Endohepatology: The endoscopic armamentarium in the hand of the hepatologist.

ABSTRACT: Recent advances in the field of hepatology include new and effective treatments for viral hepatitis. Further effort is now being directed to other disease entities, such as non-alcoholic fatty liver disease, with an increased need for assessment of liver function and histology. In fact, with the evolving nomenclature of fat-associated liver disease and the emergence of the term "metabolic-associated fatty liver disease" (MAFLD), new diagnostic challenges have emerged as patients with histologic absence of steatosis can still be classified under the umbrella of MAFLD. Currently, there is a growing number of endoscopic procedures that are pertinent to patients with liver disease. Indeed, interventional radiologists mostly perform interventional procedures such as percutaneous and intravascular procedures, whereas endoscopists focus on screening for and treatment of esophageal and gastric varices. EUS has proven to be of value in many areas within the realm of hepatology, including liver biopsy, assessment of liver fibrosis, measurement of portal pressure, managing variceal bleeding, and EUS-guided paracentesis. In this review article, we will address the endoscopic applications that are used to manage patients with chronic liver disease.

Protocol for a randomized controlled trial of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN) with vs without bupivacaine.

BACKGROUND: Pancreatic cancer is a devastating disease with less than 5% 5-year survival. Inoperable patients often present with pain. Randomized controlled trial have shown that endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) improves pain control. It is usually performed by injecting bupivacaine followed by absolute alcohol around the celiac axis. STUDY DESIGN: Single center, randomized, double blind controlled trial of EUS-CPN with and without bupivacaine in patients with inoperable malignancy (pancreatic or other) involving the celiac plexus. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on ClinicalTrials.gov (NCT04951804). DISCUSSION: We hypothesize that bupivacaine is superfluous and may actually reduce pain control by diluting the neurolytic effect of alcohol. Bupivacaine is also potentially dangerous in that it may produce serious adverse events such as arrythmias and cardiac arrest if inadvertently injected intravascularly. CONCLUSION: This randomized trial is designed to assess whether bupivacaine is of any value during EUS-CPN.

Safety and clinical efficacy of EUS-guided pelvic abscess drainage.

Background and Objectives: EUS is a potential alternative for the drainage of abscesses. The aim of this study was to determine if EUS-guided pelvic abscess drainage is technically feasible, safe, and a valid option for abscess resolution. Methods: We conducted a retrospective review from 2002 to 2020 at a single quaternary institution. EUS-guided pelvic abscess drainage via the transrectal route was performed in all patients with or without drain/stent placement. Technical and clinical success of EUS-guided pelvic abscess drainage was analyzed. Descriptive analyses and Fisher exact test were performed. Results: Sixty consecutive patients were included in the study (53.5% male; mean age, 53.8 ± 17.9 years). Pelvic abscesses occurred mainly postoperatively (33 cases; 60.0%) and from complicated diverticulitis (14 cases; 23.3%). Mean diameter was 6.5 ± 2.4 cm (80% unilocular). Drainage was performed with EUS-guided stent placement (double-pigtail plastic or lumen-apposing metal) in 74.5% of cases and with aspiration alone for the remainder. Technical success occurred in 58 cases (97%). Of those with long-term follow-up after EUS-guided pelvic abscess drainage (n = 55; 91.7%), complete abscess resolution occurred in 72.7% of all cases. Recurrence occurred in 8 cases (14.5%) and persisted in 7 patients (12.5%), 7 of which were successfully retreated with EUS-guided pelvic abscess drainage. Accounting for these successful reinterventions, the overall rate of abscess resolution was 85.5%. Abscess resolution rate improved with drain placement (83%). Accounting for 7 repeat EUS-guided pelvic abscess drainages, overall abscess resolution improved. Two deaths occurred (3.4%) because of sepsis from failed source control in patients who had previously failed medical, radiological, and surgical treatment. Conclusions: EUS-guided pelvic abscess drainage is technically feasible, safe, and an effective alternative to radiological or open surgical drainage. It also offers favorable clinical outcomes in different clinical situations.

Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial).

BACKGROUND & AIMS: Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). METHODS: In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. RESULTS: From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P = .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. CONCLUSIONS: Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. CLINICALTRIALS: gov, Number: NCT03870386.

Endoscopic Ultrasound Guided Fine Needle Aspiration versus Endoscopic Ultrasound Guided Fine Needle Biopsy for Pancreatic Cancer Diagnosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: One of the most effective diagnostic tools for pancreatic cancer is endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or biopsy (EUS-FNB). Several randomized clinical trials have compared different EUS tissue sampling needles for the diagnosis of pancreatic cancer. OBJECTIVE: To compare the diagnostic accuracy of EUS-guided FNA as EUS-FNB needles for the diagnosis of pancreatic cancer using a systematic review and meta-analysis. METHOD: A literature review with a meta-analysis was performed according to the PRISMA guide. The databases of PubMed, Cochrane and Google Scholar were used, including studies published between 2011-2021 comparing the diagnostic yield (diagnostic accuracy or probability of positivity, sensitivity, specificity, predictive value) of EUS-FNA and EUS-FNB for the diagnosis of pancreatic cancer. The primary outcome was diagnostic accuracy. Random effect models allowed estimation of the pooled odds ratio with a confidence interval (CI) of 95%. RESULTS: Nine randomized control trials were selected out of 5802 articles identified. Among these, five studies found no statistically significant difference between the EUS-FNA and EUS-FNB, whereas the other four did. The meta-analysis found EUS-FNB accuracy superior to EUS-FNA for the diagnosis of pancreatic cancer with a pooled odds ratio of 1.87 (IC 95%: 1.33-2.63). CONCLUSION: As compared to EUS-FNA, EUS-FNB seems to improve diagnostic accuracy when applied to suspicious pancreatic lesions.

Transgastric Abdominal Ultrasonography in Anesthesia and Critical Care: Review and Proposed Approach.

The use of transesophageal echocardiography (TEE) in the operating room and intensive care unit can provide invaluable information on cardiac as well as abdominal organ structures and function. This approach may be particularly useful when the transabdominal ultrasound examination is not possible during intraoperative procedures or for anatomical reasons. This review explores the role of transgastric abdominal ultrasonography (TGAUS) in perioperative medicine. We describe several reported applications using 10 views that can be used in the diagnosis of relevant abdominal conditions associated with organ dysfunction and hemodynamic instability in the operating room and the intensive care unit.

Monoclonal free light chain detection and quantification: Performances and limits of available laboratory assays.

The detection and quantification of immunoglobulin free light chains in serum and urine is recommended for the diagnosis and monitoring of monoclonal gammopathies according to the guidelines of the International Myeloma Working Group (IMWG). Several tests are currently available in the clinical laboratory to detect and quantify free light chains but although quality, efficiency, and effectiveness have been improved, the results are still variable and poorly harmonized and standardized. The present review article wants to analyze these aspects, with a keen eye on techniques, such as mass spectrometry, that could replace in the practical clinical laboratory the current methods including Bence-Jones protein assay and free light chain immunoassays.

A significant decreased in the frequency of Clostridioides difficile infection at the Italian Hospital of Desio over the last decade.

Clostridiodes difficile infection (CDI) is the most important cause of healthcare-associated diarrhea. The decreasing trend of CDI from 15% to 4% observed at the Italian Hospital of Desio over a 10-year period is due to prevention strategies. Our data highlight the importance of surveillance studies to control CDI.

A randomized noninferiority trial comparing the diagnostic yield of the 25G ProCore needle to the standard 25G needle in suspicious pancreatic lesions.

