Lamina Propria Fibrosis Research Articles

Smooth-Muscle Regeneration after Electrosurgical Endopyelotomy in a Porcine Model as Confirmed by Electron Microscopy

Endopyelotomy is the preferred treatment for ureteropelvic junction (UPJ) obstruction because of its short operating time, limited morbidity, fast recovery, and reasonable efficacy. We used tissue and immunohistochemistry staining and electron microscopy to look at the muscle regeneration following an endopyelotomy incision in a porcine model. Bilateral electrosurgical endopyelotomy was performed in six domestic pigs with placement of 7F 20-cm Percuflex double-J stents for up to 4 weeks, and urinary tracts were harvested at 3 or 5 months. Specimen evaluation included tissue staining with hematoxylin-eosin, Masson's trichrome, and Verhoeff's iodine and Van Gieson solution; histochemical staining for smooth-muscle actin, desmin and myosin staining, and electron microscopy. Each specimen was assigned a "healing" score of 0 (normal) 1 (slight changes), 2 (mild changes), or 3 (severe changes). The fibrosis score was based on six factors: muscle layer fibrosis, lamina propria fibrosis, amount of granulation tissue present, new deposits of collagen, fibrosis in the periureteral fat, and presence of myofibroblasts. The muscles were characterized with immunohistochemistry and electron microscopy. At both 3 and 5 months, the urothelium was healed, and the lamina propria was healed with focal loss. By 3 months, smooth-muscle bundles bridged the defect, and by 5 months, the whole defect was covered. Smooth muscle cells were evident by electron microscopy by 3 months, and actin and myosin could be detected by immunohistochemistry. Desmin-positive cells accounted for 50% of the population at 3 months and 40% at 5 months. The regenerated smooth-muscle bundles were oriented in different directions and intermingled with fibrous tissue. They could be distinguished easily from normal ureter under the microscope. Verifiable, functional smooth-muscle bundles bridge the endopyelotomy defect by 3 months, as confirmed by immunohistochemistry staining and electron microscopy.

Effects of Topically Applied Biomaterials on Paranasal Sinus Mucosal Healing

Recently, nasal packing made of absorbable biomaterial has become increasingly popular. Although absorbable packs are effective for hemostasis, their impact on healing mucosa is unknown. Some have felt that a biocompatible sinus dressing actually may enhance healing, particularly in areas where the mucosa has been stripped. The aim of this study was to determine the effect of topical MeroGel and FloSeal on paranasal sinus mucosal healing in a rabbit model. Bilateral maxillary sinuses of 12 New Zealand white rabbits were surgically opened and stripped of mucosa. The left maxillary sinus of six rabbits had sterile saline-soaked MeroGel placed in the antrum, and the other six rabbits received FloSeal. The right maxillary sinuses of all 12 animals were stripped and otherwise untreated to serve as stripped controls. The animals were killed at 2 weeks and specimens were examined by light microscopy. MeroGel-treated mucosa showed extensive fibrosis of the basal lamina and lamina propria, complete loss of surface epithelium, and loss of the mucociliary blanket. There was minimal resorption of the MeroGel, and MeroGel fibers were frankly incorporated into the regenerated epithelium, associated with an exuberant lymphocytic infiltrate. FloSeal-treated mucosa showed similar fibrosis of the basal lamina and lamina propria with loss of the mucociliary blanket, although to a lesser degree than the MeroGel- treated group. FloSeal showed similar incorporation into the healed mucosa with lymphocytosis. Controls showed expected submucosal gland reduction, lamina propria fibrosis, and loss of cilia, but the lamina propria fibrosis seen in the MeroGel and FloSeal groups was markedly more prominent. In a rabbit model, MeroGel and FloSeal appear to increase reactionary fibrosis of healing mucosa. These agents also appear to be incompletely resorbed and grossly incorporated into healing tissue. Mucosal healing may be impaired by the application of these agents.

