Safety and efficacy of a novel suturing device for closure of large defects after endoscopic submucosal dissection (with video).

BACKGROUND AND AIMS: Endoscopic suturing enables full closure of large defects after endoscopic submucosal dissection (ESD). However, its use is limited by the need for a double-channel endoscope. A novel closure system, the OverStitch Sx (Apollo Endosurgery, Austin, Tex, USA), compatible with any single-channel endoscope, was introduced to address these shortcomings. The aim of this study was to assess the safety and feasibility of OverStitch Sx for the closure of large defects after ESD. METHODS: This is a prospective single-center feasibility study of patients who underwent closure of large defects after ESD using the OverStitch Sx system. Main outcomes of the study are technical and clinical success, same-day discharge rate, and adverse event rate. RESULTS: Thirty-three patients were enrolled. The mean diameter of included lesions was 5.38 ± 2.52 cm. The defect occupied ≥50% of the lumen circumference in 70% of the cases. En-bloc resection, R0 resection, and curative resection were achieved in 97%, 87.5%, and 78.8% of patients, respectively. Technical success and clinical success were seen in 93.9% and 90.9% of the cases, respectively. Same-day hospital discharge was achieved in 77.4% of patients. Total adverse event rate was 35.7%, including delayed bleeding in 1 patient after rectal ESD that was managed conservatively, self-resolving rectal pain in 7 patients, rectal stricture requiring dilation in 1 patient, and temporary dysphagia in 1 patient. No immediate or delayed perforation was reported. CONCLUSIONS: OverStitch Sx enabled safe and effective closure of large defects after ESD. Future trials are needed to determine its superiority over OverStitch for the closure of defects in challenging locations. (Clinical trial registration number: NCT04361227.).

Pathologic assessment of endoscopic resection specimens with superficial carcinoma of the esophagus: current practice and practical issues.

Endoscopic resection (ER) has become the first-line therapy for early esophageal cancer and offers a treatment alternative to surgery, owing to less morbidity and better quality of life. ER techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is faster, simpler, and cheaper than ESD, but limited by its ability to resect lesions larger than 1.5 centimeters. Piecemeal EMR has limitations, including a high local recurrence rate and a suboptimal specimen for an accurate pathologic assessment. ESD, on the other hand, allows en bloc resections with negative (R0) margins, irrespective of lesion size, providing an excellent pathologic specimen, however, is technically challenging with a higher risk of complications. The evaluation of ER specimens in pathology varies slightly from institution to institution. Our review summarizes the current practices and issues in the pathologic assessment of esophageal ER specimens, which highlights the necessity of a systematic approach and standardization of both macroscopic and microscopic evaluation. There is a need for a comprehensive and standardized pathology report that will allow for uniform terminology for endoscopists, surgeons, and pathologists, which, in turn, will result in better treatment guidance.

Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II-The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer.

CONTEXT: - The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti-programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability-high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability-high CRC. OBJECTIVES: - To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. DATA SOURCES: - A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. CONCLUSIONS: - Exciting success with anti-PD-1/PD-L1 and anticytotoxic T-lymphocyte-associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability-high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti-PD-1 or anti-PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability-high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part I-Colorectal Cancer: Microsatellite Instability, Testing, and Clinical Implications.

CONTEXT: - Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker. OBJECTIVES: - To summarize the molecular pathways of CRC, with an emphasis on the MSI (mismatch repair) pathway; the recommended MSI testing algorithms and interpretation; and the prognostic and predictive role of MSI-H status in personalized treatment, including adjuvant chemotherapy, targeted therapy, and immune checkpoint inhibitor therapy. DATA SOURCES: - A PubMed (US National Library of Medicine, Bethesda, Maryland) review was performed for articles pertaining to CRC, MSI and mismatch repair systems, molecular classification, immune response, programmed death receptor-1/programmed death ligand-1, and immunotherapy. CONCLUSIONS: - Although the TNM classification of malignant tumor stage remains the key determinant of CRC prognosis and treatment, there are considerable stage-independent, interindividual differences in clinical outcome and therapy response by patients. In addition, MSI-H status has an important role in CRC management and can be reliably detected by molecular and immunohistochemistry techniques and genetic testing. Efforts must be made to identify whether MSI-H CRC is germline or sporadic to ensure appropriate treatment, accurate prognosis, and risk assessment for relatives. Microsatellite status has been recognized as a good prognostic indicator and is predictive of a poor response to 5-fluorouracil-based chemotherapy and a good response to programmed death ligand-1 inhibitor pembrolizumab in metastatic/refractory MSI-H CRC.

The Ever-Changing Landscape of Drug-Induced Injury of the Lower Gastrointestinal Tract.

