The influence of time on human breast capsule histology: smooth and textured silicone-surfaced implants

Although the histology of capsular tissue is well described in the literature, most studies in humans do not correlate histologic findings with implant age (number of years an implant was in place before sampling). As such, questions regarding the long-term histology in humans remain. The microanatomy of 93 human periprosthetic capsular tissues surrounding 22 textured and 71 smooth silicone-surfaced prostheses was studied. The implants were divided into two groups according to the time between implantation and capsulectomy: between 0 and 5 years or more than 5 years. Hematoxylin and eosin and Masson trichrome-stained sections were analyzed by light microscopy, with and without polarization. Eighteen of the textured implants contained silicone gel and four contained saline. Sixty of the smooth implants contained silicone gel, eight contained saline, and in three, the filler type was not known. For the majority of patients, surgery was performed for augmentation mammaplasty, and the implants were removed because of capsular contracture. The following histologic features were assessed: synovial-like metaplasia, villous hyperplasia, density of the collagenous capsule, alignment of collagen fibers within the capsule, and the presence of foreign material and of a foreign body reaction. The following trends were observed. In smooth implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia (p = 0.003) and villous hyperplasia; there was no significant difference in the presence of a dense collagenous capsule, the orientation of collagen fibers, or the presence of a foreign body reaction. An increase was observed in the presence of foreign material (p = 0.01). In textured implants, increasing implant duration was associated with a decrease in the presence of synovial-like metaplasia, villous hyperplasia (p = 0.003), dense collagenous architecture, and parallel orientation of collagen fibers (p = 0.017). An increase in the presence of a foreign body type reaction and foreign material (p = 0.024) was observed. In comparing textured and smooth-surfaced implants, synovial-like metaplasia was observed more often in the textured group, both at 0 to 5 years (p = 0.01) and at greater than 5 years (p < 0.01). Textured implants more often had villous hyperplasia at 0 to 5 years (p = 0.03) but not beyond 5 years. Smooth implants more often had a dense collagenous capsule than textured implants after 5 years. No significant difference was seen in the orientation of collagen fibers in capsules around smooth and textured implants at 0 to 5 years. After 5 years, the incidence of capsules with collagen fibers arranged parallel to the implant surface was significantly greater in the smooth group than in the textured group (p = 0.01). The presence of a foreign body type reaction was seen more often in the textured group between 0 and 5 years (p = 0.01) and at greater than 5 years (p < 0.01), and the presence of foreign material was more often seen in the textured group between 0 and 5 years (p = 0.06) and at greater than 5 years (p < 0.01). In summary, the cytologic changes around implants seem to be dynamic in nature, and implantation duration and shell type play a significant role. Synovial-like metaplasia, villous hyperplasia, and foreign material were more often observed in the textured group within the 0 to 5 year interval. Beyond 5 years, synovial-like metaplasia, a foreign body type reaction, and foreign material were more often observed in the textured group. Differences in the density of collagenous capsules were not significant at any time point, and collagen fibers oriented parallel to the implant surface were more often observed in the smooth group after 5 years. The significance of these findings awaits further investigation.     

Morphologic and immunohistochemical observation of explanted Proplast-Teflon temporomandibular joint interpositional implants

PURPOSE: The objective of this study was to investigate the cellular tissue response to temporomandibular joint (TMJ) Proplast-Teflon disc material by morphologic and immunohistochemical means. PATIENTS AND METHODS: Twelve patients who had been subjected to TMJ discectomy combined with insertion of a Proplast-Teflon interpositional implant (PTIPI) were recalled for removal of the alloplastic disc. The time elapsed between the Proplast-Teflon disc implantation and its removal varied between 13 and 71 months (mean, 54.6 +/- 5.8 [SEM]) The implants and periimplant tissues were examined by light microscopy and immunohistochemically using a panel of monoclonal antibodies reactive with different subclasses of leukocytes. The sections were immunostained using the alkaline phosphatase-antialkaline phosphatase (APAAP) technique. RESULTS: Fibrosis and a massive foreign body giant cell reaction were seen inside the heavily disrupted alloplastic implants and in the periimplant tissues. CD68-positive monocyte-derived cells dominated the reactive infiltrate in the implants and surrounding tissue. The CD68-positive cells also were partly positive for lysozyme. The lymphocytic infiltration contained no B cells. CONCLUSIONS: This study of the PTIPI-induced tissue reaction gave no indication of a toxic or an immunologic pathogenesis. Mechanical stress seems important in the fragmentation of the implant and induction of the foreign body reaction. It is not yet known if this fragmentation is the major contributing factor.     