Paranasal Sinus Mucosal Regeneration: The Effect of Topical Retinoic Acid

Paranasal sinus mucosa may suffer morphological and functional alterations as a result of surgical trauma. Mucosal stripping typically yields regenerated mucosa characterized by fibrosis, inflammatory infiltrate, and dysmorphic or absent cilia. The aim of this study was to determine the effect of topical retinoic acid (vitamin A) on regeneration of paranasal sinus mucosa. Both maxillary sinuses of 12 New Zealand white rabbits were surgically opened and stripped of mucosa. Six rabbits received 0.01% topical retinoic acid gel treatment to the stripped left maxillary sinus (low concentration group). The remaining six rabbits received 0.025% topical retinoic acid gel to the stripped left maxillary sinus (high concentration group). The stripped right maxillary sinus of all 12 rabbits served as the operated, untreated control to reflect the normal healing process. Six other animals served as unoperated controls. The sinus mucosa was examined by light microscopy after 14 days. Untreated regenerated mucosa showed expected changes of submucosal gland loss, basal lamina and lamina propria fibrosis, cellular atypia, and loss of cilia. Topical retinoic acid treatment appeared to result in better mucosal regeneration marked by less cellular atypia and fibrosis. Although the regenerated mucosa was still grossly abnormal, the degree of ciliary loss and cellular derangement was reduced. The lower-concentration retinoic acid group had more favorable morphology than the higher-concentration retinoic acid group, and both were improved when compared with no treatment. In a rabbit model, topical vitamin A in the form of retinoic acid gel appears to enhance regeneration of ciliated paranasal sinus mucosa. This preliminary study suggests that topical retinoids may have applicability in promoting sinus wound healing.

Clinical Quiz

A 4-year-old girl had a 3-month history of passing red blood per rectum and lower abdominal pain. Colonoscopy revealed erythematous rectal and distal sigmoid colon mucosa with a chronic nonspecific inflammatory cell infiltrate in the biopsy tissue specimen. Hemoglobin, leukocyte count, platelet count, and C-reactive protein were all normal. The symptoms recurred after 2 years, when colonscopy and rectal mucosal biopsy findings were unchanged. Hydrocortisone enemas were again prescribed. Follow-up was unsatisfactory, and the family failed to attend several hospital appointments. The patient was referred again at 14 years of age with a 2-year history of a dull ache in the lower abdomen that became worse after a bowel movement, especially if she was moving around. She also reported tenesmus. She would strain for half an hour and pass a small amount of stool and red blood. The blood would continue to drip for a couple of hours after a bowel movement. Menarche occurred when the patient was aged 12 years, with periods that were regular but heavy and associated with flooding and dysmenorrhea. The rectal bleeding showed no cyclical fluctuation but worsened after menarche. Investigation revealed hemoglobin of 7.2 g/dl, mean corpuscular volume of 74 fl, leukocyte count of 14 × 109/l, and erythrocyte sedimentation rate 29 mm/hr. Prothrombin time and partial thromboplastin time were normal. The colonoscopy examination showed erythematous rectal and distal sigmoid mucosa with dilated tortuous vessels (Fig. 1). There were several raised, flat-topped, bluish mucosal lesions in the proximal sigmoid and descending colon. There were crypt abscesses, chronic inflammatory cell infiltration, and fibrosis of lamina propria seen in rectal mucosal tissue specimens. Sigmoid and descending colon biopsy specimens were histologically normal. The patient was treated with senna and oral iron. Mesenteric angiography was normal but a technetium 99–labeled erythrocyte scan showed an abnormal focus of uptake in the abdomen.FIG. 1.A: What is the diagnosis? B: What further investigations should be conducted? Answer: The patient had extensive low-flow venous malformations of the rectum and distal colon. Ultrasound examination showed dilated venous channels around the rectum and uterus that were confirmed by computed tomographic scan (Fig. 2A). Magnetic resonance imaging showed widespread serpiginous varices within the pelvis surrounding the uterus and bladder adnexa extending toward the rectum (Fig. 2B). The wall was thick with prominent vessels in the rectum and perianal area.FIG. 2.Figure 2: ContinuedComment: Venous malformations of the rectum are uncommon lesions that present complex management problems (1). Most lesions become symptomatic with rectal bleeding in infancy or childhood. Many of these patients are treated for colitis for years before the correct diagnosis is made. The usual symptom is painless bleeding per rectum and occasional tenesmus or abdominal pain. These patients may have chronic constipation and rectal prolapse. Occasionally, venous malformations affect the sigmoid and descending colon in addition to the rectum. Venous malformations of the rectum have been described as “diffuse cavernous hemangiomas.” Mulliken et al. divided vascular lesions into pediatric hemangiomas and vascular malformations. Unlike hemangiomas, vascular malformations do not proliferate in the first few months of life, and growth is commensurate with that of the child. They may contain a combination of venous, lymphatic, capillary, or arterial components. This patient had extensive low-flow venous malformations. Several treatment options have been tried in such patients, including sclerotherapy, surgery, and radiation therapy. These are associated with significant morbidity and mortality and should be reserved for patients unable to maintain hemoglobin above 10 g/dl when treated with iron therapy and stool softeners.

