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At least 19 recordsLinked to original sources

Impact of concurrent proliferative high-risk lesions on the risk of ipsilateral breast carcinoma recurrence and contralateral breast carcinoma development in patients with ductal carcinoma in situ treated with breast-conserving therapy.

BACKGROUND: The purpose of the study was to determine the risk of ipsilateral breast carcinoma recurrence (IBCR) and contralateral breast carcinoma (CBC) development in patients with a concurrent diagnosis of ductal carcinoma in situ (DCIS) with atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). METHODS: Records of all 307 patients with DCIS treated with breast-conserving treatment (BCT) from 1968 to 1998 were analyzed. Initial pathology reports and all slides available were re-reviewed for evidence of ADH, ALH, or LCIS. Actuarial local recurrence rates were calculated. RESULTS: Fifty-five cases of DCIS were associated with ADH, 11 with ALH or LCIS, and 14 with both ADH and ALH or LCIS. Overall, IBCR occurred in 14% and no significant difference in the IBCR rate was identified for patients with proliferative lesions compared with patients without these lesions (P = 0.38). Development of CBC in patients with concurrent DCIS and ADH was 4.4 times (95% confidence interval [CI], 1.44-13.63) that in patients with DCIS alone (P < 0.01). The 15-year cumulative rate of CBC development was 22.7% in patients with ALH or LCIS compared with 6.5% in patients without these lesions (P = 0.30) and 19% in patients with ADH compared with 4.1% in patients with DCIS alone (P < 0.01). CONCLUSION: The risk of CBC development is higher with concurrent ADH than in patients with DCIS alone, and these patients may therefore be appropriate candidates for additional chemoprevention strategies. Concurrent ADH, ALH, or LCIS with DCIS is not a contraindication to BCT.

Breast Neoplasms↗

Auricular malignant neoplasms. Identification of high-risk lesions and selection of method of reconstruction.

A prospective study of 17 auricular malignant neoplasms was conducted comparing recommended margins for conventional surgical excision to the actual margins obtained after microscopically controlled excision (Mohs' chemosurgery technique) to identify lesions at high risk for inadequate excision with conventional excision. High-risk lesions included all tumors larger than 1 cm, morpheaform basal cell carcinoma, and multiply recurrent lesions of any size. Successful excision by conventional surgery would have resulted in a defect notably larger than the actual Mohs' defect in all cases. The excess tissue excised by conventional surgery averaged 180% larger than the actual defect in primary lesions and 347% larger in recurrent lesions. Methods of reconstruction used include the following: secondary intention (granulation), primary closure, skin grafts, local flaps, and meatoplasty. The incidence, indications, and usual results obtained are discussed in detail. Mohs' chemosurgery technique provides substantial benefit and should be considered in all recurrent lesions and primary lesions larger than 1 cm to reduce recurrence and minimize the resultant deformity.

Basal Cell Carcinoma↗

The value of clinical characteristics and breast-imaging studies in predicting a histopathologic diagnosis of cancer or high-risk lesion in patients with spontaneous nipple discharge.

BACKGROUND: The purpose of this study was to determine the utility of breast-imaging studies in identifying cancer and high-risk lesions among patients with spontaneous, single-duct, nipple discharge (SSND). METHODS: The medical records of 168 cases with SSND treated with duct excision between June 1998 and May 2004 were reviewed. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mammogram, ultrasound, and ductogram in predicting high-risk lesions and cancer were calculated. RESULTS: The sensitivity of mammography was 10%, the specificity 94%, the NPV 88%, and the PPV 18%. Ultrasonography had a sensitivity of 36%, specificity of 68%, PPV of 14%, and NPV of 89%. Ductography had a sensitivity of 75%, specificity of 49%, and NPV and PPV of 93% and 18%, respectively. CONCLUSIONS: Conventional imaging studies do not accurately identify cancer or high-risk lesions in patients with SSND. All patients with SSND should be offered duct excision.

