High Malignant Potential Research Articles

Value of repeated cytology for intraductal papillary mucinous neoplasms of the pancreas with high risk potential of malignancy: Is it a promising method for monitoring a malignant transformation?

ObjectivesThe efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs. MethodsForty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study. ResultsThirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size. ConclusionRepeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology.

Comparison of malignancy-prediction efficiency between contrast and non-contract CT-based radiomics features in gastrointestinal stromal tumors: A multicenter study.

This work seeks the development and validation of radiomics signatures from nonenhanced computed tomography (CT, NE‐RS) to preoperatively predict the malignancy degree of gastrointestinal stromal tumors (GISTs) and the comparison of these signatures with those from contrast‐enhanced CT. A dataset for 370 GIST patients was collected from four centers. This dataset was divided into cohorts for training, as well as internal and external validation. The minimum‐redundancy maximum‐relevance algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm were used to filter unstable features. (a) NE‐RS and radiomics signature from contrast‐enhanced CT (CE‐RS) were built and compared for the prediction of malignancy potential of GIST based on the area under the receiver operating characteristic curve (AUC). (b) The radiomics model was also developed with both the tumor size and NE‐RS. The AUC values were comparable between NE‐RS and CE‐RS in the training (.965 vs .936; P = .251), internal validation (.967 vs .960; P = .801), and external validation (.941 vs .899; P = .173) cohorts in diagnosis of high malignancy potential of GISTs. We next focused on the NE‐RS. With 0.185 selected as the cutoff of NE‐RS for diagnosis of the malignancy potential of GISTs, accuracy, sensitivity, and specificity for diagnosis high‐malignancy potential GIST was 90.0%, 88.2%, and 92.3%, respectively, in the training cohort. For the internal validation set, the corresponding metrics are 89.1%, 94.9%, and 80.0%, respectively. The corresponding metrics for the external cohort are 84.6%, 76.1%, and 91.0%, respectively. Compared with only NE‐RS, the radiomics model increased the sensitivity in the diagnosis of GIST with high‐malignancy potential by 5.9% (P = .025), 2.5% (P = .317), 10.5% (P = .008) for the training set, internal validation set, and external validation set, respectively. The NE‐RS had comparable prediction efficiency in the diagnosis of high‐risk GISTs to CE‐RS. The NE‐RS and radiomics model both had excellent accuracy in predicting malignancy potential of GISTs.

Comparison of Clinicopathological Features of Biliary Neuroendocrine Carcinoma with Adenocarcinoma

Objective: This study aimed to demonstrate the clinical features and postoperative outcomes of extrahepatic bile duct (EHBD) neuroendocrine carcinoma (NEC) and compared with those of adenocarcinoma. Methods: We retrospectively analyzed patients with EHBD cancer operated in our institution between 1995 and 2015. Results: Of 475 patients, 468 had adenocarcinoma, while 7 had NEC/mixed adenoneuroendocrine carcinoma (MANEC) in this study. There were no notable preoperative and pathological features in patients with NEC/MANEC. However, patients with NEC/MANEC had a higher recurrence rate (51.8 vs. 100%, p = 0.016), poorer relapse-free survival (RFS) time (the median RFS time: 35 vs. 12 months, p = 0.006), and poorer overall survival (OS) time (the median OS time: 60 vs. 19 months, p = 0.078) than those with adenocarcinoma. Furthermore, patients with NEC/MANEC had higher rates of liver metastasis (11.9 vs. 85.7%, p < 0.001) than those with adenocarcinoma. In multivariable regression analysis, pathological type with NEC/MANEC was a risk factor for poorer RFS (p = 0.022, hazard ratio: 6.09). Conclusions: Patients with NEC/MANEC have high malignant potential and poor outcomes. It is necessary to develop an effective approach and postoperative adjuvant treatment for patients with NEC/MANEC.

Endoscopic ultrasound-guided injective ablative treatment of pancreatic cystic neoplasms.

