Reactive Fibroblasts Research Articles

Possible Role of Natural Immune Response against Altered Fibroblasts in the Development of Post‐Operative Adhesions

Post-operative adhesion tissue fibroblasts (ATF) differ from normal peritoneal fibroblasts (NPF). Natural immune response participates in the elimination of altered cells. In this study, we investigated NPF and ATF expression patterns of immune response-related markers, and lymphokine-activated killer (LAK) cell-mediated fibroblast elimination in vitro. Primary cell cultures of both NPF and ATF obtained from the same four patients were used in the experiments. The expression of CD54, CD40 and CD120b, and allogeneic LAK cell-mediated ATF and NPF elimination were studied by flow cytometry. Average expression of CD54 in ATF was greater by 12.3-fold compared with NPF (P = 0.021), with ratios of 2.4 and 1.9-fold for CD40 (P < 0.001) and CD120b (P = 0.013), respectively. Average LAK cell-mediated fibroblast killing was 1.8 +/- 0.8-fold greater in ATF over NPF (P = 0.008). Furthermore, LAK cell-mediated fibroblast elimination correlated significantly with the increased CD40, CD54 and CD120b expression (R > 0.956; P < 0.05 for each). These results demonstrate that ATF are more susceptible to lymphocyte-mediated elimination than NPF and the development of adhesions despite this could be explained by either impaired or overwhelmed autologous natural immune response against reactive fibroblasts.

Laser Capture Microdissection of Epithelial Cancers Guided by Antibodies Against Fibroblast Activation Protein and Endosialin

Transcriptional profiling of cancer biopsies is used extensively to identify expression signatures for specific cancer types, diagnostic and prognostic subgroups, and novel molecular targets for therapy. To broaden these applications, several challenges remain. For example, the integrity of RNA extracted even from small tissue samples has to be insured and monitored. Moreover, total tumor RNA may hide the marked histologic heterogeneity of human cancers. A principle approach to this heterogeneity has been provided by laser capture microdissection performed on antibody-stained tissue sections (immuno-LCM; iLCM). In this study, we have established a procedure to assess the quality of RNA obtained from tissue sections, coupled with immunostaining using antibodies to different tumor stromal markers, and subsequent iLCM to selectively capture the cancer stroma compartments. The procedure was applied to 53 frozen specimens of human epithelial cancers. Sections were stained for histopathological evaluation, and RNA was isolated from adjacent serial sections. RNA quality was assessed by the Agilent-Bioanalyzer (Agilent, Palo Alto, CA) and by multiplex RT-PCR. Two thirds of the specimens were found to yield good to excellent RNA quality. For microdissection of the tumor stroma with reactive fibroblasts and tumor blood vessels, a rapid incubation protocol with antibodies against fibroblast activation protein (FAP) and against endosialin was developed to ensure RNA integrity for subsequent iLCM. Using these procedures, RNA from distinct tumor compartments can be isolated, analyzed, amplified, and used for transcription profiling.

Fibroblast activation protein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis

Fibroblast activation protein (FAPalpha) is a member of the cell surface dipeptidyl peptidase (DPP) family of serine proteases. In its dimer form, FAPalpha exhibits gelatinase, collagenase, and DPP activity in vitro. Reactive fibroblasts in healing wounds and stromal fibroblasts associated with epithelial tumors express FAPalpha. Idiopathic pulmonary fibrosis (IPF) is a disease of the lung characterized by progressive fibrosis with no clear etiology or molecular marker for disease activity. Recently, it has been shown that fibroblast FAPalpha expression is induced in liver cirrhosis, with an expression pattern distinct from alpha-smooth muscle actin (alpha-SMA). In this study, we determine whether FAPalpha expression is selectively induced in areas of ongoing tissue remodeling characterized by fibroblast foci in IPF. Human lung tissue was obtained from patients with IPF, centrilobular emphysema, and normal lung. Immunohistochemical studies were performed using anti-FAPalpha antibody and antibodies against alpha-SMA and CD26 (DPPIV), another member of the DPP family. We found that FAPalpha was not expressed in normal human lung tissue or tissue with evidence of centriacinar emphysema, but was induced in all patients with IPF and With a pattern distinct from that of CD26 found primarily on hyperplastic alveolar epithelium. Specifically, FAPalpha was detected in fibroblast foci and in fibrotic interstitium and not in the interstitium of adjacent architecturally normal lung. Alveolar/airway epithelium and vascular smooth muscle did not express FAPalpha. This is the first report of FAPalpha expression in IPF and our results suggest that FAPalpha is selectively induced in fibrotic foci, but not in normal or emphysematous lung. Future studies will address whether FAPalpha may be used as a marker for disease activity in IPF.

