What can patients expect in the long term from radiofrequency thermocoagulation of hemorrhoids on bleeding, prolapse, quality of life, and recurrence: "no pain, no gain" or "no pain but a gain"?

Purpose: The purpose of this study was to assess the long-term efficacy of hemorrhoidal radiofrequency thermocoagulation (RFT) on bleeding, prolapse, quality of life (QoL), and recurrence. Methods: This retrospective, single-center study, with RFT performed using procedure modified via hemorrhoid exteriorization assessed the evolution of hemorrhoidal prolapse rated by Goligher scale; bleeding and discomfort (0-10), feeling of improvement and satisfaction (-5 to +5/5) by analog scales; the impact of hemorrhoids on QoL by HEMO-FISS-QoL score. Results: From April 2016 to January 2021, 124 patients underwent surgery and 107 could be interviewed in September 2021. The average follow-up was 30 months (range, 8-62 months). The mean work stoppage was 3 days, none in 71.0% of the cases. A mean of 4,334 J was applied. No analgesics were required for 66.4% of patients. External hemorrhoidal thrombosis was the only immediate complication in 9 patients, with no long-term reported complication. Bleeding disappeared in 53 out of 102 patients or dropped from 7 to 3/10 (P<0.001). Prolapse reduced from mean grade 3 to 2 (P< 0.001), discomfort from 7 to 2/10 (P<0.001). HEMO-FISS-QoL score improved from 22 to 7/100 (P<0.001). Feeling of improvement and overall satisfaction rate are +4/5. Recurrence occurred in 21.5% of patients at 22 months, and 6 required reoperation. Of the patients, 91.6% would choose the same procedure again and 96.3% recommend it. Conclusion: RFT, although imperfect, leads to a significant improvement in hemorrhoidal symptoms and a lasting increase in QoL with minimal pain and downtime, high acceptance, and low complication and recurrence rates.

Two Metabolomics Phenotypes of Human Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease According to Fibrosis Severity.

Non-Alcoholic Fatty Liver Disease (NAFLD) is considered as the forthcoming predominant cause for hepatocellular carcinoma (HCC). NAFLD-HCC may rise in non-cirrhotic livers in 40 to 50% of patients. The aim of this study was to identify different metabolic pathways of HCC according to fibrosis level (F0F1 vs. F3F4). A non-targeted metabolomics strategy was applied. We analyzed 52 pairs of human HCC and adjacent non-tumoral tissues which included 26 HCC developed in severe fibrosis or cirrhosis (F3F4) and 26 in no or mild fibrosis (F0F1). Tissue extracts were analyzed using 1H-Nuclear Magnetic Resonance spectroscopy. An optimization evolutionary method based on genetic algorithm was used to identify discriminant metabolites. We identified 34 metabolites differentiating the two groups of NAFLD-HCC according to fibrosis level, allowing us to propose two metabolomics phenotypes of NAFLD-HCC. We showed that HCC-F0F1 mainly overexpressed choline derivatives and glutamine, whereas HCC-F3F4 were characterized by a decreased content of monounsaturated fatty acids (FA), an increase of saturated FA and an accumulation of branched amino acids. Comparing HCC-F0F1 and HCC-F3F4, differential expression levels of glucose, choline derivatives and phosphoethanolamine, monounsaturated FA, triacylglycerides were identified as specific signatures. Our metabolomics analysis of HCC tissues revealed for the first time two phenotypes of HCC developed in NAFLD according to fibrosis level. This study highlighted the impact of the underlying liver disease on metabolic reprogramming of the tumor.

Assessment of Malnutrition, Sarcopenia and Frailty in Patients with Cirrhosis: Which Tools Should We Use in Clinical Practice?

Malnutrition is a common comorbidity in patients with cirrhosis. Its prognostic value is indisputable as it greatly affects the evolution of liver diseases. It has a major impact on both morbi-mortality before and after liver transplantation. Being now integrated in the definition of malnutrition and recognized as a new entity in the international classification of diseases, physicians have taken great interest in sarcopenia. Its negative consequences on the fate of patients with cirrhosis are well-demonstrated. The concept of frailty has recently been enlarged to chronic liver diseases as symptoms of impaired global physical functioning. In this article, we will discuss the definitions of malnutrition and emphasize its links with sarcopenia and frailty. We will show the relevance of frailty and sarcopenia in the course of liver diseases. The emerging role of muscle depletion on the cardiorespiratory system will also be highlighted. The importance of body composition will be demonstrated and the main tools reviewed. Finally, we adapted the definition of malnutrition to patients with cirrhosis based on the assessment of sarcopenia together with reduced food intakes.

