Endoscopic Ultrasound-guided Fine-needle Aspiration Research Articles

Diagnostic and Prognostic Values of KRAS Mutations on EUS-FNA Specimens and Circulating Tumor DNA in Patients With Pancreatic Cancer.

INTRODUCTION:The ability of carbohydrate antigen 19-9 (CA19-9) to differentiate pancreatic cancer from other benign pancreatic lesions is unsatisfactory. This study explored the diagnostic value of KRAS gene mutations and plasma circulating tumor DNA (ctDNA) in patients with pancreatic cancer.METHODS:The prospective cohort study comprised 149 consecutive patients with solid pancreatic lesions who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). KRAS subtype mutations were analyzed by digital droplet PCR (ddPCR) in EUS-FNA histopathology tissue samples, and blood samples were sent for plasma ctDNA analysis. The final diagnosis was based on surgical resection pathology or follow-up for at least 2 years.RESULTS:Adding KRAS mutation ddPCR increased the sensitivity and accuracy of EUS-FNA from 71.4% to 91.6% (P < 0.001) and 75.8% to 88.6% (P < 0.001), respectively. By comparison, the sensitivities of circulating biomarkers ctDNA and CA19-9 were only 35.2% and 71.2%. The area under the curve of the receiver operating characteristic curve (AUC) of EUS-FNA and KRAS ddPCR combination was >0.90 for distinguishing pancreatic cancer from benign lesions, whereas the AUC of EUS-FNA and CA19-9 combination was 0.83. The median survival time was significantly shorter in patients with G12D KRAS mutations than that in patients with other mutations (180 vs 240 days, P < 0.001).DISCUSSION:FNA tissue sample KRAS mutation analysis in tissues significantly improves the diagnostic accuracy of cyto/histopathological evaluation in EUS-FNA samples. The combination of EUS-FNA and tissue sample KRAS ddPCR provided a more accurate method for pancreatic cancer diagnosis, superior to the combination of EUS-FNA and CA19-9/ctDNA. G12D KRAS mutations in pancreatic cancer were independently associated with poor overall survival.

Diagnostic accuracy and clinical impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in Positron Emission Tomography - Computed Tomography (PET-CT)-positive mediastinal lymphadenopathies in patients with thoracic or extra-thoracic malignancies

BackgroundThe high sensitivity of PET-CT can identify hypermetabolic mediastinal adenopathies during cancer management, but specificity is low and a biopsy is sometimes required to eliminate benign adenopathies. MethodsThis prospective diagnostic accuracy study included patients with hypermetabolic mediastinal lymphadenopathies revealed on PET-CT during either the initial management of a cancer, treatment evaluation, or monitoring. All patients underwent EUS-FNA. Diagnoses of malignancy based on cytological analysis following EUS-FNA were compared with clinical and radiological follow-up information. The treatment strategy decided before the results of the EUS-FNA pathology reports (Multidisciplinary Team Meeting [MTM-1]) was recorded and compared to the treatment strategy decided once pathological data from EUS-FNA were available (MTM-2). Main findingsBetween 2013 and 2018, 75 patients were included with 47 eligible and evaluable patients. Sensitivity, specificity, and positive and negative predictive values of EUS-FNA were 93%, 100%, 100% and 90%, respectively. The concordance value between the therapeutic strategies determined for MTM-1 and MTM-2 was 44.7%. There were no significant differences in the intensity of fixation on PET-CT between malignant and benign lesions. ConclusionThe diagnostic accuracy of the minimally invasive EUS-FNA procedure is sufficiently robust to avoid the need for diagnostic surgery. The combination of PET-CT and EUS-FNA may alter the therapeutic strategy that would be considered after PET-CT alone. REGISTRATIONNCT01892501

The Diagnosis of Small Gastrointestinal Subepithelial Lesions by Endoscopic Ultrasound-Guided Fine Needle Aspiration and Biopsy.

Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.

The Performance Comparison of 18F-FDG PET/MRI and 18F-FDG PET/CT for the Identification of Pancreatic Neoplasms.