Pathological changes of lungs in patients with severity acute respiratory syndrome

To evaluate the progression in morphologic changes of lungs in SARS patients. Four cases of SARS with lung tissue samples available (including one for ultrastructural examination) were enrolled into the study. Histochemical study for VG, Masson, reticulin, orcein, PAS, sirius red stains and immunohistochemical study for vimentin, desmin, smooth muscle actin, HHF-35, CD34, F8, collagen types I and III were also performed. According to the morphologic changes, lung lesions in SARS were subcategorized into 3 phases: acute exudative inflammation, fibrous proliferation and the final fibrotic stage. Two cases belonged to the acute exudative phase, in which the course was less than 20 days. The principal lesions consisted of acute alveolar exudative inflammation, hyperplasia of alveolar epithelium, necrosis, alveolar hyaline membrane formation, alveolar desquamation and focal fibroplasia. The acute exudative protein was PAS-positive. There was an increase in reticulin fiber formation. The reactive fibroblasts were highlighted by desmin and vimentin. One case belonged to the fibroproliferative stage, in which the course was around 25 days. Major lesions included proliferative interstitial pneumonia with early pulmonary fibrosis. There was also evidence of organizing pneumonia, with an increase in reticulin fiber formation, which had a glomeruloid appearance on special stain. The mesenchymal cells showed either myofibroblastic (which expressed desmin, HHF-35, smooth muscle actin and vimentin) or fibroblastic (which expressed vimentin only) differentiation. Fibroelastosis and fibroplasia was also noted. The remaining case belonged to the fibrotic stage, in which the course was around 75 days. The main features included diffuse fibrosis and honeycomb change, which were highlighted by sirius red stain. Immunohistochemistry showed mainly types I and IV collagen fibers. In all lesions, there was also an increase of number of CD68-positive macrophages. The morphologic progression in lungs of SARS patients is characterized by the development of increased fibrosis. The primitive mesenchymal cells, hyperplastic alveolar epithelial cells and macrophages play an important role in the pathogenesis.

Glutathione S-transferase pi is upregulated in the stromal compartment of hormone independent prostate cancer. Li M, Ittmann MM, Rowley DR, Knowlton AA, Vaid AK, Epner DE, Departments of Medicine, Pathology, Molceular and Cellular Biology, Baylor College of Medicine and VA Medical Center Houston, TX 77030: Prostate 2003;56(2):98–105

Glutathione S-transferase (GST) pi is a detoxifying enzyme abundant in normal prostate basal cells but only rarely expressed in prostate cancer cells. The current studies are the first to focus on GST pi in the stromal compartment of prostate tumors. We employed immunohistochemical, immunofluorescence, and Western blot analysis to measure GST pi expression and subcellular localization in 21 primary and metastatic tumors from patients with hormone independent prostate cancer, as well as seven lymph node metastases and six prostatectomy specimens. GST pi was detectable in stromal cells in 17 of the 21 hormone independent prostate tumors. GST pi tissue distribution in hormone independent tumors coincided with vimentin staining, suggesting that GST pi is expressed by reactive fibroblasts and/or myofibroblasts. The current results suggest that prostate cancer cells induce an injury response in the stroma during progression to hormone independence, which results in GST pi expression. Stromal GST pi may contribute to chemoresistence of advanced prostate cancer.

