Harshit S. Khara

Gastric outlet obstruction (GOO) is characterized by epigastric pain and postprandial vomiting secondary to mechanical obstruction. Management of GOO is usually focused on alleviating the symptoms of obstruction and can be achieved by surgical gastrojejunostomy or enteral stenting. Recent studies have shown success with EUS-guided gastroenterostomy (EUS-GE) in the management of GOO but data is limited. We, therefore, conducted a meta-analysis to evaluate the safety and efficacy of EUS-GE in the management of GOO. A comprehensive literature review was conducted by searching the Embase and PubMed databases from inception to January 2019 to identify all studies that evaluate the efficacy and safety of EUS-GE in GOO. Our primary outcome was to evaluate technical success and clinical success. Secondary outcomes were to evaluate the need for reintervention and adverse events of the procedure. Twelve studies including 285 patients were included in the meta-analysis. Technical success was achieved in 266 patients with a pooled technical success of 92% (95% confidence interval [CI]: 88%–95%). Clinical success was achieved in 90% of the patients (95% CI: 85%–94%). Recurrence of symptoms or unplanned reintervention was needed in 9% of the patients (95% CI: 6%–13%) and adverse events were reported in 12% of the patients (95% CI: 8%–16%). The heterogeneity tests among studies were nonsignificant with I2 = 0. EUS-GE is a safe and efficacious treatment modality for the management of benign and malignant GOO. Larger prospective studies are needed to further evaluate its utility in GOO.

Endoscopic ultrasound (EUS) is routinely used for diagnostic and therapeutic purposes in adults, and there is emerging literature on its feasibility and safety in children. A recent novel application is EUS-guided liver biopsy (EUS-LB), which has shown to be technically simple, safe, and provides adequate diagnostic yield in adults for evaluation of liver disease; but the use of EUS-LB has never been evaluated in the pediatric population. We report the first case series of EUS-LB in the pediatric population, performed on 3 children, 1 girl and 2 boys-ages 9, 14 and 17 respectively, using a 19-gauge EUS-fine needle aspiration needle. All three cases were performed for the evaluation of unexplained elevated liver enzymes, with above-average diagnostic yield and without any immediate or delayed complications in all children. The use of EUS-LB was pivotal in the management of all the cases. Our case series illustrates the diagnostic utility and safety of EUS-LB in pediatric patients.

Liver biopsy (LB) remains a valuable diagnostic procedure despite advancements in noninvasive assessment of hepatic parenchymal disease. It is likely that demand will continue to grow in the near term as the number of patients with nonalcoholic steatohepatitis continues to increase. LB was first described by Ehrlich in 1883, but the current technique of percutaneous LB can be traced to Menghini’s 1958 paper with the intriguing title “One-second needle biopsy of the liver.”[1] However, even today, many percutaneous liver biopsies are done without “real-time” image guidance, and not infrequently without any image guidance at all. In the last several years, the use of endoscopic ultrasound (EUS) guidance for LB has gained traction. The potential benefits for EUS-LB are numerous and include a more comfortable experience for the patient, the ability to do bilobar biopsies (decreasing sampling error),[2] and the availability of real-time imaging during the biopsy. Current needles and biopsy techniques provide liver cores that are comparable, or better than, samples obtained by the percutaneous or transjugular approaches in terms of standard outcome metrics regarding sample length and number of portal triads.[3] Adequacy for pathologic interpretation is nearly 100% across multiple studies.[456] We would like to bring attention to a recent prospective randomized trial by Bang et al. that sought to compare percutaneous LB to EUS-guided LB.[7] The results of this study are a significant outlier in the literature, and we have several concerns with the manuscript’s methodology. The authors created came up with a definition of an “optimal” LB as one being 25 mm long with >10 complete portal triads (CPTs). The meaning of “optimal” as the authors define it is unclear and without precedent in the literature. By the authors’ own criteria, only 57.9% of percutaneous LBs were “optimal,” which further underscores the nebulous and misleading use of this term. Importantly, the study showed that both percutaneous and EUS-guided techniques yielded samples that could be evaluated by a pathologist in 100% of cases. The length of what is considered an adequate LB has been something of a moving target. A highly cited reference states that a specimen length of 15 mm is adequate for diagnosis.