Using neural networks to autonomously assess adequacy in intraoperative cholangiograms.

BACKGROUND: Intraoperative cholangiography (IOC) is a contrast-enhanced X-ray acquired during laparoscopic cholecystectomy. IOC images the biliary tree whereby filling defects, anatomical anomalies and duct injuries can be identified. In Australia, IOC are performed in over 81% of cholecystectomies compared with 20 to 30% internationally (Welfare AIoHa in Australian Atlas of Healthcare Variation, 2017). In this study, we aim to train artificial intelligence (AI) algorithms to interpret anatomy and recognise abnormalities in IOC images. This has potential utility in (a) intraoperative safety mechanisms to limit the risk of missed ductal injury or stone, (b) surgical training and coaching, and (c) auditing of cholangiogram quality. METHODOLOGY: Semantic segmentation masks were applied to a dataset of 1000 cholangiograms with 10 classes. Classes corresponded to anatomy, filling defects and the cholangiogram catheter instrument. Segmentation masks were applied by a surgical trainee and reviewed by a radiologist. Two convolutional neural networks (CNNs), DeeplabV3+ and U-Net, were trained and validated using 900 (90%) labelled frames. Testing was conducted on 100 (10%) hold-out frames. CNN generated segmentation class masks were compared with ground truth segmentation masks to evaluate performance according to a pixel-wise comparison. RESULTS: The trained CNNs recognised all classes.. U-Net and DeeplabV3+ achieved a mean F1 of 0.64 and 0.70 respectively in class segmentation, excluding the background class. The presence of individual classes was correctly recognised in over 80% of cases. Given the limited local dataset, these results provide proof of concept in the development of an accurate and clinically useful tool to aid in the interpretation and quality control of intraoperative cholangiograms. CONCLUSION: Our results demonstrate that a CNN can be trained to identify anatomical structures in IOC images. Future performance can be improved with the use of larger, more diverse training datasets. Implementation of this technology may provide cholangiogram quality control and improve intraoperative detection of ductal injuries or ductal injuries.

The effect of bariatric surgery on the expression of gastrointestinal taste receptors: A systematic review.

Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour.Registration code in PROSPERO: CRD42022313992.

Defining Physiological Ketosis Following Very-Low-Calorie Diets.

INTRODUCTION: Very low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an increasingly recognized complication in diabetic patients on sodium-glucose-cotransporter-2 inhibitors (SGLT2i) undergoing surgery and requires assessment of ketones for diagnosis and monitoring. VLCD induced ketosis may confound monitoring in this group. We aimed to evaluate the influence of VLCD, compared to standard fasting, on perioperative ketone levels and acid-base balance. MATERIALS AND METHODS: Twenty-seven patients were prospectively recruited to the intervention group and 26 to the control group from two tertiary referral centres in Melbourne, Australia. Intervention group patients were severely obese (body mass index) (BMI) (≥35), undergoing bariatric-metabolic surgery, and prescribed 2 wk of VLCD preoperatively. Control group patients underwent general surgical procedures and prescribed standard procedural fasting only. Patients were excluded if diabetic or prescribed SGLT2i. Ketone and acid-base measurements were taken at regular intervals. Univariate and multivariate regression was utilised with significance defined as P < 0.005. CLINICALTRIALS: gov ID: NCT05442918. RESULTS: Patients on VLCD, compared to standard fasting, had an increased median preoperative (0.60 versus 0.21 mmol/L), immediate postoperative (0.99 versus 0.34 mmol/L) and day 1 postoperative (0.69 versus 0.21 mmol/L) ketone level (P < 0.001). Preoperative acid-base balance was normal in both groups, however VLCD patients were found to have a metabolic acidosis immediately postoperatively (pH 7.29 versus pH 7.35) (P = 0.019). Acid-base balance had normalized in VLCD patients on postoperative day 1. CONCLUSIONS: Preoperative VLCD resulted in increased pre- and postoperative ketone levels with immediate postoperative values consistent with metabolic ketoacidosis. This should be considered particularly when monitoring diabetic patients prescribed SGLT2i.

