1.Cytokeratin (pan)-positive EWSR1/FUS::CREB fusion malignant tumor in abdominopelvic cavity: a clinicopathological and molecular analysis of four cases
Fenglin ZANG ; Yong WANG ; Xiyin WEI ; Yalei WANG ; Ye LUO ; Yuhong GUO ; Tingting DING
Chinese Journal of Pathology 2025;54(6):626-631
Objective:To investigate the clinicopathological and molecular genetic characteristics of pan cytokeratin (CKpan)-positive EWSR1/FUS::CREB fusion malignant tumors in abdominopelvic cavity.Methods:Four cases of malignant tumor with CKpan-positive EWSR1/FUS::CREB fusion were selected from January 2019 to July 2024 in the Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. Their clinical, pathological, and immunohistochemical characteristics were examined. Their molecular genetic characteristics were analyzed using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS).Results:Among the 4 patients, there were 2 males and 2 females, aged 44, 44, 48 and 66 years, respectively. The tumor sites included 1 case located between the stomach and transverse colon, 1 case on the serous surface of the gastric wall, 1 case in the transverse mesocolon, and 1 case in transverse mesocolon and small mesentery. The clinical manifestations were mostly abdominal distension and abdominal pain. The maximum diameter of the tumor in the surgical resection specimen was 3.5-8.5 cm. The tumor′s cut surface was grayish-white and gray-yellow in color, with medium consistency. Microscopically, the tumor cells were mainly composed of epithelioid tumor cells, and 2 of the tumors showed that tumor cells arranged in a solid sheet or multinodular pattern, and the cytoplasm of the tumor cells was abundant, lightly stained, and the boundaries were unclear, accompanied by the formation of capsules or microcapsules, and lymphocyte and plasma cell sleeves were seen. In one case, the pseudopapillary arrangement was present, and the tumor cells were radially distributed around the fibrovascular axis. In another case, it was arranged in a pseudoacinar pattern, and the nest was surrounded by slender reticular fibers. Immunohistochemistry showed that tumor cells expressed CKpan (4/4) and WT1 (4/4, including 1 focal positive). Vimentin, CK8/18, D2-40 and S-100 were expressed in various intensities, while Calretinin was locally positive or negative. FISH showed that 2 cases had EWSR1 break-apart and 2 cases had FUS break-apart. NGS confirmed the presence of EWSR1::CREM fusion (1 case) and FUS::CREM fusion (2 cases), respectively. Except for 1 recently diagnosed case, 3 cases were followed up: 1 patient died due to tumor recurrence and metastasis (overall survival was 33 months), and 2 patients survived (1 case had recurrence 58 months after surgery, and 1 case had no recurrence or metastasis after surgery).Conclusions:CKpan-positive EWSR1/FUS::CREB fusion malignant tumor is a rare malignancy tumor with undetermined classification that tends to occur in the abdominopelvic cavity and often involves the gastrointestinal tract. Molecular testing such as FISH and NGS is helpful for a definitive diagnosis.
