Assessment of circulating VEGF as a predictive biomarker of peritoneal carcinomatosis in gastric cancer

Introduction: Early diagnosis of peritoneal carcinomatosis is difficult in patients with gastric cancer who are at high risk of developing peritoneal metastases. The measurement of serum Vascular Endothelial Growth Factor (VEGF) has proven to be a useful prognostic factor in gastric cancer, but it also could be a predictive factor for peritoneal metastases since the VEGF signalling pathway is directly involved in the development of peritoneal metastases. Methods: This is a retrospective study from 2005 to 2017. We reviewed the peritoneal recurrence pattern of a cohort of 59 gastric cancer patients in whom serum VEGF was measured before surgery and after completion of adjuvant treatment Results: Preoperative serum VEGF (pre-VEGF) level was identified as an independent prognostic factor for developing peritoneal metastases. The optimal cut-off value of pre-VEGF levels was 507 pg/mL, which presented a sensitivity of 66 % and a specificity of 78% to predict the development of peritoneal metastases. Patients with high pre-VEGF levels (>507 pg/mL) were at greater risk of developing peritoneal metastases than patients with low pre-VEGF levels (<507 pg/mL) (p=0.023). Conclusions: VEGF plays a crucial role in the development of peritoneal metastases, and serum VEGF meets the requirements of a potential predictive marker for peritoneal carcinomatosis. Therefore, the measurement of serum VEGF levels could be useful during the follow-up of patients with advanced gastric cancer.

PD-L1 regulation in colorectal cancer and role of DNA damage induced by chemotherapies

For patients with metastatic colorectal cancer (CRC), first-line therapy is based on chemotherapeutic agents, such as oxaliplatin, 5-fluorouracil and irinotecan. These drugs increase the overall survival, but resistance to therapy appears in almost 90% of patients, and the 5-year survival rate for patients with metastatic CRC is only about 12%. During the last few years, immune checkpoints blockade therapies have been developed and show good response in different cancers, including CRC with microsatellite instability (MSI). In this CRC subtype, the response rate to anti-PD-(L)1 antibodies is high thanks to the presence of neoantigens and tumor-infiltrating lymphocytes that are associated with the anti-tumor immune response. Nivolumab and pembrolizumab, two anti-PD-1 antibodies, have been approved for CRC MSI treatment. Moreover, it has been shown that the combination of chemotherapy and anti-PD-(L)1 molecules may convert cold tumors into hot tumors in which the immune system and T-cell infiltration are activated. In addition, recent studies found that DNA damage induces PD-L1 expression. ATM, ATR, DNA-PKcs and Chk1 are key sensors of the DNA damage response that regulate PD-L1 expression. This review summarizes the current knowledge on PD-L1 regulation at the genetic, epigenetic, transcriptional and translational levels. It also describes PD-L1 activation in response to chemotherapy and DNA damage. Then, it summarizes the current clinical trials that assess anti-PD-(L)1 therapies in combination with kinase inhibitors or chemotherapeutic agents in CRC.

A review on moderated-t methods for differential expression detection

With the advancement of high-throughput technology, identifying differential expression has become an essential task in multiple domains of biomedical research, such as transcriptome, proteome, metabolome. A wide variety of computational methods and statistical approaches were developed for detecting differential expression. Most of these methods were applicable to modeling expression level of the entire set of features simultaneously. In this article, we provide a review emphasizing on moderated-t methods published in last two decades. We compared similarities and differences between them, and also discussed their limitations in applications.

Capillary leak syndrome (CLS) from rituximab therapy of lymphoma

Capillary Leak Syndome (CLS) is characterized by plasma extravasation into the interstitium with resultant hypotension, anasarca, hemoconcentration, and hypoalbuminemia in the absence of albuminuria. Initially reported in Clarkson’s disease (systemic capillary leak syndrome, SCLS), CLS has been observed in multiple disease settings, the most common being sepsis. In Oncology, CLS has been reported more often as a complication from therapy, and less often from malignancy. In this case study, we documented clinical manifestation, laboratory features and radiological findings of CLS from rituximab therapy when employed in combination with a multi-agent chemotherapy regimen (EPOCH-R). Differentiating drug-induced CLS from sepsis, which presents with the same clinical features, is important in avoiding further exposure to rituximab, which could be fatal to the patient.

