AI-powered prediction of HCC recurrence after surgical resection: Personalised intervention opportunities using patient-specific risk factors.

BACKGROUND: Hepatocellular carcinoma (HCC) recurrence following surgical resection remains a significant clinical challenge, necessitating reliable predictive models to guide personalised interventions. In this study, we sought to harness the power of artificial intelligence (AI) to develop a robust predictive model for HCC recurrence using comprehensive clinical datasets. METHODS: Leveraging data from 958 patients across multiple centres in Australia and Hong Kong, we employed a multilayer perceptron (MLP) as the optimal classifier for model generation. RESULTS: Through rigorous internal cross-validation, including a cohort from the Chinese University of Hong Kong (CUHK), our AI model successfully identified specific pre-surgical risk factors associated with HCC recurrence. These factors encompassed hepatic synthetic function, liver disease aetiology, ethnicity and modifiable metabolic risk factors, collectively contributing to the predictive synergy of our model. Notably, our model exhibited high accuracy during cross-validation (.857 ± .023) and testing on the CUHK cohort (.835), with a notable degree of confidence in predicting HCC recurrence within accurately classified patient cohorts. To facilitate clinical application, we developed an online AI digital tool capable of real-time prediction of HCC recurrence risk, demonstrating acceptable accuracy at the individual patient level. CONCLUSION: Our findings underscore the potential of AI-driven predictive models in facilitating personalised risk stratification and targeted interventions to mitigate HCC recurrence by identifying modifiable risk factors unique to each patient. This model aims to aid clinicians in devising strategies to disrupt the underlying carcinogenic network driving recurrence.

The association between quality care and outcomes for a real-world population of Australian patients diagnosed with pancreatic cancer.

BACKGROUND: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival. METHODS: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. RESULTS: 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96). CONCLUSION: Capture of a concise data set has enabled quality of care to be assessed.

Patient-reported outcome measures (PROMs) in pancreatic cancer: a systematic review.

BACKGROUND: The aim of this systematic review is to examine patient-reported outcome measures (PROMs), their attributes and application in patients with pancreatic cancer (PC). METHOD: A systematic literature search was undertaken of articles published to June 2018 to identify PROMs applied in primary studies in PC. Characteristics of the included studies and PROMs were described with identified scales grouped into five domains. The psychometric properties of the identified PROMs were further assessed for reliability and validity among patients with PC. RESULTS: From 1688 studies screened, 170 were included. Almost half (48%) were conducted in patients with unresectable PC; the majority of these (68%) were evaluated in randomized controlled trials. Median questionnaire completion rates fell below 10% of the original cohort within 12 months in patients with unresectable PC compared to 75% in patients with resectable PC. Seventy PROMs were identified, 32 measuring unidimensional parameters (e.g. pain) and 35 measuring multidimensional (e.g. quality of life) constructs. Only five (7%) PROMs were disease-specific and 13 (19%) were validated in patients with PC. Fifty scales were grouped into 19 physical, 9 psychological, 6 psychiatric, 9 social and 7 other domains. CONCLUSION: Three multidimensional PROMs, the: (i) FACT-HEP in unresectable PC; (ii) QLQ-PAN26 (in conjunction with its core QLQ-C30 PROM) in resectable PC; and (iii) MDASI-GI are recommended as instruments to capture quality of life in patients with PC. Summarised scales and psychometric evaluation provide a framework to choose PROMs for scales not captured by the recommended PROMs.

Correlations between histopathological diagnosis of chemotherapy-induced hepatic injury, clinical features, and perioperative morbidity.

BACKGROUND: Chemotherapy has in some series been linked with increased morbidity after a hepatectomy. Hepatic injuries may result from the treatment with chemotherapy, but can also be secondary to co-morbid diseases. The aim of the present study was to draw correlations between clinical features, treatment with chemotherapy and injury phenotypes and assess the impact of each upon perioperative morbidity. PATIENTS AND METHODS: Retrospective samples (n= 232) were scored grading steatosis, steatohepatitis and sinusoidal injury (SI). Clinical data were retrieved from medical records. Correlations were drawn between injury, clinical features and perioperative morbidity. RESULTS: Injury rates were 18%, 4% and 19% for steatosis, steatohepatitis and SI, respectively. High-grade steatosis was more common in patients with diabetes [odds ratio (OR) = 3.33, P= 0.01] and patients with a higher weight (OR/kg = 1.04, P= 0.02). Steatohepatitis was increased with metabolic syndrome (OR = 5.88, P= 0.02). Chemotherapy overall demonstrated a trend towards an approximately doubled risk of high-grade steatosis and steatohepatitis although not affecting SI. However, pre-operative chemotherapy was associated with an increased SI (OR = 2.18, P= 0.05). Operative morbidity was not increased with chemotherapy, but was increased with steatosis (OR = 2.38, P= 0.02). CONCLUSIONS: Diabetes and higher weight significantly increased the risk of steatosis, whereas metabolic syndrome significantly increased risk of steatohepatitis. The presence of high-grade steatosis increases perioperative morbidity, not administration of chemotherapy per se.