Long-term observation of subcutaneous tissue reaction to synthetic auditory ossicle (Apaceram) in rats

The present study evaluates histological characteristics of the soft tissue response to long-term implantation of Apaceram discs composed of dense hydroxyapatite in rats. Discs were implanted into the subcutaneous tissue of 76 rats for six to 20 months. Decalcified histological sections stained with haematoxylin and eosin (H & E) and Mallory's azan were examined. Different cell types surrounding implants were counted. The greatest proportion of macrophages was found at six months (13.5 per cent). This proportion gradually decreased to four per cent at 20 months. Small numbers of lymphocytes and foreign body giant cells were observed in every group, but neither neutrophils nor osteogenesis were observed in any specimens. Results of the present study and previous related studies indicate that despite reappearance of a small number of macrophages six months after implantation, Apaceram is useful for reconstructive surgery.     

Granulomatous epididymal lesion of possible ischemic origin

In a histologic review of adult epididymides obtained at autopsy (both epididymides of 408 men) or during surgery (261 men with testicular or epididymal nontumoral pathology), a peculiar granulomatous lesion was observed in two autopsy specimens (unilateral) and three surgical specimens. The lesion was located in the caput epididymidis and consisted of a zone of necrosis that involved efferent ducts and interstitial connective tissue and was not associated with an acute inflammatory response. Immunohistochemical study with anticytokeratin antibodies showed the presence of some epithelial cells in the damaged efferent ducts. At the periphery of the lesion, where damage was less severe, the efferent ducts only showed partial necrosis of their wall through which the necrotic material was released to the ductal lumen. Inflammatory infiltrates were scanty and consisted of lymphocytes and CD68-positive macrophages. Lymphocytes were mainly located around the necrotic zone or surrounding the adjacent, well-preserved efferent ducts, whereas macrophages formed large clusters in the ductal lumen. In these clusters, cholesterol crystals and giant cells of foreign body type were frequent. Intratubular epithelial regeneration as well as proliferation of small ducts showing epithelial regeneration and numerous spermatozoa in their lumen were observed. Ceroid granulomata, spermatic granulomata, and epidermoid metaplasia of the efferent ducts were observed in some cases. On the basis of the histologic study, the following developmental stages of the lesion are suggested: ischemic necrosis, granulomatous reaction, cicatrization, and sequelae. The term "granulomatous ischemic lesion" is proposed to designate this reactive lesion.     

Therapeutic strategies for the inhibition of inducible nitric oxide synthase--potential for a novel class of anti-inflammatory agents

The objective of this work was to study in more detail the human/murine SCID arthritis model with special emphasis on characteristic features initiated by rheumatoid arthritis (RA) synovial membrane (SM) as compared to appropriate control tissues. Small tissue samples from RA-SM, healthy lymph node, healthy SM, and granulomatous tissue of human origin were implanted into the left knee joint of mice with severe combined immunodeficiency (SCID), and the joints were analysed histologically after 7 days. In addition, a time course study, including non-invasive monitoring by serological parameters (human IgM, IgG, and IL-6) and Tc-99m-scintigraphy, was performed for up to 4 weeks on RA-SM recipients. All tissue implants induced transient exudative joint inflammation while RA-SM initiated a characteristic arthritis with pannus tissue of high cellular density, erosion, multinuclear giant cells, lining cell hyperplasia, fibroblast-like cell layers, chondroideal metaplasia, and fibrin deposits. Significantly elevated levels of human immunoglobulin and characteristic signs of chronic inflammation persisted for more than 4 weeks. We conclude that the hu/mu SCID arthritis with RA-SM implants comprises features of non-specific inflammation which is also transiently seen with control tissues but develops characteristic features of chronic RA-like synovitis thereafter.     

