over 30 more often had the HPV 16 genotype than patients aged under 30 (29 % vs. 11 %, chi-square test p < 0.001). The risk of cervical intra-epithelial neoplasia of grade 2 or more (CIN2 +) when HPV 18 positive is lower than the probability associated with HPV 16 or HPV 31: 28 % vs. 58 % and 52 %, respectively (chi-square test, p = 0.005 and p = 0.05, respectively). The Digene LQ(®), a new sequence-specific hybrid capture sample preparation, is fast and efficient and allows high-throughput genotyping of 18 HR HPV types by PCR compared to traditional non-sequence-specific sample preparation methods. PMID:23299934
Halfon, Philippe; Lindemann, Maria Luisa Mateos; Raimondo, Audrey; Ravet, Sophie; Camus, Claire; Khiri, Hacčne; Pénaranda, Guillaume; Sideri, Mario; Sandri, Maria Teresa
Refined cancer models are required if researchers are to assess the burgeoning number of potential targets for cancer therapeutics in a clinically relevant context that allows a fast turnaround. Here we use tumor-associated genetic pathways to transform primary human epithelial cells from the epidermis, oropharynx, esophagus and cervix into genetically defined tumors in a human three-dimensional (3D) tissue environment that incorporates cell-populated stroma and intact basement membrane. These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through basement membrane, a complex process that is necessary for biological malignancy in 90% of human cancers. Invasion was rapid and was potentiated by stromal cells. Oncogenic signals in 3D tissue, but not 2D culture, resembled gene expression profiles from spontaneous human cancers. We screened 3D organotypic neoplasia with well-characterized signaling pathway inhibitors to distill a clinically faithful cancer gene signature. Multitissue 3D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterizing cancer progression. PMID:21102459
Ridky, Todd W; Chow, Jennifer M; Wong, David J; Khavari, Paul A
Objective Cervical intraepithelial neoplasia grades 2-3 (CIN2-3) are usually treated by cone excision, although only 30% progress to cancer and 6–50% regress spontaneously. The aim of this study was to examine the influence of clinical factors like smoking habits, number of lifetime sexual partners, age at first sexual intercourse, sexual activity span and hormonal versus non-hormonal contraception type on the regression rate of CIN2-3. Methods In this prospective population-based cohort study 170 women aged 25–40 with abnormal cytology and colposcopy-directed biopsies showing first time onset CIN2-3 were consecutively included. The interval between biopsy and cone excision was standardized to minimum 12 weeks. Regression was defined as ?CIN1 in the cone biopsy. Results The regression rate was 22%. Consistent condom use, defined as those women whose partners used condoms for all instances of sexual intercourse, was infrequent (n?=?20, 12%). In univariate analysis consistent condom use, hormonal contraception and age at first sexual intercourse significantly predicted regression. In a multivariate analysis only consistent condom use remained as an independent predictor of regression (regression rate 55%, p?=?0.001, hazard ratio?=?4.4). Conclusion Consistent condom use between punch biopsy and cone excision in first-time onset CIN2-3 patients significantly increases the regression rate.
Munk, Ane Cecilie; Gudlaugsson, Einar; Malpica, Anais; Fiane, Bent; L?vslett, Kjell I.; Kruse, Arnold-Jan; ?vestad, Irene Tveiteras; Voorhorst, Feja; Janssen, Emiel A. M.; Baak, Jan P. A.
Lobular neoplasia (LN) is a term that encompasses both lobular carcinoma in situ and atypical lobular hyperplasia. These lesions have been shown to constitute both risk indicators and nonobligate precursors of invasive breast cancer, they are relatively uncommon, and are most often identified in specimens taken for other reasons. Their incidence has increased in the last 2 decades, and novel variants, including a pleomorphic type, have been described. Loss of E-cadherin expression is recognized as a hallmark diagnostic feature of LN and invasive lobular carcinomas, and immunohistochemical (IHC) analysis using anti-E-cadherin antibodies has been proven to be a useful method to differentiate between lobular and ductal lesions. The frequent use of E-cadherin IHC analysis in routine diagnostic histopathology, however, has resulted in confusion with regard to the actual value of IHC with antibodies against E-cadherin and other proteins of the cadherin-catenin complex. This review provides an update on recent clinicopathologic and molecular data on LN and invasive lobular carcinoma and a discussion about the use and limitations of IHC with E-cadherin in diagnostic breast pathology. PMID:23759937
Dabbs, David J; Schnitt, Stuart J; Geyer, Felipe C; Weigelt, Britta; Baehner, Frederick L; Decker, Thomas; Eusebi, Vincenzo; Fox, Stephen B; Ichihara, Shu; Lakhani, Sunil R; Palacios, Jose; Rakha, Emad; Richardson, Andrea L; Schmitt, Fernando C; Tan, Puay-Hoon; Tse, Gary M; Vincent-Salomon, Anne; Ellis, Ian O; Badve, Sunil; Reis-Filho, Jorge S
Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-?, interferon-?, interleukin-1? (IL-1?), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355.
Burbelo, Peter D.; Sampaio, Elizabeth P.; Giaccone, Giuseppe; Zaman, Rifat; Kristosturyan, Ervand; Rajan, Arun; Ding, Li; Ching, Kathryn H.; Berman, Arlene; Oliveira, Joao B.; Hsu, Amy P.; Klimavicz, Caitlin M.; Iadarola, Michael J.; Holland, Steven M.
Glutathione S-transferase (GST) isoenzyme expression is altered in a variety of neoplasms and the enzymes are implicated in metabolism of carcinogens and resistance to drugs, including cisplatin. We have studied GST Alpha, Pi, Mu and microsomal isoenzyme expression by immunohistochemistry in normal and cryptorchid testes, intratubal germ cell neoplasia (ITGCN), seminoma and non-seminomatous germ cell tumours. In 16 stage II-IV malignant teratoma intermediate (MTI) both orchidectomy and post-treatment residual surgical masses were studied. All four isoenzymes were strongly expressed in Leydig and Sertoli cells. GST Pi was absent from normal spermatogonia but strongly expressed by the neoplastic germ cells of ITGCN and seminoma. GST Pi was strongly expressed in all elements of teratoma, irrespective of differentiation. There were no qualitative differences in expression between primary and post-chemotherapy metastases. GST Alpha expression in teratoma correlated with epithelial differentiation. GSTs may be important in normal spermatogenesis and protection of germ cells from teratogens and carcinogens. They may have a role in testicular tumour drug resistance but this role is not well defined. GST Pi is a new marker for ITGCN. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6
Klys, H. S.; Whillis, D.; Howard, G.; Harrison, D. J.
Current procedures for oral cancer screening typically involve visual inspection of the entire tissue surface at risk under white light illumination. However, pre-cancerous lesions can be difficult to distinguish from many benign conditions when viewed under these conditions. We have developed wide-field (macroscopic) imaging system which additionally images in cross-polarized white light, narrowband reflectance, and fluorescence imaging modes to reduce specular glare, enhance vascular contrast, and detect disease-related alterations in tissue autofluorescence. We have also developed a portable system to enable high-resolution (microscopic) evaluation of cellular features within the oral mucosa in situ. This system is a wide-field epi-fluorescence microscope coupled to a 1 mm diameter, flexible fiber-optic imaging bundle. Proflavine solution was used to specifically label cell nuclei, enabling the characteristic differences in N/C ratio and nuclear distribution between normal, dysplastic, and cancerous oral mucosa to be quantified. This paper discusses the technical design and performance characteristics of these complementary imaging systems. We will also present data from ongoing clinical studies aimed at evaluating diagnostic performance of these systems for detection of oral neoplasia.
Pierce, Mark C.; Schwarz, Richard A.; Rosbach, Kelsey; Roblyer, Darren; Muldoon, Tim; Williams, Michelle D.; El-Naggar, Adel K.; Gillenwater, Ann M.; Richards-Kortum, Rebecca
Urocortin (UCN) is a 40-aminoacid neuropeptide that regulates angiogenesis and inhibits cell proliferation. Our aim was to examine the relationship of UCN expression to the clinicopathological parameters of pancreatic ductal adenocarcinoma (PDAC) and histological grade of pancreatic intraepithelial neoplasia (PanIN). Tissue microarray was used to analyze UCN protein expression in 89 surgical specimens including 21 PanIN, 3 PDAC arising from PanIN, and 65 PDAC without PanIN. UCN immunoscores ranging from 0 to 12 were obtained by multiplying intensity (scored on a 3-point scale) by the percentage of stained cells (scored on a 4-point scale). Strong expression of UCN was detected in 5 specimens of non-neoplastic pancreatic ductal epithelia. UCN immunoscore was significantly higher in PanIN-1 than in PanIN-2 and PanIN-3 (p = 0.038) and significantly higher in well-differentiated PDAC or early American Joint Committee on Cancer (AJCC) stage PDAC than in poorly differentiated or advanced stage PDAC (p = 0.025, p = 0.018). Higher expression of UCN correlates with PDAC tumor grade and AJCC pathologic stage as well as PanIN grade. Immunohistochemical assessment of UCN may help clinicians predict tumor recurrence rate and help pathologists make a proper diagnosis. PMID:23755913
Cheng, Ming-Fang; Tsai, Wen-Chiuan; Hsia, Kan-Tai; Yang, Ya-Sung; Jin, Jong-Shiaw
In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type). PMID:16419625
Sideri, Mario; Jones, Ronald W; Wilkinson, Edward J; Preti, Mario; Heller, Debra S; Scurry, James; Haefner, Hope; Neill, Sallie
Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia. PMID:23400731
Sabo, E; Klorin, G; Montgomery, E; Drumea, K C; Ben-Izhak, O; Lachter, J; Vieth, M
Intraoperative consultations may pose considerable diagnostic challenge to the neuropathologist in diagnosing primary and metastatic neoplasms of the central nervous system (CNS). Cytological preparations in the form of squash, touch, imprint or smears are few of the available modalities in addition to the frozen section (FS). Although the latter is superior in providing both histologic patterns and cytomorphologic details yet smears are of vital importance when tissue available is limited (stereotactic biopsy), scrutinisation of intercellular matrix (astrocytoma versus oligodendroglioma) and evaluation of discohesive cells (lymphoma, pituitary adenoma) and in inflammatory lesions. This review is intended to emphasize the value, applicability and limitations of neurocytology aiming to expedite the intraoperative smear-based diagnoses of CNS neoplasia as per the World Health Organization (WHO) classification. We recommend that whenever possible, both smears and FS should be examined concomitantly and in a correlative manner. In the unlikely event of a mismatch between the findings on smear and FS, intraoperative diagnosis is primarily based on FS, if adequate tissue is available. However, each case must be evaluated on its own merit and in difficult cases relevant differential diagnoses should be offered to facilitate surgical decisions and optimally triage patient management.
Sharma, Suash; Deb, Prabal
Pancreatic cancer is an almost uniformly lethal disease, characterized by late diagnosis, early metastasis, resistance to chemotherapy, and early mutation of the Kras oncogene. Here we show that the receptor for advanced glycation endproducts (RAGE) is required for the activation of interleukin 6 (IL-6)–mediated mitochondrial signal transducers and activators of transcription 3 (STAT3) signaling in pancreatic carcinogenesis. RAGE expression correlates with elevated levels of autophagy in pancreatic cancer in vivo and in vitro, and this heightened state of autophagy is required for IL-6–induced STAT3 activation. To further explore the intersection of RAGE, autophagy, and pancreatic carcinogenesis, we created a transgenic murine model, backcrossing RAGE-null mice to a spontaneous mouse model of pancreatic cancer, Pdx1-Cre:KrasG12D/+ (KC). Targeted ablation of Rage in KC mice delayed neoplasia development, decreased levels of autophagy, and inhibited mitochondrial STAT3 activity and subsequent ATP production. Our results suggest a critical role for RAGE expression in the earliest stages of pancreatic carcinogenesis, potentially acting as the “autophagic switch,” regulating mitochondrial STAT3 signaling.
Kang, Rui; Loux, Tara; Tang, Daolin; Schapiro, Nicole E.; Vernon, Philip; Livesey, Kristen M.; Krasinskas, Alyssa; Lotze, Michael T.; Zeh, Herbert J.
