Gastric cancer in 2022:Is there still a role for endoscopic ultrasound?

Gastric cancer(GC)represents the fourth leading cause of cancer death worldwide and many factors can influence its development(diet,geographic area,genetic,Helicobacter pylori or Epstein-Barr virus infections).High quality endoscopy represents the modality of choice for GC diagnosis.The correct morphologic classification during a high-resolution endoscopy is fundamental for oncologic diagnosis,staging and therapeutic decisions.Since its initial introduction in clinical practice the endoscopic ultrasound(EUS)has been considered a valuable tool for tumor(T-)and lymph nodes(N-)staging also in GC,in order to establish the best therapeutic strategy for the patient(e.g.,upfront surgery vs neoadjuvant treatments).EUS tools as elastography,Doppler and contrast administration can improve diagnosis mainly in case of malignant lymph node evaluation.EUS has a marginal role in disease staging but has a fundamental role in case of a pre-endoscopic resection management and in the new era of endoscopic mucosal resection or submucosal dissection as minimally invasive surgery.Diagnosis and locoregional staging of GC with EUS are a method of inarguable value for the assessment of gastric wall involvement and presence of infiltrated paragastric lymph nodes.EUS can also have a role in disease restaging in those patients who have undergone neoadjuvant treatment.EUS can also have a role in the advanced phases of the disease,in facilitating palliative,minimallyinvasive treatments,such as gastroenterostomy or biliary drainages.This review intends to discuss the modern role of EUS in GC topic.

Endoscopic ultrasound and magnetic resonance imaging for re-staging rectal cancer after radiotherapy

AIM:To compare the sensitivity and specificity of two imaging techniques,endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI),in patients with rectal cancer after neoadjuvant chemoradiation therapy. And we compared EUS and MRI data with histological fi ndings from surgical specimens. METHODS:Thirty-nine consecutive patients (51.3% Male; mean age:68.2 ± 8.9 years) with histologically confirmed distal rectal cancer were examined for staging. All patients underwent EUS and MRI imaging before and after neoadjuvant chemoradiation therapy. RESULTS:After neoadjuvant chemoradiation,EUS and MRI correctly classified 46% (18/39) and 44% (17/39) of patients,respectively,in line with their histological T stage (P > 0.05). These proportions were higher for both techniques when nodal involvement was considered:69% (27/39) and 62% (24/39). When patients were sorted into T and N subgroups,the diagnostic accuracy of EUS was better than MRI for patients withT0-T2 (44% vs 33%,P > 0.05) and N0 disease (87% vs 52%,P = 0.013). However,MRI was more accurate than EUS in T and N staging for patients with more advanced disease after radiotherapy,though these differences did not reach statistical significance. CONCLUSION:EUS and MRI are accurate imaging techniques for staging rectal cancer. However,after neoadjuvant RT-CT,the role of both methods in the assessment of residual rectal tumors remains uncertain.

Endoscopic ultrasonography findings in autoimmune pancreatitis

Endoscopic ultrasonography is an established diagnostic tool for pancreatic masses and chronic pancreatitis.In recent years there has been a growing interest in the worldwide medical community in autoimmune pancreatitis (AIP),a form of chronic pancreatitis caused by an autoimmune process.This paper reviews the current available literature about the endoscopic ultrasonographic findings of AIP and the role of this imaging technique in the management of this protean disease.

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

the bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin.Consequently,preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular,histological and pathophysiological features.Intraepithelial neoplasms are reported in biliary tract,as biliary intraepithelial neoplasm(BilIN),and in pancreas,as pancreatic intraepithelial neoplasm(PanIN).Both can evolve to invasive carcinomas,respectively cholangiocarcinoma(CCA)and pancreatic ductal adenocarcinoma(PDAC).Intraductal papillary neoplasms arise in biliary tract and pancreas.Intraductal papillary neoplasm of the biliary tract(IPNB)share common histologic and phenotypic features such as pancreatobiliary,gastric,intestinal and oncocytic types,and biological behavior with the pancreatic counterpart,the intraductal papillary mucinous neoplasm of the pancreas(IPMN).All these neoplastic lesions exhibit similar immunohistochemical phenotypes,suggesting a common carcinogenic process.Indeed,CCA and PDAC display similar clinic-pathological features as growth pattern,poor response to conventional chemotherapy and radiotherapy and,as a consequence,an unfavorable prognosis.The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells.

