PSMD14 is a novel prognostic marker and therapeutic target in osteosarcoma.

BACKGROUND: Osteosarcoma is a bone tumor that is characterized by high malignancy and a high mortality rate, and that originates from primitive osteoblastic mesenchymal cells and is most common in rapidly growing long bones. PSMD14, also known as RPN11 or POH1, is a member of the JAMM isopeptidase family, which is able to remove the substrate protein ubiquitination label, thereby regulating the stability and function of the substrate protein. In this study, we explored the expression and potential biological significance of the PSMD14 deubiquitinating enzyme in osteosarcoma. METHODS: Immunohistochemical methods were used to detect the expression of PSMD14 in biopsies of 91 osteosarcoma patients, and the specimens were classified into high and low PSMD14 expression groups. The correlation between PSMD14 expression and clinical indicators and prognosis was compared.SiRNA was used to downregulate PSMD14 in two osteosarcoma cell lines (HOS and SJSA-1), and the effects of downregulation of PSMD14 on the viability, proliferation, and invasion ability of osteosarcoma cells were analyzed. RESULTS: We identified significant differences in recurrence, metastasis, and survival time of the osteosarcoma patients on the basis of PSMD14 expression. High expression of PSMD14 in osteosarcoma patients was associated with a low survival rate and high risk of metastasis and recurrence. Down-regulation of PSMD14 inhibited the viability, proliferation, and invasiveness of osteosarcoma cell lines. CONCLUSIONS: PSMD14 may be a new prognostic marker and therapeutic target for osteosarcoma.

Impact of Postoperative Radiotherapy on the Prognosis of Early-Stage (pT1-2N0M0) Oral Tongue Squamous Cell Carcinoma.

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.

Fe-Mn binary oxides improve the methanogenic performance and reduce the environmental health risks associated with antibiotic resistance genes during anaerobic digestion.

Increasing evidence indicates that metal oxides can improve the methanogenic performance during anaerobic digestion (AD) of piggery wastewater. However, the impacts of composite metal oxides on the methanogenic performance and risk of antibiotic resistance gene (ARG) transmission during AD are not fully understood. In this study, different concentrations of Fe-Mn binary oxides (FMBO at 0, 250, 500, and 1000 mg/L) were added to AD to explore the effects of FMBO on the process. The methane yield was 7825.1 mL under FMBO at 250 mg/L, 35.2% higher than that with FMBO at 0 mg/L. PICRUSt2 functional predictions showed that FMBO promoted the oxidation of acetate and propionate, and the production of methane from the substrate, as well as increasing the abundances of most methanogens and genes encoding related enzymes. Furthermore, under FMBO at 250 mg/L, the relative abundances of 14 ARGs (excluding tetC and sul2) and four mobile gene elements (MGEs) decreased by 24.7% and 55.8%, respectively. Most of the changes in the abundances of ARGs were explained by microorganisms, especially Bacteroidetes (51.20%), followed by MGEs (11.98%). Thus, the methanogenic performance of AD improved and the risk of horizontal ARG transfer decreased with FMBO, especially at 250 mg/L.

Case Report: Complete pathological remission of human chorionic gonadotrophin-producing gallbladder carcinoma with multiple liver metastases after treatment with chemotherapy plus an immune checkpoint inhibitor.

Background: Gallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy. Case presentation: We herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated ß-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC. Conclusion: chemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.

Integrase Interactor 1 (INI1) Deficiency in a Lung Cancer Patient Presents Nonresponse to Immunotherapy and Tazemetostat: A Case Report.

