Management of malignant Gastric Outlet Obstruction (mGOO) due to pancreatic cancer in the era of EUS-Gastrojejunostomy: an international practice survey and case vignette study by Pancreas 2000 from the European Pancreatic Club.

BACKGROUND: Malignant Gastric Outlet Obstruction (mGOO) has been standardly treated by surgical Gastrojejunostomy (S-GJ) or Endoscopic Stenting (ES). Recently, EUS-Gastrojejunostomy (EUS-GJ) has emerged as an alternative, despite its worldwide diffusion is heterogeneous. The aim of this survey was to assess clinical decision-making around mGOO and to explore current opinions regarding EUS-GJ. METHODS: An online survey, spread through social networks and EPC newsletter, was created exploring opinions regarding indications, contraindications, benefits/risks, availability of mGOO treatments; 2 case vignettes explored clinical decision-making in different scenarios. RESULTS: Overall, 290 pancreatologists from 44 countries responded, of whom 35% surgeons and 65% gastroenterologists. The most common treatment for mGOO was ES (86%), followed by laparoscopic GJ (76%). EUS-GJ was accessible to 59% of respondents, with 10% proficient in this technique. Gold-standard treatment for mGOO varied by specialty; 45% of gastroenterologists preferred ES, 20% EUS-GJ, and 10% surgical GJ, while among surgeons, these were 24%, 8%, and 25%, respectively. A higher annual volume of mGOO treated correlated with increased EUS-GJ adoption and reduced surgical advice. For 51%, EUS-GJ will become the primary treatment for mGOO, notably higher among gastroenterologists and high-volume centers. For 14%, EUS-GJ spread will be limited in the future, or used only when ES fails (19%). Life expectancy, disease stage and patient's frailty are the main decision driver in therapeutic choice, whereas future surgical resectability does not contraindicate any treatment for 75%. EUS-GJ's main advantages were its minimally invasive nature and clinical efficacy, offset by its steep learning curve. CONCLUSIONS: This survey revealed significant differences in the management of mGOO, depending on specialties, local expertise and treatment volume, suggesting the lack of standardized algorithms. Life expectancy and patients' frailty are the main decision drivers. Regarding EUS-GJ, its availability remains suboptimal, with learning curve as the main perceived barrier.

Hepatocellular carcinoma recurrence after direct-acting antiviral therapy: an individual patient data meta-analysis.

OBJECTIVE: The benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration. DESIGN: We pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson. RESULTS: Recurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; p<0.001), performance status (2 vs 0, RR=4.35, 95% CI 1.54 to 11.11; 2 vs 1, RR=3.7, 95% CI 1.3 to 11.11; p=0.01) and tumour burden pre-HCC treatment (multifocal vs solitary nodule, RR=1.75, 95% CI 1.25 to 2.43; p<0.001). No significant difference was observed in RR between the DAA-exposed and DAA-unexposed groups in propensity score-matched patients (RR=0.64, 95% CI 0.37 to 1.1; p=0.1). CONCLUSION: Effects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

SARS-CoV-2 infection in patients with a normal or abnormal liver.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus causing coronavirus disease 19 (COVID-19), with an estimated 22 million people infected worldwide so far although involving primarily the respiratory tract, has a remarkable tropism for the liver and the biliary tract. Patients with SARS-CoV-2 infection and no antecedent liver disease may display evidence of cytolytic liver damage, proportional to the severity of COVID-19 but rarely of clinical significance. The mechanism of hepatocellular injury is unclear and possibly multifactorial. The clinical impact of SARS-CoV-2 infection in patients with underlying chronic liver disease, a cohort whose global size is difficult to estimate, has been assessed appropriately only recently and data are still evolving. Patients with cirrhosis are at higher risk of developing severe COVID-19 and worse liver-related outcomes as compared to those with non-cirrhotic liver disease. OLT patients have an intermediate risk. Specific interventions in order to reduce the risk of transmission of infection among this high-risk population have been outlined by international societies, together with recommendations for modified treatment and follow-up regimens during the COVID-19 pandemic. When a vaccine against SARS-CoV-2 becomes available, patients with fibrotic liver disease and those with OLT should be considered as prime targets for prophylaxis of COVID-19, as all other highly susceptible subjects.

Biliopancreatic Endoscopy in Altered Anatomy.

