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Calcification and osteopontin localization in the peritoneum of patients on long-term continuous ambulatory peritoneal dialysis therapy.

BACKGROUND: Peritoneal calcification is an uncommon complication of continuous ambulatory peritoneal dialysis (CAPD), which is mainly observed in patients on long-term therapy. Although some asymptomatic patients must have microscopic calcification in their peritoneum, little information on this topic has been published. Recent studies have revealed active participation of adhesive/chemotactic protein osteopontin (OPN) in dystrophic calcification. METHODS: Peritoneal tissue was obtained by biopsy or at autopsy from 18 CAPD patients (median duration, 122 months), 5 control haemodialysis (HD) patients, and 3 pre-CAPD patients. The distribution of calcium deposits and OPN protein was determined by von Kossa staining and immunohistochemistry, respectively. Smooth muscle cells and macrophages were identified with anti-alpha smooth muscle actin (alpha-SMA) and anti-CD68 antibodies. RESULTS: Calcium deposits with various configurations were observed in specimens from 12 of the 18 CAPD patients. They included massive calcification facing the peritoneal cavity, scattered granular or crystalloid deposits in the submesothelial stroma, and oval-shaped deposits formed within hyalinized vasa. Most were present in highly sclerosed areas and accompanied by extracellular OPN precipitation. Cytoplasmic OPN was detected in infiltrating leukocytes, granulation tissue cells, fibroblast-like cells and mast cells. Computerized tomography examination also detected peritoneal calcification in seven of the CAPD patients. No calcium deposits or OPN staining was detected in control specimens. CONCLUSIONS: The results of our study suggest that microscopic peritoneal calcification is frequent in patients on CAPD for more than 10 years. Myofibroblast infiltration, OPN expression, calcium deposition, and associated OPN precipitation seem to be components of the peritoneal changes in such patients.

Adult↗

Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis.

Peritoneal membrane fibrosis, ranging from mild inflammation to severe sclerosing peritonitis, is one of the complications of peritoneal dialysis (PD). In parallel with fibrosis, the peritoneum shows a progressive increase of capillaries and vasculopathy, involved in increased small solute transport across the membrane and ultrafiltration failure. Glucose and glucose degradation products from PD solutions are responsible of stimulating transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGF-beta is a potent pro-fibrotic factor and inducer of epithelial-to-mesenchymal transition (EMT) of the MC. Local production of VEGF by transitional MC appears to play a central role in the processes leading to peritoneal angiogenesis. This review addresses the mechanism involved in peritoneal structural alteration by dialysis and points to the EMT of MC as the initiating mechanism of peritoneal injury. Information from multiple origins about TGF-beta and VEGF is integrated into EMT process in a comprehensive manner. Regulation and new targets for inhibition of EMT or its deleterious effects are discussed.

Epithelial Cells↗

Necrotic pseudoxanthomatous nodules of ovary and peritoneum in endometriosis.

The clinical and pathological features of four unusual cases of pelvic endometriosis are described. The patients, who were between the ages of 40 and 72 years, underwent operations for uterine leiomyomas in two cases, endometrial adenocarcinoma in a third case, and an enlarging abdominal mass in a fourth case. In three patients, two of whom had enlargement of one or both ovaries, multiple nodules were either attached to the peritoneum (two cases) or lay free in the peritoneal cavity (one case). In one of these cases, the intraoperative findings mimicked metastatic carcinoma. Histological examination of the peritoneal lesions, as well as the ovaries in all the cases, revealed granulomatous nodules composed of a central focus of necrotic tissue surrounded by histiocytes (pseudoxanthoma cells), hyalinized connective tissue, or both. Endometriotic glands and stroma were typically absent in the nodules and their immediate vicinity. Foci of recognizable endometriosis, however, were found in the ovaries in all the cases. In one of the ovaries, several necrotic nodules lined an endometriotic cyst; in another, a focus had an appearance transitional between endometriosis and a necrotic nodule. These necrotic pseudoxanthomatous nodules are a previously undescribed manifestation of endometriosis; they occur characteristically in older women. On histologic examination, they should be distinguished from other necrotic peritoneal and ovarian granulomas, as well as necrotic tumor.