Integrase interactor 1 (INI1)-deficient lung cancer is extremely rare, often with poor prognosis, and lacks effective treatment. Previous studies have reported the efficacy of immunotherapy and enhancer of the zeste homolog 2 (EZH2) inhibitor tazemetostat in various types of INI1-deficient tumors, such as sarcomas. However, the effectiveness of these treatments in INI1-deficient lung cancer has not yet been verified. We hereby report a case of a patient who was diagnosed with advanced squamous lung cancer with INI1 deficiency and received chemotherapy, immunotherapy, and tazemetostat treatments successively. The patient showed optimal response in the initial chemotherapy combined with anti-programmed cell death protein 1 (PD-1) immunotherapy, made rapid progress in the subsequent stage of maintenance immunotherapy, and showed nonresponse to tazemetostat. To the best of our knowledge, this is the first case of a lung cancer patient with INI1 deficiency who received tazemetostat treatment.

Clinicopathologic Features of Noninvasive Inverted Urothelial Papillary Tumor.

OBJECTIVES: Clinicopathologic features and recurrence rates of inverted noninvasive urothelial papillary tumors have been poorly characterized to date with few larger studies evaluating long-term outcomes. The spectrum of histomorphology, clinical features, and prognosis of inverted lesions of the urinary bladder are retrospectively reviewed. METHODS: Archived paraffin-embedded urothelial tumor samples from patients diagnosed with inverted urothelial papillary lesions between January 2005 and June 2020 were collated. A matched control population of patients with exophytic papillary lesions of the urothelium diagnosed during the same time period was randomly selected. The conventional clinicopathologic features of inverted urothelial papillary tumor were evaluated retrospectively and patient demographics, tumor characteristics, recurrence, and survival information were recorded. RESULTS: Lower recurrence rates were observed for inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP) relative to papillary urothelial neoplasms of low malignant potential and for low-grade papillary urothelial carcinoma with an inverted growth pattern (LG-PUCI) relative to low-grade papillary urothelial carcinomas. No recurrence was found among the inverted urothelial papilloma cases. The 2- and 5-year disease-free survival rates were 100.0% and 85.2% for IPUNLMP patients; 94.4% and 80.4% for papillary urothelial neoplasms of low malignant potential; 89.5% and 82.0% for LG-PUCI; 73.7% and 54.6% for low-grade papillary urothelial carcinoma; 40.0% and 20.0% for high-grade papillary urothelial carcinoma with an inverted growth pattern patients and 26.7% and 26.7% for high-grade papillary urothelial carcinoma. Multivariate Cox regression analysis of IPUNLMP and LG-PUCI/high-grade papillary urothelial carcinoma with an inverted growth pattern indicated that tumor number (hazard ratio=4.356; 95% CI: 1.145-16.570; P =0.031) was a powerful prognostic factor for disease-free survival. CONCLUSION: Noninvasive, papillary urothelial lesions of the bladder tend to have lower recurrence and a better outcome if an inverted growth pattern is shown.

Reductions in abundances of intracellular and extracellular antibiotic resistance genes by SiO2 nanoparticles during composting driven by mobile genetic elements.

Applying exogenous additives during the aerobic composting of livestock manure is effective for slowing down the spread of antibiotic resistance genes (ARGs) in the environment. Nanomaterials have received much attention because only low amounts need to be added and they have a high capacity for adsorbing pollutants. Intracellular ARGs (i-ARGs) and extracellular ARGs (e-ARGs) comprise the resistome in livestock manure but the effects of nanomaterials on the fates of these different fractions during composting are still unclear. Thus, we investigated the effects of adding SiO2 nanoparticles (SiO2NPs) at four levels (0 (CK), 0.5 (L), 1 (M), and 2 g/kg (H)) on i-ARGs, e-ARGs, and the bacterial community during composting. The results showed that i-ARGs represented the main fraction of ARGs during aerobic composting of swine manure, and their abundance was lowest under M. Compared with CK, M increased the removal rates of i-ARGs and e-ARGs by 17.9% and 100%, respectively. SiO2NPs enhanced the competition between ARGs hosts and non-hosts. M optimized the bacterial community by reducing the abundances of co-hosts (Clostridium_sensu_stricto_1, Terrisporobacter, and Turicibacter) of i-ARGs and e-ARGs (by 96.0% and 99.3%, respectively) and killing 49.9% of antibiotic-resistant bacteria. Horizontal gene transfer dominated by mobile genetic elements (MGEs) played a key role in the changes in the abundances of ARGs. i-intI1 and e-Tn916/1545 were key MGEs related closely to ARGs, and the maximum decreases of 52.8% and 100%, respectively, occurred under M, which mainly explained the decreased abundances of i-ARGs and e-ARGs. Our findings provide new insights into the distribution and main drivers of i-ARGs and e-ARGs, as well as demonstrating the possibility of adding 1 g/kg SiO2NPs to reduce the propagation of ARGs.