Clinical utility of stimulated cholescintigraphy using a standardized Ensure-Plus fatty meal protocol in patients with suspected functional gallbladder disorder: a retrospective study of seven-years clinical experience.

BACKGROUND: The clinical utility of fatty meal stimulated cholescintigraphy particularly using a standardized formulation in patients with suspected functional gallbladder disorder has not been extensively studied. We present our seven-year clinical experience using an Ensure plus protocol. METHODS: A retrospective study was performed on patients undergoing stimulated cholescintigraphy using Ensure Plus for evaluation of suspected functional gallbladder disorder. A gallbladder ejection fraction (GBEF) of <33% was considered abnormal. RESULTS: Of the 173 patients evaluated, 57 (33%) had an abnormal GBEF, 112 (65%) had a normal GBEF and 4 (2%) had no gallbladder visualization. Of the 57 patients with an abnormal GBEF, symptom improvement occurred in 30/31 (97%) who underwent cholecystectomy and in 17/26 (65%) who were managed conservatively (p = 0.003). Of the 112 patients with a normal GBEF, symptom improvement occurred in 8/10 (80%) who underwent cholecystectomy and 74/102 (73%) who were managed conservatively (p = 1.000). In the subgroup of 102 patients with a normal GBEF managed conservatively, those without symptomatic improvement had lower GBEFs compared to those with symptomatic improvement (median GBEF 46% versus 57%, p = 0.019). CONCLUSION: Our retrospective results support a clinical role for stimulated cholescintigraphy using Ensure Plus in the evaluation of patients with suspected functional gallbladder disorder. While an abnormal GBEF predicts good surgical outcome, our results suggest that using an absolute GBEF cut off value of <33% may not apply to all patients and hence GBEF results should only be used as an adjunct in the surgical decision-making process.

mRNA gene expression correlates with histologically diagnosed chemotherapy-induced hepatic injury.

INTRODUCTION: Chemotherapy-induced hepatic injuries (CIHI) are an increasing problem facing hepatic surgeons. It may be possible to predict the risk of developing CIHI by analysis of genes involved in the metabolism of chemotherapeutics, previously established as associated with other forms of toxicity. METHODS: Quantitative reverse transcriptase-polymerase chain reaction methodology (q-RT-PCR) was employed to quantify mRNA expression of nucleotide excision repair genes ERCC1 and ERCC2, relevant in the neutralization of damage induced by oxaliplatin, and genes encoding enzymes relevant to 5-flurouracil metabolism, [thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD)] in 233 hepatic resection samples. mRNA expression was correlated with a histopathological injury scored via previously validated methods in relation to steatosis, steatohepatitis and sinusoidal obstruction syndrome. RESULTS: Low-level DPD mRNA expression was associated with steatosis [odds ratio (OR) = 3.95, 95% confidence interval (CI) = 1.53-10.19, P < 0.003], especially when stratified by just those patients exposed to chemotherapy (OR = 4.48, 95% CI = 1.31-15.30 P < 0.02). Low expression of ERCC2 was associated with sinusoidal injury (P < 0.001). There were no further associations between injury patterns and target genes investigated. CONCLUSIONS: Predisposition to the development of CIHI may be predictable based upon individual patient expression of genes encoding enzymes related to the metabolism of chemotherapeutics.

Surgical management of pancreatic trauma in Australia.

BACKGROUND: Pancreatic trauma is rare and complex. Non-operative management of pancreatic injuries is often appropriate, and when surgical intervention is required there may be a choice between resectional or more conservative approaches. This is especially true for distal injuries. Operative management of proximal pancreatic injuries is extremely challenging and has less room for conservatism. We sought to characterize the surgical treatment of pancreatic injuries, comparing outcomes for those undergoing formal resection (FR) versus those undergoing more conservative surgical treatment. Our hypothesis was that 'biting the bullet' and resecting is not associated with worse outcomes than less invasive approaches. METHODS: All patients undergoing surgery for pancreatic injuries between June 2001 and June 2019 at the Alfred Hospital in Melbourne were included. Outcome measures including length of stay, return to theatre, total parenteral nutrition use, pancreatic fistula, intra-abdominal infection and mortality were compared between patients undergoing FR and those undergoing non-resectional procedures. RESULTS: Of nearly 60 000 trauma presentations, 194 patients sustained pancreatic injury and 51 underwent surgical intervention. Over 70% were secondary to blunt trauma. There were 27 FR and 22 non-resectional procedures. No major outcome differences were detected. FR was not associated with worse outcomes. CONCLUSION: In distal injuries, where there is doubt regarding parenchymal viability or ductal integrity, FR can safely be performed with non-inferior outcomes to more conservative surgery. Patients with high-grade proximal injuries will usually have multiple other injuries and require resuscitation, temporization and staged reconstruction.