[8] A widely cited review from the American Association for the Study of Liver Disease[9] concluded that 20 mm of tissue is adequate in length, as well as one that contains ≥10 CPTs. The 2020 multisociety British guidelines use the benchmark of 20 mm in length and more than 10 portal tracts.[10] The latest Royal College of Pathologists (RCP) guidelines also recommend LB specimens >20 mm in length.[11] Only the 2014 RCP guidelines[12] used the ≥25 mm criterion, and this was revised down to 20 mm with the latest version. Another important limitation of the study by Bang et al. is the method utilized for sample size calculation. The author’s power analysis is based on a meta-analysis,[13] which weighted use of a 19G TruCut needle, which is inferior to regular 19G needles, and is no longer used in clinical practice. Our previously published work with Franseen needles demonstrated adequate histologic yield in 78% of patients from single lobe biopsy and 100% of patients with bilobar specimens.[1415] If 78% adequacy was used for the power analysis, the sample size needed would be 290 patients (145 patients in each group) compared to only 40 in Bang’s study. Based on this, the study is significantly underpowered. A third concern is that the wrong technique was used for the EUS-guided needle biopsies in this study. The authors used a no suction technique, which has never been evaluated in a prospective study. In our experience, no suction yields inadequate specimens. We conducted a prospective randomized study of “dry” versus “wet” suction for EUS-LB.[16] (Wet suction involves priming the needle lumen with fluid and using suction with the vacuum syringe). Wet suction was superior (98% adequacy versus 80% for dry suction). Suction did not lead to tissue fragmentation. The no-suction needling technique used for this study likely contributed to lower percentage of “optimal” biopsies in the EUS-LB group. The Bang et al.’s study did a cost analysis of the two methods of LB, and not surprisingly, the percutaneous method was less expensive. This is mainly due to the added cost of sedation for an endoscopic procedure. However, the cost estimates do not consider instances in which there is an indication for an endoscopy, EUS, or colonoscopy in addition to the LB. This is a common event, and cost savings would result from doing these combined procedures. In addition, many liver biopsies done by interventional radiologists utilize a transjugular or computed tomography-guided approach, which would cost more than an ultrasound-guided biopsy which was the assumption in the cost analysis. However, providing a better patient experience is increasingly important, even if there might be a higher procedure cost. A good example is propofol sedation for endoscopic procedures, such as ERCP or colonoscopy. While it is true that many of these could be done with “conscious sedation,” deeper levels of monitored sedation provide a better patient experience, allow the endoscopist to optimize the technical aspects of their procedure, and are overall safer for the patient. EUS-LB is now widely performed around the world. Many endosonographers have embraced the EUS-LB technique and have had excellent results with an outstanding safety profile. EUS-guided LB with optimal technique can achieve outstanding histologic yields. The recent comparative study has several critical shortcomings in design and technique and cannot be relied upon for clinical decision-making. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

INTRODUCTION Linitis plastica is an intramural infiltrating anaplastic adenocarcinoma found in the stomach where it causes thickening and stiffening of the gastric wall. It is an aggressive condition, occurring in 7%–10% of primary gastric cancers.[1] It can be difficult to diagnose endoscopically due to cancer infiltrating the submucosa and muscularis propria, and hence, endoscopic appearance and superficial mucosal biopsies may both be unremarkable for signs of malignancy.