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PubMed1996

Fibrosis in the peritoneum induced by scirrhous gastric cancer cells may act as "soil" for peritoneal dissemination.

BACKGROUND: Peritoneal metastases are one reason for the poor prognosis of scirrhous gastric cancer. However, the mechanism of peritoneal metastasis remains unclear. We therefore investigated the interaction between gastric cancer cells and peritoneal fibroblasts, in vivo and in vitro. METHODS: A human scirrhous gastric cancer cell line, OCUM-2MD3, and a human peritoneal fibroblast cell line, NF-2P, were established in our laboratory. We then investigated the effect of OCUM-2MD3 cells on the peritoneum of nude mice and on the proliferation of NF-2P cells, the effect of NF-2P cells on the migratory capability of OCUM-2MD3 cells, and the peritoneal fibrosis on the development of peritoneal metastasis. RESULTS: The proliferation of peritoneal fibroblasts was recognized in areas with and without cancer cell infiltration. Serum-free conditioned medium from the OCUM-2MD3 cells had induced peritoneal fibrosis in vivo and significantly stimulated the proliferation of NF-2P cells in vitro. The molecular weight (molecular weight ratio 25,000-43,000) of the growth factors produced by the OCUM-2MD3 cells was estimated by gel filtration high performance liquid chromatography. The migratory capability of the OCUM-2MD3 cells was significantly increased by the presence of NF-2P cells. Tumorigenicity in mice with peritoneal fibrosis was greater than in mice with normal peritoneum. CONCLUSIONS: Peritoneal fibrosis, formed by a factor secreted by scirrhous gastric cancer cells, may be congenial environment ("soil") for peritoneal metastases of scirrhous gastric carcinoma.

Adenocarcinoma, Scirrhous↗

PubMed2001

Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum.

In this experimental study, the effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum was investigated. A reproducible in vitro assay was developed to study the adhesion of CC531 colon carcinoma cells to an autologous monolayer of rat mesothelial cells. Tumour cell adhesion to mesothelium pre-incubated with interleukin-1beta (IL-1beta) and epidermal growth factor (EGF) resulted in at least 60% more tumour cell adhesion at maximal stimulation (p</=0.001). Transforming growth factor-beta (TGF-beta) pre-incubation resulted in minor, though significant stimulation of cell adhesion (maximal 16%, p<0.05). The effect of IL-1beta was time- and dose-dependent. No mesothelial cell proliferation took place after pretreatment with IL-1beta, indicating that enhanced adhesion was not based on an increase in the number of mesothelial cells. Pretreatment with EGF stimulated mesothelial cell growth as measured by DNA analysis. This effect on cell growth and adhesion was dose-dependent. Additional blocking experiments with anti-IL-1beta resulted in statistically significant inhibition of IL-1beta-stimulated tumour cell adhesion (p</=0.01), demonstrating the specificity of this effect. Interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IL-6, and insulin-like growth factor (IGF-I) pre-incubation had no effect on tumour cell adhesion. These results prove that IL-1beta and EGF are significant promoting factors in tumour cell adhesion to mesothelium in vitro and may therefore account for tumour recurrence in the peritoneum in vivo.

Animals↗

PubMed1977

Does the peritoneum need to be closed at laparotomy?

Closure of vertical laparotomy wounds was randomized between a two-layer technique of continuous catgut to peritoneum and continuous nylon to sheath and a one-layer technique in which the peritoneal suture line was omitted. In 162 two-layer closures there were 4 burst abdomens and 7 wound hernias (6.8 per cent wound failures); in 164 one-layer closures there were 5 burst abdomens and 7 hernias (7.3 per cent failures). Of 21 patients in this series with jaundice, the abdominal wounds dehisced in 3, and 4 patients developed incisional hernias (33.3 per cent failures) compared with a 5.2 per cent failure rate in the 305 non-jaundiced patients (P less than 0.01). Closure of the peritoneum as a separate layer, as widely advised and practised, appears to play no significant role in the healing of the laparotomy wound.

Animals↗

PubMed1996

Peritoneal defences and peritoneum-associated lymphoid tissue.

The peritoneum is mainly protected by the innate immune system. This consists of mechanical clearance of the peritoneal cavity, activation of complement, and the actions of polymorphonuclear neutrophils and macrophages. The specific immune system, which is mediated by the activity of lymphocytes, provides a secondary amplification system that may be of great importance for patients with intraperitoneal sepsis. This review provides an overview of the relevant innate immune mechanisms and explores the possible role of peritoneum-associated lymphoid tissue.