Multiple endocrine neoplasia type 2B (MEN 2B) is a rare syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and typical phenotypic features, such as marfanoid habitus, multiple mucosal ganglioneuromas and thickened corneal nerves. Individuals with MEN 2B may develop megacolon and pseudo-obstruction due to intestinal ganglioneuromatosis simulating Hirschsprung's (HSCR) disease. We hereby describe the clinical and genetic features of a 21-year-old male patient with MEN 2B associated with pseudo-HSCR disease. The patient had MTC, pheochromocytoma, marfanoid habitus, multiple mucosal ganglioneuromas, thickened corneal nerves and severe gastrointestinal involvement. Emergent laparotomy was performed when he was presented with acute bowel obstruction. The myenteric and submucosal nerve plexuses in the small and large intestines were composed of diffusely hyperplasic, disorganized, mature ganglion cells. Genetic testing revealed a de novo ret proto-oncogene germline mutation in codon 918 in exon 16. Megacolon and pseudo-obstruction similar to the HSCR disease may develop in patients with MEN 2B. However, the observed dysmotility is the result of an abnormal proliferation of intramural ganglion cells in contrast to the absence of enteric ganglia which were present in the HSCR disease. Attentiveness about the phenotypic characteristics and unusual findings might lead to early and correct diagnosis of the MEN 2B syndrome. This approach improves the survival rate and quality of life considerably. Images Figure 1
Erdogan, Murat Faik; Gulec, Bulent; Gursoy, Alptekin; Pekcan, Mesut; Azal, Omer; Gunhan, Omer; Bayer, Atilla
Alterations in pathways mediated by retinoblastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroendocrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malignancy by postnatal day 350. By age of 380 days, 84% of Rb+/? mice exhibited lung metastases from C-cell thyroid carcinomas. Expression of a human RB transgene in the Rb+/? mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12% in Rb+/? mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors.
Nikitin, Alexander Yu.; Juarez-Perez, Maria I.; Li, Song; Huang, Leaf; Lee, Wen-Hwa
The strong link between inflammation and colorectal carcinogenesis provides the rationale for using anti-inflammatory agents for chemoprevention of colorectal cancer (CRC). Several naturally occurring substances with anti-inflammatory properties, used in a purified 'nutraceutical' form, including omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and polyphenols such as curcumin and resveratrol, have been demonstrated to have anti-CRC activity in preclinical models. As expected, these agents have an excellent safety and tolerability profile in Phase II clinical trials. Phase III randomized clinical trials of these naturally occurring substances are now beginning to be reported. The omega-3 polyunsaturated fatty acid EPA, in the free fatty acid (FFA) form, has been demonstrated to reduce adenomatous polyp number and size in patients with familial adenomatous polyposis (FAP), a finding which has prompted evaluation of this formulation of EPA for prevention of 'sporadic' colorectal neoplasia. Anti-inflammatory 'nutraceuticals' require further clinical evaluation in polyp prevention trials as they exhibit many of the characteristics of the ideal cancer chemoprevention agent, including safety, tolerability and patient acceptability. PMID:22893204
Hull, Mark A
The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report.
The purpose of this work is to explore image quantitation in small-animal positron emission tomography (PET) as a tool for following proliferation and malignant transformation of mammary intraepithelial neoplasia outgrowths in vivo in laboratory mice. The expected application of the work is preclinical evaluations of breast cancer therapeutics. For nonpalpable or prepalpable disease, current practice involves large cohorts of mice with groups sacrificed at each time point. Because of the substantial variability in tumor development, numerous mice are needed at each time point to obtain statistical power. In vivo imaging techniques have the ability to follow a single mouse over multiple time points in longitudinal studies, and therefore reduce the number of mice needed for evaluation. Longitudinal studies offer an additional increase in statistical power by being able to control for the condition of disease (e.g. tumor size) at onset of treatment. Critical to the success of this approach is the ability to extract meaningful quantitative markers of disease. The study reported here describes a computational approach to extracting quantitative markers of disease progression and proliferation in longitudinal PET studies, and an analysis of the increase in statistical power due to temporal correlations in the extracted markers.
Abbey, Craig K.; Borowsky, Alexander D.; McGoldrick, Erik T.; Gregg, Jeffery P.; Cardiff, Robert D.; Cherry, Simon R.
Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histologic evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histologic detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images showed a striking similarity to the results of H&E staining, as shown by the 100% concordance achieved by the study pathologists' diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions. PMID:22961775
Makino, Tomoki; Jain, Manu; Montrose, David C; Aggarwal, Amit; Sterling, Joshua; Bosworth, Brian P; Milsom, Jeffrey W; Robinson, Brian D; Shevchuk, Maria M; Kawaguchi, Kathy; Zhang, Ning; Brown, Christopher M; Rivera, David R; Williams, Wendy O; Xu, Chris; Dannenberg, Andrew J; Mukherjee, Sushmita
In a retrospective case-control study biopsy specimens of cervical intraepithelial neoplasia (CIN) lesions from 47 women in whom invasive cancer subsequently developed (cases) and from 94 control subjects in whom CIN was diagnosed within 6 months of the diagnosis for the matched case subject but invasive disease did not develop were tested for human papillomavirus (HPV) DNA with tissue in-situ hybridization. There were no significant differences in the frequency of detection of HPV DNA between the two groups. In a cross-sectional survey the prevalence of HPV DNA was found to be 11% in specimens without CIN, 27% in those with CIN I, 49% in those with CIN II and 56% in those with CIN III. The positivity rates for HPV 16/33 DNA increased with the severity of CIN, but this was not observed for HPV 6/11 and 18 DNA. A comparison of the results of the case-control and cross-sectional studies suggested that the younger cohort of women had higher prevalence rates of HPV DNA than the older cohort.
Caussy, D; Marrett, L D; Worth, A J; McBride, M; Rawls, W E
To investigate the role of ?-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of ?-catenin lacking the NH2-terminal 89 amino acids (?N89?-catenin) under the control of the mouse mammary tumor virus long terminal repeat. Our results show that ?N89?-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. Virgin ?N89?-catenin mammary glands resemble those found in wild-type (wt) pregnant mice and inappropriately express cyclin D1 mRNA. In contrast to wt mammary glands, which resume a virgin appearance after cessation of lactation, transgenic mammary glands involute to a midpregnant status. All transgenic females develop multiple aggressive adenocarcinomas early in life. Surprisingly, the ?N89?-catenin phenotype differs from those elicited by overexpression of Wnt genes in this gland. In particular, ?N89?-catenin has no effect on ductal side branching. This suggests that Wnt induction of ductal branching involves additional downstream effectors or modulators.
Imbert, Alexandra; Eelkema, Rachel; Jordan, Sara; Feiner, Helen; Cowin, Pamela
For several years there has been the association between the persistent HPV infection (especially with high oncogenic potency i.e. 16, 18) and the cervical intraepithelial neoplasia. The pathomechanism is probably considered with spread of the early virus gene E1, E2 and the suppressor protein p53 complexes. Further on these complexes cause the neoplastic cell transformation. There has also been described the role of impaired immune response in these cases. The abnormalities cover malformation of antigen presenting system APC, decrease of MHC-I and MHC-II heavy chains rate, decrease of the Langer-hans cells and decrease of count and cytotoxic activities of lymphocytes B and NK cells. The invasive and destructive techniques of HPV associated CIN treatment do not respect its pathogenesis. Therefore the new non surgical methods of treatment would play a major role in treatment and prevention of women especially in their reproductive period. The aim of this work was the evaluation of the Iscador QuS and Intron A role in the management of HPV associated CIN. The 60 patients with CIN and HPV have been diagnosed and treated in our clinic for 12 months. Early results present increase of regression and significant decrease of progression rates in both groups of examined women, comparing to the control group. The stationery state rates in this groups of women were similar to the control group. PMID:10375935
Jach, R; Basta, A
Introduction: Early detection of bladder carcinoma is very important clinical problem. Diagnostic yield of white light cystoscopy with random biopsies remains poor. The use of exogenous fluorescence significantly increases the sensitivity, but specificity remains low. We analyzed diagnostic efficacy of OCT during white light cystoscopy and combined use of OCT and fluorescence cystoscopy. Materials and methods: An OCT device (1280 nm wavelength with 3 mW power, 8 Fr endoscopic probe, in-depth resolution 15 ?m in tissue, lateral resolution 30 ?m, acquisition time 1.5 sec for a 200x200 pixels image) was used in combination with a standard Karl Storz fluorescence cystoscope. A 3% solution of 5-ALA was instilled intravesically for 2 hours before the procedure. Initial examination was made under white light. OCT imaging and biopsy of all fluorescence zones were performed in blue light. 20 patients were studied. The study is ongoing. Results: 80 fluorescence zones (16 exophytic and 64 flat lesions) were analyzed with OCT. All exophytic zones were correctly detected by OCT and white light cystoscopy. Out of 64 flat fluorescent areas, 56 had benign histopathology readings, with 45 of them having the benign type of OCT images. Of 8 fluorescent zones with neoplastic histopathology, OCT correctly detected all 8. Based on this preliminary data, OCT could help to avoid 80% of unnecessary biopsies/resections. Conclusion: Combined use of OCT imaging and fluorescence cystoscopy can substantially improve diagnostic yield of bladder neoplasia detection.
Zagaynova, Elena V.; Streltsova, Olga S.; Orlova, Anna G.; Shakhova, Natalia M.; Gladkova, Natalia D.; Unusova, Ekaterina E.; Iksanov, Rashid R.; Feldchtein, Felix I.
In mammals, many cytokines and growth factors stimulate members of the Janus kinase (JAK) family to transduce signals for the proliferation and differentiation of various cell types, particularly in hematopoietic lineages. Mutations in the Drosophila hopscotch (hop) gene, which encodes a JAK, also cause proliferative defects. Loss-of-function alleles result in lethality and underproliferation of diploid tissues of the larva. A dominant gain-of-function allele, Tumorous-lethal (hopTum-l), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs. We show that a single amino acid change in Hop is associated with the hopTum-l mutation. Overexpression of either wild-type hop or hopTum-l in the larval lymph glands causes melanotic tumors and lymph gland hypertrophy indistinguishable from the original hopTum-l mutation. In addition, overexpression of Hop in other tissues of the larva leads to pattern defects in the adult or to lethality. Finally, overexpression of either hop or hopTum-l in Drosophila cell culture results in tyrosine phosphorylation of Hop protein. However, overexpression of hopTum-l results in greater phosphorylation than overexpression of the wild-type. We conclude that hopTum-l encodes a hyperactive Hop kinase and that overactivity of Hop in lymph glands causes malignant neoplasia of Drosophila blood cells. Images
Harrison, D A; Binari, R; Nahreini, T S; Gilman, M; Perrimon, N
The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.
Fleming, I.D.; Black, T.L.; Thompson, E.I.; Pratt, C.; Rao, B.; Hustu, O.
The list of multiple endocrine neoplasias (MENs) that have been molecularly elucidated is growing with the most recent addition of Carney complex. MEN type 1 (MEN 1), which affects primarily the pituitary, pancreas, and parathyroid glands, is caused by mutations in the menin gene. MEN type 2 (MEN 2) syndromes, MEN 2A and MEN 2B that affect mainly the thyroid and parathyroid glands and the adrenal medulla, and familial medullary thyroid carcinoma (FMTC), are caused by mutations in the REToncogene. Finally, Carney complex, which affects the adrenal cortex, the pituitary and thyroid glands, and the gonads, is caused by mutations in the gene that codes for regulatory subunit type 1A of protein kinase A (PKA) (PRKAR1A) in at least half of the known patients. Molecular defects have also been identified in syndromes related to the MENs, like Peutz-Jeghers syndrome (PJS) (the STK11/LKB1 gene), and Cowden (CD; the PTEN gene) and von Hippel-Lindau disease (VHLD; the VHL gene). Although recognition of these syndromes at a young age generally improves prognosis, the need for molecular testing in the diagnostic evaluation of the MENs is less clear. This review presents the newest information on the clinical and molecular genetics of the MENs (MEN 1, MEN 2, and Carney complex), including recommendations for genetic screening, and discusses briefly the related syndromes PJS, CD and VHLD. PMID:11407658
Stratakis, C A
Cervical cancer is the second leading cause of cancer death among women in developing countries. Developing countries often lack infrastructure, cytotechnologists, and pathologists necessary to implement current screening tools. Due to their low cost and ease of interpretation at the point-of-care, optical imaging technologies may serve as an appropriate solution for cervical cancer screening in low resource settings. We have developed a high-resolution optical imaging system, the High Resolution Microendoscope (HRME), which can be used to interrogate clinically suspicious areas with subcellular spatial resolution, revealing changes in nuclear to cytoplasmic area ratio. In this pilot study carried out at the women's clinic of Princess Marina Hospital in Botswana, 52 unique sites were imaged in 26 patients, and the results were compared to histopathology as a reference standard. Quantitative high resolution imaging achieved a sensitivity and specificity of 86% and 87%, respectively, in differentiating neoplastic (?CIN 2) tissue from non-neoplastic tissue. These results suggest the potential promise of HRME to assist in the detection of cervical neoplasia in low-resource settings.