12 Weeks of a Ribavirin-Free Sofosbuvir and Nonstructural Protein 5A Inhibitor Regimen Is Enough to Treat Recurrence of Hepatitis C After Liver Transplantation.

Sofosbuvir (SOF) combined with nonstructural protein 5A (NS5A) inhibitors has demonstrated its efficacy in treating a recurrence of hepatitis C virus (HCV) after liver transplantation (LT). However, the duration of treatment and need for ribavirin (RBV) remain unclear in this population. Our aim was to determine whether LT recipients could be treated with an SOF + NS5A inhibitor-based regimen without RBV for 12 weeks post-LT. Between October 2013 and December 2015, 699 LT recipients experiencing an HCV recurrence were enrolled in the multicenter ANRS CO23 CUPILT cohort. We selected patients receiving SOF and NS5A inhibitor ± RBV and followed for at least 12 weeks after treatment discontinuation. The primary efficacy endpoint was a sustained virological response 12 weeks after the end of treatment (SVR12). Among these 699 patients, 512 fulfilled the inclusion criteria. Their main characteristics were: 70.1% genotype 1, 18.2% genotype 3, 21.1% cirrhosis, and 34.4% previously treated patients. We identified four groups of patients according to their treatment and duration: SOF + NS5A without RBV for 12 (156 patients) or 24 (239 patients) weeks; SOF + NS5A + RBV for 12 (47 patients) or 24 (70 patients) weeks. SVR12 values reached 94.9%, 97.9%, 95.7%, and 92.9%, respectively (P = 0.14). Only 20 patients experienced a treatment failure. Under multivariate analysis, factors such as fibrosis stage, previous treatment, HCV genotype, and baseline HCV viral load did not influence SVR12 rates in the four groups (P = 0.21). Hematological adverse events (AEs) were more common in the RBV group: anemia (P < 0.0001) and blood transfusion (P = 0.0001). CONCLUSION: SOF + NS5A inhibitors without RBV for 12 weeks constituted reliable therapy for recurrent HCV post-LT with an excellent SVR12 whatever the fibrosis stage, HCV genotype, and previous HCV treatment. (Hepatology 2018; 00:000-000).

Interventional endoscopic ultrasound: A new promising way for intrahepatic portosystemic shunt with portal pressure gradient.

BACKGROUND AND OBJECTIVES: Interventional endoscopic ultrasound (EUS) is a promising novel approach for intravascular interventions. The aim of this study was to assess the feasibility and safety of a EUS-guided intrahepatic portosystemic shunt (EGIPS) with portal pressure gradient measurement in a live porcine model. METHODS: The left hepatic vein (LHV) or the inferior vena cava (IVC) was punctured with a needle that advanced into the portal vein (PV). A guidewire was then inserted into the PV, and a needle knife was used to create an intrahepatic fistula between LHV and PV. Portal pressure was recorded. The fistula was dilated with a balloon and a biliary metal stent was deployed between LHV and PV under sonographic and fluoroscopic observation. A portocavography validated the patency of the stent. Necropsies were realized after euthanasia. RESULTS: Portosystemic stenting was achieved in 19/21 pigs. Final portocavography confirmed stent patency between PV and LHV or IVC in 17 pigs (efficacy of 81%): Four stents were dysfunctional as two were thrombosed and two were poor positioned. Portal pressure was documented before and after shunting in 20/21 pigs. Necropsies revealed that 19/21 procedures were transesophageal and two were transgastric. Hemoperitoneum and pneumothorax were found in one pig and hemothorax was found in two pigs. Morbidity was 14.2% (3/21 animals). CONCLUSION: EGIPS was feasible in 91% of cases, functional in 81%, with 14.2% per procedure morbidity. EGIPS still needs to be assessed in portal hypertension pig models with longer follow-up before being considered as an alternative when the transjugular intrahepatic portosystemic shunt fails.

