Maximizing the endosonography: The role of contrast harmonics, elastography and confocal endomicroscopy

New technologies in endoscopic ultrasound(EUS) evaluation have been developed because of the need to improve the EUS and EUS-fine needle aspiration(EUS- FNA) diagnostic rate. This paper reviews the principle, indications, main literature results, limitations and future expectations for each of the methods presented. Contrast-enhanced harmonic EUS uses a low mechanical index and highlights slowflow vascularization. This technique is useful for differentiating solid and cystic pancreatic lesions and assessing biliary neoplasms, submucosal neoplasms and lymph nodes. It is also useful for the discrimination of pancreatic masses based on their qualitative patterns; however, the quantitative assessment needs to be improved. The detection of small solid lesions is better, and the EUS-FNA guidance needs further research. The differentiation of cystic lesions of the pancreas and the identification of the associated malignancy features represent the main indications. Elastography is used to assess tissue hardness based on the measurement of elasticity. Despite its low negative predictive value, elastography might rule out the diagnosis of malignancy for pancreatic masses. Needle confocal laser endomicroscopy offers useful information about cystic lesions of the pancreas and is still under evaluation for use with solid pancreatic lesions of lymph nodes.

Noninvasive assessment of portal hypertension in cirrhosis:Liver stiffness and beyond

Liver stiffness measurement(LSM)is a good,but still limited tool to noninvasively assess complications and prognosis in patients with advanced liver disease.This review aims to consider the role of LSM for the diagnosis of portal hypertension-related complications and for assessment of prognosis in cirrhotic patients,and to highlight the drawbacks as well as some alternatives for improving the performance.Hence,this field is far from being closed,and deserves more attention.There is still a place for more carefully designed studies to find new,innovative and reliable approaches.

Extrahepatic cholangiocarcinoma:Current status of endoscopic approach and additional therapies

The prognosis of patients with advanced or unresectable extrahepatic cholangiocarcinoma is poor.More than 50%of patients with jaundice are inoperable at the time of first diagnosis.Endoscopic treatment in patients with obstructive jaundice ensures bile duct drainage in preoperative or palliative settings.Relief of symptoms(pain,pruritus,jaundice)and improvement in quality of life are the aims of palliative therapy.Stent implantation by endoscopic retrograde cholangiopancreatography is generally preferred for long-term palliation.There is a vast variety of plastic and metal stents,covered or uncovered.The stent choice depends on the expected length of survival,quality of life,costs and physician expertise.This review will provide the framework for the endoscopic minimally invasive therapy in extrahepatic cholangiocarcinoma.Moreover,additional therapies,such as brachytherapy,photodynamic therapy,radiofrequency ablation,chemotherapy,molecular-targeted therapy and/or immunotherapy by the endoscopic approach,are the nonsurgical methods associated with survival improvement rate and/or local symptom palliation.

Endoscopic ultrasound-guided tissue acquisition for the diagnosis of focal liver lesion

In patients with liver tumors,the histopathology examination can assist in diagnosis,staging,prognosis,and therapeutic management strategy.Endoscopic ultrasound(EUS)-guided tissue acquisition using fine needle aspiration(FNA)or more newly fine needle biopsy(FNB)is a well-developed technique in order to evaluate and differentiate the liver masses.The goal of the EUS-FNA or EUS-FNB is to provide an accurate sample for a histopathology examination.Therefore,malignant tumors such as hepatocarcinoma,cholangiocarcinoma and liver metastasis or benign tumors such as liver adenoma,focal hyperplastic nodular tumors and cystic lesions can be accurately diagnosed using EUS-guided tissue acquisition.EUS-FNB using 19 or 22 Ga needle provide longer samples and a higher diagnostic accuracy in patients with liver masses when compared with EUS-FNA.Few data are available on the diagnostic accuracy of EUS-FNB when compared with percutaneously,ultrasound,computer tomography or transjugulary-guided liver biopsies.This review will discuss the EUS-guided tissue acquisition options in patients with liver tumors and its efficacy and safety in providing accurate samples.The results of the last studies comparing EUS-guided liver biopsy with other conventional techniques are presented.The EUS-guided tissue acquisition using FNB can be a suitable technique in suspected liver lesions in order to provide an accurate histopathology diagnosis,especially for those who require endoscopy.