Enhanced serine palmitoyltransferase expression in proliferating fibroblasts, transformed cell lines, and human tumors.

Metastatic processes, including cell invasion, extracellular matrix degradation, and tissue remodeling, require cellular reorganization and proliferation. The cell signaling molecules required and the proteins involved in cell restructuring have not been completely elucidated. We have been studying the role of sphingolipids in normal cell activity and in several pathophysiological states. In this study we used immunohistochemistry to observe the presence of the two known subunits of serine palmitoyltransferase (SPT) in proliferating cells, in an in vitro model of wound repair, and in human malignant tissue. We report increased expression of the two subunits, SPT1 and SPT2, in the proliferating cells in these models. We also demonstrate a change in subcellular localization of the SPT subunits from predominantly cytosolic in quiescent cells to nuclear in proliferating cells. In addition, we observed SPT1 and SPT2 immunoreactivity in reactive stromal fibroblasts surrounding the carcinoma cells of some of the tumors. This enhanced SPT expression was absent in the stromal fibroblasts surrounding normal epithelial cells. Our results suggest a potential role for overexpression of SPT in the processes of cell metastasis.

Glutathione S-transferase pi is upregulated in the stromal compartment of hormone independent prostate cancer.

Glutathione S-transferase (GST) pi is a detoxifying enzyme abundant in normal prostate basal cells but only rarely expressed in prostate cancer cells. The current studies are the first to focus on GST pi in the stromal compartment of prostate tumors. We employed immunohistochemical, immunofluorescence, and Western blot analysis to measure GST pi expression and subcellular localization in 21 primary and metastatic tumors from patients with hormone independent prostate cancer, as well as seven lymph node metastases and six prostatectomy specimens. GST pi was detectable in stromal cells in 17 of the 21 hormone independent prostate tumors. GST pi tissue distribution in hormone independent tumors coincided with vimentin staining, suggesting that GST pi is expressed by reactive fibroblasts and/or myofibroblasts. The current results suggest that prostate cancer cells induce an injury response in the stroma during progression to hormone independence, which results in GST pi expression. Stromal GST pi may contribute to chemoresistence of advanced prostate cancer.

Expression of lumican in human colorectal cancer cells.

Lumican is a member of a small leucine-rich proteoglycan family and its overexpression in human breast cancer tissues is reported to influence the growth of cancer cells. In the present study, we aimed to clarify the expression of lumican mRNA and its protein in human colorectal cancer cell lines and their localization in normal and cancerous colorectal tissues. Reverse transcription-polymerase chain reaction and western blot analysis revealed lumican mRNA and its protein expression in COLO 205, DLD-1, HCT-15, SW 480 and WiDr colorectal cancer cell lines. The lumican in colorectal cancer cells had non-sulfated or poorly sulfated polylactosamine side chains. Based on its immunoreactivity, the lumican protein was found to be localized in fibroblasts and stromal tissues of normal colorectal tissues, but not in colorectal epithelial cells. In colorectal cancer tissues, the lumican was strongly localized in cancer cells in eight of 12 cancer cases. The lumican protein was also localized in epithelial cells with mild reactive dysplasia and fibroblasts adjacent to cancer cells. Lumican mRNA was expressed in cancer cells and adjacent fibroblasts, and epithelial cells. These findings may indicate that the lumican protein synthesized by cancer cells, fibroblasts and epithelial cells with mild reactive dysplasia found adjacent to cancer cells may affect the growth of human colorectal cancer cells.