Ascitic Fluid↗

PubMed1998

Depletion of the natural killer cell population in the peritoneum by AK-5 tumor cells overexpressing fas-ligand: a mechanism of immune evasion.

AK-5 tumor kills 100% hosts when injected ip and only 20-30% of animals die when the tumor cells are transplanted sc. Seventy percent of animals regress the subcutaneous tumor and exhibit total immunity against subsequent challenges of AK-5 cells by either route. Initially the 100% killing in ip-injected animals was attributed to the rapid growth of the tumor cells in the peritoneum thereby not giving enough time for the host immune system to mount an antitumor response. In the present report we have demonstrated overexpression of Fas-L by day 3 and day 4 ascitic tumor cells which depletes the peritoneum of Fas+ lymphocytes. In addition the effector cells from the ascites are ineffective in inducing cytotoxicity against tumor cells in vitro. However, splenocytes from animals bearing ip tumors possessed cytotoxicity against YAC-1 as well as AK-5 cells. We have also shown the presence of soluble Fas-L in the ascitic fluid, which induced DNA fragmentation in Fas+ Jurkat cells. Fas-L present in the tumor cells is able to induce apoptosis in activated lymphocytes and Jurkat cells, suggesting retention of its biological function. These studies implicate Fas-L in the depletion of the effector cell number and inhibition of their functional activity. They also suggest differential regulation of Fas-L expression by the tumor cells depending upon the site of transplantation.

Animals↗

PubMed1991

Malignant mesenchymoma: a very rare tumor of the peritoneum. Case report with a review of the literature.

We report the case of an 82-year-old male patient with a malignant mesenchymoma. The tumor arose from the parietal peritoneum closely attached to the ascending colon. It consisted of a larger liposarcomatous and a smaller leiomyosarcomatous component which was demonstrated by immunohistochemistry. To our knowledge this is the first report of a malignant mesenchymoma of this histological composition originating from the parietal peritoneum. The tumor was completely removed surgically, which is the treatment of choice for such tumors. In agreement with other authors, we believe that malignant mesenchymomas arise from a primitive mesenchymal cell with the capacity for totipotent differentiation.

Aged↗

PubMed1978

Histology of the intestinal peritoneum in patients with cirrhosis of the liver and ascites.

Portal hypertension and hypoalbuminemia are usually incriminated in the development of ascites in liver cirrhosis, and altered peritoneal permeability is considered only as a hypothetical possibility. Jejunal postmortem specimens were studied in 15 control patients and 16 patients dying with cirrhosis of the liver and ascites. In decompensated cirrhosis a fibrous thickening of the peritoneum was found, 159.0 +/- 96.4 micrometer (mean +/- SD) compared to 24.5 +/- 10.6 micrometer in controls (P less than 0.001). An increase in the size and number of blood vessels, lymphangiectasiae, and mononuclear cell infiltration were invariably present. These histological changes are consistent with a nonspecific chronic peritonitis. The findings indicate there is increased blood perfusion and lymph flow within the intestinal peritoneum in patients with decompensated cirrhosis of the liver and support the existence of an intestinal peritoneal factor in the pathogenesis of cirrhotic ascites.

Aged↗

PubMed1991

The use of peritoneum for vaginoplasty in 24 patients with congenital absence of the vagina.

Vaginoplasty using pelvic peritoneum (Rothman's method) was used in 24 patients with congenital absence of the vagina. The results are presented. Rothman (1972) described vaginoplasty using pelvic peritoneum. We have operated on 24 patients with the anomaly. In this report, the better technique for this operation and the results of treatment are evaluated using data from these 24 cases.

Adolescent↗

PubMed1998

The peritoneum, mesenteries and omenta: normal anatomy and pathological processes.

The peritoneum is the largest and most complexly arranged serous membrane in the body. The potential peritoneal spaces, the peritoneal reflections forming peritoneal ligaments, mesenteries, omenta and the natural flow of peritoneal fluid determine the route of spread of intraperitoneal fluid and, consequently, disease processes within the abdominal cavity. The peritoneal ligaments, mesenteries and omenta also serve as boundaries for disease processes and conduits for disease spread. The peritoneal cavity and its reflections are frequently involved by infectious, inflammatory, neoplastic and traumatic processes. Before the introduction of cross-sectional imaging, the peritoneum and its reflections could only be imaged with difficulty, often requiring invasive techniques. Computed tomography and, to a lesser extent, sonography and MR imaging allow the accurate examination of the complex anatomy of the peritoneal cavity, which is the key to understanding the pathological processes affecting it. This article reviews the normal peritoneal anatomy and its disease processes.

