A non-randomised open-label exploratory 'window of opportunity' study of TG02 treatment in patients with locally advanced primary and recurrent mutant colorectal cancer.

Background: TG02 is a peptide-based cancer vaccine eliciting immune responses to oncogenic codon 12/13 mutations. This phase 1 clinical trial (NCT02933944) assessed the safety and immunological efficacy of TG02 adjuvanted by GM-CSF in patients with -mutant colorectal cancer.

Methods: In the interval between completing CRT and pelvic exenteration, patients with resectable mutation-positive, locally advanced primary or current colorectal cancer, received 5-6 doses of TG02/GM-CSF.

Metabolic bariatric surgery generates substantial, sustained weight loss and health improvement in a real-world setting.

Background: To determine if the positive outcomes from clinical trials regarding the safety and efficacy of metabolic bariatric surgery are reproducible at a national level.

Methods: A longitudinal registry-based observation study with data collected from all persons undergoing metabolic bariatric surgery in Australia from 28 February 2012-31 December 2021 including data from 122,567 index patients who underwent 134,625 completed bariatric procedures.

Main Outcomes And Measures: Defined adverse outcomes at 90-days (unplanned readmission, intensive care admission and re-operation; death), annual change in weight (percent total body weight loss (TBWL)), diabetes treatment and need for re-operation.

Modified One Anastomosis Gastric Bypass Following Sleeve Gastrectomy for Severe Reflux and Delayed Gastric Emptying: A Prospective Trial with Clinical and Physiological Outcome Measures.

Background: Gastro-esophageal reflux (GORD) following sleeve gastrectomy (SG) is a central challenge, and precise indications for revisional surgery or the physiology have not been precisely defined. We aimed to determine whether OAGB performed for reflux post-SG (1) accelerates gastric emptying half-time, (2) reduces the frequency and severity of reflux events, and (3) improves reflux symptoms.

Methods: We undertook a prospective trial (ACTRN12616001089426).

Applications of natural language processing tools in the surgical journey.

Background: Natural language processing tools are becoming increasingly adopted in multiple industries worldwide. They have shown promising results however their use in the field of surgery is under-recognised. Many trials have assessed these benefits in small settings with promising results before large scale adoption can be considered in surgery.

Prognostic factors and survival disparities in right-sided versus left-sided colon cancer.

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in features and outcomes because of variations in embryology, epidemiology, pathology, and prognosis. This study sought to identify significant factors impacting patient survival through Bayesian modelling. Data was retrospectively analysed from a colorectal neoplasia database.

Effect of intravenous magnesium on post-operative pain following Latarjet shoulder reconstruction.

Background: Single injection ropivacaine interscalene anesthesia (ISA) is frequently used in Latarjet reconstruction to enhance post-operative analgesia. A potential limitation is the occurrence of severe rebound pain on block resolution. We investigated the effect of intravenous magnesium on post-operative pain, particularly at the transition of block resolution to multimodal analgesia.

Long-term Outcomes of Laparoscopic Sleeve Gastrectomy as a Revisional Procedure Following Adjustable Gastric Banding: Variations in Outcomes Based on Indication.

Background: Significant controversy exists regarding the indications and outcomes after laparoscopic adjustable gastric banding (LAGB) conversions to laparoscopic sleeve gastrectomy (LSG).

Aim: To comprehensively determine the long-term outcomes of sleeve gastrectomy as a revisional procedure after LAGB across a range of measures and determine predictors of outcomes.

Methods: Six hundred revision LSG (RLSG) and 1200 controls (primary LSG (PLSG)) were included.

MKP1 promotes nonalcoholic steatohepatitis by suppressing AMPK activity through LKB1 nuclear retention.

Nonalcoholic steatohepatitis (NASH) is triggered by hepatocyte death through activation of caspase 6, as a result of decreased adenosine monophosphate (AMP)-activated protein kinase-alpha (AMPKα) activity. Increased hepatocellular death promotes inflammation which drives hepatic fibrosis. We show that the nuclear-localized mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP1) is upregulated in NASH patients and in NASH diet fed male mice.

Barriers to progression through Australian obesity management pathways: Survey data from the ACTION-IO study.

Background And Objectives: Our previous work uncovered a nine-year delay, from when Australian people with obesity (PwO) first began struggling with excess weight and first discussed weight with a healthcare professional (HCP). In this study we explore barriers to having an obesity consultation, making and discussing the diagnosis of obesity and arranging a management plan, including a follow-up appointment.

Method: Australian PwO (n = 1000) and HCPs (n = 200; 50% general practitioners [GPs]), completed the Awareness, Care & Treatment In Obesity Management - An International Observation (ACTION-IO) online survey.

Modeling Intestinal Carcinogenesis Using In Vitro Organoid Cultures.