Bleeding Dieulafoy's-like lesions of the gut identified by capsule endoscopy

Dieulafoy's-like lesions (DLs-like) represent a cause of obscure gastrointestinal bleeding, enteroscopy being the main diagnostic and therapeutic procedure. Frequently, more than one enteroscopy is needed to identify the bleeding vessel. In our practice, video capsule endoscopy (VCE) identified and guided therapy in four cases of DLs-like; three of them were localized on the small bowel. We report, for the first time, a diagnosis of colonic DL-like performed by colon capsule endoscopy. Two patients presented with severe cardiovascular disorders, being hemodynamically unstable during VCE examination. Based on the VCE findings, only one invasive therapeutic procedure per patient was necessary to achieve hemostasis. VCE and enteroscopy may be regarded as complementary procedures in patients with gut DLs-like.

Noninvasive assessment of alcoholic liver disease using unidimensional transient elastography(Fibroscan~)

Unidimensional transient elastography(TE) is a noninvasive technique, which has been increasingly used in the assessment of diffuse liver diseases. This paper focuses on reviewing the existing data on the use of TE in the diagnosis of fibrosis and in monitoring disease progression in alcoholic liver disease, on the factors that may influence the result of fibrosis prediction, and last but not least, on its potential use in assessing the steatosis degree. Therefore, this field is far from being exhausted and deserves more attention. Further studies are required, on large groups of biopsied patients, in order to find answers to all the remaining questions in this field.

Relationship between cachexia and perineural invasion in pancreatic adenocarcinoma

BACKGROUND Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma(PDAC).The rapid disease progression and patient deterioration seems related to perineural invasion,but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied.As perineural invasion is difficult to be highlighted,a biomarker such as the neurotrophic factor Midkine(MK)which promotes the neuronal differentiation and the cell migration could be helpful.Also,Activin(ACV)has been described as cachexia related to PDAC.However,their role for assessing and predicting the disease course in daily practice is not known.AIM To assess the relationship between perineural invasion and cachexia and their biomarkers,MK and ACV,respectively,and their prognostic value.METHODS This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies.Patients with other causes of malnutrition were excluded.The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data.These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease.RESULTS The study comprised 114 patients with PDAC,125 controls and a supplementary group of 14 benign pancreatic tissue samples.ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls(63% vs 32% for ACV,P<0.001;47%vs 16%for MK,P<0.001),with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage(P=0.006),the presence of metastasis(P=0.04),perineural invasion(P=0.03)and diabetes(P=0.002),but with no influence on survival.No correlation between clinicopathological factors and ACV expression was noted.Cachexia,present in 19%of patients,was unrelated to ACV or MK level.Higher ACV expression was associated with a shorter survival(P=0.008).CONCLUSION The MK was a biomarker of perineural invasion,associated with tumor stage and diabetes,but without prognostic value as ACV.Cachexia was unrelated to perineural invasion,ACV level or survival.

Ulcerative colitis worsened after Clostridium difficile infection:Efficacy of infliximab

The incidence of Clostridium difficile (C. difficile) infection (CDI) is 1.8%-5.7% in admitted patients with ulcerative colitis (UC). CDI can worsen UC and increase the risk for colectomy or even death, thus necessitating therapy escalation, such as increasing the corticoid therapy or starting a biologic treatment. Several reported cases with infliximab therapy have provided favorable outcomes in UC patients with CDI, suggesting that infliximab treatment may be protective; however, the optimal infliximab treatment regimen for UC patients with CDI remains to be established. Here, we report a case of worsening UC in the presence of recurrent CDI. The patient had received prior ciprofloxacin and immunosuppressive therapy during a prolonged hospital stay. The deterioration in the patient&#x02019;s condition likely resulted from the ability of C. difficile to promote relapsing of UC by activating the immune response. Ultimately, the patient was treated with a high dose of infliximab after a low trough level of infliximab at week 8 was identified, yielding better clinical results. Infliximab was found to be safe after repetitive episodes of CDI. The trough level of infliximab was therefore a useful indicator to guide therapy and correlated well with the patient&#x02019;s outcome.

Peroral endoscopic myotomy: Time to change our opinion regarding the treatment of achalasia?

