Rectal linitis plastica as the first presentation of metastatic lobular breast cancer: an endoscopic ultrasound diagnosis.

Gastrointestinal tract is an uncommon site of breast cancer metastasis. Rectal linitis plastica (RLP) is a rare presentation of rectal neoplasia, both primary and secondary, and refers to a diffuse infiltration of the wall by an infiltrating carcinoma. Diagnostic assessment of RLP may be challenging since cross-sectional imaging and endoscopic findings may be nonspecific, and endoscopic biopsies are frequently non-diagnostic due to the submucosal disease localization. Endoscopic ultrasound (EUS) with fine needle biopsy (FNB) is widely used for the diagnostic assessment of sub-epithelial lesions of upper and lower gastrointestinal tract. However, data about the use of EUS in case of rectal linitis plastica are very poor. We present a case of rectal metastasis as the first presentation of lobular breast cancer, presenting as rectal linitis plastica and diagnosed with EUS-FNB.

Endoscopic ultrasound diagnostic gain over computed tomography and magnetic resonance cholangiopancreatography in defining etiology of idiopathic acute pancreatitis.

BACKGROUND: About 10%-30% of acute pancreatitis remain idiopathic (IAP) even after clinical and imaging tests, including abdominal ultrasound (US), contrast-enhanced computed tomography (CECT) and magnetic resonance cholangiopancreatography (MRCP). This is a relevant issue, as up to 20% of patients with IAP have recurrent episodes and 26% of them develop chronic pancreatitis. Few data are available on the role of EUS in clarifying the etiology of IAP after failure of one or more cross-sectional techniques. AIM: To evaluate the diagnostic gain after failure of one or more previous cross-sectional exams. METHODS: We retrospectively collected data about consecutive patients with AP and at least one negative test between US, CECT and MRCP, who underwent linear EUS between January 2017 and December 2020. We investigated the EUS diagnostic yield and the EUS diagnostic gain over different combinations of these cross-sectional imaging techniques for the etiologic diagnosis of AP. Types and frequency of EUS diagnosis were also analyzed, and EUS diagnosis was compared with the clinical parameters. After EUS, patients were followed-up for a median of 31.5 mo to detect cases of pancreatitis recurrence. RESULTS: We enrolled 81 patients (63% males, mean age 61 ± 18, 23% with previous cholecystectomy, 17% with recurrent pancreatitis). Overall EUS diagnostic yield for AP etiological diagnosis was 79% (20% lithiasis, 31% acute on chronic pancreatitis, 14% pancreatic solid or cystic lesions, 5% pancreas divisum, 5% autoimmune pancreatitis, 5% ductal abnormalities), while 21% remained idiopathic. US, CECT and MRCP, taken alone or in combination, led to AP etiological diagnosis in 16 (20%) patients; among the remaining 65 patients, 49 (75%) obtained a diagnosis at EUS, with an overall EUS diagnostic gain of 61%. Sixty-eight patients had negative US; among them, EUS allowed etiological diagnosis in 59 (87%). Sixty-three patients had a negative CECT; among them, 47 (74%) obtained diagnosis with EUS. Twenty-four had a negative MRCP; among them, 20 (83%) had EUS diagnosis. Twenty-one had negative CT + MRCP, of which 17 (81%) had EUS diagnosis, with a EUS diagnostic gain of 63%. Patients with biliary etiology and without previous cholecystectomy had higher median values of alanine aminotransferase (154 vs 25, P = 0.010), aspartate aminotransferase (95 vs 29, P = 0.018), direct bilirubin (1.2 vs 0.6, P = 0.015), gamma-glutamyl transpeptidase (180 vs 48, P = 0.006) and alkaline phosphatase (150 vs 72, P = 0.015) Chronic pancreatitis diagnosis was more frequent in patients with recurrent pancreatitis at baseline (82% vs 21%, P < 0.001). During the follow-up, AP recurred in 3 patients, one of which remained idiopathic. CONCLUSION: EUS is a good test to define AP etiology. It showed a 63% diagnostic gain over CECT + MRCP. In suitable patients, EUS should always be performed in cases of IAP. Further prospective studies are needed.

Applications of endoscopic ultrasound elastography in pancreatic diseases: From literature to real life.

