Abstract Objective Clinical immunohistochemistry plays an increasingly important role in pathologic diagnosis. We investigated the usefulness of an immunohistochemical panel of glypican-3 (GPC3), hepatocyte paraffin antigen-1 (HepPar-1), arginase-1 (Arg-1), cytokeratin-19 (CK19), and human epithelial membrane antigen (EMA) for the differential diagnosis of liver tumors. Methods Two hundred and thirty-five immunohistochemical sections of hepatocellular carcinoma (HCC; 120 cases), intrahepatic cholangiocarcinoma (ICC; 50 cases), combined hepatocellular and cholangiocarcinoma (CHC; 17 cases), metastatic adenocarcinoma (20 cases), and benign liver lesions (28 cases) were obtained from the Department of Pathology at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. The sensitivity and specificity of the combined biomarkers GPC3/HepPar-1/Arg-1/CK19/EMA for the differential diagnosis of HCC, ICC, and CHC were calculated and analyzed retrospectively. Results The combined biomarkers GPC3 + /CK19 - had the highest specificity (98.3%) for diagnosing HCC, with a sensitivity of 60.0%. The specificity of GPC3-/HepPar-1 - /Arg-1 - /CK19 + /EMA + for diagnosing ICC was 93.0%, with a sensitivity of 76.0%. The specificity of GPC3 + /HepPar-1 + /Arg-1 + /CK19 + /EMA + for diagnosing CHC was 95.9%, with a sensitivity of 52.9%. Conclusion The combined biomarkers GPC3/HepPar-1/Arg-1/CK19/EMA greatly improved the specificity of liver tumor diagnosis. We believe that clinical pathological work could improve the original determination of liver nodules.
Liver transplantation (LT) is effective for suitable patients with HCC and may be the only curative treatment for those with unresectable HCC. The outcomes of LT for HCC are closely related with the assessment of transplantation candidates, management of patients on the waiting list and postoperative surveillance for HCC recurrence. PET imaging plays a significant role in LT process. The applications of PET imaging in LT for HCC are reviewed in this article.
Key words:
Liver neoplasms; Liver transplantation; Tomography, emission-computed; Trends
Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and
Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial hypometabolism, however, the available evidence about the metabolic feature of CCD in patients with contralateral supratentorial hypermetabolism is lacking. This study aimed to assess the metabolic asymmetrical profile, network pattern and predisposing factors for the hypermetabolism-associated CCD, by using voxel-based asymmetry index (AI) and brain network analyses. Seventy CCD positive (CCD+) and 99 CCD negative (CCD-) patients with unilateral supratentorial hypermetabolism were introduced. Among different brain regions with AImax or AImin, striatum & thalamus was accompanied by the highest positive rate of CCD (85.7% or 70.1%, respectively). CCD+ group had significantly greater AImax (median [IQR], 0.62 [0.44-0.84] vs. 0.47 [0.35-0.61]), supratentorial hypermetabolic volume (1183.5 [399.3-3026.8] vs. 386.0 [152.0-1193.0]) and hypometabolic volume (37796.5 [24741.8-53278.0] vs. 3337.0 [1020.0-17193.0]), and lower AImin (-0.85 [-1.05--0.73] vs. -0.49 [-0.68--0.35]) compared with CCD- group (all P < 0.001). Logistic regression analysis manifested that patients with AImin located at striatum & thalamus were 16.4 times more likely to present CCD than those at frontal lobe (OR = 16.393; 95% CI, 4.463-60.207; P < 0.001), and the occurrence of CCD was also associated with AImax (OR = 49.594; 95% CI, 5.519-445.653; P < 0.001) and AImin (OR = 3.133 × 10-4, 95% CI, 1.693 × 10-5-5.799 × 10-3, P < 0.001). Brain network analysis indicated that the relative hypermetabolism in the contralateral supplementary motor cortex (SMC) and precuneus gyrus were constant in the CCD related patterns. These results demonstrated that the greater AImax, lower AImin and AImin located at striatum & thalamus should be predisposing factors for CCD in patients with unilateral supratentorial hypermetabolism. Relative increased activities in the contralateral SMC and precuneus gyrus might be attributed to a compensatory mechanism for the abnormal brain network related to CCD.