With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms (PCNs) has increased. PCNs comprise a broad differential spectrum with some PCNs having low or no malignant potential and others having high malignant potential. The morbidity and mortality rates related to major pancreatic surgical resection are high. Long-term surveillance may not only increase the financial burden and psychological stress for patients but also result in a missed malignancy. Minimally invasive endoscopic ultrasound (EUS)-guided ethanol ablation was first reported in 2005. Several other agents, such as paclitaxel, lauromacrogol, and gemcitabine, were reported to be effective and safe for the treatment of PCNs. These ablative agents are injected through a needle inserted into the cyst via transgastric or transduodenal puncture. This treatment method has been substantially developed in the last 15 years and is regarded as a promising treatment to replace surgical resection for PCNs. While several reviews of EUS-guided ablation have been published, no systematic review has evaluated this method from patient preparation to follow-up in detail. In the present review, we systematically describe EUS-guided injective ablation with regard to the indications, contraindications, preoperative treatment, endoscopic procedure, postoperative care and follow-up, evaluation method, treatment efficiency, safety profile, tips and tricks, and current controversies and perspectives.

Copy Number Alterations of Depressed Colorectal Neoplasm Predict the Survival and Response to Oxaliplatin in Proximal Colon Cancer.

Depressed colorectal neoplasm exhibits high malignant potential and shows rapid invasiveness. We investigated the genomic profile of depressed neoplasms and clarified the survival outcome and treatment response of the cancers arising from them. We examined 20 depressed and 13 polypoid neoplasms by genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations (CNAs) in an independent cohort of 37 depressed and 42 polypoid neoplasms. Finally, the CNAs were tested as biomarkers in 530 colorectal cancers (CRCs) to clarify the clinical outcome of depressed neoplasms. CNAs in MYC, CCNA1, and BIRC7 were significantly enriched in depressed neoplasms and designated as the D-marker panel. CRCs with a D-marker panel have significantly shorter progression-free survival compared with those without (p = 0.012), especially in stage I (p = 0.049), stages T1+2 (p = 0.027), and proximal cancers (p = 0.002). The positivity of the D-marker panel was an independent risk factor of cancer progression (hazard ratio (95% confidence interval) = 1.52 (1.09–2.11)). Furthermore, the proximal CRCs with D-marker panels had worse overall and progression-free survival when taking oxaliplatin as chemotherapy than those that did not. The D-marker panel may help to optimize treatment and surveillance in proximal CRC and develop a molecular test. However, the current result remains preliminary, and further validation in prospective trials is warranted in the future.

Paraganglioma presenting as a mesenteric cystic mass: A case report.

The present study aims to raise awareness about the necessity of a thorough differential diagnosis process when diagnosing paraganglioma as it is an extremely rare entity with a high malignant potential. A 64-year-old female patient was admitted to the hospital with symptoms of bowel obstruction and a palpable abdominal mass. Abdominal and pelvic computed tomography revealed a cystic heterogeneously enhanced mass. The tumor was surgically removed and then microscopically analysed. Microscopically, the mass was composed of nests of small polygonal and round cells with central vesicular nuclei, consistent with the diagnosis of mesenteric paraganglioma which was later confirmed by immunohistochemistry. The critical markers for paragangliomas, namely chromogranin A and S100, should be used as the first step in diagnosis, followed by other valuable immunohistochemical markers. A long-term follow-up is extremely important following the diagnosis of paraganglioma as all these tumors have a malignant potential.

Ovarian sex cord tumour with annular tubules in a 13-year-old female: a case report.

Sex cord tumour with annular tubules (SCTAT) is uncommon and distinctive type of sex cord-stromal tumours of the ovary which develops from sex cord cells. Most of SCTATs are strongly associated with Peutz–Jeghers syndrome (PJS) and have low malignancy potential; however, 20% of non-PJS-associated SCTATs have been reported to have high malignancy potential. Herein, we present a 13-year-old female who presented with severe abdominal pain localized in the right lower side, associated with nausea. Based on histopathological and immunohistochemical findings, the diagnosis was confirmed to be SCTAT. SCTAT of the ovary is extremely rare in the paediatric population as compared to the general population. Its occurrence among paediatrics as it was the case in the patient described in this paper may pose diagnostic challenges due to lack of clinical suspicion and therefore resulting in delay of diagnosis.