CONTEXT: -There is an ever-growing armamentarium of pharmacologic agents that can cause gastrointestinal (GI) mucosal injury, the most common symptoms being diarrhea, constipation, nausea, and vomiting. These are often self-limiting and without serious sequelae, but some symptoms are of greater concern, like drug-induced mucosal ulceration that can manifest as GI hemorrhage, stricture formation, and even perforation. Histologically, there is significant overlap between drug-induced injuries and various disease entities. A single type of medication may cause multiple patterns of injury, which can involve the entire GI tract or just some parts of it. OBJECTIVE: -To review the most common drug-induced injury patterns affecting the colon, which may be recognized by the surgical pathologist on colonic mucosal biopsies. This review does not address the injuries occurring in the upper GI tract. DATA SOURCES: -A PubMed review of English-language literature, up to December 2015, on drug-induced injury of GI tract was performed. CONCLUSIONS: -There are numerous drugs that damage the colonic mucosa. The most common drugs are included in this review according to their histologic pattern of injury. It is important for the pathologist to keep in mind that a single drug type can induce many histologic patterns of mucosal injury that can mimic many disease entities. Although there are some histologic clues helpful in the diagnosis of drug-induced colonic injury, correlation with clinical history and especially medication history is essential to improve diagnostic accuracy.

Evaluation of Quantitative Digital Pathology in the Assessment of Barrett Esophagus-Associated Dysplasia.

OBJECTIVES: Barrett esophagus (BE) is a precursor lesion that confers an increased risk of esophageal adenocarcinoma. Two issues confront the diagnosis of patients with BE: (1) sampling error at the time of endoscopy and (2) variability among pathologists in grading dysplasia. The purpose of our study was to evaluate quantitative digital pathology (QDP) as a marker of dysplasia and stratification from low-grade to high-grade dysplasia to intramucosal adenocarcinoma in BE. METHODS: Sixty-one esophageal biopsy specimens with BE were selected and divided into six groups according to the dysplasia grade. QDP image analysis was carried out by an in-house automated quantitative system on sections. The values of 110 nuclear features that analyze the morphology and chromatin texture were generated for each nucleus. RESULTS: A progressive correlation was found between nuclear morphometric features and chromatin features with BE dysplasia. The chromatin texture was the best discriminator of the class diagnosis. There was a significant difference between the chromatin features of isolated low-grade dysplasia vs low-grade dysplasia that was associated with higher grade lesions in other biopsy tissue fragments. CONCLUSIONS: QDP is a promising tool in the new era of digital pathology. Pending clinical validation studies, analysis of chromatin texture could contribute to the differential diagnosis of BE class and the detection of concomitant high-grade lesions if not sampled.

Diagnostic Approach to Hepatic Mass Lesions and Role of Immunohistochemistry.

This review provides an overview of various hepatic mass lesions and a practical diagnostic approach, including most recent immunohistochemical stains used in clinical practice. A wide variety of benign and malignant lesions present as hepatic masses, and the differential diagnosis varies. In cirrhotic liver, the commonest malignant tumor is hepatocellular carcinoma (HCC), which needs to be differentiated from macroregenerative nodules, dysplastic nodules, and other tumors. The differential diagnosis of lesions in noncirrhotic liver in younger patients includes hepatic adenoma (HA), focal nodular hyperplasia (FNH), HCC, and other primary hepatic neoplasms and metastases. In older populations, metastases remain the most common mass lesions.

Predicting OncoDx recurrence scores with immunohistochemical markers.

Recent reports suggest that immunohistochemistry (IHC) markers can be used to give prognostic information in breast cancer that is similar to that contained in the Genomic Health Inc. OncoDx recurrence score (Onco-RS). The goal of this study is to examine the potential prognostic value of a score derived from results of a simple set of IHC tests in the prediction of the Onco-RS. A score (IHC-RS) was derived to predict the Onco-RS using IHC-based quantitative and semiquantitative results from a subset of markers selected from those used in the generation of an Onco-RS score. The patient population consists of a retrospectively identified cohort of 158 women with ER-positive, HER2neu-negative breast cancer who completed OncoDx testing. A predictive model was developed to generate the IHC-RS using stepwise multiple regression incorporating Ki67 percentage and semiquantitative ER and PR scores. Using only these 3 IHC markers, the IHC-RS predicted 62% of the Onco-RS variability (adjusted R=0.624, P=0.004). In addition, analysis of outliers in the correlation between the IHC-RS and the Onco-RS reveals the possibility of sampling error as a drawback of the Onco-RS. This is contrasted against potential interlab and intralab variability and preanalytic issues that may negatively impact the implementation of an IHC-RS.