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.

Incidental Finding of a Fish Bone Perforation in the Pylorus Mimicking Acute Cholecystitis.

We present a case of a 43-year-old man with Crohn's disease who presented with epigastric and right upper quadrant abdominal pain, initially suspected to be acute cholecystitis or a Crohn's flare-up. CT revealed a curvilinear, hyperdense foreign body adjacent to the duodenum, concerning micro-perforation. Endoscopic examination confirmed findings of a 3 cm fish bone lodged in the pylorus. Endoscopic extraction was successful without significant mucosal damage, and the patient recovered well postoperatively. This case highlights the rarity of pyloric perforation secondary to fish bone ingestion and highlights the importance of considering this diagnosis in patients presenting with unexplained acute abdominal pain, as prompt recognition and intervention are essential for favorable outcomes.

Storylines of family medicine X: standing up for diversity, equity and inclusion.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'X: standing up for diversity, equity and inclusion', authors address the following themes: 'The power of diversity-why inclusivity is essential to equity in healthcare', 'Medical education for whom?', 'Growing a diverse and inclusive workforce', 'Therapeutic judo-an inclusive approach to patient care', 'Global family medicine-seeing the world "upside down"', 'The inverse care law', 'Social determinants of health as a lens for care', 'Why family physicians should care about human rights' and 'Toward health equity-the opportunome'. May the essays that follow inspire readers to promote change.

Summary outcomes of two-stage resection for advanced colorectal liver metastases.

BACKGROUND: Surgical resection is associated with improved long-term survival in patients with colorectal liver metastases (CLM). However, majority of patients have unresectable bilobar advanced liver metastases. Two-stage resection (TSR) allows selected patients to achieve complete resection when combined with chemotherapy and interventional radiological procedures. METHODS: Electronic search of the MEDLINE and PubMed databases (January 2000-October 2011) to identify studies examining the outcomes of the surgical approach of TSR of advanced CLM was undertaken. RESULTS: Twelve studies were examined. This comprised 488 patients. A median of 77% (range: 64-100%) of planned patients completed TSR. The most common reason for failure was due to disease progression observed in a median of 100% (range: 56-100%) of patients. Second-stage resection appeared to be more morbid compared to first-stage resection with higher complication rates (33% vs. 14%) and requiring more blood transfusions (3 U vs. 1 U). Completed TSR achieved a median survival of 37 (range: 18-66) months, median 3-year survival rate of 60% (range: 45-84%), and median 5-year survival rate of 48% (range: 32-70%). In patients who failed TSR, the median survival was 16 (range: 10-29) months. CONCLUSION: In carefully selected candidates with advanced bilobar CLM, the TSR approach achieves long-term survival in patients who would otherwise be considered for palliative chemotherapy only. Despite failing to complete TSR, patients had an encouraging survival outcome that appeared to compare favorably over palliative chemotherapy alone.

Two decades of experience with hepatic cryotherapy for advanced colorectal metastases.

INTRODUCTION: Only 15% of patients with colorectal liver metastases (CLM) are candidates for curative hepatectomy at time of diagnosis, limited by anatomical location and tumor burden. Ablative therapies may extend this. This study reports a single institution's long-term experience with hepatic cryotherapy for advanced CLM. METHODS: Between April 1990 and June 2009, 304 patients were curatively treated with cryotherapy. Survival was estimated by Kaplan-Meier method. Prognostic factors for survivals were determined by using univariate and multivariate analyses. RESULTS: A total of 293 patients were included into analysis. The median number of lesions treated per patient was three (range, 1-13). The median overall survival was 29 (range, 3-220) months. The 1-, 3-, 5-, and 10-year survivals were 87%, 41.8%, 24.2%, and 13.3%, respectively. A total of 161 patients developed intrahepatic recurrences: cryosite (23%); edge recurrence (14%); and within the liver remnant (78%). The median disease-free survival (DFS) was 9 (range, 1-220) months. The 1-, 3-, 5-, and 10-year DFS rates were 37.9%, 17.2%, 13.4%, and 10.8%, respectively. Univariate analysis identified four factors that significantly affect survival: node-positive primary tumor (p=0.001), preoperative CEA level (p<0.001), number of lesions (p<0.001), and use of neoadjuvant chemotherapy (p<0.001). However, only primary tumor nodal status was independently prognostic (hazards ratio=2.023; 95% confidence interval, 1.444-2.835; p<0.001). CONCLUSIONS: Hepatic cryotherapy seems to be a safe and effective ablative technique for the treatment of colorectal liver metastases and may offer long-term survival in otherwise unresectable disease.

Predictors of cure after hepatic resection of colorectal liver metastases: an analysis of actual 5- and 10-year survivors.