Adult↗

Localized and diffuse mesotheliomas of the genital tract and peritoneum in women. A clinicopathologic study of nineteen true mesothelial neoplasms, other than adenomatoid tumors, multicystic mesotheliomas, and localized fibrous tumors.

Peritoneal mesotheliomas are rare in women, compared to serous epithelial neoplasms with which they are often confused. We evaluated the clinicopathologic features of 19 true mesothelial neoplasms affecting the genital tract or peritoneum of women (other than adenomatoid tumors, benign multicystic mesotheliomas, and localized fibrous tumors) to characterize their clinicopathologic features and to determine their clinical behavior. Six tumors were localized to one anatomic site at presentation, and 13 involved more than one anatomic site. The six localized tumors were solitary, small (0.8-2.0 cm), polypoid or nodular lesions, five of which were incidental findings. All had a predominantly tubulopapillary pattern, either pure or mixed with adenomatoid-like or small solid foci. Nuclear grade ranged from 0 to 2. Mitotic figures (MF) were absent in two tumors. The mitosis count in the other four tumors was < 1 MF/10 high-power microscopic fields (HPF) (average method) and ranged from 1 to 3 MF/10 HPF (highest count method). Five patients were alive without recurrence after postoperative intervals ranging from 19 months to 9 years (median, 5 years); one patient died of metastatic gastric carcinoma at 14 months. Thirteen tumors involved more than one anatomic site and were classified as diffuse mesothelioma. Typically, these tumors were symptomatic and accompanied by ascites. The tumors had either a plaque-like or endophytic configuration. Eleven were purely epithelial mesotheliomas, and two had a minor sarcomatoid component. Tubulopapillary patterns were present in 10 tumors, usually admixed with focal adenomatoid-like or solid patterns, and three had a purely solid pattern. All 13 tumors had grade 3 nuclei. The mitosis count ranged from < 1 to 2 MF/10 HPF (average count method) with a range of 1-4 MF/10 HPF by the highest count method. Immunohistochemically, 13/13 tumors stained for cytokeratin (AE1/AE3). None were immunoreactive for polyclonal carcinoembryonic antigen (CEA), Leu-M1, or B72.3. One diffuse mesothelioma stained focally for Ber-EP4, and electron microscopy confirmed the mesothelial nature of this tumor. Nine patients died of tumor after postoperative intervals ranging from 1 month to 6 years. Eleven patients had received postoperative adjuvant intraperitoneal or systemic chemotherapy. One patient died with increased abdominal girth 8 years after operation and one course of intraperitoneal chemotherapy, though the role of mesothelioma in her death was uncertain. One patient was alive with diffuse tumor and persistent ascites 25 months after six courses of intraperitoneal chemotherapy. One patient was alive without evidence of disease 4 months after two courses of systemic chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenomatoid Tumor↗

Malignant mesothelioma of the peritoneum presenting as an inflammatory lesion: a report of four cases.

Most cases of malignant mesothelioma present with obvious diffuse tumor, and the presence of grossly visible diffuse tumor is usually cited as an important criterion for making the diagnosis. We report four cases of unsuspected malignant mesothelioma of the peritoneum presenting as localized acute inflammatory lesions. The clinical diagnoses were acute appendicitis in two cases, acute cholecystitis in the third case, and incarcerated umbilical hernia in the fourth case. In all cases tumor was not evident at initial surgical exploration or on gross pathologic examination, and the diagnosis was only made on microscopic examination of the resected specimens. All cases showed a tubulopapillary form of epithelial mesothelioma with obvious tissue invasion, but the foci of tumor were too small to be seen grossly or were present deep in fibrous tissue. On follow-up all patients developed grossly evident tumor, and one of these patients is alive without evidence of disease 5 years after presentation. We conclude that peritoneal mesotheliomas may occasionally present as inflammatory processes without grossly evident tumor and can be diagnosed by microscopic findings alone.

Adolescent↗

Differential diagnosis of peritoneal lesions of müllerian type and similar epithelial tumors of the peritoneum.