To determine the optimal imaging tool for clinical evaluation of pancreatic neoplasm by comparing the performance of 18F-FDG PET/MRI and PET/CT. Patients with suspected pancreatic neoplasms underwent PET/MRI and PET/CT in the same day prior to resection or endoscopic ultrasound-guided fine-needle aspiration. Histology served as the golden standard of lesion classification. Visual assessment on lesion type and lesion malignancy via PET/MRI and PET/CT images was compared. Standard uptake values (SUVs) of PET images from the two scanners were measured and their correlations were further evaluated. Thirty-nine patients were included for the final analysis. In visual assessment, we found MRI achieved better performance than CT in differentiating solid and cystic neoplasms, with accuracy of 100% vs. 87%, respectively. In visual malignancy diagnosis, the accuracy of PET/CT was 92.3% for overall lesions and 90.9% for cysts, while the accuracy of PET/MRI was 92.3% and 86.4%, respectively. Besides, semi-quantitative analysis achieved better specificity than visual assessment for both hybrid modalities (100% vs. 87.5% for PET/CT; 100% vs. 81.5% for PET/MR). Furthermore, strong correlation of SUV was found between PET/CT and PET/MRI, with Pearson's correlation coefficients > 0.82. In this study, we found PET/MRI and PET/CT, both using 18F-FDG as tracer, had comparable overall performance in identification of pancreatic neoplasms. Interestingly, for patients who had suspected pancreatic neoplasm but invisible FDG uptake, PET/MRI had shown exceptionally better performance, probably because MR images could detect tiny abnormal structures to improve diagnosis.

The diagnostic performance of combined conventional cytology with smears and cell block preparation obtained from endoscopic ultrasound-guided fine needle aspiration for intra-abdominal mass lesions.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the primary method for tissue acquisition of intra-abdominal masses. However, the main limitation of cytology alone is the lack of tissue architecture and inadequate samples. This study aimed to evaluate the diagnostic performance of combined conventional cytology and cell block preparation obtained from EUS-FNA of intra-abdominal masses without Rapid On-site Evaluation (ROSE). Cytologic smears and cell block slides of 166 patients undergoing EUS-FNA during 2010-2015 were reviewed by an experienced cytopathologist blinded to clinical data. 125 patients had neoplastic lesions. Pancreatic adenocarcinoma was the most common etiology (35.5%), followed by lymph node metastasis (27.7%). The mean mass size was 2.5±1.3 cm. The mean number of passes was 1.9±1.28. Tissue adequacy for conventional cytology and cell block preparation was 78.9% and 78.1%, respectively. Factors associated with tissue adequacy were assessed. For cytology, lesions of > 2.1 cm, masses in the pancreatic body or tail, malignancy, and pancreatic cancer were positively associated with adequate cellularity. For cell block preparation, lesions of > 3 cm and malignancy were associated with increased tissue adequacy. The conventional cytology alone had a sensitivity of 68.5%, a specificity of 95.7%, and an area under the receiver operating characteristics (AUROC) of 0.821. The cell block preparation alone had a sensitivity of 65.4%, a specificity of 96%, and an AUROC of 0.807. The combined conventional cytology and cell block preparation performed significantly better than either method alone (p<0.05), as demonstrated by an increased AUROC of 0.853. Furthermore, cell block detected malignancy in 9.3% of cases where the cytologic smears failed to identify malignant cells. The combined conventional cytology and cell block preparation increased the diagnostic accuracy of EUS-FNA compared to either method alone. This approach should be implemented in routine practice, especially where ROSE is unavailable.

Background features in the cytology of pancreatic neoplasms.

Cytology is a useful method for diagnosing pancreatic neoplasms. Although endoscopic ultrasound‐guided fine‐needle aspiration has recently become the mainstream method for the diagnosis of pancreatic neoplasms, pancreatic juice and pancreatic duct brushing cytology continue to be useful diagnostic methods for the investigation of pancreatic neoplasms. Diagnoses using pancreatic cytology are primarily based on the features related to tumor cells; however, evaluation of the background features provides important information that could further aid the diagnosis. Pancreatic neoplasms show various histological types, each of which is associated with its own characteristic background features. The necrotic background, desmoplastic stroma, and presence of cancer‐associated fibroblasts are background features of pancreatic ductal adenocarcinoma, a mucinous background is associated with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, and hyaline globules are observed in solid pseudopapillary neoplasms. However, some background features are associated with more than one histological type of pancreatic neoplasm, highlighting the importance to base a diagnosis on the results of a comprehensive analysis of not only the background features but also the tumor cells. Here, we provide a review of the key background cytological features of pancreatic neoplasms, which can serve as a guide to improve diagnosis and research.