Treatment policy for colonic laterally spreading tumors based on each clinicopathologic feature of 4 subtypes: actual status of pseudo-depressed type

Laterally spreading tumors (LSTs) are originally classified into 4 subtypes. Pseudo-depressed nongranular types (LSTs-NG-PD) are gaining attention because of their high malignancy potential. Previous studies discussed the classification of nongranular (LST-NG) and granular types (LST-G); however, the actual condition or indication for endoscopic treatment of LSTs-NG-PD remains unclear. We aimed to compare the submucosal invasion pattern of LSTs-NG-PD with the other 3 subtypes. A total of 22,987 colonic neoplasms including 2822 LSTs were resected endoscopically or surgically at Showa University Northern Yokohama Hospital. In these LSTs, 322 (11.4%) were submucosal invasive carcinomas. We retrospectively evaluated the clinicopathologic features of LSTs divided into 4 subtypes. In 267 LSTs resected en bloc, their submucosal invasion site was further evaluated. The frequency of LSTs in all colonic neoplasms was significantly higher in women (14.9%) than in men (11.0%). Rates of submucosal invasive carcinoma were .8% in the granular homogenous type (LSTs-G-H), 15.2% in the granular nodular mixed type (LSTs-G-M), 8.0% in the nongranular flat elevated type (LSTs-NG-F), and 42.5% in LSTs-NG-PD. Tumor size was associated with submucosal invasion rate in LSTs-NG-F and LSTs-NG-PD (P< .001). The multifocal invasion rate of LSTs-NG-PD (46.9%) was significantly higher than that of LSTs-G-M (7.9%) or LSTs-NG-F (11.8%). In LSTs-NG-PD, the invasion was significantly deeper (≥1000 μm) if observed in 1 site. For LSTs-G-M and LSTs-NG-F that may have invaded the submucosa, en bloc resection could be considered. Considering that LSTs-NG-PD had a higher submucosal invasion rate, more multifocal invasive nature, and deeper invasion tendency, regardless if invasion was only observed in 1 site, than LSTs-NG-F, we should endoscopically distinguish LSTs-NG-PD from LSTs-NG-F and strictly adopt en bloc resection by endoscopic submucosal dissection or surgery for LSTs-NG-PD. (Clinical trial registration number: UMIN 000020261.).

Differential diagnosis and management of melanocytic lesions of the ocular surface

Our purpose is to summarize the actual knowledge about melanocytic lesions of the ocular surface (conjunctival nevus, primary acquired melanosis and conjunctival melanoma),especially their clinical appearance, differential diagnosis and treatment. Conjunctival nevus is the most common benign, conjunctival melanocytic lesion. Primary acquired melanosis mainly presents in middle-aged or elderly individuals, characterized by proliferation of melanocytes of the conjunctival epithelial layer. Conjunctival melanoma is a rare tumor, it is the second most common malignant ocular surface tumor after ocular surface squamous neoplasia and the third most common ocular malignancy following choroideal malignant melanoma and ocular surface squamous neoplasia. Early recognition and proper management of conjunctival melanoma is indispensable due to its high malignant and metastatic potential. Due to frequent recurrences, the knowledge and use of intra- and postoperative adjuvant treatment modalities, and regular follow-up are necessary. Orv Hetil. 2020; 161(15): 563–574.

SLAMF3-Mediated Signaling via ERK Pathway Activation Promotes Aggressive Phenotypic Behaviors in Multiple Myeloma.

