An advanced endoscopic surgery robotic platform for removal of early-stage gastrointestinal cancer using endoscopic submucosal dissection

Two gastrointestinal (GI) cancers, stomach and colorectal cancer, have the fifth and third highest incident rates and the fourth and second highest mortality rates among all cancers, respectively. Combined, they had 2.8 million new cases and 1.6 million deaths annually. Fortunately, early-stage GI cancer has a high five-year survival rate if the tumour can be removed completely. Endoscopic Submucosal Dissection (ESD) is the gold standard for the removal of early-stage GI cancer as it has a high rate of en-bloc resection and a low rate of recurrence. However, ESD is a very technically challenging surgical operation. It has a relatively high rate of failure, including perforation of the stomach or colon. Therefore, a surgical robotic platform with high dexterity and better ergonomics is in high demand, which can ease the technical problems induced by conventional ESD procedures. In our previous study, a prototype of an endoscopic surgery robotic platform was built and the preliminary experimental results showed that the dual flexible arm robotic platform with wire-driven continuum structure was capable of increasing the efficiency and safety in performing ESD under the master-slave controlling scheme. An advanced robotic platform was built based on this prototype to achieve higher flexibility and production requirements. The design of these two platforms and experimental results will be presented in detail.

P-OGC66 Mental Health and Wellbeing Services for Patients with Upper GI Cancer

Background Cancer related distress has a major impact on quality of life. The psychosocial needs of patients post an oesophagectomy are significant and exacerbate the physical burden. The Upper GI MDT at our hospital aim to provide holistic patient centred care that equips patients mentally and physically for their treatment pathway. Formal or structured pyschoncology services are not routinely available to our patient cohort. The aim of the audit undertaken was to assess awareness of and subsequent engagement with available mental health services in patients undergoing a curative resection for oesophagogastric cancer. Methods Patients who underwent either a gastrectomy or oesophagectomy in the Upper GI Centre between Nov 2018 and May 2019 were included. They each received a questionnaire to complete anonymously. Responses were via prepaid post. Responses were collated and analysed. Results 36 questionnaires sent out with 21 patients responding (Response rate 58%). Average age:69 (age range 40-84). 18 of the 21 responses were male Time diagnosed with cancer: 57% were between 12 to 18 months post diagnosis and 43% between 6 to 11 months. Source of Information received: 43% reported verbal information provided and 38% reported written information was provided Current engagement with Mental Health Services: National, Community, and Exercise programmes were used by a very small number of patients - 6 in total out of 21 respondents Reasons for not engaging with Mental Health Services responses included ‘Not being interested or required' to ‘fearful' ‘No knowledge of service' to ‘Cant remember ' or ‘Plans to engage' 93% of respondents would recommend use of wellbeing or mental health services to someone with a diagnosis of an Upper GI Cancer Suggestions for improvements varied from use of information packs, information on life post op and more guidance needed surrounding availability of current mental health supports Conclusions Psychosocial issues need to be addressed and there is a huge deficit in current service provision. Current service is not meeting service user needs and not empowering patients how best to manage mental burden and thus contribute to maximising treatment outcomes. National Cancer Strategy acknowledges lack of access for cancer patients to pyschoncology services. The Cancer Centre is awaiting appointment of a Pyschoncology Consultant and Team in the coming months. The Upper GI MDT will seek access to this service once available for their patient cohort. In interim use limited national and community resources available. Provide education to wider team members to standardise approach providing both written and verbal information on available mental health and well being services, embed mental health awareness into daily practice with encouragement for early patient intervention if cancer related distress evident. Re Audit after introduction of these measures.

CRISPR/Cas9 in Gastrointestinal Malignancies

Gastrointestinal (GI) cancers such as colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EG), pancreatic duct adenocarcinoma (PDAC) or hepatocellular cancer (HCC) belong to the most commonly diagnosed types of cancer and are among the most frequent causes of cancer related death worldwide. Most types of GI cancer develop in a stepwise fashion with the occurrence of various driver mutations during tumor progression. Understanding the precise function of mutations driving GI cancer development has been regarded as a prerequisite for an improved clinical management of GI malignancies. During recent years, CRISPR/Cas9 has developed into a powerful tool for genome editing in cancer research by knocking in and knocking out even multiple genes at the same time. Within this review, we discuss recent applications for CRISPR/Cas9-based genome editing in GI cancer research including CRC, GC, EG, PDAC and HCC. These applications include functional studies of candidate genes in cancer cell lines or organoids in vitro as well as in murine cancer models in vivo, library screening for the identification of previously unknown driver mutations and even gene therapy of GI cancers.

