Extensive Peritoneal Metastasis Research Articles

Use of Ultrasound-Assisted, Catheter-Directed Thrombolysis in a Patient With High-Risk Pulmonary Embolism.

High-risk pulmonary embolism (PE) is a complex clinical entity associated with high mortality rates. Ultrasound-assisted, catheter-directed thrombolysis, typically used for intermediate-risk PE, may be a viable treatment approach for high-risk PE, particularly in patients at increased risk for major bleeding. This report describes a case in which ultrasound-assisted, catheter-directed thrombolysis was successfully used to treat high-risk PE in a female patient with extensive peritoneal metastases from gastric adenocarcinoma. Other examples from the literature, in which ultrasound-assisted, catheter-directed thrombolysis was used to treat high-risk PE, are also provided.

Application of 3D reconstruction and 3D printing technology in advanced ovarian cancer surgery: a retrospective study.

Advanced ovarian cancer is frequently accompanied by extensive peritoneal metastasis, complicating surgical interventions. This study aims to explore the application of 3D reconstruction and 3D printing technology in the treatment of advanced ovarian cancer. We conducted a retrospective analysis of 60 patients with stage III ovarian cancer who underwent cytoreductive surgery at Hebei University Affiliated Hospital between 2020 and 2023. Patients were randomly assigned to three groups: a 3D visualization group, a 3D visualization plus 3D printing group, and a traditional 2D CT imaging evaluation group. High-precision medical imaging techniques (e.g., CT, MRI) were employed to create digital 3D models, which were then converted into physical entities using 3D printing for surgical planning and simulation. Both the 3D visualization group and the 3D visualization plus 3D printing group demonstrated superior outcomes in terms of surgery duration and blood loss compared to the traditional 2D CT group, indicating the efficacy of 3D reconstruction and 3D printing in preoperative planning. Postoperative recovery indicators, such as hospital stay and time to first flatus, were also more favorable in the groups utilizing 3D technology. Although there were no significant differences in postoperative complications and recurrence rates among the three groups, the groups using 3D technology showed advantages in reducing certain complications. The results indicate that medical 3D technology has significant value in the surgical planning of advanced ovarian cancer, enhancing surgical precision and reducing intraoperative risks, which may aid in improving postoperative recovery.

Interferon-ε is a tumour suppressor and restricts ovarian cancer.

High-grade serous ovarian cancers have low survival rates because of their late presentation with extensive peritoneal metastases and frequent chemoresistance1, and require new treatments guided by novel insights into pathogenesis. Here we describe the intrinsic tumour-suppressive activities of interferon-ε (IFNε). IFNε is constitutively expressed in epithelial cells of the fallopian tube, the cell of origin of high-grade serous ovarian cancers, and is then lost during development of these tumours. We characterize its anti-tumour activity in several preclinical models: ovarian cancer patient-derived xenografts, orthotopic and disseminated syngeneic models, and tumour cell lines with or without mutations in Trp53 and Brca genes. We use manipulation of the IFNε receptor IFNAR1 in different cell compartments, differential exposure status to IFNε and global measures of IFN signalling to show that the mechanism of the anti-tumour activity of IFNε involves direct action on tumour cells and, crucially, activation of anti-tumour immunity. IFNε activated anti-tumour T and natural killer cells and prevented the accumulation and activation of myeloid-derived suppressor cells and regulatory T cells. Thus, we demonstrate that IFNε is an intrinsic tumour suppressor in the female reproductive tract whose activities in models of established and advanced ovarian cancer, distinct from other type I IFNs, are compelling indications of potential new therapeutic approaches for ovarian cancer.

Genetically Engineered Artificial Exosome-Constructed Hydrogel for Ovarian Cancer Therapy.