The female peritoneum is the site of various tumor-like and tumorous lesions that resemble derivatives of the primary müllerian system. Those lesions can therefore be summarized under the term secondary müllerian system. These lesions can cause problems in macroscopic and microscopic examination if clinicians or pathologists are not acquainted with them. The relationship between the derivatives of the embryonal müllerian duct and the secondary müllerian system is underscored by the expression of many different antigens, as revealed by immunohistology.

Diagnosis, Differential↗

WT1 is differentially expressed in serous, endometrioid, clear cell, and mucinous carcinomas of the peritoneum, fallopian tube, ovary, and endometrium.

The Wilms' tumor gene WT1 plays complex roles in the development of the organs of the genitourinary tract and mesothelium, as well as Wilms' tumors. Although its biologic role is still unclear, most serous carcinomas of the ovary and peritoneum, mesotheliomas, and Wilms' tumor have been shown to express WT1. A recent study, however, found no WT1 expression in serous carcinomas of the endometrium, suggesting that WT1 could be useful in identifying the primary site of serous carcinomas. We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. WT1 nuclear reactivity of any extent and intensity was considered positive. Immunohistochemical stains were evaluated semiquantitatively using a four-tiered scale. Among endometrial carcinomas, WT1 immunoreactivity was seen in 10 of 16 serous, but in none of 35 endometrioid or 18 clear cell carcinomas. Among ovarian tumors, WT1 expression was seen in 24 of 28 serous and 4 of 18 clear cell carcinomas, but in none of 11 endometrioid and 11 mucinous tumors. All 12 serous carcinomas but none of 2 endometrioid carcinomas of the fallopian tube were positive for WT1. WT1 expression was seen in 19 of 20 serous primary peritoneal carcinomas. The difference in WT1 expression was highly significant between serous and other types of tumors in all sites (p<0.0001, chi-square test), although the level of WT1 expression was significantly different among serous carcinomas arising at different sites (p<0.0001, Kruskal-Wallis test). A significant positive correlation was found between the level of p53 and WT1 expression in all carcinomas combined (r = 0.3935, p<0.0001, Spearman test), but when only serous carcinomas were analyzed, the correlation between p53 and WT1 expression levels did not reach statistical significance. Our results suggest that WT1 expression in epithelial tumors of the female genital tract may be related to cell differentiation and histologic subtypes of carcinomas, rather than to primary site of origin.

Aged↗

Cystic mesothelioma of peritoneum: occurrence in a man.

We report a case of cystic mesothelioma of the peritoneum in a 54-year-old man in whom cystic masses were removed twice by surgery at an interval of 2 years. The patient died of cardiac arrest shortly after the second operation for a concurrent unresectable colonic cancer. The pathogenesis of the disease is uncertain, but we consider it neoplastic of low grade malignancy.

Adenocarcinoma↗

Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum.

The aim of this study was to review the long-term results of cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Our goal was to identify clinical factors by which to select patients likely to benefit from a comprehensive management plan. Clinical data of 28 females who underwent surgery were retrieved from a prospective database. Major cytoreductive procedures were possible in 25 patients. Heated intraoperative or early postoperative intraperitoneal chemotherapy was also used where appropriate. The median follow-up after cytoreduction was 26.9 months. The overall median survival after cytoreduction was 45.8 months. The prognostic indicators associated with a statistically significant impact on survival were the prior surgery score (P < 0.001), the completeness of cytoreduction score (CC; P = 0.037), and response to chemotherapy prior to surgery (P = 0.012). Our findings suggest that cytoreductive surgery can be effective when combined with perioperative intraperitoneal chemotherapy. Results can be improved by excluding cases where CC seems unlikely. Extensive prior surgery without the protection of adjunctive intraperitoneal chemotherapy is associated with a poor prognosis. This may be due to disruption of anatomical planes leading to deep abdominal and pelvic dissemination intractable to further treatment.

Adult↗

Benign papillary mesothelioma of peritoneum: a histological, histochemical and ultrastructural study of six cases.