BACKGROUND AND OBJECTIVES: The aim of the study was to perform the first randomized trial comparing the diagnostic yield, bloodiness, and cellularity of the 25G standard needle (25S) and the 25G ProCore™ needle (25P). MATERIALS AND METHODS: All patients referred to the tertiary care referral center for EUS guided fine-needle aspiration (EUS-FNA) of suspicious solid pancreatic lesions were eligible. EUS-FNA was performed in each lesion with both 25S and 25P needles (the choice of the first needle was randomized), using a multipass sampling pattern, without stylet or suction. Rapid on-site evaluation was used when possible. Pap-stained slides were read by a single experienced cytopathologist, blinded to the needle type. RESULTS: One hundred and forty-three patients were recruited. Samples were positive for cancer in 122/143 (85.3%) with the 25S needle versus 126/143 (88.1%) with the 25P needle, negative in 17/143 (11.9%) with the 25S needle versus 13/143 (9.1%) with the 25P needle, and suspicious in 4/143 (2.8%) with each needle. There was no difference in any outcome based on the type of the first needle. No carryover effect was detected (P = 0.214; NS). Cumulative logistic regression analyses showed no associations between the type of needle and diagnostic yield for cancer, cellularity, or bloodiness. The difference in the yield for cancer was 2.9% (-4.2; 10.1%); with the confidence interval upper within the predetermined noninferiority margin of 15%. CONCLUSION: The 25S needle is noninferior to the 25P needle for diagnosing cancer in suspicious pancreatic lesions.

A rare case of cutaneous Papiliotrema (Cryptococcus) laurentii infection in a 23-year-old Caucasian woman affected by an autoimmune thyroid disorder with hypothyroidism.

In recent years, the frequency of infections due to saprophytic fungi has increased. Cryptococcus laurentii, recently classified as Papiliotrema laurentii, is responsible for fungemia, meningitis, and superficial infections. Here, we report the first case of cutaneous Papiliotrema (Cryptococcus) laurentii infection in a 23-year-old Caucasian woman affected by an autoimmune thyroiditis with hypothyroidism. Impairments of the immune system are often associated with unusual fungal infections, which cannot be neglected. The isolate strain was susceptible to Amphotericin B while resistant to fluconazole, itraconazole, voriconazole, and terbinafine. The patient was successfully treated with Amphotericin B.

A rare case of Clostridium paraputrificum bacteremia in a 78-year-old Caucasian man diagnosed with an intestinal neoplasm.

Clostridium like species, particularly Clostridium perfrigens, are the second most common causes of human anaerobic infections, including myonecrosis and bacteremia. Clostridium paraputrificum is an infrequent isolate, which has been identified in only 1% of reported cases of clostridial infections. We herein report a rare case of C. paraputrificum bacteremia in a 78-year-old Caucasian man diagnosed with an intestinal carcinoma and liver neoplastic lesions. The isolate was susceptible to chloramphenicol, meropenem, metronidazole, vancomycin, and resistant to clindamycin and penicillin, and the patient was successfully treated with metronidazole. Malignancy and inflammatory bowel diseases are often associated with clostridial bacteremia, which cannot be neglected.

A proposal for the ideal algorithm for the diagnosis, staging, and treatment of pancreas masses suspicious for pancreatic adenocarcinoma: Results of a working group of the Canadian Society for Endoscopic Ultrasound.

Numerous clinical pathways exist for patients presenting with a suspicious pancreatic mass. These range from direct surgical intervention following staging, with preoperative cross-sectional imaging, EUS with or without fine-needle aspiration or fine-needle core biopsy; neoadjuvant chemotherapy and/or radiation therapy; or palliation. Although international guidelines exist for pancreas cancer management, the ideal workup and treatment for a suspicious pancreas mass is unclear. During its annual meeting in September 2017 (The Forum for Canadian Endoscopic Ultrasonography), the Canadian Society of Endoscopic Ultrasound organized a working group of experienced endosonographers and hepatobiliary surgeons from across Canada to achieve this goal.

ELEMENT TRIAL: study protocol for a randomized controlled trial on endoscopic ultrasound-guided biliary drainage of first intent with a lumen-apposing metal stent vs. endoscopic retrograde cholangio-pancreatography in the management of malignant distal biliary obstruction.