C-reactive protein is a predictor of severe infective complications following gastrectomy-a retrospective analysis.

Background: Post-operative complications are the main contributing factor to increased length of stay, increased cost of care and short-term mortality experienced by patients following gastrectomy. The purpose of this study was to determine the diagnostic accuracy of C-reactive protein (CRP) in predicting complications following gastrectomy. This may assist clinicians to make better informed clinical decisions in the post-operative period. Methods: A retrospective analysis of a prospectively maintained database was performed. Sixty patients who underwent gastrectomy for gastric cancer were included. Demographic information, operative data and post-operative details such as complications, unplanned intensive care unit (ICU) admission and readmission to hospital were analysed. Complications were further analysed based on whether they were either infective or non-infective in nature. Receiver operator characteristic (ROC) analysis was performed to examine the association between CRP and post-operative morbidity. Optimum cut-offs were determined using the Youden's index. Results: From the second post-operative day (POD), CRP levels were able to predict subsequent severe infective (SI) complications following gastrectomy [area under the curve (AUC): 0.789, 95% CI : 0.636-0.941]. An optimum cut-off of 180 mg/L resulted in a sensitivity of 87.50%. The negative predictive value (NPV) at this point was 96.30%. Conclusions: CRP is a strong negative predicter of SI complications following gastrectomy. This suggests early CRP values may be useful in prompting early investigation or facilitating safer, earlier discharge from hospital. Health services may benefit by determining similar cut-offs based on their own unique patient populations.

Recurrence and outcomes of non-functional pancreatic neuroendocrine tumours post-resection: an Australian retrospective, multicentre cohort study.

INTRODUCTION: Pancreatic neuroendocrine tumours (PNETs) are heterogenous entities with variable clinical outlook. The prevalence of PNETs is increasing in Australia. Despite this, data on peri-operative management and post-operative prognosis for Australian patients is scant in the literature. METHODS: Patients from two tertiary hospitals in Victoria were recruited. Inclusion criteria included patients who underwent curative surgical resection for primary, non-functioning, PNETs without metastases from January 2011 to December 2021. Patients were identified via histopathological reports, CMBS and ICD-10 codes. Data were sourced from Electronic Medical Records, outpatient notes and letters. RESULTS: Sixty-three patients (34 Male, 29 Female) underwent surgical resection for PNETs. Fifty-three patients (84.1%) had a post-operative complication, and 21 (33.3%) had severe complications. Two patients had disease recurrence. Head PNETs had higher Ki-67% (5.33 vs. 2.72, P = 0.29), and likelihood of nodal spread (9 (36%) vs. 4 (16%), P = 0.054). Pancreatic Head resections were also associated with more frequent ICU admissions (21 (84%) vs. 18 (54.5), P = 0.024), longer ICU stays (4.05 vs. 2.17 days, P = 0.10) and hospital stays (26.76 vs. 8.27 days, P = <0.001). CONCLUSION: Within the limitations of this study, it demonstrates that surgical resection of PNET carries a significant morbidity with a low rate of recurrence. Additionally, Pancreatic head NETs may be associated with higher grades and increased likelihood of nodal metastases. Considering this, careful patient selection is paramount.

Tumor-Infiltrating Neutrophils after Neoadjuvant Therapy are Associated with Poor Prognosis in Esophageal Cancer.