Six cases of localized benign papillary mesothelioma of peritoneum were retrieved from laboratory files over a 20-year period. One presented because of pain following torsion and the remaining five were incidental findings at operation. Light microscopy showed a delicate papillary stroma covered by a single layer of mesothelial cells. The mesothelial cells often showed punctate periodic acid-Schiff staining of cytoplasm. The brush border and stroma showed alcian blue positive staining which was abrogated by prior incubation with hyaluronidase. Electron microscopy revealed typical features of mesothelial cells with long microvilli, rough endoplasmic reticulum in relation to mitochondria, bundles of microfilaments, and tight junctions. Between cells there was a series of intercommunicating channels containing occasional lymphocytes and debris. These features are compared with nodular mesothelial hyperplasia, malignant mesothelioma and adenomatoid tumours of the genital tract. The necessity to distinguish benign papillary mesothelioma from metastatic carcinoma is stressed and relies on the recognition of their mesothelial origin.

Adult↗

Relationship between the prognosis of conception and the location of pelvic involvement in endometriosis: significance of the TOP (tube, ovary, peritoneum) classification.

To determine the main factors that affect the prognosis for conception in endometriosis-associated infertility, 99 infertile patients with laparoscopically confirmed endometriosis were classified according to the new TOP classification, which we have developed to evaluate the severity of endometriosis by site, i.e., fallopian tubes (T), ovaries (O) and the peritoneum (P). According to the TOP classification, a negative correlation between the pregnancy rate after treatment and the severity of lesions was noted in case of tubal and peritoneal involvement, but not when the ovaries were involved. If there was no tubal involvement or only unilateral tubal involvement, high pregnancy rates were achieved for patients with ovarian endometrioma (87%) and for those with partial or complete posterior cul-de-sac obliteration (83%). The results suggest that for endometriosis-associated infertility, the treatment modality should be selected according to the severity of tubal involvement, which is considered to contribute to infertility more than ovarian or peritoneal lesions.

Adult↗

Long-term results of cytoreductive surgery for advanced and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum.

The aim of this study was to review the long-term results of cytoreductive surgery in the treatment of advanced primary and recurrent epithelial ovarian cancers and papillary serous carcinoma of the peritoneum. Our goal was to identify clinical factors by which to select patients likely to benefit from a comprehensive management plan. Clinical data of 28 females who underwent surgery were retrieved from a prospective database. Major cytoreductive procedures were possible in 25 patients. Heated intraoperative or early postoperative intraperitoneal chemotherapy was also used where appropriate. The median follow-up after cytoreduction was 26.9 months. The overall median survival after cytoreduction was 45.8 months. The prognostic indicators associated with a statistically significant impact on survival were the Prior Surgery Score (P < 0.001), the Completeness of Cytoreduction Score (P = 0.037) and response to chemotherapy prior to surgery (P = 0.012). Our findings suggest that cytoreductive surgery can be effective when combined with perioperative intraperitoneal chemotherapy. Results can be improved by excluding cases where completeness of cytoreduction seems unlikely. Extensive prior surgery without the protection of adjunctive intraperitoneal chemotherapy is associated with a poor prognosis. This may be due to disruption of anatomic planes leading to deep abdominal and pelvic dissemination intractable to further treatment.

Adult↗

Primary psammocarcinoma of the peritoneum.

Psammocarcinoma is a rare type of serous carcinoma arising from the ovaries or the peritoneum. Histopathologically, it has large deposits of psammoma bodies, invasion to surrounding tissues, and low-grade cytologic atypia. Biologic behavior is similar to borderline serous tumors with a favorable survival time. Primary surgical debulking with complete resection of the tumor should be the main surgical approach, while the benefit of postoperative chemotherapy remains unknown. A new case of primary peritoneal psammocarcinoma with survival after an initial diagnosis of 5.5 years is presented with a literature review.

Adenocarcinoma↗

The influence of intracellular calcium concentration on degranulation of dialysed mast cells from rat peritoneum.