Adult↗

Proliferative activity in pancreatic intraepithelial neoplasias of chronic pancreatitis resection specimens: detection of a high-risk lesion.

Patients with chronic pancreatitis have a markedly increased risk of pancreatic cancer compared with general population. Mechanism of the increased risk is not completely known. The current progression model for pancreatic ductal adenocarcinoma proposes the progression from normal ductal epithelium through a series of lesions called pancreatic intraepithelial neoplasias (PanINs) to invasive cancer. These lesions are frequently seen in chronic pancreatitis tissue. Proliferative activity in PanINs of chronic pancreatitis tissue has not been separately studied using the current nomenclature. Our study included 36 chronic pancreatitis resection specimens. A total number of 106 PanINs found within 32 resection specimens was histologically graded and then immunolabeled using a monoclonal antibody against Ki-67 that is expressed in dividing cells. The Ki-67 labeling indices in the increasing grades of PanINs were counted with following results: PanIN-1A, 0.77%; PanIN-1B, 3.26%; PanIN-2, 14.68%; and PanIN-3, 25.4%. The difference in Ki-67 labeling indices among these types of lesions was statistically significant (p<0.001, t-test). These results correlate with known genetic alterations found in chronic pancreatitis, especially with p16 inactivation that was recently described in PanINs arising in patients with chronic pancreatitis. Moreover, our findings support the currently accepted pancreatic progression model and Ki-67 immunohistochemistry might represent an efficient tool for an identification of a high-risk lesion.

Antibodies, Monoclonal↗

Suppression of cyclic coronary flow variation and reduction of restenosis with abciximab for morphologically high-risk lesions undergoing percutaneous coronary intervention.

Cyclic coronary flow variation (CCFV), a phenomenon related to repetitive accumulation of platelet aggregates at sites with endothelial injury, was reported to predict the acute ischemic complication after percutaneous coronary intervention. Platelet activation also stimulates neointimal proliferation, which is essential in the late restenosis process. Abciximab, a nonspecific antagonist to the platelet membrane glycoprotein IIb/IIIa as well as other integrins, may eliminate CCFV. A randomized study was conducted to evaluate the effect of abciximab on CCFV and restenosis in morphologically high-risk lesions. Forty-six coronary arteries with objective ischemia on the corresponding vascular territories were successfully treated. The use of abciximab successfully suppressed the occurrence of CCFV (p < or = 0.001) after balloon dilatation. In the follow-up study 3 months later, the use of abciximab predicted a lower loss index and less clinical recurrence (p = 0.008 and 0.03, respectively). The occurrence of CCFV, however, did not affect the angiographic or clinical outcome. The reduction of restenosis and clinical recurrence by the use of abciximab may thus be related to its nonglycoprotein IIb/IIIa effects, in addition to platelet inhibition.

Abciximab↗

Proliferative high-risk lesions of the breast: contribution and limits of US-guided core biopsy.