Axillary response and outcome in breast cancer patients after neoadjuvant treatment: The role of radiotherapy in reducing recurrence in ypN0 patients with initially cN+ stage.

Objective: We aim to explore the clinicopathological features associated with axillary node response and recurrence in breast cancer patients undergoing neoadjuvant treatment (NAT). Methods: We retrospectively reviewed the medical records of 486 stage I to III breast cancer patients who received NAT and surgery between 2016 and 2021. Results: A total of 486 cases were reviewed and 154 (31.7%) patients achieved breast pathological complete response (pCR) (ypT0/Tis). Of the 366 cases with initially cN+, 177 (48.4%) cases reach ypN0. Breast pCR is in high accordance to axillary pCR (81.5%). Hormone receptor (HR)-/HER2+ breast cancer patients have the highest axillary pCR rate (78.3%). Patients achieve axillary pCR have a significantly better disease-free survival (DFS) (P=0.0004). Further analysis reveals that the DFS of ypN0 and ypN1 cases are similar (P=0.9049). Moreover, DFS in patients with ypN0 (P<0.0001) and ypN1 (P<0.0001) is significantly better than that in patients with ypN2-3. For post-mastectomy ypN0 cases, radiation could only improve DFS in patients with initially cN+ stage (P=0.0499). Multivariate Cox regression analysis shows that radiation is an independent factor to improve DFS (Hazard ratio (HR): 0.288(0.098-0.841), P=0.0230). Radiation does not improve DFS in pre-cN0/ypN0 patients (P=0.1696). Conclusion: Axillary pCR rate is higher than breast pCR rate. HR-/HER2+ patients have the highest axillary pCR rate. Axillary pCR is associated with better DFS. Radiation could further improve DFS in ypN0 patients with initially positive nodal disease.

Primary hepatopancreatobiliary lymphoma: Pathogenesis, diagnosis, and management.

Primary hepatopancreatobiliary lymphoma (PHPBL) is extremely rare, which is defined as a lympho-proliferative disease confined to the hepatobiliary system and pancreas without any involvement of lymph nodes, bone marrow, or other organs. The clinical and imaging manifestations of PHPBL are variable and non-special, which are akin to those of tumors of the hepatobiliary and pancreatic systems. The overall prognosis and management of PHPBL differ from those of other tumors in the hepatobiliary system and pancreas. Proper diagnosis and prompt treatment are essential for improving clinical outcomes. Due to its rarity, the optimal treatment has not been issued. However, combination chemotherapy is considered as a standard treatment for them. This review provides an overview of the pathogenesis, diagnosis, pathology, and management of PHPBL and offers clinicians the diagnosis and management schedule for PHPBL.

Comprehensive Clinical Analysis of Gallbladder Neuroendocrine Neoplasms: A Large-Volume Multicenter Study During One Decade.