BACKGROUND: Hepatic resection of colorectal liver metastases (CLM) is now regarded the standard of care. Evaluation of true long-term survivors will demonstrate the curative potential of this therapy with cure being defined as actual 10-year survival versus a satisfactory oncological outcome of 5-year survival. Limited data exists on outcomes of patients beyond 5 years. Studying the rates of cure and predictive factors for cure are essential to define the true benefit of this therapy. METHODS: Retrospective review of a prospectively maintained hepatobiliary surgical database was performed on patients who underwent hepatic resection of CLM between 1991 and 2005 with a minimum of 5-year follow-up. Survival was calculated from the time of surgery using the Kaplan-Meier method. RESULTS: There were 455 consecutive patients with a minimum of 5-year follow-up. The actuarial median overall survival was 33 months (95% CI, 29-37%), actuarial 5-, and 10-year survival rates were 34% and 25%, respectively. Hundred twenty four patients were identified as actual 5-year survivors (27%) with their actuarial median overall survival being 11.1 years, actuarial 10-year survival rate of 59%, and a median disease-free survival of 4.9 years. Patients requiring subsequent treatment of modern systemic chemotherapy for post-resection recurrence (P = 0.003) was a negative predictors of cure from multivariate analysis. CONCLUSION: This study demonstrate that approximately one in three patients undergoing resection for CLM will become actual 5-year survivors from which approximately half will go on to survive 10-years and be cured of CLM.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. PATIENTS AND METHODS: All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. RESULTS: Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. CONCLUSION: The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.

Rapid Formation and Rupture of Multiple Abdominal Pseudoaneurysms: A Life Threatening Case of Segmental Arterial Mediolysis.

We present a 62-year-old gentleman with rapidly forming abdominal pseudoaneurysms due to segmental arterial mediolysis (SAM). With rupture of his pseudoaneurysms, he underwent angiography and successful coil embolisation. In this case, we demonstrate the potential for rapid progression of pseudoaneurysms in SAM, with the need for prompt diagnosis and urgent endovascular intervention.

Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma.

The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.

Yttrium-90 radiotherapy for unresectable intrahepatic cholangiocarcinoma: a preliminary assessment of this novel treatment option.

BACKGROUND: There are no treatment options for unresectable intrahepatic cholangiocarcinoma (ICC) with proven efficacy. The objective of this study was to present data on the safety and efficacy of a novel treatment option, yttrium-90 ((90)Y) radioembolization for unresectable ICC. METHODS: Twenty-five patients underwent resin-based (90)Y radioembolization for unresectable ICC between January 2004 and May 2009. Patients were assessed at 1 month and then at 3-month intervals after treatment. Radiologic response was evaluated with the Response Criteria in Solid Tumors (RECIST) criteria. Clinical and biochemical toxicities were prospectively recorded. Survival was calculated by the Kaplan-Meier method and potential prognostic variables were identified. RESULTS: No patient was lost to follow-up. The median follow-up was 8.1 (range, 0.4-56) months and the median survival after (90)Y radioembolization was 9.3 months. Two patients died within 1 month of treatment; the median follow-up for the remaining 23 was 8.9 (range, 1.5-56) months. Two factors were associated with an improved survival: peripheral tumor type (vs. infiltrative, P = .004) and Eastern Cooperative Oncology Group performance status of 0 (vs. 1 and 2, P < .001). On imaging follow-up of 23 patients, a partial response to treatment was observed in 6 patients (24%), stable disease in 11 patients (48%), and progressive disease in 5 patients (20%). The most common clinical toxicities were fatigue (64%) and self-limiting abdominal pain (40%). Two patients (8%) each developed grade III bilirubin and albumin toxicity. One patient (4%) developed grade III alkaline phosphatase toxicity. CONCLUSIONS: (90)Y radioembolization may be a relatively safe and efficacious treatment for unresectable ICC. In the absence of other effective therapeutic options, this treatment warrants further investigation.

Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma.

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease-free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non-TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27-72% vs. non-TACE 23-52%; complete TACE 0-28% vs. non-TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non-randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.

Building a Bridge to the Community: An Integrated Knowledge Translation Approach to Improving Participation in Community-Based Exercise for People After Stroke.

