Histologic Changes (histologic + change)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Impact of Helicobacter pylori Eradication Therapy on Histologic Change in the Distal Esophagus

HELICOBACTER, Issue 4 2006
Masanori Toyoda
Abstract Background:, Although cases of reflux esophagitis (RE) developing after treatment to eradicate Helicobacter pylori have been discussed in some detail, no reports are available concerning the histologic examination of RE both before and after eradication therapy. Materials and methods:, Sixty-one patients and 111 specimens were investigated using endoscopic and histologic techniques. The histologic findings including basal zone height, papillar height, Ki-67 labeling index, and COX-2 expression before and after treatment for H. pylori infection were compared with those in normal controls and patients with endoscopic RE. Results:, Twelve months after eradication therapy, the incidence of newly developed endoscopic RE was 20% (5/25). Basal zone height and papillar height had increased at 1 month, but had returned to pretreatment levels after 12 months of eradication therapy. The Ki-67 labeling index was significantly increased 1 and 12 months after eradication therapy compared to values before treatment. COX-2 expression gradually increased after the treatment. The phenomena linked to esophagitis appeared after eradication therapy. However, the severity and extent of these signs were not so high after the treatment of H. pylori than those in patients with overt reflux esophagitis. Focusing on the patients with hiatal hernia, papillar height and Ki-67 labeling index increased significantly after eradication therapy, values being almost the same as those in the patients with endoscopic RE. Conclusions:, Hiatal hernia plays an important role in the possible occurrence of hidden RE after treatment for a H. pylori infection. [source]


Histologic Study of Depressed Acne Scars Treated with Serial High-Concentration (95%) Trichloroacetic Acid

DERMATOLOGIC SURGERY, Issue 8 2006
ANTHONY YUG MD
BACKGROUND Acne scarring is a common manifestation that remains a therapeutic challenge to dermatologists, dermatologic surgeons, and plastic surgeons. Although multiple therapeutic modalities exist, treatment often remains inadequate. The use of high-concentration (95%) trichloroacetic acid (TCA) applied focally to atrophic acne scars has been described. OBJECTIVE The current study confirms the utility of focal application of 95% TCA to acne scars in addition to a histologic examination of this technique. METHODS Acne scars in three patients were treated with focal 95% TCA by serial application. Wooden applicators were used to apply TCA focally and repeated at 6-week intervals for a total of six treatments. Punch biopsies were performed at baseline and at 1 year postoperatively. Histologic examination was performed with routine hematoxylin/eosin, Masson trichrome, and Verhoeff-van Gieson staining. RESULTS Clinical examination revealed apparent cosmetic improvement in both depth and appearance of acne scars. Patient satisfaction was high. Histologic examination demonstrated a decrease in the depth of acne scars. In addition, increased collagen fibers and fragmentation of elastic fibers were noted. There were no complications from the procedure. CONCLUSION Focal application of high-concentration TCA to atrophic and "ice-pick" acne scars appears to produce clinical improvement. Histologic changes of this technique are described. [source]


Effects of Aspirin on the Development of Helicobacter pylori -Induced Gastric Inflammation and Heterotopic Proliferative Glands in Mongolian Gerbils

HELICOBACTER, Issue 1 2008
Guo Qing Li
Abstract Background: Helicobacter pylori infection is a major cause of gastritis and gastric carcinoma. Aspirin has anti-inflammatory and antineoplastic activity. The aim of the present study was to determine the effects of aspirin on H. pylori -induced gastritis and the development of heterotopic proliferative glands. Methods: H. pylori strain SS1 was inoculated into the stomachs of Mongolian gerbils. Two weeks after inoculation, the animals were fed with the powder diets containing 0 p.p.m. (n = 10), 150 p.p.m. (n = 10), or 500 p.p.m. (n = 10) aspirin. Mongolian gerbils were killed after 36 weeks of infection. Uninfected Mongolian gerbils (n = 10) were used as controls. Histologic changes, epithelial cell proliferation and apoptosis, and prostaglandin E2 (PGE2) levels of gastric tissue were determined. Results: H. pylori infection induced gastric inflammation. Administration of aspirin did not change H. pylori -induced gastritis, but alleviated H. pylori -induced hyperplasia and the development of heterotopic proliferative glands. Administration of aspirin accelerated H. pylori -associated apoptosis but decreased H. pylori -associated cell proliferation. In addition, the increased gastric PGE2 levels due to H. pylori infection were suppressed by treatment with aspirin, especially at the dose of 500 p.p.m. Conclusions: Aspirin alleviates H. pylori -induced hyperplasia and the development of heterotopic proliferative glands. Moreover, aspirin increases H. pylori -induced apoptosis. We demonstrated the antineoplastic activities of aspirin in H. pylori -related gastric carcinogenesis. [source]


Clinical and pathological effects of short-term cyanide repeated dosing to goats

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2005
B. Soto-Blanco
Abstract The purpose of this work is to determine and describe the effects of subacute cyanide toxicity to goats. Eight female goats were divided into two groups. The first group of five animals was treated with 8.0 mg KCN kg,1 body weight day,1 for seven consecutive days. The second group of three animals was treated with water as controls. Complete physical examination, including observation for behavior changes, was conducted before and after dosing. One treated animal was euthanized immediately after dosing. Later, two of the remaining treated animals and a control goat were euthanized after a 30-day recovery period. Euthanized animals were necropsied and tissues were collected and prepared for histologic studies. Clinical signs in treated goats were transient and included depression and lethargy, mild hyperpnea and hyperthermia, arrhythmias, abundant salivation, vocalizations, expiratory dyspnea, jerky movements and head pressing. Two goats developed convulsions after day 3 of treatment. One animal developed more permanent behavioral changes as she became less dominant and aggressive. Histologic changes included mild hepatocellular vacuolation and degeneration, mild vacuolation and swelling of the proximal convoluted tubules of the kidneys and spongiosis of the white matter (status spongiosis) of the cerebral white tracts, internal capsule, cerebellar peduncles, spinal cord and peripheral nerves. In summary, sub-lethal cyanide intoxication in goats resulted in behavioral changes, and during the treatment period animals showed delayed signs of toxicity. Significant histologic lesions in goats were observed and need to be characterized further. Copyright © 2005 John Wiley & Sons, Ltd. [source]