Clinical microbiological case: cardiac tamponade due to hemorrhagic pericarditis in a non-immunocompromised woman from south-eastern United States

Four days after the initial pericardiocentesis, the patient underwent localized pericardectomy due to re-accumulation of pericardial fluid. (Figure 1) Full-thickness pericardial biopsy was also performed. Negative serology included: human immunodeficiency virus types I and II, human T-cell leukemia virus types I and II, cytomegalovirus immunoglobulin M (CMV IgM), Venereal Disease Research Laboratory (VDRL), antinuclear antibody, native DNA antibody, Smith (SM) antibody, and ribonucleoprotein (RNP) antibody. Her complement (CH50, C3, C4) levels were normal. Serum rheumatoid factor and urine Histoplasma capsulatum antigen were nondetectable. Blood cultures for bacteria, mycobacteria and viruses remained sterile for 21 days. Histopathological examination of the pericardial biopsy showed organizing hemorrhage and prominent lymphocytic infiltration of the stroma. (Figure 2a) Intranuclear and intracytoplasmic inclusions within the reactive fibroblasts showed an ‘Owl’s eye’ pattern, characteristic of active CMV infection [1–3] (Figure 2b). CMV-specific IgG serum levels were 102 IU. A 28-day treatment with ganciclovir (5mg/kg body weight every 12 h) was commenced, and a maintenance dose (5mg/kg body weight daily) was given during the last 2 weeks. After discontinuation of antiviral therapy, no clinical relapses were noticed during the 12-month follow-up.

Thermal capsular shrinkage: Basic science and clinical applications

Recently, the use of thermal energy to shrink the redundant glenohumeral joint capsule in patients with instability has generated a great deal of interest. Proponents assert that the procedure avoids the need for an open stabilization and it may be used as an adjunct to an open or arthroscopic capsulolabral repair. The use of nonablative thermal energy to shrink soft-tissue collagen appears to induce ultra-structural and mechanical changes at or above 60°C. The microscopic changes reflect the unwinding of the collagen triple helix and loss of the fiber orientation. The fibrils contract into a shortened state and reactive fibroblasts have been shown to grow into this treated area and synthesize the collagen matrix. The biomechanical properties of the tissue do not appear to be detrimentally altered if shrinkage is limited to less than 15% and if ablation or excess focal treatment is avoided. The endpoint of optimal shrinkage is not known and clinical estimations of tissue changes and volumetric reduction are used as guides to treatment. The first clinical follow-up study was only recently published in the peer-reviewed literature and prior preliminary reports were optimistic regarding the use of thermal energy for the treatment of glenohumeral instability. Thermal capsular shrinkage has been used as an adjunct to a capsulolabral repair, as well as an isolated treatment for the disorders of internal impingement and multidirectional instability. Additional evaluation is necessary to determine the optimal quantity of energy needed for tissue shrinkage without inadvertent tissue destruction. The long-term clinical effect, mechanical properties, and durability of the newly produced collagen need to be analyzed further. The basic science and clinical applications of this newly applied technology are reviewed in this article.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 6 (July-August), 2001: pp 624–635

Expression of the fibroblast activation protein during mouse embryo development.

Human Fibroblast Activation Protein (FAP), a member of the serine prolyl oligopeptidase family, is a type II cell surface glycoprotein that acts as a dual-specificity dipeptidyl-peptidase (DPP) and collagenase in vitro. Its restricted expression pattern in embryonic mesenchyme, in wound healing and in reactive stromal fibroblasts of epithelial cancers, has suggested a role for the FAP protease in extracellular matrix degradation or growth factor activation in sites of tissue remodeling. The FAP homologue in Xenopus laevis has been reported to be induced in the thyroid hormone-induced tail resorption program during tadpole metamorphosis supporting a role for FAP in tissue remodeling processes during embryonic development. However, Fap-deficient mice show no overt developmental defects and are viable. To study the expression of FAP during mouse embryogenesis, a second Fap-deficient mouse strain expressing beta-Galactosidase under the control of the Fap promoter was generated by homologous recombination (Fap-/- lacZ mice). FAP deficiency was confirmed by the absence of FAP-specific dipeptidyl-peptidase activity in detergent-soluble extracts isolated from 17.5 d.p.c. Fap-/- lacZ embryos. We report that Fap-/- lacZ mice express beta-Galactosidase at regions of active tissue remodeling during embryogenesis including somites and perichondrial mesenchyme from cartilage primordia.

