Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

Hepatocytic ballooning in non-alcoholic steatohepatitis: Dilemmas and future directions.

Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in 'real life' situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.

A Near-Infrared Fluorescent Probe for Recognition of Hypochlorite Anions Based on Dicyanoisophorone Skeleton.

A novel near-infrared (NIR) fluorescent probe (SWJT-9) was designed and synthesized for the detection of hypochlorite anion (ClO-) using a diaminomaleonitrile group as the recognition site. SWJT-9 had large Stokes shift (237 nm) and showed an excellent NIR fluorescence response to ClO- with the color change under the visible light. It showed a low detection limit (24.7 nM), high selectivity, and rapid detection (within 2 min) for ClO-. The new detection mechanism of SWJT-9 on ClO- was confirmed by 1H NMR, MS spectrum, and the density functional theory (DFT) calculations. In addition, the probe was successfully used to detect ClO- in HeLa cells.

Endoscopic submucosal dissection for colorectal lesions: outcomes from a United States experience.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is commonly used in Asia for resection of large non-pedunculated colorectal polyps (LNPCPs) and early (T1) colorectal cancers. It allows for en bloc removal and is often curative. We describe outcomes of colorectal ESD from a United States (US) academic medical center and compare this to international experiences. METHODS: Retrospective review was performed of colonic lesions referred to the University of Chicago Medical Center for ESD from 2012 to 2020. Clinical and procedural data were collected. RESULTS: The study included 78 lesions with mean size of 29.7 mm (range 10-100 mm). The overall en bloc resection rate was 73.1% (n = 57). Between the first and second half of the study, it improved from 61.5 to 84.6% (p = 0.02). Histology showed adenocarcinoma in fifteen lesions (19.2%). Of all neoplastic lesions (n = 68), resection with negative margins (R0) was achieved in 54 cases (79.4%). Adverse events occurred in 9 cases (11.5%), but most (n = 6, 66.7%) were successfully treated endoscopically. Follow-up endoscopy was performed in 46 patients (59.0%) at a mean interval of 6.8 months (SD ± 5.0 months) with two case of recurrent lesion (4.3%). CONCLUSIONS: This study shows successful colorectal ESD outcomes at a US tertiary center. The en bloc resection rate was lower than other cohorts, but a learning curve was demonstrated. The R0 resection, lesion recurrence, and adverse event rates were similar to other non-Asian experiences, but not as favorable as in Asia [Fuccio et al. in Gastrointest Endosc 86:74-86.e17, 2017]. Increased ESD training in the US can help optimize utilization and outcomes.

The Pyroptosis-Related Gene Prognostic Index Associated with Tumor Immune Infiltration for Pancreatic Cancer.

Pancreatic cancer (PC) is one of the most fatal malignancies. Pyroptosis, a type of inflammatory cell death, likely plays a critical role in the development and progression of tumors. However, the relationship between pyroptosis-related genes (PRGs) and prognosis and immunity to PC is not entirely clear. This study, aimed at identifying the key PRGs in PC, highlights their prognostic value, immune characteristics, and candidate drugs for therapies. We screened 47 differentially expressed PRGs between PC and normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Afterwards, a pyroptosis-related gene prognostic index (PRGPI) was constructed based on eight PRGs (AIM2, GBP1, HMGB1, IL18, IRF6, NEK7, NLRP1 and PLCG1) selected by univariate and multivariate Cox regression analysis and LASSO regression analysis, and verified in two external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. We found that the PC patients in the PRGPI-defined subgroups not only reflected significantly different levels of infiltration in a variety of immune cells, such as M1 macrophages, but also showed differential expression in genes of the human leukocyte antigen (HLA) family and immune checkpoints. Additionally, molecular characteristics and drug sensitivity also stayed close to the PRGPI risk scores. Therefore, PRGPI may serve as a valuable prognostic biomarker and may potentially provide guidance toward novel therapeutic options for PC patients.

LRRK2 is a candidate prognostic biomarker for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. METHODS: Bioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay. RESULTS: Bioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan-Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein-protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR. CONCLUSION: We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.