1. Mast cells, isolated from rat peritoneum, were studied under tight-seal, whole-cell recording conditions. Membrane conductance, membrane capacitance and the concentration of free intracellular Ca2+, [Ca2+]i, were measured simultaneously. 2. [Ca2+]i could be accurately buffered to values between 0 and 1.5 microM only if relatively high concentrations of calcium buffers (in the millimolar range) were added to the pipette filling solution against which the cytoplasm was dialysed. At lower buffer concentrations [Ca2+]i was markedly increased by hyperpolarizing the membrane. 3. When added to the pipette, guanosine-3-thio-triphosphate (GTP-gamma-S), a nonhydrolysable analogue of guanosine triphosphate, stimulated a 3.3-fold increase in membrane capacitance, which is indicative of mast cell degranulation (Fernandez, Neher & Gomperts, 1984). 4. In weakly buffered cells, GTP-gamma-S also induced a transient increase in [Ca2+]i which, usually, preceded degranulation. Calcium buffers at 1-5 mM concentration suppressed this transient. 5. High [Ca2+]i alone did not induce degranulation. However, it markedly accelerated GTP-gamma-S-induced degranulation. When [Ca2+]i was buffered to zero, an appreciable fraction of cells degranulated in response to GTP-gamma-S, but very slowly, and only after a long lag phase. 6. Transient increases in [Ca2+]i, evoked either by GTP-gamma-S, or by voltage changes, did not elicit capacitance changes during the lag phase, but accelerated the GTP-gamma-S-induced degranulation response at later times. 7. Internally applied inositol 1,4,5-trisphosphate (IP3) also induced transient increases in [Ca2+]i which did not lead to secretion in the absence of GTP-gamma-S. 8. It is concluded that an increase in [Ca2+]i is neither necessary nor sufficient for secretion from dialysed mast cells. [Ca2+]i, however, acts synergistically with other stimuli to promote secretion. It is the more efficient the more time the other stimulus had been allowed for priming the cell.

Action Potentials↗

Starch granulomatosis of the peritoneum.

Starch glove powder is used extensively by surgeons in Britain and is generally considered innocuous so that precautions to prevent granuloma formation, previously taken when talc glove powder was in use, are now neglected. Reported here are five cases of starch granulomatosis of the peritoneum occurring over a period of a few months. This condition requires reoperation within a limited time for its diagnosis and may be confused macroscopically with disseminated malignant disease or tuberculosis or may simply cause adhesions. Recognition is dependent on a high degree of suspicion by both surgeon and histopathologist, as special histological techniques may be necessary. Consequently, it is only in a minority of the florid cases that a diagnosis is made, and the condition would appear to be much more common than is generally realized. A plea is made for scrupulous care to avoid starch powder contamination of the operative field.

Adult↗

Lung cancer and mesothelioma in the pleura and peritoneum among Swedish insulation workers.

OBJECTIVES: To estimate the risk of cancer and death in Swedish insulation workers some years after their exposure to asbestos had stopped. One hypothesis was that the risk of lung cancer would tend to decrease some years after the exposure had ended. METHODS: In a cohort study the cancer morbidity and cause of death was investigated in 248 insulation workers and compared with the corresponding morbidity and mortality in the general population. Due to stringent regulations, exposure to asbestos of all types had almost ended in Sweden in the mid-1970s. Through a questionnaire, surviving insulation workers were asked about their exposure to asbestos and their smoking habits. RESULTS: Between 1970 and 1994 there were 86 deaths compared with the 46.0 expected (standardised incidence ratio (SIR) 1.9; 95% confidence interval (95% CI) 1.5 to 2.3), the increase was mainly due to an increased cancer mortality. The morbidity was increased for lung cancer (11 cases v 2.5 expected (SIR 4.4; 95% CI 2.2 to 7.9)), peritoneal mesothelioma (seven cases; no expected incidence could be calculated as the occurrence is too rare in the general population), cancer in pancreas (five cases v 0.7 expected (SIR 7.1; 95% CI 2.3 to 16.7)). No cases of pleural mesothelioma were found. The risk of lung cancer did not tend to approach that of the general population after the exposure to asbestos decreased. CONCLUSIONS: In the 1980s and the early 1990s, Swedish insulation workers still have a highly increased risk of diseases related to asbestos. The attributable risk for death and cancer was about 50%. The study also confirms the previous finding that mesothelioma in insulation workers seems to be situated in the peritoneum more often than in the pleura.

Aged↗