Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

Different Patterns of Care and Survival Outcomes in Transplant-Centre Managed Patients with Early-Stage HCC: Real-World Data from an Australian Multi-Centre Cohort Study.

The management of early-stage hepatocellular carcinoma (HCC) is complex, with multiple treatment strategies available. There is a paucity of literature regarding variations in the patterns of care and outcomes between transplant and non-transplant centres. We conducted this real-world multi-centre cohort study in two liver cancer referral centres with an integrated liver transplant program and an additional eight non-transplant HCC referral centres across Australia to identify variation in patterns of care and key survival outcomes. Patients with stage Barcelona Clinic Liver Cancer (BCLC) 0/A HCC, first diagnosed between 1 January 2016 and 31 December 2020, who were managed at a participating site, were included in the study. Patients were excluded if they had a history of prior HCC or if they received upfront liver transplantation. A total of 887 patients were included in the study, with 433 patients managed at a liver cancer centre with a transplant program (LTC) and 454 patients managed at a non-transplant centre (NTC). Management at an LTC did not significantly predict allocation to resection (adjusted OR 0.75, 95% CI 0.50 to 1.11, p = 0.148). However, in those not receiving resection, LTC and NTC patients were systematically managed differently, with LTC patients five times less likely to receive upfront ablation than NTC patients (adjusted OR 0.19, 95% CI 0.13 to 0.28, p < 0.001), even after adjusting for tumour burden, as well as for age, gender, liver disease aetiology, liver disease severity, and medical comorbidities. LTCs exhibited significantly higher proportions of patients undergoing TACE for every tumour burden category, including those with a single tumour measuring 2 cm or less (p < 0.001). Using multivariable Cox proportional hazards analysis, management at a transplant centre was associated with reduced all-cause mortality (adjusted HR 0.71, 95% CI 0.51 to 0.98, p = 0.036), and competing-risk regression analysis, considering liver transplant as a competing event, demonstrated a similar reduction in risk (adjusted HR 0.70, 95% CI 0.50 to 0.99, p = 0.041), suggesting that the reduced risk of death is not fully explained by higher rates of transplantation. Our study highlights systematic differences in HCC care between large volume liver transplant centres and other sites, which has not previously been well-described. Further work is needed to better define the reasons for differences in treatment allocation and to aim to minimise unwarranted treatment variation to maximise patient outcomes across Australia.

Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels.

BACKGROUND: Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections. AIMS: We aimed to determine whether infections were associated with high anti-tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections. METHODS: Two retrospective studies were performed, a descriptive cohort study and a matched case-control study. For the matched case-control study, cases of infection occurring on anti-TNF agents were matched in a 1:2 ratio to controls of anti-TNF treated patients without infections. RESULTS: In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty-four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti-TNF drug levels in infection cases were 3.9 µg/mL for infliximab and 6.0 µg/mL for adalimumab. In the case-control study, 32 cases of infection in 27 anti-TNF treated patients were matched with 64 anti-TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 µg/mL versus 5.5 µg/mL for infliximab (P = 0.72) and 6.0 µg/mL versus 9.9 µg/mL for adalimumab (P = 0.34). CONCLUSION: Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti-TNF levels.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

Effectiveness and safety of cold snare polypectomy and cold endoscopic mucosal resection for nonpedunculated colorectal polyps of 10-19 mm: a multicenter observational cohort study.

