Vessels that encapsulate tumour clusters vascular pattern in hepatocellular carcinoma.

Vessels that encapsulate tumour clusters (VETC) is a distinct histologic vascular pattern associated with a novel mechanism of metastasis. First described in human cancers in 2004, its prevalence and prognostic significance in hepatocellular carcinoma (HCC) has only been appreciated in the past decade with a rapidly increasing body of literature. A robust biomarker of aggressive disease, the VETC pattern is easy to recognise but relies on histologic examination of tumour tissue for its diagnosis. Radiological recognition of the VETC pattern is an area of active research and is becoming increasingly accurate. As a prognostic marker, VETC has consistently proven to be an independent predictor of disease recurrence and overall survival in patients with HCC undergoing resection and liver transplantation. It can also guide treatment by predicting response to other therapies such as transarterial chemoembolisation and sorafenib. Without prospective randomised-controlled trials or routine evaluation of VETC in clinical practice, there are currently no firm treatment recommendations for VETC-positive tumours, although some perspectives are provided in this review based on the latest knowledge of their pathogenesis - a complex interplay between tumour angiogenesis and the immune microenvironment. Nevertheless, VETC has great potential as a future biomarker that could take us one step closer to precision medicine for HCC.

Approaches to spatially resolving the tumour immune microenvironment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common and deadly cancer worldwide. Many factors contribute to mortality and place an individual at high risk of developing HCC, including viral infection, alcohol intake, metabolic-associated disease, autoimmunity and genetic liver disorders. Although there are many therapeutics available, much about this disease remains to be understood. This is most evident when investigating the tumour microenvironment (TME). Both innate and adaptive immune cells have been associated with carcinogenesis within the TME of HCC patients. The ability to interrogate the TME more thoroughly with spatial technologies continues to improve, both at the experimental and analytical stages. This review provides insight into technologies available to investigate the TME, and how such technologies are beneficial for improving our understanding of HCC carcinogenesis.

Portal vein embolization with absolute ethanol to induce hypertrophy of the future liver remnant.

BACKGROUND: Preoperative portal vein embolization (PVE) is widely used prior to major liver resection to reduce the risk of post-hepatectomy liver failure (PHLF). We evaluated the efficacy and safety of PVE using absolute ethanol. METHODS: Consecutive patients undergoing preoperative PVE between February 2003 and February 2020 at a high-volume tertiary institution were retrospectively reviewed. Hypertrophy of the future liver remnant (FLR) was determined by comparing volumetric data using semi-automated software on computed tomography or magnetic resonance imaging before and after PVE. Efficacy of absolute ethanol was evaluated by the percentage increase in the FLR volume and the ratio of the FLR to the total liver volume (TLV). Technical success and complications following PVE were evaluated. Feasibility of hepatectomy following PVE and the incidence of PHLF were determined. RESULTS: Sixty-two patients underwent preoperative PVE using absolute ethanol. The technical success rate was 95.2%. Median time interval between PVE and follow-up imaging was 34 days (range 6-144 days). The mean increase in FLR volume and ratio of the FLR to TLV were 43.6 ± 34.4% and 12.3 ± 7.7% respectively. Major adverse events occurred in 3 cases (4.8%) and did not preclude consideration of surgery. Forty-two patients (67.8%) proceeded to surgery for intended hepatectomy of which 36 patients (58.1%) underwent liver resection. Major post-operative complications occurred in 4 patients (11.1%) and there were no cases of PHLF. CONCLUSION: Preoperative PVE with absolute ethanol is effective and safe in inducing hypertrophy of the FLR before partial hepatectomy to prevent PHLF.

Prevalence and outcomes of Clostridioides difficile infection in liver transplant recipients.

BACKGROUND AND AIM: Data are limited on whether Clostridioides difficile infection (CDI) in the first year after liver transplantation (LT) is associated with increased mortality. In an Australian setting without hypervirulent strain of C. difficile we investigated the prevalence, risk factors, and patient survival associated with CDI in LT. METHODS: Consecutive patients who underwent deceased-donor LT from 2007 to 2017 were studied retrospectively. Prevalence and long-term outcomes of LT recipients with and without CDI were examined in the entire LT cohort. A case-control study was performed to investigate risk factors associated with CDI. RESULTS: Six hundred and forty-nine patients underwent LT, of which 32 (4.9%) were diagnosed with CDI within the first 12 months post-LT. There was no difference in patient survival in the overall LT cohort on Kaplan-Meier analysis when stratified by CDI status (log-rank test, p = .08). Furthermore, age was the only predictor of mortality on Cox regression (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, p = .03). On multivariable logistic regression, rifaximin pre-LT reduced risk (odds ratio (OR) 0.22, 95% CI 0.65-0.74, p = .01) whereas antibiotics pre-LT (OR 7.02, 95% CI 1.26-39.01, p = .03) and length of hospital stay after LT (OR 1.03, 95% CI 1.01-1.06, p = .02) were associated with increased risk of CDI. CONCLUSIONS: Within the local setting of our study, CDI within 12 months post-LT is of low severity, associated with pre-LT antibiotic exposure and longer hospital stay but no survival impact after LT. Rifaximin use pre-LT reduced the risk of CDI post-LT.