PURPOSE: To retrospectively correlate high-risk proliferative breast lesions (radial scar, atypical lobular hyperplasia, lobular carcinoma in situ and papillary lesions) diagnosed on core biopsy with the definitive histopathological diagnosis obtained after surgical excision or with the follow-up, in order to assess the role of core biopsy in such lesions. To discuss the management of the patient after a core biopsy diagnosis of high-risk proliferative breast lesion. MATERIAL AND METHODS: We evaluated 74 out of 1776 core biopsies consecutively performed on 67 patients. The histopathologic findings were as follows: 11 radial scars (RS), 3 atypical lobular hyperplasias (ALH), 3 lobular carcinomas in situ (LCIS), 57 benign papillary lesions. All patients underwent bilateral mammography, whole-breast ultrasound with a linear-array broadband transducer, and core biopsy with a 14 Gauge needle and a mean number of samples of 5 (range 4-7). Sixty-two of 67 patients, for a total of 69/74 lesions, underwent surgical biopsy despite benign histopathologic findings, mostly because of highly suspicious imaging for malignancy (BIRADS 4-5), whereas 5 patients refused surgery and have been followed up for a least 18 months and are still being followed up (2 with RS, 1 with ADH and 2 with papillary lesions). RESULTS: Among the core biopsied lesions with a diagnosis of RS (n = 11) pathology revealed one ductal carcinoma in situ (DCIS) (this case was characterized by granular microcalcifications on mammography and by a mass with irregular margins on ultrasound). Also in the group of ADH (n = 3) pathology revealed one DCIS (lesion not visible on mammography but depicted as a suspicious mass on US). In the group of LCIS (n = 3) pathologists found an invasive lobular carcinoma (ILC). Among the benign papillary lesions (n = 57) histopathologic analysis of the surgical specimen revealed 7 malignant lesions (4 papillary carcinomas and 3 DCIS), whose mammographic and ultrasound findings were indistinguishable from benign lesions. Altogether there were 10 false negative results (underestimation) out of 74 core biopsies with a diagnosis of high-risk proliferative breast lesions. CONCLUSION: The high rate of histological underestimation after core biopsy (10/74) (13.5%) demands a very careful management of patents with a core biopsy diagnosis of high-risk proliferative breast lesions, especially in the case of RS, lobular neoplasia and papillary lesions. However, the high imaging suspicion for malignancy prompts surgery. It is possible to assume that, when there is a low imaging suspicion for malignancy, when enough tissue has been sampled for pathology and no atypia is found within the lesions, surgery is not mandatory but a very careful follow-up is recommended. We must underline that there is no agreement regarding the quantity of tissue to sample. Vacuum-assisted biopsy may lead to better results, although there is as yet no proof that it can actually replace surgery in this group of lesions, since it seems only to reduce but not abolish the histological underestimation.

Adult↗

A high-risk lesion for invasive breast cancer, ductal carcinoma in situ, exhibits frequent overexpression of retinoid X receptor.

The development of prevention strategies for breast cancer will require a molecular map of carcinogenesis. We have investigated gene expression patterns in premalignant and early carcinomatous human breast lesions that confer to the patient varying risks for developing invasive breast cancer. The relative expression levels of one of the retinoid receptors, retinoid X receptor (RXR), was determined by in situ hybridization to 58 biopsy specimens; RXR mRNA grain density over each lesion was compared to that over the normal ductal/lobular units in each section. Overexpression of RXR mRNA was observed in 66% of noncomedo ductal carcinoma in situ (DCIS), which confer a >8-fold increase in breast cancer risk, and 88% of comedo DCIS lesions, which are associated with a yet higher risk. In contrast, only 8% of lesions that confer little or no increase in breast cancer risk overexpressed RXR mRNA (P = 0.0008). Limited in situ hybridization data using retinoic acid receptor (RAR) riboprobes showed overexpression of RAR alpha, but not RAR beta or -gamma, in only a modest percentage (36%) of cases, suggesting that all members of the retinoid receptor superfamily are not similarly regulated. Immunohistochemistry performed on 52 DCIS specimens for alpha, beta, and gamma isoforms of RXR confirmed its overexpression at the protein level and implicate RXR alpha as the predominant overexpressed form. The data indicate that RXR overexpression is associated with an increased risk for the development of invasive breast cancer in human breast lesions and suggest the hypothesis that it is causally involved in breast oncogenesis. The implications for retinoid chemoprevention are discussed.

Biomarkers, Tumor↗

Benign melanocytic lesions: risk markers or precursors of cutaneous melanoma?