In Australia mortality from melanoma is decreasing but increasing for nonmelanoma skin cancer

Mortality from melanoma is decreasing in Australia since 2013. Deaths from non-melanoma skin cancer are increasing.

Bladder-sparing trimodal therapy versus radical cystectomy for muscleinvasive bladder cancer: A systematic review and meta-analysis of comparative studies

Objective: To compare oncologic outcomes between patients with muscle-invasive bladder cancer who were treated with radical cystectomy (RC) or trimodal therapy (TMT). Materials and Methods: The primary sources were the PubMed, Embase, and Cochrane Library electronic databases. Studies published between June 1990 and July 2017 that evaluated combination bladder-sparing surgery for a bladder tumour with radiotherapy (RT) and chemotherapy compared with RC surgery alone for MIBC were included. Published data were extracted and used to calculate the 5-year overall survival rates. The secondary efficacy endpoints were disease-free survival and local and distant recurrence. Results: Nine studies incorporating 15,160 cases were included in the final analysis. Pooled data from 8 studies that assessed overall survival rates for 15,089 patients showed no significant differences in this metric between the TMT and RC groups (HR: 1.27; 95% CI, 0.98-1.63; P=0.066). No significant differences were found between TMT and RC in the subgroup analyses according to the lymph node stage (Nx), age and physiclal status (PS) stage, but differences were found for patients with node-negative disease (HR: 1.36; 95% CI, 1.02-1.81; P=0.036). Disease-free survival and local and distant recurrence did not differ significantly between the techniques. Conclusion: RC seems to be suitable for node-negative disease patients. TMT yielded survival outcomes similar to those of patients who underwent RC. Given the inherent limitations of the included studies, future well-designed RCTs are needed to confirm and update the findings of this analysis.

Limitations of regenerative medicine and cell therapy in cancer therapy

In this paper, the mathematical regularity of the formation of cancer is deduced by the theory of the change and stability of gravitational wave field. The relationship between cancer and DNA information changes is presented. The cancer record of the cell DNA, which does not have a sudden mutation, needs to go through a long smooth evolutionary process.

Radiotherapy cancer treatment modeling with fractional or ordinary derivative

This short communication presents two versions of the cancer treatment model, the ordinary derivative version and the fractional derivative version. The two models were used to simulate a cancer treatment process of a cancer patient with an initial tumor volume of 28.4 cm3 . The simulated final volumes produced by the fractional derivative version were 28.17 cm3 and 5.68 cm3 the normal cells and tumor respectively, while those of the ordinary derivative version were 16.97 cm3 and 0.0 cm3 . In addition, the fractional derivative version was used to simulate a no-treatment process with an initial tumor volume of 5 cm3 , and the final volumes were 4.91 cm3 and 17.41 cm3 for the normal cells and tumor respectively. It was concluded that the radiotherapy treatment process was better simulated with the fractional derivative model.

Checking in with immune checkpoint inhibitors: Results of a needs assessment survey of Canadian rheumatologists

Objectives: Immune checkpoint inhibitors (ICI) are associated with immune-related adverse events (irAE), including autoimmune rheumatologic diseases. The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) undertook a survey to understand the needs of Canadian rheumatologists. Methods: A 25-item survey was developed. It was distributed via electronic mail to 574 members of the Canadian Rheumatology Association (CRA). Results were summarized using descriptive statistics. Results: Over 25% of the respondents were not familiar with irAE. 48.7% reported being ‘slightly or not confident’ in providing advice regarding irAE. Conclusion: The survey highlighted the strong rationale to develop clinical practice guidelines for managing irAE.