Peroral endoscopic myotomy(POEM) is a new endoscopic treatment for achalasia. Compared to the classical surgical myotomy, POEM brings at least the advantage of minimal invasiveness. The data provided until now suggest that POEM offers excellent short-term symptom resolution, with improvement of dysphagia in more than90% of treated patients, with encouraging manometric outcomes and low incidence of postprocedural gastroesophageal reflux. The effectiveness of this novel therapy requires long-term follow-up and comparative studies with other treatment modalities for achalasia. This technique requires experts in interventional endoscopy, with a learning curve requiring more than 20 cases, including training on animal and cadaver models, and with a need for structured proctoring during the first cases. This review aims to summarize the data on the technique, outcomes, safety and learning curve of this new endoscopic treatment of achalasia.

Prognostic factors of response to endoscopic treatment in painful chronic pancreatitis

AIM To evaluate the endoscopic treatment efficacy and prognostic factors of long-term response to treatment for painful chronic pancreatitis.METHODS This retrospective analysis identified 168 patients with painful chronic pancreatitis hospitalized during January 2010-January 2015 in a Romanian tertiary referral center. Data on demographics, medical history, alcohol consumption, smoking habit, clinical parameters, type and number of endoscopic procedures and hospital admissions number were collected from the medical charts and analyzed. The absence or substantial reduction of pain(mild pain) at the end of the follow-up associated with the technical success of endotherapy was considered as clinical success. RESULTS Among the 168 patients with painful chronic pancreatitis admitted to our department during the study period, 39(23.21%) had optimal response to the medical therapy. One hundred and twenty-nine patients required endoscopic treatment. The median follow-up period was 15 mo(range, 0-60 mo). Overall, technical success of endotherapy was achieved in 105 patients(81.39%). More than two-thirds of patients(82.78%) had substantial improvement of pain after the endoscopic treatment, including frequency and severity of the pain attacks. Patients younger than 40 years had significantly more successful endoscopic procedures(P = 0.041). Clinical success was higher in non-smoking patients(P = 0.003). The hospital admission rate was higher in patients with recognized alcohol consumption(P = 0.03) and in smokers(P = 0.027). The number and location of pancreatic stones and locations of strictures did not significantly influence the technical success(P > 0.05) or the clinical success(P > 0.05).CONCLUSION Younger age than 40 years can be considered an important factor positively influencing endoscopic treatment outcome in patients with painful chronic pancreatitis.

Malnutrition and non-compliance to nutritional recommendations in patients with cirrhosis are associated with a lower survival

BACKGROUND Malnutrition is frequently encountered in patients with cirrhosis and appears to significantly impact their prognosis.While evaluating the burden of malnutrition in cirrhosis is gathering momentum,as suggested by multiple recently published reports,there is still a persistent scarcity of solid data in the field,especially with regards to the role of nutritional interventions.AIM To assess the prevalence of malnutrition in patients with advanced cirrhosis and to evaluate its impact on survival.METHODS One hundred and one consecutive patients with advanced cirrhosis were screened for malnutrition using the Subjective Global Assessment(SGA)criteria and the mid-arm circumference(MAC).Malnutrition was defined as SGA class B and C and MAC<10th percentile.All patients were interviewed regarding their food intake using an adapted questionnaire.Subsequently,total energy intake was calculated and further subdivided in main nutrients.The data were then compared to the available recommendations at the time of analysis to assess adherence.RESULTS 54/79 patients(68.4%)in the decompensated group had malnutrition,while only 3/22 patients(13.6%)were malnourished in the compensated group.After a median follow-up time of 27 mo(0-53),the overall mortality was 70%.Survival was significantly lower among patients with malnutrition.The mortality rates were 50%at 1 year and 63%at 2 years for the patients with malnutrition,compared to 21%at 1 year and 30%at 2 years for patients without malnutrition(P=0.01).On multivariate analysis,the factors independently associated with mortality were age,creatinine level and adherence to the protein intake recommendations.The mortality was lower in patients with the appropriate protein intake:8%at 1 year and 28%at 2 years in the adherent group,compared to 47%at 1 year and 56%at 2 years in the non-adherent group.CONCLUSION The prevalence of malnutrition is high among patients with advanced cirrhosis and might be related in part to a low adherence to nutritional recommendations,especially with regards to protein intake.