BACKGROUND: This study aimed to comprehensively investigate the clinicopathologic characteristics and therapeutic situations of gallbladder neuroendocrine neoplasms (GB-NENs) in the real world via a multicenter, large-scale cohort study. METHODS: The study searched for patients in 143 hospitals in China and enrolled 154 patients with GB-NENs diagnosed in 40 hospitals between 2004 and 2021. Clinicopathologic characteristics and therapeutic approaches were analyzed retrospectively. RESULTS: The median age at the initial diagnosis of the patients with GB-NENs was 63 years (range 33-83 years), and 61.7% of the patients were women. Tumor-node-metastasis staging classified 92 patients as stage 3 or above. Based on the 2019 World Health Organization classification, 96 cases (62.3%) were confirmed pathologically as poorly differentiated neuroendocrine carcinomas, 13 cases (8.4%) as well-differentiated neuroendocrine tumors, and 45 cases as mixed neuroendocrine-non-neuroendocrine neoplasms. The liver was the most frequent metastatic site. Immunohistochemistry showed that synaptophysin was most frequently positive (80.4%), followed by chromogranin A (61.7%), and CD56 (58.4%). Computed tomography and magnetic resonance imaging showed more common clear boundaries (25/39 cases) and invasive growth features (27 cases). None of these cases had an accurate diagnosis before surgery, with a misdiagnosis rate of 100%. Surgical resection is the main treatment, and platinum-based chemotherapeutic regimens were preferred as adjuvant therapies for patients with GB-NENs. The available survival data for 74 patients showed an overall survival rate of 59% at 1 year, 33% at 3 years, and 29% at 5 years. No significant difference was found between the patients treated with and those treated without adjuvant chemotherapy. CONCLUSIONS: Gallbladder neuroendocrine neoplasms have high malignancy and a poor prognosis. Importantly, this large-scale cohort study significantly improves our understanding of GB-NENs and will benefit the exploration of its mechanism and treatment modes. Further investigation is necessary to explore the management of this disease.

Successful treatment of pancreatic accessory splenic hamartoma by laparoscopic spleen-preserving distal pancreatectomy: A case report.

BACKGROUND: Pancreatic accessory spleen (PAS) is an uncommon congenital abnormality of the spleen. Spleen hamartoma (SH) is also rare. Moreover, hamartoma in the PAS has not been reported thus far. We report the first case here. CASE SUMMARY: A 26-year-old male presented with a one-month history of left upper quadrant abdominal pain, and computerized tomography (CT) examination suggested a mass in the pancreas tail. The patient then attended our hospital for diagnosis and treatment. Ultrasonography, CT, and magnetic resonance imaging revealed a solid mass with cystic degeneration growing from the tail of the pancreas. The tumor marker carbohydrate antigen 19-9 (CA19-9) increased to 96.7 U/mL (normal range 0-37 U/mL). An epidermoid cyst in a PAS was considered preoperatively. However, a malignant tumor cannot be ruled out. We performed laparoscopic surgery, and two pancreatic masses were found growing from the pancreatic tail. The two masses were so closely connected that preoperative imaging examinations suggested only one mass. We carefully isolated the masses from the splenic artery and vein. A laparoscopic spleen-preserving distal pancreatectomy was successfully performed. On pathological examination, the masses were well-defined, homogeneous red-tan, 4 × 3, and 4.5 × 1.5 in size, respectively. One of them was cystically degenerated. On microscopical examination, the mass contained unorganized small slit-like vascular channels enclosing red blood cells and lined with plump endothelial cells. No area of cytologic atypia was identified. Focal lymphoid aggregates were found in the intravascular areas. White pulp or fibrosis was not observed. The final diagnosis was pancreatic accessory SH with cystic degeneration. After the operation, CA19-9 was reduced to normal. The patient recovered well, and the 34-mo follow-up period was uneventful. CONCLUSION: Here, we report the first case of pancreatic accessory SH. A laparoscopic spleen-preserving distal pancreatectomy was successfully performed. The patient recovered well and had a good prognosis.

Liver cancer heterogeneity modeled by in situ genome editing of hepatocytes.