Histochemical and immunohistochemical characterization of foamy histiocytes (muciphages and xanthelasma) of the rectum.

Despite being relatively common in the rectum, foamy histiocytes have received scant attention as to the antecedent lesion that causes them to form or their histologic characterization on the types of muco-substances they accumulate. One-hundred consecutive tissue sections of the rectum from an equal number of patients were reviewed for the presence of foamy histiocytes, evaluated for their associated histologic features, and examined histochemically for five types of mucin. Immunohistochemical and electron microscopic studies were performed. Forty (40%) of the rectal biopsy tissues contained foamy histiocytes. Patients presented with diarrhea, hematochezia, intestinal habit change, constipation, hemorrhoids, and abdominal pain. Endoscopically, 19 patients were thought to have rectal nodules or polyps. Histologically, 25 of the patients had regenerative changes in the adjacent mucosa and 14 had hyperplastic changes. In 36 patients (90%), the foamy histiocytes were located superficially in the lamina propria. Associated changes indicated that they are found in areas that are subject to an injury that is in a healing phase. These changes included mild fibrosis and chronic inflammation of lamina propria with mild architectural distortion. Thirty-five (88%) cases showed staining for D-PAS, Alcian blue stain pH 2.5, and the cocktail Alcian blue stain/PAS. Mucicarmine was positive in 25 (63%) cases. The Alcian blue stain pH 1.0 was positive in 19 (59%) of 32 cases. Ultrastructural studies showed electron-dense globules. Two cases were histologically identical to the other 38 but they did not stain for any mucin. Ultrastructural features disclosed clear vacuoles and thus represent a xanthelasma of the rectum. The foamy cells in all cases were confirmed to be histiocytes by immunohistochemistry and electron microscopy. Although muciphages and xanthelasma of the rectum may mimic polyps endoscopically, they are not related to any specific symptom or clinical finding, despite the fact that they probably represent remnants of a previous injury. Muciphages contain neutral, weakly acidic or strongly acidic mucin. The main type of acidic mucin is sialomucin with a smaller component of sulfated mucin.

Radiation-induced pseudocarcinomatousproliferations of the urinary bladder: A report of 4 cases

Four cases of radiation cystitis that caused diagnostic difficultybecause of an epithelial proliferation with architectural complexity and reactive cytologic atypia are described. The patients, 2 male, 2 female, were from 43 to 77 years of age. Two presented with hematuria. Cystoscopy disclosed abnormalities in 3 patients. Microscopic examination showed irregularly shaped and arranged aggregates of epithelial cells in the upper and mid zones of the lamina propria. The cells, which typically showed at least mild, and sometimes severe, pleomorphism, were usually transitional, but squamous differentiation was seen focally in 3 cases. Ulceration of the overlying epithelium was present in all cases and was prominent and associated with conspicuous fibrin and hemorrhage in one of them. Edema of the lamina propria was present in 3 cases, whereas lamina propria fibrosis and chronic inflammation were present in all cases. The presence in all 4 cases of vascular ectasia and other changes characteristic of radiation injury, such as atypical fibroblasts, prompted investigation of the clinical history in 2 cases in which the pathologist was unaware that the patient had received radiation. Pseudocarcinomatous proliferations in the bladder caused by radiation injury have received limited attention in the literature. Our cases illustrate the potential diagnostic errors with which these lesions may be associated.