Tumors and new endoscopic ultrasound-guided therapies

With the advent of linear echoendoscopes, endoscopic ultrasound (EUS) has become more operative and a new field of oncological application has been opened up. From tumor staging to tissue acquisition under EUS-guided fine-needle aspiration, new operative procedures have been developed on the principle of the EUS-guided puncture. A hybrid probe combining radiofrequency with cryotechnology is now available, to be passed through the operative channel of the echoendoscope into the tumor to create an area of ablation. EUS-guided fine-needle injection is emerging as a method to deliver anti-tumoral agents inside the tumor. Ethanol lavage, with or without paclitaxel, has been proposed for the treatment of cystic tumors in non-resectable cases and complete resolution has been recorded in up to 70%-80%. Many other chemical or biological agents have been investigated for the treatment of pancreatic adenocarcinoma: activated allogenic lymphocyte culture (Cytoimplant), a replication-deficient adenovirus vector carrying the tumor necrosis factor-α gene, or an oncolytic attenuated adenovirus (ONYX-015). The potential advantage of treatment under EUS control is the real-time imaging guidance into a deep target likethe pancreas which is extremely difficult to reach by a percutaneous approach. To date there are no randomized controlled trials to confirm the real clinical benefits of these treatments compared to standard therapy so it seems wise to reserve them only for experimental protocols approved by ethics committees.

Outcome of endotherapy for pancreas divisum in patients with acute recurrent pancreatitis

AIM:To assess the rate of relapses of acute pancreatitis(AP),recurrent AP(RAP)and the evolution of endosonographic signs of chronic pancreatitis(CP)in patients with pancreas divisum(PDiv)and RAP.METHODS:Over a five-year period,patients with PDiv and RAP prospectively enrolled were divided into two groups:(1)those with relapses of AP in the year before enrollment were assigned to have endoscopic therapy(recent RAP group);and(2)those free of recurrences were conservatively managed,unless they relapsed during follow-up(previous RAP group).All patients in both groups entered a follow-up protocol that includedclinical and biochemical evaluation,pancreatic endoscopic ultrasonography(EUS)every year and after every recurrence of AP,at the same time as endoscopic retrograde cholangiopancreatography(ERCP).RESULTS:Twenty-two were treated by ERCP and 14were conservatively managed during a mean follow-up of 4.5±1.2 years.In the recent RAP group in whom dorsal duct drainage was achieved,AP still recurred in11(57.9%)after the first ERCP,in 6 after the second ERCP(31.6%)and in 5 after the third ERCP(26.3%).Overall,endotherapy was successful 73.7%.There were no cases of recurrences in the previous RAP group.EUS signs of CP developed in 57.9%of treated and 64.3%of untreated patients.EUS signs of CP occurred in 42.8%of patients whose ERCPs were successful and in all those in whom it was unsuccessful(P=0.04).There were no significant differences in the rate of AP recurrences after endotherapy and in the prevalence of EUS signs suggesting CP when comparing patients with dilated and non-dilated dorsal pancreatic ducts within each group.CONCLUSION:Patients with PDiv and recent episodes of AP can benefit from endoscopic therapy.Effective endotherapy may reduce the risk of developing EUS signs of CP at a rate similar to that seen in patients of previous RAP group,managed conservatively.However,in a subset of patients,endotherapy,although successful,did not prevent the evolution of endosonographic signs of CP.