BACKGROUND: In esophageal cancer (EC), there is a paucity of knowledge regarding the interplay between the tumor immune microenvironment and response to neoadjuvant treatment and, therefore, which factors may influence outcomes. Thus, our goal was to investigate the changes in the immune microenvironment with neoadjuvant treatment in EC by assessing the expression of immune related genes and their association with prognosis. METHODS: We examined the transcriptome of paired pre- and post-neoadjuvant treated EC specimens. Based on these findings, we validated the presence of tumor-infiltrating neutrophils using CD15+ immunohistochemistry in a discovery cohort of patients with residual pathologic disease. We developed a nomogram as a predictor of progression-free survival (PFS) incorporating the variables CD15+ cell count, tumor regression grade, and tumor grade. RESULTS: After neoadjuvant treatment, there was an increase in genes related to myeloid cell differentiation and a poor prognosis associated with high neutrophil (CD15+) counts. Our nomogram incorporating CD15+ cell count was predictive of PFS with a C-index of 0.80 (95% confidence interval [CI] 0.68-0.9) and a concordance probability estimate (CPE) of 0.77 (95% CI 0.69-0.86), which indicates high prognostic ability. The C-index and CPE of the validation cohort were 0.81 (95% CI 0.69-0.91) and 0.78 (95% CI 0.7-0.86), respectively. CONCLUSIONS: Our nomogram incorporating CD15+ cell count can potentially be used to identify patients at high risk of recurrent disease and thus stratify patients who will benefit most from adjuvant treatment.

Telemedicine versus face-to-face follow up in general surgery: a randomized controlled trial.

BACKGROUND: Telemedicine provides healthcare to patients at a distance from their treating clinician. There is a lack of high-quality evidence to support the safety and acceptability of telemedicine for postoperative outpatient follow-up. This randomized controlled trial-conducted before the COVID-19 pandemic-aimed to assess patient satisfaction and safety (as determined by readmission, reoperation and complication rates) by telephone compared to face-to-face follow-up after uncomplicated general surgical procedures. METHODS: Patients following laparoscopic appendicectomy or cholecystectomy and laparoscopic or open umbilical or inguinal hernia repairs were randomized to a telephone or face-to-face outpatient clinic. Patient demographics, perioperative details and postoperative outcomes were compared. Patient satisfaction was assessed via a standardized Likert-style scale. RESULTS: One hundred and twenty-three patients were randomized over 12 months. Mean consultation times were significantly shorter for telemedicine than face-to-face clinics (telemedicine 10.52 ± 7.2 min, face-to-face 15.95 ± 9.96 min, P = 0.0021). There was no difference between groups in the attendance rates, nor the incidence or detection of postoperative complications. Of the 58 patients randomized to the telemedicine arm, 40% reported high, and 60% reported very high satisfaction with the method of clinic follow-up. CONCLUSION: Telemedicine postoperative follow-up is safe and acceptable to patients and could be considered in patients undergoing uncomplicated benign general surgery.

Economic burden of complications and readmission following oesophageal cancer surgery.

BACKGROUND: Oesophageal cancer is the seventh most prevalent malignancy globally, and the sixth most common cause of cancer-related death. Oesophageal cancer is also one of the most costly cancers to treat. The aim of this study was to assess the financial impact of post-operative morbidity and hospital readmissions following oesophagectomy for oesophageal cancer. METHODS: A retrospective analysis was performed on a prospectively maintained database of patients with oesophageal cancer who underwent an oesophagectomy at a single centre between July 2014 and June 2019 (N = 56). Readmission costs were also assessed in this cohort for 12 months post-operatively. RESULTS: The total median cost for oesophagectomy in this cohort was AU$57 250. Major complications occurred in 40% of patients, with a median total admission cost of AU$74 606, significantly higher than patients with either minor or no complications (median admission cost of AU$52 713, P < 0.001). Patients whose operation was complicated by an anastomotic leak had a higher median admission cost than those without a leak (AU$104 328 and AU$54 972 respectively, P < 0.001). Cost centres representing the greatest proportion of costs were theatre resources and surgical ward care (medical and nursing). A total of 110 readmissions in 25 patients were recorded in the 12 months post-operatively, the majority for gastroscopy and dilatation of anastomotic stricture. CONCLUSION: Post-oesophagectomy morbidity greatly increases cost of care. In addition to the clinical benefits, interventions to minimize post-operative complications are likely to result in substantial cost savings.

Body Composition Differences Between Excess Weight Loss ≥ 50% and < 50% at 12 Months Following Bariatric Surgery.

