Peritoneal melanosis associated with metastatic melanoma previously treated with targeted and immune checkpoint inhibitor therapy.

Peritoneal melanosis is an uncommon benign condition, the pathophysiology of which is unclear. Macroscopically, it appears as diffuse dark brown or black pigmentation within the peritoneum, mimicking more sinister conditions such as metastatic melanoma. It has been described in a variety of contexts, but only exceedingly rarely in association with metastatic melanoma, with only two previous published case reports. We present a case of peritoneal melanosis associated with metastatic melanoma involving the spleen, previously treated with targeted and immune checkpoint inhibitor therapy. With increasing reports of melanoma regression manifesting as cutaneous tumorous melanosis in patients treated with immune checkpoint inhibitors, we postulate that, similarly, immunotherapy and tumour regression might have a role to play in the pathogenesis of the peritoneal pigmentation in this case.

Dioxin and endometriosis: a new possible relation based on epigenetic theory.

Endometriosis is a chronic disease characterized by the growth of endometrial-like glands and stroma outside the uterine cavity. Nowadays, the exact etiology of endometriosis is unclear and the interaction between a variety of environmental physical and chemical compounds may potentially promote the disease in women with an individual susceptibility. The first demonstration of a relation between an environmental factor and endometriosis was obtained with the chronic dietary exposure of a primate colony to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Besides the well-known dioxin's pathway of action, several papers are focusing on the role of epigenetic mechanisms, a way through which the genome responds to the environment and can lead to permanent changes in gene expression until affecting the phenotypes or cause disease. In this review, we focus on the possible role of dioxin epigenetics modification in endometriosis.

Spontaneous mesenteric hematoma associated to warfarin with surgical resolution. / [Hematoma mesentérico espontáneo asociado a warfarina con resolución quirúrgica.]

Spontaneous mesenteric hematoma isinfrequent. It has been related to prolonged anticoagulation, mainly with warfarin. No definitive treatment has been established; A treatment is suggested in hemodynamically stable patients, while in patients in shock, the surgical treatment is suggested. Our goal is topresent the case of a mesenteric hematoma associated with prolonged conservative anticoagulation with surgical resolution. Female patient with 67 years old, consulted for 24 hours of evolution abdominal pain and signs of peritonism; Computed tomography was performed with a diagnosis of spontaneous mesenteric hematoma. In the context of a clinically stable patient anticoagulated with warfarin, emergency laparotomy with intestinal resection of the segment affected by the hematoma was decided. Pathological anatomy reports massive submucosal hemorrhage. Conclusion: Surgical behavior in patients with hemodynamically stable peritonism can be safe and effective

El hematoma mesentérico espontáneo es una entidad infrecuente. Se lo ha relacionado con anticoagulación prolongada, principalmente con el uso de warfarina. No se ha establecido un tratamiento estándar hasta la fecha; sugiriéndose en pacientes hemodinámicamente estables un tratamiento conservador, mientras que en pacientes inestables el tratamiento quirúrgico. Nuestro objetivo es presentar el caso de un hematoma mesentérico asociado a anticoagulación prolongada con resolución quirúrgica. Paciente de sexo femenino de 67 años de edad, consultó por dolor abdominal de 24 horas de evolución y signos de peritonismo; se realizó tomografía computada con diagnóstico de hematoma mesentérico espontáneo. En el contexto de una paciente clínicamente estable anticoagulada con warfarina, se decidió laparotomía de urgencia con resección intestinal del segmento afectado por el hematoma. El informe de anatomía patológica revela hemorragia masiva submucosa. Conclusión: La conducta quirúrgica en pacientes con peritonismo, estables hemodinámicamente, puede considerarse seguro y efectivo.

Comparison of a chymase inhibitor and hyaluronic acid/carboxymethylcellulose (Seprafilm) in a novel peritoneal adhesion model in rats.

Adhesion formation that occurred after alkali-induced injury of the cecum was used as a novel adhesion model in rats, and it was compared with that of a common adhesion model after abrading the cecum. Using the novel adhesion model, inhibition of adhesion formation by a chymase inhibitor, Suc-Val-Pro-PheP(OPh)2, and by sodium hyaluronate/carboxymethylcellulose (Seprafilm) was evaluated, and their mechanisms were assessed. The degree of adhesion formation was more severe and more stable in the alkali-induced injury model than in the abrasion-induced injury model. Both the chymase inhibitor and Seprafilm showed significant attenuation of the degree of adhesion 14 days after alkali-induced injury. Chymase activity in the cecum was significantly increased after alkali-induced injury, but it was significantly attenuated by the chymase inhibitor and Seprafilm. Myeloperoxidase and transforming-growth factor (TGF)-ß levels were significantly increased after alkali-induced injury, but they were attenuated by both the chymase inhibitor and Seprafilm. At the level of the adhesions, the numbers of both chymase-positive cells and TGF-ß-positive cells were significantly increased, but their numbers were reduced by the chymase inhibitor and Seprafilm. In conclusion, a chymase inhibitor attenuated the degree of adhesions to the same degree as Seprafilm in a novel peritoneal adhesion model that was more severe and more stable than the common adhesion model, and not only the chymase inhibitor, but also Seprafilm reduced the chymase increase at the adhesions.

