Analysis of Expression of the ANG1, CaSR and FAK Proteins in Uterine Fibroids.

Understanding the molecular factors involved in the development of uterine myomas may result in the use of pharmacological drugs instead of aggressive surgical treatment. ANG1, CaSR, and FAK were examined in myoma and peripheral tissue samples taken from women after myoma surgery and in normal uterine muscle tissue samples taken from the control group. Tests were performed using tissue microarray immunohistochemistry. No statistically significant differences in ANG1 expression between the tissue of the myoma, the periphery, and the normal uterine muscle tissue of the control group were recorded. The CaSR value was reduced in the myoma and peripheral tissue and normal in the group of women without myomas. FAK expression was also lower in the myoma and periphery compared to the healthy uterine myometrium. Calcium supplementation could have an effect on stopping the growth of myomas.

Serum Selenium Concentration as a Potential Diagnostic Marker for Early-Stage Colorectal Cancer: A Comparative Study.

BACKGROUND Selenium deficiency is an established risk factor for colorectal cancer. The aim of the present study was to determine selenium levels in blood samples obtained from colorectal cancer patients compared with the levels of this element in the blood of patients who had undergone hernia repair and cholecystectomy. MATERIAL AND METHODS The study group consisted of 49 patients diagnosed with colorectal cancer at our institution. The comparison group consisted of 29 and 26 patients undergoing hernia repair and cholecystectomy, respectively. The histological staging level was evaluated on a 4-grade scale. Serum selenium concentration was quantified by inductively coupled mass spectrometry using methane to reduce polyatomic interference. RESULTS Colorectal cancer patients had significantly lower serum selenium concentration than the comparison patients (67.24±15.55 µg/L vs 78.81±12.93 µg/L; P<0.001), and selenium concentration was below the reference range in a high percentage of colorectal cancer patients. However, among the colorectal cancer patients, no significant difference in cancer grading was observed according to selenium concentration (P=0.235). Serum selenium concentration in the patients was evaluated on the basis of 5 independent variables (R=0.6250): age (P=0.011), number of leukocytes (P=0.010), family history of cancer (P=0.045), dietary supplements (P=0.023), and exposure to chemical factors (P=0.057). CONCLUSIONS This study supports findings from previous studies that low serum selenium levels are associated with colorectal cancer and that selenium deficiency may be a risk factor for colorectal cancer.

Effects of Spherical and Rod-like Gold Nanoparticles on the Reactivity of Human Peripheral Blood Leukocytes.

Gold nanoparticles (GNPs) are widely used in the technological and biomedical industries, which is a major driver of research on these nanoparticles. The main goal of this study was to determine the influence of GNPs (at 20, 100, and 200 µg/mL concentrations) on the reactivity of human peripheral blood leukocytes. Flow cytometry was used to evaluate the respiratory burst activity and pyroptosis in monocytes and granulocytes following incubation with GNPs for 30 and 60 min. Furthermore, the concentration of interleukin-1ß (IL-1ß) in human blood samples was assessed using enzyme-linked immunosorbent assay (ELISA) after their incubation with GNPs for 24 h. Under the conditions tested in the study, the GNPs did not significantly affect the production of reactive oxygen species in the granulocytes and monocytes that were not stimulated using phorbol 12-myristate 13-acetate (PMA) in comparison to the samples exposed to PMA (p < 0.05). Compared to the control sample, the greatest significant increase in the mean fluorescence intensity of the granulocytes occurred in the samples incubated with CGNPs = 100 and 200 µg/mL for tinc = 30 and 60 min (p < 0.05). From our results, we conclude that the physicochemical properties of the nanoparticles, chemical composition, and the type of nanoparticles used in the unit, along with the unit and incubation time, influence the induced toxicity.

Estrogen Receptor (ER) and Progesterone Receptor (PgR) Expression in Endometrial Cancer-An Immunohistochemical Assessment.