Owing to the insidious onset of ovarian cancer, most patients are in the advanced stage with extensive peritoneal metastasis when they are diagnosed. Treatment of peritoneal metastasis from advanced ovarian cancer remains a significant challenge. Inspired by the massive macrophages in the peritoneal environment, here, we reported an artificial exosome-based peritoneal-localized hydrogel to domesticate peritoneal macrophages as the therapeutic target for realizing potent ovarian cancer therapy, where artificial exosomes derived from genetically sialic-acid-binding Ig-like lectin 10 (Siglec-10)-engineered M1-type macrophages were chemically designed as gelator. Upon triggering immunogenicity with X-ray radiation, our hydrogel encapsulating efferocytosis inhibitor MRX-2843 enabled a cascade regulation to orchestrate polarization, efferocytosis, and phagocytosis of peritoneal macrophages for realizing robust phagocytosis of tumor cells and powerful antigen presentation, offering a potent approach for ovarian cancer therapy via bridging the innate effector function of macrophages with their adaptive immune response. Moreover, our hydrogel is also applicable for potent treatment of inherent CD24-overexpressed triple-negative breast cancer, providing an emerging therapeutic regimen for the most lethal malignancies in women.

Bidirectional Chemotherapy in Advanced Colorectal Cancer Peritoneal Metastases.

Colorectal cancer (CRC) patients with extensive peritoneal metastases who are not candidates for CRS-HIPEC have poor prognoses. We evaluated the role of systemic and intra-peritoneal (IP) chemotherapy in these patients. CRC patients with confirmed peritoneal metastasis were enrolled. After implantation of IP chemoport patients received weekly IP paclitaxel in incremental doses of 20 mg/m2 with systemic chemotherapy. The primary end-points were the feasibility, safety, and tolerance (perioperative complications), and the secondary end-point was the clinico-radiological response. Patients included in the study were registered between January 2018 and November 2021. IP chemoport was implanted in 18 patients of which 14 patients underwent successful instillation of IP chemotherapy. Four patients did not receive IP chemotherapy in view of port-site infection for which IP ports were removed. The median age was 39 years (range: 19-61 years). The site of the primary tumor was equal in the colon and rectum. Fifty percent of patients had signet ring-cell adenocarcinoma, and 21% had poorly differentiated adenocarcinoma. The median serum of CEA level was 12.27 ng/mL (1.63-116.16 ng/mL). The median PCI score was 25 (18-35). The median number of IP chemotherapy cycles (weekly) was 3.5 (1-12 cycles). In 14.3% of patients, IP chemoport had to be removed due to block and infection. Three, five, and four patients had clinico-radiologically disease progression, stable disease, and partial response, respectively. One patient underwent subsequent successful CRS-HIPEC. There were no grade 3-5 (CTCAE 3.0) complications. Incremental doses of IP paclitaxel with systemic chemotherapy is safe and feasible in selected colorectal adenocarcinoma patients with peritoneal metastases without any serious adverse events.

Carrier-free multifunctional nanomedicine for intraperitoneal disseminated ovarian cancer therapy

BackgroundOvarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25–30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect.Methods and resultsIn this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice.ConclusionIn summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer.Graphical

The Role of Diffusion Weighted Imaging in suspected cases of ovarian cancer

BackgroundOvarian cancer is a common gynecological malignancy and often diagnosed late with extensive peritoneal and nodal metastasis. Diffusion-weighted imaging (DWI) provides valuable information about the structural properties of the tissue and has shown great value in cancer imaging. Recently developed post-processing three-dimensional apparent diffusion coefficient (3D ADC) map has a significant value in variable tumors yet its role in ovarian cancer is not well established. We aim to evaluate the added value of DWI and 3D ADC maps in the diagnosis of ovarian masses, detection of nodal and peritoneal deposits, and so appropriate management planning.ResultsConventional MRI and DWI were performed to fifty-one patients with complex cystic or solid adnexal lesions depicted by gynecological ultrasonography. Results were compared with surgical and histopathologic findings revealing 23/51 (45%) had malignant ovarian tumors and 28/51 (55%) had benign ovarian pathologies. The mean 3D ADC values were 0.977 ± 0.32, 0.934 ± 0.27, and 0.956 ± 0.25 × 10−3 mm2/s for ovarian, nodal, and peritoneal malignancy respectively which were significantly lower than the mean 3D ADC values of benign ovarian lesions, non-metastatic lymph nodes and benign peritoneal lesions/fat which were measured 1.516 ± 0.6, 1.208 ± 0.25, and 1.46 ± 0.43 × 10−3 mm2/s respectively.ConclusionAdding DWI and 3D ADC maps to routine MRI improves the sensitivity, specificity, and accuracy for detecting ovarian malignancy, nodal, and peritoneal metastasis. They also provide qualitative data helping in the differentiation of malignant and non-malignant entities.