Mechanistic study and precision treatment of primary liver cancer (PLC) are hindered by marked heterogeneity, which is challenging to recapitulate in any given liver cancer mouse model. Here, we report the generation of 25 mouse models of PLC by in situ genome editing of hepatocytes recapitulating 25 single or combinations of human cancer driver genes. These mouse tumors represent major histopathological types of human PLCs and could be divided into three human-matched molecular subtypes based on transcriptomic and proteomic profiles. Phenotypical characterization identified subtype- or genotype-specific alterations in immune microenvironment, metabolic reprogramming, cell proliferation, and expression of drug targets. Furthermore, single-cell analysis and expression tracing revealed spatial and temporal dynamics in expression of pyruvate kinase M2 (Pkm2). Tumor-specific knockdown of Pkm2 by multiplexed genome editing reversed the Warburg effect and suppressed tumorigenesis in a genotype-specific manner. Our study provides mouse PLC models with defined genetic drivers and characterized phenotypical heterogeneity suitable for mechanistic investigation and preclinical testing.

Successful treatment of pancreatic schwannoma by enucleation: A case report.

RATIONALE: Pancreatic schwannomas are extremely rare and are difficult to diagnose preoperatively. Over the past 50 years, only 96 cases of pancreatic schwannoma have been reported in English literature. Herein, we report a case of pancreatic schwannoma treated with enucleation. PATIENT CONCERNS: A 66-year-old woman visited a local hospital due to ventosities. Ultrasonography and computed tomography revealed a pancreatic mass. She visited our hospital for further diagnosis and treatment. DIAGNOSIS AND INTERVENTIONS: Magnetic resonance imaging revealed a tumor in the pancreatic body, and a solid pseudopapillary tumor was considered preoperatively. During the surgery, a pancreatic mass was found growing in the pancreatic body and tail. A successful tumor enucleation was performed. The mass was 7 × 6 × 3 cm in size with a thin capsule. Pathological examination revealed that the tumor was mainly composed of spindle-shaped cells with a palisading arrangement and no atypia. Both hypercellular and hypocellular areas were visible. Immunohistochemical staining showed that protein S-100 was strongly positive. The tumor was diagnosed as a benign schwannoma originating from the pancreatic body and tail. OUTCOMES: Postoperatively, the patient showed good recovery. During the 24-month follow-up period, the patient remained well and free of complications. LESSONS: Pancreatic schwannomas are extremely rare and difficult to diagnose using imaging examinations. Enucleation is a safe and efficacious treatment for exophytic pancreatic schwannomas.

Dynamic profiling of immune microenvironment during pancreatic cancer development suggests early intervention and combination strategy of immunotherapy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has little response to immune checkpoint inhibitors. An in-depth understanding of the immune microenvironment from a comprehensive and dynamic perspective is critical to generate effective therapeutic strategies for PDAC. METHODS: Using mass cytometry and immunohistochemistry, we explored the dynamic changes of tumor-infiltrating immune cells during the development of PDAC in a genetically engineered mouse model (KrasG12D/+; Trp53R172H/+; Pdx1-cre) and human specimens. PD-L1-/- mice were crossed with KrasG12D/+; TgfßR2flox/flox; Ptf1a-cre mice to achieve early depletion of PD-L1 in pancreatic cancer. Combination therapy of Arginase-1 (Arg-1) inhibitor and anti-PD-1 mAb was validated in syngeneic mouse models. FINDINGS: Two different stages of immunosuppression with unique features were observed in both mouse model and human specimens. Early stage of immunosuppression featured highly abundant Tregs during acinar-to-ductal metaplasia, despite of a prominent and continuous presence of effector lymphocytes. The differentiation/activation branch of Ly-6C+ monocytes changed from a BST2+/MHC-II+ phenotype to an Arg-1+ phenotype over time during PDAC development. The late stage of immunosuppression thus featured the presence of a large number of myeloid suppressive cells together with a significant reduction of effector lymphocytes. Removal of PD-L1 from the beginning efficiently triggered anti-tumor immunity and significantly prolonged survival in PDAC-developing mice. Targeting Arg1+ macrophages with an Arg-1 inhibitor synergized with anti-PD-1 immunotherapy and led to PDAC-specific immune memory. INTERPRETATION: By demonstrating the coevolution of histopathology and immunology in PDAC, this study highlights the necessity and value of early intervention and combinational approach in leveraging immunotherapy to treat pancreatic cancer. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Quantitative evaluation of hepatic steatosis using novel ultrasound technology normalized local variance (NLV) and its standard deviation with different ROIs in patients with metabolic-associated fatty liver disease: a pilot study.