Evaluation of palliative treatments in unresectable pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) presents as unresectable disease in 80% of patients. Limited Australian data exists regarding management and outcome of palliative management for PDAC. This study aims to: (i) identify patients with PDAC being managed with palliative intent; (ii) assess the type of palliative management being used. METHODS: A prospectively maintained pancreatic database at Western Health (2015-2017) was used to identify patient demographics; stage and multidisciplinary decision regarding resectability and operative interventions; palliative care; use of chemotherapy, radiotherapy and; management of exocrine and endocrine insufficiency. Data on chemotherapy use, number of hospital admissions, emergency department attendances and intensive care unit admissions 30 days prior to death were recorded. RESULTS: One-hundred and eleven patients had diagnosis of PDAC, 15% with locally advanced and 45% with metastatic PDAC. Among the locally advanced and metastatic PDAC, 48% received biliary stent insertions, 93% had palliative care referral, 45% received palliative chemotherapy and 10% received radiotherapy. Dietitian referral occurred in 79% and 36% were prescribed with a pancreatic enzyme replacement therapy. Diabetes mellitus was present in 52% of which 31% was new onset. Within 30 days prior to death, 11% patients received palliative chemotherapy, 32% were hospitalized and 11% visited an emergency department more than once. Sixty-five percent died in hospital. CONCLUSION: A high proportion of patients diagnosed with locally advanced and metastatic PDAC received palliative care referrals and appropriate level of end-of-life care. Further prospective studies are necessary, examining the management and impacts of pancreatic insufficiency in this group.

Management of bile leak following blunt liver injury: a proposed guideline.

BACKGROUND: Bile leak following blunt liver trauma is uncommon. Management is difficult due to complex vasculo-biliary and liver parenchymal injury and lack of consensus on optimal care compared with bile leak following elective hepatectomy especially in regards to endoscopic retrograde pancreaticocholangiography (ERCP) timing and patient selection. METHODS: This is a retrospective cohort study from a level 1-trauma centre of patients with bile leak following blunt liver injury between July 2010 and December 2019 identified from the trauma registry. Clinical data retrieved include patient demographics, injury severity score, liver injury grading and its associated complications and treatment. This was supplemented by surgical audit database and patients' electronic medical record. RESULTS: There were 31 bile leaks amongst 639 patients with blunt liver trauma (4.9%). Bile leak was associated with higher liver injury grade (odds ratio (OR) 36, P = 0.001), hepatic embolization (OR 16, P = 0.003) and need for trauma laparotomy (OR 14, P = 0.024). ERCP was performed in 58.1% (n = 18). This was complicated in 27.7% (n = 5) by mild pancreatitis (n = 1) and intra-abdominal sepsis (n = 4) requiring surgical drainage of abscess (n = 2) and liver resection (n = 1). Bile leak settled conservatively (including percutaneous drainage) without ERCP in the remaining patients (41.9%). Overall mortality was not increased in those with bile leak (P = 0.998). CONCLUSION: Bile leaks resolved conservatively in 41.9% of patients. Complications following ERCP were seen in 27.7%, frequently requiring intervention. Failure of conservative management was more likely in patients with hepatic embolization, in whom early ERCP remains appropriate. ERCP should otherwise be reserved for those who fail conservative management to minimize infective complications.

Splenic autotransplantation: a systematic review.