Elastography is a non-invasive method widely used to measure the stiffness of the tissues, and it is available in most endoscopic ultrasound machines, using either qualitative or quantitative techniques. Endoscopic ultrasound elastography is a tool that should be applied to obtain a complementary evaluation of pancreatic diseases, together with other imaging tests and clinical data. Elastography can be informative, especially when studying pancreatic masses and help the clinician in the differential diagnosis between benign or malignant lesions. However, further studies are necessary to standardize the method, increase the reproducibility and establish definitive cut-offs to distinguish between benign and malignant pancreatic masses. Moreover, even if promising, elastography still provides little information in the evaluation of benign conditions.

Gastric per-oral endoscopic myotomy: Indications, technique, results and comparison with surgical approach.

Gastroparesis is a chronic disease of the stomach that causes a delayed gastric emptying, without the presence of a stenosis. For 30 years the authors identified pylorospasm as one of the most important pathophysiological mechanisms determining gastroparesis. Studies with EndoFLIP, a device that assesses pyloric distensibility, increased the knowledge about pylorospasm. Based on this data, several pyloric-targeted therapies were developed to treat refractory gastroparesis: Surgical pyloroplasty and endoscopic approach, such as pyloric injection of botulinum and pyloric stenting. Notwithstanding, the success of most of these techniques is still not complete. In 2013, the first human gastric per-oral endoscopic myotomy (GPOEM) was performed. It was inspired by the POEM technique, with a similar dissection method, that allows pyloromyotomy. Therapeutical results of GPOEM are similar to surgical approach in term of clinical success, adverse events and post-surgical pain. In the last 8 years GPOEM has gained the attention of the scientific community, as a minimally invasive technique with high rate of clinical success, quickly prevailing as a promising therapy for gastroparesis. Not surprisingly, in referral centers, its technical success rate is 100%. One of the main goals of recent studies is to identify those patients that will respond better to the therapies targeted on pylorus and to choose the better approach for each patient.

NTRK fusions in colorectal cancer: clinical meaning and future perspective.

INTRODUCTION: Despite the efforts of the scientific community, the prognosis of metastatic colorectal cancer (mCRC) remains poor. Actionable gene fusions such as Neurotrophic Tropomyosin Receptor Kinases (NTRK) rearrangements are rare but might represent a new target to improve outcomes in this setting. The first-generation TRK inhibitors, larotrectinib and entrectinib, have demonstrated efficacy and safety in mCRC cancer patients exhibiting NTRK pathogenic fusions. Moreover, second-generation molecules are emerging, able to overcome the acquired resistance to NTRK blocking. AREAS COVERED: This review aims to report the current knowledge and the available evidence on NTRK fusion in mCRC, with a focus on molecular bases, clinical characteristics, prognostic meaning, and new therapeutic approaches, from the perspective of the clinical oncologist. EXPERT OPINION: Considering the limited options associated with the treatment of mCRC patients, the possibility of identifying new molecular biomarkers is an urgent clinical need. The availability of new molecular targets and the combinations of different agents might represent the true breakthrough point, allowing for change in the clinical course of colorectal cancer patients.

Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders.

Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn's disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.

Feasibility and Accuracy of Transduodenal Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Solid Lesions Using a 19-Gauge Flexible Needle: A Multicenter Study.

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the go-to method for obtaining samples from gastrointestinal tract and pancreatic lesions. When the transduodenal approach is utilized, the use of a more flexible needle, such as a nitinol 19-gauge (G) needle, has been recommended. The aim of this study was to evaluate the feasibility and accuracy of 19-G flexible aspiration needles in obtaining samples from solid lesions through a transduodenal approach. METHODS: This was a retrospective analysis of prospectively collected data from eight Italian endoscopy centers. Consecutive patients with solid lesions who underwent transduodenal EUS-FNA with a 19-G flexible needle were included. RESULTS: A total of 201 patients were enrolled. According to histology, EUS, radiology and 12 months of follow-up, 151 patients had malignant lesions and 50 patients had benign lesions. EUS-FNA was feasible in all cases. An adequate histologic sample was obtained in all except eight cases (96.1%). The sensitivity of EUS-FNA was 92.1% (95% confidence interval [CI], 86.8%-95.7%), and the specificity was 100% (95% CI, 90.5%-100%). The positive predictive value was 100% (95% CI, 93.4%-100%), and the negative predictive value was 74% (95% CI, 62.8%-82.7%). The diagnostic accuracy was 93.5% (95% CI, 89.2%-96.5%). CONCLUSION: The transduodenal approach for obtaining samples from solid lesions using a 19-G flexible needle seems feasible and accurate.