Elevated serum dipeptidyl peptidase IV (CD26, EC 3.4.14.5) activity in experimental liver cirrhosis.

Dipeptidyl peptidase IV (DPP IV) is a cell surface ectoenzyme widely distributed in the rat body, present on the epithelial cells of the brush border membranes (e.g. bile canaliculi) and on the surface of reactive lymphocytes and fibroblasts. DPP IV has been implicated in hepatocyte-extracellular matrix interactions, fibroblast activation and proliferation and in T-cell activation. Aberrant DPP IV expression was found in human liver cirrhosis, and elevated serum DPP IV activity was reported in patients with primary biliary cirrhosis and chronic hepatitis C virus infection. The aim of the study was to examine serum DPP IV activity in experimental liver cirrhosis. Liver cirrhosis was induced by administering diethyl-nitrosamine, phenobarbital and CCl4 in Fischer-344 male rats (n = 22). Phenobarbital-treated (n = 9) and nontreated (n = 9) male rats were used as controls. Serum DPP IV activity was measured using a microplate-based continuous-monitoring assay. Recombinant rat DPP IV was used as standard and Gly-Pro-PNA was used as substrate. Enzyme activity was given in nmol mL-1 min-1 (U L-1). Significantly higher DPP IV activity was found in the sera of rats with experimental liver cirrhosis (39.2 +/- 3.7; mean +/- SD) compared to phenobarbital-treated (11 +/- 4, P < 0.000002) and nontreated (10.9 +/- 0.9, P < 0.000002) rats. There was a positive correlation between DPP IV activity and concentrations of aspartate aminotransferase (r = 0.73, P = 0.0001) and alanine aminotransferase (r = 0.69, P = 0.0004). The significantly higher serum DPP IV activity found in experimental liver cirrhosis is in concordance with human observations. The elevation was probably not due to the enzyme induction effect of phenobarbital. In this experimental model, serum DPP IV seems to be an indicator for chronic liver injury.

Fibroblast Activation Protein, a Dual Specificity Serine Protease Expressed in Reactive Human Tumor Stromal Fibroblasts

Proteolytic degradation of extracellular matrix (ECM) components during tissue remodeling plays a pivotal role in normal and pathological processes including wound healing, inflammation, tumor invasion, and metastasis. Proteolytic enzymes in tumors may activate or release growth factors from the ECM or act directly on the ECM itself, thereby facilitating angiogenesis or tumor cell migration. Fibroblast activation protein (FAP) is a cell surface antigen of reactive tumor stromal fibroblasts found in epithelial cancers and in granulation tissue during wound healing. It is absent from most normal adult human tissues. FAP is conserved throughout chordate evolution, with homologues in mouse and Xenopus laevis, whose expression correlates with tissue remodeling events. Using recombinant and purified natural FAP, we show that FAP has both dipeptidyl peptidase activity and a collagenolytic activity capable of degrading gelatin and type I collagen; by sequence, FAP belongs to the serine protease family rather than the matrix metalloprotease family. Mutation of the putative catalytic serine residue of FAP to alanine abolishes both enzymatic activities. Consistent with its in vivo expression pattern determined by immunohistochemistry, FAP enzyme activity was detected by an immunocapture assay in human cancerous tissues but not in matched normal tissues. This study demonstrates that FAP is present as an active cell surface-bound collagenase in epithelial tumor stroma and opens up investigation into physiological substrates of its novel, tumor-associated dipeptidyl peptidase activity.

Heterotopic neogenesis of skeletal muscle induced in the adult rat diaphragmatic peritoneum: ultrastructural and transplantation studies.