BACKGROUND: The relationship between weight loss and body composition is undefined after bariatric surgery. The objective of this study was to compare body composition changes in patients with excess weight loss ≥ 50% (EWL ≥ 50) and < 50% at 12 months post-operatively (EWL < 50). METHODS: A prospective cohort study was completed on patients undergoing bariatric surgery at two tertiary hospitals between 2017 and 2021. Body composition was measured with dual-energy X-ray absorptiometry immediately before surgery, and at 1, 6, and 12 months post-operatively. Body mass index (BMI), fat mass (FM), lean body mass (LBM), and skeletal muscle index (SMI) trajectories were analysed between patients with EWL ≥ 50% and EWL < 50%. RESULTS: Thirty-seven patients were included in this series (EWL ≥ 50% n = 25, EWL < 50% n = 12), comprising of both primary and revisional bariatric surgery cases, undergoing a sleeve gastrectomy (62.2%), Roux-en-Y gastric bypass (32.4%), or one anastomosis gastric bypass (5.4%). The EWL ≥ 50% group demonstrated a more optimal mean FM-to-LBM loss ratio than the EWL < 50% group. EWL ≥ 50% patients lost 2.0 kg more FM than EWL < 50% patients for each 1 kg of LBM lost. EWL ≥ 50% was also associated with an increase in mean SMI% over 12 months (5.5 vs. 2.4%; p < 0.0009). Across the whole cohort, the first month after surgery accounted for 67.4% of the total LBM reduction that occurred during the 12-month post-operative period. CONCLUSION: This data suggests EWL ≥ 50% is associated with a more optimal body composition outcome than EWL < 50%. LBM reduction occurs predominantly in the early post-operative period.

Potential Clinical Utility of a Targeted Circulating Tumor DNA Assay in Esophageal Adenocarcinoma.

OBJECTIVE: To explore the clinical utility of circulating tumor DNA (ctDNA) in esophageal adenocarcinoma (EAC) by developing a cost-effective and rapid technique utilising targeted amplicon sequencing. SUMMARY OF BACKGROUND DATA: Emerging evidence suggests that levels of ctDNA in the blood can be used to monitor treatment response and in the detection of disease recurrence in various cancer types. Current staging modalities for EAC such as computerised tomography of the chest/abdomen/pelvis (CT) and positron emission tomography (PET) do not reliably detect occult micro-metastatic disease, the presence of which signifies a poor prognosis. After curative-intent treatment, some patients are still at high risk of recurrent disease, and there is no widely accepted optimal surveillance tool for patients with EAC. METHODS: Sixty-two patients with EAC were investigated for the presence of ctDNA using a tumor-informed approach. We designed a custom targeted amplicon sequencing panel of target specific primers covering mutational foci in 9 of the most commonly mutated genes in EAC. Serial blood samples were taken before and after neoadjuvant treatment (NAT), and during surveillance. RESULTS: Somatic mutations were detected in pre-treatment biopsy samples of 55 out of 62 (89%) EAC patients. Mutations in TP53 (80%) were the most common. Out of these 55 patients, 20 (36%) had detectable ctDNA at baseline. The majority (90%) of patients with detectable ctDNA had either locally advanced tumors, nodal involvement or metastatic disease. In patients with locally advanced tumors, disease free survival (DFS) was more accurately stratified using pre-treatment ctDNA status [HR 4.34 (95% CI 0.93-20.21); P = 0.05] compared to nodal status on PET-CT. In an exploratory subgroup analysis, patients who are node negative but ctDNA positive have inferior DFS [HR 11.71 (95% CI 1.16-118.80) P = 0.04]. In blood samples taken before and following NAT, clearance of ctDNA after NAT was associated with a favourable response to treatment. Furthermore, patients who are ctDNA positive during post-treatment surveillance are at high risk of relapse. CONCLUSIONS: Our study shows that ctDNA has potential to provide additional prognostication over conventional staging investigation such as CT and PET. It may also have clinical utility in the assessment of response to NAT and as a biomarker for the surveillance of recurrent disease.

Pre-operative low muscle mass is associated with major complications and lower recurrence-free survival after gastric cancer surgery.