Atropine poisoning after drinking Indian tonic water

After 13.5 years in vivo a 2-0 Terylene frontalis loop was excised because of an insufficiency. Histology showed a persisting giant cell reaction while lymphocytes were almost totally absent. The fibrils of the suture seemed to be intact. However, they were separated by ingrowing connective tissue which, on theoretical grounds, should improve the function of the frontal muscle on the upper eyelid. Therefore, insufficiency of the loop was probably caused by the (subclinical) foreign body reaction or the long-lasting mechanical stress leading to tissue damage.     

Capsular synovial metaplasia as a common response to both textured and smooth implants

Recent reports suggested that the presence of synovial metaplasia in the capsular tissues of breast implants is greater with textured-shelled implants compared with smooth. Textured implants, however, have become popular only in the last few years. Therefore, the studies do not address the possibility that synovial metaplasia may be a dynamic process related to time (e.g., implant age) rather than implant shell surface. In the current study, 159 implant capsules (85 patients) removed between February of 1992 and July of 1993 at UCLA Medical Center were evaluated histologically and correlated with clinical data, including the age of implants. Synovial metaplasia was identified in 40 percent (64 of 159) of the capsule specimens. A logistic regression analysis that removed the effect of implant age demonstrated no correlation of implant shell type (textured versus smooth) with the presence of synovial metaplasia. Gel bleed, implant location, pericapsular fluid, implant rupture, and capsular contracture also did not have any significant association with synovial metaplasia in the current study. The incidence of synovial metaplasia appears to decrease with age (77 percent at < 5 years; 22 percent at > 15 years). Our findings suggest that synovial metaplasia is not rare and in fact may be a fairly common transitional histologic finding. It may be part of the common progression that occurs at the implant-capsule interface. The clinical significance remains unknown.     

Breast capsule persistence after breast implant removal

Breast implant capsules are a foreign body immune response to breast implants. It has been proposed that capsulectomy after breast implant removal was unnecessary, as the body resorbs the capsule when the implant, the impetus for the foreign body response, is removed. We report eight women with persistent capsules 10 months to 17 years after silicone breast implant removal.     

Update in systemic fluoride therapy

From January 1990 to August 1994, more than 6000 patients with silicone-gel breast implants were clinically assessed regarding their implant status. Of these, 82 patients requested removal of their implants (150 implants). Of the 150 implants that were removed, 24 (16%) demonstrated calcified capsules. All 12 patients with calcification demonstrated this finding bilaterally. All calcified capsules demonstrated discrete calcified plaques on their inner surface. All 12 patients presented with Baker class IV contractures, with pain as their chief complaint. One patient demonstrated calcification on a routine chest radiograph. One patient demonstrated a stippled appearance on xeromammogram. Capsular calcification was related to the duration of implantation. All 6 implants that had been in place for 23 to 26 years were associated with calcification. These implants were all of the thick-walled Dacron-backed type. All thick-walled Dacron-backed implants that were removed in this study were associated with calcification. Of the 69 implants that had been inserted for 11 to 20 years, 18 (26.1%) were associated with calcification. Fifteen of these 16 implants were ruptured. None of the implants that had been in place for 10 years or less demonstrated calcification.     

Impression cytology in atopic dermatitis

PURPOSE: This study aimed to describe the ocular surface disorder in patients with atopic dermatitis (AD). DESIGN: A prospective case-controlled study. PARTICIPANTS: A total of 44 patients with active AD seen at Kobe University School of Medicine, Department of Ophthalmology, during 1994 through 1996 and 22 normal control subjects were studied. INTERVENTION: The subjects underwent routine ophthalmic examinations, tear film break-up time (BUT), Schirmer test, and conjunctival impression cytology. MAIN OUTCOME MEASURES: Patients and control subjects were compared for tear function parameters, goblet cell density, and conjunctival squamous metaplasia grade. The relation of duration and recurrences of AD to the ocular surface disorder also was looked for. RESULTS: The duration of atopic disease ranged from 18 to 32 years (mean, 22.8 years). The average for exacerbations was 4.5 times. Chronic allergic conjunctivitis with superficial punctate keratitis was the most frequent clinical presentation. The BUT and Schirmer test values were significantly lower in patients with AD compared with those of the control subjects. Impression cytology showed goblet cell loss and conjunctival squamous metaplasia, both of which related to the number of recurrences of AD rather than the duration of disease. Facial atopy and allergic keratoconjunctivitis (AKC) related to the metaplasia of the ocular surface (P < 0.001). Patients with reduced goblet cell density also showed low BUT levels (P < 0.001). CONCLUSION: Ocular surface disorder of AD characterized by goblet cell loss and conjunctival squamous metaplasia seemed to evolve independently of the duration of disease but worsen with increased number of flare-ups. Direct epithelial damage by the allergic reaction, disorder of tear quality, and quantity may be important in the genesis of the atopic ocular surface disease.     