Humans↗

PubMed2000

In vitro peritonitis: basic inflammatory reactions in a two-chamber coculture model of human peritoneum.

We developed an in vitro model of the peritoneum by coculturing human umbilical vein endothelial cells (HUVEC) and human peritoneal mesothelial cells (HPMC) to gather information on peritoneal physiology and to closer reflect the in vivo situation in humans. HUVEC and HPMC were seeded on collagen-coated polytetraflourethylene-insert membranes of pore size 3 microm. HUVEC were grown on the bottom of the membrane and HMPC on the top. The confluent cells were monitored by measuring transepithelial resistance and by confocal microscopy. The transmigration of PMNs as an important mechanism during secondary peritonitis was studied in this two-chamber model. PMNs were isolated by density separation. After stimulation of HMPC with the complement factor 5 split product C5a (1 ng/ml) or tumor necrosis factor-alpha (TNF-alpha; 10 or 50 microg/ml) for 1 h, 1 x 10(6) PMN were given to the lower compartment. Controls were cocultured cells without stimulation. After 1, 2, and 6 h nonadherent PMNs in the upper compartment were harvested and counted, interleukin-8 was measured in each compartment, and cells on the membrane were paraffin-embedded for immunohistochemistry. Each experiment was performed four times. Cells grew to confluence within 2-5 days and were detected on their respective seeding side by CD34 and cytokeratin 18 counterstaining. Transmigration of PMNs after C5a or TNF-alpha stimulation showed a significant time-dependent increase between 1 h and 6 h (P<0.05). PMNs were found in significantly higher numbers after stimulation with either C5a or TNF-alpha at 1, 2, and 6 h than without stimulation. After stimulation of HPMC, interleukin-8 secretion to the apical compartment increased in a time-dependent fashion, resulting in a gradient between the two chambers. Linear regression analysis revealed significant correlation between transmigrated PMN and interleukin-8 in stimulated cocultures; no correlation was found in controls. This new in vitro peritoneum consisting of cocultured mesothelial and endothelial cells may allow more detailed assessment of peritoneal pathophysiology. Generation of an interleukin-8 gradient affecting the migration of PNMs across the cocultured membrane represents a parameter which may be addressed in further studies.

Cell Culture Techniques↗

PubMed2001

Carbon dioxide pneumoperitoneum reduces levels of TNF-a mRNA in the brain, liver, and peritoneum in mice.

BACKGROUND: Cytokines are important regulators of the biological response to surgical stress. The aim of this study was to determine whether the CO(2) pneumoperitoneum would change the expression of TNF-a mRNA in the visceral organs, including the brain, in mice. METHODS: Mice were randomly assigned to one of six groups: control, anesthesia alone, insufflation with carbon dioxide, insufflation with air, laparotomy by short incision, or laparotomy by long incision. The brain, liver, jejunum, and peritoneum were harvested either 3 or 24 h after surgery. Levels of TNF-a mRNA in each tissue was measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The air insufflation group showed higher TNF-a mRNA levels in the brain and liver than the short-incision group. Levels of TNF-a mRNA in the brain, liver, and peritoneum were lower in the CO(2) pneumoperitoneum group than in the air insufflation group. Plasma IL-6 and catecholamine in the urine were lower in the CO(2) pneumoperitoneum group than the air insufflation group. CONCLUSION: Reduced synthesis of TNF-a in the visceral organs, including the brain, is correlated with a less marked biologic response to laparoscopic surgery.

Animals↗

PubMed1999

Characteristic alterations of the peritoneum after carbon dioxide pneumoperitoneum.

OBJECTIVE: Any route of entry into the abdomen contributes to alterations of the intraperitoneal organs with different clinical consequences. Characteristic alterations of the peritoneum after CO2 pneumoperitoneum used in laparoscopic surgery is examined. METHODS: A CO2 pneumoperitoneum with an intraperitoneal pressure of 6 mmHg was applied for 30 min in 32 nude mice. In the course of 4 days, the animals were killed and the peritoneal surface of the abdominal wall was studied by means of scanning electron microscopy. RESULTS: Already 2 h after release of the pneumoperitoneum, mesothelial cells were bulging up. The intercellular clefts thereby increased in size, and the underlying basal lamina became visible. This reaction peaked after 12 h. Subsequently, peritoneal macrophages and lymphocytes filled all gaps, thereby recovering the basal lamina. CONCLUSION: The morphologic integrity of the peritoneum is temporarily disturbed by a CO2 pneumoperitoneum.