Comparison between Two Types of 22-Gauge Fine-Needle Biopsy for Solid Pancreatic Tumors

Background: Tissue sampling using endoscopic ultrasound-guided fine-needle aspiration is the gold standard for diagnosing malignant pancreatic tumors; however, its sensitivity and specificity are highly variable. Thus, fine-needle biopsy using cutting needles has been developed to overcome current limitations and improve diagnostic yield. Our study compared two fine-needle biopsy needles for tissue sampling for pancreatic solid lesions. Materials and Methods: Samples obtained from patients with pancreatic solid lesions using the 22-gauge fine-needle biopsy needles (Franseen needle or reverse bevel needle) were retrospectively analyzed. The primary outcomes were diagnostic yield and sample adequacy. The secondary outcome was diagnostic performance. The analysis was performed using 2 × 2 tables to calculate sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for each needle type. Proportions were compared using the Z test. For quantitative variables, a comparative analysis was performed using Student’s t test. Qualitative and unpaired outcome variables were described using Fisher’s exact test. Results: Sixty-three patients with pancreatic lesions were included in the analysis. The fine-needle biopsy Franseen and reverse bevel groups included 33 and 30 patients, respectively. An adequate sample was obtained in 97% of patients in the Franseen needle group versus 80% in the reverse bevel needle group; the diagnostic yields in these groups were 93.9 and 66.7%, respectively. Neither differences between needle passes nor complications were noted. The sensitivity and specificity were 93.5 and 100%, respectively, in the fine-needle biopsy Franseen group, versus 71 and 100%, respectively, in the reverse bevel needle group. Conclusions: The Franseen needle was more effective for sampling pancreatic tumors than the reverse bevel needle.

Endoscopic ultrasound-guided through-the-needle microforceps biopsy and needle-based confocal laser-endomicroscopy increase detection of potentially malignant pancreatic cystic lesions: A single-center study.

BACKGROUNDCurrently, there is insufficient data about the accuracy in the diagnosing of pancreatic cystic lesions (PCLs), especially with novel endoscopic techniques such as with direct intracystic micro-forceps biopsy (mFB) and needle-based confocal laser-endomicroscopy (nCLE).AIMTo compare the accuracy of endoscopic ultrasound (EUS) and associated techniques for the detection of potentially malignant PCLs: EUS-guided fine needle aspiration (EUS-FNA), contrast-enhanced EUS (CE-EUS), EUS-guided fiberoptic probe cystoscopy (cystoscopy), mFB, and nCLE.METHODSThis was a single-center, retrospective study. We identified patients who had undergone EUS, with or without additional diagnostic techniques, and had been diagnosed with PCLs. We determined agreement among malignancy after 24-mo follow-up findings with detection of potentially malignant PCLs via the EUS-guided techniques and/or EUS-guided biopsy when available (EUS malignancy detection). RESULTSA total of 129 patients were included, with EUS performed alone in 47/129. In 82/129 patients, EUS procedures were performed with additional EUS-FNA (21/82), CE-EUS (20/82), cystoscopy (27/82), mFB (36/82), nCLE (44/82). Agreement between EUS malignancy detection and the 24-mo follow-up findings was higher when associated with additional diagnostic techniques than EUS alone [62/82 (75.6%) vs 8/47 (17%); OR 4.35, 95%CI: 2.70-7.37; P < 0.001]. The highest malignancy detection accuracy was reached when nCLE and direct intracystic mFB were both performed, with a sensitivity, specificity, positive predictive value, negative predictive value and observed agreement of 100%, 89.4%, 77.8%, 100% and 92.3%, respectively (P < 0.001 compared with EUS-alone). CONCLUSIONThe combined use of EUS-guided mFB and nCLE improves detection of potentially malignant PCLs compared with EUS-alone, EUS-FNA, CE-EUS or cystoscopy.