Histologic changes in channel catfish, Ictalurus punctatus Rafinesque, fed diets containing graded levels of gossypol,acetic acid

AQUACULTURE NUTRITION, Issue 4 2010
J.J. EVANS
Abstract A study was performed to evaluate the histologic changes among fingerling channel catfish, Ictalurus punctatus Rafinesque, fed purified diets containing gossypol from gossypol,acetic acid. The catfish were maintained on diets with 0, 300, 600, 900, 1200 or 1500 mg gossypol kg,1 diet for 12 weeks, and histologic samples from the stomach, proximal and distal intestines, pancreas, liver, and spleen were obtained from fish in all groups. Stomach sections exhibited significant gastric gland necrosis in fish fed 600 mg gossypol kg,1 diet or higher. Non-existent-to-mild enterocyte vacuolization loss, inflammatory cell infiltration, and hyperplastic lamina propria were noted in the intestinal sections from gossypol-fed fish, but no significant differences in severity scores were noted. The pancreas from fish fed doses of gossypol above 600 mg gossypol kg,1 diet exhibited significant mild-to-severe necrosis, and livers from fish fed 900 and 1500 mg gossypol kg,1 diet exhibited significantly higher pigment deposition. No other significant histologic differences were observed in the fish fed diets containing gossypol,acetic acid. The data in this study indicates that at least 600,900 mg gossypol kg,1 purified diet can cause statistically significant histologic changes in fingerling channel catfish, suggesting that gossypol should remain at concentrations below 600 mg gossypol kg,1 diet. [source]


Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatment

CANCER, Issue 12 2010
Alexandra S. Brown MD
Abstract BACKGROUND: A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment. METHODS: Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated. RESULTS: Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively. CONCLUSIONS: Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN. Cancer 2010. © 2010 American Cancer Society. [source]


Bacterial motif DNA as an adjuvant for the breakdown of immune self-tolerance to pyruvate dehydrogenase complex

HEPATOLOGY, Issue 3 2002
David E. J. Jones
Bacterial DNA containing unmethylated CpG dinucleotide motifs is immunostimulatory to mammals, skewing CD4+ T-cell responses toward the Th1 phenotype. Autoreactive T-cell responses seen in primary biliary cirrhosis (PBC) are typically of the Th1 phenotype, raising the possibility that bacterial DNA might play a role in the generation of pathologic autoimmunity. We therefore studied the effects of CpG motif-containing oligodeoxynucleotides (ODN) on responses to pyruvate dehydrogenase complex (PDC, the autoantigen in PBC) in a murine model. Sensitization of SJL/J mice with non,self-PDC has been shown to result in induction of autoreactive T-cell responses to PDC sharing characteristics with those seen in patients with PBC. Administration of CpG ODN to SJL/J mice at the time of sensitization with PDC resulted in a significant skewing of splenic T-cell response to self-PDC, with significant augmentation of the Th1 cytokine response (interleukin [IL] 2 and interferon [IFN] gamma) and reduction of the Th2 response (IL-4 and IL-10). In fact, CpG ODN seemed to be more effective at biasing the response phenotype and as effective at inducing liver histologic change as complete Freund's adjuvant (CFA), the standard adjuvant used for induction of Th1 responses in murine autoimmune and infectious immunity models. In conclusion, our findings raise the possibility that bacteria play a role in the development of autoimmunity (in PBC at least) through the potential of their DNA to shift the T-cell responses toward the phenotype associated with autoimmune damage. Moreover, this study suggests caution in the therapeutic use of CpG ODN as vaccine adjuvants. [source]


Porokeratosis-like Changes in Chondrodermatitis Nodularis Helicis:Consequence or Coincidence?

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005
R.N. Page
Background:, Chondrodermatitis nodularis helicis (CNH) is a condition with known predisposing factors, but of unknown etiology. A variety of opinions exist as to the cause of this condition, without consensus. Design: We reviewed 111 cases of CNH from 103 patients at our laboratory. p53 immunohistochemical staining, which is over expressed in basilar epidermal cells of porokeratosis, was performed in a representative sample of CNH cases. Histologic changes characteristic of porokeratosis were qualified as a 1) parakeratotic column of keratinocytes 2) an attenuated to absent granular layer, and 3) adjacent or underlying dyskeratosis of keratinocytes, present in columns or aggregates. Results: Porokeratosis-like changes were identified in 77 of 111 cases. p53 staining was noncontributory. Conclusion: The presence of these porokeratosis-like changes in 69% of cases is intriguing. It is not clear whether or not this could possibly represent a causative mechanism or, perhaps, an otherwise coincident histologic change. The presence of porokeratosis-like changes in CNH provides a possible hypothesis in relationship to its etiology, at the very least, it could provide some histologic clue as to the presence of this deep dermal process in superficial biopsies. [source]


Methotrexate-related leukoencephalopathy without radiation therapy: Distribution of brain lesions and pathological heterogeneity on two autopsy cases