BACKGROUND: The role of benign melanocytic lesions as precursors and not only as risk markers for the development of cutaneous melanoma is controversial. OBJECTIVE: The purpose of the study was to assess the frequency of the histologic association of benign melanocytic lesions with cutaneous melanoma of a maximum thickness of 1.00 mm. The possibility that the spatial association of benign lesions with melanoma may be coincidental was also investigated. METHODS: The study subjects representing 289 cases of cutaneous melanoma of maximum thickness 1.00 mm (or less) were examined histologically for the presence of an associated benign melanocytic lesion(s), including lentiginous melanocytic proliferation; junctional, compound, or intradermal nevus; dysplastic nevus; and congenital nevus contiguous with or adjacent to the melanoma. The effects of age, tumor thickness, level of invasion, histologic type, and anatomic site on the association of benign melanocytic lesions with melanoma were assessed. In the control subjects 40 basal cell carcinomas and 38 compound nevi (not dysplastic) randomly chosen and matched for age (+/- 1 year) and site (head/neck, trunk, upper and lower limbs) with a melanoma case were examined to assess the proportion of these cases associated with benign lesions compared with the matched melanoma cases. RESULTS: A nevus was associated with melanoma in 51% of cases (n = 147). Of these, 82 (56%) were dysplastic nevi, 61 (41%) were common acquired nevi, and 4 (3%) were congenital nevi. Lentiginous melanocytic proliferation was present in the epidermis adjacent to 219 melanomas (75%) and in 44% of these cases (n = 97) a coexisting nevus was also present. CONCLUSION: The results of this study lend further support to the concept of common acquired nevi and dysplastic nevi as precursors of cutaneous melanoma. In addition, lesions diagnosed clinically as simple lentigo and solar lentigo may be important as potential precursors of melanoma, particularly in the elderly.

Adult↗

Sow shoulder lesions: risk factors and treatment effects on an Ontario farm.

The objectives of this study were to identify risk factors for the development of shoulder lesions in lactating sows and to determine if an effective, economical, and practical treatment could be designed. The study was conducted at a 300-sow farrow-to-finish swine farm in Ontario between July and December 2004. Sow data were recorded on either the day of or 1 d after entering the farrowing crate and before farrowing had occurred. The right and left shoulders of the sows were assigned a score between 0 (normal) and 4 (lesion > 2.3 cm in diam.) on d 1 of the study and weekly thereafter throughout lactation. If a lesion developed, sows were randomly placed into 1 of 3 treatment groups. Groups consisted of a control group that received no treatment, a group that had a 0.2-cm thick, 60 x 60-cm, stainless steel plate attached to the bottom of the farrowing crate, and a group that had a 3.8-cm thick, 60 x 60-cm rubber mat attached to the bottom of the farrowing crate. Of the 310 sows involved in the study, 107 (34%) developed a lesion with a score of 3 or 4. Multivariate regression analysis identified body condition at weaning, flank-to-flank measurements at weaning, breed, parity, farrowing room section, and weaning weight of the litter as significantly associated with development of a shoulder lesion of score 3 or 4. The average number of days for the lesions to be completely resolved was 25 for sows receiving rubber mats, 32 for the controls, and 39 for the sows receiving stainless steel plates. Rubber mats attached to the bottom of the farrowing crates decreased the time required to heal the lesions when compared with controls. The low cost per mat (less than 0.90 dollars factoring in repeated use) makes it an economical and effective treatment.

Animals↗

[PLasma lipids and cardiovascular risk: lesions in the community].

We examined serum cholesterol levels and lipoprotein profiles as possible risk factors for the development of coronary heart disease by means of a review of epidemiological studies. At present a great body of literature reinforces the evidence of the etiologic role of total and LDL cholesterol and the magnitude of benefits deriving from its treatment. No convincing evidence has been put forward to indicate that the undoubtedly favourable effects of cholesterol lowering on coronary heart disease risk are offset by untoward effect on non-cardiovascular disease rates.

Cardiovascular Diseases↗

Thalamic vascular lesions. Risk factors and clinical course for infarcts and hemorrhages.