Pierce, Mark C.; Kayembe, Mukendi K.; Ramogola-Masire, Doreen; Richards-Kortum, Rebecca
Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder. PMID:20724516
Sura, R; French, R A; Goldman, B D; Schwartz, D R
Despite advances in diagnosis and treatment of prostate cancer, development of metastases remains a major clinical challenge. Research efforts are dedicated to overcome this problem by understanding the molecular basis of the transition from benign cells to prostatic intraepithelial neoplasia (PIN), localized carcinoma, and metastatic cancer. Identification of proteins that inhibit dissemination of cancer cells will provide new perspectives to define novel therapeutics. Development of antimetastatic drugs that trigger or mimic the effect of metastasis suppressors represents new therapeutic approaches to improve patient survival. This review focuses on different biochemical and cellular functions of metastasis suppressors known to play a role in prostate carcinogenesis and progression. Ten putative metastasis suppressors implicated in prostate cancer are discussed. CD44s is decreased in both PIN and cancer; Drg-1, E-cadherin, KAI-1, RKIP, and SSeCKS show similar expression between benign epithelia and PIN, but are downregulated in invasive cancer; whereas, maspin, MKK4, Nm23 and PTEN are upregulated in PIN and downregulated in cancer. Moreover, the potential role of microRNA in prostate cancer progression, the understanding of the cellular distribution and localization of metastasis suppressors, their mechanism of action, their effect on prostate invasion and metastasis, and their potential use as therapeutics are addressed. PMID:22886631
Khamis, Zahraa I; Iczkowski, Kenneth A; Sang, Qing-Xiang Amy
Gastric cancer is the second leading cause of cancer death worldwide. Predisposing factors include achlorhydria, Helicobacter pylori infection, oxyntic atrophy and TFF2-expressing metaplasia. In parietal cells, apical potassium channels comprising the KCNQ1 alpha subunit and the KCNE2 beta subunit provide a K(+) efflux current to facilitate gastric acid secretion by the apical H(+)K(+)ATPase. Accordingly, genetic deletion of murine Kcnq1 or Kcne2 impairs gastric acid secretion. Other evidence has suggested a role for KCNE2 in human gastric cancer cell proliferation, independent of its role in gastric acidification. Here, we demonstrate that 1-year-old Kcne2(-/-) mice in a pathogen-free environment all exhibit a severe gastric preneoplastic phenotype comprising gastritis cystica profunda, 6-fold increased stomach mass, increased Ki67 and nuclear Cyclin D1 expression, and TFF2- and cytokeratin 7-expressing metaplasia. Some Kcne2(-/-) mice also exhibited pyloric polypoid adenomas extending into the duodenum, and neoplastic invasion of thin walled vessels in the sub-mucosa. Finally, analysis of human gastric cancer tissue indicated reduced parietal cell KCNE2 expression. Together with previous findings, the results suggest KCNE2 disruption as a possible risk factor for gastric neoplasia. PMID:20625512
Roepke, Torsten K; Purtell, Kerry; King, Elizabeth C; La Perle, Krista M D; Lerner, Daniel J; Abbott, Geoffrey W
Nodular fasciitis (NF) is a relatively common mass-forming and self-limited subcutaneous pseudosarcomatous myofibroblastic proliferation of unknown pathogenesis. Due to its rapid growth and high mitotic activity, NF is often misdiagnosed as a sarcoma. While studying the USP6 biology in aneurysmal bone cyst and other mesenchymal tumors, we identified high expression levels of USP6 mRNA in two examples of NF. This finding led us to further examine the mechanisms underlying USP6 overexpression in these lesions. Upon subsequent investigation, genomic rearrangements of the USP6 locus were found in 92% (44 of 48) of NF. Rapid amplification of 5'-cDNA ends identified MYH9 as the translocation partner. RT-PCR and direct sequencing revealed the fusion of the MYH9 promoter region to the entire coding region of USP6. Control tumors and tissues were negative for this fusion. Xenografts of cells overexpressing USP6 in nude mice exhibited clinical and histological features similar to human NF. The identification of a sensitive and specific abnormality in NF holds the potential to be used diagnostically. Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event. PMID:21826056
Erickson-Johnson, Michele R; Chou, Margaret M; Evers, Barbara R; Roth, Christopher W; Seys, Amber R; Jin, Long; Ye, Ying; Lau, Alan W; Wang, Xiaoke; Oliveira, Andre M
Summary Background: Multiple endocrine neoplasia type 1 (MEN1), also called Wermer syndrome, is an autosomal dominant disorder characterized by tumors of the parathyroid glands, the anterior pituitary, and the endocrine pancreas. Case Report: Here, we report a case of MEN1. Our patient was a 44-year-old woman who manifested typical features of MEN1, including insulinoma, pituitary tumors, and parathyroidoma, and exhibited multiple lipomas and a gastrinoma with duodenal ulcers. She was admitted to our hospital because of recurrent massive bleeding of the upper gastrointestinal tract and hypoglycemia. The first operation for pituitary tumors was performed when she was 40 years old. According to these examinations and her clinical course, the patient was diagnosed with insulinoma and gastrinoma. She subsequently underwent surgery for the pancreatic tumors. The majority of these tumor cells were immunohistochemically positive for insulin and negative for glucagon. Conclusions: This case suggests that multiple lipomas, insulinoma and gastrinoma may provide clues for a diagnosis of MEN1.
Li, Jianzhong; Zeng, Lixian; Yang, Yidong; Zhan, Yashi; Tao, Jin; Wu, Bin
Squamous cell carcinoma of the cervix (SCC) is preceded by a premalignant condition known as cervical intraepithelial neoplasia (CIN). The majority of cases of CIN regress spontaneously; however, methods are needed to identify those lesions likely to progress. Increased blood vessel density, signifying angiogenesis, is an independent prognostic indicator in a number of cancers, although little is known about its significance in premalignant lesions. The aim of the present study was to determine the relationship between vessel density, expression of the potent angiogenic factor vascular endothelial growth factor (VEGF) and CIN grade. Using immunohistochemistry, mean vessel density (MVD) and VEGF expression were assessed in samples from 54 patients who had undergone cone biopsy for CIN or hysterectomy for SCC and from 16 patients with no cervical pathology. There were significant increases in MVD and VEGF expression from normal cervix through CIN I to CIN III to invasive SCC, but no difference in mean vessel diameter between groups. There was a strong correlation between mean vessel density and VEGF expression, and both were associated with histological grade of CIN. The original MVDs for a small group of patients later presenting with recurrent disease were found to be equal to or greater than the mean for their histological grade. We conclude that the onset of angiogenesis is an early event in premalignant changes of the cervix due, in part, to enhanced expression of VEGF by the abnormal epithelium. Images Figure 1 Figure 3
Dobbs, S. P.; Hewett, P. W.; Johnson, I. R.; Carmichael, J.; Murray, J. C.
The aim of our study was to identify the frequency of expression of p16INK4a (CDKN2A) and HPV (human papilloma virus) in different grades of conjunctival intraepithelial neoplasia (CIN). Twelve specimens including CIN I (2), II (3), III (5), and CIN with beginning invasion (2), as well as 15 control specimens, were stained with antibodies against p16INK4a and MIB1. The presence of HPV was examined by PCR. p16 as well as MIB1 were significantly elevated in CIN compared to control specimens (p<0.01) without correlation with the differentiation grade. Only two cases with CIN grade 3 contained HPV 16. As few control specimens also showed increased p16INK4a expression, p16INK4a seems not to be a very reliable marker for the exact determination of CIN. It could serve as an additional diagnostic tool besides the morphological characterization. Our study suggested that p16INK4a elevation is not associated with HPV infection.
Auw-Haedrich, Claudia; Martin, Gottfried; Spelsberg, Helga; Sundmacher, Rainer; Freudenberg, Nikolaus; Maier, Philip; Reinhard, Thomas
Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.
Ramanujam, N; Mitchell, M F; Mahadevan, A; Warren, S; Thomsen, S; Silva, E; Richards-Kortum, R
Recent in situ hybridization studies have suggested the presence of human papillomavirus type 6 (HPV-6) DNA in ovarian cancer cells. An association between HPV and ovarian neoplasia of low malignant potential (LMP) has not been previously identified. Paraffin-embedded tissue blocks from 24 patients with LMP ovarian tumors were screened for human papillomavirus DNA. The patients ranged in age from 18 to 73 years. Corresponding microscopic slides from each tissue block were reviewed to confirm the histopathologic diagnosis. For identification of HPV genome, deparaffinized sections were subjected to the polymerase chain reaction to achieve amplification of DNAs of HPV types 6, 11, 16, and 18. For each HPV type, a 120-base-pair region of the E6 gene was targeted for amplification. Human papillomaviral DNA was not detected in the tissue specimens subjected to polymerase chain reaction. These results suggest that HPV types 6, 11, 16, and 18 are not likely to play a role in LMP ovarian tumors. These results do not totally exclude possible contributions of other HPV types. PMID:2172118
McLellan, R; Buscema, J; Guerrero, E; Shah, K V; Woodruff, J D; Currie, J L
Context Hyperparathyroidism and/or parathyroid hyperplasia, medullary thyroid carcinoma (MTC) and pheochromocytomas compose the hallmarks of the multiple endocrine neoplasia type 2A (MEN 2A) syndrome. Revisiting a report in 1939 of a patient with hyperparathyroidism and parathyroid hyperplasia led to a search for evidence of MEN 2A. Evidence Acquisition From medical records and discussion with family members, longitudinal follow-up of the patient and her descendants was obtained. Molecular diagnostics were integrated in the care of subsequent generations. The literature on hyperparathyroidism and MEN 2A was reviewed. Results Children of the proband exhibited all components of MEN 2A and the RET mutation of 634 TGC>zCGC. The pedigree was typical for this mutation. Papers on anthropologic studies demonstrate skeletal evidence of hyperparathyroidism in humans centuries ago. Conclusions The initial report of the proband preceded the publications defining both MTC and MEN 2A. The values of in-depth family histories and genetic analyses are exemplified.
Sisson, James C.; Giordano, Thomas J.; Raymond, Victoria M.; Doherty, Gerard M.; Gruber, Stephen B.
Gastric cancer (GC) is still a leading cause of cancer-related death worldwide, and environmental, genetic, and epigenetic DNA changes are involved in the process of gastric carcinogenesis. The objective of this study was to establish the extent of DNA methylation at various CpG islands in GC and in precancerous changes [gastric noninvasive neoplasia (NIN)]. Eighty-one gastric samples were analyzed using methylation-specific PCR at several CpG islands. Thirty-eight samples were obtained at surgery [19 neoplastic (GC) and 19 nonneoplastic cancer-surrounding tissues (sGC)] and 43 at endoscopy (biopsies in 23 NIN patients and 20 controls). Hypermethylation of TPEF (a growth inhibitor), PTGER3 (a prostaglandin receptor isoform), and MINT31 (a promoter locus regulating calcium channels that is involved in p53 mutation) discriminated NIN and GC from normal mucosa, suggesting an early role as initiating events, whereas hypermethylation at ARGHAP20 developed with the progression from NIN to GC. MINT31 hypermethylation predicted persistence or worsening of NIN and cancer development. In conclusion, these data support a progressive accumulation of aberrant methylations in NIN and GC at various CpG islands with distinct time courses. With hypermethylation, the genes involved in regulating the balance between apoptosis and cell proliferation may become silenced and trigger gastric tumorigenesis. Hypermethylation of MINT31 predicted NIN persistence, as well as progression to higher grade or to GC, and might be used as a marker of GC risk. PMID:22179688
Negrini, Massimo; Miotto, Elena; Sabbioni, Silvia; Cardin, Romilda; Rugge, Massimo; Tieppo, Chiara; Piciocchi, Marika; Maddalo, Gemma; Nitti, Donato; Farinati, Fabio
Background United Kingdom (U.K.) and United States (U.S.) guidelines for risk stratification after polypectomy differ, as do recommended surveillance intervals. Objective To compare risk of advanced colorectal neoplasia at one-year colonoscopy among patients cross-classified by U.S. and U.K. surveillance guidelines. Design Pooled analysis of four prospective studies, 1984-1998. Setting Academic and private clinics in the U.S. Patients 3226 post-polypectomy patients with 6-18 month follow-up colonoscopy. Measurements Rates of advanced neoplasia (adenoma ? 1cm, high-grade dysplasia, >25% villous histology, or invasive cancer) at one year, compared across U.S. and U.K. risk categories. Results Advanced neoplasia (95% CI) was detected one year post-polypectomy in 3.8% (2.7%-4.9%) of lower-risk and 11.2% (9.8%-12.6%) of higher-risk patients, by U.S. criteria. Using U.K. criteria, 4.4% (3.3%-5.4%), 9.9% (8.3%-11.5%), and 18.7% (14.8%-22.5%) of low-, intermediate-, and high-risk patients, respectively, presented with advanced neoplasia; U.K. high-risk patients comprised 12% of all patients. All U.S. lower-risk patients were low-risk by U.K. criteria; however, since the U.K. guidelines do not consider histological features, more patients are classified as low-risk. U.S. higher-risk patients distributed across the three U.K. categories. Considering all patients with advanced neoplasia, 26.3% were reclassified by the U.K criteria to a higher and 7.0% to a lower risk category, with a net 19% benefiting from two-year earlier detection. Overall, substitution of U.K. for U.S. guidelines resulted in an estimated 0.03 additional colonoscopies per five years per patient. Limitations Patients were enrolled 15-20 years ago; colonoscopy quality measures were unavailable. Patients lacking follow-up colonoscopy or with surveillance colonoscopy after 6-18 months, and those with cancer or insufficient baseline adenoma characteristics were excluded (2076/5302). Conclusions Application of the U.K. guidelines in the U.S. could identify a subset of patients whose high risk may warrant a one-year clearing colonoscopy, without substantially increasing colonoscopy rates.