NEUROPATHOLOGY, Issue 2 2009
Jun Matsubayashi
This report concerns two rare autopsy cases of methotrexate (MTX)-related leukoencephalopathy without radiation therapy. In the first case, there were widespread necrotic foci with prominent spheroids, that is, disseminated necrotizing leukoencephalopathy (DNL), mainly in the cerebral white matter. In contrast, in the second case, there were widespread demyelinated foci without significant axonal changes, which we would like to name disseminated demyelinating leukoencephalopathy (DDL), mainly in the cerebral white matter. We emphasize that the pathology of pure MTX-related leukoencephalopathy is not uniform, and may show at least two kinds of histologic change. Furthermore, both cases did not develop significant vascular changes, which are usually induced by radiation therapy. The distribution of the lesions in two cases was examined by large specimens, including hemisphere specimens. The distribution of the lesions in the brain of our cases was also different. In the first case, the DNL lesions were predominantly distributed in the frontal and temporal lobes. In the second case, the DDL lesions were prominently localized in the occipital lobe. To our knowledge, this is the first report describing not only the pathological findings of MTX-related leukoencephalopathy without irradiation but also the precise distributions of the lesions. [source]


A Randomized Trial to Determine the Influence of Laser Therapy, Monopolar Radiofrequency Treatment, and Intense Pulsed Light Therapy Administered Immediately after Hyaluronic Acid Gel Implantation

DERMATOLOGIC SURGERY, Issue 5 2007
MITCHEL P. GOLDMAN MD
BACKGROUND Hyaluronic acid-based dermal fillers, such as hyaluronic acid gel (Restylane, Q-Medical AB, Uppsala, Sweden), are widely used for tissue augmentation of the nasolabial folds. Additional dermatologic treatments using infrared light, radiofrequency (RF), and intense pulsed light (IPL) are also important tools for facial rejuvenation. This study was designed to evaluate whether these therapies could be safely administered immediately after hyaluronic acid gel treatment without compromising the effect of the dermal filler. OBJECTIVE The objective of this study was to confirm or refute any possible subtractive effects of augmentation of the nasolabial folds when followed by 1,320-nm Nd:YAG laser, 1,450-nm diode laser, monopolar RF, and/or IPL treatments. METHODS Thirty-six patients with prominent nasolabial folds were treated with hyaluronic acid gel implantation on one side of the face and hyaluronic acid gel followed by one of the nonablative laser/RF/IPL therapies on the contralateral side of the face. RESULTS There were no statistically significant differences between wrinkle severity or global aesthetic scores for hyaluronic acid gel implantation alone and hyaluronic acid gel with laser/RF/IPL treatment at any time point. In a small sample, histologic changes were not apparent after laser/RF/IPL treatment. CONCLUSIONS Based on this small pilot study, laser, RF, and IPL treatments can safely be administered immediately after hyaluronic acid gel implantation without reduction in overall clinical effect. [source]


Histometric and Histochemical Analysis of the Effect of Trichloroacetic Acid Concentration in the Chemical Reconstruction of Skin Scars Method

DERMATOLOGIC SURGERY, Issue 10 2006
SUNG BIN CHO MD
BACKGROUND Atrophic scars can be induced by various causes, including severely inflamed acne, chicken pox, and trauma. Many treatment modalities are used for reconstructing and improving the appearance of scars with various treatment results. OBJECTIVE A recent report shows the clinical efficacy of the chemical reconstruction of skin scars (CROSS) method, which consists of the focal application of trichloroacetic acid (TCA) in a higher concentration. Histometric analysis of the CROSS method, however, has not yet been established. METHODS In this study, five hairless mice were used to evaluate the effect of the CROSS method and to analyze the difference between the CROSS method and simple TCA application. RESULTS Similar histologic changes were observed in the two methods, including epidermal and dermal rejuvenation with new collagen deposition. These changes, however, were more prominent in the CROSS method,treated areas, particularly when 100% TCA was used. CONCLUSION The results of this study suggest that treatment of atrophic scars using the CROSS method is more effective than simple application of TCA in activating fibroblasts in the dermis and increasing the amount of collagen. [source]


Deep Phenol Peeling and Fat Injection: Treatment Option for Perioral Wrinkles in a Scleroderma Patient

DERMATOLOGIC SURGERY, Issue 7 2005
Yitzhack Ramon MD
Background Scleroderma is characterized by abnormal growth of connective tissue, often manifested with hard and tight skin. The viscous properties of the skin are impaired, and the main histologic changes include a thicker dermis, absence of pilosebaceous units, and a decreased space between collagen bundles. Often these patients have wound healing problems. Objective The objective was to demonstrate a case of scleroderma that had deep phenol perioral peeling and fat injection into the lips. According to our bibliographic search, this is the first report in the English literature of using these modalities in scleroderma patients. Methods A 64-year-old woman suffering from scleroderma for more than 20 years came for improvement of her perioral appearance. We decided to manage her deep perioral wrinkles by deep peeling using the Baker formula and concomitantly to use autologous fat injection to augment her thin lips. Results The healing of our patient after these two interventions was uneventful, and satisfactory results have been obtained. Conclusion Based on our experience, this intervention may be suggested for patients suffering from scleroderma after a detailed explanation of the possible wound healing difficulties is provided to the patients. [source]


Curiosity and cure: Translational research strategies for neural repair-mediated rehabilitation