BACKGROUND : Cold snare polypectomy (CSP) is the standard of care for the resection of small (< 10 mm) colonic polyps. Limited data exist for its efficacy for medium-sized (10-19 mm) nonpedunculated polyps, especially conventional adenomas. This study evaluated the effectiveness and safety of CSP/cold endoscopic mucosal resection (C-EMR) for medium-sized nonpedunculated colonic polyps. METHODS : A prospective multicenter observational study was conducted of all morphologically suitable nonpedunculated colonic polyps of 10-19 mm removed by CSP/C-EMR between May 2018 and June 2021. Once resection was complete, multiple biopsies were taken of the margins circumferentially and centrally. The primary outcome was the incomplete resection rate (IRR), based on residual polyp in these biopsy specimens. Secondary outcomes were recurrence rate at first surveillance colonoscopy and rates of adverse events (AEs). RESULTS : CSP/C-EMR was performed for 350 polyps (median size 15 mm; 266 [76.0 %] Paris 0-IIa classification) in 295 patients. Submucosal injection was used for 87.1 % (n = 305) of polyps. Histology showed 68.6 % adenomas, 26.0 % sessile serrated lesions (SSLs) without dysplasia, 4.0 % SSL with dysplasia, and 1.4 % hyperplastic polyps. The IRRs based on margin or central biopsies being positive were 1.7 % (n = 6) and 0.3 % (n = 1), respectively. The polyp recurrence rate was 1.7 % (n = 4) at first surveillance colonoscopy - completed for 65.4 % (n = 229) of polyps at a median interval of 9.7 months. AEs occurred in 3.4 % (n = 10) of patients: four with post-polypectomy pain; three self-limiting post-polypectomy bleeds; two post-polypectomy-syndrome-like presentations; and one intraprocedural bleed treated with clips. There were no perforations. CONCLUSION : CSP/C-EMR for morphologically suitable nonpedunculated colonic polyps of 10-19 mm is effective and safe, including for conventional adenomas. Rates of incomplete resection and recurrence were low, with few AEs. Studies directly comparing this method with hot snare resection are required.

Over-The-Scope Clip for the Immediate Management of Stapfer Type-1 Duodenal Perforation during Endoscopic Retrograde Cholangiopancreatography.

Iatrogenic Stapfer type-1 duodenal perforations during endoscopic retrograde cholangiopancreatography (ERCP) typically necessitate surgical management and carry significant morbidity and mortality risk. Here, we present a case of a large duodenal perforation during ERCP managed endoscopically with an over-the-scope clip (OTSC) and describe the subsequent post-procedural management. An 80-year-old woman presented to the emergency department with acute cholangitis. Abdominal ultrasound scan revealed a dilated biliary tree with echogenic material in the common hepatic and intrahepatic ducts. The patient proceeded to ERCP, where filling defects consistent with stones were found in the proximal main bile duct on cholangiogram. Stone retrieval was complicated by a large iatrogenic perforation of the infero-lateral duodenal wall, distal to the major ampulla (Stapfer type-1). Following unsuccessful attempts to close the defect using through-the-scope clips, a decision was made to attempt closure endoscopically using an OTSC. The duodenoscope was exchanged for a forward-viewing gastroscope mounted with the OTSC. The perforation defect was fully suctioned into the cap and the clip was successfully deployed. Subsequent on-table fluoroscopy with contrast injection did not demonstrate any extra-luminal contrast leak. The patient developed a post-procedure infra-duodenal collection, however, made a complete recovery with bowel rest, negative pressure regulation at the site of the OTSC using a dual-lumen nasogastric/nasojejunal feeding tube and intravenous piperacillin-tazobactam. Thus, OTSCs potentially offer a safe and effective endoscopic treatment modality for the immediate management of ERCP-related Stapfer type-1 duodenal perforations.

Liver disease severity predicts carcinogenesis of dysplastic liver nodules in cirrhosis.

While dysplastic liver nodules in cirrhosis are pre-malignant, little is known about the predictors of hepatocarcinogenesis of these lesions. This was a retrospective observational study of subjects with cirrhosis who had at least one hypervascular, non-malignant intrahepatic nodule on imaging while undergoing outpatient management by a tertiary hepatology referral centre between Jan 2009 and Jan 2019. Clinical and biochemical parameters were collected. The primary endpoint was transformation to hepatocellular carcinoma (HCC) as determined by Liver Imaging Reporting and Data System. During the study period, 163 non-malignant hypervascular nodules were identified in 77 patients; 147 had at least 6 months of follow up imaging and 16 received upfront radiofrequency ablation upon detection. During a median follow up of 38.5 months (IQR 16.5-74.5), 25 (17%) of the 147 hypervascular nodules being monitored transformed to HCC. On multivariate analysis, Child-Pugh grade was found to be the only independent predictor of nodule transformation into HCC (p = 0.02). Those with Child-Pugh B and C liver disease had a 10.1 (95% CI 1.22-83.8; p = 0.03) and 32.6-fold (95% CI 2.3-467; p = 0.01) increased risk respectively for HCC transformation compared to Child-Pugh A subjects. This large, single centre study demonstrates that around 20% of dysplastic nodules in cirrhotic patients undergo hepatocarcinogenesis during follow up, and that Child Pugh grade is the only independent predictor of transformation to HCC. Additional prospective studies are warranted to better understand the risk profile of these nodules, and how best they should be managed.