Animals↗

PubMed1986

Cytosol estrogen receptor content of female parietal peritoneum.

The ovarian and peritoneal mesothelium are believed to derive from the same embryonal coelomic epithelium. Neoplastic proliferation of these epithelia is sometimes grossly and histologically similar. Recently estrogen receptors have been identified in gynecologic neoplasms. With the use of standard techniques, the parietal peritoneum was assessed for estrogen receptor content in 17 women undergoing celiotomy for various reasons. All peritoneal specimens were negative for estrogen receptor content. This suggests a heterogeneous origin of the peritoneal surface epithelium and that peritoneum may not be müllerian in origin.

Chromatography, Paper↗

PubMed1991

Endometriosis associated with massive ascites and absence of pelvic peritoneum.

Although massive ascites associated with endometriosis has been reported in rare cases, this patient was also noted to have massive destruction of the pelvic peritoneum. Failure of medical suppression necessitated total abdominal hysterectomy and bilateral salpingo-oophorectomy. Several months after surgery ascites resolved, possibly with reestablishment of the pelvic peritoneum.

Adult↗

PubMed1994

Cystic mesothelioma of the peritoneum: a rare cause of 'ascites' in children.

A 2-year-old girl presented with a 3-month history of progressive painless abdominal distension. Results of the clinical examination suggested massive ascites, but no other symptoms or signs could be elicited. There was no history of any other illness preceding the onset of distension. Ultrasonography and a computed tomography scan confirmed gross ascites, with multiple thin-walled loculi throughout the abdomen, from the diaphragm to the pelvis. The preoperative diagnosis was intraabdominal lymphangioma. During laparotomy, multiple transparent cysts were found throughout the peritoneum. There was no evidence of malignancy in any organ, and the cysts appeared almost completely avascular. Histological and ultrastructural appearances were those of benign cystic mesothelioma of the peritoneum, a condition that hitherto has been recognized only in adults. It is thought to represent a borderline variant between a truly benign adenomatoid lesion and the better-known malignant mesothelioma. The experience with adult cases suggests a high potential for recurrence but no progression to malignancy. It is possible that some cases of intraabdominal lymphangioma may have been misdiagnosed in the past; future cases should be fully evaluated, both immunohistochemically and ultrastructurally, to establish the true incidence of mesothelial proliferative disease in children.

Ascites↗

PubMed2004

Regulation of expression of tissue plasminogen activator and plasminogen activator inhibitor-1 by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions.

OBJECTIVE: As part of our ongoing studies to understand the biologic mechanisms of wound repair that lead to postoperative adhesions, we have identified characteristics of an adhesion phenotype that differs between fibroblasts that are obtained from human normal peritoneum and adhesions. In this study, we sought to examine whether stimulation of aerobic metabolism would alter differential expression of tissue plasminogen activator and plasminogen activator inhibitor-1, thereby creating a milieu likely to be less favorable to postoperative adhesion development. To examine this issue, we used a compound, dichloroacetic acid, that stimulates the pyruvate dehydrogenase complex, which causes pyruvate to be metabolized in the Kreb's cycle rather than being converted into lactate, thereby switching anaerobic to aerobic metabolism. STUDY DESIGN: Human fibroblasts from normal peritoneum and adhesions were cultured in the absence or presence of dichloroacetic acid (100 microg/mL) for 24 hours, under normal and hypoxic (2% O(2)) conditions. Real-time reverse transcriptase-polymerase chain reaction of tissue plasminogen activator, plasminogen activator inhibitor-1, and a housekeeping gene beta-actin was performed with messenger RNA that was extracted from all treatment points. RESULTS: Dichloroacetic acid stimulated normal peritoneal fibroblast tissue plasminogen activator messenger RNA expression under hypoxic conditions. In adhesion fibroblasts, dichloroacetic acid treatment enhanced tissue plasminogen activator messenger RNA expression under both normoxic and hypoxic conditions. Plasminogen activator inhibitor-1 messenger RNA expression was unaltered by dichloroacetic acid in normoxic normal peritoneal fibroblasts; but during culture under hypoxic conditions, dichloroacetic acid reduced plasminogen activator inhibitor-1 messenger RNA expression. Similarly, in adhesion fibroblasts, dichloroacetic acid reduced plasminogen activator inhibitor-1 messenger RNA expression under both normoxic and hypoxic conditions. As a result, in normal peritoneal fibroblasts under hypoxic conditions and in adhesion fibroblasts under normoxic and hypoxic conditions, dichloroacetic acid greatly increased the tissue plasminogen activator/plasminogen activator inhibitor-1 ratios. CONCLUSION: These findings confirm that fibroblasts from adhesions are characterized by reduced tissue plasminogen activator and increased plasminogen activator inhibitor-1 production. These observations are extended to show the stimulation of oxidative metabolism by dichloroacetic acid increases tissue plasminogen activator expression under hypoxic conditions. Dichloroacetic acid reduces plasminogen activator inhibitor-1 production by hypoxic normal peritoneal fibroblasts and adhesion fibroblasts under hypoxic conditions. The resultant increases in the tissue plasminogen activator/plasminogen activator inhibitor-1 ratios would favor the development of a fibrinolytic milieu, which would be expected potentially to limit postoperative adhesion development. Thus, regulation of metabolic activity of peritoneal cells may provide a target for future interventions for the reduction of the development of postoperative adhesions, particularly as intervention relates to the healing of peritoneal sites that previously had adhesions. (eg, sites of potential adhesion reformation).