BACKGROUND: People who have had a stroke and are living in the community have low levels of physical activity, which reduces their functional capacity and increases risks of developing secondary comorbid conditions. Exercise delivered in community centers can address these low levels of physical activity; however, implementing evidence-based programs to meet the needs of all community stakeholders is challenging. OBJECTIVES: The objective of this study was to determine implementation factors to facilitate participation in relevant exercise and physical activity for people with chronic health conditions, like stroke. DESIGN: The design consisted of a qualitative observational study using an integrated knowledge translation approach. METHODS: Supported by an integrated knowledge translation approach, a series of focus groups-with stakeholder group representation that included people who had had a stroke and care partners, community organizations (ie, support groups, community center staff), health care providers, and exercise deliverers-was conducted. During the focus groups, participants provided perspectives on factors that could influence implementation effectiveness. Focus groups were recorded, transcribed, and thematically analyzed. RESULTS: Forty-eight stakeholders participated. Based on the themes, a new implementation model that describes the importance of relationships between community centers, clinicians, and people who have had a stroke is proposed. The development of partnerships facilitates the implementation and delivery of exercise programs for people with ongoing health needs. These partnerships address unmet needs articulated in the focus groups and could fill a gap in the continuity of care. CONCLUSIONS: Data from this study support the need for the community sector to offer a continuing service in partnership with the health system and people with chronic health needs. It indicates the potential of clinicians to partner with people with chronic health conditions and empower them to improve participation in relevant health behaviors, like community-based exercise.

Reducing inflow occlusion, occlusion duration and blood loss during hepatic resections.

BACKGROUND: To assess the changes in blood loss during hepatic resection with improved haemostatic devices such as a bipolar sealing device and a topical haemostatic agent. METHODS: This retrospective clinical study of prospectively collected data will assess hepatic resections performed by a single surgeon between 2005 and 2013, with the introduction of the two haemostatic techniques in 2009. RESULTS: A total of 371 hepatic resections (214 from 2005 to 2008 and 157 from 2009 to 2013) were included in this study. Compared with the conventional hepatic resection (2005-2008), the use of haemostatic techniques (2009-2013) significantly reduced the need for inflow occlusion (OR: 0.37, 95% CI: 0.24-0.57, P < 0.001), overall occlusion time (20.8 min versus 25.9 min, P = 0.04) and transfusion requirement (4.6% versus 12%, OR: 0.35, 95% CI: 0.14-0.90, P = 0.02). Mean overall blood loss was reduced post-2009; however, the decrease was not statistically different (401.3 mL versus 470.8 mL, P = 0.27). Subgroup analysis revealed that blood loss was more than halved post-2009 compared with pre-2009 for patients who received pre-operative chemotherapy (324.6 mL versus 738.5 mL, P = 0.005). CONCLUSION: The use of a bipolar sealing device and a topical haemostatic agent reduces the need for inflow occlusion, overall occlusion time and transfusions in all patients compared with conventional hepatic resections.

Impact of treatment modality and number of lesions on recurrence and survival outcomes after treatment of colorectal cancer liver metastases.

BACKGROUND: Ablative strategies have been used to treat and facilitate hepatic resection (HR) in patients with otherwise unresectable colorectal liver metastases (CLM). We evaluated the efficacy of HR, concomitant HR and ablation and isolated ablation on recurrence and survival outcomes after treatment of CLM in patients with 1-4 and ≥5 lesions, respectively. METHODS: A retrospective review of a prospectively collected hepatobiliary surgery database was performed on patients who underwent treatment for isolated CLM between 1990 and 2010. Pre-operative and treatment characteristics were compared between patients who underwent HR, concomitant HR and ablation and ablation alone. The impact of treatment modality on survival and recurrence outcomes was determined. RESULTS: A total of 701 patients met inclusion criteria; 550 patients (78%) had 1-4 lesions and 151 patients (22%) had ≥5 lesions. Overall median survival for the entire cohort was 35 months with 5- and 10-year survival of 33% and 20%, respectively. Overall median and 5-year recurrence-free survival (RFS) was 13 months and 21%, respectively. For patients with 1-4 lesions, median survival was 37 months with 5-year survival of 36%. Stratified by procedure type, 5-year survival was 41% in patients who underwent HR, 35% in patients who underwent concomitant HR and ablation and 13% in patients who underwent ablation alone (P<0.001). For patients with ≥5 lesions, median survival was 28 months with 5-year survival of 23% without difference between treatment groups (P=0.078). CONCLUSIONS: HR appears to be the most effective strategy for patients with 1-4 lesions. When ≥5 lesions are present, ablative strategies are useful in facilitating HR in otherwise unresectable patients.

Viewing metastatic colorectal cancer as a curable chronic disease.

Improved survival of colorectal cancer has been made over the last 3 decades; reasons may be attributed to early detection through screening, and better treatment options. Advancements in modern systemic chemotherapy for colorectal cancer include oxaliplatin-based and irinotecan-based combination and the introduction of biological agents such as bevacizumab and cetuximab. Systemic therapies need to be used in patients with high risk stage II and stage III colorectal cancer and in patients with metastatic disease. Evidence for liver resection and ablation, pulmonary metastasectomy and/or radiofrequency ablation, and cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for metastasis to sites of the liver, lung, and peritoneum respectively are well established. The biggest challenge is to select the right patients for metastasectomy and to pursue metastatic disease as a chronic disease to ensure appropriate personalized therapy, pursue second-line therapies or repeat surgeries, and minimize toxicities of therapies.