Endometrial cancer (EC) is one of the most common types of cancer in Poland and worldwide. Many risk factors lead to the pathogenesis of this disease, such as lifestyle choices, BMI, the medicines used in breast cancer therapy, and Lynch syndrome. EC cells show the expression of estrogen receptors (ERs) and progesterone receptors (PgR). These receptors occur in multiple isoforms and have a significant influence on the operation of cells. The loss of ER and PgR expression is associated with a poor prognosis. We assessed tissue slides that were obtained from 103 women with EC diagnoses of various grades, stages, and histological types. In this study, we used computer image analyses to increase the objectivity of the assessment. We proved that, in the tissue of patients with high-grade (G3) EC, the expression of PgR is significantly lower than that in the tissues of patients with low-grade EC. We also observed that PgR is significantly expressed in EC with a low FIGO stage and in the endometroid type of EC (which rarely becomes malignant compared to serous type). The expression of ERb1 was lower in patients with EC at the IV FIGO stage than in patients with stage III EC. These findings confirm that the loss of ER and PgR expression is connected with a poor prognosis.

Immunohistochemical Expression of the SERPINA3 Protein in Uterine Fibroids.

BACKGROUND: SERPINA3 (α-1-antichymotrypsin, AACT, ACT) is produced by the liver and released into plasma in an anti-inflammatory response and plays a role as a modulator of extracellular matrix (ECM) by inhibiting serine proteases. Numerous studies proved an increased level of SERPINA3 in many types of cancer, which could be linked to SERPINA3's anti-apoptotic function. AIM: In the context of progressive ECM fibrosis during the development of uterine fibroids, which are one of the most common hypertrophic changes within the uterus, it is interesting to describe the level of SERPINA3 protein in this type of lesion and the surrounding tissues. METHODS: We used immunohistochemical staining of the SERPINA3 protein and compared the intensity of the signal between the myoma tissue and the surrounding normal tissue. RESULTS: We showed a surprising reduction in the amount of the SERPINA3 protein within uterine fibroids compared to surrounding tissues. CONCLUSION: This observation sheds new light on the role of this protein in the formation of proliferative changes and suggests that understanding the mechanism of its action may become the basis for the development of new diagnostic and therapeutic tools.

Grossly Bloody Colostrum-The Need for Staff Education and Maternal Support.

BACKGROUND: Grossly bloody colostrum is defined as the presence of brownish or bloody-colored colostrum. The frequency is determined to be 0.1% of all births, and no predisposing factor for its occurrence was determined. The purpose of this study was to find factors that increase the probability of the syndrome and the possible influence of the presence of erythrocytes (red blood cells-RBCs) in breast milk on the symptoms of maternal milk intolerance in newborns. METHODS: Here, 2 mL of colostrum was collected from 137 participants on postpartum days 1-3, separately from each breast, and transferred to the laboratory. For microscopic analysis, 0.5 mL of colostrum was centrifuged and then stained using the May-Grünwald-Giemsa method. Using an Olympus BX 43 light microscope at 400× total magnification, samples were visually assessed for the presence of RBCs. Additionally, the participants completed a questionnaire regarding their health status, observation of feeding tolerance of the newborn, observed milk color and other factors. RESULTS: The number of RBCs in the yellow or white colostrum samples ranged from 8 to 1000 RBCs/mL and was found in 24.8% of cases. Regardless of the number of RBCs, the color of the milk was white (28.5%) or yellow (66.4%). Only one participant (0.7%) presented classical bloody-stained colostrum with visible bloody-milk colorization. We did not observe the influence of any analyzed factor as the reason for the increased number of RBCs in the colostrum. CONCLUSIONS: The presence of RBCs in breast milk did not cause milk intolerance among newborns and was independent of the analyzed factors. Mothers should be supported, and in view of the overall composition of breast milk, especially the content of immune cells in colostrum, even a temporary interruption in breast milk feeding in the case of grossly bloody colostrum is not recommended.

Knowledge of HPV and HPV Vaccination among Polish Students from Medical and Non-Medical Universities.

Human papillomavirus (HPV) is a common sexually transmitted infection that can cause both benign and malignant lesions. HPV vaccines, preferably administered before the onset of sexual activity, have demonstrated remarkable efficacy in preventing HPV-related cancers. The impact of a healthcare provider's recommendation on HPV vaccine acceptance is substantial. Therefore, medical students must undergo thorough training in this domain. This study compares fundamental understanding and viewpoints regarding HPV and anti-HPV vaccines among Polish students pursuing medical and non-medical sciences. This study was based on the authors' questionnaire, and the results were statistically analyzed. The participants in this study were 1025 students (medical sciences students-520 respondents in total; and non-medical sciences students-505 respondents in total). According to the results, medical students' knowledge about the consequences of HPV infection and vaccination against HPV was significantly greater. To date, numerous publications have investigated the understanding of particular social, gender, parental, etc., groups about vaccination, but the knowledge of students at different universities-medical and other-has not been compared. Social awareness is still insufficient, even in groups of medical students. There is much to be done to educate and encourage preventive behavior in those not receiving primary prevention in early childhood.