Mast cells and histamine are triggering the NF-κB-mediated reactions of adult and aged perilymphatic mesenteric tissues to acute inflammation.

This study aimed to establish mechanistic links between the aging-associated changes in the functional status of mast cells and the altered responses of mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation. We used an in vivo model of acute peritoneal inflammation induced by lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats. We analyzed contractility of isolated MLVs, mast cell activation, activation of nuclear factor-κB (NF-κB) without and with stabilization of mast cells by cromolyn or blockade of all types of histamine receptors and production of 27 major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric tissues and blood. We found that the reactivity of aged contracting lymphatic vessels to LPS-induced acute inflammation was abolished and that activated mast cells trigger NF-κB signaling in the mesentery through release of histamine. The aging-associated basal activation of mesenteric mast cells limits acute inflammatory NF-κB activation in aged mesentery. We conclude that proper functioning of the mast cell/histamine/NF-κB axis is necessary for reactions of the lymphatic vessels to acute inflammatory stimuli as well as for interaction and trafficking of immune cells near and within the collecting lymphatics.

Safety assessment of nylon as used in cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of nylon polymers, which function in cosmetics primarily as bulking and opacifying agents. The Panel reviewed relevant animal and human data related to these large polymers and determined that they are not likely to penetrate the skin. Whatever residual monomers may be present were not present at a sufficient level to cause any reactions in test subjects at the maximum ingredient use concentration. Accordingly, the Panel concluded that these ingredients are safe in the present practices of use and concentration.

Safety assessment of Tin(IV) oxide as used in cosmetics.

Tin(IV) oxide functions as an abrasive, bulking, and opacifying agent in cosmetic products and is used at concentrations up to 0.4% in rinse-off products and up to 1.3% in leave-on products. The Cosmetic Ingredient Review Expert Panel (Panel) noted that tin(IV) oxide is a water-insoluble inorganic metal compound and should not be percutaneously absorbed; therefore, systemic exposure is not likely. Studies of dermal application of tin(IV) oxide were considered to determine toxicity at the site of application. The Panel concluded that tin(IV) oxide is safe in the present practices of use and concentration.

Mesenterial, omental, and peritoneal disorders in antiretroviral-treated HIV/AIDS patients: spectrum of cross-sectional imaging findings.

In the era of highly active antiretroviral therapy, radiologists are increasingly confronted with a progressively aging HIV-infected population with improved immune function and survival, in whom a wide spectrum of infectious and neoplastic opportunistic disorders may be encountered. Furthermore, HIV / AIDS patients commonly have unspecific symptoms and physical signs, multicentric or coexisting diseases, so that diagnostic imaging studies are crucial to correctly identify and stage HIV-related abnormalities. Currently, volumetric multidetector CT (MDCT) provides comprehensive assessment and confident post-treatment follow-up of opportunistic abnormalities involving the mesentery, omentum, and peritoneum. In this pictorial essay, the cross-sectional imaging appearances of opportunistic disorders involving the mesentery, peritoneum, or both compartments in HIV / AIDS patients are reviewed, with emphasis on those MDCT findings that may be helpful for differential diagnosis along with knowledge of the degree of immune suppression as measured by the CD4 lymphocyte count. Familiarity with the varied spectrum of HIV-related opportunistic disorders encountered in antiretroviral - treated patients and their imaging appearances should allow radiologists to improve their confidence in the characterization of abnormal findings observed on abdominal cross-sectional imaging studies.

A20 and ABIN-3 possibly promote regression of trehalose 6,6'-dimycolate (TDM)-induced granuloma by interacting with an NF-kappa B signaling protein, TAK-1.