Identification of a five-immune gene model as an independent prognostic factor in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to identify a new prognostic model of HCC based on differentially expressed (DE) immune genes. METHODS: The DE immune genes were identified based on an analysis of 374 cases of HCC and 50 adjacent non-tumor specimens from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, Lasso regression, and multivariate Cox analysis were used to construct the model based on the training group. Survival analysis and the receiver operating characteristic (ROC) curves were used to evaluate model performance. The testing group and the entire group were subsequently used for validation of the model. RESULTS: A five-immune gene model consisted of HSPA4, ISG20L2, NDRG1, EGF, and IL17D was identified. Based on the model, the overall survival was significantly different between the high-risk and low-risk groups (P = 7.953e-06). The AUCs for the model at 1- and 3-year were 0.849 and 0.74, respectively. The reliability of the model was confirmed using the validation groups. The risk score was identified as an independent prognostic parameter and closely related to the content of immune cells from human HCC specimens. CONCLUSION: We identified a five-immune gene model that can be used as an independent prognostic marker for HCC.

Histologic changes caused by injection of a novel submucosal lifting agent for endoscopic resection in GI lesions.

BACKGROUND AND AIMS: ORISE Gel is a recently introduced, U.S. Food and Drug Administration-approved submucosal lifting agent used in endoscopic resection of GI lesions. Histologically evident gel deposits in resected specimens may pose a potential diagnostic pitfall. To aid in recognition of this procedure-related artifact, we report the largest histologic series of ORISE Gel in endoscopic and surgical resection specimens to date. METHODS: Fifty-eight EMR/endoscopic submucosal dissection (ESD) specimens with ORISE Gel injection and 5 interval surgical resection specimens with previous ORISE Gel injection were included. Patient demographics and endoscopy reports were obtained. Histologic slides from all cases were reviewed. Histochemical stains were performed on select cases. RESULTS: Fifty-one EMR and 7 ESD specimens were identified. In 51 of 58 (88%) endoscopic resection specimens, amorphous, pale blue-gray, finely granular material was evident in the submucosa, as well as focally within the mucosa in 4 cases. Most cases showed homogeneous near-complete filling of the submucosa with this material, whereas a few demonstrated areas of condensation and retraction. Mucicarmine and periodic acid-Schiff stains were negative for mucin. Interval surgical resection specimens revealed extensive deposition of dense, eosinophilic material with associated multinucleated giant cells in the submucosa in all cases, with transmural extension in 3 cases. CONCLUSION: ORISE Gel injection during endoscopic resection of GI lesions results in deposition of amorphous, blue-gray material seen in histologic sections, whereas interval surgical resection specimens demonstrate dense, eosinophilic material with an associated giant cell reaction. Awareness of these artifacts will help avoid misinterpretation of their presence as pathologic findings.

GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Down-regulating Expression of GNAI2.

BACKGROUND & AIMS: Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans. METHODS: B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c+ or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+ cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses. RESULTS: GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+ DCs and MDSCs; and decreased numbers of CD8+ DCs. IL6 was mainly produced by CD4+/CD11b+, but not CD8+, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+ cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival. CONCLUSIONS: GNAI1;3 suppresses DSS-plus-AOM-induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+ cells and IL6 in CD4+/CD11b+ DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients.

Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies.

Data on pathologic changes of the 2019 novel coronavirus disease (COVID-19) are scarce. To gain knowledge about the pathology that may contribute to disease progression and fatality, we performed postmortem needle core biopsies of lung, liver, and heart in four patients who died of COVID-19 pneumonia. The patients' ages ranged from 59 to 81, including three males and one female. Each patient had at least one underlying disease, including immunocompromised status (chronic lymphocytic leukemia and renal transplantation) or other conditions (cirrhosis, hypertension, and diabetes). Time from disease onset to death ranged from 15 to 52 days. All patients had elevated white blood cell counts, with significant rise toward the end, and all had lymphocytopenia except for the patient with leukemia. Histologically, the main findings are in the lungs, including injury to the alveolar epithelial cells, hyaline membrane formation, and hyperplasia of type II pneumocytes, all components of diffuse alveolar damage. Consolidation by fibroblastic proliferation with extracellular matrix and fibrin forming clusters in airspaces is evident. In one patient, the consolidation consists of abundant intra-alveolar neutrophilic infiltration, consistent with superimposed bacterial bronchopneumonia. The liver exhibits mild lobular infiltration by small lymphocytes, and centrilobular sinusoidal dilation. Patchy necrosis is also seen. The heart shows only focal mild fibrosis and mild myocardial hypertrophy, changes likely related to the underlying conditions. In conclusion, the postmortem examinations show advanced diffuse alveolar damage, as well as superimposed bacterial pneumonia in some patients. Changes in the liver and heart are likely secondary or related to the underlying diseases.