NEOPLASIA SÓLIDA PSEUDOPAPILAR PANCREÁTICA MIMETIZANDO TUMOR NEUROENDÓCRINO DE BAIXO GRAU

Introduction: Solid pseudopapillary neoplasms (SPN) and pancreatic neuroendocrine tumors (NET) are rare diseases that are generally incidental findings in imaging tests. SPN is a low-grade tumor with good prognosis that more commonly affects young female patients. Pancreatic NET has a significant variability in outcomes, with low malignant potential in non-progressing tumors that are welldifferentiated. Both tumors may appear very similar in imaging tests and immunohistochemical (IHC) evaluation, which makes the differential diagnosis challenging, especially in small lesions. Case report: The authors present the case of a 34-year-old male with a medical history of a primary mediastinal germ cell tumor. The patient had no symptoms. Follow-up abdominal CT scan evidenced a single, well-delimited nodular lesion in the pancreatic neck, measuring 17mm in diameter. The patient was submitted to an endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) and after IHC analysis, there was a diagnostic suspicion of low-grade pancreatic NET. Central pancreatectomy (CP) was performed and complete lesion analysis evidenced a pancreatic SPN. Conclusion: The SPN can mimic low-grade nonfunctioning pancreatic NETs in imaging tests and EUSFNA IHC evaluation.

Conversion surgery for undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a case report

BackgroundUndifferentiated carcinoma with osteoclast-like giant cells (UCOGCs) is a rare subtype of pancreatic cancer (PC), and its clinicopathological characteristics are still unclear. Herein, we report a case of initially unresectable UCOGC that was successfully resected after FOLFIRINOX therapy.Case presentationA 63-year-old man was referred to us for evaluation of a pancreatic mass detected by computed tomography (CT) during a medical checkup. Computed tomography showed a 7.5-cm tumor located in the pancreatic head and body, which involved the common hepatic artery (CHA), gastroduodenal artery (GDA), and main portal vein (PV) with tumor thrombus. UCOGC was suspected by endoscopic ultrasonography-guided fine needle aspiration, and the patient was diagnosed with unresectable locally advanced pancreatic cancer. After ten cycles of FOLFIRINOX, the tumor size decreased to 3 cm and the tumor thrombus in the main portal trunk had disappeared in the follow-up CT scan. However, the patient experienced severe adverse drug reactions, including neutropenia and liver dysfunction. Therefore, we performed pancreatoduodenectomy with portal vein resection. The pathological diagnosis was UCOGC with a negative tumor margin. He was treated with FOLFIRINOX, and remains recurrence-free for 6 months after surgery.ConclusionsWe experienced a case undergoing conversion surgery for unresectable UCOGC, which resulted in R0 resection. FOLFIRINOX could be a possible regimen to achieve conversion surgery for UCOGC.

Gastrointestinal: Endoscopic ultrasound of rectal subepithelial lesion mimicking gastrointestinal stromal tumor.

A 60-year-old man presented with anorexia, weight loss, and constipation for 3 months. On peri-rectal examination, a bulge was palpated in the rectum. He underwent colonoscopy, which showed large subepithelial lesion (SEL) starting from anorectal junction extending proximally till rectosigmoid junction obliterating the lumen without complete obstruction (Fig. 1a). Contrast-enhanced computed tomography of the pelvis showed a large lobulated heterogeneous enhancing soft tissue lesion within the rectum (Fig. 1b). Endoscopic ultrasound (EUS) was performed, which showed a large well defined lobulated hetero-echoic lesion (70 × 63 mm) with multiple cystic spaces in peri-rectal area (Fig. 1c). Possibility of rectal malignant gastrointestinal stromal tumor (GIST) was considered looking at CT and EUS image. To confirm our diagnosis, EUS-guided fine needle aspiration (FNA) was performed. During FNA, dark brownish fluid was aspirated (Fig. 2a). Possibility of bleed within tumor was considered because of dark brownish fluid aspiration; however, black pigments were noticed on slide preparation (Fig. 2b). Histopathological examination showed pleomorphic cells with abundant brownish pigment with multinucleation suggestive of malignant melanoma (Fig. 2c). Patient was advised for surgery and referred to the surgeons. Malignant melanoma is an extremely rare and aggressive tumor of the rectum. It accounts for 0.5–4% of all anorectal malignancies and < 1% of all melanomas. It is most common site of primary gastrointestinal melanoma followed by stomach, small intestine, and colon. Patients usually present in the fifth or sixth decade, and it is more common in female patients. Anorectal melanomas usually appear as ulcerated polypoidal lesions rather than SEL. EUS is an important diagnostic tool in diagnosis and differentiation of SEL. There is lack of characterization of anorectal melanoma on EUS because of rarity of tumor. Yonal et al. described the EUS morphological features of esophageal melanoma as iso to hypoechoic solid tumor mass with variable areas of internal hyper-echogenicity and anechoic cystic spaces, similar to the findings from our case. Morphological features of some SELs are confusing; therefore, EUS FNA plays an important role in differentiation of SELs. Therapy in anorectal melanomas is dictated by the local staging of disease and also the presence of lymph node and distant metastases. Multidisciplinary approach is required depending on the stage of tumor. Surgery has been the mainstay of treatment for anorectal melanoma. Although these tumors are usually radio-resistant and chemo-resistant, combination of chemotherapy and immunotherapy remains a therapeutic option for advanced metastatic disease. Overall, 5-year survival is only 3–22%, and survival in recurrent or metastatic disease is less than 10 months. Although a rare entity, anorectal melanoma can mimic GIST and may be a differential during the evaluation of rectal SEL. Early diagnosis of tumor is of paramount importance for favorable prognosis.

