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Atypical ductal hyperplasia diagnosed at stereotaxic core biopsy of breast lesions: an indication for surgical biopsy.

OBJECTIVE: The purpose of this study was to evaluate the prevalence of carcinoma found at surgical biopsy of lesions identified as atypical ductal hyperplasia by stereotaxic core breast biopsy. SUBJECTS AND METHODS: Stereotaxic core biopsies of 264 mammographically evident lesions were done with the patients lying prone on a dedicated stereotaxic table, with an automated gun and a 14-gauge needle. Atypical ductal hyperplasia was identified in 25 (9%) of 264 lesions, including four (3%) of 159 masses and 21 (20%) of 105 lesions evident as calcifications. Surgical biopsy was recommended in all 25 of these cases and was performed in 21. Results of stereotaxic core biopsy and surgery in these 21 cases were reviewed and correlated. RESULTS: Of 21 cases identified as atypical ductal hyperplasia at stereotaxic core biopsy that were subsequently evaluated with surgical biopsy, histopathologic analysis of the surgical specimen yielded benign histologic findings without atypia in four (19%), atypical ductal hyperplasia in six (29%), and carcinoma in 11 (52%). Of the 11 carcinomas, histologic findings showed ductal carcinoma in situ in eight (73%) and invasive ductal carcinoma in three (27%). CONCLUSION: The finding of atypical ductal hyperplasia at stereotaxic core breast biopsy is an indication for surgical biopsy because of the high prevalence of ductal carcinoma in these lesions.

Biopsy, Needle↗

Triphasic helical CT of hepatic focal nodular hyperplasia: incidence of atypical findings.

OBJECTIVE: The objective of this paper is to assess the findings of focal nodular hyperplasia of the liver as depicted by triphasic helical CT. MATERIALS AND METHODS: Triphasic helical CT scans (arterial, portal vein, and delayed phase scans) in 12 patients with hepatic focal nodular hyperplasia were reviewed to assess the frequency of findings on each phase. The final diagnosis of focal nodular hyperplasia was proven by surgery or biopsy in eight cases and by additional imaging studies and clinical follow-up in four cases. RESULTS: Only two of the 12 patients had CT features that could be considered typical of focal nodular hyperplasia. The other patients had one or more findings considered to be atypical and more suggestive of a primary or metastatic hypervascular malignant hepatic neoplasm, such as an enhancing capsule, lack of a central scar, early draining veins, rapid washout of contrast material on the portal vein phase or persistent enhancement on the delayed phase, and interim growth. CONCLUSION: Although classic or typical triphasic helical CT manifestations of focal nodular hyperplasia do occur, atypical features are common and can mimic those of primary or metastatic hypervascular hepatic neoplasms. In these latter cases, additional imaging studies, such as a 99mTc-sulfur colloid liver scan, an MR scan, or a percutaneous biopsy, are essential for correct diagnosis.

Adult↗

Effects of an extract of Serenoa repens on dogs with hyperplasia of the prostate gland.

OBJECTIVE: To determine effects of an extract of Serenoa repens on dogs with prostatic hyperplasia. ANIMALS: 20 mature male dogs with benign prostatic hyperplasia. PROCEDURE: Dogs were assigned to 3 comparable groups on the basis of prostatic volume per kg of body weight and degree of prostatic hyperplasia determined histologically. Dogs in 2 groups were treated for 91 days (8 received 500 mg, PO, q 8 h [1,500 mg/d], and 6 received 100 mg, PO, q 8 h [300 mg/d]). The control group of 6 dogs did not receive medication. Effects of treatment on prostatic volume, prostatic weight, prostatic histologic characteristics, radiographic and ultrasonographic assessment of prostatic size, results of CBC, serum biochemical analyses, and urinalysis, serum testosterone concentration, and semen characteristics were determined. At the termination of the study, all dogs were euthanatized, and necropsies were performed. Investigators conducting tests and interpreting results were not aware of treatment group of each dog. RESULTS: Treatment did not affect prostatic weight, prostatic volume, or prostatic histologic scores, libido, semen characteristics, radiographs of the caudal portion of the abdomen, prostatic ultrasonographs, or serum testosterone concentrations. Results of CBC, serum biochemical analyses or urinalysis, and body weights did not change during treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with an extract of S repens for 91 days did not significantly affect the prostate gland of dogs. Adverse effects were not evident. Although products containing extracts of S repens are widely advertised for men with prostatic hyperplasia, beneficial or harmful effects of this plant extract were not found in dogs with prostatic hyperplasia.

