Hug sign in intraprocedural cone-beam-CT to predict short-term response to combined treatment of hepatocellular carcinoma.

OBJECTIVES: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle. MATERIALS AND METHODS: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded. RESULTS: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis. CONCLUSION: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected.

Safety and efficacy of endoscopic ultrasound-guided radiofrequency ablation for pancreatic insulinoma: A single-center experience.

BACKGROUND/OBJECTIVES: Insulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a recent technique that has emerged as a minimally invasive therapeutic option for patients with pancreatic lesions not eligible for surgery. In this study, we aimed to describe a series of patients with unresectable pancreatic insulinoma treated with EUS-RFA. METHODS: This is a single-center, retrospective study including all consecutive patients with functioning pancreatic insulinoma undergoing EUS-RFA for surgical unfitness or surgery refusal, between March 2017 and September 2021. Technical success (i.e., complete mass ablation), adverse event rate and severity, clinical and radiologic outcomes (i.e., symptom remission with a normal concentration of blood glucose, and the presence of intralesional necrosis), and post-procedural follow-up were assessed. RESULTS: A total of 10 patients (mean age: 67.1 ± 10.1years; F:M 7:3) were included. The mean size of insulinoma was 11.9 ± 3.3 mm. Technical success and clinical remission were achieved in 100% of patients. Only one (10%) patient was successfully treated with two RFA sessions. Two procedure-related early adverse events occurred, including two (20%) cases of mild abdominal pain. No major complications were observed. The complete radiologic response within 3 months after EUS-RFA was observed in all patients (100%). After a median follow-up of 19.5 (range12-59) months, symptom remission and persistent euglycemia were assessed in all the patients. CONCLUSIONS: Data from this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for pancreatic insulinomas in patients unwilling or unable to undergo surgery with medium-term efficacy.

COntrolling NUTritional Status (CONUT) as Predictive Score of Hospital Length of Stay (LOS) and Mortality: A Prospective Cohort Study in an Internal Medicine and Gastroenterology Unit in Italy.

BACKGROUND: Hospital malnutrition affects nearly 30% of patients in medical wards and correlates with worse outcomes. An early assessment is necessary to stratify the risk of short-term outcomes and mortality. The predictive role of COntrolling NUTritional status (CONUT) score in this context has not yet been elucidated in Western countries. We aimed to test CONUT at admission as a predictive score of hospital outcomes, in an Internal Medicine and Gastroenterology Department of an Italian Tertiary Care University hospital. METHODS: We prospectively enrolled patients admitted to our center, stratifying them into the four CONUT classes (normal = 0-1; mild = 2-4; moderate = 5-8; severe = 9-12 points) according to serum albumin (g/dL), total lymphocyte count (/mm3), and total cholesterol (mg/dL); the primary outcome measure was length of stay (LOS) and the secondary one was in-hospital mortality. RESULTS: Out of a total of 203 patients enrolled, 44 (21.7%) patients had a normal status (0-1), 66 (32.5%) had a mild impairment (2-4), 68 (33.5%) had a moderate impairment (5-8), and 25 (12.3%) a severe impairment (9-12). The mean LOS was 8.24 ± 5.75 days; nine patients died. A moderate-severe CONUT correlated with a higher LOS at the univariate [HR 1.86 (95% CI 13.9-3.47); p < 0.0001] and multivariate analysis [HR 1.52 (95% CI 1.10-2.09); p = 0.01]. The CONUT score was also a predictor of mortality, with an AUC of 0.831 (95% CI 0.680-0.982) and with an optimal cut-off at 8.5 points. Nutritional supplementation within 48 h from admission correlated with lower mortality [OR 0.12 (95% CI 0.02-0.56) p = 0.006]. CONCLUSIONS: CONUT is a reliable and simple predictor of LOS and in-hospital mortality in medical wards.

Incidence and Impact of Refeeding Syndrome in an Internal Medicine and Gastroenterology Ward of an Italian Tertiary Referral Center: A Prospective Cohort Study.

Background: Refeeding syndrome (RS) is a neglected, potentially fatal syndrome that occurs in malnourished patients undergoing rapid nutritional replenishment after a period of fasting. The American Society for Parenteral and Enteral Nutrition (ASPEN) recently released new criteria for RS risk and diagnosis. Real-life data on its incidence are still limited. Methods: We consecutively enrolled patients admitted to the Internal Medicine and Gastroenterology Unit of our center. The RS risk prevalence and incidence of RS were evaluated according to ASPEN. The length of stay (LOS), mortality, and re-admission rate within 30 days were assessed. Results: Among 203 admitted patients, 98 (48.3%) were at risk of RS; RS occurred in 38 patients (18.7% of the entire cohort). Patients diagnosed with RS had a higher mean LOS (12.5 days ± 7.9) than those who were not diagnosed with RS (7.1 ± 4.2) (p < 0.0001). Nine patients (4.4%) died. Body mass index (OR 0.82; 95% CI 0.69−0.97), RS diagnosis (OR 10.1; 95% CI 2.4−42.6), and medical nutritional support within 48 h (OR 0.12; 95% CI 0.02−0.56) were associated with mortality. Conclusions: RS incidence is high among clinical wards, influencing clinical outcomes. Awareness among clinicians is necessary to identify patients at risk and to support those developing this syndrome.