Upregulation of PODXL and ITGB1 in pancreatic cancer tissues preoperatively obtained by EUS-FNAB correlates with unfavorable prognosis of postoperative pancreatic cancer patients.

The upregulation of PODXL and ITGB1 in surgically resected pancreatic cancer tissues is correlated with an unfavorable postoperative prognosis. The aim of this study was to investigate whether PODXL and ITGB1 are useful preoperative markers for the prognosis of postoperative pancreatic cancer patients in comparison with the TNM staging system. Immunohistochemistry was performed using anti-PODXL and anti-ITGB1 antibodies on 24 pancreatic cancer tissue samples preoperatively obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy. Cox proportional hazards regression analysis was performed to investigate if the UICC TNM stage and upregulation of PODXL and ITGB1 were correlated with postoperative overall survival rates. Univariate analysis revealed that PODXL, TNM stage, lymphatic invasion and the combination of PODXL with ITGB1 are correlated with postoperative survival. Multivariate analysis demonstrated TNM stage and the combination of PODXL with ITGB1 to be correlated with postoperative survival, and the combination of PODXL with ITGB1 most accurately predicted the postoperative outcomes of pancreatic cancer patients before resection. Therefore, upregulation of PODXL and ITGB1 may indicate preoperative neoadjuvant therapy for pancreatic cancer patients by accurately predicting the postoperative prognosis.

Double Ki-67 and synaptophysin labeling in pancreatic neuroendocrine tumor biopsies

BackgroundPancreatic neuroendocrine tumors (PanNETs) are frequently detected on endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens. The conventional methods for evaluating the Ki-67 labeling index (Ki67LI) in EUS-FNAB specimens are laborious, and their results are difficult to interpret. More practical and easy methods for evaluating the Ki67LI in PanNETs from EUS-FNAB specimens is increasing in need. MethodsWe used double Ki-67 and synaptophysin (double Ki-Syn) antibody cocktail; Ki67LI, total Ki-67 positive cells, and total tumor cells were counted and compared with those detected on conventional single Ki-67 immunostaining (single Ki-67) of 96 PanNETs [Grade 1 (G1), 68 cases (71%); G2, 26 (27%); G3, 2 (2%)] from EUS-FNAB specimens. ResultsThe tumor grading between double Ki-Syn and single Ki-67 immunolabeling was highly concordant (correlation, 0.95; Fisher's exact test, P < 0.001). Seven EUS-FNAB specimens (7%) had discrepant results, of which 2 were removed through surgical resection and showed the same tumor grade as that detected on double Ki-Syn immunolabeling. Fifty-four specimens (56%) had higher Ki-67 positive tumor cell counts on single Ki-67 immunolabeling. Sixty-two specimens (65%) had higher total tumor cell counts on double Ki-Syn immunolabeling. The number of specimens with less than 500 total counted tumor cells were significantly reduced when double Ki-Syn immunolabeling was applied [P = 0.046; single Ki-67, 17 specimens (18%); double Ki-Syn, 9 specimens (9%)]. ConclusionDouble Ki-Syn immunolabeling enables the accurate counting of the number of proliferating tumor cells without including inflammatory and contaminant epithelial cells compared with single Ki-67 immunolabeling in PanNETs from EUS-FNAB specimens.

The Role of Interleukin 1 Beta in Differentiating Malignant from Benign Pancreatic Cysts.