Translational inhibitor protein, PSP

The efficacy of thalidomide in the treatment of erythema nodosum leprosum is a well established fact; there is also accumulating evidence of its therapeutic value in a number of other inflammatory and immune-mediated conditions. In addition, thalidomide has been shown to be an inhibitor of angiogenesis induced by basic fibroblast growth factor (bFGF). Nevertheless, its mechanism of action remains speculative. Using guinea pigs, orally administered thalidomide significantly enhanced the response of multinucleated foreign body giant cells (p<0.05) in subcutaneously implanted polyvinyl alcohol sponges. Furthermore, the drug exerted a dual effect in that it reduced vascular density (p<0.05), which was not abolished by recombinant human bFGF, and at the same time amplified the granulomatous response with and without bFGF (p<0.05 and p<0.01, respectively). The results of our experiments represent a further step toward understanding the mechanism of action of thalidomide, with implications for its potential use in wound healing and scar formation as well as in the control of tumorigenesis.     

Biomechanics of A-to-T flap design

We present two types of "new" foreign body granulomas caused by the injectable aesthetic microimplants Bioplastique and Artecoll. We report the clinical and histopathologic findings in five patients who had undergone treatment of mainly facial contour abnormalities with one of these implants. All patients were women, and the mean age was 45 years (age range 24-72 years). Two patients presented after treatment with Bioplastique; in three patients, augmentation was achieved by using Artecoll. Unsatisfactory cosmetic effects led to excision of the implants in four patients; in one patient, parts of the implant were excised during another cosmetic intervention. Subsequent histopathologic examination showed features of foreign body granulomas with distinctive cystic spaces. The clue to the diagnosis is the particular configuration of these cystic spaces and the characteristic shape of the foreign bodies. Bioplastique granuloma presents with irregularly shaped cystic spaces of varying size containing jagged, translucent, nonbirefringent foreign bodies whereas Artecoll granuloma shows numerous round vacuoles nearly identical in size and shape enclosing round and sharply circumscribed, translucent, nonbirefringent foreign bodies. These specific histopathologic findings unequivocally allow the correct diagnosis in spite of sparse clinical information.     

Uniform persistence in a generalized prey-predator system with parasitic infection

Self-reinforced poly-L-lactide (SR-PLLA) and self-reinforced polyglycolide (SR-PGA) pins were implanted intra-articularly and directly into the bone of the distal femur of rats at three levels: above, on the same level, and under the surface. For the controls only channels were drilled, or the controls were not operated at all. The follow-up times were 3, 6, and 12 weeks for SR-PGA and 3, 6, 12, and 24 weeks for SR-PLLA. The macroscopic appearance and histologically the villus reaction, the mononuclear phagocytosis and giant cells, the neutrophils, the lymphocytes, the plasma cells, the eosinophils, and the mast cells were analyzed. In the histologic analysis, the most favorable implantation depth was found to be under the surface where the contact between the implants and bone was best, and the orifice was covered with new trabecular bone at 3 weeks. This was especially seen in intra-articular implantation. In general, the tissue responses were mild, and could also be explained in the statistical analysis by a normal postoperative tissue response and faster biodegradation of PGA.     