Hepatic involvement in COVID-19 patients: Pathology, pathogenesis, and clinical implications.

During the clinical course of coronavirus disease 2019 (COVID-19), it has been observed that hepatic injury occurs in a significant proportion of patients, particularly in those with severe or critical illness. Mild increase in sinusoidal lymphocytic infiltration, sinusoidal dilatation, steatosis and multifocal hepatic necrosis are the pathologic changes reported. Direct viral-induced cellular injuries and potential hepatotoxicity from therapeutic drugs are two likely underlying mechanisms. In addition, the pre-existing chronic liver disease exacerbated during COVID-19, and COVID-19-related hyperinflammatory reactions may contribute to liver injury as well. Further studies of additional autopsy cases will help clarifying these possibilities.

Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China.

The outbreak of SARS-CoV-2 has become a pandemic with significant mortality. Published studies described clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between sexes and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear sex difference.

Identification and Preservation of Arm Lymphatic System in Axillary Dissection for Breast Cancer to Reduce Arm Lymphedema Events: A Randomized Clinical Trial.

BACKGROUND: Controversy in axillary reverse mapping in axillary lymph node dissection (ALND) possibly results from incomplete recognition of the arm lymphatic system (ALS) and its compromise to oncological safety. The iDEntification and Preservation of ARm lymphaTic system (DEPART) technique facilitates complete identification of ALS; therefore, its use may decrease the occurrence of arm lymphedema. This study aimed to examine the arm lymphedema rate, locoregional recurrence, and feasibility to perform DEPART in ALND. METHODS: Patients from February 2013 to October 2017 from two tertiary referral centers were randomly assigned to two groups. In the study group, indocyanine green and methylene blue (MB) were utilized to identify arm sentinel nodes, and 0.1 ml MB was injected into the arm sentinel nodes to reveal the subsequent-echelon nodes and lymphatics. Gross arm lymph nodes were examined by intraoperative partial frozen section and were removed if positive. Arm lymphedema, local recurrence, regional recurrence, and distant metastasis were recorded at different follow-up examinations. RESULTS: Arm sentinel nodes were identified in 573 (83.2%) patients. Subsequent-echelon nodes and lymphatics were visualized in 558 (97.4%) patients. Metastatic arm nodes were identified in 38 (6.8%) patients. The arm lymphedema rate was 3.3% (18/543) in the study group versus 15.3% (99/648) in the control group (p < 0.001) after 37-month median follow-up. Regional recurrence showed no difference between the two groups (1.4% and 1.2%, respectively) (p = 0.392). CONCLUSIONS: DEPART can benefit breast cancer patients who undergo ALND, reducing the arm lymphedema rate without adversely affecting the morbidity of regional recurrence.

Surgical Management of the Axilla in Breast Cancer Patients with Negative Sentinel Lymph Node: A Method to Reduce False-Negative Rate.

BACKGROUND: False-negative rate (FNR) of sentinel lymph node dissection (SLND) has not been eliminated. The study was conducted to optimize the surgical resection of axilla in patients with negative sentinel lymph node (SLN) for the purpose of eradicating false-negative (FN) events of SLND. METHODS: A total of 312 clinically node-negative patients without neoadjuvant therapy underwent SLND with indocyanine green (ICG), methylene blue and the combination of ICG and methylene blue. Axillary dissection was performed subsequently regardless of the status of SLN. Lymph nodes were sent for pathological examination separately by serial resection every 0.5 cm away from marginally visualized SLNs. RESULTS: SLND was successfully conducted in 98.1% (306/312) of patients using methylene blue, ICG, and its combination. Further examination revealed 97 true-positive, 189 true-negative, and 13 FN results. The overall FNR was 11.8% (13/110). A horizontal line 1.5 cm away from the superior vSLN and a vertical line 1.5 cm away from the medial vSLN formed a zone of lower outer quadrant (LOQ) in axilla. Surgical resection of LOQ 'en bloc' showed a FNR of zero. CONCLUSIONS: The surgical management of axilla may benefit negative SLN patients with potential nodal involvement, reducing the FNR of SLND to zero. TRIAL REGISTRATION NUMBER AND AGENCY: This study was registered with the Chinese Clinical Trial Registry (ChiCTR1800014247).

Dissection-enabled scaffold-assisted resection (DeSCAR): a novel technique for resection of residual or non-lifting GI neoplasia of the colon (with video).