Current perspectives on the tumor microenvironment in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous inflammation-driven malignancy, which, despite significant advances in management, continues to portend a poor prognosis. Recent advances in basic and translational research have increasingly defined the role of the tumor microenvironment in the development and progression of HCC and facilitated the development of novel molecular targets. The hepatoma microenvironment is characterised by an immunosuppressive milieu of immune cells and tumor vasculature that is both structurally and functionally abnormal. Normalising the tumor microenvironment by adopting a multipronged approach that targets both carcinogenic processes and the immunosuppressive milieu has been supported by pre-clinical and clinical data. In this review, we summarise the current understanding of the hepatoma microenvironment, its influences and dynamic interactions with tumor cells, the vasculature and the gut. Finally, we discuss how manipulating the tumor microenvironment continues to shape the evolving landscape of HCC therapy.

HCC screening: assessment of an abbreviated non-contrast MRI protocol.

BACKGROUND: Hepatocellular carcinoma (HCC) guidelines recommend ultrasound screening in high-risk patients. However, in some patients, ultrasound image quality is suboptimal due to factors such as hepatic steatosis, cirrhosis, and confounding lesions. Our aim was to investigate an abbreviated non-contrast magnetic resonance imaging (aNC-MRI) protocol as a potential alternative screening method. METHODS: A retrospective study was performed using consecutive liver MRI studies performed over 3 years, with set exclusion criteria. The unenhanced T2-weighted, T1-weighted Dixon, and diffusion-weighted sequences were extracted from MRI studies with a known diagnosis. Each anonymised aNC-MRI study was read by three radiologists who stratified each study into either return to 6 monthly screening or investigate with a full contrast-enhanced MRI study. RESULTS: A total of 188 patients were assessed; 28 of them had 42 malignant lesions, classified as Liver Imaging Reporting and Data System 4, 5, or M. On a per-patient basis, aNC-MRI had a negative predictive value (NPV) of 97% (95% confidence interval [CI] 95-98%), not significantly different in patients with steatosis (99%, 95% CI 93-100%) and no steatosis (97%, 95% CI 94-98%). Per-patient sensitivity and specificity were 85% (95% CI 75-91%) and 93% (95% CI 90-95%). CONCLUSION: Our aNC-MRI HCC screening protocol demonstrated high specificity (93%) and NPV (97%), with a sensitivity (85%) comparable to that of ultrasound and gadoxetic acid contrast-enhanced MRI. This screening method was robust to hepatic steatosis and may be considered an alternative in the case of suboptimal ultrasound image quality.

Gastric Cancer Screening in Common Variable Immunodeficiency.

Individuals with common variable immunodeficiency (CVID) have an increased risk of gastric cancer, and gastrointestinal lymphoma, yet screening for premalignant gastric lesions is rarely offered routinely to these patients. Proposed screening protocols are not widely accepted and are based on gastric cancer risk factors that are not applicable to all CVID patients. Fifty-two CVID patients were recruited for screening gastroscopy irrespective of symptoms or blood results and were compared to 40 controls presenting for gastroscopy for other clinical indications. Overall, 34% of CVID patients had intestinal metaplasia (IM), atrophic gastritis or moderate to severe non-atrophic gastritis, which can increase the risk of gastric cancer, compared to 7.5% of controls (p < 0.01). Focal nodular lymphoid hyperplasia, a precursor lesion for gastrointestinal lymphoma, was seen in eight CVID patients (16%), one of whom was diagnosed with gastrointestinal lymphoma on the same endoscopy. High-risk gastric pathology was associated with increased time since diagnosis of CVID, smoking, Helicobacter pylori, a low-serum pepsinogen I concentration, and diarrhea, but not pepsinogen I/II ratio, iron studies, vitamin B12 levels or upper gastrointestinal symptoms. There was a lower rate of detection of IM when fewer biopsies were taken, and IM and gastric atrophy were rarely predicted by the endoscopist macroscopically, highlighting the need for standardized biopsy protocols. The prevalence of premalignant gastric lesions in patients with CVID highlights the need for routine gastric screening. We propose a novel gastric screening protocol to detect early premalignant lesions and reduce the risk of gastric cancer and gastric lymphoma in these patients.

Lesson of the month 1: Splinter haemorrhages as a pointer to gastrointestinal malignancy.

A 58-year-old man was referred for review due to the finding of splinter haemorrhages and digital infarcts. Further questioning revealed a history of unintentional weight loss and calf pain. There were no other clinical features of endocarditis, and no clear cause for the splinter haemorrhages on initial investigations. The discovery of widespread thromboembolic disease prompted a search for malignancy and an eventual diagnosis of oesophageal adenocarcinoma. Splinter haemorrhages resolved with anticoagulation and directed treatment of the underlying malignancy. This case report reminds clinicians of the potentially broad differential diagnosis associated with this clinical sign.

Evaluation and outcomes of patients with obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding (OGIB) is defined as recurrent or persistent bleeding or presence of iron deficiency anaemia after evaluation with a negative bidirectional endoscopy. OGIB accounts for 5% of gastrointestinal bleeding and presents a diagnostic challenge. Current modalities available for the investigation of OGIB include capsule endoscopy, balloon assisted enteroscopy, spiral enteroscopy and computed tomography enterography. These modalities overcome the limitations of previous techniques. Following a negative bidirectional endoscopy, capsule endoscopy and double balloon enteroscopy remain the cornerstone of investigation in OGIB given their high diagnostic yield. Long-term outcome data in patients with OGIB is limited, but is most promising for capsule endoscopy. This article reviews the current literature and provides an overview of the clinical evaluation of patients with OGIB, available diagnostic and therapeutic modalities and long-term clinical outcomes.