In vitro 3D microfluidic peritoneal metastatic colorectal cancer model for testing different oxaliplatin-based HIPEC regimens.

Objectives: Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments. Methods: We determined the effects of current therapy options using a 3D static disease model on human colon carcinoma cell lines (HCT 116) and transforming growth factor-ß1 induced epithelial-to-mesenchymal transition (EMT) HCT 116 lines at 37 °C and 42 °C for 30, 60, and 120 min. We determined oxaliplatin's half maximal inhibitory concentrations in a 3D static culture by using viability assay. Clinical practices of HIPEC were applied in the developed model. Results: EMT-induced HCT 116 cells were less sensitive to oxaliplatin treatment compared to non-induced cells. We observed increased cytotoxicity when increasing the temperature from 37 °C to 42 °C and extending the treatment duration from 30 to 120 min. We found that 200 mg/m2 oxaliplatin administered for 120 min is the most effective HIPEC treatment option within the framework of clinic applications. Conclusions: The tool map provide insights into creating more realistic pre-clinical tools that could be used for a patient-based drug screening.

Laparoscopic extraction of a symptomatic upper abdominal pedunculated parietal peritoneal lipoma arising intermittent abdominal pain: a case report.

INTRODUCTION: Lipomas arising in the parietal peritoneum are rare, and some of them cause abdominal pain due to torsion of the pedunculated peritoneum. We encountered a case of parietal peritoneal lipoma arising upper peritoneum. In this report, we describe the detail of clinical presentation and discuss its potential pathogenesis and treatment strategy. CASE PRESENTATION: 45 year-old Japanese female patient presented with long-lasting intermittent pain in the left upper abdominal region. Abdominal imaging showed a well-defined fatty mass measuring 40 mm in size, suggesting a parietal peritoneal lipoma. Laparoscopy revealed a tumor with a twisted peduncle; however, no adhesion of the surrounding tissues and ischemic changes were visible. The tumor was easily removed by dissection of the tumor pedicle. CONCLUSION: Parietal peritoneal lipoma often shows pedunculated form and it causes abdominal pain by the torsion of tumor pedicle. Therefore, this type of lipoma should be considered a more aggressive surgery.

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge.

Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

Laboratory investigation of peritoneal fluids: an updated practical approach based on the available evidence.

Even though analysis of peritoneal fluids (PF) is often requested to medical laboratories for biochemical and morphological tests, there is still no mutual agreement on what the most appropriate way is to manage PF samples and which tests should be appropriately executed. In this update, we tried to identify the most useful tests for PF analysis to establish best practice indications. We performed a literature review and examined available guidelines to select the most appropriate tests by an evidence-based approach. Accordingly, the basic PF profile should include (1) serum to effusion albumin gradient and (2) automated cell counts with differential analysis. This profile allows to determine the PF nature, differentiating between 'high-albumin gradient' and 'low-albumin gradient' effusions, which helps to identify the pathophysiological process causing the ascites formation. Restricted to specific clinical situations, additional tests can be requested as follows: PF lactate dehydrogenase (LDH) and glucose, to exclude (LDH) or confirm (glucose) secondary bacterial peritonitis; PF total protein, to differentiate ascites of cardiac origin from other causes; PF (pancreatic) amylase, for the identification of pancreatic ascites; PF bilirubin, when a choleperitoneum is suspected; PF triglycerides, in differentiating chylous from pseudochylous ascites and PF creatinine, to detect intraperitoneal urinary leakage.

Inferior vena cava reconstruction with non-fascial autologous peritoneum: Retrospective study and literature review.

BACKGROUND: Inferior vena cava (IVC) resection is essential for complete (R0) excision of some malignancies. However, the optimal material for IVC reconstruction remains unclear. Our objective is to demonstrate the efficacy, safety, and advantages of using Non-Fascial Autologous Peritoneum (NFAP) for IVC reconstruction. To conduct a literature review of surgical strategies for tumors involving the IVC. METHODS: We reviewed all IVC reconstructions performed at our institution between 2015 and 2023. Preoperative, operative, postoperative, and follow-up data were collected and analyzed. RESULTS: A total of 33 consecutive IVC reconstructions were identified: seven direct sutures, eight venous homografts (VH), and 18 NFAP. With regard to NFAP, eight tubular (mean length, 12.5 cm) and 10 patch (mean length, 7.9 cm) IVC reconstructions were performed. Resection was R0 in 89% of the cases. Two patients had Clavien-Dindo grade I complications, 2 grade II, 2 grade III and 2 grade V complications. The only graft-related complication was a case of early partial thrombosis, which was conservatively treated. At a mean follow-up of 25.9 months, graft patency was 100%. There were seven recurrences and six deaths. Mean overall survival (OS) was 23.4 months and mean disease-free survival (DFS) was 14.4 months. According to our results, no statistically significant differences were found between NFAP and VH. CONCLUSIONS: NFAP is a safe and effective alternative for partial or complete IVC reconstruction and has many advantages over other techniques, including its lack of cost, wide and ready availability, extreme handiness, and versatility. Further comparative studies are required to determine the optimal technique for IVC reconstruction.

Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer.

High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients' ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of 'core ascitic EV-associated proteins' but also defined their subset unique to HGSC ascites. Using single-cell RNA sequencing data, we mapped the origin of HGSC-specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non-malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type-specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.

Peritoneal Carcinomatosis: When Everything Is Not What It Seems.

Malignant peritoneal mesothelioma (MPM) is a rare neoplasm with a low incidence rate worldwide but high morbidity and mortality rates. Due to its rarity, the studies are scarce. We present a case of a 73-year-old woman admitted to the internal medicine unit with constitutional syndrome, abdominal pain, and ascites. Throughout the investigation, aspects suggestive of peritoneal carcinomatosis were identified. An extensive study was then carried out in an attempt to identify the primary tumor, which proved to be unsuccessful. During the two weeks of hospitalization, the patient's clinical condition worsened, with an increase in ascites and a deterioration in her general health. This case was then discussed with an oncology consultant, and it was decided to biopsy a peritoneal implant with the support of interventional radiology. MPM was then diagnosed through histopathology. With this case, the authors intend to highlight that, although rare, this diagnosis should be considered when appropriate and that even in the suspicion of secondary disease, the primary tumor should always be identified, as localized MPM may be curable.

Unification and orificing of two functional noncommunicating uterine horns through the created neovagina using peritoneum.

OBJECTIVE: To demonstrate the surgical approach for Müllerian agenesis with bilateral uterine remnants containing functional endometrium. DESIGN: Stepwise demonstration of the technique with narrated video footage. SETTING: Reproductive surgery unit of a tertiary university hospital. PATIENT: An 18-year-old adolescent was admitted to a tertiary university hospital with complaints of primary amenorrhea and cyclic pelvic pain. Physical examination and magnetic resonance imaging scans suggested a complex Müllerian abnormality. The patient had uterine remnants with bilateral functional endometrium and cervicovaginal agenesis. INTERVENTION: An operation was planned to reconstruct her anatomy by providing a neovagina and anastomosing the uterine remnants. Gonadotropin-releasing hormone analogs were prescribed to suppress her menstruation until the procedure. The operation was performed in the third month after the initial diagnosis. A laparoscopy was conducted, revealing approximately 5 × 6-cm bilateral uterine horns with healthy adnexa. As the first step, a neovagina was created using a modified peritoneal pull-down technique, a standard approach in our clinic. A vaginal incision was made, and a blind vaginal dissection was performed to reach the peritoneum vaginally. Subsequently, an acrylic vaginal mold was inserted. The vaginal orifice was laparoscopically incised using ultrasonic energy with guidance from the inserted vaginal acrylic mold. The orifice was gradually dilated with larger molds. The entire pelvic peritoneum was dissected circularly, and the distal part of the dissected peritoneum was pulled down using four 2.0 Vicryl sutures at 0°, 90°, 180°, and 270° from the opened vaginal orifice. The uterine cavities of both remnants were incised, and two separate Foley catheters were placed in both cavities. A mold with a hole was used to insert the catheters through the vagina. Both catheters were secured in the cavities with Prolene sutures pulled up from the anterior abdominal wall. The next step involved uterine anastomosis. The uterine remnants were unified through continuous suturing, resulting in the formation of a normally shaped uterus. In the final step, the created uterus and neovagina were anastomosed. The patient received instructions on how to perform mold exercises and follow-up care. MAIN OUTCOME MEASURE: Description of laparoscopic management of a rare Müllerian abnormality. RESULTS: The postoperative magnetic resonance imaging scan at 1 month revealed healed unified uterine cavities and vagina. The patient experienced spontaneous menstruation in the second month after surgery and now maintains regular menses with an approximately 9-10 cm functional vagina. Within 3 months after surgery, the visual analogue scale scores for chronic pelvic pain and dysmenorrhea decreased from 9 to 2-3. CONCLUSIONS: Müllerian abnormalities are exceptionally rare, and their spectrum is broad, making it challenging to identify an exact surgical method to restore functional anatomy. Therefore, a customized surgical approach should be designed for each patient on the basis of their unique condition.