BACKGROUND AND PURPOSE: The data of patients with an MRI-confirmed diagnosis of thalamic stroke were analyzed to identify risk factors and to describe the clinical syndromes according to the thalamic arterial territory involved. METHODS: We examined the records of all patients with a diagnosis of thalamic stroke confirmed by MRI who attended the National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" from 1987 through 1995. A database containing demographic features, risk factors, clinical course, type and mechanism of stroke, and vascular territory was analyzed. RESULTS: Twenty-eight patients (19 men and 9 women; mean age, 48.2 years) had MRI-confirmed thalamic stroke. Infarct was present in 22 patients and hemorrhage in 6. Eleven (39.3%) patients were younger than 45 years. In these young patients, cigarette smoking was the main risk factor associated with the development of stroke. In young patients, isolated and multiple thalamic lesions were present in almost equal proportions. The remaining 17 patients were older adults (45 to 84 years of age). In such patients, most lesions were multiple and were associated with atherosclerosis-predisposing factors. The main distinguishing clinical feature for hemorrhages and paramedian infarcts in comparison with infarcts in the other thalamic territories was the presence of an altered level of consciousness. No patient died as a direct result of the stroke. CONCLUSIONS: Thalamic stroke commonly occurs in young adults. and its mechanism is often undetermined. Increased awareness of this type of stroke in young adults should lead to better delineation of its clinical features, course, and management.

Adolescent↗

Fibrocystic condition and "at risk" lesions in asymptomatic breasts: a morphologic study of postmenopausal women.

A series of postmenopausal women who had died without noticing any clinical breast disease in their anamnesis (100 cases, age range 46-90 years, average age 62 years) were submitted to bilateral subcutaneous mastectomy during autopsy in order to evaluate the morphologic profile of asymptomatic mammary glands, at different ages. Submacroscopic changes were found and removed to be processed for histology. Results were as follows: a) 46% of cases did not show any change; b) 54% of cases showed benign changes, namely a fibrocystic condition; c) 14% of cases had in addition epithelial lobular hyperplasia with low grade atypia and d) 3% of cases showed atypical borderline lobules (ABL), i.e., terminal ductal-lobular units characterized by severe epithelial atypia. Such lesions cannot be easily distinguished from "in situ" carcinoma, and are currently considered at morphologic risk for subsequent cancer when found in breast biopsies. Our data show that: 1) ABL do not represent a common finding in women who never complained of breast pathology during life; 2) ABL are not related to older age; 3) Fibrocystic condition is quite frequent at subclinical levels also in asymptomatic aging women. The latter statement confirms the opinion that fibrocystic condition should be considered as a common "functional" change. On the contrary, the rarity of ABL gives us a further indirect evidence of their possible precancerous significance. The risk of subsequent development of cancer from the collateral mammary gland could be theoretically higher when ABL are found in breast biopsies of fertile and premenopausal women, who have a longer period of life expectation.

Aged↗

p16(INK4a) alterations in chronic pancreatitis-indicator for high-risk lesions for pancreatic cancer.

BACKGROUND: p16(INK4a) alterations are considered to be an early event in pancreatic tumorigenesis and have been described in duct lesions adjacent to pancreatic cancers. This study evaluates whether duct lesions in chronic pancreatitis tissues of patients without pancreatic cancer also harbor genetic alterations in the p16(INK4a) tumor-suppressor gene, and thus represent high-risk precursors for pancreatic cancer. METHODS: Tissues were obtained from 20 pancreatic specimens taken from patients operated on for histologically verified chronic pancreatitis. Pancreatic intraductal neoplasias (PanIN) were identified in hematoxylin-and-eosin-stained slides. p16 protein expression was investigated immunohistochemically in all specimens. DNA from PanIN and non-PanIN tissue was analyzed genetically for p16(INK4a) mutations by single-strand conformation variation analysis and direct sequencing of the encoding region. Additionally, p16(INK4a) promoter methylation was analyzed by a methylation specific polymerase test. RESULTS: PanIN-1a lesions were identified in 10 of the 20 chronic pancreatitis specimens. Four of these 10 PanIN specimens (40%), but none of the 20 non-PanIN tissues, revealed a loss of p16 expression in immunohistochemistry. The mutational analysis of the p16(INK4a) gene showed 1 known polymorphism (c.442G > A; A148T) but no mutations. Two of the 10 specimens with PanIN revealed an inactivating hypermethylation of the p16(INK4a) promoter. CONCLUSIONS: This study shows for the first time that p16(INK4a) alterations can be observed in a considerable number of PanIN1 in chronic pancreatitis tissues not associated with pancreatic cancer. Therefore, p16(INK4a) alterations, especially promoter methylation, might indicate high-risk precursors in chronic pancreatitis that might progress to cancer.