BACKGROUND AND AIMS: As a result of previous manipulation or submucosal invasion, GI lesions referred for EMR frequently have flat areas of visible tissue that cannot be snared. Current methods for treating residual tissue may lead to incomplete eradication or not allow complete tissue sampling for histologic evaluation. Our aim is to describe dissection-enabled scaffold-assisted resection (DeSCAR), a new technique combining circumferential ESD with EMR for removal of superficial non-lifting or residual "islands" with suspected submucosal involvement/fibrosis. METHODS: From 2015 to 2017, lesions referred for EMR were retrospectively reviewed. Cases were identified where lifting and/or snaring of the lesion was incomplete and the DeSCAR technique was undertaken. Cases were reviewed for location, previous manipulation, rates of successful hybrid resection, and adverse events. RESULTS: Twenty-nine lesions underwent DeSCAR because of non-lifting or residual "islands" of tissue. Fifty-two percent of the patients were male and 48% were female; average age was 66 years (standard deviation ±9.9 years). Lesions were located in the cecum (n = 10), right side of the colon (n = 12), left side of the colon (n = 4), and rectum (n = 3). Average size was 31 mm (standard deviation ±20.6 mm). Previous manipulation had occurred in 28 of 29 cases (83% biopsy, 34% resection attempt, 52% tattoo). The technical success rate for resection of non-lifting lesions was 100%. There was one episode of delayed bleeding but no other adverse events. CONCLUSIONS: DeSCAR is a feasible and safe alternative to argon plasma coagulation and avulsion for the endoscopic management of non-lifting or residual GI lesions, providing en bloc resection of tissue for histologic review. Further studies are needed to demonstrate long-term eradication and for comparison with other methods.

Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles.

Intraductal papillary mucinous neoplasm is considered a precursor lesion to pancreatic adenocarcinoma. These are further classified into four histologic subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. The first aim of this study was to assess the interobserver variability among five gastrointestinal pathologists in diagnosing intraductal papillary mucinous neoplasm subtypes by morphology alone. The second aim of the study was to compare intraductal papillary mucinous neoplasm subtypes, which received consensus diagnoses (≥80% agreement) with their respective mucin immunoprofiles (MUC1, MUC2, MUC5AC, MUC6, and CDX2). A consensus histologic subtype was reached in 58% of cases (29/50) among the five gastrointestinal pathologists. Overall there was moderate agreement (κ=0.41, P<0.01) in subtyping intraductal papillary mucinous neoplasms without the use of immunohistochemistry. The histologic subtype with the best interobserver agreement was intestinal type (κ=0.56, P<0.01) followed by pancreatobiliary, gastric, mixed, and oncocytic types (κ=0.43, P<0.01; κ=0.38, P<0.01; κ=0.17, P<0.01; κ=0.08, P<0.04, respectively). Both kappa values for mixed and oncocytic subtypes were likely artificially low due to the underrepresentation of these subtypes in this study and not a true indication of poor interobserver agreement. Following an intradepartmental consensus meeting between two gastrointestinal pathologists, 68% of cases (34/50) received a consensus intraductal papillary mucinous neoplasm subtype. Sixty-nine percent of cases (11/16) that did not receive a consensus intraductal papillary mucinous neoplasm subtype could be classified based on their respective immunoprofiles. Standardizing the use of immunohistochemistry with a mucin immunopanel (MUC1, MUC2, MUC5AC, and MUC6) may improve the agreement of diagnosing intraductal papillary mucinous neoplasm histologic subtypes.

Safety and efficacy of EMR for sporadic, nonampullary duodenal adenomas: a single U.S. center experience (with video).

BACKGROUND AND AIMS: EMR is increasingly used for resection of sporadic, nonampullary duodenal adenomas (SNDAs), but there are no guidelines for the management of these lesions. The aims of this study were to evaluate the safety and efficacy of EMR exclusively for SNDAs and to determine the factors predictive of outcomes. METHODS: We performed a retrospective review of patients with SNDAs referred for endoscopic therapy from 2006 to 2013. The outcomes studied were successful endoscopic resection, major adverse events, early and late recurrences, and clinical remission. RESULTS: Sixty-eight patients with SNDAs were included and 51 (75%) underwent EMR. The mean adenoma size was 22.0 ± 8.9 mm. Successful resection was achieved in 49 of 51 patients (96.1%), and major adverse events were noted in 8 of 51 patients (15.7%). Early and late recurrences were noted in 25.6% and 5.2% of patients, respectively, and were treated endoscopically. Clinical remission was achieved in 89.7% of patients after a median follow-up of 15 months. Presence of villous histology was associated with increased recurrence (P = .019), but no association of recurrence was noted with other endoscopic features or resection technique. Large adenoma size (P = .0057) and need for intraprocedural hemostasis (P = .006) were associated with increased adverse events, but no association of adverse events was noted with location or resection technique. CONCLUSIONS: Large duodenal adenomas can be effectively managed with EMR at a referral center with experienced endoscopists. However, EMR has a significant recurrence rate, especially early recurrence, and the risk of adverse events is not negligible. Endoscopic therapy is successful in managing recurrent adenomas.

