Current management strategies for peritoneal mesothelioma

Mesothelioma of the peritoneum is a distinct entity that requires multidisciplinary care to improve oncological outcomes. In this article, we review the current management strategies discussed at the PSOGI meeting in Washington DC 2016 and provide evidence based recommendations for diagnosis and management of this disease

Lack of Oncological Benefit from Bursectomy in Radical Gastrectomy: A Systematic Review

Background: Resection of the omental bursa has been suggested to reduce peritoneal recurrence and facilitate a complete oncological resection during a gastrectomy. The addition of this procedure increases technical complexity and prolongs the procedure. Published data regarding the oncological benefit of this procedure are conflicting. We hypothesized that a bursectomy during a radical gastrectomy does not improve overall survival. Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline, a comprehensive literature search of 3 electronic databases (PubMed, Scopus, and Embase) was conducted to identify the clinical studies that compared bursectomy with no-bursectomy in radical gastrectomy for gastric adenocarcinoma. Qualitative and quantitative data synthesis was performed using RevMan software. A random-/fixed-effect modeling was used depending upon the heterogeneity. Bias and quality assessment tools were applied. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019116556). Results: Of 8 studies assessing the role of bursectomy in gastric adenocarcinoma, 6 (75%) were included – of which 2 (33%) are randomized controlled trials. Of 2,904 patients, 1,273 (%) underwent a bursectomy. There was no statistically significant difference in either overall survival (hazard ratio [HR] = 0.89, 95% CI 0.75–1.06, I2 = 14%) or disease recurrence (HR = 1.01, 95% CI 0.84–1.20, I2 = 22%) in the bursectomy group compared to the no-bursectomy group. Conclusion: There is no additional oncological benefit of adding bursectomy to radical gastrectomy in all patients with gastric adenocarcinoma

SerpinB3 Drives Cancer Stem Cell Survival in Glioblastoma

Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced with radiation. Finally, we found that SerpinB3 knockdown increased the efficacy of radiation in pre-clinical models. Taken together, our findings identify a GBM CSC-specific survival mechanism involving a cysteine protease inhibitor, SerpinB3, and provide a potential target to improve the efficacy of GBM therapies against therapeutically resistant CSCs

Refining colorectal cancer classification and clinical stratification through a single-cell atlas

Background Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells. Results Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance. Conclusions Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patient

Redefining tumor classification and clinical stratification through a colorectal cancer single-cell atlas

Colorectal cancer (CRC), a disease of high incidence and mortality, exhibits a large degree of inter- and intra-tumoral heterogeneity. The cellular etiology of this heterogeneity is poorly understood. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes that significantly stratifies overall survival in more than 1,500 CRC patients with bulk transcriptomic data. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development. Competing Interest Statement: The authors have declared no competing interest

Are We Ready for Hyperthermic Intraperitoneal Chemotherapy in the Upfront Treatment of Ovarian Cancer?

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Surgical Treatment of Peritoneal Carcinomatosis from Gastric Cancer

Peritoneal carcinomatosis from gastric cancer is considered a fatal disease with limited treatment options. Recent advances in the understanding of the disease process, systemic chemotherapy, and application of cytoreductive surgery and hyperthermic chemoperfusion have shown promising results in the management of this difficult disease. Novel therapies such as extensive intraperitoneal lavage and intraperitoneal targeted agents are being applied in the management of this disease. We review the current literature in this field and describe the rationale behind some of these advances

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: Where do we stand?

Plain Language Summary Patients with colorectal cancer that has spread to the lining of the abdomen (peritoneum) benefit from surgery to remove all the cancer. The addition of certain types of intra-abdominal chemotherapy during surgery improves survival for select patients.</p