Background and Objectives: Anatomical post-surgical alterations of the upper gastrointestinal (GI) tract have always been challenging for performing diagnostic and therapeutic endoscopy, especially when biliopancreatic diseases are involved. Esophagectomy, gastrectomy with various reconstructions and pancreaticoduodenectomy are among the most common surgeries causing upper GI tract alterations. Technological improvements and new methods have increased the endoscopic success rate in these patients, and the literature has been rapidly increasing over the past few years. The aim of this systematic review is to identify evidence on the available biliopancreatic endoscopic techniques performed in the altered post-surgical anatomy of upper GI tract. Materials and Methods: We performed a systematic search of PubMed, MEDLINE, Cochrane Library, and SCOPUS databases. Study-level variables extracted were the last name of the first author, publication year, study design, number of patients, type of post-surgical anatomical alteration, endoscopic technique, success rate and endoscopic-related adverse events. Results: Our primary search identified 221 titles, which was expanded with studies after the citation search. The final full-text review process identified 52 articles (31 retrospective studies, 8 prospective studies and 13 case reports). We found several different techniques developed over the years for biliopancreatic diseases in altered anatomy, in order to perform both endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP). They included enteroscopy-assisted ERCP (double and single balloon enteroscopy-ERCP, spiral enteroscopy-ERCP) laparoscopic assisted ERCP, EUS-Directed transgastric ERCP, EUS-directed transgastric intervention, gastric access temporary for endoscopy, and percutaneous assisted trans prosthetic endoscopic therapy. The success rate was high (most of the techniques showed a success rate over 90%) and a low rate of adverse events were reported. Conclusions: We suggest the considerationof the novel techniques when approaching patients with altered anatomy who require biliopancreatic endoscopy, focusing on the surgery type, success rate and adverse events reported in the literature.

Endoscopic Retrograde Cholangiopancreatography (ERCP) for Suspected Mirizzi Syndrome Type IV as Both a Diagnostic and Bridge-to-Surgery Procedure.

Mirizzi syndrome (MS) is a challenging diagnosis due to its similar presentation with other biliary diseases; thus, the role of endoscopy is sometimes unclear, especially in altered anatomy. Radiological examinations may usually suspect it, but deeper examinations could be necessary to confirm it. Endoscopic retrograde cholangiopancreatography (ERCP) certainly has a therapeutic role in cases of jaundice, cholangitis or concurrent choledocolithiasis, although surgery is without doubt the definitive treatment in most of the cases. Therefore, surgeons may have a clearer picture of the condition of the biliary tree with respect to fistulas thanks to ERCP, particularly in patients with a higher grade of MS (type higher than 2 in the Csendes classification). Therefore, a complete removal of biliary stones is sometimes not possible due to size and location, so biliary stenting becomes the only option, even if transitory. Our brief report is a further demonstration of the fundamental role of ERCP in managing MS, even when it has no long-term therapeutic aim but is performed as bridge-to-surgery, especially in cases with a more difficult biliary anatomy due to the type of fistula. Moreover, we truly suggest discussing patients affected with MS in a multidisciplinary board, preferably in tertiary hepatobiliary centers.

Navigating the Labyrinth: When the "Mesenterium Commune" Turns Colonoscopy into an Endoscopic Rollercoaster.

These images involved the case of a 51-year-old woman who had a history of chronic abdominal pain, iron deficiency, and diarrhoea but no blood or mucus in her stool. She had never undergone major abdominal surgery, and her past medical evaluation diagnosed her with celiac disease, leading to the adoption of a gluten-free diet alleviating most of her gastrointestinal symptoms. However, years later, her abdominal pain returned, so she underwent an abdominal ultrasound, revealing non-specific bowel loop dilation, and a weakly positive faecal occult blood test led to a colonoscopy. Despite many efforts to advance the scope beyond the transverse colon, colonoscopy was arduous and not complete, even after several changes in decubitus and abdominal compressions. Therefore, a virtual colonoscopy was conducted, revealing no intraluminal masses, but the entire colon was located on the left side of the abdomen. Indeed, the results showed sigma and that most of the colon was curled up in the small pelvis. This rare anatomical variant, known as "Mesenterium commune" (MC), is a type of gut malrotation that develops in childhood due to a lack of omphalomesenteric loop rotation during the embryonic period. This condition can lead to episodes of intestinal obstruction, potentially resulting in an acute abdomen and leading to surgical correction. Symptoms include chronic recurring abdominal pain, nausea, vomiting, and occasionally bloody stools. Few cases of this extremely rare condition have been reported in the literature so far.