BACKGROUND: Splenectomy is a surgical procedure indicated in a variety of medical conditions including trauma. Post-operatively, there is a lifelong risk of developing overwhelming sepsis from encapsulated bacteria, most commonly due to Streptococcus pneumoniae. Splenic autotransplantation has been proposed as a method to recover splenic function in patients requiring splenectomy with otherwise normal spleens. This study aims to systematically review the literature to determine the efficacy of spleen autotransplantation. METHODS: MEDLINE, PubMed and the Cochrane Library were searched for all studies assessing splenic autotransplantation (January 1947 to July 2018). Data were extracted on study characteristics, outcomes assessed, including spleen scintigraphy results, blood film counts and serum immunoglobulin (Ig) levels. RESULTS: Data were obtained from 18 primary studies. All studies demonstrated return of regenerated spleen tissue in the majority of their patients (95.3%) on spleen scintigraphy. In 12 studies, 90.2% of patients had blood films return to normal following transplantation. Ig levels were shown to return to normal in all 12 studies where it was assessed. In 11 studies, 3.7% of patients had post-operative complications. In five studies, 1.3% of patients had post-operative infections in the follow-up period. CONCLUSION: Splenic autotransplantation is a safe procedure with minimal complications that can return splenic filtration function and Ig levels to normal ranges. It has not been confirmed whether autotransplantation provides meaningful protection against overwhelming post-splenectomy infections.

The Upper Gastrointestinal Cancer Registry (UGICR): a clinical quality registry to monitor and improve care in upper gastrointestinal cancers.

PURPOSE: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. PARTICIPANTS: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation. FINDINGS TO DATE: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile. FUTURE PLANS: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.

Surgical outcomes for duodenal adenoma and adenocarcinoma: a multicentre study in Australia and the United Kingdom.

BACKGROUND: Pancreaticoduodenectomy is often required in patients with duodenal adenoma and adenocarcinoma and these patients generally have soft pancreatic texture and small pancreatic ducts, the two most significant factors associated with post-operative pancreatic fistula (POPF). The aims of the study were to evaluate the rate of POPF and long-term outcomes for patients with duodenal adenoma and adenocarcinoma who underwent curative resection. METHODS: This retrospective study (2004-2014) examined patients treated surgically with non-ampullary duodenal tumours (NADTs) in two hepatopancreaticobiliary units in Victoria, Australia, and Swansea, UK. RESULTS: There were 49 resections performed including 33 pancreaticoduodenectomies, five pancreas-preserving total duodenectomies and 11 segmental duodenal resections. Median length of follow-up was 23.5 months. Final histopathology revealed 18 duodenal adenomas and 31 adenocarcinomas. POPF rate for NADTs was 28.9% (of which 54.5% were grade C) compared to 14.5% for all other pathologies. Grade C POPF was associated with poorer survival outcomes (hazard ratio = 6.73; P = 0.005). The 5-year overall survival for patients with duodenal adenocarcinoma was 66.5%. CONCLUSION: Due to the soft pancreatic texture and small pancreatic duct, pancreatic resection for NADTs is associated with a high rate of POPF which contributes to reduced survival. Nevertheless, surgery is associated with favourable 5-year survival compared to pancreatic resection for pancreatic adenocarcinoma.

Ga-68 octreotate PET/CT and Tc-99m heat-denatured red blood cell SPECT/CT imaging of an intrapancreatic accessory spleen.

Intrapancreatic accessory spleens are relatively uncommon and can be difficult to distinguish from neuroendocrine tumours on CT, MRI and somatostatin receptor scintigraphy. We present the case of a 26-year-old woman with an incidentally diagnosed pancreatic lesion confirmed to be an intrapancreatic accessory spleen on Tc-99m heat-denatured red blood cell single photon emission computed tomography/CT.

Fine needle aspiration in the management of benign thyroid cysts.

BACKGROUND: Resolution of cystic thyroid lesions after aspiration occurs in 8-45% of cases, the remainder require treatment for residual tumour or recurrent cysts. The aim of this study was to identify patient characteristics that predict cyst recurrence to enable these patients to undergo early surgery. METHODS: A retrospective analysis of 123 patients with benign thyroid cysts that were suitable for conservative management was undertaken. Demographic, clinical, ultrasound and fine needle aspiration cytology data were collated for patients who underwent surgery or were managed conservatively. Univariate and multivariate analyses were performed to identify factors predictive of cyst recurrence. RESULTS: Of the 123 patients, 43 underwent surgery consequent on cyst recurrence or persistent symptoms after aspiration, and 80 were treated by aspiration alone. There were 17 males and 106 females, of mean age 45.5 years. The mean cyst size was 27 mm. Those undergoing surgery had a significantly greater mean cyst size (P = 0.001). The only factor predicting cyst recurrence on univariate analysis was absence of follicular cells on initial aspiration (P = 0.005). Multivariate analysis confirmed absence of follicular cells as an independent characteristic predicting recurrence, the odds ratios for recurrence was 3.18 (95%CI 1.39-7.29). CONCLUSION: The present study suggests consideration of early surgery for patients with thyroid cysts with absence of follicular cells on initial cytology.