PURPOSE: The purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard. METHODS: We prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure. RESULTS: The distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5-33%)/ moderate (> 33-66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: - 0.449, p = 0.008; - 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038). CONCLUSION: The NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value.

Radiomics Analysis of Contrast-Enhanced CT for the Preoperative Prediction of Microvascular Invasion in Mass-Forming Intrahepatic Cholangiocarcinoma.

BACKGROUND: Microvascular invasion (MVI) has been shown to be closely associated with postoperative recurrence and metastasis in patients with intrahepatic cholangiocarcinoma (ICC). We aimed to develop a radiomics prediction model based on contrast-enhanced CT (CECT) to distinguish MVI in patients with mass-forming ICC. METHODS: 157 patients were included and randomly divided into training (n=110) and test (n=47) datasets. Radiomic signatures were built based on the recursive feature elimination support vector machine (Rfe-SVM) algorithm. Significant clinical-radiologic factors were screened, and a clinical model was built by multivariate logistic regression. A nomogram was developed by integrating radiomics signature and the significant clinical risk factors. RESULTS: The portal phase image radiomics signature with 6 features was constructed and provided an area under the receiver operating characteristic curve (AUC) of 0.804 in the training and 0.769 in the test datasets. Three significant predictors, including satellite nodules (odds ratio [OR]=13.73), arterial hypo-enhancement (OR=4.31), and tumor contour (OR=4.99), were identified by multivariate analysis. The clinical model using these predictors exhibited an AUC of 0.822 in the training and 0.756 in the test datasets. The nomogram combining significant clinical factors and radiomics signature achieved satisfactory prediction efficacy, showing an AUC of 0.886 in the training and 0.80 in the test datasets. CONCLUSIONS: Both CECT radiomics analysis and radiologic factors have the potential for MVI prediction in mass-forming ICC patients. The nomogram can further improve the prediction efficacy.

Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study.

OBJECTIVE: We investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC). METHODS: In this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers. RESULTS: Among 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6-11.4) and the median OS was 17.7 months (95% CI: not estimable). CONCLUSIONS: Lenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR2100044476.

Primary cystic and solid neuroendocrine tumor of the retroperitoneum: A case report.

RATIONALE: Primary neuroendocrine tumors (NETs) of the retroperitoneum are extremely rare. The purpose of this case report is to highlight the unusual growth pattern and radiologic features of primary retroperitoneal NETs. PATIENT CONCERNS: A 46-year-old woman was found to have a retroperitoneal cystic and solid mass during a physical checkup. DIAGNOSES: The mass was mainly multiseptated in the cystic portion and had a bead-like, lobulated appearance. The solid portion showed restricted diffusion on diffusion-weighted imaging and obvious homogeneous enhancement. The cystic portion showed ring-like and septal enhancement. The patient was diagnosed with a grade 2 (G2) NET of the retroperitoneum after surgery. INTERVENTIONS: The patient underwent resection of the large retroperitoneal tumor. OUTCOMES: The patient returned 20 months later with tumor recurrence in the retroperitoneum. She was enrolled in a clinical trial for sulfatinib, and the mass was considerably reduced in size after 4 months. During a nearly 1.5-year follow-up, the mass gradually became slightly enlarged. The expression of somatostatin receptor 2 (SSTR2) was detected, and somatuline was administered as the current treatment. LESSONS SUBSECTIONS: When a retroperitoneal mass presents as a well-defined cystic or solid hypervascular mass with a fibrous capsule, a primary retroperitoneal NET should be considered in the differential diagnosis.

