Comparing artificial intelligence to humans for endoscopic diagnosis of gastric neoplasia: An external validation study.

OBJECTIVES: Artificial intelligence (AI) uses deep learning functionalities that may enhance the detection of early gastric cancer during endoscopy. An AI-based endoscopic system for upper endoscopy was recently developed in Japan. We aim to validate this AI-based system in a Singaporean cohort. METHODS: There were 300 de-identified still images prepared from endoscopy video files obtained from subjects that underwent gastroscopy in National University Hospital (NUH). Five specialists and 6 non-specialists (trainees) from NUH were assigned to read and categorize the images into "neoplastic" or "non-neoplastic." Results were then compared with the readings performed by the endoscopic AI system. RESULTS: The mean accuracy, sensitivity, and specificity for the 11 endoscopists were 0.847, 0.525, and 0.872, respectively. These values for the AI-based system were 0.777, 0.591, and 0.791, respectively. While AI in general did not perform better than endoscopists on the whole, in the subgroup of high-grade dysplastic lesions, only 29.1% were picked up by the endoscopist rating, but 80% were classified as neoplastic by AI (P = 0.0011). The average diagnostic time was also faster in AI compared with endoscopists (677.1 s vs 42.02 s (P < 0.001). CONCLUSION: We demonstrated that an AI system developed in another health system was comparable in diagnostic accuracy in the evaluation of static images. AI systems are faster and not fatigable and may have a role in augmenting human diagnosis during endoscopy. With more advances in AI and larger studies to support its efficacy it would likely play a larger role in screening endoscopy in future.

A hydrogel-based mechanical metamaterial for the interferometric profiling of extracellular vesicles in patient samples.

The utility of mechanical metamaterials for biomedical applications has seldom been explored. Here we show that a metamaterial that is mechanically responsive to antibody-mediated biorecognition can serve as an optical interferometric mask to molecularly profile extracellular vesicles in ascites fluid from patients with cancer. The metamaterial consists of a hydrogel responsive to temperature and redox activity functionalized with antibodies to surface biomarkers on extracellular vesicles, and is patterned into micrometric squares on a gold-coated glass substrate. Through plasmonic heating, the metamaterial is maintained in a transition state between a relaxed form and a buckled state. Binding of extracellular vesicles from the patient samples to the antibodies on the hydrogel causes it to undergo crosslinking, induced by free radicals generated via the activity of horseradish peroxidase conjugated to the antibodies. Hydrogel crosslinking causes the metamaterial to undergo fast chiral re-organization, inducing amplified changes in its mechanical deformation and diffraction patterns, which are detectable by a smartphone camera. The mechanical metamaterial may find broad utility in the sensitive optical immunodetection of biomolecules.

Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

Academy of Medicine, Singapore clinical guideline on endoscopic surveillance and management of gastric premalignant lesions.

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.

Surfactant-guided spatial assembly of nano-architectures for molecular profiling of extracellular vesicles.

The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration - spatial organization and distribution - in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis.

PIPAC-OX: A Phase I Study of Oxaliplatin-Based Pressurized Intraperitoneal Aerosol Chemotherapy in Patients with Peritoneal Metastases.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel laparoscopic, intraperitoneal chemotherapy delivery technique aiming to improve drug distribution and tissue penetration to treat peritoneal metastases. Thus far, PIPAC oxaliplatin is conducted at an arbitrary dose of 92 mg/m2. We conducted a phase I study to establish safety and tolerability. PATIENTS AND METHODS: We used a 3+3 dose-escalation design of PIPAC oxaliplatin for patients with peritoneal metastases from gastrointestinal tumors, after failure of at least first-line chemotherapy. Dose levels were planned at 45, 60, 90, and 120 mg/m2. RESULTS: This study included 16 patients with 24 PIPAC procedures (8 gastric; 5 colorectal; and 1 gallbladder, pancreas, and appendix cancer each). Median age and peritoneal cancer index (PCI) score were 62 years and 17, respectively. Two patients developed pancreatitis (grade 2 and 3) at 45 mg/m2, necessitating cohort expansion. Another patient developed grade 2 pancreatitis at 90 mg/m2. There were no other dose-limiting toxicities, and the highest-dose cohort (120 mg/m2) tolerated PIPAC well. Pharmacokinetic analyses demonstrated good linearity between dose and maximum concentration (r 2 = 0.95) and AUC (r 2 = 0.99). On the basis of RECIST, 62.5% and 50% had stable disease after one and two PIPAC procedures, respectively. A total of 8 patients underwent two PIPAC procedures, with improvement of median PCI and peritoneal regression grade score from 15 to 12 and 2.5 to 2.0, respectively. CONCLUSIONS: The recommended phase II dose is 120 mg/m2. Future studies should further delineate the efficacy and role of PIPAC oxaliplatin for peritoneal metastases.See related commentary by de Jong et al., p. 1830.