Martinez, Maria Elena; Thompson, Patricia; Messer, Karen; Ashbeck, Erin L.; Lieberman, David A.; Baron, John A.; Ahnen, Dennis J.; Robertson, Douglas J.; Jacobs, Elizabeth T.; Greenberg, E. Robert; Cross, Amanda J.; Atkin, Wendy
Six hundred and fifty-nine patients with cervical neoplasia were treated by either vaporization (395 patients) or excisional conization (264 patients) with various Lasers. The complications associated with the therapies were examined with reference to the Laser sources and in the local anesthesia and non anesthesia groups. Six hundred and thirty-nine patients were treated on an outpatient basis without local anesthesia (37.7%) or with local anesthesia (62.3%). During the procedures, the patients complained of pain and a hot sensation in the lower abdomen in 64.6% in the vaporization (vapor) group and 60.7% in the conization (cone) group. In the local anesthesia group, 2.9% of the vapor and 4.0% of cone group complained of nothing. Uncontrollable bleeding during the procedures was most common in 12.8% and 32.3% in the CO2 vapor and cone groups, respectively. Misirradiation of the vaginal wall and vulva occurred in 3.3% in all vapor groups. On the other hand, the incidence of burns to both areas in all cone groups was 7.2%. The patients who were given an analgesic were 1.3% in all vapor groups and 2.5% in all cone groups. Delayed bleeding in those who received some treatment to stop it occurred in 14.7% in all vapor groups and also in 11.0% in all cone groups. Cervical stenosis was seen in 3.8% in all vapor groups and in 8.6% in all cone groups. No infection of the lasered site was observed in the vapor groups, but was observed in 0.8% in the cone groups. The culture test showed both E. coli positive. PMID:8089597
Wakita, K; Kuramoto, H; Sasaki, N; Izumi, T; Nishijima, M
The persistent activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is oncogenic and involved in colorectal neoplasia. Mutations of both regulatory subunit and catalytic subunit of PI3K have been demonstrated in colon cancers. In the present study, we show that heterozygous disruption of the phosphatase and tensin homolog (PTEN) tumor suppressor gene promoted tumor progression in APC(min/+) mice. Number and size of intestinal tumors were significantly increased in mice bearing both adenomatous polyposis coli (APC) and PTEN mutations. While APC(min/+)PTEN(+/+) mice developed adenomas, invasive carcinomas developed in APC(min/+)PTEN(+/-) mice. Large tumors often resulted in intestinal intussusception and early death of APC(min/+)PTEN(+/-) mice. Targeted array revealed that osteopontin (OPN) was the leading gene whose expression was strongly induced by deficiency of PTEN. In colon cancer cells, gain-of-function mutation of PI3K robustly increased levels of OPN and treatment with OPN reduced growth factor deprivation-induced programmed cell death. Moreover, OPN expression was strongly increased in Ras-induced transformation of intestinal epithelial cells in a PI3K-dependent manner. Inhibition of OPN expression by specific small interfering RNA reduced uncontrolled growth and invasiveness of Ras-transformed intestinal epithelial cells. Thus, our results suggest that the PI3K pathway promotes the transformation of intestinal adenoma to adenocarcinoma. OPN, a downstream effector of PI3K, protects transformed intestinal epithelial cells from programmed cell death and stimulates their anchorage-independent growth. PMID:17693663
Shao, Jinyi; Washington, M Kay; Saxena, Romil; Sheng, Hongmiao
Objective To relate aspects of online colposcopic image assessment to the diagnosis of grades 2 and 3 cervical intraepithelial neoplasia (CIN2+). Methods To simulate colposcopic assessment, digitized cervical images were obtained at enrollment after acetic acid application from 919 women referred for equivocal or minor cytologic abnormalities into the ASCUS-LSIL Triage Study. For each, two randomly assigned evaluators from a pool of 20 colposcopists assessed images using a standardized tool on-line. We calculated the accuracy of these assessments for predicting histologic CIN2+ over the two years of study. For validation, a subset of on-line results was compared to same-day enrollment colposcopic assessments. Results Identifying any acetowhite lesion in images yielded high sensitivity: 93% of women with CIN2+ had at least one acetowhite lesion. However, 74% of women without CIN2+ also had acetowhitening, regardless of human papillomavirus (HPV) status. The sensitivity for CIN2+ of an on-line colpophotographic assessment of high grade disease was 39%. The sensitivity for CIN2+ of a high grade diagnosis by Reid Index scoring was 30%, and individual Reid Index component scores had similar levels of sensitivity and specificity. The performance of on-line assessment was not meaningfully different from that of same-day enrollment colposcopy, suggesting that these approaches have similar utility. Conclusion Finding acetowhite lesions identifies women with CIN2+, but using subtler colposcopic characteristics to grade lesions is insensitive. All acetowhite lesions should be assessed with biopsy to maximize sensitivity of colposcopic diagnosis with good specificity.
Massad, L. Stewart; Jeronimo, Jose; Katki, Hormuzd A.; Schiffman, Mark
Background: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. Methods: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. Results: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. Conclusion: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically.
Daayana, S; Elkord, E; Winters, U; Pawlita, M; Roden, R; Stern, P L; Kitchener, H C
Nestin expression reportedly correlates with aggressive growth, metastasis, poor prognosis and presence of cancer stem cells (CSCs) in various tumors. In this study, we determined the expression and role of nestin in cervical intraepithelial neoplasia (CIN) and cervical cancer. We performed immunohistochemical and in situ hybridization analyses of nestin in 26 cases for each stage of CIN and 55 cervical cancer tissue samples. To examine the role of nestin in cervical cancer cells, we stably transfected expression vectors containing nestin cDNA into ME-180 cells. We studied the effects of increased nestin expression on cell proliferation, cell motility, invasion as well as sphere and soft agar formation. Nestin was not localized in the squamous epithelium in normal cervical tissues, but it was weakly expressed in the basal squamous epithelium of CIN 1. In CIN 2, nestin was localized to the basal to lower 2/3 of the squamous epithelium, whereas in CIN 3, it was localized to the majority of the squamous epithelium. Nestin was detected in all cases of invasive cervical cancer. Nestin mRNA was expressed in both ME-180 and CaSki cells. Growth rate, cell motility and invasion ability of stably nestin-transfected ME-180 cells were not different from empty vector-transfected ME-180 (mock cells). However, the nestin-transfected ME-180 cells formed more colonies and spheres compared to the mock cells. These findings suggest that nestin plays important roles in carcinogenesis and tumor formation of cervical cancer cells. Nestin may closely correlate with regulation of CSCs.
SATO, ATSUKI; ISHIWATA, TOSHIYUKI; MATSUDA, YOKO; YAMAMOTO, TETSUSHI; ASAKURA, HIROBUMI; TAKESHITA, TOSHIYUKI; NAITO, ZENYA
We report the results of a comparative evaluation of in vivo fluorescence and Raman spectroscopy for diagnosis of oral neoplasia. The study carried out at Tata Memorial Hospital, Mumbai, involved 26 healthy volunteers and 138 patients being screened for neoplasm of oral cavity. Spectral measurements were taken from multiple sites of abnormal as well as apparently uninvolved contra-lateral regions of the oral cavity in each patient. The different tissue sites investigated belonged to one of the four histopathology categories: 1) squamous cell carcinoma (SCC), 2) oral sub-mucous fibrosis (OSMF), 3) leukoplakia (LP) and 4) normal squamous tissue. A probability based multivariate statistical algorithm utilizing nonlinear Maximum Representation and Discrimination Feature for feature extraction and Sparse Multinomial Logistic Regression for classification was developed for direct multi-class classification in a leave-one-patient-out cross validation mode. The results reveal that the performance of Raman spectroscopy is considerably superior to that of fluorescence in stratifying the oral tissues into respective histopathologic categories. The best classification accuracy was observed to be 90%, 93%, 94%, and 89% for SCC, SMF, leukoplakia, and normal oral tissues, respectively, on the basis of leave-one-patient-out cross-validation, with an overall accuracy of 91%. However, when a binary classification was employed to distinguish spectra from all the SCC, SMF and leukoplakik tissue sites together from normal, fluorescence and Raman spectroscopy were seen to have almost comparable performances with Raman yielding marginally better classification accuracy of 98.5% as compared to 94% of fluorescence.
Majumder, S. K.; Krishna, H.; Sidramesh, M.; Chaturvedi, P.; Gupta, P. K.
AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for early oesophageal squamous neoplasia from a National Registry. METHODS: A Prospective cohort study from 8 tertiary referral centres in the United Kingdom. Patients with squamous high grade dysplasia (HGD) and early squamous cell carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA treatment, patients were followed up 3 monthly. Residual flat dysplasia was treated with RFA until complete reversal dysplasia (CR-D) was achieved or progression to invasive Squamous cell cancer defined as infiltration into the submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from start of treatment, long term durability, progression to cancer and adverse events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50% at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54). Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients (20%) required endoscopic dilatations for symptomatic structuring after treatment. Two of these patients have required serial dilatations thereafter for symptomatic dysphagia with a median of 4 dilatations per patient. The other 2 patients required only a single dilatation to achieve an adequate symptomatic response. One patient developed cancer during follow up after end of treatment protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our series 50% patients responded at 12 mo. These figures are lower than limited published data.
Haidry, Rehan J; Butt, Mohammed A; Dunn, Jason; Banks, Matthew; Gupta, Abhinav; Smart, Howard; Bhandari, Pradeep; Smith, Lesley Ann; Willert, Robert; Fullarton, Grant; John, Morris; Di Pietro, Massimo; Penman, Ian; Novelli, Marco; Lovat, Laurence B
We have used subunit-specific monoclonal antibodies (MAbs) and immunohistochemistry to examine the distribution of integrin alpha 6 beta 4 in normal ectocervical epithelium and various grades of cervical intraepithelial neoplasia (CIN). Antibodies were first characterised by immunoprecipitation from two surface-labelled tumour cell lines. Monoclonal antibody G71 was found to precipitate integrin beta 4 from BeWo but not T47D cells, while other anti-beta 4 antibodies precipitated beta 4 from both cell lines. Both G71 and an antiserum to the C-terminal peptide of beta 4 precipitated free beta 4 from surface-iodinated BeWo cells. Neither antibody recognised truncated beta 4 chains observed at approximately 160 kDa. These data suggest that different isoforms of beta 4 are expressed in different tumour cell lines, and that there may be a pool of beta 4 at the cell surface that is not complexed to alpha 6. In normal cervix, both the alpha 6 and beta 4 subunits occur at the basal surface of the basal cell layer. In CIN, the distribution is markedly altered, with strong expression of alpha 6 and beta 4 in the upper cell layers of the ectocervical epithelium. All 40 cases of CIN that were studied exhibited this alteration. Furthermore, the extent of extrabasal staining appeared to correspond with the grade of CIN. The form of integrin beta 4 recognised by antibody G71 also appears in the upper cell layers in CIN, but it shows a more restricted distribution than the normal isoform. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5
Aplin, J. D.; Dawson, S.; Seif, M. W.
Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma-HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy. PMID:22685591
Ekeowa-Anderson, Arucha L; Purdie, Karin J; Gibbon, Karen; Byrne, Carolyn R; Arbeit, Jeffrey M; Harwood, Catherine A; O'Shaughnessy, Ryan F L
We performed a preliminary study involving 10 dogs to assess the applicability of body MRI for staging of canine diffuse hematopoietic neoplasia. T1-weighted (before and after intravenous gadolinium), T2-weighted, in-phase, out-of-phase, and short tau inversion recovery pulse sequences were used. By using digital region of interest (ROI) and visual comparison techniques, relative parenchymal organ (medial iliac lymph nodes, liver, spleen, kidney cortex, and kidney medulla) signal intensity was quantified as less than, equal to, or greater than that of skeletal muscle in 2 clinically normal young adult dogs and 10 dogs affected with either B-cell lymphoma (n = 7) or myelodysplastic syndrome (n = 3). Falciform fat and urinary bladder were evaluated to provide additional perspective regarding signal intensity from the pulse sequences. Dogs with nonfocal disease could be distinguished from normal dogs according to both the visual and ROI signal-intensity relationships. In normal dogs, liver signal intensity on the T2-weighted sequence was greater than that of skeletal muscle by using either the visual or ROI approach. However in affected dogs, T2-weighted liver signal intensity was less than that of skeletal muscle by using either the ROI approach (10 of 10 dogs) or the visual approach (9 of 10 dogs). These findings suggest that the comparison of relative signal intensity among organs may have merit as a research model for infiltrative parenchymal disease (ROI approach) or metabolic effects of disease; this comparison may have practical clinical applicability (visual comparison approach) as well.
Feeney, Daniel A; Sharkey, Leslie C; Steward, Susan M; Bahr, Katherine L; Henson, Michael S; Ito, Daisuke; O'Brien, Timothy D; Jessen, Carl R; Husbands, Brian D; Borgatti, Antonella; Modiano, Jaime F
Purpose More than 1,300,000 prostate needle biopsies are performed annually in the U.S. with up to 16% incidence of isolated high-grade prostatic intraepithelial neoplasia (HGPIN). HGPIN has low predictive value for identifying prostate cancer (PCA) on subsequent needle biopsies in PSA screened populations. In contemporary series, PCA is detected in about 20% of repeat biopsies following a diagnosis of HGPIN. Further, discrete histological subtypes of HGPIN with clinical implication in management have not been characterized. The TMPRSS2-ERG gene fusion that has recently been described in PCA has also been demonstrated to occur in a subset of HGPIN. This may have significant clinical implications given that TMPRSS2-ERG fusion PCA is associated with a more aggressive clinical course. Experimental Design In this study we assessed a series of HGPIN lesions and paired PCA for the presence of TMPRSS2-ERG gene fusion. Results Fusion positive HGPIN was observed in 16% of the 143 number of lesions, and in all instances the matching cancer shared the same fusion pattern. 60% of TMPRSS2-ERG fusion PCA had fusion negative HGPIN. Conclusions Given the more aggressive nature of TMPRSS2-ERG PCA, the findings of this study raise the possibility that gene fusion positive HGPIN lesions are harbingers of more aggressive disease. To date, pathological, molecular and clinical parameters do not help stratify which men with HGPIN are at increased risk for a cancer diagnosis. Our results suggest that the detection of isolated TMPRSS2-ERG fusion HGPIN would improve the positive predictive value of finding TMPRSS2-ERG fusion PCA in subsequent biopsies.
Mosquera, Juan-Miguel; Perner, Sven; Genega, Elizabeth M; Sanda, Martin; Hofer, Matthias D.; Mertz, Kirsten D.; Paris, Pamela L.; Simko, Jeff; Bismar, Tarek A.; Ayala, Gustavo; Shah, Rajal B.; Loda, Massimo; Rubin, Mark A.
We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome predisposing to tumors of the parathyroid, endocrine pancreas, anterior pituitary, adrenal glands, and diffuse neuroendocrine tissues. The MEN1 gene has been assigned, by linkage analysis and loss of heterozygosity, to chromosome 11q13 and recently has been identified by positional cloning. In this study, a total of 84 families and/or isolated patients with either MEN1 or MEN1-related inherited endocrine tumors were screened for MEN1 germ-line mutations, by heteroduplex and sequence analysis of the MEN1 gene-coding region and untranslated exon 1. Germ-line MEN1 alterations were identified in 47/54 (87%) MEN1 families, in 9/11 (82%) isolated MEN1 patients, and in only 6/19 (31.5%) atypical MEN1-related inherited cases. We characterized 52 distinct mutations in a total of 62 MEN1 germ-line alterations. Thirty-five of the 52 mutations were frameshifts and nonsense mutations predicted to encode for a truncated MEN1 protein. We identified eight missense mutations and five in-frame deletions over the entire coding sequence. Six mutations were observed more than once in familial MEN1. Haplotype analysis in families with identical mutations indicate that these occurrences reflected mainly independent mutational events. No MEN1 germ-line mutations were found in 7/54 (13%) MEN1 families, in 2/11 (18%) isolated MEN1 cases, in 13/19 (68. 5%) MEN1-related cases, and in a kindred with familial isolated hyperparathyroidism. Two hundred twenty gene carriers (167 affected and 53 unaffected) were identified. No evidence of genotype-phenotype correlation was found. Age-related penetrance was estimated to be >95% at age >30 years. Our results add to the diversity of MEN1 germ-line mutations and provide new tools in genetic screening of MEN1 and clinically related cases.
Giraud, S; Zhang, C X; Serova-Sinilnikova, O; Wautot, V; Salandre, J; Buisson, N; Waterlot, C; Bauters, C; Porchet, N; Aubert, J P; Emy, P; Cadiot, G; Delemer, B; Chabre, O; Niccoli, P; Leprat, F; Duron, F; Emperauger, B; Cougard, P; Goudet, P; Sarfati, E; Riou, J P; Guichard, S; Rodier, M; Meyrier, A; Caron, P; Vantyghem, M C; Assayag, M; Peix, J L; Pugeat, M; Rohmer, V; Vallotton, M; Lenoir, G; Gaudray, P; Proye, C; Conte-Devolx, B; Chanson, P; Shugart, Y Y; Goldgar, D; Murat, A; Calender, A
The morbidity and mortality of individuals with multiple endocrine neoplasia type 1 (MEN1) can be reduced by early diagnosis of MEN1 and related endocrine tumors. To find factors contributing to early diagnosis, we collected clinical information on MEN1 patients through a MEN study group, "MEN Consortium of Japan" and analyzed the time of initial symptom-dependent detection of parathyroid tumors, gastro-entero-pancreatic neuroendocrine tumors (GEPNETs) and pituitary tumors, and that of tumor detection-dependent MEN1 diagnosis in 560 patients. Main tumors were identified up to 7.0 years after symptoms appeared and there was no difference in age at the diagnosis of GEPNETs alone between probands and family members. In patients with typical symptoms (peptic ulcers, urolithiasis, fasting hypoglycemia, bone fracture/loss and amenorrhea), the mean interval between symptom manifestation and tumor detection was extended up to 9.6 years. In particular, 21.7% (5/23) of patients with amenorrhea were diagnosed with pituitary tumors in under one year. In patients with peptic ulcers (from parathyroid tumors or GEPNETs) and urolithiasis (from parathyroid tumors), the interval was positively correlated with age at tumor detection. The interval between tumor detection and MEN1 diagnosis was also prolonged to approximately four years in patients with fasting hypoglycemia (from GEPNETs) and amenorrhea. A substantial delay in the diagnosis of symptom-related tumors and subsequent MEN1 and inadequate screening of GEPNETs in family members were indicated. A greater understanding of MEN1 may assist medical practitioners to make earlier diagnoses, to share patients' medical information and to give family members sufficient disease information. PMID:22673601
Yamazaki, Masanori; Suzuki, Shin-ichi; Kosugi, Shinji; Okamoto, Takahiro; Uchino, Shinya; Miya, Akihiro; Imai, Tsuneo; Kaji, Hiroshi; Komoto, Izumi; Miura, Daishu; Yamada, Masanobu; Uruno, Takashi; Horiuchi, Kiyomi; Sato, Ai; Miyauchi, Akira; Imamura, Masayuki; Sakurai, Akihiro
Background:The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis.Methods:The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic.Results:HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively.Conclusion:Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor. PMID:24030075
Carreira, H; Coutinho, F; Carrilho, C; Lunet, N
OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.
Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.
Background Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett’s esophagus. Objective Evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate- and high-grade squamous intraepithelial neoplasia (MGIN, HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC). Design Prospective cohort study. Setting Tertiary referral center. Patients Esophageal unstained lesions (USLs) were identified using Lugol’s chromoendoscopy. Inclusion: at least 1 flat (type 0-IIb) USL ?3cm, USL-bearing esophagus ?12 cm, and a consensus diagnosis of MGIN, HGIN, or ESCC by two expert GI pathologists. Exclusion: prior endoscopic resection or ablation, stricture, or any non-flat mucosa. Interventions Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies, followed by focal RFA of USLs, if present. Main outcome measures Complete response (CR) at 12 months, defined as absence of MGIN, HGIN or ESCC in TA; CR after one RFA session; neoplastic progression from baseline; and adverse events. Results 29 patients (14 male, mean age 60.3 years) with MGIN (18), HGIN (10), or ESCC (1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3-months, after one RFA session, 86% of patients (25/29) were CR. At 12-months, 97% (28/29) of patients were CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution. Limitations Single center study with limited number of patients. Conclusions In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile.
Bergman, Jacques JGHM; Zhang, Yueming; He, Shun; Weusten, Bas; Xue, Liyan; Fleischer, David E; Lu, Ning; Dawsey, Sanford M; Wang, Gui-Qi
Background Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of pro-inflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10?/? mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10?/? mice with chronic colitis as compared with bromelain derived from stem. Results Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 16 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (p = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% vs. 66%; p< 0.02), with fewer neoplastic lesions/colon (p = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. Conclusions These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease.
Hale, Laura P.; Chichlowski, Maciej; Trinh, Chau T.; Greer, Paula K.
Human leukocyte antigens (HLAs) present foreign antigens to the immune system and may be important determinants of cervical neoplasia. Previously published associations between HLA and cervical neoplasia exhibit considerable variation in findings. The biomarkers of cervical cancer risk (BCCR) case-control study addressed the role of specific HLA alleles as cofactors in the development of high-grade cervical intraepithelial neoplasia (HG-CIN) based on the most consistent evidence from published literature. Cases (N = 381) were women with histologically-confirmed HG-CIN attending colposcopy clinics and controls (N = 884) were women from outpatient clinics with normal cytological screening smears. Subjects were mainly of French-Canadian descent. Cervical specimens were tested for human papillomavirus (HPV) DNA and HLA genotypes by PGMY L1 consensus primer PCR and a PCR sequence-specific primer method, respectively. Unlike other studies, the DQB1*03 and DRB1*13 allele groups were not associated with risk of HG-CIN. The B7-DRB1*1501-DQB1*0602 haplotype was associated with a 41% overall reduction in HG-CIN risk (odds ratio [OR] = 0.59; 95% confidence interval [CI]: 0.36-0.96), and an 83% reduction in risk of HG-CIN among HPV 16 or HPV 18-positive subjects (OR = 0.17; 95%CI: 0.05-0.54). Paradoxically, however, the same haplotype was associated with HPV 16/18 infection risk among controls (OR = 8.44, 95%CI: 1.12-63.73). In conclusion, the B7-DRB1*1501-DQB1*0602 haplotype was protective against HG-CIN, especially in individuals infected with oncogenic HPV, but the mechanism of the association seems to involve multiple steps in the natural history of HPV and CIN. PMID:18351579
Ades, Steven; Koushik, Anita; Duarte-Franco, Eliane; Mansour, Nabil; Arseneau, Jocelyne; Provencher, Diane; Gilbert, Lucy; Gotlieb, Walter; Ferenczy, Alex; Coutlée, François; Roger, Michel; Franco, Eduardo L
Childhood pheochromocytoma in the setting of multiple endocrine neoplasia type 2 (MEN2) remains rare and has not been reported under the age of 12. We present an 8-year-old female with known MEN 2A, C634Y RET mutation, diagnosed with a 6?cm pheochromocytoma requiring laparoscopic adrenalectomy. Given this patient's age at diagnosis, screening guidelines should recommend annual screening beginning at age 8 for patients with MEN 2B or MEN 2A codons 630 or 634 RET mutations. J. Surg. Oncol. 2013 108:203-206. © 2013 Wiley Periodicals, Inc. PMID:23868299
Rowland, Kathryn J; Chernock, Rebecca D; Moley, Jeffrey F
Introduction Because of the small size of in situ mammary cancers in mouse models, high-resolution imaging techniques are required to effectively observe how lesions develop, grow and progress over time. The purpose of this study was to use magnetic resonance (MR) imaging to track in vivo the transition from in situ neoplasia to invasive cancer in a transgenic mouse model of human cancer. Methods MR images of 12 female C3(1) SV40 Tag mice that develop mammary intraepithelial neoplasia (MIN) were obtained. MIN is believed to be similar to human ductal carcinoma in situ (DCIS) and is considered a precursor of invasive tumors. Images were serially obtained from 10-21 weeks of age at 2-3 week intervals. MIN lesions were identified based on their morphology on MR images. Lesions were followed over time and several lesion features were measured including volume, growth rate and morphology. For those MIN lesions that progressed to invasive cancer the progression time was measured. Results Overall, 21 MIN lesions were initially detected at an average initial volume of 0.3 ± 0.2 mm3 with an average growth rate of -0.15 ± 0.66 week-1. Even though all mice were inbred to express the SV40 Tag transgene in the mammary epithelium and expected to develop invasive carcinoma, the individual MIN lesions took vastly different progression paths: (i) 9 lesions progressed to invasive tumors with an average progression time of 4.6 ± 1.9 weeks; (ii) 2 lesions regressed, i.e., were not detected on future images; and (iii) 5 were stable for over 8 weeks, and were demonstrated by a statistical model to represent indolent disease. Conclusions To our knowledge, the results reported here are the first measurements of the timescale and characteristics of progression from in situ neoplasia to invasive carcinoma and provide image-based evidence that DCIS may be a non-obligate precursor lesion with highly variable outcomes. In addition, this study represents a first step towards developing methods of image acquisition for identifying radiological characteristics that might predict which in situ neoplasias will become invasive cancers and which are unlikely to progress.