Perianal injection of polydimethylsiloxane (Bioplastique implants) paste in the treatment of soiling: pilot study in rats to determine migratory tendency and locoregional reaction

Not much is known about the specific pathophysiologic mechanisms of soiling. Although the causes of soiling may vary, it is mostly associated with anorectal disorders that can deform the contour of the anus and anal canal. In most cases, this disorder can be treated successfully by medical or surgical therapy. If this appropriate treatment is not available or fails, reconstruction of the contour deformity of the anus by perianal (submucosal) injection of soft tissue bulking agents may be successful. PURPOSE: The main purpose of this pilot study was to evaluate locoregional reaction and distant migration after local perianal injection of solid polydimethylsiloxane elastomer particles (Bioplastique implants). METHODS: Twelve Lewis rats received a local perianal injection of Bioplastique implants. Six of them received an additional perianal injection of gentamicin. Six weeks after injection, the rats were euthanized. RESULTS: Microscopically, the local tissue reaction was that of a quiescent foreign body reacting with encapsulation. Microscopic examinations could not reveal any migration to locoregional lymph nodes, liver, spleen, lungs, or brain. CONCLUSION: We conclude that, because of minimum local reaction and lack of evidence of distant migration, polydimethylsiloxane elastomer particle paste (Bioplastique implants) seems to be a potentially safe substance for local perianal injection.     

Impact of glutaraldehyde on calcification of pericardial bioprosthetic heart valve material

BACKGROUND: This study was conducted to investigate the impact of the preservation method of bioprosthetic heart valve materials on calcification rates and biocompatibility of the biologic tissue. METHODS: In subcutaneous rat implants, conventionally preserved bioprosthetic heart valve material was compared with bovine pericardium that was treated with L-glutamic acid to reduce residual glutaraldehyde released from the fixed tissue. Both these methods were compared with bovine pericardium that was stabilized by a dye-mediated photooxidation reaction without glutaraldehyde. Biocompatibility of these biomaterials was tested in vitro using human endothelial cell cultures. RESULTS: Conventionally preserved bovine pericardium with a high amount of glutaraldehyde incorporated into the tissue resulted in severe calcification 63 days after subcutaneous implantation in rats (165.4 +/- 20 mg Ca2+/g dry weight). Postfixation treatment with L-glutamic acid, which reduces free, unbound aldehyde groups, showed a significant decrease in calcification (89.6 +/- 14 mg Ca2+/g dry weight). Glutaraldehyde-free preservation by dye-mediated photooxidation showed no calcification after 63 days of subcutaneous implantation (1.0 +/- 0.4 mg Ca2+/g dry weight). Regular endothelial cell proliferation was observed on photooxidized and L-glutamic acid-treated tissue, whereas conventionally treated tissue caused endothelial cell death. CONCLUSIONS: This study underlines the detrimental role of glutaraldehyde in the calcification process of bioprosthetic heart valve materials and emphasizes alternative preservation methods that reduce or avoid the use of glutaraldehyde.     

Recommendations for the molecular diagnosis of familial adenomatous polyposis

OBJECTIVES: We investigated the relationships between gastric metaplasia occurring during the healing and scarring stages of duodenal ulcers and Helicobacter pylori by examining the course of gastric metaplasia in H. pylori-eradicated and non-eradicated patients. METHODS: One hundred and six H. pylori-positive patients with active duodenal ulcers were assigned to either a non-eradication group or an eradication group. The non-eradication group received lansoprazole for 6 wk, followed by an H2-receptor antagonist. The eradication group also received amoxicillin and metronidazole for 1 wk, in addition to lansoprazole, after initial endoscopic examination. In both groups, biopsy specimens were obtained from the ulcer margin in the active stage and from the center of the scar in the scarring stage. Specimens were examined microscopically as well as by rapid urease test to assess the extent of gastric metaplasia and to detect the presence of H. pylori. RESULTS: The extent of gastric metaplasia increased as the ulcers healed. The extent of gastric metaplasia was of a lesser degree in the non-eradication group than in the eradication group at the time of healing, and this tendency became increasingly apparent in the course of follow-up, resulting in reduced defense mechanisms against acidity to promote the recurrence of ulcers. In the eradication group, among those in whom eradication was successful, gastric metaplasia presented a well-developed appearance with abundant intracellular mucus and remained in this condition for a prolonged period, resulting in adequate defense mechanisms against acidity to prevent the recurrence of ulcers. CONCLUSION: By the eradication of H. pylori, gastric metaplasia becomes well-developed and remains so for a prolonged period. Thus, the eradication of H. pylori appears to play a role in the prevention of ulcer recurrences by developing adequate defenses against acidity.     