Animals↗

Transforming growth factor-beta1 expression and the role of angiotensin-converting enzyme inhibitor on perianastomotic intimal hyperplasia in polytetrafluoroethylene graft implanted in rabbit carotid artery.

The purpose of this study was to evaluate the relationship between intimal hyperplasia and transforming growth factor-beta1 (TGF-beta1) mRNA expression in synthetic arterial grafts and also to clarify the effect of angiotensin-converting enzyme inhibitor (ACEI) on perianastomotic intimal hyperplasia and TGF-beta1 mRNA expression. Thirty New Zealand White rabbits were randomly divided into two groups (15 each); one group was administered Captopril 10 mg/kg/day per os as an ACE inhibitor, and the other group received on saline as a vehicle from 7 days prior to operation until the graft was harvest (1, 8, or 14 weeks). A 10-mm segment of an expanded polytetrafluoroethylene graft (3 mm in diameter) was implanted in the right common carotid artery of the rabbits; 15 rabbits had by-pass grafting alone (Graft Alone group) and the other 15 rabbits had by-pass graft along with the ACEI (Graft plus ACEI group). The artery grafts were harvested. The intima to media height ratio (IMHR) and the TGF-beta1 mRNA expression level in perianastomotic graft tissue by reverse transcription-polymerase chain reaction (RT-PCR). The IMHRs gradually increased from 1 to 14 weeks in both groups (vs. 1 wk in each group, p<0.05). The IMHRs of the Graft plus ACEI group were comparable to those of Graft Alone group at 1 week, but significantly lower at 8 and 14 weeks (vs. Graft Alone group, p<0.05). The TGF-beta1 mRNA expression levels of the Graft plus ACEI group were clearly lower than those of the Graft Alone group at 1 and 8 weeks (vs. Graft Alone group, p<0.05), but similar at 14 weeks. TGF-beta1 in the synthetic artery graft of the Graft Alone group was up-regulated as early as 1 week after the operation, when no definitive development of a quantifiable neointima was observed. The TGF-beta1 mRNA expression of the Graft Alone group was highest at 8 weeks and lowest at 14 weeks (vs. 1 week, *p<0.05), but such time-dependent changes were not observed in the Graft plus ACEI group. The results indicated that ACEI reduced intimal hyperplasia in the grafts of the Graft plus ACEI group and also suppressed TGF-beta1 mRNA expression in perianastomotic intimal hyperplasia tissues to the normal artery level. Perianastomotic intimal hyperplasia in synthetic arterial graft is considered to be related to TGF-beta1, the expression of which is locally mediated by angiotensin II and, therefore, suppressed by ACEI.

Anastomosis, Surgical↗

Argyrophil cell hyperplasia associated with chronic corpus gastritis in gastric ulcer disease.

Argyrophil cell (AC) hyperplasia in corpus mucosa was investigated in 53 patients with chronic gastric ulcer disease not previously treated with antisecretory drugs. Mucosal biopsies were taken stepwise from the posterior wall in the corpus area of the stomach. Of 117 biopsy sites, 28 showed gastritis without atrophy, 85 showed chronic atrophic gastritis of varying degrees while 4 biopsies showed a normal mucosa. About one third (38%) showed a normal AC pattern. Of the remaining two thirds (62%), 45% had simple AC hyperplasia, 18% had linear and 37% had micronodular AC hyperplasia. A strong association was found between focal (linear/micronodular) AC hyperplasia and chronic atrophic gastritis. It is concluded that focal AC hyperplasia is a common phenomenon in gastric ulcer patients and is inherently related to the spontaneous development of atrophy in the corpus mucosa of these patients.

Adult↗

A case of unilateral adrenal hyperplasia: the diagnostic dilemma of hyperaldosteronism.