LncRNA ABHD11-AS1, regulated by the EGFR pathway, contributes to the ovarian cancer tumorigenesis by epigenetically suppressing TIMP2.

ObjectiveEpithelial ovarian cancer (EOC) is a common gynecologic malignancy characterized by extensive peritoneal metastasis and high mortality rate. ABHD11 Antisense RNA1 (ABHD11‐AS1) has recently been identified as a regulator of growth and metastasis in multiple tumors, including EOC. However, the biological function and potential mechanism of ABHD11‐AS1 in EOC remains poorly understood.MethodsImmunohistochemistry, western blot, and qRT‐PCR analysis were used to determine the expression pattern of ABHD11‐AS1 and epidermal growth factor receptor (EGFR) in both EOC tissues and cell lines, respectively. Colony formation, transwell and wound healing assays were performed to evaluate the roles of EGFR and ABHD11‐AS1 on the capacity of cell proliferation, migration, and invasion. Western blot analysis was performed to measure the regulation of EGFR pathway on STAT3. Moreover, chromatin immunoprecipitation was employed to demonstrate the interaction between ABHD11‐AS1 and STAT3. RNA immunoprecipitation was subjected to prove the direct binding between ABHD11‐AS1 and EZH2. Immunofluorescence staining was performed to measure the expression and localization of TIMP2. EOC mouse model was conducted for validating the role of ABHD11‐AS1 in vivo.ResultsEGFR and ABHD11‐AS1 were highly expressed in EOC tissues and cell lines. Knockdown of EGFR or ABHD11‐AS1 inhibited cell growth, migration, and invasion of EOC cells. Expression of ABHD11‐AS1 was regulated by the activation of EGFR signaling pathway, mediated by STAT3. Besides, ABHD11‐AS1 was shown to silence TIMP2 by binding to chromatin‐modifying enzyme EZH2. Furthermore, inhibition of EGFR pathway or ABHD11‐AS1 repressed the tumor growth of EOC.ConclusionWe defined the regulatory relationship between the EGFR signaling pathway, ABHD11‐AS1, EZH2, and TIMP2 suggesting that ABHD11‐AS1 may act as an oncogene and a potential target for antitumor therapies in ovarian cancer.

Ulcerated duodenal gastrointestinal stromal tumor – Demonstration of an interesting radiological sign (the Torricelli-Bernoulli sign)

The Torricelli-Bernoulli sign is a useful computed tomographic sign seen in ulcerated/necrotic gastrointestinal stromal tumor (GIST) or leiomyosarcoma characterized by the collection of air in the nondependent aspect of larger gastrointestinal cavitating tumors. This sign is based on the physical principle of the law of Torricelli's and Bernoulli's principle. Herein, we describe this interesting imaging sign in an adult male with malignant duodenal GIST with extensive hepatic, peritoneal, omental, and lymph nodes (though rare in GIST) metastasis. The patient succumbed few days after admission.

Modeling Ovarian Cancer Multicellular Spheroid Behavior in a Dynamic 3D Peritoneal Microdevice.

Ovarian cancer is characterized by extensive peritoneal metastasis, with tumor spheres commonly found in the malignant ascites. This is associated with poor clinical outcomes and currently lacks effective treatment. Both the three-dimensional (3D) environment and the dynamic mechanical forces are very important factors in this metastatic cascade. However, traditional cell cultures fail to recapitulate this natural tumor microenvironment. Thus, in vivo-like models that can emulate the intraperitoneal environment are of obvious importance. In this study, a new microfluidic platform of the peritoneum was set up to mimic the situation of ovarian cancer spheroids in the peritoneal cavity during metastasis. Ovarian cancer spheroids generated under a non-adherent condition were cultured in microfluidic channels coated with peritoneal mesothelial cells subjected to physiologically relevant shear stress. In summary, this dynamic 3D ovarian cancer-mesothelium microfluidic platform can provide new knowledge on basic cancer biology and serve as a platform for potential drug screening and development.