Pathomorphological Changes in Mammary Glands of 16 Patients Who Underwent Surgical Aquafilling® Removal: A Single-Center Study.

BACKGROUND Aquafilling® is a soft-tissue filler used in various procedures, including breast plastic surgery. Proponents claim it to be safe and effective without causing serious adverse effects. This study aimed to describe histological changes in breast tissue resulting from potentially harmful effects of Aquafilling®. MATERIAL AND METHODS Tissue samples were collected from 16 patients who underwent surgical removal of Aquafilling®. Histopathological evaluations were performed on hematoxylin and eosin-stained slides, with photographs captured using an Olympus BX 43 light microscope and an XC 30 digital camera at 40×, 100×, and 400× total magnification. RESULTS Inflammatory infiltrates, mainly consisting of macrophages and lymphocytes, were observed in the images. Tissue necrosis was visible in some areas. Fibrosis foci and blood vessels with thickened walls and detached endothelium were identified within mammary adipose tissue. CONCLUSIONS Due to the variety of clinical symptoms and presence of inflammation in all examined women, we recommend histopathological examinations for all cases of Aquafilling® surgical removal. The examination should include information on the extent of inflammation, progression of adipose and muscle tissue damage, and assessment of fibrosis severity. This will help clinicians make informed decisions about Aquafilling® use in patients and improve patient outcomes.

Diagnostic Problems in C3 Glomerulopathy.

BACKGROUND: C3 glomerulopathies (C3GN) are a group of rare kidney diseases associated with impaired complement regulation. The effects of this disease include the accumulation of complement C3 in the kidneys. Based on the clinical data, as well as light, fluorescence, and electron microscopy results, the diagnoses were verified. The study group consisted of biopsy specimens, which were obtained from 332 patients who were diagnosed with C3 glomerulopathy. In all cases, histopathological examinations were performed; deposits of complement C3 and C1q components, as well as the immunoglobulins IgA, IgG, and IgM, were identified using immunofluorescence. Furthermore, electron microscopy was also performed. RESULTS: The histopathological examination results presented cases of C3GN (n = 111) and dense deposit disease (DDD; n = 17). The non-classified (NC) group was the most numerous (n = 204). The lack of classification was due to the poor severity of the lesions, even on the electron microscopic examination or in the presence of intense sclerotic lesions. CONCLUSIONS: In cases of suspected C3 glomerulopathies, we believe an electron microscopy examination is necessary. This examination is beneficial in mild-to-extremely-severe cases of this glomerulopathy, where the lesions are barely discernible when using immunofluorescence microscopy.

Prevalence of HPV and Assessing Type-Specific HPV Testing in Cervical High-Grade Squamous Intraepithelial Lesions in Poland.

The prevalence and distribution of oncogenic human papillomavirus (HPV) genotypes in women who underwent screening for cervical cancer in the Wielkopolska region, Poland, were assessed, and the correlation of genotypes with the histological results was evaluated. Cervical samples were collected from 2969 women for cervical cancer screening. Participants were screened by liquid-based cytology and HPV genotyping (n = 1654) and referred to colposcopy and punch biopsy (n = 616) if recommended. HPV genotypes 16, 31, 52, 66, 53, and 51 are the most frequent types in the studied population. Genotypes 16 and 31 account for nearly one-fifth of the infections of diagnosed HPV infections. HPV 16, 31, and 52 are found in nearly 80% of premalignant HSIL lesions (CIN 2 and CIN 3). That leads to the conclusion that vaccination programs should cover as many types of HPV as possible and shows the urgent need to vaccinate the Polish population with a 9-valent vaccine.

Expression of E4 Protein and HPV Major Capsid Protein (L1) as A Novel Combination in Squamous Intraepithelial Lesions.