Endoscopic management of gastrointestinal leaks and fistulae: What option do we have?

Gastrointestinal leaks and fistulae are serious, potentially life threatening conditions that may occur with a wide variety of clinical presentations. Leaks are mostly related to post-operative anastomotic defects and are responsible for an important share of surgical morbidity and mortality. Chronic leaks and long standing post-operative collections may evolve in a fistula between two epithelialized structures. Endoscopy has earned a pivotal role in the management of gastrointestinal defects both as first line and as rescue treatment. Endotherapy is a minimally invasive, effective approach with lower morbidity and mortality compared to revisional surgery. Clips and luminal stents are the pioneer of gastrointestinal (GI) defect endotherapy, whereas innovative endoscopic closure devices and techniques, such as endoscopic internal drainage, suturing system and vacuum therapy, has broadened the indications of endoscopy for the management of GI wall defect. Although several endoscopic options are currently used, a standardized evidence-based algorithm for management of GI defect is not available. Successful management of gastrointestinal leaks and fistulae requires a tailored and multidisciplinary approach based on clinical presentation, defect features (size, location and onset time), local expertise and the availability of devices. In this review, we analyze different endoscopic approaches, which we selected on the basis of the available literature and our own experience. Then, we evaluate the overall efficacy and procedural-specific strengths and weaknesses of each approach.

EUS-guided tissue acquisition in chronic pancreatitis: Differential diagnosis between pancreatic cancer and pseudotumoral masses using EUS-FNA or core biopsy.

Background and Objective: EUS-FNA sensitivity for malignancy in parenchymal masses of patients with concurrent chronic pancreatitis (CP) has been reported to be unsatisfactory. The aim of the present study was to directly compare the diagnostic accuracy of EUS-FNA and EUS-fine-needle biopsy (FNB) in differentiating between inflammatory masses and malignancies in the setting of CP. Methods: We performed a retrospective analysis of prospective, multicentric databases of all patients with pancreatic masses and clinico-radiological-endosonographic features of CP who underwent EUS-FNA or FNB. Results: Among 1124 patients with CP, 210 patients (60% males, mean age: 62.7 years) with CP and pancreatic masses met the inclusion criteria and were enrolled. In the FNA group (110 patients), a correct diagnosis was obtained in all but 18 cases (diagnostic accuracy 83.6%, sensitivity 69.5%, specificity 100%, positive predictive value [PPV] 100%, and negative predictive value [NPV] 73.9%); by contrast, among 100 patients undergoing FNB, a correct diagnosis was obtained in all but seven cases (diagnostic accuracy 93%, sensitivity 86.8%, specificity 100%, PPV 100%, and NPV 87%) (P = 0.03, 0.03, 1, 1, and 0.07, respectively). At binary logistic regression, focal pancreatitis (odds of event occurrence [OR]: 4.9; P < 0.001), higher Ca19-9 (OR: 2.3;P= 0.02), and FNB (OR: 2.5; P < 0.01) were the only independent factors associated with a correct diagnosis. Conclusion: EUS-FNB is effective in the differential diagnosis between pseudotumoral masses and solid neoplasms in CP, showing higher diagnostic accuracy and sensitivity than EUS-FNA. EUS-FNB should be considered the preferred diagnostic technique for diagnosing cancer in the setting of CP.

Focal Autoimmune Pancreatitis: A Simple Flow Chart for a Challenging Diagnosis.

Autoimmune pancreatitis is a chronic fibroinflammatory autoimmune mediated disease of the pancreas. Clinically, obstructive painless jaundice and upper abdominal pain are the main symptoms. Focal AIP is characterized by segmental involvement of pancreatic parenchyma and it is often radiologically represented by a pancreatic mass. In these cases, the diagnosis can be very challenging, since it may be easily confused with pancreatic cancer. Therefore, we suggest a combined approach of imaging tests as the diagnostic workup. EUS study combined with CEUS and elastography, if available, increases the accuracy of the method to rule out cancer. Moreover, the lesion should always be sampled under EUS guidance to obtain a cyto/histological diagnosis. The diagnostic workup should also include the use of diagnostic clinical criteria (extrapancreatic lesions, steroid response) and laboratory findings (CA 19.9 and IgG4 evaluations).

Endoscopic ultrasound-guided sampling of solid pancreatic masses: the fine needle aspiration or fine needle biopsy dilemma. Is the best needle yet to come?