Trends in ovarian, fallopian tube, and primary peritoneal cancer incidence, mortality, and survival: A 15-year population-based analysis.

OBJECTIVE: To characterize trends in ovarian, fallopian tube, and primary peritoneal cancer incidence and incidence-based mortality based on histology and site of origin. METHODS: We obtained age-adjusted incidence and incidence-based mortality for patients with ovarian, fallopian tube, and primary peritoneal cancer from 2000 to 2019 from the US SEER 17 database. Joinpoint 4.9.1.0 was used to characterize log-linear time trends. RESULTS: The incidence and incidence-based mortality of all cancers trended down during the study period. The incidence of epithelial cancers decreased from 2004 to 2019 (AAPC -1.2%, p < 0.001), including that of high-grade (2006-2019: APC -1.2%, p < 0.05) and low-grade (2003-2019: APC -2.4%, p < 0.05) epithelial cancers. There was no change in incidence or incidence-based mortality for ovarian stromal and germ cell cancers. CONCLUSION: There has been a decrease in the incidence and incidence-based mortality of ovarian, fallopian tube, and primary peritoneal cancer, primarily due to reductions in advanced stage epithelial cancers originating in the ovary, fallopian tube, or peritoneum.

Nanomechanical Analysis of Living Small Extracellular Vesicles to Identify Gastric Cancer Cell Malignancy Based on a Biomimetic Peritoneum.

Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.

Solid epithelioid peritoneal mesothelioma with pulmonary metastasis in feline.

Mesothelioma is a rare malignant neoplasm that affects the mesothelial cells lining the thoracic and abdominal cavities, such as the pleura, peritoneum, and pericardium. It is most prevalent in dogs and cattle, but the causes of this disease in animals are uncertain. In felines, it mainly affects the pleura, with an unfavorable prognosis. This paper explores a rare case of metastatic peritoneal mesothelioma in a 2-year-old female mixed breed cat, emphasizing its uniqueness due to the feline's age. The patient, previously treated at a private clinic, presented moderate abdominal distension as the only clinical sign. Abdominal ultrasound and peritoneal fluid cytology led to the provisional diagnosis of mesothelioma/carcinomatosis. One day after exploratory laparotomy, the animal died and was subsequently sent for necropsy. During macroscopic analysis, nodules were observed in the peritoneum, diaphragm, omentum, stomach serosa, and large intestine, and the diagnosis of solid epithelioid peritoneal mesothelioma with lung metastasis was confirmed after microscopic analysis. The diagnosis of mesothelioma is challenging, and the importance of immunohistochemical panels with specific markers such as cytokeratin AE1/AE3 and calretinin is highlighted. Considering that mesothelioma is a pathology with a poor prognosis, it is essential to include this disease in the list of differential diagnoses within veterinary oncology.

O mesotelioma é uma neoplasia maligna rara que afeta as células mesoteliais que revestem as cavidades torácica e abdominal, como a pleura, o peritônio e o pericárdio. É mais prevalente em cães e bovinos, mas as causas desta doença em animais são incertas. Nos felinos acomete principalmente a pleura, com prognóstico desfavorável. Este artigo explora um caso raro de mesotelioma peritoneal metastático em uma gata sem raça definida de 2 anos de idade, enfatizando sua singularidade devido à idade do felino. O paciente, previamente atendido em clínica particular, apresentava distensão abdominal moderado como único sinal clínico. A ultrassonografia abdominal e a citologia do líquido peritoneal levaram ao diagnóstico provisório de mesotelioma/carcinomatose. Um dia após a laparotomia exploratória, o animal veio a óbito e posteriormente encaminhado para necropsia. Durante a análise macroscópica, foram observados nódulos no peritônio, diafragma, omento, serosa estomacal e intestino grosso e o diagnóstico de mesotelioma peritoneal epitelioide sólido com metástase pulmonar foi confirmado após análise microscópica. O diagnóstico do mesotelioma é desafiador, sendo destacada a importância de painéis imunohistoquímicos com marcadores específicos como citoqueratina AE1/AE3 e calretinina. Considerando que o mesotelioma é uma patologia de prognóstico ruim, é fundamental incluir esta doença na lista de diagnósticos diferenciais dentro da oncologia veterinária.

Efficacy and safety of bevacizumab in patients with low-grade serous ovarian cancer.