During the course of a mild chemical peritonitis, new skeletal muscle fibers develop and persist over a twelve-month interval in the diaphragmatic peritoneum. Light and electron microscopic studies revealed that the ectopic fibers developed from myoblasts and myotubes to fully differentiated muscle cells in the same manner as normally situated skeletal muscle. The ectopic fibers were separated from the intrinsic muscle by dense connective tissue and an elastic lamina. Diaphragms taken from normal rats and transplanted to the omentum of isogeneic recipients also developed skeletal muscle neogenesis in the same ectopic location as in the normal diaphragm. Satellite cells, reactive fibroblasts in the peritoneum, mesenchymal stem cells or blood-borne myoblast precursor cells could be the source of these ectopic muscle fibers. The results of the present studies, however, cannot provide conclusive evidence for the origin of the new muscle fibers. Regardless of their source, the methods employed may represent a unique model for the development and prolonged maintenance of skeletal muscle fibers in a heterotopic location in vivo.

Clonal Composition of Malignant Fibrous Histiocytoma: Analysis by PCR-Based Assay of the Human Androgen Receptor Gene (HUMARA)

Malignant fibrous histiocytoma (MFH), the most common soft-tissue sarcoma, consists mainly of two different cell populations: histiocytelike and fibroblastlike cells. It has been suggested to contain a large amount of reactive histiocytes and fibroblasts hard to distinguish from the tumor cells. In this study, the clonality of MFH was determined by analyzing the patterns of X chromosome inactivation at the human androgen receptor gene (HUMARA) using DNA samples from archival snap-frozen and paraffin-embedded tissues. All the eleven informative female heterozygotes without severe inflammation showed the monoclonal pattern; 8 storiform-pleomorphic (6 distinct, 2 relative monoclonal pattern) and 3 myxoid (3 distinct monoclonal pattern) subtype. Although normal tissue DNA, amplifiable by the polymerase chain reaction, valid for the assay was not available in these cases, statistically at least 5 cases are monoclonal (p = 0.037 <0.05), even when markedly skewed lyonization were to primarily exist in the normal tissue at the highest rate as ever reported (33%). Experiments using the mixture of monoclonal and polyclonal DNA at varying ratios have suggested that a distinct monoclonal pattern is obtained only when the monoclonal component exceeds 80%. Our study demonstrates that most cells that are present in MFH are monoclonal in origin which may be the population of tumor cells.

Mouse fibroblast-activation protein--conserved Fap gene organization and biochemical function as a serine protease.

The human fibroblast-activation protein (FAP), a member of the serine protease family, was discovered as an inducible type-II cell-surface glycoprotein selectively expressed by reactive stromal fibroblasts of epithelial cancers and healing wounds. Antibodies directed against human FAP have a clinical use for antibody-based tumor imaging. As part of an effort to generate animal models of FAP expression in epithelial tumorigenesis and wound healing, we previously cloned the cDNA encoding the mouse FAP homolog. In this study, we used PCR/restriction-fragment length polymorphism, identified in interspecific back-crosses between Mus musculus and Mus spretus, to map the Fap gene locus to a region of mouse chromosome 2, known to be syntenic to the previously identified FAP gene locus on human chromosome 2q23. The Fap gene spans approximately 60 kb and contains 26 exons ranging in size from 46 bp to 195 bp. This genomic organization is very similar to that of the human FAP locus. Similar to the gene encoding dipeptidyl peptidase IV (DPP IV), the nucleotides encoding the serine protease consensus motif, WGWSYGG, are split between two exons, a feature distinct from classical serine proteases. Consistent with the similarity to DPP IV, a chimeric FAP fusion protein expressed in a baculovirus system has dipeptidyl peptidase activity.

Pressure ulcer accelerated healing with local injections of granulocyte macrophage-colony stimulating factor

This is the first report of granulocyte macrophage-colony stimulating factor (GM-CSF) inducing accelerated healing of a sacral pressure ulcer in a bedridden patient with bilateral hemiplegia. GM-CSF was diluted and injected locally around and into the ulcer bed every 2-3 days for 2 weeks, then weekly for 4 weeks until complete healing occurred. A new firm granulation tissue was noted within a few days. The ulcer showed 85% healing within 2 weeks and 100% by 2 months. Healing started from the periphery and from within the ulcer bed at sites of GM-CSF injections. It was slower at areas where there was complete necrosis and detachment of skin from underlying tissue. The ulcer remained closed until the patient's sudden death 9 months later. A biopsy of granulation tissue showed inflammatory cells and reactive fibroblasts. The potential role of GM-CSF and growth factors in pressure ulcer therapy and wound healing are discussed.