Fine needle aspiration (FNA) is currently the standard of care for sampling pancreatic solid masses by using endoscopic ultrasound (EUS). The accuracy of the technique is reported to be high, especially if coupled with the rapid on site evaluation (ROSE), and it has a high safety profile. However, FNA presents some limitations, such as the small amount of tissue that can be collected and the inability of obtaining a core tissue with intact histological architecture, which is relevant to perform immunohistochemical analysis, molecular profiling and, therefore, targeted therapies. Moreover, the presence of the ROSE by an expert cytopathologist is very important to maximize the diagnostic yield of FNA technique; however, it is not widely available, especially in small centers. Hence, the introduction of EUS fine needle biopsy (FNB) with a new generation of needles, which show a high safety profile too and a satisfying diagnostic accuracy even in the absence of ROSE, could be the key to overcome the limitations of FNA. However, FNB has not yet shown diagnostic superiority over FNA. Considering all the technical aspects of FNA and FNB, the different types of needle currently available, comparisons in term of diagnostic yield, and the different techniques of sampling, a tailored approach should be used in order to determine the needle that is most appropriate for the different specific scenarios.

Virtual Chromoendoscopy With FICE for the Classification of Polypoid and Nonpolypoid Raised Lesions in Ulcerative Colitis.

GOALS: The aim of this study was to analyze the performance of Fuji Intelligent Color Enhancement (FICE) using the classification of Kudo in the differentiation of neoplastic and non-neoplastic raised lesions in ulcerative colitis (UC). BACKGROUND: The Kudo classification of mucosal pit patterns is an aid for the differential diagnosis of colorectal polyps in the general population, but no systematic studies are available for all forms of raised lesions in UC. STUDY: All raised, polypoid and nonpolypoid, lesions found during consecutive surveillance colonoscopies with FICE for long-standing UC were included. In the primary prospective analysis, the Kudo classification was used to predict the histology by FICE. In a post hoc analysis, further endoscopic markers were also explored. RESULTS: Two hundred and five lesions (mean size, 8 mm; range, 2 to 30 mm) from 59 patients (mean age, 56 y; range, 21 to 79 y) were analyzed. Twenty-three neoplastic (11%), 18 hyperplastic (9%), and 164 inflammatory (80%) lesions were found. Thirty-one lesions (15%), none of which were neoplastic, were unclassifiable according to Kudo. After logistic regression, a strong negative association resulted between endoscopic activity and neoplasia, whereas the presence of a fibrin cap was significantly associated with endoscopic activity. Using FICE, the sensitivity, specificity, and positive and negative likelihood ratios of the Kudo classification were 91%, 76%, 3.8, and 0.12, respectively. The corresponding values by adding the fibrin cap as a marker of inflammation were 91%, 93%, 13, and 0.10, respectively. CONCLUSIONS: FICE can help to predict the histology of raised lesions in UC. A new classification of pit patterns, based on inflammatory markers, should be developed in the setting of UC to improve the diagnostic performance.

Loss of expression of µ-protocadherin and protocadherin-24 in sporadic and hereditary nonpolyposis colorectal cancers.

Colorectal cancer (CRC) is a neoplastic disease in which normal mucosa undergoes a process of malignant transformation due to the progressive accumulation of molecular alterations affecting proto-oncogenes and oncosuppressor genes. Some of these modifications exert their carcinogenic potential by promoting a constitutive activation of the ß-catenin signaling proliferation pathway, and when present, loss of cadherin expression also significantly contributes to the same effect. Using a combined approach of molecular and immunohistochemical analysis, we have previously demonstrated that most sporadic CRCs exhibit a down-regulated expression of a cadherin, named µ-protocadherin, that is generally observed in association with a higher proliferation rate and a worse prognosis. The aim of this report was to perform a comparative immunohistochemical assessment of µ-protocadherin and a similar cadherin, named protocadherin-24, in sporadic CRC and hereditary nonpolyposis colorectal cancer. The data obtained put in evidence that double-negative CRCs, lacking both the analyzed protocadherins, are more represented among sporadic tumors, whereas double-positive CRCs, maintaining their expression, exhibit an opposite trend. As expected, loss of protocadherin expression was accompanied by nuclear localization of ß-catenin and increased positivity of the Ki-67 proliferation marker. This finding is consistent with the different clinical evolution of the 2 considered CRC sets according to which patients with hereditary nonpolyposis colorectal cancer experience a better prognosis as compared with those affected by a sporadic CRC.