New era for pancreatic endoscopic ultrasound: From imaging to molecular pathology of pancreatic cancer

With recent advances in molecular pathology and the development of new chemotherapy regimens,the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma(PDAC)is becoming appealing for stratifying patients for prognosis and response to a defined treatment.Archival formalin-fixed,paraffinembedded samples are a useful source of genomic deoxyribonucleic acid;nevertheless,most studies employed formalin-fixed,paraffin-embedded samples deriving from surgical specimens,which are therefore representative of<20%of PDAC patients.Indeed,the development of a reliable methodology for endoscopic ultrasound-guided tissue acquisition,stabilization,and analysis is crucial for the development of molecular markers for clinical use in order to achieve“personalized medicine”.With the development of new needles,this technique is able to retrieve a high quantity and quality of PDAC tissue that can be used not only for diagnosis but also for mutational and transcriptome evaluations and for the development of primary cell or tissue cultures.In the present editorial,we discuss the current knowledge regarding the use of endoscopic ultrasound as a tool to obtain samples for molecular analyses,its possible pitfalls,and its use for the development of disease models such as xenografts or organoids.

Feasibility of therapeutic endoscopic ultrasound in the bridge-to-surgery scenario:The example of pancreatic adenocarcinoma

Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma,as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments.Jaundice,gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity,resulting in potentially deleterious chemotherapy discontinuation,whose resumption relies on effective,prompt and long-lasting management of these complications.Although therapeutic endoscopic ultrasound(t-EUS)can potentially offer some advantages over comparators,its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery.This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy,gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario.Proof-ofconcept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery.Moreover,the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation,potentially resulting in higher subsequent resectability.Available evidence is discussed in this short paper,together with technical notes that might be useful for endoscopists and surgeons operating in this scenario.No published evidence supports restricting t-EUS in potential surgical candidates,especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy.Bridge-to-surgery tEUS deserves further prospective evaluation.

Fetal radiation exposure: Is monitoring really needed?

The effect of fetal radiation during endoscopic retro-grade cholangiopancreatography (ERCP) on pregnant women is a very interesting topic. Smith et al recently estimated the fetal radiation exposure in pregnant women undergoing ERCPs using thermoluminescent dosimeters (TLDs). The authors concluded that TLDs are unnecessary during ERCP with modified techniques. We believe that an extreme caution is needed in clinical practice before drawing such conclusions when they are not strongly supported by enough experimental evidence. Therefore, we recommend that fetal radiation exposure be monitored in clinical practice by using dosimeters, bearing in mind that all relevant techniques to control and minimize the exposure must be applied.

Endoscopic ultrasound radiofrequency ablation of pancreatic insulinoma in elderly patients:Three case reports

BACKGROUND Endoscopic ultrasound(EUS)-guided radiofrequency ablation(RFA)has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery,in order to obtain clinical syndrome regression.Data on the safety and long-term effectiveness of this approach are scarce,and EUS-RFA procedures are not standardized.CASE SUMMARY The present case series reports 3 elderly patients with a pancreatic insulinoma and comorbidities,locally treated by EUS-guided RFA with clinical success in terms of hypoglycemic symptoms.RFA procedures were performed during deep sedation,under EUS control with a 19 G needle,an electrode 5-mm in size at a power of 30 W and multiple RFA applications during the same session in order to treat the whole area of the lesions.Immediate relief of symptoms was evident in 2 patients after the first EUS-RFA,while in the third patient a second endoscopic treatment was needed.All 3 patients are symptom-free without need of medications after 24 mo of follow-up with imaging follow-up showing no disease recurrence.A single adverse event of intraprocedural bleeding occurred,which was successfully treated endoscopically.CONCLUSION EUS-RFA represents an effective and safe alternative to surgery for the treatment of insulinomas in elderly patients at high surgical risk.However,larger multicenter studies withlonger follow-up are needed in order to better assess its safety and clinical success.