Background and Aim: The frequency of detection of pancreatic cystic lesions (PCLs) in magnetic resonance imaging performed for reasons unrelated to the pancreas reaches up to 13.5%. The aim of this study was to evaluate the role of cyst fluid interleukin 1 beta (IL1β) and different endoscopic ultrasound (EUS) features in differentiating premalignant/malignant from benign pancreatic cysts. In addition, to evaluate the role of pancreatic cyst fluid carcinoembryonic antigen (CEA) in differentiating mucinous from nonmucinous pancreatic cysts. Methods: This study was conducted on 73 patients with PCLs. EUS-guided fine-needle aspiration (EUS-FNA) was performed on all patients. Estimation of IL1β and CEA levels in aspirated specimens were carried out. Results: Pancreatic cyst fluid IL1β level could not differentiate between premalignant/malignant and benign pancreatic cysts. At a cutoff value of 19.81 ng/mL pancreatic cyst fluid CEA has 64.3% sensitivity and 84.4% specificity in differentiating mucinous from nonmucinous pancreatic cyst. EUS can differentiate between premalignant/malignant pancreatic cysts and benign cysts with a sensitivity of 66.7%, specificity of 69.2% Conclusions: Pancreatic cyst fluid IL1β level cannot differentiate between premalignant/malignant and benign pancreatic cysts. CEA level can help in differentiation between mucinous and nonmucinous cysts. EUS can be useful in differentiation between premalignant/malignant pancreatic cysts and benign cysts.

Primary mucosa-associated lymphoid tissue lymphoma of the entire esophagus diagnosed by endoscopic ultrasound-guided fine needle aspiration.

Primary mucosa-associated lymphoid tissue lymphoma of the entire esophagus diagnosed by endoscopic ultrasound-guided fine needle aspiration.

Serial EUS-Guided FNA for the Surveillance of Pancreatic Cysts: A Study of Long-Term Performance of Tumor Markers.

The natural history of KRAS mutations in mucinous pancreatic cysts (MPCs) over time remains to be fully understood. The aim of this study was to examine the performance of DNA markers and assess changes of KRAS mutationsover time. Patients who underwent EUS-FNA of pancreatic cysts with at least two separate molecular analysis results were included in the study. We assessed the baseline patient and cyst characteristics, and DNA fluid analysis. The presence of either a KRAS mutation, or a CEA > 192ng/ml was used as the diagnostic standard for mucinous cysts when surgical pathology was not available. A total of 933 pancreatic cyst fluid samples were collected, including 117 with ≥ 2 FNAs. Examinations were performed over a median of 30months (range 1-115months). Forty-three (36%) had a mutant KRAS on the index analysis out of which 26 had a change in their KRAS status to the wild-type. Eighty-one (64%) had a wild-type KRAS on the index analysis out of which 18 had change in their KRAS status to mutant type. There was no significant difference in the index cyst characteristics,presence of symptoms, or main duct involvement based on KRAS status change. Increasing age was associated with a changing KRAS mutation status (p = 0.023). KRAS mutations gain and loss in pancreatic cyst fluid appears to occur frequently during long-term surveillance of MPCs. Age appears to be the only predictor for KRAS change over time.

How to Approach Submucosal Lesions in the Gastrointestinal Tract: Different Ideas between China and USA.

Between 2019 and 2020, the author Gao pursued advanced endoscopic training at the University of Mississippi Medical Center in the USA. She experienced certain different ideas between the East (China) and the West (USA) in terms of endoscopic approach to the submucosal tumors (SMTs) or lesions in the gastrointestinal (GI) tract. In the West (USA), when SMTs are found on gastroscopy, the main goal of endoscopists is to obtain a tissue diagnosis through endoscopic ultrasound-guided fine-needle aspiration or biopsy (EUS-FNA or FNB) or single incision needle-knife biopsy (SINK); if immunohistochemical tests confirmed the GISTs, the first-line treatment is local surgery, that is, diagnosis before treatment, whereas in China, SMTs will be completely resected with endoscopic technology for those with no lymph node metastasis or extremely low risk of lymph node metastasis. There may not be pathological tissue at first, that is, treatment before diagnosis.

A New Preoperative Scoring System for Predicting Aggressiveness of Non-Functioning Pancreatic Neuroendocrine Neoplasms.