OBJECTIVE: To report the successful laparoscopic surgical management of a case of right unilateral adrenal hyperplasia. METHODS: We present a case of unilateral adrenal hyperplasia and review the pertinent literature. The effectiveness of surgical treatment of unilateral adrenal hyperplasia is evaluated. RESULTS: A 50-year-old man had a 7-year history of hypertension, which had been treated with antihypertensive medications. On initial assessment, he was taking long-acting diltiazem, 240 mg twice a day, and his blood pressure was 150/84 mm Hg. He was noted to have recurrent hypokalemia, low plasma renin activity, increased plasma aldosterone concentration, and high urinary aldosterone levels. Magnetic resonance imaging of the adrenal glands revealed a normal left adrenal gland and fullness of the right adrenal gland. Selective adrenal vein catheterization showed findings consistent with a right-sided adrenal gradient. Surgical removal of the right adrenal gland laparoscopically alleviated his symptoms and cured his hypertension and hypokalemia. Pathologic examination of the right adrenal gland revealed diffuse hyperplasia of the zona fasciculata and zona reticularis. Plasma aldosterone, renin, and potassium levels returned to normal postoperatively, and his blood pressure declined to 120/70 mm Hg. At 1-year follow-up, the patient remained normotensive without the need for antihypertensive agents. CONCLUSIONS: This rare type of hyperaldosteronism, known as unilateral adrenal hyperplasia, is difficult to categorize not only because it fails to typify a conventional subtype but also because it is difficult to confirm the pathologic diagnosis. Recognition of the variety of provocative, biochemical, and imaging results that may be seen in this disorder is important in making the correct diagnosis. Determining unilaterality of disease by selective adrenal vein sampling can result in a cure of hypertension and hypokalemia by surgical resection.

Adrenal Glands↗

Prostate elastosis: a microscopic feature useful for the diagnosis of postatrophic hyperplasia.

BACKGROUND: Elastosis of the prostate may be seen on needle biopsy and radical prostatectomy specimens, but its significance is unknown. Prostatic atrophy (or postatrophic hyperplasia) is one of the most frequent mimics of prostatic adenocarcinoma. OBJECTIVE: To observe the frequent occurrence of elastosis of the prostate stroma in areas of postatrophic hyperplasia. DESIGN: A step-section method was used to cut the posterior lobe (or peripheral zone) in coronal planes at intervals of 0.3 to 0.5 cm in 100 consecutive autopsy specimens of men older than 40 years. Elastosis was detected because of a basophilic tinge of the stroma on hematoxylin-eosin stain and confirmed using elastic fiber stains. Presence of elastosis correlated with the following variables: age, prostatic atrophy (simple, hyperplastic, or sclerotic), local arteriosclerosis, histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. For statistics, a stepwise linear regression method adjusted for age was used. RESULTS AND CONCLUSIONS: Elastosis was found in 65 of the prostates examined and was significantly more frequent with increasing age (P <.001), prostatic atrophy (P <.001), and local arteriosclerosis (P <.02). There was no significant relation to histologic carcinoma, high-grade prostatic intraepithelial neoplasia, benign or malignant nephrosclerosis, generalized atherosclerosis, nodular prostatic hyperplasia, and acute inflammation. The correlation with local arteriosclerosis favors a possible role of ischemia to its etiopathogenesis. The absence of correlation to neoplastic and preneoplastic lesions and the striking spatial relationship of elastosis to prostatic atrophy (or postatrophic hyperplasia) add a new microscopic feature for the diagnosis of this latter lesion, helping in the differential diagnosis with prostate adenocarcinoma.

Adult↗

Extranodal posttransplant plasmacytic hyperplasia with subsequent posttransplant plasmacytic malignancy: six-year interval case report and review of the literature.

Posttransplant lymphoproliferative disorders (PTLDs) represent a morphologic, immunophenotypic, and genotypic spectrum of disease. Most recently, Knowles et al divided PTLDs into 3 distinct categories: (1) plasmacytic hyperplasia, (2) polymorphic B-cell hyperplasia and polymorphic B-cell lymphoma, and (3) immunoblastic lymphoma and multiple myeloma. Although one form of PTLD may progress to another form, only 1 previous case has been reported in which multiple myeloma developed 14 months after an original diagnosis of plasmacytic hyperplasia. The type of solid organ transplant was not specified in that case. We report a post--cardiac transplant plasmacytic hyperplasia developing 7 years posttransplant. Six years subsequent to the plasmacytic hyperplasia, the patient developed a posttransplant plasmacytic malignancy, supported by morphology, flow cytometric immunophenotyping, and genotypic studies. Since we have no data to support disseminated bony disease or an abnormal serum protein, we have not used the term "multiple myeloma" for this case.