Pulmonary complications of portal hypertension:The overlooked decompensation

The systemic nature of cirrhosis and portal hypertension has long been recognized,and the amount of data characterizing the interplay between each system is becoming ever so complex.Lung involvement was among the first described associated entities in cirrhosis,with reports dating back to the late nineteenth century.However,it appears that throughout the years,interest in the pulmonary complications of portal hypertension has generally faded,especially in contrast to other decompensating events,as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers.Despite affecting up to 10%-15%of patients with advanced liver disease and having a proven prognostic impact,hepato-pulmonary syndrome,porto-pulmonary hypertension,and hepatic hydrothorax are frequently misdiagnosed,mistreated,or misinterpreted.This lack of precision might adversely impact patient care,referral to expert centers,and,ultimately,liver disease-related mortality and successful transplantation odds.The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities.The paper focuses on the essential theoretical aspects,addressing the most critical knowledge gaps on the one hand and,on the other hand,critically discussing one key issue for each complication.

Contrast-enhanced guided endoscopic ultrasound procedures

Contrast-enhanced endoscopic ultrasound(CH-EUS)can overcome the limi-tations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours.Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions,further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS.This review details the knowledge based on the available data on contrast-guided procedures.The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions,which occur in select cases.Additionally,the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage,and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented.Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours,in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Surgical management of hydatid cyst disease of the liver: An improvement from our previous experience?

BACKGROUND Hydatid liver disease remains an important issue in endemic areas,which may require immediate surgery.Although laparoscopic surgery is on the rise,the presence of certain complications may require conversion to the open approach.AIM To compare the results of laparoscopic treatment and the open approach in the context of a 12-year single institution experience,and to perform a further comparison between results from the current study and those from a previous study.METHODS Between January 2009 and December 2020,247 patients underwent surgery for hydatic disease of the liver in our department.Of the 247 patients,70 underwent laparoscopic treatment.A retrospective analysis between the two groups was performed,as well as a comparison between current and previous laparoscopic experience(1999-2008).RESULTS There were statistically significant differences between the laparoscopic and open approaches regarding the cyst dimension,location,and presence of cystobiliary fistula.There were no intraoperative complications in the laparoscopic group.The cutoff value for the cyst size regarding the presence of cystobiliary fistula was 6.85 cm(P=0.001).CONCLUSION Laparoscopic surgery still plays an important role in the treatment of hydatid disease of the liver,with an increase in its usage over the course of years that has shown benefits regarding the postoperative recovery with a decreased rate of intraoperative complications.Although experienced surgeons can perform laparoscopic surgery in the most difficult conditions,there are some selection criteria that need to be maintained for higher quality results.

Diagnostic challenges in non-cirrhotic portal hypertension-porto sinusoidal vascular disease

Non-cirrhotic portal hypertension consists of a group of diseases characterized by signs and complications of portal hypertension,which differ from cirrhosis through histological alterations,hemodynamic characterization and,clinical outcome.Because of the similarities in clinical presentation and imaging signs,frequently these patients,and particularly those with porto-sinusoidal vascular disease(PSVD),are misdiagnosed as having liver cirrhosis and thus raising difficulties in their diagnosis.The most challenging differentiation to be considered is between PSVD and cirrhosis and,although not pathognomonic,liver biopsy is still the standard of diagnosis.Although they still require extended validation before being broadly used,new non-invasive methods for the diagnosis of porto-sinusoidal vascular disease,like transient elastography,contrast-enhanced ultrasound or metabolomic profiling,have shown promising results.Another issue is the differentiation between PSVD and chronic extrahepatic portal vein obstruction,especially now when it is known that 40%of patients suffering from PSVD develop portal vein thrombosis.In this particular case,once the portal vein thrombosis occurred,the diagnosis of PSVD is impossible according to the current guidelines.Moreover,so far,the differentiation between PSVD and sinusoidal obstruction syndrome has not been clear so far in particular circumstances.In this review we highlighted the diagnostic challenges regarding the PSVD,as well as the current techniques used in the evaluation of these patients.