DEVELOPMENTAL NEUROBIOLOGY, Issue 9 2007
Bruce H. Dobkin
Abstract Clinicians who seek interventions for neural repair in patients with paralysis and other impairments may extrapolate the results of cell culture and rodent experiments into the framework of a preclinical study. These experiments, however, must be interpreted within the context of the model and the highly constrained hypothesis and manipulation being tested. Rodent models of repair for stroke and spinal cord injury offer examples of potential pitfalls in the interpretation of results from developmental gene activation, transgenic mice, endogeneous neurogenesis, cellular transplantation, axon regeneration and remyelination, dendritic proliferation, activity-dependent adaptations, skills learning, and behavioral testing. Preclinical experiments that inform the design of human trials ideally include a lesion of etiology, volume and location that reflects the human disease; examine changes induced by injury and by repair procedures both near and remote from the lesion; distinguish between reactive molecular and histologic changes versus changes critical to repair cascades; employ explicit training paradigms for the reacquisition of testable skills; correlate morphologic and physiologic measures of repair with behavioral measures of task reacquisition; reproduce key results in more than one laboratory, in different strains or species of rodent, and in a larger mammal; and generalize the results across several disease models, such as axonal regeneration in a stroke and spinal cord injury platform. Collaborations between basic and clinical scientists in the development of translational animal models of injury and repair can propel experiments for ethical bench-to-bedside therapies to augment the rehabilitation of disabled patients. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source]


Gastroduodenal reflux induces group IIa secretory phospholipase A2 expression and activity in murine esophagus

DISEASES OF THE ESOPHAGUS, Issue 5 2010
David Mauchley
SUMMARY Exposure of esophageal epithelium to gastric and duodenal contents results in the histologic changes of hyperproliferation and mucosal thickening. We have previously shown that presence of secretory phospholipase A2 (sPLA2) is necessary to produce these histologic changes in a murine model of gastroduodenal reflux. We sought to determine the influence of gastroduodenal reflux (GDR) on sPLA2 protein and mRNA levels as well as enzyme activity in esophageal tissue. BALB/c (sPLA2+/+) mice (n= 28) underwent side-to-side surgical anastomosis of the first portion of the duodenum and GE junction (DGEA) resulting in continuous exposure of esophageal mucosa to mixed gastric and duodenal contents. Sham control mice (n= 14) underwent laparotomy, esophagotomy and closure. Real-time RT PCR was used to quantitate the influence of GDR on group IIa sPLA2 expression. Immunofluorescent staining was quantitated by digital microscopy using a specific antibody to identify and locate sPLA2 protein. A colorimetric assay was used to quantify total sPLA2 activity after standardization of protein levels. Statistical analysis was conducted using Student's t -test. Group IIa sPLA2 mRNA and protein levels were increased at 4 and 8 weeks compared with sham controls. This increase occurred in a time-dependent manner and correlated with esophageal mucosal thickness. Furthermore, sPLA2 enzyme activity was increased significantly at 4 and 8 weeks compared with untreated controls. The expression of group IIa sPLA2 as well as sPLA2 activity is induced by GDR. This novel finding indicates that sPLA2 may play a role in the development of the histologic changes produced by GDR in esophageal mucosa. [source]


Effects of high-intensity focused ultrasound on the intervertebral disc: A potential therapy for disc herniations

JOURNAL OF CLINICAL ULTRASOUND, Issue 7 2006
Carina Forslund PhD
Abstract Purpose. To determine the potential application of high-intensity focused ultrasound for the minimally invasive treatment of herniated intervertebral discs by developing a probe that produces sufficiently high temperature locally to shrink collagen fibers (65,75°C). Materials and Methods. A 5-mm ultrasound probe was produced with a geometric focal length of 15 mm. The probe produced 2.5 W of acoustic power and was operated at a frequency of 4.1 MHz. Measurements of temperature increase were performed in discs from bovine tails. In vivo experiments were performed to assess histologic changes in the disc as well as in nerve root and muscle. Results. Sufficient temperature increase to produce collagen shrinkage was observed close to the focus of the ultrasound. Temperature measurements in vertebral end plates showed a temperature increase of only 4°C after 60-second exposure of the disc. In vivo experiments revealed histologic changes in the disc consistent with collagen shrinkage, with no adverse effects seen in surrounding tissues. Conclusions. The experiments demonstrated the feasibility of high-intensity focused ultrasound in the treatment of contained herniated discs. This technique has several advantages over other thermal treatment modalities. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:330,338, 2006 [source]


Rippled-pattern trichoblastoma with apocrine differentiation arising in a nevus sebaceus: report of a case and review of the literature

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 11 2009
Brian L. Swick
A 36-year-old man developed a papular growth in a portion of a nevus sebaceus on the post-auricular scalp. Excision showed typical histologic changes of nevus sebaceus including epidermal papillomatosis with reduced numbers of hair follicles as well as numerous sebaceous glands high in the dermis that focally emptied directly to the overlying epidermis. Histologic sections of the papular growth at the superior pole of the nevus sebaceus showed a proliferation of cytologically bland basaloid epithelial tumor lobules both in the superficial dermis, with multiple connections to the epidermis, and within the deeper dermis in a nodular growth pattern demonstrating papillary mesenchymal bodies. Ductal structures with apocrine-type decapitation secretion were present. There was prominent palisading of nuclei in rows parallel to one another, alternating with bands of homogenous eosinophilic stromal material forming a ripple pattern resembling the Verocay bodies of schwannoma. The histologic features resembled those of rippled-pattern trichoblastoma with apocrine differentiation arising in a nevus sebaceus, an association not previously described. We discuss this case as well as review the literature on rippled-pattern trichoblastoma. [source]


Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas.