Re-purposing of curcumin as an anti-metastatic agent for the treatment of epithelial ovarian cancer: in vitro model using cancer stem cell enriched ovarian cancer spheroids.

Malignant epithelial ovarian cancer (EOC) spheroids high frequently are detected in the malignant ascites of the patients with the extensive peritoneal metastasis of ovarian cancer, which represent a significant obstacle to efficacious treatment. Clinical data also suggested that EOC spheroids play a putative role in the development of chemoresistance. Since standard surgery and conventional chemotherapy is the only available treatment, there is an urgent need to identify a more effective therapeutic strategy. Recent studies demonstrated that curcumin exerts an anticancer effect in a variety of human cancers including ovarian cancer. This study evaluates anti-peritoneal metastasis and chemoresistance of curcumin related to the EOC spheroids. In this study, we confirm that the high invasive EOC cells forming the spheroids express a high level of a cancer stem cell (CSC) marker, aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which was significantly down-regulated by curcumin treatment. Curcumin treatment markedly enhances the sensitivity of EOC spheroids to cisplatin in a dose-dependent manner. Our experiments provided evidence that curcumin could abolish the sphere-forming capacity of EOC cells in a dose-dependent manner. Moreover, curcumin substantially suppressed the growth of the pre-existed EOC spheroids, inhibited the adhesion of EOC spheroids to ECM as well as the invasion of EOC spheroids to the mesothelial monolayers. We propose to re-purpose curcumin as anti-metastatic and chemoresistant agent for EOC management in combination with conventional regimen. Further preclinical studies are necessary to validate the anti-cancer effect of curcumin in patients with EOC.

An Unexpected Diagnosis from ERCP for Ascending Cholangitis and Ampullary Mass: Extranodal Diffuse Large B-Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is a histological subtype of non-Hodgkin lymphoma (NHL) that accounts for approximately 25% of all NHL cases. DLBCL usually presents as an enlarging mass, most commonly as nodal enlargement in the neck or axilla. Systemic B-symptoms are often reported, including severe night sweats, fever, and weight loss. Extranodal disease has been reported in up to 30 percent of cases, and the diagnosis of DLBCL is most commonly made with excisional lymph node biopsy. A 73 y/o F with a PMH of anemia presented with painless jaundice, abdominal pain, and weight loss. Physical was remarkable for jaundice and sclera icterus. Labs were positive for a WBC of 18.4, ALT of 73, AST of 57, ALKP of 786, total bilirubin of 3.7, direct bilirubin of 3.2, LDH of 247, and lipase of 859. US abdomen showed marked intra- and extra-hepatic biliary dilation, gallbladder distention, and abrupt termination of the CBD in the pancreatic head. CT scan confirmed biliary dilation with extensive peritoneal metastases or lymph nodes. A CA 19-9 level was 8894. An ERCP with cytology brushing and ampulla biopsy revealed an ampullary mass, a 1.5 cm dilated intrahepatic biliary tract, and a 5 cm distal and mid-common bile duct stricture beginning at the ampulla. A PET-CT scan was obtained, which showed abnormal uptake in posterior mediastinal, right axillary, right cardiophrenic, mesentery, and retroperitoneum lymph nodes, as well as in the right liver lobe and the pancreatic head and tail. Cytology brushing revealed atypical cells, and ampullary biopsy revealed DLBCL. This case of DLBCL was unique for multiple reasons. The initial symptoms of painless jaundice, abdominal pain, subjective fevers, and recent weight loss are not typical presenting symptoms of DLBCL; no rapidly enlargement mass or nodal enlargement of the neck and axilla was present. Her symptoms could have been explained solely by her ascending cholangitis. It was also remarkable how the clinical presentation resembled pancreatic adenocarcinoma but was actually due to a DLBCL with significant distant metastasis. This less common extranodal presentation would not have been expected given her complaints, as additional symptoms or a diagnosis would have presumably been previously suspected. Lastly, the majority of DLBCL diagnoses are made with excisional lymph node biopsy, but this case's diagnosis was interestingly made from an ampullary mass biopsy from an ERCP for ascending cholangitis.