2.Cytokeratin (pan)-positive EWSR1/FUS::CREB fusion malignant tumor in abdominopelvic cavity: a clinicopathological and molecular analysis of four cases
Fenglin ZANG ; Yong WANG ; Xiyin WEI ; Yalei WANG ; Ye LUO ; Yuhong GUO ; Tingting DING
Chinese Journal of Pathology 2025;54(6):626-631
Objective:To investigate the clinicopathological and molecular genetic characteristics of pan cytokeratin (CKpan)-positive EWSR1/FUS::CREB fusion malignant tumors in abdominopelvic cavity.Methods:Four cases of malignant tumor with CKpan-positive EWSR1/FUS::CREB fusion were selected from January 2019 to July 2024 in the Department of Pathology, Tianjin Medical University Cancer Hospital, Tianjin, China. Their clinical, pathological, and immunohistochemical characteristics were examined. Their molecular genetic characteristics were analyzed using fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS).Results:Among the 4 patients, there were 2 males and 2 females, aged 44, 44, 48 and 66 years, respectively. The tumor sites included 1 case located between the stomach and transverse colon, 1 case on the serous surface of the gastric wall, 1 case in the transverse mesocolon, and 1 case in transverse mesocolon and small mesentery. The clinical manifestations were mostly abdominal distension and abdominal pain. The maximum diameter of the tumor in the surgical resection specimen was 3.5-8.5 cm. The tumor′s cut surface was grayish-white and gray-yellow in color, with medium consistency. Microscopically, the tumor cells were mainly composed of epithelioid tumor cells, and 2 of the tumors showed that tumor cells arranged in a solid sheet or multinodular pattern, and the cytoplasm of the tumor cells was abundant, lightly stained, and the boundaries were unclear, accompanied by the formation of capsules or microcapsules, and lymphocyte and plasma cell sleeves were seen. In one case, the pseudopapillary arrangement was present, and the tumor cells were radially distributed around the fibrovascular axis. In another case, it was arranged in a pseudoacinar pattern, and the nest was surrounded by slender reticular fibers. Immunohistochemistry showed that tumor cells expressed CKpan (4/4) and WT1 (4/4, including 1 focal positive). Vimentin, CK8/18, D2-40 and S-100 were expressed in various intensities, while Calretinin was locally positive or negative. FISH showed that 2 cases had EWSR1 break-apart and 2 cases had FUS break-apart. NGS confirmed the presence of EWSR1::CREM fusion (1 case) and FUS::CREM fusion (2 cases), respectively. Except for 1 recently diagnosed case, 3 cases were followed up: 1 patient died due to tumor recurrence and metastasis (overall survival was 33 months), and 2 patients survived (1 case had recurrence 58 months after surgery, and 1 case had no recurrence or metastasis after surgery).Conclusions:CKpan-positive EWSR1/FUS::CREB fusion malignant tumor is a rare malignancy tumor with undetermined classification that tends to occur in the abdominopelvic cavity and often involves the gastrointestinal tract. Molecular testing such as FISH and NGS is helpful for a definitive diagnosis.
3.Computer-vision-based artificial intelligence for detection and recognition of instruments and organs during radical laparoscopic gastrectomy for gastric cancer: a multicenter study
Kecheng ZHANG ; Zhi QIAO ; Li YANG ; Tao ZHANG ; Fenglin LIU ; Dachuan SUN ; Tianyu XIE ; Lei GUO ; Canrong LU
Chinese Journal of Gastrointestinal Surgery 2024;27(5):464-470
Objective:To investigate the feasibility and accuracy of computer vision-based artificial intelligence technology in detecting and recognizing instruments and organs in the scenario of radical laparoscopic gastrectomy for gastric cancer.Methods:Eight complete laparoscopic distal radical gastrectomy surgery videos were collected from four large tertiary hospitals in China (First Medical Center of Chinese PLA General Hospital [three cases], Liaoning Cancer Hospital [two cases], Liyang Branch of Jiangsu Province People's Hospital [two cases], and Fudan University Shanghai Cancer Center [one case]). PR software was used to extract frames every 5–10 seconds and convert them into image frames. To ensure quality, deduplication was performed manually to remove obvious duplication and blurred image frames. After conversion and deduplication, there were 3369 frame images with a resolution of 1,920×1,080 PPI. LabelMe was used for instance segmentation of the images into the following 23 categories: veins, arteries, sutures, needle holders, ultrasonic knives, suction devices, bleeding, colon, forceps, gallbladder, small gauze, Hem-o-lok, Hem-o-lok appliers, electrocautery hooks, small intestine, hepatogastric ligaments, liver, omentum, pancreas, spleen, surgical staplers, stomach, and trocars. The frame images were randomly allocated to training and validation sets in a 9:1 ratio. The YOLOv8 deep learning framework was used for model training and validation. Precision, recall, average precision (AP), and mean average precision (mAP) were used to evaluate detection and recognition accuracy.Results:The training set contained 3032 frame images comprising 30 895 instance segmentation counts across 23 categories. The validation set contained 337 frame images comprising 3407 instance segmentation counts. The YOLOv8m model was used for training. The loss curve of the training set showed a smooth gradual decrease in loss value as the number of iteration calculations increased. In the training set, the AP values of all 23 categories were above 0.90, with a mAP of 0.99, whereas in the validation set, the mAP of the 23 categories was 0.82. As to individual categories, the AP values for ultrasonic knives, needle holders, forceps, gallbladders, small pieces of gauze, and surgical staplers were 0.96, 0.94, 0.91, 0.91, 0.91, and 0.91, respectively. The model successfully inferred and applied to a 5-minutes video segment of laparoscopic gastroenterostomy suturing.Conclusion:The primary finding of this multicenter study is that computer vision can efficiently, accurately, and in real-time detect organs and instruments in various scenarios of radical laparoscopic gastrectomy for gastric cancer.
