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Objective Laparoscopic appendectomy is a common operation that is frequently performed by junior surgical residents. We investigated the effect of a structured training program on the proficiency of junior residents in acquiring skills necessary in this operation. Design and Participants This is a randomized pilot trial. Between December 2014 and July 2018, twenty junior residents were recruited for this study. 11 were randomized to receive a structured training program of supervised, task-specific training. Each resident subsequently performed ten cases of laparoscopic appendectomy with their performance assessed for the last 5. The GOALS scale was used as the primary endpoint. Secondary endpoints were perioperative outcomes. The effect of intervention on these outcomes were evaluated assuming a linear mixed effect multi-level model. The study was single-blinded as the assessors did not know which group each resident belonged to. Results There were no statistically significant differences in the total GOALS score or any of its individual domains. After adjusting for the number of operations done within the trial, the mean difference between the total GOALS score was 0.07 (95% CI -0.76 to 0.90, P=0.866). Blood loss, hospital stay and postoperative complication rates were similar. There was suggestion of a shorter operative time (effect estimate -9.03, 95% CI -19.56 to 1.50) in the intervention arm although statistical significance was not achieved. No avoidable adverse events due to this study were recorded. Conclusion Structured training program did not significantly improve surgical performance and outcomes in laparoscopic appendectomy in this pilot trial. Despite these findings, residents can still potentially mount their learning curves in laparoscopy earlier in a safe environment with such a program which is especially important in the era of minimally invasive surgery.

360 Background: PIPAC is a novel, laparoscopic intraperitoneal chemotherapy delivery technique which aims to improve on hyperthermic intraperitoneal chemotherapy (HIPEC), ameliorating drug distribution and tissue penetration. Thus far, PIPAC has been conducted with oxaliplatin chemotherapy in Europe, at an arbitrary dose of 92mg/m2; 150mg/m2 was found to be intolerable. We conducted a dose-escalation phase 1 study to establish the safety, tolerability and recommended phase 2 dose (RP2D) for PIPAC in Asian patients. Methods: This phase 1 study of oxaliplatin administered via PIPAC was designed as a traditional 3+3 dose escalation study for patients with predominant peritoneal metastasis from a gastrointestinal primary tumor, after failure of standard therapies. Dose levels were planned at 45, 60, 90 and 120mg/m2. Repeat doses of PIPAC were permitted, 6 weeks apart. Dose limiting toxicities (DLT) were defined as any clinically relevant grade 3 adverse events occurring within 28 days after PIPAC. Results: This study included 16 patients (25 PIPAC procedures; 8 gastric, 4 colorectal and 1 gallbladder, pancreas and appendix cancer each). Median age was 62 years, with a median peritoneal carcinomatosis index (PCI) score of 17 (range 1 - 39). Two patients developed pancreatitis (grade 2 and 3) on day 6 and day 9 after PIPAC administration at the dose cohort of 45mg/m2, necessitating cohort expansion to 6 patients. One patient was noted to have asymptomatic grade 3 hyperamylasemia (90mg/m2 cohort). There were no other DLTs and all 3 patients in the highest dose cohort (120mg/m2) tolerated PIPAC well. Nine patients who underwent a 2nd PIPAC procedure had a decrease in PCI score from 18.4 to 15.5; one patient at 120mg/m2 had an improvement in PCI from 30 to 12. Conclusions: The RP2D of PIPAC with oxaliplatin is 120mg/m2. Single agent PIPAC is well tolerated, and future studies with PIPAC must consider a bi-directional approach with the incorporation of systemic therapy, with either chemotherapy or immunotherapy to improve efficacy. Clinical trial information: NCT03172416.

BackgroundPressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel laparoscopic intraperitoneal chemotherapy technique, with advantages such as homogeneous distribution of aerosol and deeper tissue penetration. Thus far, PIPAC oxaliplatin has been administered at an arbitrary dose of 92 mg/m2.AimWe aim to determine the dose-related safety profile and tolerability of PIPAC oxaliplatin using an evidence-based approach. The secondary aim is to evaluate clinic-pathologic response and the pharmacokinetic profile.MethodsThis is a phase I 3+3 dose escalation study for gastric and colorectal cancer with predominant peritoneal metastasis starting at a dose of 45 mg/m2. Safety is assessed according to Clavien-Dindo Classification and Common Terminology Criteria for Adverse Events (version 4.0). Clinico-pathologic response is assessed using the Peritoneal Regression Grading Score, Peritoneal Cancer Index, and Response Evaluation Criteria In Solid Tumour criteria (version 1.1). Pharmacokinetic analysis is performed using Inductively Coupled Plasma-Mass Spectrometry assay. This trial is registered on ClinicalTrials.gov (NCT03172416).ConclusionsThis phase I study can provide the scientific basis to identify the optimal dose for PIPAC with oxaliplatin such that the benefits of this novel and promising intraperitoneal chemotherapy delivery technique can be maximized.

Biosensors have emerged as new alternatives in environmental toxicity assessment. In the development of biosensors for heavy metals detection in environment, whole cells are highly favored as these cells are able to reflect the real toxicity effects of heavy metals to living organisms. For heavy metals detection, the integration of several types of cells such as bacteria, cyanobacteria, and algae into biosensors development has been widely reported. The usage of other cells such as plant cell, protozoa, and yeast has been reported as well. Although these biosensors are highly sensitive to heavy metals, the detection is still limited to the heavy metals which are bioavailable to the cells. Besides, the response of whole cells to wide range of heavy metals makes them excellent tools for wide spectrum screening but lack of specificity in detection. Whole cells are living entities with complex biochemical processes, which make the optimization of whole cell-based biosensors a tedious process, while maintaining the stability and storability are still challenging tasks. Although naturally occurring cells are highly favored, some reports show that recombinant cells can be a choice with better performance. In this paper, the usage of whole cells in biosensors for heavy metals detection and some of the current issues which are tied to the development of these biosensors are reviewed.

Background Per-Oral Endoscopic Myotomy (POEM) has been adopted as a treatment option for Achalasia, with similar efficacy and safety profile as laparoscopic Heller Myotomy. However, issues of acid reflux and reflux oesophagitis have often plagued these patients. We aim to evaluate the clinical outcomes and resolution of reflux disease among individuals post-POEM. Methods A prospective review was performed for all patients who have undergone POEM from January 2014 to December 2017, with individuals analysed at the 1 year mark post-POEM. Subjective assessment of reflux was performed using self-administered questionnaires, with 24h pH impedence test and high resolution manometry providing objective correlation. Results Forty-three individuals underwent POEM during the 4 year period. The median age was 52 years (range, 24–78), with half being males (53.5%). The individuals had a median ASA score of 2 (range, 1–3). Majority of the individuals had type II achalasia (58.1%) followed by type I (34.9%) and type III (7%). Patients presented with dysphagia (88.4%) and reflux (10%); symptomatic for a median of 36 months (range, 3–540). One-third required the use of proton pump inhibitors (PPI) for symptomatic relief, with 35% receiving prior interventions for achalasia. These patients had a median Integrated Relaxation Pressure (IRP) of 23.6 mmHg (range, 4.6–160) and a median Eckardt score of 6 (range, 1 -11). One-third developed complications such as mucosal injury (18.6%), carbon dioxide pneumoperitoneum (16.3%) and bleeding (4.7%). The median length of stay was 3 days (range, 1–6). At the 1 year mark, 86% reported improvement in dysphagia (p: 0.043) with 66% having reduction in ratings for their severity (p: 0.002) and frequency (p: 0.05) of reflux. The median IRP (23 vs 13 mmHg) was also significantly lower (p: 0.005). However, only 38.5% correlated with a normal acid exposure on the impedence test (p: 0.592). Conclusion POEM is a promising solution in the management of achalasia given good clinical response for dysphagia and reflux. However, excessive lower oesophageal acid exposure may still be present in almost half of these patients, which may be alleviated with the use of long term use of PPI. Disclosure All authors have declared no conflicts of interest.