The management of non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) is still controversial. This study aimed to develop a new scoring system for treatment decisions at initial diagnosis based on the identification of the predictive factors for aggressive NF-PanNENs. Seventy-seven patients who had been pathologically diagnosed with NF-PanNENs were enrolled. We retrospectively reviewed 13 variables that could be assessed preoperatively. Univariate and multivariate stepwise logistic regression analyses were performed to identify factors for the aggressiveness of NF-PanNENs, and a scoring system was developed by assigning weighted points proportional to their β regression coefficient. Tumor size > 20 mm on contrast-enhanced computed tomography, tumor non-vascularity, and Ki-67 labeling index ≥5% on endoscopic ultrasound-guided fine-needle aspiration specimens were identified as independent factors for predicting the aggressiveness of NF-PanNENs. The new scoring system, developed using the identified factors, had an excellent discrimination ability, with area under the curve of 0.92 (95% CI, 0.85–0.99), and good calibration (p = 0.72, Hosmer-Lemeshow test). Ten-year overall survival rates in low-risk (0 point), intermediate-risk (1 to 2 points), and high-risk (3 to 4 points) groups were 100%, 90.9%, and 24.3%, respectively. This new scoring system would be useful for treatment decisions and prognostic prediction at initial diagnosis.

Utility of endoscopic ultrasound-guided fine-needle aspiration in pancreatic cancer patients who failed to obtain a pathological diagnosis in surgical exploration.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows for the analysis of diagnostic tissue specimens from various regions. For pancreatic tumors, especially un-resectable ones, how to obtain pathological confirmation is important for determining sub-sequent treatment. The purpose of this study is to investigate the clinical utility of EUS-FNA in patients who failed to obtain a pathological diagnosis in surgical exploration. Patients who underwent EUS-FNA due to unsuccessful biopsy in surgical exploration in our center were retrospectively reviewed. All of the patients were diagnosed with resectable disease before surgery but were found to be unresectable during surgery. The positive rate of pathological diagnosis of EUS-FNA was analyzed. A total of 11 patients were included in this study, among which 8 were males and 3 were females. The median age of the patients was 55 years (range, 48 to 73 years). The median lesion size was 34 mm (range, 25 to 44 mm). The median number of needle passes was 3 (range, 1 to 3). Two patients underwent biliary stent implantation while 3 patients underwent gastrojejunostomy before EUS-FNA. The technical success rate of EUS-FNA was 100% (11/11); 10 (90.9%, 10/11) samples were positive and 1 was negative (being inadequate). Intraoperative biopsy is the first choice diagnostic modality for unresectable pancreatic neoplasms. However, for patients who fail to obtain a pathological diagnosis in surgical exploration, EUS-FNA is still worth an attempt.

Usefulness of endoscopic ultrasound for acquiring the pathological diagnosis of gastrointestinal lymphoma

Background and study aimsThis study aims to assess the value of endoscopic ultrasound (EUS) for acquiring a pathological diagnosis of gastrointestinal lymphoma (GIL). Patients and methodsWe retrospectively reviewed all GIL patients who underwent EUS from November 2011 to July 2020 at Fudan University Shanghai Cancer Center. All patients with pathologically confirmed GIL were included. The characteristics of the lesions were recorded, and the efficacy for acquiring pathologic diagnosis between white light endoscopy (WLE) and EUS was analyzed. ResultsIn total, 404 patients with GIL who underwent EUS examination were included in this study. GIL was confirmed in 143 cases by after EUS judgment biopsy (AEJ biopsy), 11 cases by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), 293 cases by WLE biopsy, and 10 cases by surgical pathology for repeated negative pathologic results from EUS and WLE. Among all cases, 78.71% (318/404) were T1-T2, whereas 32.18% (130/404) were determined to have multiple lesions in the digestive tract wall. The positive rates of the WLE biopsy and AEJ biopsy of the involved gastric wall were 77.93% (293/376) and 89.38% (143/160), respectively. Twelve cases showed diffuse thickening of the gastric wall, and the total positive rate of EUS was 91.67% but 0% for WLE with this type of GIL. The total positive rate and positive rate during the first examination of EUS were all significantly higher than those of WLE. Moreover, 19.68% of the patients showed negative results during their WLE examination and then received a positive pathologic diagnosis upon EUS examination, but none had the opposite process. ConclusionsEUS was found to be a better tool for acquiring a pathological diagnosis of GIL than conventional WLE, especially for GIL similar to linitis plastica.