Usefulness of the Hook knife in flexible endoscopic myotomy for Zenker's diverticulum.

AIM: To investigate the outcome of flexible endoscopic myotomy performed with the Hook knife in patients with symptomatic Zenker's diverticulum (ZD). METHODS: All consecutive patients treated for ZD at our institution between 7/2012 and 12/2016 were included. The flexible endoscopic soft diverticuloscope-assisted technique with endoclips placement and Hook knife myotomy were performed in all patients. Here we report a retrospective review of prospectively collected data. Demographics, dysphagia score (Dakkak and Bennett), associated symptoms and adverse events were collected pre-procedure, at 2 and 6 mo post-procedure, and at the end of the follow-up period. Clinical success was defined as at least 1-point improvement in dysphagia score and a residual dysphagia score ≤ 1, with no need for reintervention. Dysphagia scores were compared before treatment and at end-of-follow-up using the Wilcoxon test. RESULTS: Twenty-four patients were included. Mean size of ZD was 3.0 cm (range 2-8 cm). Mean number of sessions was 1.17/patient (range 1-3 sessions). Overall clinical success was 91.7%. Two adverse events (8.3%) occurred, and both were managed conservatively. No bleeding or perforation was reported. Mild pain was reported by 9 patients (37.5%). Median hospital stay was 1 d (range 1-6). Median follow-up was 19.5 mo (range 6-53). Mean ± SD dysphagia score was 2.25 ± 0.89 before treatment and decreased to 0.41 ± 0.92 at end-of-follow-up (P < 0.001). Regurgitation and cough dropped from 91.7% and 50% to 12.5% and 0% at the end of follow-up, respectively. Recurrence was observed in 3 patients, and all 3 were symptom-free after one more session. CONCLUSION: The Hook knife, used in the soft diverticuloscope-assisted technique setting, is efficient and safe for treatment of ZD.

Specificities of Human Hepatocellular Carcinoma Developed on Non-Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue Extracts ¹H-NMR Spectroscopy.

There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD. To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis (n = 9), normal liver (n = 6) and NAFLD (n = 13). Metabolomics was performed using 1H-NMR Spectroscopy on tissue extracts and combined to multivariate statistical analysis. In HCC compared to NTT, statistical models showed high levels of lactate and phosphocholine, and low level of glucose. Shared and Unique Structures (SUS) plots were performed to remove the impact of underlying disease on the metabolic profile of HCC. HCC-cirrhosis was characterized by high levels of ß-hydroxybutyrate, tyrosine, phenylalanine and histidine whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. In addition, the overexpression glutamine/glutamate on HCC-NAFLD was confirmed by both Glutamine Synthetase (GS) immuno-staining and NMR-spectroscopy glutamine quantification. This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processes.

Long-term outcome of endoscopic ultrasound-guided pelvic abscess drainage: a two-center series.

Background and study aim Endoscopic ultrasound (EUS)-guided pelvic abscess drainage has been reported but long-term data remain limited. This two-center study evaluated long-term outcome of EUS-guided pelvic abscess drainage. Patients and methods Between May 2003 and December 2015, 37 consecutive patients were treated for perirectal or perisigmoid abscesses via EUS-guided drainage using plastic or lumen-apposing metal stent (LAMS). Clinical success was defined as complete resolution of the abscess on follow-up computed tomography (CT) scan at 4 weeks with symptom relief. Long-term success was defined as abscess resolution without the need for surgery and without recurrence on long-term follow-up (> 12 months). Results Median abscess size was 60 mm (interquartile range 41 - 70). Causes were postsurgical (n = 31, 83.8 %) or secondary to medical conditions (n = 6, 16.2 %). EUS-guided drainage involved needle aspiration (n = 4), plastic stent placement (n = 29) or LAMS placement (n = 4 patients). Technical and clinical success was achieved in 37 patients (100 %; 95 % confidence interval [CI] 91 - 100) and 34 patients (91.9 %; 95 %CI 78 - 98), respectively (5 patients needed a second EUS-guided intervention within 14 days after drainage). One patient required surgery and one required best supportive care owing to persistent abscess. Early complications were perforation requiring surgery (n = 1), stent migration (n = 1), and rectal discomfort (n = 1). At a median follow-up of 64 months (IQR 19 - 81), two patients experienced abscess recurrence, at 3 and 12 months, respectively, and were treated surgically. Long-term success was achieved in 32 of 37 patients (86.5 %; 95 %CI 71 - 95). Conclusion EUS-guided drainage of pelvic abscess is safe, has good long-term outcome, and should be considered as an alternative to percutaneous and surgical drainage.

Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study.

BACKGROUND & AIMS: HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy. METHODS: From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator's discretion. The primary efficacy end point was a sustained virological response (SVR) 12weeks after the end of treatment. RESULTS: The SVR rate 12weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p<0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs. CONCLUSIONS: Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence. LAY SUMMARY: The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.

Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative experience of 101 procedures at a single center.

BACKGROUND AND STUDY AIM: Endoscopic ultrasound (EUS)-guided biliary access is an alternative to percutaneous access after failed endoscopic retrograde cholangiopancreatography (ERCP). This report presents 7 years' cumulative experience of EUS-guided biliary drainage for obstructive jaundice in patients with failed ERCP. PATIENTS AND METHODS: Between February 2006 and February 2013, 101 patients (malignant = 98, benign = 3) with previous failed ERCP underwent an EUS intra- or extrahepatic approach with transluminal stenting or an EUS-guided rendezvous procedure with transpapillary stent placement. A single endoscopist performed all procedures. RESULTS: A total of 71 patients underwent the intrahepatic approach (66 hepatogastrostomies and 5 EUS-guided rendezvous), and 30 underwent the extrahepatic approach (26 choledochoduodenostomies, 1 choledochojejunostomy, 1 choledochoantrostomy, and 2 EUS-guided cholangiographies). Technical and clinical success rates were 98.0 % and 92.1 %, respectively. There was no difference in efficacy between hepatogastrostomies and choledochoduodenostomies (94 % vs. 90 %; P = 0.69) or in major complications (10.6 % vs. 6.7 %; P = 1). Adverse events occurred in 12 patients (11.9 %): 10 in the hepatogastrostomy group (2 limited pneumoperitoneum, 1 hepatic hematoma, 5 bile leakage, 2 sepsis), and 2 in the choledochoduodenostomy group (1 arteriobiliary fistula and 1 sepsis). There were six procedure-related deaths, five among the first 50 patients and one among the last 51 patients. Hepatogastrostomy vs. choledochoduodenostomy, plastic vs. metal stenting, stent-in-stent vs. 1 stent, nasobiliary drain, or postoperative octreotide infusion were not prognostic of bile leakage. CONCLUSION: EUS-guided biliary drainage is an efficient technique, but is associated with significant morbidity that seems to decrease with the learning curve. It should be performed in tertiary care centers in selected patients. Prospective randomized studies are needed to compare EUS-guided biliary drainage with percutaneous transhepatic cholangiography drainage.

Large balloon dilation post endoscopic sphincterotomy in removal of difficult common bile duct stones: a literature review.

Endoscopic sphincterotomy (ES) is the standard therapy in common bile duct (CBD) stones extraction. Large stones (≥ 12 mm) or multiple stones extraction may be challenging after ES alone. Endoscopic sphincterotomy followed by large balloon dilation (ESLBD) has been described as an alternative to ES in these indications. Efficacy, safety, cost-effectiveness and technical aspects of the procedure have been here reviewed. PubMed and Google Scholar search resulted in forty-one articles dealing with CBD stone extraction with 12 mm or more dilation balloons after ES. ESLBD is at least as effective as ES, and reduces the need for additional mechanical lithotripsy. Adverse events rates are not statistically different after ESLBD compared to ES for pancreatitis, bleeding and perforation. However, particular attention should be paid in patients with CBD strictures, which is identified as a risk factor of perforation. ESLBD is slightly cost-effective compared to ES. A small sphincterotomy is usually performed, and may reduce bleeding rates compared to full sphincterotomy. Dilation is performed with 12-20 mm enteral balloons. Optimal inflation time is yet to be determined. The procedure can be performed safely even in patients with peri-ampullary diverticula and surgically altered anatomy. ESLBD is effective and safe in the removal of large CBD stones, however, small sphincterotomy might be preferred and CBD strictures should be considered as a relative contraindication.