Mass-spectrometry-based quantitation of Her2 in gastroesophageal tumor tissue: comparison to IHC and FISH.

BACKGROUND: Trastuzumab has shown a survival benefit in cases of Her2-positive gastroesophageal cancer (GEC). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) currently determine eligibility for trastuzumab-based therapy. However, these low-throughput assays often produce discordant or equivocal results. METHODS: We developed a targeted proteomic assay based on selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels (amol/µg) of Her2-SRM protein in cell lines (n = 27) and GEC tissues (n = 139). We compared Her2-SRM protein expression with IHC/FISH, seeking to determine optimal SRM protein expression cutoffs in order to identify HER2 gene amplification. RESULTS: After demonstrating assay development, precision, and stability, Her2-SRM protein measurement was observed to be highly concordant with the HER2/CEP17 ratio, particularly in a multivariate regression model adjusted for SRM expression of the covariates Met, Egfr, Her3, and HER2 heterogeneity, as well as their interactions (cell lines r (2) = 0.9842; FFPE r (2) = 0.7643). In GEC tissues, Her2-SRM protein was detected at any level in 71.2 % of cases. ROC curves demonstrated that Her2-SRM protein levels have a high specificity (100 %) at an upper-level cutoff of >750 amol/µg and sensitivity of 75 % at a lower-level cutoff of <450 amol/µg for identifying HER2 FISH-amplified tumors. An "equivocal zone" of 450-750 amol/µg of Her2-SRM protein was analogous to IHC2+ but represented fewer cases (9-16 % of cases versus 36-41 %). CONCLUSIONS: Compared to IHC, targeted SRM-Her2 proteomics provided more objective and quantitative Her2 expression with excellent HER2/CEP17 FISH correlation and fewer equivocal cases. Along with its multiplex capability for other relevant oncoproteins, these results demonstrate a refined HER2 protein expression assay for clinical application.

Complete endoscopic mucosal resection is effective and durable treatment for Barrett's-associated neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal carcinoma (IMC) is treated by complete eradication of areas of BE by endoscopic mucosal resection (EMR). By using this approach, histologic analysis also can be performed. We investigated the effectiveness, safety, and durability of this approach, as well as its use in diagnosis after a single referral. METHODS: We collected data from 107 patients who were referred to the Center for Endoscopic Research and Therapeutics at the University of Chicago for BE (mean length, 3.6 cm) with suspected HGD or IMC, from August 2003 through December 2012. All patients underwent EMR and were followed up through January 2014 (mean follow-up time, 40.6 mo). The primary outcome was treatment efficacy (complete eradication of BE and associated neoplasia); secondary outcomes included safety, durability, and accuracy of diagnosis. RESULTS: BE was eradicated completely by EMR in 80.4% (86 of 107) of patients based on intention-to-treat analysis, and in 98.8% (79 of 80) of patients based on per-protocol analysis. The diagnosis was changed for 25% of patients after EMR, including 4 cases that initially were diagnosed as HGD by biopsy analysis and subsequently were found to have evidence of submucosal invasion when EMR specimens were assessed. Strictures and symptomatic dysphagia developed in 41.1% and 37.3% of patients, respectively, with an average of 2.3 dilations required. Perforations occurred in 2 patients after EMR and in 1 patient after dilation. HGD and IMC recurred in 1 patient each; both were treated successfully with EMR. Based on pathology analysis of the most recently collected specimens, 71.6% of patients (53 of 74) were in complete remission from intestinal metaplasia and 100% were in complete remission from HGD (74 of 74) or cancer (74 of 74). CONCLUSIONS: For patients with BE with HGD or neoplasia, complete EMR is an effective and durable treatment and is a relatively safe technique. Specimens collected by EMR also can be analyzed histologically to aid in diagnosis. The common complication of EMR is esophageal stricture, which can be addressed with endoscopic dilation.