Aim: To investigate the efficacy and safety of bevacizumab in patients with recurrent low-grade serous ovarian carcinoma. Materials & methods: The data of patients who received at least two cycles of bevacizumab in combination with chemotherapy were retrospectively recorded. Results: The median age of 51 patients was 56 (range: 33-75) years. The complete response rate was 10.4% and the partial response rate was 43.7%. The objective response rate was 54.1%. Median progression-free survival was 15.9 months (95% CI: 9.1-22.6) and median overall survival was 42.5 months (95% CI: 37.2-47.8). Conclusion: Bevacizumab with chemotherapy is an effective option for treating recurrent ovarian low-grade serous carcinoma.

Pattern of recurrence in endometrial cancer. The murderer always returns to the scene of the crime.

BACKGROUND: Endometrial cancer recurrence occurs in about 18 % of patients. This study aims to analyze the pattern recurrence of endometrial cancer and the relationship between the initial site of primary disease and the relapse site in patients undergoing surgical treatment. METHODS: We retrospectively reviewed all surgically treated patients with endometrial cancer selecting those with recurrence. We defined primary site disease as uterus, lymph nodes, or peritoneum according to pathology analysis of the surgical specimen. The site of recurrence was defined as vaginal cuff, lymph nodes, peritoneum, and parenchymatous organs. Our primary endpoint was to correlate the site of initial disease with the site of recurrence. RESULTS: The study enrolled 1416 patients. The overall recurrence rate was 17,5 % with 248 relapses included in the study. An increase of 9.9, 5.7, and 5.7 times in the odds of relapse on the lymph node, peritoneum, and abdominal parenchymatous sites respectively was observed in case of nodal initial disease (p < 0.001). A not significant difference in odds was observed in terms of vaginal cuff relapse (OR 0.9) between lymph node ad uterine primary disease (p = 0.78). An increasing OR of 8.7 times for nodal recurrences, 46.6 times for peritoneum, and 23.3 times for parenchymatous abdominal recurrences were found in the case of primary peritoneal disease (p < 0.001). CONCLUSION: Endometrial cancer tends to recur at the initial site of the disease. Intraoperative inspection of the adjacent sites of primary disease and targeted instrumental examination of the initial sites of disease during follow-up are strongly recommended.

Cxcl17 is a proinflammatory chemokine and promotes neutrophil trafficking.

CXCL17, a novel member of the CXC chemokine class, has been implicated in several human pathologies, but its role in mediating immune response is not well understood. Characteristic features of immune response include resident macrophages orchestrating successive and structured recruitment of neutrophils and monocytes to the insult site. Here, we show that Cxcl17 knockout (KO) mice, compared to the littermate wildtype (WT) control, were significantly impaired in peritoneal neutrophil recruitment post-lipopolysaccharide (LPS) challenge. Further, the KO mice show dysregulated Cxcl1, Cxcr2, and IL6 levels, all of which directly impact neutrophil recruitment. Importantly, the KO mice showed no difference in monocyte recruitment post LPS-challenge or in peritoneal macrophage levels both in unchallenged and LPS-challenged mice. We conclude that Cxcl17 is a proinflammatory chemokine, and that it plays an important role in the early proinflammatory response by promoting neutrophil recruitment to the insult site.

HDAC1/2 control mesothelium/ovarian cancer adhesive interactions impacting on Talin-1-α5ß1-integrin-mediated actin cytoskeleton and extracellular matrix protein remodeling.

BACKGROUND: Peritoneal metastasis, which accounts for 85% of all epithelial ovarian carcinoma (EOC) metastases, is a multistep process that requires the establishment of adhesive interactions between cancer cells and the peritoneal membrane. Interrelations between EOC and the mesothelial stroma are critical to facilitate the metastatic process. No data is available so far on the impact of histone acetylation/deacetylation, a potentially relevant mechanism governing EOC metastasis, on mesothelial cells (MCs)-mediated adhesion. METHODS: Static adhesion and peritoneal clearance experiments were performed pretreating mesenchymal-like MCs and platinum-sensitive/resistant EOC cell lines with MS-275-a Histone deacetylase (HDAC)1-3 pharmacological inhibitor currently used in combination trials. Results were acquired by confocal microscopy and were analyzed with an automated Opera software. The role of HDAC1/2 was validated by genetic silencing. The role of α4-, α5-α1 Integrins and Fibronectin-1 was validated using specific monoclonal antibodies. Quantitative proteomic analysis was performed on primary MCs pretreated with MS-275. Decellularized matrices were generated from either MS-275-exposed or untreated cells to study Fibronectin-1 extracellular secretion. The effect of MS-275 on ß1 integrin activity was assessed using specific monoclonal antibodies. The role of Talin-1 in MCs/EOC adhesion was analyzed by genetic silencing. Talin-1 ectopic expression was validated as a rescue tool from MS-275-induced phenotype. The in vivo effect of MS-275-induced MC remodeling was validated in a mouse model of peritoneal EOC dissemination. RESULTS: Treatment of MCs with non-cytotoxic concentrations of MS-275 caused a consistent reduction of EOC adhesion. Proteomic analysis revealed several pathways altered upon MC treatment with MS-275, including ECM deposition/remodeling, adhesion receptors and actin cytoskeleton regulators. HDAC1/2 inhibition hampered actin cytoskeleton polymerization by downregulating actin regulators including Talin-1, impairing ß1 integrin activation, and leading to abnormal extracellular secretion and distribution of Fibronectin-1. Talin-1 ectopic expression rescued EOC adhesion to MS-275-treated MCs. In an experimental mouse model of metastatic EOC, MS-275 limited tumor invasion, Fibronectin-1 secretion and the sub-mesothelial accumulation of MC-derived carcinoma-associated fibroblasts. CONCLUSION: Our study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis.