The signaling lymphocytic activation molecule family 3 (SLAMF3) is a member of the immunoglobulin superfamily expressed on T, B, and natural killer cells and modulates the activation and cytotoxicity of these cells. SLAMF3 is also expressed on plasma cells from patients with multiple myeloma (MM), although its role in MM pathogenesis remains unclear. This study found that SLAMF3 is highly and constitutively expressed on MM cells regardless of disease stage and that SLAMF3 knockdown/knockout suppresses proliferative potential and increases drug-induced apoptosis with decreased levels of phosphorylated ERK protein in MM cells. SLAMF3-overexpressing MM cells promote aggressive myeloma behavior in comparison with cytoplasmic domain-truncated SLAMF3 (ΔSLAMF3) cells. SLAMF3 interacts directly with adaptor proteins SH2 domain-containing phosphatase 2 (SHP2) and growth factor receptor bound 2 (GRB2), which also interact with each other. SLAMF3 knockdown, knockout, ΔSLAMF3, and SHP2 inhibitor-treated MM cells decreased phosphorylated ERK protein levels. Finally, serum soluble SLAMF3 (sSLAMF3) levels were markedly increased in advanced MM. Patients with high levels of sSLAMF3 progressed to the advanced stage significantly more often and had shorter progression-free survival times than those with low levels. This study revealed that SLAMF3 molecules consistently expressed on MM cells transmit MAPK/ERK signals mediated via the complex of SHP2 and GRB2 by self-ligand interaction between MM cells and induce a high malignant potential in MM. Furthermore, high levels of serum sSLAMF3 may reflect MM disease progression and be a useful prognostic factor. IMPLICATIONS: SLAMF3 may be a new therapeutic target for immunotherapy and novel agents such as small-molecule inhibitors.

Role of Central Hypo-enhancement in the Hepatic Arterial Phase of Dynamic Computed Tomography in Patients with Mass-Forming Intrahepatic Cholangiocarcinoma.

The enhancement pattern in the hepatic arterial phase (HAP) of dynamic computed tomography (CT) is reportedly a prognostic marker in patients with intrahepatic cholangiocarcinoma (IHCC). This study was performed to clarify the significance of central hypo-enhancement in the HAP in patients with mass-forming IHCC. Forty patients who had undergone initial surgical resection for mass-forming IHCC were enrolled. The dynamic CT was scanned 40s after contrast agent injection as the HAP. A radiologist classified the patients into three groups based on the vascular pattern: the hyper-enhancement group (Hyper group), rim-enhancement group (Rim group), and hypo-enhancement group (Hypo group). The surgical specimens were immunohistochemically stained for hypoxia-inducible factor 1 (HIF-1). The correlation with clinicopathological findings and HIF-1 expression was investigated. The Hyper, Rim, and Hypo groups comprised 8, 7, and 25 patients, respectively. There were no significant correlations between the groups and clinicopathological factors. Overall survival (OS) was significantly worse in the Hypo than in the Hyper group (p = 0.03). OS was also significantly worse in the Rim + Hypo group (i.e., hypo-enhancement in the central tumor) than in the Hyper group (p = 0.04). Furthermore, inclusion in the Rim + Hypo group was a prognostic factor for OS (hazard ratio 6.68). High HIF-1 expression in the central part of the tumor was correlated with central hypo-enhancement (Hyper group: 25% and Rim + Hypo group: 72%). Central hypo-enhancement was a prognostic factor in patients with IHCC. The high malignant potential of tumors with central hypo-enhancement might be associated with HIF-1 upregulation.

Long-term outcomes of endoscopic treatment for colorectal laterally spreading tumor: a large-scale multicenter retrospective study from China

Laterally spreading tumor (LST) is a type of precancerous lesion of colorectal cancer with high malignant potential. The present study aimed to evaluate long-term outcomes of endoscopic treatment for LST in Chinese patients. This study was a retrospective review of data collected from 653 included patients with LST from six regional representative hospitals in China between January 2007 and January 2017. Demographic characteristics, endoscopic features of LST, operation-related data, and follow-up results were collected and analyzed. LST-granular type (LST-G, 80.3%) was much more common than LST-non-grandular type (LST-NG, 19.7%). The overall submucosal invasion rate of all LSTs was 6.1% and the submucosal invasion rate of LST-NG was significantly higher than that of LST-G (6.79% vs. 3.87%, p = 0.000). The en bloc resection rate of ESD and EMR treatment was 96% and 93.7%, respectively, with pathologic R0 resection rate of 90.1% and 82.8%. After an average duration of follow-up about 34.52 ± 11.76months, the recurrence rate of ESD was 3.47%, and the recurrence rate of EMR was 8.8% after an average follow-up of about 38.44 ± 4.42months. However, the recurrence rate of ESD was much lower than piecemeal EMR for LST (3.47% vs. 8.62%, p = 0.017). Retroflexion-assisted technique applied for resection of rectal LST was associated with a significantly shortened operating time (85.40min vs. 174.18min, p = 0.002). Endoscopic resection is a safe and efficient modality for the treatment of colorectal LST with a relatively low recurrence rate and shortened operating time with the use of retroflexion.