OBJECTIVE: The objective of this paper is to examine the role of NF-kappa B inhibitors A20 and ABIN-family proteins in the trehalose 6,6'-dimycolate (TDM)-induced model of tuberculous granulomatous lesions. MATERIALS AND METHODS: BALB/c mice were twice injected i.p. with w/o/w emulsions that contain TDM at a 1 week-interval. The mice were killed at days 0, 3, 7, 14, or 21 after the last injection. The mRNA and protein levels of A20 and ABIN-family proteins were measured by real-time PCR using mRNA or protein extract from the lesions. The activation status of NF-kappa B was analyzed by Western blotting and immunohistochemistry. Finally, the protein extracts were immunoprecipitated by anti-ABIN-3 antibody to identify the protein that potentially interacts with ABIN-3. RESULTS: The activation of NF-kappa B pathway coincided with granuloma development, while A20 and ABIN-3 increased in accordance with granuloma regression. TAK-1 protein was co-precipitated with ABIN-3 by immunoprecipitation using anti-ABIN-3 antibody. CONCLUSION: The results suggest that ABIN-3 contributed to granuloma regression by interacting with TAK-1 and, as a consequence, inhibiting activation of NF-kappa B pathway.

Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis.

To test the hypothesis that bacterial contamination of menstrual blood could be a local biologic event in the development of endometriosis, menstrual blood was cultured and bacterial endotoxin was measured in menstrual blood and peritoneal fluid. Our results suggest that compared with control women, higher colony formation of Escherichia coli in menstrual blood and endotoxin levels in menstrual fluid and peritoneal fluid in women with endometriosis may promote Toll-like receptor 4-mediated growth of endometriosis.

Experimental intraperitoneal infusion of OK-432 in rats: evaluation of peritoneal complications and pathology.

PURPOSE: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose of this study was to evaluate both its safety and pathologic effects after the infusion of OK-432 into the peritoneal cavity of rats. MATERIALS AND METHODS: Twenty male rats were used in this study. Twelve rats were infused intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal saline (group 1: the treated group); four rats each were infused intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group 3), and served as the control groups. An abdominal ultrasonographic examination was performed both before and after the infusions in all rats. Three rats in group 1 and one rat in each of groups 2 and 3 were sacrificed each week following the infusion. Gross and microscopic evaluations of the peritoneum and abdominal cavity were performed on each rat. RESULTS: In group 1, the abdomen was clear on gross inspection and the peritoneum was unremarkable on microscopic examination. In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and inflammation and fibrosis of the peritoneum were demonstrated microscopically. In group 3, no specific abnormalities were noted on gross or microscopic examinations. CONCLUSION: Leakage or abnormal infusion of OK-432 solution into the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal cystic lesions does not result in any significant complications.

Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis.

Dysfunction in macrophage-mediated phagocytosis of aberrant cells that undergo retrograde transport to the peritoneal cavity is considered an important factor in the development of endometriosis. However, the mechanisms responsible for the loss of function of macrophages remain largely unknown. Herein, we report that prostaglandin (PG) E(2), via the EP2 receptor-dependent signaling pathway, inhibits the expression of CD36 in peritoneal macrophages, resulting in reduced phagocytic ability. PGE(2)-mediated inhibition of macrophage phagocytic capability was restored by ectopic expression of CD36. Treatment with PGE(2) inhibited CD36-dependent phagocytosis of peritoneal macrophages and increased the number and size of endometriotic lesions in mice. In contrast, blockade of PGE(2) production by cyclooxygenase inhibitors enhanced the phagocytic ability of peritoneal macrophages and reduced endometriotic lesion formation. Taken together, our findings reveal a potential mechanism of immune dysfunction during endometriosis development and may contribute to the design of an effective prevention/treatment regimen.

Subcutaneous and intraperitoneal lipogranulomas following subcutaneous injection of olive oil in Sprague-Dawley rats.

Olive oil is commonly employed as a solubilizing agent for lipophilic materials in preclinical studies in rodents. Here we report that following subcutaneous (SC) injection of olive oil to Sprague-Dawley (SD) rats, local SC lipogranulomas formed, which were associated with an unusual location of the same changes in the peritoneum. Macroscopically, multifocal white spots were found over the liver and mesentery. Histologically, lipid granulomas were seen in the SC injection site, as well as on the capsular or serosal surface of the abdominal organs. No abnormal clinical signs were noted except for swelling at the injection site. The olive oil may have reached the peritoneal cavity from the SC tissue passively via the lymphatic vessels or actively after engulfment by antigen-presenting cells via the lymphatic or blood vessels. These findings are of particular importance for drug safety assessments, as the occurrence of lipogranulomas in locations distant from the site of administration may lead to misinterpretation of histological results. We suggest that these aberrations may be induced by the administration of olive oil as a vehicle.

Choice of hemostatic agent influences adhesion formation in a rat cecal adhesion model.