We aim to describe the relationship between the immunohistochemical expression patterns of HPV E4 markers and the presence of HPV major capsid protein (L1) in cervical tissues obtained by biopsy of patients with abnormal liquid-based cytology (LBC) results, HR HPV infections, or clinically suspicious cervix. A novel HPV-encoded marker, SILgrade-E4 (XR-E4-1), and an HPV (clone K1H8) antibody were used to demonstrate the expression in terminally differentiated epithelial cells with a productive HPV infection in the material. A semiquantitative analysis was performed based on light microscope images. The level of E4 protein decreased with the disease severity. Patients with LSIL-CIN 1 and HSIL-CIN 2 diagnoses had significantly lower levels of HPV major capsid protein (L1) than those without confirmed cervical lesions. Our analysis confirms a higher incidence of L1 in patients with molecularly diagnosed HPV infections and excluded lesions of LSIL-CIN 1 and HSIL-CIN 2. Further studies on the novel biomarkers might help assess the chances of the remission of lesions such as LSIL-CIN 1 and HSIL-CIN 2. Higher levels of E4 protein and L1 may confirm a greater probability of the remission of lesions and incidental infections. In the cytological verification or HPV-dependent screening model, testing for E4 protein and L1 expression may indicate a group with a lower risk of progression of histopathologically diagnosed lesions.

IgG autoantibodies against ACE2 in SARS-CoV-2 infected patients.

How frequently autoantibodies against angiotensin-converting enzyme 2 (ACE2) occur in patients infected by SARS-CoV-2 is understudied and limited to investigations on a small sample size. The presence of these antibodies may contribute to the long-lasting effects of COVID-19 observed in some individuals, particularly if IgG-class antibodies would emerge in patients. This study assessed the prevalence of IgG autoantibodies against ACE2 in 1139 patients infected with SARS-CoV-2 and examined their relationship with severity, demographic characteristics, and status of vaccination against influenza. The overall prevalence of anti-ACE IgG antibodies in our cohort was 1.5%. Most of these individuals were men (76.5%) and underwent mild COVID-19, but some severe and asymptomatic cases were also observed. Patients with severe infection had twofold higher titers than mild and asymptomatic cases. Age, comorbidities, and influenza vaccination status were not related to antibody prevalence. The prevalence of IgG anti-SARS-CoV-2 antibodies (against nucleocapsid protein and S2 subunit, but not against receptor-binding domain) was higher in the subset with ACE2 autoantibodies. Further research is required to understand the potential spectrum and duration of effects of IgG autoantibodies against ACE2 in patients after SARS-CoV-2 infection, particularly concerning long COVID-19.

Surgical removal of Aquafilling localized to different sites.

<b><br>Introduction:</b> Aquafilling, a widely used soft-tissue filler since 2005, shows multiple adverse effects, necessitating the development of effective methods for its removal. We present a surgical method for removal of Aquafilling present in the breasts, breasts with migration to the chest and/or the abdomen, and the buttocks, and elaborate and discuss the advantages of this method.</br> <b><br>Aim:</b> The aim of this study was to present a surgical method for removal of Aquafilling (soft-tissue filler) present in the breasts, breasts with migration to the chest and/or the abdomen, and the buttocks, and to elaborate the advantages of this proposed technique.</br> <b><br>Materials and methods:</b> The surgical Aquafilling removal method described here was used in 25 patients (age, 21-53 years). The technique was used to remove Aquafilling present in the breasts (14 patients), breasts with migration to the chest and/or the abdomen (7 patients), and the buttocks (3 patients). The detailed course of Aquafilling removal surgery and postoperative treatment for these three types of cases is described.</br> <b><br>Results:</b> Surgical removal of Aquafilling with the described method did not cause any of the previously described ailments in each patient, excluding one patient who only showed significant pain reduction in both breasts preceding each menstruation cycle.</br> <b><br>Conclusions:</b> The method described herein can be recommended for removal of Aquafilling present in the breasts, breasts with migration to the chest and/or the abdomen, and buttocks, since it allowed thorough Aquafilling removal and decreased the local inflammatory state and the risk of potential carcinogenesis.</br>.

Relationship between Humoral Response in COVID-19 and Seasonal Influenza Vaccination.