Clinical Research of Intraperitoneal Implantation of Sustained-release 5-Fluorouracil in Advanced Colorectal Cancer

Background: The objective of this study was to investigate the safety and long-term clinical effect of intraperitoneal implantation of sustained-release 5-fluorouracil in patients with advanced colorectal cancer during radical resection. Methods: A total of 202 patients with advanced colorectal cancer undergoing radical operations were randomly divided into an experimental group (98 cases, intraoperative intraperitoneal implantation of sustained-release 5-fluorouracil 600 mg as local chemotherapy) and a control group (104 cases, without local chemotherapy). The clinical data of the two groups was compared including toxicity, complications, local recurrence rate, distant metastasis, disease-free survival, and 1-, 3-, and 5-year survival rates. Results: Both groups of patients were followed up for more than 5 years, the longest follow-up time was 7.5 years. Bone marrow suppression, hepato-renal function, postoperative anastomotic leakage, pelvic effusion, incision infection, the incidence of intestinal obstruction, venting time, and hospital stay after operation (days) between two groups had no statistical significant difference. Locoregional recurrence and liver metastasis rate were decreased significantly in experimental group (P = 0.04 and 0.04). Extensive peritoneal metastasis and other organ metastasis rates had no significant difference between two groups. In the experimental group, 1-, 3-, and 5-year survival rates were higher than in the control group (95.92 vs 87.50 %, 77.55 vs 64.42 %, and 56.12 vs 40.38 %), which had significant difference. Disease-free survival (DFS) of the experimental group was higher than that of the control group (χ2 = 5.00, P = 0.025). Conclusions: Intraperitoneal implantation of sustained-release 5-fluorouracil is safe for advanced colorectal cancer during radical resection, which can reduce locoregional recurrence rate and liver metastasis rate. The long-term efficacy was reliable, and long-term survival and disease-free survival rate can be improved.

Impact of cytoreductive surgery on survival in gastric cancer patients with peritoneal metastasis

To investigate the survival benefit of cytoreductive surgery in gastric cancer patients with peritoneal metastasis. Clinicopathological data of 151 advanced gastric adenocarcinoma patients with extensive peritoneal metastasis who were identified by surgical exploration between May 2008 and April 2015 in Xijing Hospital of Digestive Diseases were analyzed retrospectively. Of all the patients, 32 cases were treated by cytoreductive surgery with local radical tumor resection and regional lymph node cleaning, combined with fluorouracil-based adjuvant chemotherapy after surgery (cytoreductive surgery combined with chemotherapy group); 39 caseswere only treated by cytoreductive surgery group(cytoreductive surgery group);23 caseswere treated bysurgical exploration combined with fluorouracil-based adjuvant chemotherapy after surgery(surgical exploration combined with chemotherapy group) and 57 cases were only treated bysurgical exploration (surgical exploration group). The overall survival of four groups were analyzed and compared. Among the 151 patients, 148 (98.0%) patients were followed up. The median follow up time was 7.2 months (range 1.4-61.2). The median survival of cytoreductive surgery combined with chemotherapy group, cytoreductive surgery group, surgical exploration combined with chemotherapy group and surgical exploration group was 11.9(95% CI: 8.8-15.1) months, 7.1(95% CI: 3.2-11.1) months, 8.2(95% CI:4.6-11.8) and 5.4(95% CI:4.4-6.4) months, respectively(P < 0.01). Cytoreductive surgery can prolong the survival of gastric adenocarcinoma patients with extensive peritoneal metastasis. Cytoreductive surgery combined with chemotherapy may provide more benefit for patients, and can be used as a choice of treatment in these patients.

Clinical research of intraperitoneal implantation of sustained-release 5-fluorouracil in advanced colorectal cancer.