Primary vaginal adenocarcinomas are one of the rarest malignant neoplasms, which develop in the female genital tract. Because of the extremely low incidence, their clinical and pathologic characteristics are still obscure. Recently, we experienced a case of vaginal adenocarcinoma that appeared 7 yr after hysterectomy because of cervical intraepithelial neoplasia. The patient, a 65-yr-old obese woman, was diagnosed as having adenocarcinoma in the vaginal stump and was treated by simple tumor excision and radiation. Immunohistochemical and molecular biologic examinations indicated a potential association with human papilloma virus infection in the development of the vaginal adenocarcinoma. There has been no evidence of recurrence for 3 yr after the operation. PMID:24071878
Shibata, Takashi; Ikura, Yoshihiro; Iwai, Yasuhiro; Tokuda, Hisato; Cho, Yuka; Morimoto, Noriyuki; Nakago, Satoshi; Oishi, Tetsuya
Background Recently, more detailed histopathological variables such as perineural invasion (PNI), lymphovascular invasion (LVI), and\\u000a high-grade prostatic intraepithelial neoplasia (HGPIN) have been investigated as prognostic factors for adverse pathologic\\u000a findings on the radical prostatectomy specimen. We aim to determine whether these pathological factors are associated with\\u000a adverse pathologic features after robot-assisted laparoscopic radical prostatectomy (RALP).\\u000a \\u000a \\u000a \\u000a \\u000a Methods All 407 patients who underwent RALP
Jae Hung Jung; Jae Won Lee; Francis Raymond P. Arkoncel; Nam Hoon Cho; Kwang Jin Kim; Jae Mann Song; Sung Jin Kim; Koon Ho Rha
Objective: To describe practical experiences in the sharing of very large digital data bases of histopathological imagery via the Internet, by investigators working in Europe, North America, and South America. Materials: Experiences derived from medium power (sampling density 2.4 pixels/?m) and high power (6 pixels/?m) imagery of prostatic tissues, skin shave biopsies, breast lesions, endometrial sections, and colonic lesions. Most of the data included in this paper were from prostate. In particular, 1168 histological images of normal prostate, high grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) were recorded, archived in an image format developed at the Optical Sciences Center (OSC), University of Arizona, and transmitted to Ancona, Italy, as JPEG (joint photographic experts group) files. Images were downloaded for review using the Internet application FTP (file transfer protocol). The images were then sent from Ancona to other laboratories for additional histopathological review and quantitative analyses. They were viewed using Adobe Photoshop, Paint Shop Pro, and Imaging for Windows. For karyometric analysis full resolution imagery was used, whereas histometric analyses were carried out on JPEG imagery also. Results: The three applications of the telecommunication system were remote histopathological assessment, remote data acquisition, and selection of material. Typical data volumes for each project ranged from 120 megabytes to one gigabyte, and transmission times were usually less than one hour. There were only negligible transmission errors, and no problem in efficient communication, although real time communication was an exception, because of the time zone differences. As far as the remote histopathological assessment of the prostate was concerned, agreement between the pathologist's electronic diagnosis and the diagnostic label applied to the images by the recording scientist was present in 96.6% of instances. When these images were forwarded to two pathologists, the level of concordance with the reviewing pathologist who originally downloaded the files from Tucson was as high as 97.2% and 98.0%. Initial results of studies made by researchers belonging to our group but located in others laboratories showed the feasibility of making quantitative analysis on the same images. Conclusions: These experiences show that diagnostic teleconsultation and quantitative image analyses via the Internet are not only feasible, but practical, and allow a close collaboration between researchers widely separated by geographical distance and analytical resources.
Montironi, R; Thompson, D; Scarpelli, M; Bartels, H G; Hamilton, P W; Da Silva, V D; Sakr, W A; Weyn, B; Van Daele, A; Bartels, P H
Objective To determine risk factors for the development of vulvar intraepithelial neoplasia (VIN 2/3), and factors associated with recurrence. Methods A retrospective chart review of 303 patients with VIN 2/3 evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic information, risk factors, treatment type, pathologic diagnosis, and recurrence/outcome information. Recurrent disease was defined as a diagnosis of VIN 2/3 and/or invasive vulvar cancer after initial treatment of VIN 2/3. Patients with VIN 1 and patients with invasive disease, including microinvasion, were excluded. Results The median age at diagnosis was 47 years (range 14–87). 33% of patients were symptomatic, with pruritus being the most common presenting symptom. Smoking history was available for 299 patients, with 40% reporting current tobacco use and 26% reporting previous use. Primary treatment included excision (n=176, 59%), laser ablation (n=40, 13%), imiquimod (n=22, 7.4%), excision with laser (n=24, 8.1%), or excision with imiquimod (n=10, 3.4%). Margin status was available for 147 patients. 92 patients (62.6%) were noted to have positive margins, which were associated with larger tumor size (p=0.004). 87 patients (28.7%) developed recurrent disease and it was associated with smoking (p<0.001), larger lesion size (p=0.016), and positive margins (p=0.005). Furthermore, higher rates of recurrence were associated with laser (41.9%) compared with excision (26.4%) or imiquimod (13.6%) (p=0.003). 7 patients (2.3%) recurred with invasive disease a median of 109 months (range 12–327) from initial VIN 2/3 diagnosis. Conclusions This large cohort of women with VIN2/3 further delineates the demographic and clinical factors associated with VIN2/3. High rates of recurrence were noted and found to be associated with smoking, large lesion size, positive margins, and treatment with laser ablation.
Wallbillich, J.J.; Rhodes, H.E.; Milbourne, A.M.; Munsell, M.F.; Frumovitz, M.; Brown, J.; Trimble, C.L.; Schmeler, K.M.
Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue specimens from 15 oral cancer patients. Improved contrast between neoplastic and healthy tissue was observed using 2-NBDG and EGF-Alexa 647.
Schwarz, Richard Alan
Multiple endocrine neoplasia type 1 (MEN1; formerly known as Wermer syndrome) is a rare disorder characterized by the combined occurrence of two or more tumors involving parathyroid, pancreatic islets and anterior pituitary glands; some other tumors have also been described. In most cases it is inherited in an autosomic dominant manner but it may occur sporadically. The MEN1 gene (MEN1) is located on chromosome 11q13, it is composed of ten exons that encode a 610 amino acid protein called menin. Menin, with no homology to any other known protein, interacts with several different proteins and plays an important role in regulation of cell growth, cell cycle, genome stability and synapse plasticity. Familiar MEN1 has a high degree of penetrance with clinical or biochemical manifestations of the disease in 80% and 98%, respectively, by the fifth decade. Clinical manifestations are related to tumor localizations and their secretory products. Hyperparathyroidism is the most common feature of MEN1 (95% of patients), pancreatic islet tumors or pancreatic NET (neuroendocrine tumor) occur in 40-70% and pituitary tumors in 30-40% of MEN 1 patients. In addition, other tumors, such as adrenal cortical tumors, carcinoid tumors, lipomas, angiofibromas, colagenomas and meningiomas may be present. Occurrence of de novo mutations appear in 10% of all patients with MEN1. A correlation between genotype and phenotype has not been found and, even more, combinations of these tumors may be different in members of the same family. Untreated patients have a decreased life expectancy, with a 50% probability of death by the age of 50 years and the cause of death is mostly directly related to MEN1, being the most important causes malignant pancreatic neuroendocrine tumors (NET) and thymic carcinoids. Treatment for each type of endocrine tumor is generally similar as in non-MEN1 associated tumors, but results are less successful according to multiplicity of tumors, higher metastatic disease, larger and more aggressive tumors and more resistant to treatment. The prognosis might improve by preclinical tumor diagnosis and appropriated treatment. PMID:23435440
Gaztambide, S; Vazquez, F; Castańo, L
Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082
Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth
Increased nucleolar size and number are hallmark features of many cancers. In prostate cancer, nucleolar enlargement and increased numbers are some of the earliest morphological changes associated with development of premalignant prostate intraepithelial neoplasia (PIN) lesions and invasive adenocarcinomas. However, the molecular mechanisms that induce nucleolar alterations in PIN and prostate cancer remain largely unknown. We verify that activation of the MYC oncogene, which is overexpressed in most human PIN and prostatic adenocarcinomas, leads to formation of enlarged nucleoli and increased nucleolar number in prostate luminal epithelial cells in vivo. In prostate cancer cells in vitro, MYC expression is needed for maintenance of nucleolar number, and a nucleolar program of gene expression. To begin to decipher the functional relevance of this transcriptional program in prostate cancer, we examined FBL (encoding fibrillarin), a MYC target gene, and report that fibrillarin is required for proliferation, clonogenic survival, and proper ribosomal RNA accumulation/processing in human prostate cancer cells. Further, fibrillarin is overexpressed in PIN lesions induced by MYC overexpression in the mouse prostate, and in human clinical prostate adenocarcinoma and PIN lesions, where its expression correlates with MYC levels. These studies demonstrate that overexpression of the MYC oncogene increases nucleolar number and size and a nucleolar program of gene expression in prostate epithelial cells, thus providing a molecular mechanism responsible for hallmark nucleolar alterations in prostatic neoplasia.
Koh, Cheryl M.; Gurel, Bora; Sutcliffe, Siobhan; Aryee, Martin J.; Schultz, Denise; Iwata, Tsuyoshi; Uemura, Motohide; Zeller, Karen I.; Anele, Uzoma; Zheng, Qizhi; Hicks, Jessica L.; Nelson, William G.; Dang, Chi V.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.