BACKGROUND: Low muscle mass (LMM) has been associated with post-operative morbidity. This study aimed to examine the relationship between pre-operative LMM and major post-operative complications and survival in patients undergoing curative resection for gastric cancer. METHODS: A single-centre retrospective cohort study was conducted on consecutive patients who underwent surgical resection for gastric adenocarcinoma between 2008 and 2018. Patient demographics, radiological parameters, pathological data and complications were recorded. Skeletal muscle index was calculated using OsiriX software by manually measuring the cross-sectional skeletal muscle area at the third lumbar vertebra and correcting to the patient's height. Univariate and multivariate analyses were used to identify the risk factors associated with the outcomes. RESULTS: A total of 62 patients (36 males, mean age 68.3 ± 1.5 years) met the inclusion criteria. Twenty-six (41.9%) patients had LMM pre-operatively. Demographic data in the non-LMM and LMM groups were equally matched except for body mass index (27.6 ± 0.8 kg/m2 versus 24.3 ± 1.1 kg/m2 ; P = 0.012) and serum albumin (36.7 ± 0.7 g/L versus 33.8 ± 1.0 g/L; P = 0.017), which were higher in the non-LMM. LMM was associated with higher incidence of total (35.5% versus 64.5%; P = 0.006), minor (40% versus 60%; P = 0.030), major (9.1% versus 90.9%; P = 0.004) post-operative complications and decreased recurrence-free survival (hazard ratio 2.29; 95% confidence interval 1.10-4.77; P = 0.027). CONCLUSION: LMM is a significant independent risk factor for major post-operative complications and recurrence-free survival after gastrectomy. Pre-operative identification of LMM could be a useful tool for prognostication and may identify a group suitable for prehabilitation.

Health economic analysis of curative-intent gastrectomy for gastric carcinoma and the costs related to post-operative complications.

BACKGROUND: The management of post-gastrectomy complications requires considerable resources and is likely associated with a substantial economic burden. The objectives of this study were to perform a cost analysis of admissions following gastrectomy for gastric carcinoma and then to quantify the financial impact of post-operative complications. METHODS: A retrospective analysis was conducted in patients that underwent a gastrectomy from 2008 to 2019. Demographic data, operative information, post-operative complications and facility costs were compared. RESULTS: A total of 74 patients underwent a curative-intent gastrectomy during the study period. The 36 (48.6%) patients that had no complications had a median total admission cost of AU$29 228. A total of 21 (28.4%) patients had a minor complication and 17 (23.0%) patients had a major complication, with a median total admission cost of AU$36 592 and AU$71 808, respectively. The difference across all three groups was statistically significant. In patients who had major complications compared to those without complications, there was a significant increase in the cost of intensive care services, theatre resources and nursing care. Across the whole cohort, the principal cost centres accounting for the largest proportion of total cost were theatre equipment and resources (33.9%), nursing care on the ward (23.0%) and staffing time of the surgical team (16.7%). CONCLUSION: The surgical management of gastric cancer carries a substantial cost burden. The presence and severity of post-operative complications is strongly associated with increasing cost. Minimizing complications, in addition to obvious clinical benefits, enables a large reduction in costs of care.

Recent insights into the biology of Barrett's esophagus.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), an aggressive cancer with a poor prognosis. Our understanding of the pathogenesis and Barrett's metaplasia is incomplete, and this has limited the development of new therapeutic targets and agents, risk stratification ability, and management strategies. This review outlines current insights into the biology of BE and addresses controversies surrounding cell of origin, cellular reprogramming theories, updates on esophageal epithelial barrier function, and the significance of goblet cell metaplasia and its association with malignant change. Further research into the basic biology of BE is vital as it will underpin novel therapies and improve our ability to predict malignant progression and help identify the minority of patients who will develop EAC.

Contrast-enhanced sonographic appearances of two primary hepatic epithelioid angiomyolipomas.