DNA, Neoplasm↗

Early nodular hyperplasia of the liver occurring with inflammatory bowel diseases in association with thioguanine therapy.

CONTEXT: Nodular hyperplasia (also referred to as nodular regenerative hyperplasia and nodular regenerative hyperplasia of the liver) is a sequel to therapy with thioguanine in patients with hematologic malignancies. Recently, 6-thioguanine has been used to treat patients with inflammatory bowel disease who have been resistant to other forms of therapy. OBJECTIVE: To study liver biopsies from 3 patients with inflammatory bowel disease who had received thioguanine for more than a year, and who had elevated serum liver enzyme values and underwent percutaneous liver biopsy. DESIGN: Percutaneous liver biopsies and histologic examinations were performed, including staining with the reticulin silver impregnation method. RESULTS: All 3 patients had foci of nodular regenerative hyperplasia, which was best seen with the reticulin silver impregnation method. CONCLUSIONS: Thioguanine-treated inflammatory bowel disease patients are at risk for the development of nodular hyperplasia. Reticulin-stained histologic sections are necessary to recognize this change. Further studies are needed to determine the frequency and significance of this change.

Adult↗

Hypergastrinemia and enterochromaffin-like cell hyperplasia.

UNLABELLED: The enterochromaffin-like (ECL) cells, the most frequent endocrine cells of the oxyntic mucosa of the stomach, are under the trophic stimulus of gastrin. These cells undergo a hyperplastic increase in variety of hypergastrinemic diseases. The most widely accepted nomenclature for the description of hyperplastic proliferation has been retrospectively arranged in a sequence presumed to reflect a temporal evolution of the proliferative process. A comparative, prospective study aimed to verify, in human hypergastrinemic diseases such as atrophic body gastritis (ABG), Zollinger-Ellison syndrome (ZES) and antral gastrin cell hyperfunction (AGCH), the effect of exposure of ECL cells to different pattern of gastrin hypersecretion, is lacking. To this purpose, we studied a series of consecutive patients with ABG, ZES and AGCH at the time of first diagnosis. MATERIAL AND METHODS: The patients included in this study (124 ABG, 18 ZES and 10 AGCH) were selected on the basis of two previously performed screening studies aimed to diagnose these diseases. All patients at the time of diagnosis underwent gastroscopy, with multiple biopsies of the gastric body mucosa for the evaluation of qualitative pattern of ECL cells hyperplasia, and basal fasting gastrin determination. A sample of hypergastrinemic patients from each group was further investigated by meal-stimulation of gastrin secretion and quantitative morphometry for CgA positive gastric body endocrine cells. RESULTS: AGCH patients showed only the normal or simple hyperplasia pattern. In the ZES group, simple and linear grades accounted for 38.4 percent and 46.1 percent, respectively. MEN-I patients showed only these two patterns. The majority of ABG patients showed the presence of micronodular pattern (59.7 percent). A correlation analysis between fasting gastrin levels and grade of hyperplasia (r = 0.5580, p < 0.0001), indicates that the greater the gastrin levels, the higher is the degree of severity of ECL hyperplasia pattern. In conclusion, our data support the role of gastrin as the selective contributor to the progression of ECL cell hyperplasia in humans.

Adolescent↗

Surgical treatment and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia: 56 cases (1994-1997).