Clinical impact of TROP2 in non-small lung cancers and its correlation with abnormal p53 nuclear accumulation.

Tumor-associated calcium signal transducer 2 (TROP2) is a cell-surface glycoprotein involved in the high malignant potential of several cancers. Antibody-drug conjugates that target TROP2 represent a promising approach for the treatment of TROP2-expressing cancers including lung cancer and breast cancer. TROP2 expression was tested by immunohistochemistry in lung adenocarcinoma (ADC) and squamous cell carcinoma samples, and its correlation with clinicopathological factors, including survival rate and p53 mutation, was statistically analyzed. We found that increased TROP2 expression was significantly associated with a poor clinical course in patients with ADC, but not in patients with squamous cell carcinoma. A more significant association with poor outcome was seen in ADC cases with a high histological grade as well as those without the epidermal growth factor receptor (EGFR) mutation. A significant correlation between TROP2 expression and abnormal p53 nuclear accumulation/expression was also found in ADC. In the present study, we discovered a significant correlation between TROP2 expression and p53 mutation in ADC, and that TROP2 expression was a prognostic factor in ADC cases with a high histological grade as well as those without the EGFR mutation. Signals mediated by mutated p53 might influence TROP2 expression in ADC.

Comparison of Malignancy-Prediction Efficiency between Contrast and Non-Contract CT Based Radiomics Features in Gastrointestinal Stromal Tumours: A Multicenter Study

Background and Aim: To develop and validate radiomics signature from non-enhanced computed tomography (CT, NE-RS) to predict the malignancy potential of gastrointestinal stromal tumours (GIST) preoperatively and compare it with radiomics signature from contrast-enhanced CT. Method: A total of 370 GIST patients from four centres were divided into the training, internal validation, and external validation cohort. Minimum redundancy maximum relevance (mRMR) algorithm, and least absolute shrinkage and selection operator (LASSO) algorithm were used to filter unstable features. (1) NE-RS and CE-RS were built and compared for the prediction of malignancy potential of GIST using the area under the curve (AUC). (2) The radiomics model, with a combination of tumour size and NE-RS, was also developed. Results: The AUC values were comparable between NE-RS and CE-RS in the training (0.965 versus 0.936; P=0.251), internal validation (0.967 versus 0.960; P=0.801) and external validation (0.941 versus 0.899; P=0.173) cohorts in diagnosis of high malignancy potential of GISTs. We next focused on the NE-RS. With 0.185 selected as the cut-off of NE-RS for diagnosis of the malignancy potential of GISTs, accuracy, sensitivity, and specificity for diagnosis high-malignancy potential GIST was 90.0, 88.2, and 92.3%, respectively, in the training cohort; 89.1, 94.9, and 80.0%, respectively, in the internal validation cohort; and 84.6, 76.1, and 91.0%, respectively, in the external cohort. Compared with only NE-RS, the radiomics model increased the sensitivity in the diagnosis of GIST with high-malignancy potential by 5.9 (P=0.025), 2.5 (P=0.317), 10.5% (P=0.008) in the training, internal validation, and external validation cohort, respectively. Conclusions: The NE-RS had comparable prediction efficiency in diagnosis of high-malignant potential of GISTs to CE-RS. The NE-RS and radiomics model both had excellent accuracy in predicting malignancy potential of GISTs. Funding Statement: This work was supported by grants from Shanghai Municipal Key Clinical Specialty (Grant No. shslczdzk05902). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Ethical approval obtained from all four participating hospitals. All patents provided written informed consent.