Balancing Efficacy and Tolerability of First-Line Systemic Therapies for Advanced Hepatocellular Carcinoma: A Network Meta-Analysis.

Background: Atezolizumab + bevacizumab represent the current standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, direct comparison with other combination treatments including immune checkpoint inhibitors (ICI) + tyrosine kinase inhibitors (TKIs) are lacking. Objectives: This network meta-analysis (NMA) aims to indirectly compare the efficacy and the safety of first-line systemic therapies for unresectable advanced HCC. Method: A literature search of MEDLINE, Embase, and SCOPUS databases was conducted up to October 31, 2022. Phase 3 randomized controlled trials (RCTs) testing TKIs, including sorafenib and lenvatinib, or ICIs reporting overall survival (OS) and progression-free survival (PFS) were included. Individual survival data were extracted from OS and PFS curves to calculate restricted mean survival time. A Bayesian NMA was performed to compare treatments in terms of efficacy (15- and 30-month OS, 6-month PFS) and safety, represented by grade ≥3 (severe) adverse events (SAEs). The incremental safety-effectiveness ratio as measure of net health benefit was calculated as the difference in SAE probability divided by survival difference between the 2 most effective treatments. Results: Nine RCTs enrolling 6,600 patients were included. Atezolizumab plus bevacizumab showed the highest probability (88%) of achieving the 30-month OS landmark. Lenvatinib showed a probability of 86% of achieving best PFS outcomes. ICI monotherapies ranked as most tolerable. Atezolizumab plus bevacizumab showed the best net health benefit for OS, compared to durvalumab plus tremelimumab. When evaluating the net health benefit for PFS, at a willingness-to-risk threshold of 10% of SAEs for life-month gained, atezolizumab plus bevacizumab was favoured in 78% of cases, while at threshold of 30% of SAEs for life-month gained, lenvatinib was favoured in 76% of cases. Conclusions: Atezolizumab plus bevacizumab is the best treatment in terms of net benefit and therefore it should be recommended as standard of care. Compared to atezolizumab plus bevacizumab, lenvatinib monotherapy had the best net benefit for PFS when physicians and patients are available to accept a higher risk of toxicity.

A rare case of pedunculated ampulloma: EUS view and resection.

Video 1Video showing a rare case of pedunculated ampulloma: imaging evaluation and resection technique.

The Role of Endoscopy in the Palliation of Pancreatico-Biliary Cancers: Biliary Drainage, Management of Gastrointestinal Obstruction, and Role in Relief of Oncologic Pain.

Therapeutic endoscopy permits many and various treatments for cancer palliation in patients with bilio-pancreatic cancers, enabling different options, supporting patients during their route to oncologic treatments, and trying to improve their quality of life. Therefore, both endoscopic and endoscopic ultrasound (EUS)-guided techniques are performed in this scenario. We performed a literature review focusing on the role of endoscopy in the palliation of those advanced pancreatic and biliary cancers developing malignant biliary obstruction (MBO), gastric outlet obstruction (GOO), and pain unresponsive to medical therapies. Therefore, we explored and focused on the clinical outcomes of endoscopic procedures in this scenario. In fact, the endoscopic treatment is based on achieving biliary drainage in the case of MBO through endoscopic retrograde cholangiopancreatography (ERCP) or EUS-guided biliary drainage (EUS-BD), while GOO is endoscopically treated through the deployment of an enteral stent or the creation of EUS-guided gastro-entero-anastomosis (EUS-GEA). Furthermore, untreatable chronic abdominal pain is a major issue in patients unresponsive to high doses of painkillers, so EUS-guided celiac plexus neurolysis (CPN) or celiac ganglia neurolysis (CGN) helps to reduce dosage and have better pain control. Therefore, therapeutic endoscopy in the palliative setting is an effective and safe approach for managing most of the clinical manifestations of advanced biliopancreatic tumors.

Complete intraperitoneal maldeployment of a lumen-apposing metal stent during EUS-guided gastroenteroanastomosis for malignant gastric outlet obstruction: rescue retrieval with peritoneoscopy through natural orifice transluminal endoscopic surgery.

Video 1Case showing a complete intraperitoneal maldeployment of a lumen-apposing metal stent during EUS-guided gastro-entero-anastomosis for malignant gastric outlet obstruction, which was rescued through a retrieval with peritoneoscopy through natural orifice transluminal endoscopic surgery.