4.Computer-vision-based artificial intelligence for detection and recognition of instruments and organs during radical laparoscopic gastrectomy for gastric cancer: a multicenter study
Kecheng ZHANG ; Zhi QIAO ; Li YANG ; Tao ZHANG ; Fenglin LIU ; Dachuan SUN ; Tianyu XIE ; Lei GUO ; Canrong LU
Chinese Journal of Gastrointestinal Surgery 2024;27(5):464-470
Objective:To investigate the feasibility and accuracy of computer vision-based artificial intelligence technology in detecting and recognizing instruments and organs in the scenario of radical laparoscopic gastrectomy for gastric cancer.Methods:Eight complete laparoscopic distal radical gastrectomy surgery videos were collected from four large tertiary hospitals in China (First Medical Center of Chinese PLA General Hospital [three cases], Liaoning Cancer Hospital [two cases], Liyang Branch of Jiangsu Province People's Hospital [two cases], and Fudan University Shanghai Cancer Center [one case]). PR software was used to extract frames every 5–10 seconds and convert them into image frames. To ensure quality, deduplication was performed manually to remove obvious duplication and blurred image frames. After conversion and deduplication, there were 3369 frame images with a resolution of 1,920×1,080 PPI. LabelMe was used for instance segmentation of the images into the following 23 categories: veins, arteries, sutures, needle holders, ultrasonic knives, suction devices, bleeding, colon, forceps, gallbladder, small gauze, Hem-o-lok, Hem-o-lok appliers, electrocautery hooks, small intestine, hepatogastric ligaments, liver, omentum, pancreas, spleen, surgical staplers, stomach, and trocars. The frame images were randomly allocated to training and validation sets in a 9:1 ratio. The YOLOv8 deep learning framework was used for model training and validation. Precision, recall, average precision (AP), and mean average precision (mAP) were used to evaluate detection and recognition accuracy.Results:The training set contained 3032 frame images comprising 30 895 instance segmentation counts across 23 categories. The validation set contained 337 frame images comprising 3407 instance segmentation counts. The YOLOv8m model was used for training. The loss curve of the training set showed a smooth gradual decrease in loss value as the number of iteration calculations increased. In the training set, the AP values of all 23 categories were above 0.90, with a mAP of 0.99, whereas in the validation set, the mAP of the 23 categories was 0.82. As to individual categories, the AP values for ultrasonic knives, needle holders, forceps, gallbladders, small pieces of gauze, and surgical staplers were 0.96, 0.94, 0.91, 0.91, 0.91, and 0.91, respectively. The model successfully inferred and applied to a 5-minutes video segment of laparoscopic gastroenterostomy suturing.Conclusion:The primary finding of this multicenter study is that computer vision can efficiently, accurately, and in real-time detect organs and instruments in various scenarios of radical laparoscopic gastrectomy for gastric cancer.