Histopathological Changes in Kock Pouch

To investigate whether tumour recurrence or histological changes occur in the Kock pouch, periodic endoscopy with biopsy of the pouch was performed in 15 patients 6 to 66 months after radical cystectomy and urinary diversion for invasive bladder cancer. Endoscopy was undertaken 1 to 4 times in each patient (a total of 37 times in all patients). During endoscopy, random biopsies were taken from the pouch wall, and from the afferent and the efferent nipples. The histological changes were graded as: (1) villous atrophy (grade 0 to 3, 0: nearly normal; 1: shortening, villi/crypt of Lieberkuhn [length] between 1.5 and 4.0; 2: moderate flattening, villi/crypt < 1.5; and 3: almost complete disappearance of villi); (2) fibrosis; and (3) chronic inflammation (grade 0 to 3, based on the amount of fibrous tissue and inflammatory cell infiltration in the lamina propria, respectively). There was no dysplasia or malignant tumour in the Kock pouch in any of the 15 patients. The histology of the ileum changed in terms of villous atrophy, fibrosis and chronic inflammation in the lamina propria and thickening of the muscularis mucosa. The same grade of villous atrophy of the pouch wall, the afferent and the efferent nipples was only found in 3 patients. More fibrosis and less chronic inflammation in the lamina propria were found at the efferent nipple than at the afferent nipple or pouch wall in 8 patients and 5 patients, respectively. Thickening of the muscularis mucosa was found in 13 of 15 patients (86.7%). In conclusion, there was no dysplasia or recurrent tumour in the Kock pouch in patients who were followed for up to 66 months. Various grades of histological changes of the ileum in terms of villous atrophy, fibrosis and chronic inflammation of the lamina propria, and thickening of the muscularis mucosa were found in the pouch wall, and in the afferent and efferent nipples. More fibrosis and less chronic inflammation were commonly observed at the efferent nipple than at the afferent nipple or pouch wall. The degree of histological changes varied even among patients followed over the same period after operation. The time to progression of villous atrophy also varied. The histological changes in some patients were dissimilar even at the same site of the Kock pouch.

Mucosal Pathology of the Nose and Sinuses: A Study in Experimental Maxillary Sinusitis in Rabbits Induced by Streptococcus Pneumoniae, Bacteroides Fragilis, and Staphylococcus Aureus

Unilateral maxillary sinusitis was experimentally induced in New Zealand White rabbits with Streptococcus pneumoniae serotype 3, Bacteroides fragilis NCTC 9343, and Staphylococcus aureus V8 in order to study possible differences in the inflammatory response of the sinus and nasal mucosa at different time-intervals during a 12-week period of infection. The initial sinus mucosal response, most pronounced in pneumococcal sinusitis, was characterized by leukocytosis, epithelial desquamation, and squamous cell metaplasia. Tissue reactions at later intervals included fibrosis of lamina propria, gland involution, polyp formation, and bone remodelling, and were most pronounced in S. aureus and B. fragilis sinusitis. The nasal mucosa was altered with a redistribution of goblet cells, development of polyps in the ethmoidal region, involution of Bowman's glands and locally, areas of degenerated olfactory sensory epithelium. These findings endorse that the degree of local pathology depends on the infecting microorganism's specific pathogenetic factors. However, local tissue factors guiding the cellular inflammatory proliferative and regenerative processes are also of fundamental importance for the type of pathological changes occurring in an infected nasal or sinus mucosa.

ヒト下鼻甲介における年令変化 組織学的研究

The age-related histological changes of the human inferior nasal turbinates were studied by means of morphometric and other quantitative techniques. The specimens used in this study Were 100 inferior turbinates (31 females and 69 males) obtained at autopsy. They were from 1.3 to 84 years of age and without any apparent nasal pathology.The height of mucous epithelial layer and the number of basal cells decreased with age. Although the incidence of epithelial atrophy increases, obvious age effects are not observed in the incidence of epithelial squamous metaplasia and in the population density of goblet cells.The thickness of basement membrane under epithelial layer increases with age accompanied by marked hyalinization. The incidence of loosening of the basement membrane, however, does not apparently change with age.In lamina propria, the number of infiltrating small round cells and the proportion of glandular tissue area to lamina propria decreased with age. As the age advances, the intimal thickening of muscular arteries and fibrosis of lamina propria are obviously observed.Although these changes are caused by either or both intrinsic and extrinsic factors, these changes should be interpreted as a whole to elucidate the age-related histological changes of the entire inferior nasal turbinate.