Celiac plexus neurolysis in pancreatic cancer:The endoscopic ultrasound approach

Pain in pancreatic cancer is often a major problem of treatment.Administration of opioids is frequently limited by side effects or insufficient analgesia.Endoscopic ultrasound-guided celiac plexus neurolysis(EUS-CPN)represents an alternative for the palliative treatment of visceral pain in patients with pancreatic cancer.This review focuses on the indications,technique,outcomes of EUS-CPN and predictors of pain relief.EUS-CPN should be considered as the adjunct method to standard pain management.It moderately reduces pain in pancreatic cancer,without eliminating it.Nearly all patients need to continue opioid use,often at a constant dose.The effect on quality of life is controversial and survival is not influenced.The approach could be done in the central position of the celiac axis,which is easy to perform,or in the bilateral position of the celiac axis,with similar results in terms of pain alleviation.The EUS-CPN with multiple intraganglia injection approach seems to have better results,although extended studies are still needed.Further trials are required to enable more confident conclusions regarding timing,quantity of alcohol injected and the method of choice.Severe complications have rarely been reported,and great care should be taken in choosing the site of alcohol injection.

Diagnosis of cirrhosis and portal hypertension:imaging,non-invasive markers of fibrosis and liver biopsy

The concept of‘cirrhosis’is evolving and it is now clear that compensated and decompensated cirrhosis are completely different in terms of prognosis.Furthermore,the term‘advanced chronic liver disease(ACLD)’better reflects the continuum of histological changes occurring in the liver,which continue to progress even after cirrhosis has developed,and might regress after removing the etiological factor causing the liver disease.In compensated ACLD,portal hypertension marks the progression to a stage with higher risk of clinical complication and requires an appropriate evaluation and treatment.Invasive tests to diagnose cirrhosis(liver biopsy)and portal hypertension(hepatic venous pressure gradient measurement and endoscopy)remain of crucial importance in several difficult clinical scenarios,but their need can be reduced by using different non-invasive tests in standard cases.Among non-invasive tests,the accepted use,major limitations and major benefits of serum markers of fibrosis,elastography and imaging methods are summarized in the present review.

Metabolomics: From liver chiromancy to personalized precision medicine in advanced chronic liver disease

Currently there is a lack of accurate biomarkers for diagnosis and prognosis in advanced liver diseases. Either the occurrence of first decompensation, or diagnosis of acute on chronic liver failure, severe alcoholic hepatitis, or hepatocellular carcinoma(HCC), none of the available biomarkers are satisfactory. Metabolomics is the newest of omics, being much closer than the others to the actual phenotype and pathologic changes that characterizes a certain condition. It deals with a much wider spectrum of low molecular weight bio-compounds providing a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication and therapy. Until now metabolomics was applied in a wide spectrum of liver conditions, but the findings were contradictory. This review proposes a synthesis of the existing evidences of metabolomics use in advanced chronic liver diseases, decompensated liver cirrhosis, severe alcoholic hepatitis and HCC.

Primary Small Bowel Melanoma or Small Bowel Metastasis with Vanishing Primary Cutaneous Lesion

The small bowel represents one of the main sites for cutaneous melanoma metastasis;however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year-old woman admitted for nausea, heartburn, abdominal pain, change in bowel habits and weight loss. Contrast-enhanced CT revealed a small bowel mass. Surgical resection of a 6 cm ileal tumour with regional mesenteric lymphadenectomy and end-to-end anastomosis was performed. Histopathological findings indicated the presence of an ileal melanoma metastasis. Subsequent dermatological examination identified a cutaneous lesion on the right forearm, however no malignant cells were found at the histopathological exam. Whole body PET CT with FDG identified multiple frontal and parietal lesions. Genetic testing was positive for BRAF gene V600 E mutation. The patient underwent multiple neurosurgical procedures for the resection of cerebral metastases. Palliative external radiation and chemotherapy was also attempted. After approximately 2 years after the diagnosis, the patient died following multiple episodes of intracranial hypertension.

Hepatocellular carcinoma extracellular vesicle ECG score as a diagnostic tool close to the ideal

Introduction In recent decades,numerous indicators for early detection and monitoring of hepatocellular carcinoma(HCC)have been suggested and published in reputable journals.These markers have gained recognition and endorsement from prominent international associations such as the European Association for the Study of the Liver(EASL),the Asian Pacific Association for the Study of the Liver(APASL),as well as national professional organizations like the American Association for the Study of Liver Diseases(AASLD),among others.