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2005
A study of 226 cases
Background:, Neurofibromatosis, type 1, is associated with cutaneous melanin pigmentation, but an association with ordinary melanocytic nevi has not been described. Methods:, This retrospective case-control study was designed to see if neurofibromas in patients with neurofibromatosis, type 1 (NF-1) differ from sporadic neurofibromas (SN) in their incidence of associated melanocytic nevi and other histologic features. Slides from 114 NF-1 were compared with 112 SN and 300 intradermal melanocytic nevi (IDN). Results:, Small lentiginous melanocytic nevi were identified over 13 NF-1 (11%) but no SN (P = 0.0002). Compared with other NF-1, NF-1 with nevi were more frequently associated with melanocytic hyperplasia, giant melanosomes and diffuse neurofibroma (P < 0.03). Compared with SN, NF-1 were also more frequently associated with melanocytic hyperplasia, lentigo simplex-like changes, diffuse neurofibroma and plexiform neurofibroma (P < 0.001). Sebaceous hyperplasia (14%), dermal elastosis (9%), lipomatous change (8%), epithelial cysts (4%) and keratin granulomas or folliculitis (3%) were not significantly different in prevalence between NF-1, SN and the control group of IDN. Conclusions:, This study suggests that there is a difference in the potential for melanocytic proliferation in NF-1 compared with SN. NF-1, SN and IDN are associated with a similar range of incidental histologic changes. [source]


Relationship of clinical and pathologic response to neoadjuvant chemotherapy and outcome of locally advanced breast cancer,

JOURNAL OF SURGICAL ONCOLOGY, Issue 1 2002
Csaba Gajdos MD
Abstract Background and Objectives Neoadjuvant chemotherapy in locally advanced breast cancers produces histologically evaluable changes and frequently reduces the size of the primary tumor. Local clinical response to neoadjuvant chemotherapy may correlate with response of distant metastases. Therefore, clinical or pathological factors, which predict or assess response to treatment, may predict outcome after consideration for initial extent of disease. Methods To identify pretreatment characteristics of locally advanced breast cancers which predict clinical and pathologic response to neoadjuvant chemotherapy as well as survival and to assess the utility of postoperative histologic changes, we retrospectively studied one hundred forty-four patients with locally advanced breast cancer treated with neoadjuvant chemotherapy between January 1975 and July 1996. Patients were identified through pathology records of the Mount Sinai Medical Center and via one of the author's clinical databases. Pathologic and clinical responses to neoadjuvant chemotherapy were correlated with survival. Stepwise logistic regression was used to identify variables most significantly related to clinical response and pathologic axillary lymph node involvement. Results Complete clinical response with no palpable tumor was noted in 7/86 patients (8%) and complete pathologic response was achieved in 18/138 patients (13%). Both clinical (P,=,0.038) and pathologic response (P,=,0.011) were related to tumor size at the time of diagnosis: smaller tumors were more likely to respond to chemotherapy than larger tumors. Histologic evidence of chemotherapeutic effect, i.e., cytoplasmic vacuolization, change in the number of mitoses and localized fibrosis in lymph nodes did not correlate with clinical or pathologically measured response. Clinical and pathologic response was not associated with age, histology, differentiation, or type of chemotherapy. No residual tumor was found in the axillary nodes of 27% (37) of the patients. Age and complete pathologic response were the only variables significantly related to pathologic nodal status. Eighty-four percent of the 61 patients under 50 years of age had nodal involvement compared to 65% of older patients (P,=,0.014). Fifty percent of complete pathologic responders had positive axillary lymph nodes compared to 76% of patients who did not have a complete pathologic response (P,=,0.020). Distant disease-free (P,=,0.039) and overall survival (P,=,0.035) were related to the number of involved axillary lymph nodes. After consideration for pathologic lymph node status, no other variable was significantly related to distant disease-free or overall survival in multivariate analysis. No variable was significantly related to local disease-free survival. Age, clinical tumor size, clinical lymph node status, clinical response, type of chemotherapy, histology, differentiation, chemotherapy effects on primary tumor and lymph nodes, decline in the number of mitoses, and degree of fibrosis in nodes were not predictive of distant recurrence or overall survival. Conclusions This study of patients treated with neoadjuvant chemotherapy for locally advanced breast cancers found little evidence that measurable clinical or pathologic changes attributable to chemotherapy predicted survival. Axillary lymph node status, associated with young age, was the most important prognostic indicator in these patients. J. Surg. Oncol. 2002;80:4,11. © 2002 Wiley-Liss, Inc. [source]


Pirfenidone Treatment Decreases Transforming Growth Factor-,1 and Matrix Proteins and Ameliorates Fibrosis in Chronic Cyclosporine Nephrotoxicity

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2002
Fuad S. Shihab
Chronic cyclosporine (CsA) nephrotoxicity is characterized by tubulointerstitial fibrosis. Pirfenidone (PFD) is a novel antifibrotic compound that was shown to prevent and even reverse fibrosis. The mechanism of action of PFD is unclear but involves inhibition of transforming growth factor-, (TGF-,). Salt-depleted rats were administered CsA, CsA + PFD, vehicle (VH) or VH + PFD and sacrificed at 28 days. Physiologic and histologic changes were studied in addition to TGF-,1, plasminogen activator inhibitor-1 (PAI-1) and biglycan mRNA expressions by Northern blot. TGF-,1 immunohistochemistry was also performed. Treatment with PFD ameliorated CsA-induced fibrosis by about 50% (p <,0.05). CsA-induced decrease in creatinine clearance improved with PFD but the difference was not significant. TGF-,1, PAI-1 and biglycan mRNA expressions increased with CsA (p <,0.05 vs. VH) but strikingly improved with PFD treatment (p <,0.05 vs. CsA), which brought the levels down to VH levels. PFD treatment also decreased TGF-,1 protein expression by 80%. These results demonstrate that PFD can attenuate renal fibrosis in this model. PFD was associated with a decrease in TGF-,1 expression, which, in turn, was associated with a decrease in matrix deposition. These experiments suggest that PFD can be clinically useful for preventing chronic CsA nephrotoxicity and may prove to be helpful in other progressive renal diseases. [source]


Histologic changes in channel catfish, Ictalurus punctatus Rafinesque, fed diets containing graded levels of gossypol,acetic acid