Epithelioid hepatic angiomyolipoma (Epi-HAML) is a rare hepatic tumor frequently misdiagnosed as hepatocellular carcinoma (HCC). Unlike conventional angiomyolipoma (AML), Epi-HAML contains minimal amount of adipose tissue, which is a radiological distinguishing feature between AML and HCC. Two patients were referred for management of incidentally found hepatic lesions confirmed to be Epi-HAML on post-resection tissue analysis. CT and MRI findings were suggestive of HCC. Contrast-enhanced ultrasound demonstrated intratumoral shunting, a feeding artery, and early draining hepatic vein. These findings should alert radiologists to the possibility of Epi-HAML. Furthermore, these features may be better assessed by contrast-enhanced ultrasound due to its superior dynamic temporal resolution.

Body Composition Changes Following a Very-Low-Calorie Pre-Operative Diet in Patients Undergoing Bariatric Surgery.

BACKGROUND: Fatty liver in obese patients increases the technical difficulty of bariatric surgery. Pre-operative weight loss with a very-low-calorie diet (VLCD) is commonly used to facilitate surgery. Few studies have quantified the systemic effect of rapid pre-operative weight loss on body composition. The objective of this study is to evaluate body composition changes in bariatric surgery patients undergoing a VLCD. METHODS: Body composition assessments were performed between August 2017 and January 2019 using dual-energy X-ray absorptiometry immediately before and after a 2-week VLCD at St Vincent's Hospital Melbourne. Data collected prospectively pre- and post-VLCD included total body weight, excess body weight, body mass index (BMI), lean body mass (LBM), fat mass (FM) and bone mineral content (BMC). The pre- and post-operative results were compared. RESULTS: Forty-four patients completed both the 2-week VLCD and body composition assessments. Following a 2-week VLCD, patients lost a mean of 4.5 kg (range - 0.3 to 9.5) in a total body weight and 8.8% (range - 0.9 to 17.1) of excess body weight, with a mean reduction in body mass index of 1.6 kg/m2 (range - 0.2 to 3.1). Loss of LBM was 2.8 kg and was significantly greater than loss of FM, 1.7 kg (p < 0.05). BMC changes were insignificant. CONCLUSION: A VLCD is an effective tool for pre-operative weight reduction. In this cohort, a large amount of the total weight loss was attributed to a loss of lean body mass. The impact of significant lean body mass loss and its relationship to short- and long-term health outcomes warrants further assessment.

Pericytes Promote Malignant Ovarian Cancer Progression in Mice and Predict Poor Prognosis in Serous Ovarian Cancer Patients.

PURPOSE: The aim of this study was to investigate the role of pericytes in regulating malignant ovarian cancer progression. EXPERIMENTAL DESIGN: The pericyte mRNA signature was used to interrogate ovarian cancer patient datasets to determine its prognostic value for recurrence and mortality. Xenograft models of ovarian cancer were used to determine if co-injection with pericytes affected tumor growth rate and metastasis, whereas co-culture models were utilized to investigate the direct effect of pericytes on ovarian cancer cells. Pericyte markers were used to stain patient tissue samples to ascertain their use in prognosis. RESULTS: Interrogation of two serous ovarian cancer patient datasets [the Australian Ovarian Cancer Study, n= 215; and the NCI TCGA (The Cancer Genome Atlas), n= 408] showed that a high pericyte score is highly predictive for poor patient prognosis. Co-injection of ovarian cancer (OVCAR-5 & -8) cells with pericytes in a xenograft model resulted in accelerated ovarian tumor growth, and aggressive metastases, without altering tumor vasculature. Pericyte co-culture in vitro promoted ovarian cancer cell proliferation and invasion. High αSMA protein levels in patient tissue microarrays were correlated with more aggressive disease and earlier recurrence. CONCLUSIONS: High pericyte score provides the best means to date of identifying patients with ovarian cancer at high risk of rapid relapse and mortality (mean progression-free survival time < 9 months). The stroma contains rare yet extremely potent locally resident mesenchymal stem cells-a subset of "cancer-associated fibroblasts" that promote aggressive tumor growth and metastatic dissemination, underlying the prognostic capacity of a high pericyte score to strongly predict earlier relapse and mortality.