OBJECTIVE: To determine signalment, clinical signs, concurrent diseases, response to surgical treatment, and long-term outcome of ferrets with bilateral adrenal tumors or adrenal hyperplasia. DESIGN: Retrospective study. ANIMALS: 56 ferrets with bilateral adrenal tumors or adrenal hyperplasia confirmed histologically following subtotal bilateral adrenalectomy. PROCEDURE: Medical records of all ferrets with bilateral adrenal tumors or hyperplasia examined between 1994 and 1997 were reviewed. Ferrets underwent a subtotal bilateral adrenalectomy or a unilateral adrenalectomy initially, followed by a unilateral subtotal adrenalectomy when tumors or hyperplasia later developed on the contralateral adrenal gland. A long-term follow-up of a minimum of 18 months after final adrenal gland surgery was obtained by examination of medical records and follow-up telephone conversations. RESULTS: Clinical signs of hyperadrenocorticism included bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy (or unilateral adrenalectomy followed by contralateral unilateral subtotal adrenalectomy) was effective with a mortality rate of < 2%. Only 3 (5%) ferrets required glucocorticoid or mineralocorticoid replacement following subtotal bilateral adrenalectomy. Recurrence after bilateral adrenalectomy was 15% with a mean long-term follow-up period of 30 months. CONCLUSIONS AND CLINICAL RELEVANCE: Bilaterally symmetric alopecia, return to male sexual behavior in castrated male ferrets, or swollen vulva in spayed female ferrets are indicative of adrenal tumors or adrenal hyperplasia in ferrets. Surgical treatment of bilateral adrenal disease by subtotal bilateral adrenalectomy is effective, with a low rate of complications and postoperative recurrence rate.

Adrenal Gland Neoplasms↗

Estimation of neovascularisation in hyperplasia and carcinoma of endometrium using a "power" angio-Doppler technique.

The aim of this study was to estimate neovascularisation in hyperplasia and carcinoma of the endometrium using a "power" angio-Doppler technique. One hundred and eighty-two postmenopausal patients with irregular bleeding from the sexual organs were investigated. Age of the patients ranged between 46 and 78 years. No neovascularisation in a control group of women with normal histopathological results of the endometrium was observed. The sensitivity of this method with reference to the diagnosis of hyperplasia and cancer of the endometrium was 12.2% and 81.2%, respectively. The specificity and positive prediction values were equal to 100% each in both pathologies. The values of the analysed flow indices in the neovascular arteries in endometrial cancer were significantly lower (p<0.05) (properly PI-0.92+/-0.12; RI-0.46+/-0.08) in comparison to the corresponding values in hyperplasia of the endometrium (PI-1.38+/-0.28 and RI-0.66+/-0.18). In conclusion, using a "power" angio-Doppler technique irregular vascularity of the endometrium in a group of patients with hyperplasia was observed in 12.2% of all patients and in 81.2% of those with cancer of the endometrium. The analysis of the values of the blood flow qualitative parameters in the neovascularisation areas in the endometrium at the significance level of PI < or = 1.0; RI < or = 0.5 and TAMV > 18.0 cm can help determine the essential element in the differential diagnosis of benign and malicious lesions. Transvaginal ultrasonography with a "power" angio-Doppler technique can be a valuable diagnostic method in hyperplasia and cancer of the endometrium, especially useful in the early stages of these pathologies.

Adenocarcinoma↗

Results of liver transplantation for nodular regenerative hyperplasia.

Liver transplantation has been performed in individuals with a pretransplant clinical diagnosis of cirrhosis but with nodular regenerative hyperplasia histologically. The purpose of this report is to investigate the results of liver transplantation in patients proven to have nodular regenerative hyperplasia post-transplant. A retrospective review was undertaken of four patients who underwent liver transplantation with a histologic diagnosis of nodular regenerative hyperplasia. All were felt to be cirrhotic on clinical grounds. Final histology of the explanted liver was confirmed by a single pathologist. Their ages ranged from 39 to 54 years, and three of the four were male. Three had pretransplant needle liver biopsies, two percutaneous and one transjugular. All revealed nonspecific reactive changes. Ultrasound and MRI were interpreted as consistent with cirrhosis in four of four and three of four cases, respectively. Portal vein flow was hepatopedal in three and absent in one. Pretransplant clinical characteristics and frequency were as follows: bleeding varices two, clinical ascites three, encephalopathy three, and impaired hepatic synthetic function two. All four patients underwent successful liver transplantation. There were no episodes of acute rejection. All are alive and well with normal graft function 2 to 4 years post-transplant. We conclude the following. 1) Patients with clinical end-stage liver disease due to underlying nodular regenerative hyperplasia can successfully undergo transplantation. 2) Nodular regenerative hyperplasia can present with signs and symptoms of liver failure, is difficult to diagnose by needle biopsy, and can be difficult to discriminate clinically from cirrhosis. 3) Although each case must be individually evaluated transplantation may be the optimal therapy in patients presenting with complications of liver failure.