AQUACULTURE NUTRITION, Issue 4 2010
J.J. EVANS
Abstract A study was performed to evaluate the histologic changes among fingerling channel catfish, Ictalurus punctatus Rafinesque, fed purified diets containing gossypol from gossypol,acetic acid. The catfish were maintained on diets with 0, 300, 600, 900, 1200 or 1500 mg gossypol kg,1 diet for 12 weeks, and histologic samples from the stomach, proximal and distal intestines, pancreas, liver, and spleen were obtained from fish in all groups. Stomach sections exhibited significant gastric gland necrosis in fish fed 600 mg gossypol kg,1 diet or higher. Non-existent-to-mild enterocyte vacuolization loss, inflammatory cell infiltration, and hyperplastic lamina propria were noted in the intestinal sections from gossypol-fed fish, but no significant differences in severity scores were noted. The pancreas from fish fed doses of gossypol above 600 mg gossypol kg,1 diet exhibited significant mild-to-severe necrosis, and livers from fish fed 900 and 1500 mg gossypol kg,1 diet exhibited significantly higher pigment deposition. No other significant histologic differences were observed in the fish fed diets containing gossypol,acetic acid. The data in this study indicates that at least 600,900 mg gossypol kg,1 purified diet can cause statistically significant histologic changes in fingerling channel catfish, suggesting that gossypol should remain at concentrations below 600 mg gossypol kg,1 diet. [source]


Cartilage degradation biomarkers predict efficacy of a novel, highly selective matrix metalloproteinase 13 inhibitor in a dog model of osteoarthritis: Confirmation by multivariate analysis that modulation of type ii collagen and aggrecan degradation peptides parallels pathologic changes

ARTHRITIS & RHEUMATISM, Issue 10 2010
Steven Settle
Objective To demonstrate that the novel highly selective matrix metalloproteinase 13 (MMP-13) inhibitor PF152 reduces joint lesions in adult dogs with osteoarthritis (OA) and decreases biomarkers of cartilage degradation. Methods The potency and selectivity of PF152 were evaluated in vitro using 16 MMPs, TACE, and ADAMTS-4 and ADAMTS-5, as well as ex vivo in human cartilage explants. In vivo effects were evaluated at 3 concentrations in mature beagles with partial medial meniscectomy. Gross and histologic changes in the femorotibial joints were evaluated using various measures of cartilage degeneration. Biomarkers of cartilage turnover were examined in serum, urine, or synovial fluid. Results were analyzed individually and in combination using multivariate analysis. Results The potent and selective MMP-13 inhibitor PF152 decreased human cartilage degradation ex vivo in a dose-dependent manner. PF152 treatment of dogs with OA reduced cartilage lesions and decreased biomarkers of type II collagen (type II collagen neoepitope) and aggrecan (peptides ending in ARGN or AGEG) degradation. The dose required for significant inhibition varied with the measure used, but multivariate analysis of 6 gross and histologic measures indicated that all doses differed significantly from vehicle but not from each other. Combined analysis of cartilage degradation markers showed similar results. Conclusion This highly selective MMP-13 inhibitor exhibits chondroprotective effects in mature animals. Biomarkers of cartilage degradation, when evaluated in combination, parallel the joint structural changes induced by the MMP-13 inhibitor. These data support the potential therapeutic value of selective MMP-13 inhibitors and the use of a set of appropriate biomarkers to predict efficacy in OA clinical trials. [source]


Interferon-,,dependent inhibition of B cell activation by bone marrow,derived mesenchymal stem cells in a murine model of systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 9 2010
Francesca Schena
Objective Bone marrow,derived mesenchymal stem cells (BM-MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of immune-mediated diseases. This study was undertaken to assess the influence of murine BM-MSCs on the activation of B cells in (NZB × NZW)F1 mice as an animal model of systemic lupus erythematosus (SLE). Methods We evaluated the in vitro effects of BM-MSCs on the proliferation and differentiation to plasma cells of splenic mature B cell subsets, namely follicular and marginal zone B cells isolated from (NZB × NZW)F1 mice. Lupus mice were also treated with BM-MSCs, and serum autoantibodies, proteinuria, histologic changes in the kidney, and survival rates were monitored. Results BM-MSCs inhibited antigen-dependent proliferation and differentiation to plasma cells of follicular and marginal zone B cells in vitro. This inhibitory effect was dependent on interferon-, (IFN,) and was mediated by cell-to-cell contact, involving the programmed death 1 (PD-1)/PD ligand pathway. In vivo treatment with BM-MSCs did not affect the levels of anti,double-stranded DNA antibodies or proteinuria. However, a reduction in glomerular immune complex deposition, lymphocytic infiltration, and glomerular proliferation was observed. Conclusion Our findings indicate that BM-MSCs affect B cell receptor,dependent activation of both follicular and marginal zone B cells from lupus mice. This inhibitory effect is IFN,-dependent and cell contact,dependent. MSCs in vivo do not affect the production of autoantibodies, the level of proteinuria, or the mortality rates. Nonetheless, the significant improvement in histologic findings in the kidney supports the potential role of MSCs in the prevention of glomerular damage. [source]


Mast cell,derived tryptase inhibits apoptosis of human rheumatoid synovial fibroblasts via rho-mediated signaling