5.Pathological diagnosis of gastric adenocarcinoma with enteroblastic differentiation in endoscopic biopsies
Fenglin ZANG ; Yong WANG ; Ruijun TANG ; Xiyin WEI ; Yuhong GUO ; Yalei WANG ; Tingting DING
Chinese Journal of Clinical and Experimental Pathology 2024;40(12):1282-1287
Purpose To investigate the diagnosis and the clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation(GAED)in biopsy,and to provide data for the pathological evaluation of endoscopic resection of early gastric cancer.Methods 26 GAED biopsy specimens were collected,and the clinicopathological features were ana-lyzed by re-reading slides,immunohistochemistry and with paired radical surgery specimen.Results Serum AFP was de-tected in 16 patients before operation,and 11 patients(68.75%)were elevated.The initial diagnosis rate and follow-up rate of GAED in biopsy were 42.31%and 92.31%.Among the biopsy specimens,5 cases of GAED were accompanied by conventional gastric adenocarcinoma,and the positive rates of SALL4 and Glypican-3 were high(both 78.57%).The accom-panying cancers in the radical resection specimens include con-ventional gastric adenocarcinoma,hepatoid adenocarcinoma,and low adhesion adenocarcinoma,with the positive rate of SALL4(81.25%),Glypican-3(75%),and AFP(62.5%).GAED was more prone to deep invasion of the gastric wall and lymph node metastasis than conventional gastric adenocarcinoma.A-mong the 6 cases of early GAED,3 cases(50%)were lymph node-positive.Conclusion GAED is easy to be missed in biop-sy,and more attention should be paid to its tissue morphology and immunophenotype.GAED needs to be excluded in the histo-logical type of endoscopic curative resection of early gastric canc-er.
6.Pathological diagnosis of gastric adenocarcinoma with enteroblastic differentiation in endoscopic biopsies
Fenglin ZANG ; Yong WANG ; Ruijun TANG ; Xiyin WEI ; Yuhong GUO ; Yalei WANG ; Tingting DING
Chinese Journal of Clinical and Experimental Pathology 2024;40(12):1282-1287
Purpose To investigate the diagnosis and the clinicopathological characteristics of gastric adenocarcinoma with enteroblastic differentiation(GAED)in biopsy,and to provide data for the pathological evaluation of endoscopic resection of early gastric cancer.Methods 26 GAED biopsy specimens were collected,and the clinicopathological features were ana-lyzed by re-reading slides,immunohistochemistry and with paired radical surgery specimen.Results Serum AFP was de-tected in 16 patients before operation,and 11 patients(68.75%)were elevated.The initial diagnosis rate and follow-up rate of GAED in biopsy were 42.31%and 92.31%.Among the biopsy specimens,5 cases of GAED were accompanied by conventional gastric adenocarcinoma,and the positive rates of SALL4 and Glypican-3 were high(both 78.57%).The accom-panying cancers in the radical resection specimens include con-ventional gastric adenocarcinoma,hepatoid adenocarcinoma,and low adhesion adenocarcinoma,with the positive rate of SALL4(81.25%),Glypican-3(75%),and AFP(62.5%).GAED was more prone to deep invasion of the gastric wall and lymph node metastasis than conventional gastric adenocarcinoma.A-mong the 6 cases of early GAED,3 cases(50%)were lymph node-positive.Conclusion GAED is easy to be missed in biop-sy,and more attention should be paid to its tissue morphology and immunophenotype.GAED needs to be excluded in the histo-logical type of endoscopic curative resection of early gastric canc-er.
7.Characteristics and management approaches of patients admitted to isolation ward in public general hospitals under regular epidemic prevention and control of coronavirus disease 2019
Chunxia GUO ; Fenglin WANG ; Yuxiong WENG ; Lixia WANG ; Hua WANG ; Wei LI ; Xin ZHENG ; Jiahong XIA
Chinese Journal of Infectious Diseases 2023;41(9):588-592
Objective:To investigate the characteristics and management approaches of patients admitted to the isolation wards in public general hospitals under regular epidemic prevention and control measures of coronavirus disease 2019 (COVID-19).Methods:All patients admitted to the isolation ward in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from May 14, 2020 to April 15, 2021 were enrolled, and the general information, illness severity, preliminary diagnosis and transfer department of the patients were analyzed.Results:Out of the 2 292 patients admitted to the isolation ward, critical patients accounted for 34.34% (787 cases), surgical system patients accounted for 80.06% (1 835 cases) and internal medicine system patients accounted for 19.94% (457 cases), fever patients accounted for 11.30% (259 cases). All patients successfully completed COVID-19 screening, and no COVID-19 patients were detected. Among the total enrolled patients, 2 201 patients were promptly transferred to the corresponding departments for further treatment, with an average transfer time of 0.55 day. The remaining 91 patients were discharged from the isolation ward with an average hospitalization stay of 1.27 days.Notably, there were no COVID-19 cross-infection occurred between patients and medical staff in the isolation ward.Conclusions:Scientific and efficient management of isolation wards ensure timely screening and effective treatment for patients, and simultaneously achieving "zero" infection for both medical staff and patients.