BACKGROUND & AIMS: Endoscopic ultrasound guided-biliary drainage (EUS-BD) is a promising alternative to endoscopic retrograde cholangiopancreatography (ERCP); however, its growth has been limited by a lack of multicenter randomized controlled trials (RCT) and dedicated devices. A dedicated EUS-BD lumen- apposing metal stent (LAMS) has recently been developed with the potential to greatly facilitate the technique and safety of the procedure. We aim to compare a first intent approach with EUS-guided choledochoduodenostomy with a dedicated biliary LAMS vs. standard ERCP in the management of malignant distal biliary obstruction. METHODS: The ELEMENT trial is a multicenter single-blinded RCT involving 130 patients in nine Canadian centers. Patients with unresectable, locally advanced, or borderline resectable malignant distal biliary obstruction meeting the inclusion and exclusion criteria will be randomized to EUS-choledochoduodenostomy using a LAMS or ERCP with traditional metal stent insertion in a 1:1 proportion in blocks of four. Patients with hilar obstruction, resectable cancer, or benign disease are excluded. The primary endpoint is the rate of stent dysfunction needing re-intervention. Secondary outcomes include technical and clinical success, interruptions in chemotherapy, rate of surgical resection, time to stent dysfunction, and adverse events. DISCUSSION: The ELEMENT trial is designed to assess whether EUS-guided choledochoduodenostomy using a dedicated LAMS is superior to conventional ERCP as a first-line endoscopic drainage approach in malignant distal biliary obstruction, which is an important and timely question that has not been addressed using an RCT study design. TRIAL REGISTRATION: Registry name: ClinicalTrials.gov. Registration number: NCT03870386. Date of registration: 03/12/2019.

Multiple Parasitic Infestation in a Nine-month-old Patient: A Case Report.

We are reporting the case of a nine-month-old Pakistani female with complaint of growth retardation who presented multiple intestinal parasitic infections. Probably because of contamination with fecal matter, the initial microscopic examination of the urinary sample revealed the presence of eggs of Enterobius vermicularis, cysts of Entamoeba coli, and an organism similar to mites. Stool samples were obtained after two weeks and microscopic investigation confirmed the presence of Enterobius vermicularis eggs, cysts of Entamoeba coli, and hookworm eggs. The patient was immediately subjected to mebendazole therapy associated with trimethoprim-sulfamethoxazole, to which she responded well. Follow-up stool re-examinations performed 15 and 30 days after the treatment tested negative for all parasitic ova and cysts. This study reflects the importance of considering multiple parasitic infestations in low socio-economic populations and highlights the need of improving poor hygienic conditions to prevent such infections, in particular in children.

An assessment of the yield of EUS in patients referred for dilated common bile duct and normal liver function tests.

OBJECTIVE: This study aims to determine the yield of EUS in patients with common bile duct (CBD) dilation and normal liver function tests (LFTs). MATERIALS AND METHODS: Between October 2000 and December 2016, all patients referred for EUS for unexplained CBD dilatation (CBD ≥7 mm), with normal aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin and no history of sphincterotomy, were eligible. Linear-array EUS was performed by one of the two experienced endosonographers. Data were extracted from a prospectively maintained database. RESULTS: Of 29,920 upper gastrointestinal EUS procedures performed, 840/29,920 (3%) were for unexplained CBD dilation. Of 840 patients, 199 (24%) had normal LFTs, 99% were Caucasian, 46% had biliary-type abdominal pain, and 41% were postcholecystectomy. EUS diagnosed choledocholithiasis (CDL) or sludge in 18/199 (9%) patients (7/18 had CBD sludge only). No other pathology was diagnosed. Of 18 CDL patients, 15 (83%) had an intact gallbladder, and all 15 patients had cholelithiasis. The frequency of CDL or sludge in postcholecystectomy patients was only 3.7% (3/82); none of these patients were younger than 69 years of age. Regression analyses showed no associations between EUS diagnosis of CDL or sludge and biliary-type abdominal pain, other symptoms, sex, or race. Each additional year of age was associated with an increase in the risk of CDL or sludge by a factor of 1.05 (odds ratio: 1.05; P = 0.034). SUMMARY: In patients with CBD dilation and normal LFTs, the only significant pathology identified is CBD stones or sludge (almost exclusively in elderly patients with cholelithiasis). CONCLUSION: EUS should be avoided in patients with dilated bile ducts and normal LFTs, especially if under 65 years of age and postcholecystectomy.