ARTHRITIS & RHEUMATISM, Issue 4 2010
Norifumi Sawamukai
Objective An abundance of mast cells are found in the synovium of patients with rheumatoid arthritis (RA). However, the role of mast cells in the pathogenesis of RA remains unclear. This study was undertaken to elucidate a role for mast cells in RA by investigating the antiapoptotic effects of tryptase, a major product of mast cells, on RA synovial fibroblasts (RASFs). Methods RA synovial tissue was obtained from RA patients during joint replacement surgery, and histologic changes in the tissue were examined. The expression of cell surface molecules and apoptotic markers on RASFs were detected by flow cytometry. Rho activation was determined using a pull-down assay. Results Mast cells, bearing both c-Kit and tryptase, accumulated in the sublining area of proliferating synovial tissue from RA patients. Protease-activated receptor 2 (PAR-2), a receptor for tryptase, was expressed on RASFs in the lining area, close to tryptase-positive mast cells in the RA synovium. Fas-mediated apoptosis of RASFs was significantly inhibited, in a dose-dependent manner, by the addition of tryptase, and this effect correlated with increased activation of Rho kinase. Furthermore, Y27632, a Rho kinase inhibitor, reduced the antiapoptotic effect of tryptase on RASFs, suggesting that Rho was responsible for the antiapoptotic effects of tryptase. Conclusion These results demonstrate that tryptase has a strong antiapoptotic effect on RASFs through the activation of Rho. Thus, we propose that the release of tryptase by mast cells leads to the binding of tryptase to PAR-2 on RASFs and inhibits the apoptosis of RASFs via the activation of Rho. Such mechanisms could play a pivotal role in the marked proliferation of RASFs and hyperplasia of synovial tissue seen in RA synovium. [source]


Parathyroid hormone 1,34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in rats

ARTHRITIS & RHEUMATISM, Issue 10 2009
Je-Ken Chang
Objective Parathyroid hormone 1,34 (PTH[1,34]), a parathyroid hormone analog, shares the same receptor, PTH receptor 1, with parathyroid hormone,related peptide (PTHrP). This study was undertaken to address the hypothesis that PTH(1,34) inhibits terminal differentiation of articular chondrocytes and in turn suppresses the progression of osteoarthritis (OA). Methods We studied the effect of PTH(1,34) on human articular chondrocytes with azacytidine (azaC),induced terminal differentiation in vitro and on papain-induced OA in the knee joints of rats. In the in vitro study, we measured the levels of messenger RNA for SOX9, aggrecan, type II collagen, type X collagen, alkaline phosphatase (AP), Indian hedgehog (IHH), Bcl-2, and Bax by real-time polymerase chain reaction, levels of glycosaminoglycan (GAG) by dimethylmethylene blue assay, and rate of apoptosis by TUNEL staining. In the in vivo study, we evaluated the histologic changes in GAG, type II collagen, type X collagen, and chondrocyte apoptosis in the articular cartilage of rat knees. Results AzaC induced terminal differentiation of human chondrocytes, including down-regulation of aggrecan, type II collagen, and GAG and up-regulation of type X collagen, alkaline phosphatase, and IHH. Apoptosis was reversed by 3,10 days of treatment with 10 nM PTH(1,34). SOX9 expression was not changed by either azaC or PTH(1,34) treatment. Bcl-2 and Bax were up-regulated on day 10 and day 14, respectively, after azaC induction of terminal differentiation, but PTH(1,34) treatment did not reverse this effect. Furthermore, PTH(1,34) treatment reversed papain-induced OA changes (decreasing GAG and type II collagen, and increasing type X collagen and chondrocyte apoptosis) in the knee joints of rats. Conclusion Our findings indicate that PTH(1,34) inhibits the terminal differentiation of human articular chondrocytes in vitro and inhibits progression of OA in rats in vivo, and may be used to treat OA. [source]


Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment

ARTHRITIS & RHEUMATISM, Issue 10 2009
S. Bar-Yehuda
Objective Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A3 adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. Methods OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 ,g/kg given twice daily) was initiated. The A3 adenosine receptor antagonist MRS1220 (100 ,g/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O,fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. Results CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-,B signaling pathway, resulting in down-regulation of tumor necrosis factor ,. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. Conclusion CF101 deregulated the NF-,B signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA. [source]


Calcification of articular cartilage in human osteoarthritis

ARTHRITIS & RHEUMATISM, Issue 9 2009
M. Fuerst
Objective Hypertrophic chondrocyte differentiation is a key step in endochondral ossification that produces basic calcium phosphates (BCPs). Although chondrocyte hypertrophy has been associated with osteoarthritis (OA), chondrocalcinosis has been considered an irregular event and linked mainly to calcium pyrophosphate dihydrate (CPPD) deposition. The aim of this study was to determine the prevalence and composition of calcium crystals in human OA and analyze their relationship to disease severity and markers of chondrocyte hypertrophy. Methods One hundred twenty patients with end-stage OA undergoing total knee replacement were prospectively evaluated. Cartilage calcification was studied by conventional x-ray radiography, digital-contact radiography (DCR), field-emission scanning electron microscopy (FE-SEM), and synovial fluid analysis. Cartilage calcification findings were correlated with scores of knee function as well as histologic changes and chondrocyte hypertrophy as analyzed in vitro. Results DCR revealed mineralization in all cartilage specimens. Its extent correlated significantly with the Hospital for Special Surgery knee score but not with age. FE-SEM analysis showed that BCPs, rather than CPPD, were the prominent minerals. On histologic analysis, it was observed that mineralization correlated with the expression of type X collagen, a marker of chondrocyte hypertrophy. Moreover, there was a strong correlation between the extent of mineralization in vivo and the ability of chondrocytes to produce BCPs in vitro. The induction of hypertrophy in healthy human chondrocytes resulted in a prominent mineralization of the extracellular matrix. Conclusion These results indicate that mineralization of articular cartilage by BCP is an indissociable process of OA and does not characterize a specific subset of the disease, which has important consequences in the development of therapeutic strategies for patients with OA. [source]


Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function

ARTHRITIS & RHEUMATISM, Issue 8 2009
Lars Stangenberg
Objective To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis. Methods The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin,selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil,endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay. Results SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose-dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor , was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration. Conclusion A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions. [source]


GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis

ARTHRITIS & RHEUMATISM, Issue 3 2009
Jan Piet van Hamburg
Objective Rheumatoid arthritis is associated with the infiltration of T helper cells into the joints. It is unclear whether interferon-, (IFN,),producing Th1 cells or the novel T helper subset, interleukin-17 (IL-17),producing Th17 cells, are the pathogenic mediators of joint inflammation in chronic nonautoimmune arthritis. Therefore, this study was aimed at examining whether the Th2-specific transcription factor GATA-3 can regulate arthritis, in an experimental murine model, by modulating Th1 and/or Th17 cell polarization. Methods Arthritis was induced with methylated bovine serum albumin (mBSA) in both wild-type and CD2 T cell,specific GATA-3 (CD2,GATA-3),transgenic mice. At days 1 and 7 after the induction of arthritis, knee joints were scored macroscopically for arthritis severity and for histologic changes. Single-cell suspensions were generated from the spleens, lymph nodes, and inflamed knee joints. Cytokine expression by CD4+ T cells was determined using flow cytometry, and IL-17 expression in the inflamed knee joints was determined by enzyme-linked immunosorbent assay. Analyses of gene expression were performed for Th17-associated factors. Results Wild-type mice developed severe joint inflammation, including massive inflammatory cell infiltration and bone erosion that increased significantly over time, reaching maximal arthritis scores at day 7. In contrast, only mild joint inflammation was observed in CD2,GATA-3,transgenic mice. This mild effect was further accompanied by systemic and local reductions in the numbers of IL-17+IFN,, and IL-17+IFN,+, but not IL-17,IFN,+, CD4+ T cells, and by induction of Th2 cytokine expression. Moreover, GATA-3 overexpression resulted in reduced gene expression of the Th17-associated transcription factor retinoic acid,related orphan receptor ,t. Conclusion These results indicate that enforced GATA-3 expression protects against severe joint inflammation and bone erosion in mice, accompanied by reduced differentiation of Th17 cells, but not Th1 cells, during mBSA-induced arthritis. [source]


Histologic changes associated with false-negative sentinel lymph nodes after preoperative chemotherapy in patients with confirmed lymph node-positive breast cancer before treatment

CANCER, Issue 12 2010
Alexandra S. Brown MD
Abstract BACKGROUND: A wide range of false-negative rates has been reported for sentinel lymph node (SLN) biopsy after preoperative chemotherapy. The purpose of this study was to determine whether histologic findings in negative SLNs after preoperative chemotherapy are helpful in assessing the accuracy of SLN biopsy in patients with confirmed lymph node-positive disease before treatment. METHODS: Eighty-six patients with confirmed lymph node-positive disease at presentation underwent successful SLN biopsy and axillary dissection after preoperative chemotherapy at a single institution between 1994 and 2007. Available hematoxylin and eosin-stained sections from patients with negative SLNs were reviewed, and associations between histologic findings in the negative SLNs and SLN status (true negative vs false negative) were evaluated. RESULTS: Forty-seven (55%) patients had at least 1 positive SLN, and 39 (45%) patients had negative SLNs. The false-negative rate was 22%, and the negative predictive value was 67%. The negative SLNs from 17 of 34 patients with available slides had focal areas of fibrosis, some with associated foamy parenchymal histiocytes, fat necrosis, or calcification. These histologic findings occurred in 15 (65%) of 23 patients with true-negative SLNs and in only 2 (18%) of 11 patients with false-negative SLNs (P = .03, Fisher exact test, 2-tailed). The lack of these histologic changes had a sensitivity and specificity for identifying a false-negative SLN of 82% and 65%, respectively. CONCLUSIONS: Absence of treatment effect in SLNs after chemotherapy in patients with lymph node-positive disease at initial presentation has good sensitivity but low specificity for identifying a false-negative SLN. Cancer 2010. © 2010 American Cancer Society. [source]


Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma,

CANCER, Issue 7 2003
Markus G. Müller Ph.D.
Abstract BACKGROUND Understanding the development and progression of head and neck squamous cell carcinoma is key in the quest for the early diagnosis and prevention of this type of malignancy. The current study correlated early biochemical and histologic changes in oral tissue with spectral features in fluorescence, reflectance, and light scattering spectra acquired in vivo to diagnose early stages of oral malignancies. METHODS A total of 91 tissue sites from 15 patients with varying degrees of malignancy (normal, dysplastic, and cancerous sites) and 8 healthy volunteers were analyzed with 3 spectroscopic techniques. Direct biochemical information regarding oral tissue native fluorophores was obtained with intrinsic fluorescence spectroscopy by fitting a linear combination of collagen and the reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence spectra to the intrinsic tissue fluorescence spectra excited with 337 nanometer (nm) and 358-nm laser light. Diffuse reflectance spectroscopy was used to provide information regarding tissue absorption and structure, such as hemoglobin concentration and stroma density, by measuring the wavelength-dependent absorption and scattering coefficients. By subtracting the diffusely reflected component from the measured reflectance, light scattering spectroscopy (LSS) information resulting from single backscattering from epithelial cell nuclei was obtained. LSS provides information concerning the size distribution of cell nuclei. RESULTS These optically extracted tissue parameters provide biochemical or structural information in vivo without the need for tissue excision, and can be used to diagnose tissue abnormalities. By combining the information provided by the three techniques, a method known as trimodal spectroscopy, a sensitivity and specificity of 96% and 96%, respectively, in distinguishing cancerous/dysplastic (mild, moderate, and severe) from normal tissue was achieved. In addition, the authors were able to distinguish dysplastic from cancerous tissue with a sensitivity of 64% and a specificity of 90%. CONCLUSIONS The results of the current study demonstrated that Trimodal spectroscopy is a highly sensitive and specific technique with which to diagnose tissue abnormalities. Cancer 2003;97:1681,92. © 2003 American Cancer Society. DOI 10.1002/cncr.11255 [source]