The effect of menopausal hormone therapy on gastrointestinal cancer risk and mortality in South Korea: a population-based cohort study

Background The effect of menopausal hormone therapy (MHT) on gastrointestinal (GI) cancers is controversial, and no research has been conducted in the East. This study investigates the association between MHT and GI cancer risks in South Korea. Methods A prescription-based cohort study was conducted using the NHIS Sample Cohort (2002–2013) of Korea. We used 1:5 propensity score matching, and 22,577 MHT users and 111,113 non-users were selected. Kaplan–Meier survival curves with log-rank tests were used. Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Landmark analysis was used to determine dose–response relationship. Results The median follow-up was 79.6 of months. Kaplan–Meier survival curve showed less frequent GI cancer diagnoses in MHT users compared to non-users (0.13 vs. 0.16 per 100,000 person-years). Menopausal hormone therapy was associated with decreased incidence of GI cancer (HR = 0.809, 95%CI = 0.691–0.946) and colorectal cancer (CRC) (HR = 0.757, 95%CI = 0.577–0.995). Gastric cancer (GC) incidence showed marginal significance (HR = 0.787, 95%CI = 0.605–1.023). The mortality from GI cancer was lower in MHT users than in non-users (HR = 0.737, 95%CI = 0.547–0.993). The relationship between MHT and GI cancer was stronger with increasing MHT dose in terms of both incidence (Ptrend = 0.0002) and mortality (Ptrend = 0.0064). Conclusions The association between MHT use and reduced risks of GI cancers was attributed to CRC and GC and showed a dose–response relationship in a population-based cohort study.

Evaluating the effects of duloxetine on prophylaxis of oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: A randomized double-blind placebo controlled clinical trial

Background Oxaliplatin is a key drug in treatment of gastrointestinal (GI) cancer. Peripheral neuropathy (PN) is a troublesome and dose-dependent adverse effect of oxaliplatin. It can occur in two distinct forms: acute and chronic. Its incidence is estimated about 65-98%, of which 22% of cases need to stop chemotherapy. In some cases, PN has a long-lasting effect on patient's quality of life (QOL). Therefore, this study was done to evaluate efficacy of duloxetine on prevention of oxaliplatin- induced peripheral neuropathy (OIPN) in patients with GI cancer. Methodology In this randomized and double -blind clinical trial study conducted in a tertiary teaching hospital, eligible patients were divided into two groups. Treatment group received duloxetine the day before initiation of chemotherapy regimen at a dose of 30 mg/day for one week and then, the dose was titrated up to 60 mg/day until 12 weeks. For placebo group, one placebo capsule was prescribed daily for one week followed by 2 capsules daily until 12 weeks. In each of chemotherapy courses, PN was assessed using national cancer institute-common terminology criteria for adverse effects (NCI-CTCAE v4.03). Also, chemotherapy -related QOL at the baseline and 12 weeks was assessed by functional assessment of cancer treatment gynecologic oncology group - neurotoxicity (FACT/GOG-NTX). Results Forty patients were randomly assigned to treatment and placebo groups which were similar to each other in terms of chemotherapy regimen, type, and stage of cancer. Analysis of results obtained from the NCI-CTCAE (v4.03) showed that duloxetine could prevent worsening of paresthesia more than placebo ( P = 0.025) and patients in duloxetine group experienced less peripheral sensory neuropathy ( P = 0.001) than placebo group. Analysis of results obtained from the FACT/GOG-NTX demonstrated a significant worsening of tingling and discomfort in hands ( P = 0.002, 0.001, respectively) and feet ( P = 0.017, 0.019, respectively) in placebo group compared to duloxetine group. Also, patients experienced more cold temperature -induced pain in extremities ( P = 0.001) in placebo group compared to duloxetine group. On the other hand, duloxetine could not improve QOL ( P = 0.06) and had not significant effects on trouble feeling the shape of small objects in hand ( P = 0.420) or trouble buttoning buttons ( P = 0.086). The P-value < 0.05 was considered to be statistically significant.

Germline HLA-B evolutionary divergence influences the efficacy of immune checkpoint blockade therapy in gastrointestinal cancer

Background The human leukocyte antigen class I (HLA-I) genotype has been linked with differential immune responses to infectious disease and cancer. However, the clinical relevance of germline HLA-mediated immunity in gastrointestinal (GI) cancer remains elusive. Methods This study retrospectively analyzed the genomic profiling data from 84 metastatic GI cancer patients treated with immune checkpoint blockade (ICB) recruited from Peking University Cancer Hospital (PUCH). A publicly available dataset from the Memorial Sloan Kettering (MSK) Cancer Center (MSK GI cohort) was employed as the validation cohort. For the PUCH cohort, we performed HLA genotyping by whole exome sequencing (WES) analysis on the peripheral blood samples from all patients. Tumor tissues from 76 patients were subjected to WES analysis and immune oncology-related RNA profiling. We studied the associations of two parameters of germline HLA as heterozygosity and evolutionary divergence (HED, a quantifiable measure of HLA-I evolution) with the clinical outcomes of patients in both cohorts. Results Our data showed that neither HLA heterozygosity nor HED at the HLA-A/HLA-C locus correlated with the overall survival (OS) in the PUCH cohort. Interestingly, in both the PUCH and MSK GI cohorts, patients with high HLA-B HED showed a better OS compared with low HLA-B HED subgroup. Of note, a combinatorial biomarker of HLA-B HED and tumor mutational burden (TMB) may better stratify potential responders. Furthermore, patients with high HLA-B HED were characterized with a decreased prevalence of multiple driver gene mutations and an immune-inflamed phenotype. Conclusions Our results unveil how HLA-B evolutionary divergence influences the ICB response in patients with GI cancers, supporting its potential utility as a combinatorial biomarker together with TMB for patient stratification in the future.