Genus-level identification of dermatophytes by MALDI-TOF MS after 2 days of colony growth.

Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) is becoming a popular technology in clinical microbiology. It is a fast and highly specific method for the routine identification of micro-organisms. In this study, we evaluated the suitability of dermatophyte identification after only 2 days of colony growth using MALDI-TOF MS. Two protein extraction protocols were also evaluated consisting of either formic acid alone or of ethanol-formic acid-acetonitrile to achieve a complete protein extraction. Morphology-based techniques were used as the diagnostic standard methods and MALDI-TOF MS results were obtained using the manufacturer's spectral library. Using the formic acid protein extraction protocol after 2 days of colony growth, 70 and 46% of dermatophytes were properly identified at the genus and species-level respectively. The addition of ethanol-formic acid-acetonitrile extraction protocol increased the identification to 90 and 62%. Based on our observations, we propose a two-step workflow for the fast and reliable identification of dermatophytes after only 2 days of colony growth. This flow chart consists of a first direct deposition procedure with the addition of formic acid, followed by a complete protein extraction when dermatophyte identification is not successful. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, a two-step workflow for the identification of clinical dermatophytes using MALDI-TOF analysis and commercially available spectral library was developed. The workflow consists of an initial direct deposition of the sample on the MALDI plate and formic acid protein extraction at 2 days of growth culture; if dermatophyte identification is not successful, a complete protein extraction using ethanol-formic acid-acetonitrile is subsequently performed. Using this workflow, the correct isolate identifications increase up to 90%; of these, 27% are identified at the genus-level, providing sufficient information to start an antifungal treatment. The method here proposed represents a fast and useful approach to differentiate dermatophytes grown in culture.

Endoscopic ultrasound-guided FNA of pelvic lesions: A large single-center experience.

BACKGROUND: Pelvic endoscopic ultrasound-guided fine-needle aspiration (PEUS-FNA) of rectal or perirectal lesions is safe, minimally invasive, and well tolerated. It provides valuable information, which can greatly influence patient management. Herein, the authors present what to their knowledge is the largest series to date of PEUS-FNA. METHODS: PEUS-FNA specimens were retrieved from the archives of the study institution from January 2001 to March 2015. Only patients with solid pelvic lesions were examined. The cytopathology findings, immunohistochemistry, corresponding histology, and clinical data were collected. For analysis of accuracy, atypical or suspicious results were classified as "negative." The sensitivity and specificity of PEUS-FNA were calculated in a subset of patients with available surgical pathology. RESULTS: A total of 127 cases meeting the current study criteria were obtained from patients who underwent PEUS-FNA at the study institution between January 2001 and March 2015. The mean age of the patients was 60 years, and 53% were female. Pelvic lesions were comprised of 72% masses and 28% lymph nodes, with a mean mass diameter of 27.38 mm (range, 5-100 mm). PEUS-FNA was positive for malignancy in 45% of cases, atypical/suspicious in 4.7% of cases, and negative for malignancy in 50.3% of cases. Surgical pathology was available for 44 patients. PEUS-FNA demonstrated 89.3% sensitivity, 100% specificity, a diagnostic accuracy of 93.2%, a positive predictive value of 100%, and a negative predictive value of 84.2%. No complications were noted. CONCLUSIONS: PEUS-FNA is safe and effective for the investigation of pelvic lesions. Cancer Cytopathol 2016;124:836-41. © 2016 American Cancer Society.