Adult↗

Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.

This study was conducted to determine if osteoporosis in male leprosy patients is caused by testicular atrophy. Bone volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), and trabecular separation (TbSp) were measured in two areas in decalcified paraffin sections of lumbar bones from 29 male leprosy and 6 male nonleprosy autopsy cases. We found significant differences in the average BV/TV measurements among the 7 patients with nodular Leydig cell hyperplasia (BV/TV 12.24%) and the 22 patients without hyperplasia (BV/TV 7.35%) and 6 patients without leprosy (BV/TV 12.98%). Bone volume was maintained in patients with nodular Leydig cell hyperplasia, and we determined no clinical factor other than the Leydig cell hyperplasia that reflected the bone volume. The osteoporosis of male leprosy patients was attributed to secondary gonadal dysfunction due to testicular atrophy, and Leydig cell hyperplasia appears to preserve bone volume.

Aged↗

Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer.

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibitor type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expression and the prognostic significance of these enzymes in endometrial hyperplasia and cancer. We used immunohistochemical staining to localize uPA and PAI-1 antigens and evaluate their expression, and the enzyme-linked immunosorbent assay (ELISA) to measure their levels during the progression of endometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematically weak in simplex hyperplasia and are moderate in complex hyperplasia. In the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was found only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic glands and at the apex of the malignant cells. The PAI-1 immunoreactivity was weak to moderate in 95.4% of carcinomas, with a diffuse signal mostly distributed in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen concentrations were significantly higher in endometrial carcinoma than in endometrial hyperplasia (p<0.05) and in normal endometrium (p<0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was not statistically significant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prognostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carcinoma there is a progressive increase in expression of uPA and PAI-1 than in normal endometrial tissue. In carcinoma tissues, the high expression of uPA is unregulated in the surrounding stroma tissue, particularly in the most aggressive histopathologic variants. UPA and PAI-1 may be factors associated with invasive behavior in endometrial carcinoma independent of other clinicopathological parameters.

Adenocarcinoma↗

[Quantitative evaluation of the activity of nuclear Ca2+/Mg2+-dependent endonucleases in hyperplasia and cancer of the endometrium].

Endometrial carcinoma is the most incident cancer of human reproductive system. There are unequivocal evidences of relationship between complex and atypical hyperplasia and development of cancer. Apoptosis plays a significant role in the maintenance of equilibrium between cell death and proliferation and contributes to prevention of tumorigenesis. Internucleosomal DNA fragmentation known as one of the most important criteria of apoptosis cannot be used for evaluating the risk of cancer development because it reflects the current level of apoptosis but is useless for evaluating the real limits of apoptosis intensity in certain types of tissue. For estimating the possibility of apoptosis development in endometrial tissues, a new method of quantitation of nuclear Ca(2+)/Mg(2+)-dependent endonuclease (NCME) activity has been developed. Fifteen samples of normal endometrial tissues at middle proliferative, secretory, premenstrual, and menstrual phases, 43 samples of hyperplastic endometrial tissues, 13 samples of endometrial polyps, and 17 samples of endometrial adenocarcinoma were collected by diagnostic curettage of the uterine cavity and by hysterectomy (carcinomas). The material was examined by 1) TUNEL method and 2) agarose gel electrophoresis of DNA cleaved by nuclear CME in isolated cell nuclei in the presence of Ca(2+) and Mg(2+) ions, followed by quantitation of CME activity. The activity of NCME was found to decrease from normal endometrium (1.1 +/- 0.12 U, without significant changes throughout the menstrual cycle) through polyps (0.9 +/- 0.15 U), cystic hyperplasia (0.45 +/- 0.06 U, p < 0.01), and adenomatous hyperplasia (0.32 +/- 0.08 U, p < 0.01) to adenocarcinoma (0.37 +/- 0.11 U, p < 0.01 for well differentiated, 0.16 +/- 0.08 U, p < 0.01 for moderately differentiated, and 0.03 +/- 0.02 U, p < 0.01 for poorly differentiated samples). The TUNEL-specific staining pattern in normal endometrium varied in a wide range during the menstrual cycle (from poorly stained individual cells in the proliferative phase to intensely stained cell clusters in the premenstrual phase). At the same time the difference between the normal endometrium in the proliferative phase and pathologically changed endometrium (hyperplasia or cancer) could not be detected by the TUNEL technique. Hence, TUNEL is useless for predicting cancer development in hyperplasia and precancer. By contrast, evaluation of NCME activity helps detect the early disorders in the proliferative processes coursing in endometrial tissues and thus prevent tumor development.