Development and validation of a nomogram based on CT images and 3D texture analysis for preoperative prediction of the malignant potential in gastrointestinal stromal tumors

BackgroundGastrointestinal stromal tumors (GISTs), which are the most common mesenchymal tumors of the digestive system, are treated varyingly according to the malignancy. The purpose of this study is to develop and validate a nomogram for preoperative prediction of the malignant potential in patients with GIST.MethodsA total of 440 patients with pathologically confirmed GIST after surgery in our hospital from January 2011 to July 2019 were retrospectively analyzed. They were randomly divided into the training set (n = 308) and validation set (n = 132). CT signs and texture features of each patient were analyzed and predictive model were developed using the least absolute shrinkage and selection operator (lasso) regression. Then a nomogram based on selected parameters was developed. The predictive effectiveness of nomogram was evaluated by the area under receiver operating characteristic (ROC) curve (AUC). Concordance index (C-index) and calibration plots were formulated to evaluate the reliability and accuracy of the nomogram by bootstrapping based on internal (training set) and external (validation set) validity. The clinical application value of the nomogram was determined through the decision curve analysis (DCA).ResultsTotally 156 GIST patients with low-malignant (very low and low risk) and 284 ones with high-malignant potential (intermediate and high risk) are enrolled in this study. The prediction nomogram consisting of size, cystoid variation and meanValue had an excellent discrimination both in training and validation sets (AUCs (95% confidence interval(CI)): 0.935 (0.908, 0.961), 0.933 (0.892, 0.974); C-indices (95% CI): 0.941 (0.912, 0.956), 0.935 (0.901, 0.982); sensitivity: 81.4, 90.6%; specificity: 75.0, 75.7%; accuracy: 88.0, 88.6%, respectively). The calibration curves indicated a good consistency between the actual observation and nomogram prediction for differentiating GIST malignancy. Decision curve analysis demonstrated that the nomogram was clinically useful.ConclusionThis study presents a prediction nomogram that incorporates the CT signs and texture parameter, which can be conveniently used to facilitate the preoperative individualized prediction of malignancy in GIST patients.

Artificial Intelligence Assisted Standard White Light Endoscopy Accurately Characters Early Colorectal Cancer: A Multicenter Diagnostic Study

Background: Early detection and treatment under endoscopy have effectively decreased the mortality of colorectal cancer (CRC). But it is difficult to detect early CRC under white light endoscopy (WLE). Artificial intelligence (A.I.) assisted diagnose system are accumulated, but early CRC assisting diagnosis system is lack due to clinical design and sample size limitation. We propose to establish a propagable AI-assisted early CRC diagnosis and characterization system (ECRC-CAD). Methods: Establishing algorithms were implemented in four (i.e., municipal, provincial, rural) hospitals of China. All patients who completed WLE from January 2016 to July 2019 were enrolled. Early CRC is diagnosed by pathological examination. Images of intraepithelial neoplasm (IN-ECRC) were included in the case group, and precancerous conditions and serrate lesion without intraepithelial neoplasm (NIN-ECRC) were randomly sampled in corresponding quantity included to control group. These images were randomly assigned (8:1:1) to the training, optimizing datasets and internal datasets. The evaluating indexes of diagnostic performance include sensitivity, specificity, positive predictive value, and negative predictive value. Findings: The largest new CRC endoscopic image database to date were established, which included 4,390 images of IN-ECRC. The diagnostic accuracy was 0·963 (95% CI, 0·941-0·978) in the internal validation set, and 0·835 (95% CI, 0·805-0·862) of identifying IN-ECRC in external datasets. ECRC-CAD achieved better diagnostic accuracy than the expert endoscopist (0·885 [95% CI, 0·859-0·907] vs 0.505 [95% CI, 0·411–0·598]; p<0.0001). The sensitivity, specificity, positive, and negative predictive value were significantly higher for ECRC-CAD than the expert endoscopist (p<0.0001). Interpretation: ECRC-CAD can identify early CRC and characterize neoplasms with high malignant potential; the performance is better comparing with expert endoscopists. Spreading of ECRC-CAD to regions with different medical levels can assist in CRC screening and prevention. Funding Statement: This research was supported by Major Science and Technology Project of Zhejiang Provincial (2020C03030), Natural Science Foundation of Fujian Province (2019-CXB-31), Science and technology program of Guangdong Province (2016A020213002), and National Natural Science Foundation of China (81773956). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Each participating institute has ethical approval by independent ethics Committee according to the Helsinki declaration. The informed consent of retrospective cohort was exempted by the institutional review boards as the secondary use of clinical data without any intervention. In the prospective study, each patient was informed and signed informed consent.