There is evidence that vaccination against seasonal influenza can improve innate immune responses to COVID-19 and decrease disease severity. However, less is known about whether it could also impact the humoral immunity in SARS-CoV-2 infected patients. The present study aimed to compare the SARS-CoV-2 specific humoral responses (IgG antibodies against nucleocapsid; anti-N, receptor binding domain; anti-RBD, subunit S2; anti-S2, and envelope protein; anti-E) between non-hospitalized, COVID-19 unvaccinated, and mild COVID-19 convalescent patients who were and were not vaccinated against influenza during the 2019/2020 epidemic season (n = 489 and n = 292, respectively). The influenza-vaccinated group had significantly higher frequency and titers of anti-N antibodies (75 vs. 66%; mean 559 vs. 520 U/mL) and anti-RBD antibodies (85 vs. 76%; mean 580 vs. 540 U/mL). The prevalence and concentrations of anti-S2 and anti-E antibodies did not differ between groups (40-43%; mean 370-375 U/mL and 1.4-1.7%; mean 261-294 U/mL) and were significantly lower compared to those of anti-RBD and anti-N. In both groups, age, comorbidities, and gender did not affect the prevalence and concentrations of studied antibodies. The results indicate that influenza vaccination can improve serum antibody levels produced in response to SARS-CoV-2 infection.

Immunohistochemical Expression of Vitamin D Receptor in Uterine Fibroids.

One of the many factors involved in the development of uterine fibroids is vitamin D deficiency. One aspect of this deficiency is decreased serum concentration of calcidiol-25(OH)D, a metabolite of D3 vitamin. The active form of vitamin D3, which arises after numerous enzymatic reactions, is calcitriol-1,25(OH)2D3; this compound is transported to various body tissues. Vitamin D possesses extra-genomic effects due to its influence on various signaling pathways, i.e., through activating tyrosine kinases and by genomic effects via binding to a specific nuclear receptor, vitamin D receptor (VDR). The vitamin D/VDR complex regulates the expression of genes and is involved in the pathogenesis of fibroids. Numerous studies have shown that vitamin D supplementation reduces fibroid size. It has also been shown that the expression of VDR in myoma tissue is significantly lower than in the uterine muscle tissue at the tumor periphery. However, the expression of VDR in non-myoma uterine muscle has not previously been investigated. Our VDR expression studies were performed immunohistochemically with tissue microarrays (TMA) in three tissue groups: 98 uterine myoma tissues, 98 uterine tissues (tumor margin), and 12 tissues of normal uterine muscle (i.e., without fibroids). A statistical analysis showed significantly lower VDR expression in uterine muscle at the periphery of the fibroid than in healthy uterine muscle. Lower expression of VDR at the periphery of the myoma compared to that in normal uterine muscle may indicate potential for new myomas. This observation and the described reduction in the size of fibroids after vitamin D supplementation supports the hypothesis of causal development of uterine fibroids and may be useful for the prevention of re-development in the event of their excision from the uterus.

The role of selected molecular factors in ovarian cancer metastasis.

The main reason for treatment failure in ovarian cancer is chemoresistance and the presence of metastasis. Ascites, whichallows the physical movement of cancer cells, the lymphovascular pathway, and several molecular factors and signalling axes, are involved in metastasis. Ascites, with the involvement of cytokines and chemokines, MAPK/STAT1 and NOTCH as well as CXCL12/CXCR4 signaling pathways and circulating anoikis induces cancer dissemination, in particular to the peritoneum and omentum. The spread of lymphatic and bloodstream cancer cells is a multi-stage process. Tumour infiltration of the stroma and lymphovascular space (LVSI) produces biologically active cancer-associated fibroblasts and macrophages (CAFs, TAMs) that secrete numerous cytokines, chemokines and growth factors, inhibit NK function, induce epithelial-mesenchymal transition (EMT), resulting in an increase of the metastatic potential of cancer cells and the formation of cancer stem cells (CSCs). Overexpression of some genes, and microRNAs, in LVSI-(LMGS) associated with metastasis has been identified. The role of extracellular vesicles (EVs) transporting metastasis-associated factors has been described as has the role of cancer stem cells (CSCs) in chemotherapy resistance and metastasis. Sirtuins, enzymes involved in metastasis formation, have also been detected. Certain types of microRNAs (miR-509-3p, microRNA-506-3p) and melatonin have been shown to inhibit metastasis.

Evaluation of CD10 expression as a diagnostic marker for colorectal cancer.