8.Mismatch repair protein expression of colorectal cancer: a retrospective analysis of 3 428 cases
Ying LIU ; Yuhong GUO ; Ye LUO ; Lin SUN ; Shuai ZHAO ; Bing SHAO ; Fenglin ZANG ; Zhiqiang QIU ; Baocun SUN ; Yan SUN
Chinese Journal of Pathology 2021;50(4):369-375
Objective:To analyze the expression of mismatch repair (MMR) proteins in colorectal cancers (CRC) and to evaluate the feasibility and potential pitfalls of immunohistochemistry (IHC) analysis for MMR.Methods:The IHC sections for MMR proteins were reviewed in 3 428 cases of resected CRC without neoadjuvant therapy at Tianjin Medical University Cancer Institute and Hospital from July 2014 to October 2018. For the cases with unclear MMR IHC results during the initial review, IHC staining was repeated and microsatellite instability (MSI) analysis was performed. Relationships between the expression of MMR proteins and MSI status as well as the clinicopathological parameters were analyzed.Results:IHC staining for MMR was repeated in 28 (0.8%) cases due to poor quality of original IHC sections. Inconsistent results between the original diagnosis and re-diagnosis were found in 119 (3.5%) cases, mainly resulting from PMS2 and MLH1. Finally, 261 (7.6%) cases of CRC showed mismatch repair deficiency (dMMR), mainly from the deficiency of both MLH1 and PMS2 (43.3%,113/261). In the 14 cases with MSI results, the concordant of MSI and MMR was 13 cases. In the 29 dMMR cases with next generation sequencing (NGS) results, the concordant of MSI-high and dMMR was 93.1%(27/29). The cases with inconsistent results between MSI and MMR showed negative expression of MSH6 or PMS2. Twenty-one CRC showed negative expression of MLH1 and partially positive (or weak positive) expression of PMS2, or negative expression of MSH2 and partially positive (or weak positive) expression of MSH6. Among the 19 cases with MSI results, 16 cases were MSI-high, two cases were MSI-low, and one case was microsatellite stable. Compared with mismatch repair proficiency (pMMR), dMMR was more frequently detected in female patients younger than 50 years old, with family history, at early stage (Ⅰ-Ⅱ) CRC, and in the tumors from right colon,with poor differentiation, or mucinous adenocarcinoma/signet ring cell carcinoma (all P<0.05). Conclusions:At present, IHC staining is a clinically effective and convenient method to detect MMR expression, but the operating process and result assessment remain variable and need to be standardized. MSI analysis can be performed in the difficult-to-evaluate cases for MMR to enhance prognostic evaluation and treatment option.