Adult↗

Prophylactic mastectomy for precancerous and high-risk lesions of the breast.

The candidates for prophylactic mastectomy are those who have a family history of breast cancer, multiple fibrocystic masses that have been biopsied or are too numerous to biopsy appropriately, or patients who previously have had cancer in one breast. The decision to perform the subcutaneous mastectomy is one that must be made by the surgeons involved, in consultation with the patient and her husband. The data from subcutaneous mastectomies appear promising and the technical results have improved as experience has been gained. However, 5 to 10 more years are necessary to determine whether this procedure decreases the incidence of breast cancer in these high-risk patients.

Adult↗

Thin < or = 1 mm level III and IV melanomas are higher risk lesions for regional failure and warrant sentinel lymph node biopsy.

BACKGROUND: Thin melanomas have become increasingly prevalent, and lesions 1 mm or less in thickness are frequently diagnosed. They are considered highly curable when treated with wide local excision alone with reported 5-year disease free survivals of 95% to 98%. However, thin Clark level III and IV melanomas may have an increased potential for metastasizing and late recurrence because of dermal lymphatics located at the interface of the papillary and reticular dermis. We have addressed this controversial area by reviewing the outcomes of patients with invasive thin (< or = 1.0 mm thick) melanomas. METHODS: We reviewed 415 invasive melanomas from 1983-1995 in the Rhode Island tumor registries which kept records of both tumor thickness and Clark levels. Sixty-eight (16.4%) of the 415 invasive melanomas were thin (< or = 1.0 mm in thickness) and were treated by wide local excision only. In situ lesions were excluded. Thirty-eight (56%) of the 68 thin melanomas were either Clark level III or IV. RESULTS: Seven (18.4%) of the 38 level III and IV thin melanomas had a recurrence at a minimum follow-up of 36 months. Median time to recurrence was 52 months, and the average measured depth of tumor thickness was 0.84 mm. Only one (3.3%) of 30 level II melanomas recurred (P < .05). CONCLUSIONS: Thin level III and IV melanomas are at increased risk for late recurrence when compared with all thin melanomas. Because there is effective adjuvant therapy with alpha interferon for patients with stage III melanoma to treat regional and systemic disease, and because sentinel lymph node biopsy (SLNB) offers minimal morbidity, we suggest using SLNB to accurately stage and treat all patients with thin melanoma that are high Clark levels that are at increased risk for metastases.

Adult↗

Risk lesions in cirrhosis and development of hepatocellular carcinoma: an autopsy study.

Non-neoplastic morphologic changes in various types of cirrhosis were evaluated in relationship to the presence or absence of hepatocellular carcinoma (HCC), using autopsy livers from Hokuriku (Japan) and Los Angeles (USA). Macronodular cirrhosis was closely related to HCC in B-viral cirrhosis, alcoholic cirrhosis and cirrhosis of uncertain type. Liver cell dysplasia was most frequently seen in cases with and without HCC in B-viral cirrhosis but was significantly more frequent with HCC in cases of alcoholic cirrhosis and cirrhosis of uncertain type. Nodular bulging activity within regenerative nodules was closely related to HCC in alcoholic cirrhosis. A positive relationship between HCC and Mallory bodies was found in non-alcoholic cirrhosis. These data suggest that patients with macronodular cirrhosis, liver cell dysplasia, nodular bulging activity and Mallory bodies may have an increased risk of developing, or having HCC dependent on the etiology of cirrhosis. The geography and race differences had some relationship to the incidence of HCC.

Autopsy↗