Contrast-Enhanced Ultrasound in the Short-Term Evaluation of Hepatocellular Carcinoma after Locoregional Treatment.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) with second-generation contrast agents performed 1 month after hepatocellular carcinoma (HCC) treatment is almost as sensitive as contrast-enhanced computed tomography (CECT) in depicting the residual tumor. However, the efficacy of CEUS performed early after the procedure is still debated. AIM: We evaluated the diagnostic accuracy (DA) of CEUS for the assessment of tumor response shortly after locoregional therapy in patients with unresectable HCC. METHODS: Ninety-four patients with 104 HCC lesions who were scheduled to receive percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization, or combined treatment were enrolled in this study. With CECT at 1-month as the reference standard, the DA of CEUS performed 48-h after the procedure was evaluated. Patients were followed-up to look for tumor or disease progression. RESULTS: Based on CECT findings, 43/104 lesions were diagnosed as having residual viability after 1 month. CEUS performed 48 h after treatment detected residual tumor in 34/43 nodules with treatment failure at CECT with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 79.1, 96.7, 94.4, 86.8, and 89%, respectively. There was a high degree of concordance between CEUS and CECT (kappa coefficient = 0.78). A hyperemic halo was detectable in 35 lesions without a statistically significant difference between concordant and discordant cases. In patients with uninodular disease responders according to 48 h CEUS had a significantly longer mean overall survival and time to progression compared to nonresponders. CONCLUSION: CEUS performed 48 h after treatment can be considered a reliable modality for the evaluation of the real extent of necrosis and has prognostic value in the assessment of HCC.

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers.

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide: Portal vein tumor thrombosis (PVTT) occurs in about 35%-50% of patients and represents a strong negative prognostic factor, due to the increased risk of tumor spread into the bloodstream, leading to a high recurrence risk. For this reason, it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care, due to its antiangiogenetic action, although it can grant only a poor prolongation of life expectancy. Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition, including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement, tumor biological aggressiveness, complications caused by portal hypertension, patient's clinical features and tolerance to antineoplastic treatments. The median survival has been reported to range between 2.7 and 4 mo in absence of therapy, but it can vary from 5 mo to 5 years, thus depicting an extremely variable scenario. For this reason, it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

Interventional oncology treatments for unresectable early stage HCC in patients with a high risk for intraprocedural bleeding: Is a single-step combined therapy safe and feasible?

PURPOSE: This study was designed to assess the feasibility and safety of a single-step combined therapy using radiofrequency ablation and transarterial chemoembolization (RFA + TACE) in patients with hepatocellular carcinoma (HCC) and uncontrolled coagulopathy. The study also aimed to compare the effectiveness of this approach with TACE alone, performed in a control group. MATERIAL AND METHODS: One hundred and forty-three consecutive cirrhotic patients having a single HCC < 8 cm were enrolled in this observational prospective single-center study from January 2010 to June 2017 and were divided, according to coagulation tests, into three groups (A: low risk; B: intermediate risk and C: high risk of bleeding). The feasibility and safety of a single-step combined treatment (RFA followed by TACE) were evaluated in terms of technical success rate, periprocedural complications, and laboratory values variations. Tumor response obtained at 1-month CT follow-up for group C was compared with that of control group, composed by 16 matched patients with severe coagulopathy and single HCC < 8 cm, who underwent only TACE in a previous period, performed by the same operator. RESULTS: Technical success was achieved in all patients, without any major complications. Minor complications rate was significantly higher in group C after RFA; however, the patients were successfully treated with subsequent TACE therapy, without any differences between pre- and post-procedural laboratory values. One-month complete response rates were similar in all the three groups; however, the response rates of group C were significantly higher as compared to that of the control TACE Group (p < .001). CONCLUSION: The single-step RFA plus TACE therapy allows expansion of the indication for percutaneous thermal ablation, allowing to also include cases previously contraindicated due to the procedural high-risk of complications associated with bleeding, thus improving short-term patient outcome.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma.

AIM: To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC). METHODS: The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS: One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002). CONCLUSION: The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

A pilot study of capsule endoscopy after a standard meal for the detection and grading of oesophageal varices in cirrhotic patients.