BackgroundThe objective of this study was to investigate the safety and long-term clinical effect of intraperitoneal implantation of sustained-release 5-fluorouracil in patients with advanced colorectal cancer during radical resection.MethodsA total of 202 patients with advanced colorectal cancer undergoing radical operations were randomly divided into an experimental group (98 cases, intraoperative intraperitoneal implantation of sustained-release 5-fluorouracil 600 mg as local chemotherapy) and a control group (104 cases, without local chemotherapy). The clinical data of the two groups was compared including toxicity, complications, local recurrence rate, distant metastasis, disease-free survival, and 1-, 3-, and 5-year survival rates.ResultsBoth groups of patients were followed up for more than 5 years, the longest follow-up time was 7.5 years. Bone marrow suppression, hepato-renal function, postoperative anastomotic leakage, pelvic effusion, incision infection, the incidence of intestinal obstruction, venting time, and hospital stay after operation (days) between two groups had no statistical significant difference. Locoregional recurrence and liver metastasis rate were decreased significantly in experimental group (P = 0.04 and 0.04). Extensive peritoneal metastasis and other organ metastasis rates had no significant difference between two groups. In the experimental group, 1-, 3-, and 5-year survival rates were higher than in the control group (95.92 vs 87.50 %, 77.55 vs 64.42 %, and 56.12 vs 40.38 %), which had significant difference. Disease-free survival (DFS) of the experimental group was higher than that of the control group (χ2 = 5.00, P = 0.025).ConclusionsIntraperitoneal implantation of sustained-release 5-fluorouracil is safe for advanced colorectal cancer during radical resection, which can reduce locoregional recurrence rate and liver metastasis rate. The long-term efficacy was reliable, and long-term survival and disease-free survival rate can be improved.

Targeting JAK1/STAT3 signaling suppresses tumor progression and metastasis in a peritoneal model of human ovarian cancer.

JAK/STAT3 is one of the major signaling pathways that is aberrantly activated in ovarian cancer and associated with tumor progression and poor prognosis in patients with ovarian cancer. In this study, we evaluated the therapeutic potential of targeting JAK/STAT3 signaling in ovarian cancer using a peritoneal dissemination mouse model. We developed this mouse model by injecting a metastatic human ovarian cancer cell line, SKOV3-M-Luc, into the peritoneal cavity of immunodeficient mice. This model displayed a phenotype similar to late-stage ovarian cancer, including extensive peritoneal metastasis and ascites production. The constitutive activation of STAT3 in human ovarian cancer cells appeared to be mediated by an autocrine cytokine loop involving the IL6 family of cytokines and JAK1 kinase. shRNA-mediated knockdown of JAK1 or STAT3 in ovarian cancer cells led to reduced tumor growth, decreased peritoneal dissemination, and diminished ascites production, suggesting a critical role of STAT3 in ovarian cancer progression. Similar results were obtained when a small-molecule inhibitor (JAKi) of the JAK1 kinase was used to treat ovarian cancer in this model. In addition, we found that the expression level of IL6 was correlated with activation of STAT3 in ovarian cancer cells both in vitro and in vivo, suggesting a potential application of IL6 as a biomarker. Altogether, our results demonstrate that targeting JAK1/STAT3, using shRNA knockdown or a small-molecule inhibitor, effectively suppressed ovarian tumor progression and, therefore, could be a potential novel therapeutic approach for treating advanced ovarian cancer.

Evidence for the antagonistic form of CXC‐motif chemokine CXCL10 in serous epithelial ovarian tumours