Mouse models of intestinal carcinogenesis are very powerful tools for studying the impact of specific mutations on tumor initiation and progression. Mutations can be studied both singularly and in combination using conditional alleles that can be induced in a temporal manner. The steps in intestinal carcinogenesis are complex and can be challenging to image in live animals at a cellular level.

Changes in Oesophageal Transit, Macro-Reflux Events, and Gastric Emptying Correlate with Improvements in Gastro-Intestinal Symptoms and Food Tolerance Early Post Sleeve Gastrectomy.

Purpose: There are significant alterations in gastro-intestinal function, food tolerance, and symptoms following sleeve gastrectomy (SG). These substantially change over the first year, but it is unclear what the underlying physiological basis for these changes is. We examined changes in oesophageal transit and gastric emptying and how these correlate with changes in gastro-intestinal symptoms and food tolerance.

Mechanisms underlying the efficacy of a rodent model of vertical sleeve gastrectomy - A focus on energy expenditure.

Objective: Bariatric surgery remains the only effective and durable treatment option for morbid obesity. Vertical Sleeve Gastrectomy (VSG) is currently the most widely performed of these surgeries primarily because of its proven efficacy in generating rapid onset weight loss, improved glucose regulation and reduced mortality compared with other invasive procedures. VSG is associated with reduced appetite, however, the relative importance of energy expenditure to VSG-induced weight loss and changes in glucose regulation, particularly that in brown adipose tissue (BAT), remains unclear.

Comparison of quality of life, symptom and functional outcomes following surgical treatment for colorectal neoplasia.

Background: Colorectal surgical procedures can have a significant impact on quality-of-life (QoL), functional and symptom outcomes. This retrospective study conducted in a tertiary care center evaluated the influence of four colorectal surgical procedures on patient-reported outcome measures (PROMs).

Methods: 512 patients undergoing colorectal neoplasia surgery between June 2015 and December 2017 were identified via the Cabrini Monash Colorectal Neoplasia database.

Factors affecting the post-operative outcomes in patients aged over 80 following colorectal cancer surgery.

Purpose: In 2019, in Australia, there were 500,000 people aged 85 and over. Traditionally, clinicians have adopted the view that surgery is not desirable in this cohort due to increasing perioperative risk, perceived minimal clinical benefit, and shortened life expectancy. This cohort study is aimed at investigating postoperative outcomes from elective and non-elective colorectal cancer surgery in patients aged 80 and over.

Memory CD4 T cells that co-express PD1 and CTLA4 have reduced response to activating stimuli facilitating HIV latency.

Programmed cell death 1 (PD1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) suppress CD4 T cell activation and may promote latent HIV infection. By performing leukapheresis (n = 21) and lymph node biopsies (n = 8) in people with HIV on antiretroviral therapy (ART) and sorting memory CD4 T cells into subsets based on PD1/CTLA4 expression, we investigate the role of PD1 and CTLA 4 in HIV persistence. We show that double-positive (PD1CTLA4) cells in blood contain more HIV DNA compared with double-negative (PD1CTLA4) cells but still have a lower proportion of cells producing multiply spliced HIV RNA after stimulation as well as reduced upregulation of T cell activation and proliferation markers.

The first international Delphi consensus statement on Laparoscopic Gastrointestinal surgery.

Background: Laparoscopic surgery has almost replaced open surgery in many areas of Gastro-Intestinal (GI) surgery. There is currently no published expert consensus statement on the principles of laparoscopic GI surgery. This may have affected the training of new surgeons.

Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours.

ADAM10 is a transmembrane metalloprotease that sheds a variety of cell surface proteins, including receptors and ligands that regulate a range of developmental processes which re-emerge during tumour development. While ADAM10 is ubiquitously expressed, its activity is normally tightly regulated, but becomes deregulated in tumours. We previously reported the generation of a monoclonal antibody, 8C7, which preferentially recognises an active form of ADAM10 in human and mouse tumours.

Intestinal stem cell aging signature reveals a reprogramming strategy to enhance regenerative potential.

The impact of aging on intestinal stem cells (ISCs) has not been fully elucidated. In this study, we identified widespread epigenetic and transcriptional alterations in old ISCs. Using a reprogramming algorithm, we identified a set of key transcription factors (Egr1, Irf1, FosB) that drives molecular and functional differences between old and young states.

Tubularized and Effaced Gastric Cardia Mimicking Barrett Esophagus Following Sleeve Gastrectomy: Protocolized Endoscopic and Histological Assessment With High-resolution Manometry Analysis.

Objective: To describe expected endoscopic and histological changes at gastro-esophageal junction (GEJ) and define diagnostic paradigms for Barrett esophagus (BE) postsleeve gastrectomy (SG).

Summary Background Data: De novo incidence of BE post SG was reported as high as 18.8%.