Serum Small Proline-Rich Protein 2A (SPRR2A) Is a Noninvasive Biomarker in Gastric Cancer.

OBJECTIVE: Since early diagnosis is very important for treating gastric cancer (GC), we aimed to detect serum small proline-rich protein2A (SPRR2A) to verify its diagnostic value for GC patients. METHODS: Serum samples were collected from 200 patients with GC, 100 patients with gastritis, 40 patients with rectal cancer (RC), 50 patients with colon cancer (CC), and 100 healthy controls. An enzyme-linked immunosorbent assay (ELISA) detection kit was applied to measure serum SPRR2A concentration. The correlations between serum SPRR2A and carcinoembryonic antigen (CEA), clinical pathological parameters of GC, and receiver operating characteristic (ROC) curve were also analyzed. RESULTS: The median serum SPRR2A concentration in GC patients was significantly higher than those in healthy controls and gastritis or colorectal cancer patients (P < 0.001). Serum SPRR2A concentration at a cut-off value of 80.7 pg/ml yielded an AUC of 0.851, with 75.7% sensitivity and 74.5% specificity for discriminating GC patients from healthy people. The AUC for the serum SPRR2A concentration combined with the CEA concentration was 0.876, with 79.7% sensitivity and 78.7% specificity. Similarly, serum SPRR2A discriminated GC patients from gastritis patients with an AUC of 0.820, with 90.5% sensitivity and 61.7% specificity. The AUC for the serum SPRR2A concentration combined with the CEA concentration was 0.848, with 87.8% sensitivity and 68.1% specificity. The serum SPRR2A levels in GC patients were associated with lymph node metastasis and the tumor-node-metastasis (TNM) stage (P < 0.05). There was an obvious difference in serum SPRR2A expression between GC patients before and after surgery (P < 0.0001). CONCLUSION: These results suggest that serum SPRR2A can be used as an effective marker for GC.

Sarcomatoid hepatocellular carcinoma mimicking hepatic abscess: A case report.

RATIONALE: Primary sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of morphologic hepatocellular carcinoma reported on less than 1% of surgical pathology specimens. Herein, we report a rare case of SHC. The case in question was initially misdiagnosed as a liver abscess due to the clinical and radiological similarity between these 2 pathologies. Ultrasound(US)- and contrast-enhanced ultrasound (CEUS)- guided biopsies are helpful in making an accurate diagnosis under the appropriate biopsy area and angle of puncture. PATIENT CONCERNS: A 56-year old male presented to our hospital with a 2-month history of dull, upper abdominal pain without radiation. DIAGNOSES: Upon initial investigation with computed tomography, a cystic mass was found in the hepatic V segment and an infectious etiology was presumed. Further diagnostic examination with CEUS and magnetic resonance imaging suggested a hepatic abscess. However, a diagnosis of atypical intrahepatic cholangiocarcinoma was not excluded. The patient received the standard antibiotic treatment without alleviation of his symptoms. Through 3 diagnostic US-and CEUS-guided biopsies over a 3-month period, the pathological diagnosis of SHC was finally confirmed. INTERVENTIONS: The patient was diagnosed by 3 diagnostic US-and CEUS-guided biopsies, the pathological diagnosis of SHC was finally confirmed. OUTCOMES: Due to the delay in diagnosis, the patient was not a candidate for surgical resection, and showed dissemination of the lesion to the portal vein. Therefore, treatment with chemotherapy was initiated. After 4 courses of this regimen, tumor progression was found on enhanced magnetic resonance imaging. Therefore, the patient received immunotherapy and targeted therapy with limited response. The patient passed away 3 months later due to tumor progression. LESSONS: A hepatic abscess should be considered as a malignant lesion when clinical symptoms do not resolve upon standard treatment. US- and CEUS- guided biopsies are helpful in making an accurate diagnosis under the appropriate biopsy area and angle of puncture.