Hepatic resection for transplantable hepatocellular carcinoma for patients within Milan and UCSF criteria.

BACKGROUND: Liver transplantation is believed to be the best treatment option for selected patients with hepatocellular carcinoma (HCC). However, the shortage of organs and the risk of tumor progression while on the waiting list has hampered this effective treatment modality from being routinely offered. Hence, the second option of hepatic resection must be considered. The aim of this study is to report the results of hepatic resection in transplantable patients. METHODS: From 1991 to 2009, 97 patients underwent liver resection for HCC. Thirty patients (31%) met transplant criteria [(Milan/University of California San Francisco (UCSF) Liver Transplant Criteria]. Outcomes after hepatic resection were evaluated with disease-free survival (DFS) and overall survival as the endpoints by stratification of transplant eligibility. RESULTS: There were 30 patients within the UCSF transplant criteria and 16 patients within the Milan transplant criteria. By using either transplant criteria, patients survived an actuarial median survival of 102 months. Patients selected based on the Milan criteria had a median DFS of 55 months and patients selected based on the UCSF criteria had a median DFS of 42 months. Patients who were Child Pugh B (UCSF criteria P<0.001) and with cirrhosis had a poorer outcome after hepatic resection (UCSF criteria P=0.011, Milan criteria P=0.002). CONCLUSIONS: Long-term DFS and overall survival may be achieved through hepatic resection for transplantable HCC. This is an effective option and may be regarded as a first-line treatment option. Patients with Child Pugh B or are cirrhotics may benefit more from a transplantation than a resection.

Optimizing the surgical effort in patients with advanced neuroendocrine neoplasm hepatic metastases: a critical analysis of 40 patients treated by hepatic resection and cryoablation.

BACKGROUND: Surgical extirpation of neuroendocrine neoplasms hepatic metastases (NENHM) provides the best opportunity of long-term survival but is not feasible in the majority of patients given the widespread presentation of liver disease. Combining resection with local ablation can potentially expand the resection criteria and thereby improve survival. The present study critically evaluates the progression-free survival (PFS) and overall survival (OS) of patients with NENHM who underwent concomitant hepatic resection and cryoablation. METHODS: Forty patients with NENHM underwent concomitant hepatic resection and cryoablation between December 1992 and June 2010. PFS and OS were determined; clinicopathologic and treatment-related factors associated with PFS and OS were evaluated through univariate and multivariate analyses. RESULTS: The median follow-up for the patients who were alive was 61 months (range, 1 to 162 mo). The median PFS and OS after hepatic resection were 22 and 95 months, respectively. Five-year and 10-year OS rate was 61% and 40%, respectively. One independent factor was associated with OS: histologic grade (P=0.001). One independent factor was associated with PFS: extrahepatic disease (P=0.003). CONCLUSION: Concomitant hepatic resection and cryoablation to achieve tumor debulking is associated with excellent survival outcomes in selected patients. This approach may increase the number of patients with borderline resectable disease undergoing surgical management of advanced NENHM.

Surgical resection of hepatic metastases from neuroendocrine neoplasms: a systematic review.

BACKGROUND: Neuroendocrine tumours (NET) most commonly metastasize to the liver. Hepatic resection of NET hepatic metastases (NETHM) has been shown to improve symptomology and survival. METHODS: A systematic review of clinical studies before September 2010 was performed to examine the efficacy of hepatic resection for NETHM. As a secondary end-point, the impact of treatment on safety and symptomology were determined and prognostic variables were identified. The quality of each study was also assessed using predefined criteria incorporating 9 characteristics. Clinical outcome was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: Twenty-nine included reported survival outcomes with a median 3-, 5- and 10-year overall survival of 83% (range, 63-100%), 70.5% (range, 31-100%), and 42% (range, 0-100%), respectively. The median progression-free survival (PFS) was 21 months (range, 13-46 months) and median 1-,3-,5- and 10-year PFS of 63% (range, 50-80 %), 32% (range, 24-69%), 29% (range, 6-66%) and 1% (range, 0-11%), respectively. Poor histologic grade, extra-hepatic disease and a macroscopically incomplete resection were associated with a poor prognosis. Studies reported a median rate of symptomatic relief from surgery in 95% of patients (range, 50-100%). CONCLUSION: Hepatic resection for NETHM provides symptomatic benefit and is associated with favourable survival outcomes although the majority of patients invariably develop disease progression.