Cell Hypoxia↗

PubMed2004

Regulation of matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1 by dichloroacetic acid in human fibroblasts from normal peritoneum and adhesions.

OBJECTIVE: To examine the role of stimulation of aerobic metabolism on the differential expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), which are differentially regulated in fibroblasts isolated from normal human peritoneum and adhesions. DESIGN: Tissue culture study. SETTING: University research laboratory. PATIENT(S): Human fibroblasts cultures from normal peritoneum and adhesions that were exposed to dichloroacetic acid (DCA; 0 and 100 microg/mL) for 24 hours under normal and hypoxic conditions. MAIN OUTCOME MEASURE(S): Real-time reverse-transcription polymerase chain reaction of MMP-1, TIMP-1, and beta-actin. RESULT(S): Dichloroacetic acid stimulated peritoneal fibroblast MMP-1 mRNA expression under normoxic conditions; this stimulation was lost during hypoxia. In adhesion fibroblasts, DCA increased MMP-1 mRNA expression; this effect was reversed by hypoxia. Expression of TIMP-1 mRNA was insignificantly increased by DCA in normal peritoneal and adhesion fibroblasts under normoxic conditions; however under hypoxic conditions, DCA reduced TIMP-1 mRNA expression from both. CONCLUSION(S): Regulation of metabolic activity of peritoneal cells may provide a target for future interventions for reduction of development of postoperative adhesions, particularly as it relates to healing of peritoneal sites that did not previously have adhesions as opposed to sites that underwent lysis of preexistent adhesions.

Cell Hypoxia↗

PubMed2005

Electron-microscopic alterations of the peritoneum after both cold and heated carbon dioxide pneumoperitoneum.

BACKGROUND: Carbon-dioxide (CO(2)) is used universally as an insufflation agent to create a laparoscopic pneumoperitoneum. In this study, we aimed to examine the electron and light microscopic alterations of the peritoneum after both cold-dry and heated-humidified CO(2) pneumoperitoneum. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were used in this study. The rats were separated into three groups each comprising 10 rats. Group-I: (Control group): Gas insufflation was not applied to these animals. Group-II: These animals received standard cold-dry (21 degrees C, 2% relative humidity) CO(2). Group-III: These animals received heated-humidified (40 degrees C, 98% relative humidity) CO(2). In groups II and III, peritoneal gas was emptied 2 h after pneumoperitoneum application. All rats were killed after 12 h. Peritoneal samples were examined both by scanning electron and light microscopy by two different pathologists who were not aware of the groups. RESULTS: According to light microscopic examination; in group II and III, cellular response (increased lymphocyte) was significantly higher than the control group (P < 0.01). Similarly, in group II cellular response was significantly higher than group III. (P < 0.01). There was no difference in increased capillarity among all groups. (P > 0.05). According to scanning electron microscopic examination, in group I, normal peritoneum was covered by a sheet of flat mesothelial cells densely covered with microvilli. No intercellulary clefts and no free basal lamina were detected. In group II, drastic alterations of the surface layer were seen. The mesothelial cells had extreme desquamation, and the basal membrane was clearly visible. In group III, the mesothelial cells had bulged up to the surface layer and retracted. Intercellulary clefts become visible, but the basal lamina was not seen. CONCLUSIONS: Electron and light microscopic examination revealed that heated-humidified CO(2) results in less peritoneal alteration than cold-dry CO(2.) Accordingly, we believe that heated-humidified CO(2) is more suitable for pneumoperitoneum application in laparoscopic surgery especially in selected cases.

Animals↗