Evaluating the Use of microRNA Blood Tests for Gastric Cancer Screening in a Stratified Population-Level Screening Program: An Early Model-Based Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer. METHODS: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice). The model was evaluated for 25 years with a healthcare perspective and accounted for test characteristics, compliance, disease progression, cancer recurrence, costs, utilities, and mortality. The outcomes measured included incremental cost-effectiveness ratios, cancer stage at diagnosis, and thresholds for significant variables. RESULTS: The miRNA-based screening was found to be cost-effective with an incremental cost-effectiveness ratio of $40 971/quality-adjusted life-year. Key drivers included test costs, test accuracy, cancer incidence, and recurrence risk. Threshold analysis highlights the need for high accuracy of miRNA tests (threshold sensitivity: 68%; threshold specificity: 77%). A perfect compliance to screening would double the cancer diagnosis in early stages compared to the current practice. Probabilistic sensitivity analysis reported the miRNA-based screening to be cost-effective in >95% of iterations for a willingness to pay of $70 000/quality-adjusted life-year (approximately equivalent to 1 gross domestic product/capita) CONCLUSIONS: The miRNA-based screening intervention was found to be cost-effective and is expected to contribute immensely in early diagnosis of cancer by improving screening compliance.

Recent Advances in Intra-peritoneal Chemotherapy for Gastric Cancer.

Peritoneal metastasis (PM) frequently occurs in patients with gastric cancer (GC) and confers a dismal prognosis despite advances in systemic chemotherapy. While systemic chemotherapy has poor peritoneal penetration, intraperitoneal (IP) chemotherapy remains sequestered, resulting in high peritoneal drug concentrations with less systemic side-effects. The first application of IP treatment was hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) for gastric cancer peritoneal metastasis (GCPM); but was associated with an increased morbidity and mortality rate without significantly improving overall survival (OS). While CRS confers limited benefit, the potential role of prophylactic HIPEC and laparoscopic neoadjuvant HIPEC are currently being evaluated. Combination systemic and IP chemotherapy (SIPC) gained popularity in the 1990s, since it provided the benefits of IP treatment while reducing surgical morbidity, demonstrating promising early results in multiple Phase II trials. Unfortunately, these findings were not confirmed in the recent PHOENIX-GC randomized controlled trial; therefore, the appropriate treatment for GCPM remains controversial. Small observational studies from Japan and Singapore have reported successful downstaging of PM in GC patients receiving SIPC who subsequently underwent conversion gastrectomy with a median OS of 21.6-34.6 months. Recently, the most significant development in IP-directed therapy is pressurized IP aerosol chemotherapy (PIPAC). Given that aerosol chemotherapy achieves a wider distribution and deeper penetration, the outcomes of multiple ongoing trials assessing its efficacy are eagerly awaited. Indeed, IP-directed therapy has evolved rapidly in the last 3 decades, with an encouraging trend toward improved outcomes in GCPM, and may offer some hope for an otherwise fatal disease.

Exosome-templated nanoplasmonics for multiparametric molecular profiling.

Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.

Cutaneous port-site recurrence secondary to tumour seeding following implantation of an intraperitoneal chemotherapy access port for gastric cancer.

Intraperitoneal chemotherapy has shown promising results for the treatment of peritoneal carcinomatosis in gastric cancer. However, the implantation of an intraperitoneal chemotherapy port may be associated with catheter-related complications. The authors describe a case of cutaneous port-site recurrence secondary to tumour seeding from an intraperitoneal chemotherapy access port.

ELSA recommendations for minimally invasive surgery during a community spread pandemic: a centered approach in Asia from widespread to recovery phases.

BACKGROUND: The COVID-19 pandemic has resulted in significant changes to surgical practice across the worlds. Some countries are seeing a tailing down of cases, while others are still having persistent and sustained community spread. These evolving disease patterns call for a customized and dynamic approach to the selection, screening, planning, and for the conduct of surgery for these patients. METHODS: The current literature and various international society guidelines were reviewed and a set of recommendations were drafted. These were circulated to the Governors of the Endoscopic and Laparoscopic Surgeons of Asia (ELSA) for expert comments and discussion. The results of these were compiled and are presented in this paper. RESULTS: The recommendations include guidance for selection and screening of patients in times of active community spread, limited community spread, during times of sporadic cases or recovery and the transition between phases. Personal protective equipment requirements are also reviewed for each phase as minimum requirements. Capability management for the re-opening of services is also discussed. The choice between open and laparoscopic surgery is patient based, and the relative advantages of laparoscopic surgery with regard to complications, and respiratory recovery after major surgery has to be weighed against the lack of safety data for laparoscopic surgery in COVID-19 positive patients. We provide recommendations on the operating room set up and conduct of general surgery. If laparoscopic surgery is to be performed, we describe circuit modifications to assist in reducing plume generation and aerosolization. CONCLUSION: The COVID-19 pandemic requires every surgical unit to have clear guidelines to ensure both patient and staff safety. These guidelines may assist in providing guidance to units developing their own protocols. A judicious approach must be adopted as surgical units look to re-open services as the pandemic evolves.