Experimental study of the biocompatibility of four root canal sealers and their influence on the zinc and calcium content of several tissues

Four root canal sealers (AH-26, Roth 811, CRCS, and Sealapex) were tested for tissue biocompatibility in rat connective tissue. Each sealer was placed in Teflon tubes and implanted subcutaneously in Wistar-Furth rats. The implants were removed after 7, 14, and 21 days, fixed, and histologically prepared for microscopical evaluation. Brain, liver, kidneys, and uterus were removed from the animals killed at the first experimental period (7 days) and analyzed for zinc and calcium concentration by flame atomic absorption spectrophotometry. In total, 100 specimens were examined. At the seventh day, the most irritant material was seen to be AH-26, but this inflammatory reaction decreased with time. Roth 811 and Sealapex caused moderate-to-severe inflammatory reaction, whereas CRCS caused mild to moderate. CRCS and Roth 811 induced redistribution of zinc, whereas AH-26 induced changes in calcium content in some organs.     

The detection of ductal carcinoma in situ at mammographic screening enables the diagnosis of small, grade 3 invasive tumours

This study was carried out to assess the frequency of ductal carcinoma in situ (DCIS) occurring within and surrounding grade 3 invasive tumours and the effect of its detection on size and nodal stage of invasive carcinomas at mammographic detection. Grade 3 tumours with either no associated DCIS or DCIS only within the invasive component were significantly larger in size than tumours with surrounding DCIS (P < 0.02) and were less likely to be under or equal to 10 mm in size (0% or 13% vs 30% respectively, P < 0.02). Tumours with mammographic calcification were more likely to be less than or equal to 10 mm in size than non-calcific tumours (32% vs 11% respectively, P < 0.05). This was because of the high frequency of tumours less than or equal to 10 mm in size in the linear/branching calcification group. Tumours showing calcification without a mass also appear to be a group with good prognostic features, with a mean size of 13 mm, 33% being 10 mm or less in size and only 17% being node positive. We have found that the presence of surrounding DCIS enables earlier detection of grade 3 invasive carcinomas because of the presence of mammographically visible calcification. Detection of calcification suggestive of DCIS should remain an important part of mammographic screening.     

Guided bone regeneration around dental implants in the atrophic alveolar ridge using a bioresorbable barrier. An experimental study in the monkey

The aim of this study was to evaluate guided bone regeneration (GBR) around dental implants placed in atrophic alveolar ridges using an experimental, nonporous bioresorbable barrier. In 8 Rhesus monkeys, the maxillary canines and lateral incisors were extracted bilaterally and the remaining alveoli were reduced to create atrophic ridges. After a healing period of 3 months, soft tissue expansion was performed using a subperiosteal tissue expander. After 1 month of tissue expansion, and IMZ implant was placed in the atrophic ridge on each side in such a way that its coronal 4 mm to 5 mm remained circumferentially exposed above the bone level. The test implants were covered with a bioresorbable barrier made of poly (D,L-lactid-co-trimethylencarbonate) in a 70/30 ratio, whereas the control implants were covered with a nonresorbable expanded polytetrafluoroethylene (e-PTFE) barrier. The e-PTFE barriers were stabilized with titanium minipins while the bioresorbable barriers were analogously fixed using bioresorbable minipins made of poly (L-lactid-co-D,L-lactid) 70/30. Clinical healing progressed uneventfully in both groups and no soft tissue dehiscences occurred. Histometric and histomorphometric analyses were performed 5 months post surgery. Both test and control implants exhibited direct bone-to-implant contact to variable extents. The mean direct mineralized bone-to-implant contact length fraction was 32% of the total implant length in the test sites and 58% in the control sites. Control sites exhibited significantly greater bone fill compared to the experimental sites (P < 0.001). Histologic observations of test specimens demonstrated a moderate inflammatory reaction related to the degradation and resorption products of the barrier. In conclusion, the nonresorbable e-PTFE GBR barrier was found to be superior to the bioresorbable barriers tested in the present investigation.