Clear-cell carcinoma of the larynx: A report of an unusual case

Clear-cell carcinoma (CCC) of the larynx is an extremely rare neoplasm with high malignancy potential and poor outcome. We herein report the 11th case of CCC of the larynx in a 42-year-old female who was managed with definitive radiochemotherapy. Due to a paucity of this entity, treatment option is not clearly defined, however, considering its grave nature, surgery should be offered primarily along with adjuvant radiotherapy with or without chemotherapy.

Clinicopathological and molecular characteristics of abdominal desmoid tumors in the Chinese population: A single-center report of 15 cases.

Desmoid tumors (DTs), derived from the abdomen, are a type of rare and aggressive borderline tumor exhibiting high recurrence and malignant potential. The aim of the present study was to investigate the clinicopathological and molecular characteristics of abdominal DT in a Chinese population and to provide clues for selecting the optimal treatment strategy for different types of abdominal DT. The clinicopathological data of 15 consecutive patients with DT was collected. Matched fresh-frozen tumor tissues and peripheral blood samples were used to detect mutations of adenomatous polyposis coli gene (APC), β-catenin (CTNNB1) and MutY DNA glycosylase (MUTYH) using Sanger sequencing. Pearson's test was conducted to analyze the differences between sporadic DT and familial adenomatous polyposis (FAP) associated with DT. Time to progress (TTP) and overall survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. A review of the patient clinicopathological characteristics revealed that FAP-associated DT exhibited a higher rate of abdominal surgery history (P=0.011), with no significant differences in any other characteristics. Sequencing revealed that mutations in the APC, CTNNB1 and MUTYH genes were common in DT, and only one patient harbored no mutations in these genes. Survival analyses revealed that patients with FAP exhibited shorter TTP (P=0.030). Log-rank test demonstrated a tendency towards shorter TTP in the cases where an R2 resection was performed (P=0.072) and a tendency towards poor prognosis in the cases of DT associated with FAP (P=0.087). In conclusion, Abdominal DTs were prone to occur in patients with FAP with a history of abdominal surgery. Mutations in the APC, CTNNB1 and MUTYH genes were detected in patients with DTs. To the best of our knowledge, this is the first study of abdominal DT occurrence in patients with MUTYH-associated FAP. The prognosis of DT associated with FAP may be worse compared with that of sporadic DT.