Kamikawa Double-Flap Reconstruction After Minimally Invasive Ivor-Lewis Esophagectomy.

Despite the high incidence of reflux esophagitis, there are few reports of antireflux modifications for minimally invasive Ivor-Lewis esophagectomy. We present the case of a 63-year-old man with mid-thoracic esophageal squamous cell carcinoma who underwent minimally invasive Ivor-Lewis esophagectomy after neoadjuvant chemoradiotherapy. Laparoscopic dissection, gastric tube creation, and mobilization was performed. Thoracoscopic esophageal dissection, subcarinal, paraesophageal and diaphragmatic lymphadenectomy were performed, followed by esophagogastric anastomosis with double seromuscular flap reconstruction to recreate the lower esophageal sphincter. The operation was completed in 618 minutes with 200 mL blood loss and the patient recovered uneventfully. A morphologic sphincter was seen on postoperative contrast study.

Palliative radiotherapy in symptomatic locally advanced gastric cancer: A phase II trial.

To evaluate the response and quality of life of palliative gastric radiotherapy in patients with symptomatic locally advanced gastric cancer. Patients with bleeding, pain or obstruction and were treated with palliative gastric radiotherapy to a dose of 36 Gy in 12 daily fractions. The primary outcomes were symptom response rates. Secondary outcomes included overall survival, adverse events and proportion of patients with ≥10-point absolute improvement in the fatigue, nausea/vomiting and pain subscales in the EORTC Qualify of Life Questionnaire C30 (EORTC QLQ-C30) and dysphagia/pain subscales in the gastric specific module (STO22) at the end of RT and 1 month after the completion of radiotherapy. Fifty patients were accrued. Median survival duration was 85 days. 40/50 patients (80%) with bleeding, 2/2 (100%) patients with obstruction and 1/1 (100%) patient with pain responded to radiotherapy. Improvements fatigue, nausea/vomiting and pain subscales of the EORTC QLQ-C30 was seen in 50%, 28% and 44% of patients at the end of RT and in 63%, 31% and 50% of patients 1 month after RT. Improvements in dysphagia/pain subscales of the STO22 was seen in 42% and 28% of patients at then end of RT and 44% and 19% of patients 1 month after RT. Two patients (5%) had grade 3 anorexia and gastritis. Palliative gastric radiotherapy was effective, well tolerated and resulted in improvement in fatigue, dysphagia and pain at the end of radiotherapy and 1 month after the completion of radiotherapy in a significant proportion of patients.

Enhanced recovery versus conventional care in gastric cancer surgery: a meta-analysis of randomized and non-randomized controlled trials.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols have been successfully integrated into peri-operative management of different cancer surgeries such as colorectal cancer. Their value for gastric cancer surgery, however, remains uncertain. METHODS: A search for randomized and observational studies comparing ERAS versus conventional care in gastric cancer surgery was performed according to PRISMA guidelines. Random-effects meta-analyses with inverse variance weighting were conducted, and quality of included studies was assessed using the Cochrane risk-of-bias tool and Newcastle-Ottawa scale (PROSPERO: CRD42017080888). RESULTS: Twenty-three studies involving 2686 patients were included. ERAS was associated with reduced length of hospital stay (WMD-2.47 days, 95% CI - 3.06 to - 1.89, P < 0.00001), time to flatus (WMD-0.70 days, 95% CI - 1.02 to - 0.37, P < 0.0001), and hospitalization costs (WMD-USD$ 4400, 95% CI - USD$ 5580 to - USD$ 3210, P < 0.00001), with consistent results across open and laparoscopic surgery. Postoperative morbidity and 30-day mortality were similar, although a higher rate of readmission was observed in the ERAS group (RR = 1.95, 95% CI 1.03-3.67, P = 0.04). Patients in the ERAS arm had significantly attenuated C-reactive protein levels on days 3/4 and 7, interleukin-6 levels on days 1, and 3/4, and tumor necrosis factor-α levels on days 3/4 postoperatively. CONCLUSION: Compared to conventional care, ERAS reduces hospital stay, costs, surgical stress response and time to return of gut function, without increasing post-operative morbidity in gastric cancer surgery. However, precaution is necessary to reduce the increased risk of hospital readmission when adopting ERAS.