[2] EUS has emerged as an important tool for the diagnosis and staging of this disease. We report four cases of linitis plastica diagnosed and/or imaged through EUS. CASE REPORTS Case #1 A 37-year-old female presented with vomiting, abdominal pain, early satiety, and weight loss. A recent CT scan had shown moderate ascites, diffuse gastric wall thickening, and nodular thickening of the mesentery, all concerning for malignancy. Diagnostic paracentesis revealed atypical cells and suspicious for cancer. Diagnostic esophagogastroduodenoscopy (EGD) and staging EUS were performed together. EGD revealed congested, friable, and nodular mucosa which was biopsied [Figure 1, Case 1]. EUS revealed severe diffuse gastric wall thickening for which fine-needle aspiration (FNA) was performed [Figure 1, Case 1]. Pathology and cytology results were consistent with high-grade adenocarcinoma of gastric origin. The patient was referred to oncology where palliative chemotherapy was started for Stage IV gastric adenocarcinoma. She continues to do well currently.Figure 1: Endoscopic and endosonographic views, with surgical pathology and cytopathology findings of linitis plastica.Case #2 A 79-year-old female with dysphagia was diagnosed with poorly differentiated adenocarcinoma with signet-ring cell features of the gastric cardia through biopsies obtained during the EGD. Subsequent positron-emission tomography scan revealed an area of intense uptake in the gastric antrum and pylorus which had appeared endoscopically normal. Repeat EGD with EUS showed mucosal thickening in the distal gastric body for which biopsies and FNA were performed [Figure 1, Case 2]. Interestingly, the endoscopic biopsies showed only inflammation and atypical cells, while FNA cytology revealed poorly differentiated adenocarcinoma with signet-ring cell features and confirming the diagnosis of linitis plastica. With palliative therapies, the patient went on to survive 6 months from the time of diagnosis. Case #3 A 60-year-old female presented for the evaluation of nausea, vomiting, early satiety, and unintentional weight loss after an outside hospital workup revealed poor peristalsis on an upper GI series and abnormal antral mucosa on an EGD. Pathology from outside biopsies only noted parietal gland hyperplasia and minimal chronic inflammation. Repeat EGD along with EUS was performed at our hospital. Endoscopic appearance was remarkable for diffusely thickened folds in the gastric body and the antrum with significant lack of distensibility which was biopsied [Figure 1, Case 3]. EUS showed diffuse wall thickening in the antrum and prepyloric stomach, extending through the mucosa into the submucosa, and muscularis propria for which FNA was performed [Figure 1, Case 3]. Again, in this case, the endoscopic biopsies only revealed reactive gastropathy and infiltrating lymphocytes, while FNA cytology showed poorly differentiated carcinoma. The patient went on to have a subtotal gastrectomy with gastrojejunostomy and duodenojejunostomy followed by chemoradiation. With the help of adjuvant therapy, the patient survived a year from the time of diagnosis. Case #4 A 54-year-old female with intractable vomiting, abdominal pain, and weight loss who had been recently diagnosed with gastric adenocarcinoma at an outside facility was referred for staging EUS. Repeat EGD at the time of EUS revealed a malignant gastric tumor infiltrating the entire stomach with protrusion into the mid-gastric body which was biopsied. Pathology was positive for high-grade signet-ring cell adenocarcinoma [Figure 1, Case 4]. EUS staged the mass at T3NxMx but could not be advanced beyond the gastric body due to the tumor obstruction [Figure 1, Case 4]. FNA was not performed due to already having a diagnosis. The patient is being set up for neoadjuvant chemotherapy and surgical follow-up. DISCUSSION Linitis plastica is generally a late-presenting malignancy with poor curative options. The stomach has a rich lymphatic supply, facilitating the spread of cancer cells, and poor sensation resulting in few alarm symptoms early on.[3] EGD with biopsy is a typical starting point when an upper gastrointestinal malignancy is suspected but can miss the diagnosis, as revealed in two of our four cases. Oftentimes it is not until the tumor has spread significantly, resulting in severe symptoms, that it is detectable by EGD. By this point, it is rare that treatment options other than palliative will be offered, as the overall 5-year survival rate even in resectable disease ranges from 10% to 30%.[4] EUS is a valuable tool for both detecting and staging linitis plastica with accuracy based on multiple studies ranging from 64% to 92% for T staging and from 50% to 90% for N staging.[5] EUS-FNA can easily be performed in the same setting at the time of initial EGD, as mucosal biopsies are often negative, thus increasing the diagnostic yield, as our second and third cases illustrate. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.