Abstract We present image findings of 18 F-FDG, 68 Ga-FAPI, and 68 Ga-DOTATATE PET/CT in a 35-year-old woman with multiple metastases of pancreatic neuroendocrine tumor. The images of PET/CTs using 3 different tracers all showed multiple foci of increased activities in the liver and pancreas body, in which 68 Ga-FAPI PET/CT displayed the highest tumor-to-liver ratios. However, 68 Ga-DOTATATE PET/CT detected more small metastatic lymph node and bone metastases, which were missed by both FDG and FAPI PET/CT.
Fibroblast activation protein (FAP) is highly expressed in many tumor types and constitutes a promising target for tumor-specific delivery of therapeutic radionuclides. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is a novel radiopharmaceutical based on a novel bidentate inhibitor of FAP that is excreted more slowly than its monomeric counterparts. Still, the efficacy of radiotherapy is mitigated by cascades of DNA damage repair signaling in tumor cells including those via Poly(ADP-ribose) polymerase (PARP). We hereby aimed to evaluate the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in combination with a PARP inhibitor, Olaparib, in the 4T1 murine triple negative breast cancer (TNBC) model. The therapeutic efficacy was visualized using 18F-FDG and [68Ga]Ga-FAPI-04 positron emission imaging/computer tomography (PET/CT). Our results demonstrated that Olaparib suppressed BALB/3T3 fibroblasts in vitro and sensitized the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in mice bearing 4T1 tumors via enhancement of DNA damage. Treatment-associated toxicity was tolerable with only mild leukopenia. Therefore, the combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and Olaparib is a feasible treatment against TNBC.
1701 Objectives It is important to evaluate disease severity of primary hyperparathyroidism (PHPT) for making decisions not only about the surgical treatment but also for monitoring patients who do not undergo parathyroid surgery. We investigated the relationship between quantitative markers based on Tc-99m MIBI parathyroid SPECT/CT and biochemical markers as well as clinical features in patients with PHPT. Methods 60 PHPT patients performed three procedures, dual-phase Tc-99m MIBI planar scintigraphy, delayed SPECT/CT, and ultrasonography after treatment with calcitonin were retrospectively enrolled. The pathologic volume (PV) of each lesion was measured following parathyroidectomy. For the 38 patients showed positive scintigraphy and no sign of thyroid nodule by ultrasonography, lesion-to-background ratio (LBR), metabolic volume (MV) and total lesion uptake ratio (TLUR) were measured. Also, their relationship with symptoms, preoperative serum intact parathyroid hormone (iPTH), calcium values before (Ca1) and after (Ca2) calcium-lowering medications were analyzed. Results 63 lesions were found in 60 patients including 49 single entopic parathyroid adenomas, six multiple parathyroid adenomas, seven parathyroid hyperplasias and one parathyroid carcinoma. The symptomatic PHPT patients (SPP) had significantly higher TLUR than the asymptomatic PHPT patients (ASPP). However, there were no significant differences between the SPP and the ASPP in terms of PV, MV, and LBR values. TLUR was strongly correlated with PV, iPTH, and Ca1. However, LBR, MV, and TLUR were not correlated with Ca2. LBR was significantly correlated with PV and Ca1, but not correlated with serum iPTH. Conclusions TLUR with a strong correlation with biochemical markers and clinical features appears to be a promising quantitative marker in evaluating disease severity for PHPT patients, especially for ASPP.
Background Primary liver cancer includes three subtypes: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and combined hepatocellular carcinoma. Patients with primary liver cancer experienced poor prognosis and high mortality, so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer. Prostate-specific membrane antigen (PSMA) expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently, but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited. Aim To study the expression of PSMA in HCC, CCA, and liver cirrhosis. Methods A total of 446 formalin-fixed paraffin-embedded (FFPE) liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital. Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens (213 HCC, 203 CCA, and 30 liver cirrhosis). The tumor compartment and the associated neovascular endothelium were separately analyzed. PSMA expression was examined by two certified pathologists, and the final results were presented in a 4-point scoring system (0-3 points). Correlation between PSMA expression and clinicopathological information was also assessed. Results PSMA was expressed primarily in the neovascular endothelium associated with tumors. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%; P = 0.001) but was only 6.6% in liver cirrhosis (P = 0.000). HCC cases had more 3-score PSMA staining than CCA had (89/213, 41.8% vs 35/203, 17.2%; P = 0.001). PSMA expression correlated positively with the stage and grade of HCC and CCA. In both liver cancer subtypes, there were more PSMA+ cases in stages III-V diseases than in stages I and II. High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage. There was no significant association of PSMA expression with sex, age, region, α-fetoprotein, hepatitis B surface antigen, or tumor size in both tumor subtypes. Conclusion Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.
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