Aim: We aimed to determine the potential of CD10 as a marker for the early diagnosis of adenocarcinoma of the colon. Background: Adenocarcinoma is diagnosed in one out of 20 individuals in the USA and western European countries. Its prognosis and treatment depend largely on the severity of the disease at the time of diagnosis. Additional new biological markers are being sought that can help diagnose colon cancer at an early stage. One such marker present in both serum and tumor tissue is CD10. Methods: CD10 concentrations were tested by ELISA and immunohistochemistry in serum and tissue samples, respectively, from 113 patients diagnosed histopathologically and treated for adenocarcinoma of the colon. Additionally, the ROC curve with optimal cut-off point based on Youden's criterion was calculated for CD10. Results: Serum concentrations of CD10 and its tissue expression in patients diagnosed with adenocarcinoma of the colon correlate with cancer staging based on the Astler-Coller-Dukes classification. To ascertain the optimal cut-off point for CD10 as a predictor of belonging to the study group, ROC curve was prepared for CD10. Optimal cut-off point for CD10 was 0.57, with prediction of belonging to the study group for CD10 ≥ 0.57. Conclusion: CD10 can be a useful marker in the early diagnosis of adenocarcinoma of the colon.

The absence of early malignant changes in women subjected to Aquafilling breast augmentation on the basis of E-cadherin and N-cadherin immunohistochemical expression.

The use of Aquafilling can be associated with a variety of health complications. The filler is an inflammatory process trigger at the site of tissue contact. The aim of this study was to semiquantitatively compare the immunohistochemical expression of E-cadherin and N-cadherin in tissue material from two groups of patients. The first group underwent surgical removal of Aquafilling from the breast, while the second was subjected to breast augmentation with implants or breast lifts (control group). The study group consisted of tissue samples from 16 patients who had Aquafilling removed, while the control group comprised samples from 16 patients who underwent breast augmentation with implants or breast lifts. Histopathology, immunohistochemistry and morphometric analyses were performed, taking into account the number of immunopositive cells and also the immunohistochemical reaction area for E-cadherin and N-cadherin. There were significantly more immunopositive N-cadherin cells in both groups. The immunohistochemical reaction area for N-cadherin did not differ between the two groups. However, the immunohistochemical reaction area for E-cadherin was significantly larger in the test group than in the control group. Moreover, the reaction area for N-cadherin was significantly smaller than that for E-cadherin. In the control group, no significant differences were detected between the immunohistochemical reaction area for N-cadherin and E-cadherin. Immunohistochemical evaluation of N-cadherin and E-cadherin tissue expression may be useful in assessing early cell junction changes. Furthermore, semiquantitative morphometric analysis allows these alterations to be more precisely determined.

Current Knowledge of Silver and Gold Nanoparticles in Laboratory Research-Application, Toxicity, Cellular Uptake.

Silver and gold nanoparticles can be found in a range of household products related to almost every area of life, including patches, bandages, paints, sportswear, personal care products, food storage equipment, cosmetics, disinfectants, etc. Their confirmed ability to enter the organism through respiratory and digestive systems, skin, and crossing the blood-brain barrier raises questions of their potential effect on cell function. Therefore, this manuscript aimed to summarize recent reports concerning the influence of variables such as size, shape, concentration, type of coating, or incubation time, on effects of gold and silver nanoparticles on cultured cell lines. Due to the increasingly common use of AgNP and AuNP in multiple branches of the industry, further studies on the effects of nanoparticles on different types of cells and the general natural environment are needed to enable their long-term use. However, some environmentally friendly solutions to chemically synthesized nanoparticles are also investigated, such as plant-based synthesis methods.

Usefulness of rebiopsy in the case of mesangial pathology.

Immunologically different types of glomerulopathies show varied symptoms and clinical courses. Unlike in lupus nephritis, repeated biopsy is rarely performed in cases of mesangial glomerulonephritis. We reviewed 200 cases wherein rebiopsy was performed in patients with diagnosed mesangial glomerular pathology over a 30-year period and analyzed the symptoms follow-up in these cases. Further, we evaluated the morphological changes between the first and final biopsies to identify cases of histological progression and histological remission and examined the correlation between such changes and clinical symptoms. The time between the first and last biopsies ranged from 7 months to 35 years. The most common for the initial biopsy was nephrotic syndrome, followed by non-nephrotic proteinuria; other symptoms occurred rarely. Histological progression occurred at various stages of observation, ranging from within a few months to after several years. Histological progression and remission were detected in 118 and 3 patients, respectively, whereas there was no difference in morphological findings between the first and last biopsies in 79 patients. Rebiopsy is useful in patients who do not respond adequately to treatment, and especially in those with increased clinical symptoms. Moreover, electron microscopic examination is necessary to discover early signs of histological progression.