Adenocarcinoma↗

Vitamin D receptor and PCNA expression in severe parathyroid hyperplasia of uremic patients.

OBJECTIVE: To clarify the role of vitamin D receptor (VDR) expression in parathyroid proliferation and resistance of parathyroid glands to 1,25(OH)2D3 with secondary hyperparathyroidism (SHPT). METHODS: This study used archive parathyroid with 7 uremic patients. The expression of proliferation cell nuclear antigen (PCNA) and VDR was evaluated in nineteen-surgically excised parathyroid tissues, including 11 diffuse hyperplasia (DH-type) and 8 nodular hyperplasia (NH-type) of parathyroid glands, by immunohistochemistry (avidin-biotin complex method). RESULTS: The weight of parathyroid in SHPT was remarkably increased by 16.1 times. The numbers of parathyroid cells were increased by 1.86 times. The rate of PCNA was remarkably increased in parathyroid hyperplasia with SHPT compared with that in control group [(6.35 +/- 3.36)@1000 vs (1.73 +/- 1.31)@1000, P < 0.001]. The number of PCNA in DH-type was lower than that in NH-type (P < 0.001). The density of VDR in the parathyroid with SHPT was significantly decreased [(40.28 +/- 13.13)% vs (83.79 +/- 3.77)%, P < 0.001], VDR immunoreactivity expression in NH-type was lower than that in DH-type [(27.14 +/- 4.12)% vs (49.84 +/- 7.33)%, P < 0.001]. A significantly negative correlation was found between VDR density and the weight of the parathyroid (r = -0.46, P < 0.05), the same as VDR and PCNA (r = -0.75, P < 0.001). CONCLUSION: VDR density was significantly decreased in parathyroid tissue of uremic patients showing nodular hyperplasia compared with that in diffuse hyperplasia and there was significantly negative correlation between VDR density and the weight of the parathyroid, and this may contribute to the progression of SHPT. Furthermore, VDR deficiency may cause the resistance of parathyroid cells to 1,25(OH)2D3, in part.

Adult↗

[Evaluation of diagnosis of endometrial hyperplasia by curettage].

OBJECTIVE: To evaluate the accuracy of diagnosing endometrial hyperplasia (EH) by curettage. METHODS: 150 cases who had been diagnosed as EH by curettage and received hysterectomy shortly after were studied retrospectively. All of the specimens obtained from curettage and operation underwent pathological examination. The results of pathological diagnosis of these two kinds of specimens were compared. Proliferating cell nuclear antigen (PCNA) expression was examined by immunohistochemistry in 38 cases diagnosed as complex atypical hyperplasia (CAH). RESULTS: Fifty-three cases were diagnosed as simple hyperplasia (SH), eleven cases as complex hyperplasia (CH), twenty-six cases as simple atypical hyperplasia (SAH), and sixty cases as CAH by curettage. Rediagnosis was made for all patients after hysterectomy. Pathological examination of the specimens from operation diagnosed 65 cases as SH, 7 cases as CH, 15 cases as SAH, 29 cases as CAH, and 34 cases as EC. The general accuracy of histological diagnosis by curettage was 76.7% approximately 92.6%. Coexistence with EC was more common in cases with SAH and CAH than in cases with SH and CH (chi(2) = 26.3, P < 0.01). Coexistence with EC was more common in cases with CAH than in cases with SAH (chi(2) = 9.78, P < 0.005). Among the CAH cases, coexistence with EC was more common in postmenopausal patients than in premenopausal patients (chi(2) = 3.93, P < 0.05). Among the CAH cases, the positive rate of PCNA expression was higher and strength of positivity greater in those cases with EC (Uc = 3.66, P < 0.05). CONCLUSION: The accuracy of curettage is rather high in diagnosing SH and relatively low in diagnosing CAH. CAH often coexists with EC. Examination of PCNA expression may help differentiate between CAH and EC.

Adult↗