INTRODUCTION: Hemostatic agents are frequently used during abdominal surgery and some are linked to adhesion formation. We sought to evaluate the impact of several commonly used hemostatic agents on adhesion formation in a rat peritoneal model. METHODS: In our study, Wister outbred rats underwent laparotomy and excision of a portion of their peritoneum to initiate adhesion formation process. One of six different hemostatic agents, namely, activated starch microspheres (Arista AH; Medafor Inc., Minneapolis, MN), glutaraldehyde activated collagen (BioGlue; Cryolife Inc., Kennesaw, GA), thrombin coated collagen microspheres (FloSeal; Baxter Inc., Deerfield, IL), thrombin activated fibrin polymer (Tisseel, Baxter), polyethylene glycol polymer (CoSeal, Baxter), or oxidized cellulose (Surgicel; Ethicon Inc., Somerville, NJ), was placed in the area of peritoneal defect. All animals were sacrificed on post-op day 7 and strength and extent of adhesion formation was determined. Histopathological examination of rat caecum was also performed. RESULTS: Arista and CoSeal showed significantly lower adhesion formation than controls (P < 0.05). Higher adhesion scores were seen in BioGlue (P < 0.05) treated rats. Additionally, histopathologic examination showed that BioGlue caused statistically more inflammation and necrosis than controls (P < 0.05). Total adhesion score increased with residual amount of agent present at 7 d. CONCLUSIONS: Use of Arista and CoSeal may help in reducing peritoneal adhesions after intra-abdominal surgeries. Furthermore, there appears to be a relationship between the creation of inflammation and necrosis in tissues and the eventual formation of adhesions. This could aid in improving the design of these agents in the future.

Normal saline induces oxidative stress in peritoneal mesothelial cells.

BACKGROUND: Peritoneal adhesions are the most common complication of the abdominal surgery. Normal saline is frequently used to rinse the peritoneal cavity during abdominal surgery, although there is no well-established data describing effect of such procedure on the process of formation of peritoneal adhesions. METHODS: Effect of 0.9% NaCl solution on viability, oxidative stress, and fibrinolytic activity of human peritoneal mesothelial cells maintained in in vitro culture was evaluated. RESULTS: Exposure of mesothelial cells to 0.9% NaCl induces oxidative stress, derangement of their structure with subsequent increased release of tissue factor (+75%) and plasminogen activator inhibitor-1 (+19%), and simultaneous suppression of tissue plasminogen activator release (-39%). In effect, ration tissue plasminogen activator/plasminogen activator inhibitor-1 was reduced in 0.9% NaCl-treated cells by 50%. Pretreatment of cells with precursor of glutathione synthesis: L-2-oxothiazolidine-4-carboxylic acid prevented these changes. CONCLUSIONS: Oxidative stress in the peritoneal mesothelium caused by 0.9% NaCl activates their procoagulant activity and impairs fibrinolytic properties of these cells. These effects disqualify 0.9% NaCl as rinsing solution during abdominal surgery.

Overnight mesothelial cell exfoliation: a magic tool for predicting future ultrafiltration failure in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Continuous exposure of the peritoneal membrane to dialysis solutions during long-term dialysis results in mesothelial cell loss, peritoneal membrane damage, and thereby, ultrafiltration (UF) failure, a major determinant of mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). Unfortunately, none of tests available today can predict long-term UF decline. Here, we propose a new tool to predict such a change. PATIENTS AND METHODS: Mesothelial cells from 8-hour overnight effluents (1.36% glucose dialysis solution) were harvested, co-stained with cytokeratin (a mesothelial marker) and TUNEL (an apoptotic marker), and were counted using flow cytometry in 48 patients recently started on CAPD. Adequacy of dialysis, UF, nutrition status, dialysate cancer antigen 125 (CA125), and a peritoneal equilibration test (3.86% glucose peritoneal dialysis solution) were simultaneously assessed and were re-evaluated 1 year later. RESULTS: The numbers of total and apoptotic mesothelial cells were 0.19 +/- 0.19 million and 0.08 +/- 0.12 million cells per bag, respectively. Both numbers correlated well with the levels of end dialysate-to-initial dialysate (D/D(0)) glucose, dialysate-to-plasma (D/P) creatinine, and sodium dipping. Notably, the counts of cells of both types in patients with diabetes or with high or high-average transport were significantly greater than the equivalent counts in nondiabetic patients or those with low or low-average transport. A cut-off of 0.06 million total mesothelial cells per bag had sensitivity of 1 and a specificity of 0.75 in predicting a further decline in D/D(0) glucose and a sensitivity of 0.86 and a specificity of 0.63 to predict a further decline in UF over a 1-year period. In contrast, dialysate CA125 and other measured parameters had low predictive values. CONCLUSIONS: The greater the loss of exfoliated cells, the worse the expected decline in UF. The ability of a count of mesothelial cells to predict a future decline in UF warrants further investigation in clinical practice.