Patients with high-grade, serous epithelial ovarian carcinoma (HGSOC) are generally diagnosed with extensive peritoneal metastases, and exhibit 5-year survival rates <30%. A subset of these tumours, defined as "immunoreactive," overexpress mRNA encoding the T-cell-recruiting chemokine CXCL10 (10-kDa interferon gamma-induced protein; C-X-C motif chemokine 10). Tumour-infiltrating CD4(+) CD8(+) T-cells are a well-documented, positive prognostic indicator for HGSOC patients; paradoxically, however, patients diagnosed with HGSOC (overexpressing CXCL10 and therefore theorised to recruit T-cells) typically exhibit poor survival. Recently, an "antagonistic" CXCL10 variant was identified that inhibited leucocyte recruitment to inflamed liver in vivo (Casrouge et al., J Clin Invest 2011;121:308-17). We hypothesised that "immunoreactive" HGSOC might also express antagonistic CXCL10, interfering with leucocyte recruitment and contributing to poor patient prognosis. CXCL10 expression was analysed in HGSOC tissues grouped according to pathology, grade and FIGO stage at diagnosis, and its localisation and association with T-cells established by immunohistochemical staining in tissue microarrays. CXCL10 expression was increased in a subset of serous epithelial tumour samples; however, it did not correlate well with CD45-positive tumour infiltrate. Immunoprecipitation and de novo sequence analysis of CXCL10 identified the N-terminally cleaved, "antagonistic" variant of CXCL10 specifically in malignant tumours, and not in benign ovarian disease. The data demonstrate the presence of the antagonistic form of CXCL10 in HGSOC for the first time, and provide a partial explanation for reduced leucocyte infiltration observed in these tumours. We suggest that CXCL10 cleavage and subsequent antagonism of immune cell recruitment may be a feature of the "immunoreactive" HGSOC subtype, leading to early impairment of the immune response and subsequently worsening patient prognosis.

Validation and Clinical Use of the Japanese Classification of Colorectal Carcinomatosis: Benefit of Surgical Cytoreduction Even without Hyperthermic Intraperitoneal Chemotherapy

Background: This study aimed to validate an easy to use practical classification of peritoneal metastasis arising from colorectal cancer. Patients and Methods: Data from 2,134 consecutive patients who underwent resection for colorectal cancer at a single institution were reviewed. Peritoneal metastasis was classified depending on extent into three groups (P1–P3). The macroscopic radical resection rates and survival of patients with colorectal cancer complicated with peritoneal metastasis were analyzed. Results: Of the 2,134 patients, 116 (5.4%) had peritoneal metastasis. Among them, 20 (17.2%) underwent macroscopic radical resection. Tumor location on the right side was associated with more extensive peritoneal metastasis (p = 0.010). Male gender (p = 0.0027), liver metastasis (p = 0.0021), and P3 peritoneal metastasis were independent risk factors for noncurative resection. The Cox proportional hazards model showed that gender (p = 0.031), operation period (p = 0.031), and macroscopic radical resection for colorectal cancer and peritoneal metastasis (p = 0.031) were independent prognostic factors. Conclusions: Being female with left colon cancer complicated with P1 or P2 peritoneal metastasis is a good indicator for macroscopic radical resection if liver metastasis is absent. The present classification helped to determine surgical indication for patients with colorectal cancer complicated with synchronous peritoneal metastasis in routine clinical practice.

Malignant ovarian melanoma with extensive pelvic and peritoneal metastasis: a case report and literature review

Malignant ovarian melanoma with extensive pelvic and peritoneal metastasis: a case report and literature review

Functional significance of VEGF-a in human ovarian carcinoma: Role in vasculogenic mimicry

Ovarian cancer is a silent killer, and shows early extensive tumor invasion and peritoneal metastasis. The microcirculation of most tumors includes cooperation of pre-existing vessels, intussusceptive microvascular growth, postnatal vasculogenesis, glomeruloid angiogenesis, and vasculogenic mimicry (VM). VM is critical for a tumor blood supply and is asscociated with aggressive features and metastasis. Our studies highlight the plasticity of aggressive human ovarian carcinoma cells and call into question the underlying significance of their ability to form VM in vitro induced by VEGF-a. These studies also show their clinicalpathological features of the cancers with human Paraffin-embedded tumor tissue samples. Results show that the process: VEGF-a→EphA2→MMPs→VM is the main pathway for VM formation and VEGF-a appears to play an important role in the formation of VM based on our in vitro assays and clinical immunohistochemical analyses. VM-targeting strategies for ovarian cancer include anti-VEGF-a treatment, knocking down the EphA2 gene and using antibodies against human MMPs if the tumor is VM positive. This strategy may be of significant value in laying the foundation for a more explicit anti-tumor angiogenesis therapy.