Mesothelioma in the pleura, pericardium and peritoneum: Recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: Mesothelioma is a rare malignancy of the serosal membranes that is commonly related to exposure to asbestos. Despite extensive research and clinical trials, prognosis to date remains poor. Consistent, comprehensive and reproducible pathology reporting form the basis of all future interventions for an individual patient, but also ensures that meaningful data are collected to identify predictive and prognostic markers. METHODS AND RESULTS: This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the international consensus mesothelioma reporting data set. It describes the 'core' and 'non-core' elements to be included in pathology reports for mesothelioma of all sites, inclusive of clinical, macroscopic, microscopic and ancillary testing considerations. An international expert panel consisting of pathologists and a medical oncologist produced a set of data items for biopsy and resection specimens based on a critical review and discussion of current evidence, and in light of the changes in the 2021 WHO Classification of Tumours. The commentary focuses particularly upon new entities such as mesothelioma in situ and provides background on relevant and essential ancillary testing as well as implementation of the new requirement for tumour grading. CONCLUSION: We recommend widespread and consistent implementation of this data set, which will facilitate accurate reporting and enhance the consistency of data collection, improve the comparison of epidemiological data, support retrospective research and ultimately help to improve clinical outcomes. To this end, all data sets are freely available worldwide on the ICCR website (www.iccr-cancer.org/data-sets).

Role of tenascin C in lesion formation in early peritoneal endometriosis.

OBJECTIVE: To identify cytokines or extracellular matrix components that contribute to adhesion to, and invasion of, the peritoneum, proximal to lesions in the early phase of endometriosis. DESIGN: Laboratory-based study. SETTING: University Hospital and Laboratory of Animal Science. PATIENTS AND ANIMALS: Five women with ovarian endometrioma, 138 wild-type (WT) C57BL/6N mice, and 48 Tenascin C (Tnc) knockout (TncKO) mice. INTERVENTIONS: To establish a murine endometriosis model, 20 pieces of minced uterine tissue fragments from each horn were administered intraperitoneally to syngeneic mice. Three days later, endometriotic lesions and peritoneal tissues were collected. Separately, we transfected human peritoneal mesothelial cells (HMrSV5) or human endometrial stromal cells (hESCs) with Tnc small interfering ribonucleic acid. MAIN OUTCOME MEASURES: We employed a polymerase chain reaction array to profile gene expression in the murine peritoneum, in both peritoneum distal to lesions and peritoneum surrounding lesions (PSL). The expression of upregulated genes in the PSL was verified in the peritoneal samples by real-time reverse transcription-polymerase chain reaction. TncKO mice were used to investigate the role of Tnc in the development of endometriosis. We evaluated the proliferative activity or inflammatory state of lesions by Ki67 or CD3 immunostaining. Intraperitoneal distribution of macrophages was assessed by fluorescence-activated cell sorting. Using Tnc small interfering ribonucleic acid, we examined the invasive capacity of hESCs in a coculture system with HMrSV5. RESULTS: Tnc gene expression was significantly higher in PSL than in peritoneum distal to lesions. The weight and number of TncKO lesions in TncKO hosts were lower than those of WT lesions in WT hosts. In contrast, the weight and number of nonattached TncKO lesions in TncKO hosts were higher than those of nonattached WT lesions in WT hosts. We observed decreased Ki67-positive cells or H-scores for CD3, a lower proportion of M1 macrophages, and a higher proportion of M2 macrophages in TncKO lesions in TncKO recipients. Silencing of Tnc expression in hESCs and HMrSV5 diminished the invasivity of hESCs. CONCLUSION: Tnc may be a crucial factor in the development of early peritoneal endometriosis.