36 Integrated Molecular Pathology as a Predictor of Malignant Transformation of Pancreatic Cysts: A 6-Year Follow-Up

INTRODUCTION: 2018 ACG guidelines recommend surgical evaluation for pancreatic cysts with high-risk features. Integrated Molecular Pathology (IMP) combines molecular and biochemical analysis with cytology to improve prediction of malignant transformation. We aim to characterize the long-term performance of IMP. METHODS: All pancreatic cystic lesions from prospectively acquired patients with EUS-FNA and IMP (PancraGEN, Interpace Diagnostics) from 9/2010 to 9/2013 were retrospectively analyzed. Known pancreatic adenocarcinoma, serous cystadenoma, or pseudocyst were excluded. Data on patient demographics; EUS and cross-sectional imaging; cyst fluid biochemical and molecular analysis; and cytology were collected. Cystic lesions with low malignant potential were classified as “benign” or “statistically indolent” by IMP and “statistically higher risk” or “aggressive” for those with high malignant potential. Final diagnosis was based on surgical pathology when available, repeat biopsy or imaging, and on length of clinical follow up. RESULTS: 69 patients with mean age 69.9; 36.2% male were included. Median follow-up was 68.5 months (0.4–99.6); 3 patients were lost to follow-up. Average cyst size was 2.3 cm (0.2–15.3). 22/69 (31.9%) cysts were in the head, 13/69 (18.8%) in the neck, 23/69 (33.3%) in the body, and 11/69 (15.9%) in the tail of the pancreas. 10 patients underwent resection or enucleation. IMP classified 38/69 (55.1%) as benign, 27/69 (39.1%) as statistically indolent, 1/69 (1.4%) as statistically higher risk, 2/69 (2.9%) as aggressive, and 1/69 (1.4%) as indeterminate. Final diagnosis was pancreatic adenocarcinoma in 5/69 (7.2%), mucinous cystadenoma in 10/69 (14.5%), branch type IPMN in 37/69 (53.6%), serous cystadenoma in 13/69 (18.8%), and indeterminate in 4/69 (5.8%). Final diagnosis of adenocarcinoma was in 2/38 (5.3%) classified as benign by IMP, 2/27 (7.4%) statistically indolent lesions, 0/1 (0%) statistically higher risk lesions, 1/2 (50%) aggressive lesions, and 0/1 (0%) indeterminate lesions. A composite of high malignant potential on IMP or high-risk features based on ACG guidelines yielded a sensitivity of 100%, specificity of 81.3%, PPV of 29.4%, and NPV of 100% (Table 1). CONCLUSION: Combining high-risk features based on ACG guidelines with IMP is a valuable predictor of malignant transformation of pancreatic cysts, with high sensitivity and NPV based on median 6-year follow-up, which to our knowledge is the longest reported thus far.

2543 Duodenal Traditional Serrated Adenoma (TSA) Presenting as Small Bowel Intussusception

INTRODUCTION: Intestinal intussusception is the telescoping of a proximal into an adjacent distal segment of the gastrointestinal (GI) tract. Intussusception is rare in adults, accounting for less than 5% of all mechanical bowel obstructions. Approximately 80-90% of intussusceptions in adults are secondary to an underlying pathological process, including malignant lesions, polyps, or Meckel's diverticulum. Therefore, when intussusception occurs in adults, further investigation to determine the etiology is warranted. CASE DESCRIPTION/METHODS: A 48 year-old female without significant past medical history developed severe, episodic abdominal pain six to eight weeks prior to presentation with associated nausea and occasional emesis. Recent CT scan of the abdomen and pelvis with contrast demonstrated small bowel intussusception in the area of the ligament of Treitz (Figure 1). Laboratory investigations were notable for microcytic anemia. She was referred to gastroenterology and underwent extended esophagogastroduodenoscopy (EGD) which revealed a 4 cm mass in the fourth portion of the duodenum (Figure 2). Initial mucosal biopsy suggested a possible tubulovillous adenoma with low-grade dysplasia. She subsequently underwent surgical resection of the small bowel mass with duodeno-jejunostomy. Surgical pathology revealed a traditional serrated adenoma (TSA) with low-grade dysplasia forming a cluster of polyps ranging from 0.5 to 4.3 cm in size (Figure 3). She did well postoperatively and was discharged on post-operative day 6. She will be undergoing colonoscopy after recovering from surgical intervention. DISCUSSION: Of the three types of serrated adenomas, TSA is the least common, accounting for only 5% of serrated polyps. These are commonly found in the colorectum and have rarely been described in other portions of the GI tract. The first case of TSA of the duodenum was not described until 2004. More recently, TSAs have been detected throughout the upper GI tract. However, reports of TSAs causing small bowel intussusception have not been described. This novel case highlights the importance of considering this in the differential for any adult with proximal small bowel intussusception. Importantly, TSAs of the upper GI tract may represent more aggressive lesions with high malignant potential and should be excised to rule out the possibility of a developing malignancy.