Effect of nonablative laser energy on the joint capsule: An in vivo rabbit study using a holmium: YAG laser

Background and Objective The nonablative application of holmium:yttrium-aluminum-garnet (Ho:YAG) laser energy to the joint capsule of patients with glenohumeral instability has been found to shrink capsular tissue and to help stabilize the joint. The purpose of this study was to evaluate the effect of nonablative laser energy on the short-term histological properties of joint capsular tissue in an in vivo rabbit model. Study Design/Materials and Methods Eighteen mature New Zealand white rabbits were used in this study. One randomly selected stifle was treated with laser energy, and the contralateral stifle was sham-operated. Animals were euthanized immediately after surgery (day 0), at 7 days postsurgery and 30 days postsurgery. Specimens were processed for histology and transmission electron microscopy. Results Laser-treated samples at day 0 showed diffuse hyalinization of collagen with nuclear karyorrhexis of fibroblasts. Laser-treated tissue at 7 days postsurgery revealed fibroblast proliferation around and into acellular hyalinized regions of collagen. At 30 days postlaser treatment, areas of fused collagen were greatly reduced as large reactive fibroblasts migrated and secreted matrix. Conclusion This study illustrates the short-term in vivo tissue response to nonablative laser treatment, where acellular hyalinized regions of collagen are infiltrated by fibroblasts that have used the treated collagen as the framework for migration and secretion of new collagen matrix in order for tissue repair to proceed. Lasers Surg. Med. 20:164–171, 1997. © 1997 Wiley-Liss, Inc.

Effect of nonablative laser energy on the joint capsule: an in vivo rabbit study using a holmium:YAG laser.

The nonablative application of holmium:yttrium-aluminum-garnet (Ho:YAG) laser energy to the joint capsule of patients with glenohumeral instability has been found to shrink capsular tissue and to help stabilize the joint. The purpose of this study was to evaluate the effect of nonablative laser energy on the short-term histological properties of joint capsular tissue in an in vivo rabbit model. Eighteen mature New Zealand white rabbits were used in this study. One randomly selected stifle was treated with laser energy, and the contralateral stifle was sham-operated. Animals were euthanized immediately after surgery (day 0), at 7 days postsurgery and 30 days postsurgery. Specimens were processed for histology and transmission electron microscopy. Laser-treated samples at day 0 showed diffuse hyalinization of collagen with nuclear karyorrhexis of fibroblasts. Laser-treated tissue at 7 days postsurgery revealed fibroblast proliferation around and into acellular hyalinized regions of collagen. At 30 days postlaser treatment, areas of fused collagen were greatly reduced as large reactive fibroblasts migrated and secreted matrix. This study illustrates the short-term in vivo tissue response to nonablative laser treatment, where acellular hyalinized regions of collagen are infiltrated by fibroblasts that have used the treated collagen as the framework for migration and secretion of new collagen matrix in order for tissue repair to proceed.

Ischemic Fasciitis

Ischemic fasciitis, also called atypical decubital fibroplasia, was recently described as a distinctive fibroblastic proliferation occurring predominantly in elderly, bed-ridden individuals. This entity can easily be misdiagnosed as a malignant process. A 70-year-old, white male presented with an enlarging right hip mass. Fine needle aspiration yielded spindled and ovoid cells with ample cytoplasm and occasional nuclear atypia. The histologic features of a subsequent biopsy and resection specimen included a zonal pattern of fibrinoid necrosis with surrounding reactive fibroblasts, histiocytes and vascular proliferation, which are characteristic of ischemic fasciitis. Ischemic fasciitis can be mistaken clinically, cytologically and histologically for sarcoma. The cytologic findings seen in this case, when combined with the clinical history, were sufficient to avoid misdiagnosis of malignancy in a benign, proliferative lesion.