Background and study aim: This study aimed to evaluate the feasibility of a novel laser system for endoscopic submucosal dissection (ESD) of gastric epithelial neoplasia. Patients and methods: A total of 10 patients underwent ESD by a single expert endoscopist. A thulium 2-?m wavelength laser system was used for ESD procedures. Instead of using endoscopy knives, a 550-?m flexible silica fiber was inserted through the working channel of the endoscope. Results: In all patients, ESD was completed using only the thulium laser, without the need for endoscopy knives. The median total procedure time was 49 minutes (range 35 - 203). In 8 /10 patients (80 %), no active bleeding was observed during ESD. The final pathologic mapping revealed low-grade dysplasia (n = 4), differentiated adenocarcinoma (n = 5), and signet ring cell carcinoma (n = 1). Curative resection was achieved in 9 /10 patients (90 %). There were no significant complications, such as delayed bleeding or perforation. Conclusions: The thulium laser system was feasible in ESD of gastric epithelial neoplasia. PMID:23884792
Cho, Jun-Hyung; Cho, Joo Young; Kim, Mi-Young; Jeon, Seong Ran; Lee, Tae Hee; Kim, Hyun Gun; Jin, So Young; Hong, Su Jin
Approximately 10% of ulcerative colitis patients develop colorectal neoplasia. At present, identification of this subset is markedly limited and necessitates lifelong colonoscopic surveillance for the entire ulcerative colitis population. Better risk markers are needed to focus surveillance onto the patients most likely to benefit. Using array-based comparative genomic hybridization, we analyzed single, non-dysplastic biopsies from three patient groups: ulcerative colitis progressors (n=9) with cancer or high-grade dysplasia at a mean distance of 18 cm from the analyzed site; ulcerative colitis nonprogressors (n=8) without dysplasia during long-term surveillance; and non-ulcerative colitis normal controls (n=2). Genomic DNA from fresh colonic epithelium purified from stroma was hybridized to 287 (low-density) and 4,342 (higher-density) feature bacterial artificial chromosome arrays. Sample-to-reference fluorescence ratios were calculated for individual chromosomal targets and globally across the genome. The low-density arrays yielded pronounced genomic gains and losses in 3 of 9 (33%) ulcerative colitis progressors but in none of the 10 control patients. Identical DNA samples analyzed on the higher density arrays, using a combination of global and individual high variance assessments, distinguished all 9 progressors from all 10 controls. These data confirm that genomic alterations in ulcerative colitis progressors are widespread, even involving single non-dysplastic biopsies far distant from neoplasia. They therefore show promise toward eliminating full colonoscopic surveillance with extensive biopsy sampling in the majority of ulcerative colitis patients.
Bronner, Mary P.; Skacel, Marek; Crispin, David A.; Hoff, Peter D.; Emond, Mary J.; Lai, Lisa A.; Tubbs, Raymond R.; Rabinovitch, Peter S.; Brentnall, Teresa A.
AIM: To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnification endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS: Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and treatment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stomachs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with white-light imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the “microvascular pattern and surface pattern” classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI: 78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar’s test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by ME-NBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI: 73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar’s test (P < 0.05). CONCLUSION: Higher diagnostic accuracy, sensitivity and specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.
Wang, Shu-Fang; Yang, Yun-Sheng; Wei, Li-Xin; Lu, Zhong-Sheng; Guo, Ming-Zhou; Huang, Jin; Peng, Li-Hua; Sun, Gang; Ling-Hu, En-Qiang; Meng, Jiang-Yun
Background: Neuroendocrine neoplasia (NEN) are a rare and heterogenous tumour entity. The subgroup with unknown primary tumour (N-CUP) seems to have a worse prognosis as resection of the primary is necessary for cure. The diagnostics and therapeutic algorithms for N-CUP in a German single centre are presented.Patients/Methods: Analysis of the surgical databank showed 35 cases of N-CUP in 261 cases with NEN from gastroenteropancreatic and lung origin over 2 decades (03/1990-03/2011). Three groups were built: K1 - primary detection after operative exploration (n = 10), K2 - unknown primary after operative exploration (n = 10) and K3 - no operative exploration for various reasons (n = 13).Results: Initially 13.4 % (35/261) of patients presented as N-CUP, after intensified diagnostics 12.7 % (33/261) and after operative exploration 8.8 % (23/261) remained with unknown primary tumour. The sex ratio was 1 : 1, the median age is significantly higher in N-CUP [63.8 years (y) vs. 55.9 y, p = 0.004), the 5-year-survival is lower (58 vs. 72 %, n. s.). compared to NEN with known primary. Operative exploration was performed in 60.6 % (20/33), 30 % (6/20) of them were found to have inoperable situations, in 20 % (4/20) single site metastases were removed completely and in 50 % (10/20) a primary tumour was detected (8 × midgut, 2 × pancreas) intraoperatively. In these cases 70 % (7/10) got complete tumour resection (R0) and in 30 % (3/10) primary tumour resection with debulking of liver metastasis was done. In K3 (39.4 %, 13/33) most patients [69.2 % (9/13)] were treated with chemotherapy. The median age in K1 was significantly lower than in K3 (54.9 y vs. 68.3 y, p = 0.028), male dominance was seen in K3 (3,3 : 1, n. s.). The average Ki-67 index was 4.3, 23.8 and 53 % in K1, K2 and K3 (p < 0.0001 for K1 and K3 and p = 0.035 for K2 and K3), respectively. The death rate was 20, 30 and 76.9 % in K1, K2 and K3, respectively.Conclusion: Primary tumours of the midgut and pancreas are often found in the subset of well differentiated neuroendocrine CUP syndrome after open surgical exploration. A high rate of complete tumour resection and cure can be achieved in these cases. After common diagnostic tools (CT, MRI and somatostatin receptor scintigraphy), immunhistochemistry can give important hints (CDX-2 for midgut, TTF-1 for lung and thyroid) for a primary lesion. Also in single site metastasis without primary tumour detection a good clinical outcome is seen after complete resection. PMID:23508839
Begum, N; Hubold, C; Buchmann, I; Thorns, C; Bouchard, R; Lubienski, A; Schlöricke, E; Zimmermann, M; Lehnert, H; Bruch, H-P; Bürk, C G
Background A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in MLL-related leukemia. Recently, we have established the MLL-SEPT2 gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified MLL and SEPT2 gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of MLL-SEPT2-associated myeloid neoplasms so far described in the literature. Methods Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: CBFB-MYH11 (n = 13), PML-RARA (n = 12); RUNX1-RUNX1T1 (n = 12), normal karyotype (n = 11), and MLL gene fusions other than MLL-SEPT2 (n = 10). We also studied all three MLL-SEPT2 myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient. Results When compared with normal controls, we found a 12.8-fold reduction of wild-type SEPT2 and MLL-SEPT2 combined expression in cases with the MLL-SEPT2 gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type MLL and MLL-SEPT2 combined expression (p = 0.028). The down-regulation of SEPT2 in MLL-SEPT2 myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other MLL gene fusions). In addition, MLL expression was also down-regulated in the group of MLL fusions other than MLL-SEPT2, when compared with the normal control group (p = 0.023) Conclusion We found a significant down-regulation of both SEPT2 and MLL in MLL-SEPT2 myeloid neoplasias. In addition, we also found that MLL is under-expressed in AML patients with MLL fusions other than MLL-SEPT2.
Background: Parathyroid disease occurs sporadically or as part of hereditary multiple endocrine neoplasia (MEN) syndrome. The aim of this study was to evaluate the possible role of the RET proto-oncogene not only in hereditary MEN 2–associated hyperparathyroidism but also in different forms of sporadic hyperparathyroidism. Methods: We investigated 22 patients with parathyroid disease whose family history and results of laboratory
Frank Willeke; Martin P. Hauer; Rene Buchcik; Johannes F. Gebert; Matthias Hahn; Guido Fitze; Gunhild Mechtersheimer; Peter Möller; Hans-Detlev Saeger; Christian Herfarth; Hans K. Schackert
We assessed a possible role for high-risk human papillomavirus (HPV) testing in the policy after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 (moderate to severe dysplasia). According to the Dutch guidelines follow-up after treatment consists of cervical cytology at 6, 12 and 24 months. Colposcopy is only performed in case of abnormal cervical cytology. In this observational study
M A E Nobbenhuis; C J L M Meijer; A J C van den Brule; L Rozendaal; F J Voorhorst; E K J Risse; R H M Verheijen; T J M Helmerhorst
OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain reaction assay for detection of human papillomavirus infection for prognostic value in the triage strategies for high-grade (grade 2 or 3) cervical intraepithelial neoplasia in women referred for colposcopy after abnormal Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a colposcopic clinic providing care for
Ervin Adam; Raymond H. Kaufman; Zuzana Berkova; Joseph Icenogle; William C. Reeves
Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia
The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined
SK Jonas; C Benedetto; A Flatman; RH Hammond; L Micheletti; C Riley; PA Riley; DJ Spargo; M Zonca; TF Slater
Background: There is no study of circumferential EMR in patients with Barrett's esophagus containing early stage malignant lesions. This study investigated the effectiveness and safety of circumferential EMR by using a simple snare technique without cap. Method: Patients with Barrett's esophagus containing multifocal high-grade intraepithelial neoplasia or intramucosal cancer, and patients with endoscopically nonidentifiable early stage malignant mucosal changes incidentally
Stefan Seewald; Thawatchai Akaraviputh; Uwe Seitz; Boris Brand; Stefan Groth; Gerardo Mendoza; Xikun He; Frank Thonke; Manfred Stolte; Soeren Schroeder; Nib Soehendra
Objective: The NHS Bowel Cancer Screening Programme (BCSP) uses faecal occult blood (FOB) testing to select patients aged 60–69 years for colonoscopy. Aim: To examine the association between aspirin use and the detection of colorectal neoplasia in screened patients undergoing colonoscopy. Methods: Data were collected prospectively on individuals who underwent colonoscopy following a positive FOB test in the South of
Thomas J. W. Lee; Mark A. Hull; Praveen T. Rajasekhar; Gayle M. Clifford; Mary Ritchie; Peter James; Richard J. Q. McNally; Matthew D. Rutter; Colin J. Rees
Previous studies suggest that high parity increases the risk of cervical cancer. We studied the risk of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN3) in a Finnish cohort of grand multiparous (GM) women (at least five children) with low prevalence of sexually transmitted infections (STI). The Finnish Cancer Registry data revealed 220 CC and 178 CIN3 cases among 86
M Hinkula; E Pukkala; P Kyyrönen; P Laukkanen; P Koskela; J Paavonen; M Lehtinen; A Kauppila
Objective: Phaeochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2) pro- duce adrenaline, whereas those with von Hippel-Lindau (VHL) syndrome do not. This study assessed whether these distinctions relate to differences in expression of the transporters responsible for uptake and storage of catecholamines - the noradrenaline transporter and the vesicular monoamine trans- porters (VMAT 1 and VMAT 2).
Thanh-Truc Huynh; Karel Pacak; Frederieke M Brouwers; Mones S Abu-Asab; Robert A Worrell; MacClellan M Walther; Abdel G Elkahloun; David S Goldstein; Susannah Cleary; Graeme Eisenhofer
THE INDUCTION OF COLORECTAL NEOPLASIA BY A MIXTURE HIGH IN BROMINA TED TRIHALOMETHANES (THMS) ADMINISTERED IN THE DRINKING W A TER TO MALE F344/N RA TS. Abstract: The THMs are the most widely distributed and concentrated of the chlorine disinfection by-products (D...