9.Clinical value of anti-oxidative stress biomarkers for diagnosing in-stent restenosis and in-stent reocclusion after coronary stent implantation in advanced-aged patients
Fenglin ZHANG ; Changjiang PAN ; Tao LIU ; Tao GONG ; Xiang FANG ; Youdong HU ; Ying CHEN ; Hualan ZHOU ; Dianxuan GUO ; Xia LI
Chinese Journal of Geriatrics 2019;38(2):119-123
Objective To study the clinical value of anti-oxidative stress biomarkers for diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.Methods A total of 72 advanced-aged patients with in-stent restenosis and in-stent reocclusion after coronary stent implantation were successively recruited in this retrospective study from February 2010 to November 2017.Changes in serum superoxide dismutase 3(SOD3),nitric oxide(NO),endothelial cell nitric oxide synthase(eNOS)and malondialdehyde(MDA)levels were measured.Results Serum 1evels of SOD3,NO and eNOS decreased and serum MDA levels were elevated in advanced-aged patients with in-stent restenosis.There were significant differences in serum levels of SOD3,NO,eNOS and MDA between the advanced-aged patients without in-stent restenosis and the advanced-aged patients with multivessel in-stent restenosis or reocclusion[(20.0±3.2) × 103U/L vs.(10.9±3.9) ×103U/L,(61.2±14.2)μmol/L vs.(28.3±17.2)μmol/L,(75.9±24.7)ng/L vs.(33.0±119.6)ng/L,(2.2±1.4)nmol/L vs.(11.7±3.1)nmol/L,respectively,P<0.01].Patients with 50-69% restenosis had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with 100% restenosis[(21.3 ± 2.9) × 103 U/L vs.(10.3 ± 4.0) × 103 U/L,(59.7 ± 16.7) μmol/L vs.(38.3 ±16.3)μmol/L,(74.5±21.1)ng/L vs.(41.9±26.8)ng/L,(2.6±3.9 nmol/L)vs.(10.1±3.1)nmol/L,respectively,P < 0.01].Patients with left ventricular ejection fraction (LVEF) ≥ 55 % had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with LVEF<30% [(21.0±4.1) × 103 U/L vs.(5.3±1.9) × 103 U/L,(60.1 ± 14.2)μmol/L vs.(29.0± 13.2)μmol/L,(74.7±25.1)ng/L vs.(39.3 ± 20.3) ng/L,(2.3 ± 1.5) nmol/L vs.(10.0 ± 3.9) nmol/L,respectively,P <0.01].Serum levels of SOD3,NO and eNOS were higher and MDA levels were lower in patients with New York Heart Association(NYHA)Class Ⅰ than in patients with NYHA Class Ⅳ[(22.1±3.5)×103U/L vs.(9.7±2.9) × 103 U/L,(62.9± 13.9)μmol/L vs.(24.9± 13.3)μmol/L,(76.7±26.7) ng/L vs.(41.9±21.5)ng/L,(2.7± 1.9)nmol/L vs.(8.7±3.8)nmol/L,respectively,P<0.01].Conclusions Serum level changes of anti-oxidative stress biomarkers such as SOD3,NO and eNOS may have clinical value in diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.
10.Effects of epinephrine and phenylephrine on evoked potentials in a rat model of acute hemorrhagic shock
Fenglin GUO ; Xiangyang GUO ; Jun WANG
Chinese Journal of Anesthesiology 2018;38(9):1069-1072
Objective To evaluate the effects of epinephrine and phenylephrine on evoked potentials in a rat model of acute hemorrhagic shock. Methods Eighteen SPF healthy male Sprague-Dawley rats, aged 11 weeks, weighing 250-350 g, were divided into 3 groups ( n=6 each) using a random number table meth-od: acute hemorrhagic shock group ( HS group) , epinephrine group ( E group) and phenylephrine group ( P group). The animals were anesthetized with intraperitoneal 10% chloral hydrate 300 mg∕kg and tracheos-tomized, and spontaneous breathing was kept. Acute hemorrhagic shock was induced by withdrawing 40% of the blood volume from the right internal jugular vein. Epinephrine 2 μg·kg-1 ·min-1 ( 0. 01 mg∕ml, 0. 3 ml) and phenylephrine 20μg·kg-1·min-1 (0. 1 mg∕ml, 0. 3 ml) were intravenously infused after the end of blood letting in E and P groups, respectively. Mean arterial pressure ( MAP ) , somatosensory evoked po-tential (SSEP) and motor evoked potentials (MEP) were recorded before blood letting, at the time of with-drawing 20%of the blood volume, at the end of blood letting, and at 3 min after administration ( at the corre-sponding time point in group HS) . Results The MAP and amplitudes of MEP and SSEP were significantly decreased at the end of blood letting than at the time of withdrawing 20% of the blood volume in three groups (P<0. 05). Compared with HS group, the MAP and amplitudes of MEP and SSEP were significantly in-creased at 3 min after administration in E group, and the MAP was increased at 3 min after administration ( P<0. 05 or 0. 01) , and no significant change was found in amplitudes of MEP and SSEP in P group ( P>0. 05) . Conclusion Epinephrine exerts no effect on evoked potential monitoring, however, phenylephrine affects the accuracy of evoked potential monitoring in a rat model of acute hemorrhagic shock.

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