BACKGROUND: Capsule endoscopy has been proposed as an alternative to fibreoptic endoscopy for oesophageal varices evaluation in cirrhotics. However, it shows only moderate sensitivity compared to fibreoptic endoscopy. AIM: To compare post-meal capsule endoscopy to fibreoptic endoscopy, based on the hypothesis that meal-induced increase of portal pressure can enhance its sensitivity. METHODS: Twenty-five patients were submitted to fibreoptic endoscopy and, after a standard meal, capsule endoscopy. RESULTS: Post-meal capsule endoscopy detected varices in the 18 patients in whom fibreoptic endoscopy detected varices plus 3 more subjects (sensitivity 100%, specificity 70%); large varices in the 4 patients in whom fibreoptic endoscopy graded varices as large, plus 5 more subjects; red markers in the 5 patients in whom fibreoptic endoscopy detected red markers, plus 3 more subjects. High-risk varices were identified in 11 patients by post-meal capsule endoscopy and in 10 by fibreoptic endoscopy (sensitivity 100%, specificity 93.8%). CONCLUSIONS: Post-meal capsule endoscopy identified more varices, large varices and red markers than fibreoptic endoscopy. The two methods detected similar proportions of high-risk varices. These data suggest that a standard meal can enhance the sensitivity of capsule endoscopy in the detection and grading of oesophageal varices in cirrhotics.

Gut microbiota and metabolic syndrome.

Symbiosis is the result of the relationship between gut microbiota and human surfaces; in fact, it regulates many functions such as metabolic and protective ones. It is widely known that any changes in the microbes in gut microbiota (dysbiosis) and the regulation of mucosal and systemic host's immunity have been linked to different diseases such as metabolic syndromes and associated disorders. Recent studies report an aberrant gut microbiota and an alteration of gut microbial metabolic activities in obese subjects, with an important influence of a number of human physiological functions. Most studies suggest that diet, especially the high-fat low-fiber western-style diet, dramatically impacts on gut microbiota composition and functions in those patients with metabolic syndrome. A deeper knowledge of a specific microbiota profile associated with increased risk of metabolic disease and its subsequent modification induced by prebiotics, probiotics or targeted antibiotics will be necessary for the development of new therapeutic approaches in the treatment of metabolic disease.

Microscopic colitis.

Microscopic colitis may be defined as a clinical syndrome, of unknown etiology, consisting of chronic watery diarrhea, with no alterations in the large bowel at the endoscopic and radiologic evaluation. Therefore, a definitive diagnosis is only possible by histological analysis. The epidemiological impact of this disease has become increasingly clear in the last years, with most data coming from Western countries. Microscopic colitis includes two histological subtypes [collagenous colitis (CC) and lymphocytic colitis (LC)] with no differences in clinical presentation and management. Collagenous colitis is characterized by a thickening of the subepithelial collagen layer that is absent in LC. The main feature of LC is an increase of the density of intra-epithelial lymphocytes in the surface epithelium. A number of pathogenetic theories have been proposed over the years, involving the role of luminal agents, autoimmunity, eosinophils, genetics (human leukocyte antigen), biliary acids, infections, alterations of pericryptal fibroblasts, and drug intake; drugs like ticlopidine, carbamazepine or ranitidine are especially associated with the development of LC, while CC is more frequently linked to cimetidine, non-steroidal antiinflammatory drugs and lansoprazole. Microscopic colitis typically presents as chronic or intermittent watery diarrhea, that may be accompanied by symptoms such as abdominal pain, weight loss and incontinence. Recent evidence has added new pharmacological options for the treatment of microscopic colitis: the role of steroidal therapy, especially oral budesonide, has gained relevance, as well as immunosuppressive agents such as azathioprine and 6-mercaptopurine. The use of anti-tumor necrosis factor-α agents, infliximab and adalimumab, constitutes a new, interesting tool for the treatment of microscopic colitis, but larger, adequately designed studies are needed to confirm existing data.

[Chronic hepatitis C virus infection: clinical picture and treatment possibilities]. / Infezione cronica da HCV: inquadramento clinico e possibilita' terapeutiche.

It has been estimated that between 1.5 and 2 million people in Italy have anti-HCV antibodies. The vast majority are chronically infected with HCV and are unaware of the infection. Chronic hepatitis C is asymptomatic during most of its course, which lasts decades. The diagnosis is based on anti-HCV antibodies and, subsequently, an HCV-RNA test, to be performed in all subjects with persistently elevated ALT and in those who are at risk of HCV infection. The identification of infected subjects allows prophylaxis of advanced liver disease, cirrhosis and hepatocellular carcinoma by antiviral treatment, which is effective in about 50% of patients. The current standard of care for chronic HCV infection is the combination of pegylated interferon and ribavirin. Their dosage and the duration of therapy are tailored to the HCV genotype and the time to viral response. The frequent occurrence of adverse events, mainly hematological, requires careful monitoring, dose reduction in some cases, and, rarely, the use of erythrocyte or leukocyte growth factors. A new class of drugs for HCV treatment, the direct acting antivirals, is currently under development. Two of these drugs, the viral protease inhibitors boceprevir and telaprevir, are awaiting registration in Europe for use in association with pegylated interferon and ribavirin. These drugs are expected to ameliorate the virus eradication rates in patients who have not received previous antiviral treatment and, more importantly, to accomplish effective treatment in those patients who are partial responders to the current standard of care.