Two models for meningeal neoplasia have been developed in rats using intrathecal injection of 9L gliosarcoma and Walker 256 carcinosarcoma cells. Tumor cells were injected in unanesthe- tized animals through an indwelling catheter inserted at the cisterna magna to the level of the lumbar enlargement of the spinal cord. Survival of rats was dependent on the number of tumor cells
Kimberly L. Kooistra; Moses Rodriguez; Garth Powis; Tony L. Yaksh; Gail J. Harty; Joan F. Hilton; Edward R. Laws
No standard screening programs exist to detect vulvar carcinoma or its precursor lesions, and therefore gynecologists, dermatologists and other healthcare providers in this field should be aware of the clinical features, behavior and management of the different existing premalignant vulvar lesions, squamous vulvar intraepithelial neoplasia (VIN), vulvar Paget's disease and melanoma in situ. In 2004, a new classification for squamous VIN was introduced by the International Society for the Study of Vulvar Disease, subdividing squamous VIN into the HPV-related usual type, and into differentiated type, which is associated with lichen sclerosus. This review describes the relevant aspects of squamous VIN, vulvar Paget's disease and melanoma in situ, its epidemiological characteristics, diagnosis, management and malignant potential. PMID:20504079
Terlou, Annelinde; Blok, Leen J; Helmerhorst, Theo J M; van Beurden, Marc
The recent finding that lobular, and not ductal intraepithelial neoplasia (DIN) displays loss of E-cadherin expression has greatly facilitated the categorization of a large proportion of morphologically ambiguous intraepithelial neoplasias into ductal or lobular types. One reason for such morphologic ambiguity is the presence of comedo-type necrosis within an intraepithelial lesion that otherwise shows archetypal cytologic and architectural features of lobular intraepithelial neoplasia (LIN). The clinicopathologic features of 18 such cases are described in this report. These 18 cases of classic LIN were accumulated from the recent databases of 6 institutions. All cases, by definition, showed no expression of E-cadherin. The 18 patients, all women, were 41 to 85 years of age (mean 61.3). The lesions were initially identified in an excisional biopsy or mastectomy in 12 cases and in an incisional/core biopsy in the remaining 6 cases. An associated invasive carcinoma was present in 12 (67%) of 18 cases (7 classic lobular, 1 pleomorphic lobular, 1 ductal, 1 mixed lobular and ductal, 1 tubular, and 1 case with ductal and lobular carcinomas as separate foci). The average age of the 6 patients with pure LIN (ie, LIN without an invasive component (62.5 y) was not significantly different from the 12 patients in which there was an invasive component (60.7 y) (P = 0.78). The lesions had associated calcifications, typically within the necrotic foci, in 10 (55%) of 18 cases. Immunoreactivity for estrogen receptor, progesterone receptor (in >10% of lesional cells), and high-molecular weight keratin was present in 17/18 (94%), 15/18 (83%) and 17/18 (94%) of cases, respectively. Overexpression of HER2/neu, as assessed immunohistochemically, was absent in all 15 cases available for such evaluation. Foci of DIN, separate from the lobular lesions, were present in 6 (33%) of 18 cases. LIN with necrosis seems to occur at an older age than classic LIN, is commonly associated with invasive carcinoma and is significantly more frequently associated with lobular than ductal invasive carcinoma. When present without an invasive component, it may be mistaken for DIN 2 (grade 2 ductal carcinoma in situ). Although the necrosis suggests a ductal phenotype for these intraepithelial proliferations, architectural and cytologic features, high-molecular weight keratin[+], estrogen receptor[+], progesterone receptor[+], and human epidermal growth factor receptor 2 /neu[-] immunoprofile, frequent association with invasive lobular carcinoma, and lack of immunoreactivity for E-cadherin, strongly suggests that these lesions are within the morphologic spectrum of lobular neoplasia. Long-term follow-up studies are required to define the true natural history of these lesions. However, because classic LIN with necrosis is apparently rare in its pure form, reexcision is recommended when this lesion is detected in isolation in a core biopsy. PMID:17063087
Fadare, Oluwole; Dadmanesh, Farnaz; Alvarado-Cabrero, Isabel; Snyder, Robert; Stephen Mitchell, J; Tot, Tibor; Wang, Sa A; Ghofrani, Mohiedean; Eusebi, Vincenzo; Martel, Maritza; Tavassoli, Fattaneh A
Lobular neoplasia (LN) is a risk factor for bilateral breast cancer without consensus as to its appropriate management. The authors report on a retrospective multi-institutional study concerning 52 patients in whom a diagnosis of LN was made after core needle biopsy (CNB) and who subsequently underwent surgical excision. The excision specimens revealed seven cases of invasive carcinoma and three cases of ductal carcinoma in situ, indicating an underestimation of lesions at CNB in 19% of cases, and in particular in those patients with pleomorphic LN, and when clinical, radiological masses were detected. This lesion is increasingly being diagnosed by CNB due to widespread screening. Follow-up surgical excision should be performed in order to examine the whole lesion in the case of masses or when the histologic specimen reveals a pleomorphic subtype. In other cases, annual mammographic surveillance should be undertaken due to the persistent long-term risk of developing bilateral breast cancer. PMID:17629481
Lavoué, Vincent; Graesslin, Olivier; Classe, Jean Marc; Fondrinier, Eric; Angibeau, Hélčne; Levęque, Jean
The objective of this retrospective study is to report and analyse the incidence of and risk factors for post-transplant malignant neoplasia (PTMN) in feline renal transplant recipients (cases, n = 45) and compare incidence to a population of cats that did not receive a transplant (controls, n = 79). Information from the medical records of cases regarding signalment, blood work and concomitant disease, post operative cyclosporine concentrations, survival time (ST), and whether PTMN developed, the type of PTMN, time to occurrence (TTO), and ST after diagnosis was gathered. PTMN occurred in 11 of 45 (24%) cases, of which, four were lymphoma. Median TTO of all PTMN was 1020 days. Median TTO of lymphoma was 454 days. Median ST after diagnosis of PTMN was 15 days. No risk factors were identified. Compared with control cats, cases had more than six times higher odds of developing PTMN compared with control cats (P < 0.01). PMID:19222830
Schmiedt, C W; Grimes, J A; Holzman, G; McAnulty, J F
Thymic neuroendocrine (NE) tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1). They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT) at the time of parathyroid surgery for primary hyperparathyroidism (PHPT) in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.
Sadacharan, Dhalapathy; Reddy, Sagili Vijaya Bhaskar; Agrawal, Vinita; Agarwal, Gaurav
Thymic neuroendocrine (NE) tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1). They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT) at the time of parathyroid surgery for primary hyperparathyroidism (PHPT) in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting. PMID:23961499
Sadacharan, Dhalapathy; Reddy, Sagili Vijaya Bhaskar; Agrawal, Vinita; Agarwal, Gaurav
Insulinoma is a rare neuroendocrine tumor, most commonly originating from the pancreas, which is either sporadic or familial as a component of multiple endocrine neoplasia type 1 syndrome (MEN1). It is characterized by increased insulin secretion leading to hypoglycemia. Surgical removal is considered the treatment of choice, with limited side effects and relatively low morbidity and mortality, both being improved by the laparoscopic procedure. We present the case of a 30-year-old patient with MEN1 and recurrent insulinoma with severe hypoglycemic episodes who could not be surgically treated due to the adherence of the tumor to large blood vessels and to prior multiple surgical operations. He was treated by repeated embolization using spherical polyvinyl alcohol particles, resulting in shrinkage of the tumor, improvement of the frequency and severity of the hypoglycemic episodes, and better quality of life.
Peppa, Melpomeni, E-mail: firstname.lastname@example.org ['Attikon' University Hospital, Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Brountzos, Elias; Economopoulos, Nicolaos ['Attikon' University Hospital, Second Radiology Department, Athens University Medical School (Greece); Boutati, Eleni ['Attikon' University Hospital, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Pikounis, Vasilios ['Attikon' University Hospital, Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Patapis, Paul ['Attikon' University Hospital, Third Surgery Department, Athens University Medical School (Greece); Economopoulos, Theofanis; Raptis, Sotirios A. ['Attikon' University Hospital, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece); Hadjidakis, Dimitrios ['Attikon' University Hospital, Endocrine Unit, Second Department of Internal Medicine-Propaedeutic, Research Institute and Diabetes Center, Athens University Medical School (Greece)
The aim of this study is to investigate the distribution and roles of podoplanin/D2-40-positive pericryptal stromal cells in superficial colorectal epithelial neoplasia. A total of 105 superficial colorectal epithelial tumors were examined: 65 tubular/tubulovillous adenomas, 32 adenocarcinomas in situ, and 8 submucosally invasive adenocarcinomas. Immunohistochemical analysis was performed using the monoclonal antibody to podoplanin/clone D2-40, which is reactive in both lymphatic endothelial cells and activated stromal cells, but negative in vascular endothelial cells. We found 50 (78 %) of 65 tubular/tubulovillous adenomas, 30 (94 %) of 32 adenocarcinomas in situ, and all 8 (100 %) submucosally invasive adenocarcinomas had podoplanin/D2-40-positive pericryptal stromal cells, whereas all normal colorectal mucosae had no podoplanin/D2-40-positive pericryptal stromal cells. The presence of podoplanin/D2-40-positive pericryptal stromal cells is associated with epithelial tumorigenesis in the colorectum. PMID:23306662
Nakayama, Hirofumi; Enzan, Hideaki; Yasui, Wataru
Vulval squamous cell carcinoma appears to arise via 2 distinct pathways. A significant minority are associated with oncogenic human papillomavirus (HPV) infection and undifferentiated vulval intraepithelial neoplasia (VIN). However, the majority arises in the absence of HPV, on a background of chronic inflammation. Until recently, it was assumed that lichen sclerosus was the underlying inflammatory condition in the majority of HPV-negative cancers. This pathway of carcinogenesis has been less well studied than the HPV pathway. Emerging evidence implicates differentiated VIN (DVIN), rather than lichen sclerosus, as the most likely precursor lesion in HPV-negative vulval squamous cell carcinoma. Here we discuss the clinical and molecular evidence that implicates DVIN as a lesion with a high malignant potential. This lesion is probably underdiagnosed and may be undertreated. Better recognition of DVIN by gynecologists and pathologists may therefore offer an opportunity to prevent some vulval cancers. PMID:21946295
Kokka, Fani; Singh, Naveena; Faruqi, Asma; Gibbon, Karen; Rosenthal, Adam N
Multiple endocrine neoplasia type 1 is an autosomal dominant cancer syndrome characterized by pituitary, parathyroid and enteropancreatic endocrine tumors, which is caused by germline mutations of the tumor suppressor gene MEN1. In the case reported here, the patient had family with this disease whose germline MEN1 mutation was undetectable by conventional sequencing analysis. Further investigations involving polymorphism analyses, gene dose assay and nucleotide sequencing identified a large germline deletion of approximately 29 kilobase pairs spanning the whole MEN1 gene. The deletion was flanked by Alu repetitive sequences, suggesting unequal homologous recombination as the deletion mechanism. The polymorphism linkage data suggested that an asymptomatic son of the proband did not carry the family mutation. More direct evidence was obtained by gene dose assay and deletion-specific polymerase chain reaction, which demonstrated the normal MEN1 gene dosage and the absence of the deletion breakpoints in this asymptomatic subject and thus definitely excluded the possibility of disease predisposition. PMID:17000701
Fukuuchi, Atsushi; Nagamura, Yuko; Yaguchi, Hiroko; Ohkura, Naganari; Obara, Takao; Tsukada, Toshihiko
Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.
de Menezes Montenegro, Fabio Luiz; Lourenco, Delmar Muniz; Tavares, Marcos Roberto; Arap, Sergio Samir; Nascimento, Climerio Pereira; Neto, Ledo Mazzei Massoni; D'Alessandro, Andre; Toledo, Rodrigo Almeida; Coutinho, Flavia Lima; Brandao, Lenine Garcia; de Britto e Silva Filho, Gilberto; Cordeiro, Anoi Castro; Toledo, Sergio Pereira Almeida
Background Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. Methodology/Principal Findings This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10?/? mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-? mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10?/? mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability. Conclusions/Significance Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.
Chichlowski, Maciej; Westwood, Greg S.; Abraham, Soman N.; Hale, Laura P.
Objective To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer. Data sources Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished. Results One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g. Conclusions In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.
ABSTRACT Objectives: This study intends to analyze some statistical data concerning Cervical Intraepithelial Neoplasia diagnosed in our hospital. Material and Methods: Our study concerning the incidence of Cervical Intraepithelial Neoplasia (CIN) covers the 2000-2009 time-span, the data being collected from the Histopathology Exams (HPE) registers. Results: During this period, CIN lesions were discovered in 1256 cases and Cervical Intraglandular Dysplasia (CIGD) in 53 cases. CIN I, CIN II and CIN III lesions represented 65.92%(828 cases), 19.67% (247 cases), and 14.41% (181 cases) of the total CIN cases, respectively. There were 26 cases combined with cervical carcinoma (2.07% of all CIN cases, 3.56% of the 731 cervical cancer cases). The mean patients' age was 44.65± 9.83 years for all cervical dysplasia cases, 44.58± 9.75 years for all CIN cases, 43.81±9.22, 46.50±10.17, and 45.46±11.05 years for CIN I, CIN II, and CIN III, respectively, and 46.45 ± 11.63 years for CIGD. The t-test revealed the following significant differences: all cases versus CIN I (p<0.05) and CIN II (p<0.01), CIGD versus CIN I (p<0.05), all cases versus CIN II (p<0.01), CIN I versus CIN II (p<0.0001) and versus CIN III (p<0.05). The mean age of the 731 cervical cancer cases diagnosed in our hospital during that same period was 52.94±12.96 years,and it was statistically significantly different from the mean ages of patients with CIN I, II and III (p <0.00000001) and with CIGD (p<0.0005). Conclusions: Early detection of CIN is of utmost importance for preventing cervical cancer, a serious and frequent health problem in Romania.
DASCAU, Voicu; FURAU, Gheorghe; FURAU, Cristian; PAIUSAN, Lucian; RADU, Adriana; STANESCU, Casiana
Disseminated neoplasia (DN) is a pathological condition reported for several species of marine bivalves throughout the world, but its aetiology has not yet been satisfactorily explained. It has been suggested that chemical contamination could be a factor contributing to neoplasia. The aim of the present study was to compare cell and tissue biomarkers and the transcription level of cancer-related genes in cockles (Cerastoderma edule) affected by DN with those of healthy cockles in relation to che