Abstract. Programmed death ligand-1 (PD-L1) is a potentially important tumor immunotherapy target. However, whether PD-L1 expression is associated with survival in nasopharyngeal carcinoma (NPC) remains controversial. The aim of the present study was to investigate the association between PD-L1 expression and prognosis in NPC. The expression of PD-L1 was assessed in tumor specimens from 120 patients with NPC using immunohistochemistry. Staining was evaluated using the H-score method. The associations between PD-L1 expression and clinical characteristics and prognosis were analyzed. Overall, 78% of the patients had stage I-III and 22% had stage IV disease. The estimated 5-year overall survival (OS) and disease-free survival (DFS) rates for the entire cohort were 87.5 and 70.1%, respectively. PD-L1 expression was detected in 85 (71%) patients and was localized to the tumor cells. High tumor expression of PD-L1 (median H-score ≥5) was associated with significantly poorer OS (P=0.023) and DFS (P=0.002). Univariate analysis indicated that low PD-L1 expression was associated with better DFS compared with high PD-L1 expression (HR=0.163, 95% CI: 0.044-0.600, P=0.006 for DFS). Multivariate analysis revealed that T stage (HR=8.190, P=0.023) and PD-L1 expression level (HR=0.124, 95% CI: 0.031-0.509; P=0.001) served as independent prognostic factors for DFS. In conclusion, tumor PD-L1 expression was found to be a significant prognostic factor in NPC, and high PD-L1 expression may be of prognostic value for recurrence and metastasis following conventional treatments.

BackgroundSmall cell carcinoma of the cervix (SCCC) is a very rare tumor. Due to its rarity and the long time period, there is a paucity of information pertaining to prognostic factors associated with survival. The objective of this study was to determine whether clinicopathologic finings or immunohistochemical presence of molecular markers predictive of clinical outcome in patients with SCCC.Methodology and FindingsWe retrospectively reviewed a total of 293 patients with SCCC (47 patients from Cancer Center of Sun Yat-sen University in china, 71 patients from case report of china journal, 175 patients from case report in PubMed database). Of those 293 patients with SCCC, the median survival time is 23 months. The 3-year overall survival rates (OS) and 3-year disease-free survival rates (DFS) for all patients were 34.5% and 31.1%, respectively. Univariate and multivariate analysis showed that FIGO stage (IIb–IV VS I–IIa, Hazard Ratio (HR) = 3.08, 95% confidence interval (CI) of ratio = [2.05, 4.63], P<0.001), tumor mass size (≥4 cm VS <4 cm, HR = 2.37, 95% CI = [1.28, 4.36], P = 0.006) and chromogranin A (CgA) (Positive VS Negative, HR = 1.81, 95% CI = [1.12, 2.91], P = 0.015) were predictive of poor prognosis. CgA stained positive was found to be highly predictive of death in early-stage (FIGO I–IIa) patient specifically.ConclusionsPatients with SCCC have poor prognosis. FIGO stage, tumor mass size and CgA stained positive may act as a surrogate for factors prognostic of survival. CgA may serve as a useful marker in prognostic evaluation for early-stage patients with SCCC.

Objective: Using a block-designed BOLD-fMRI to explore the neural basis of spatial working memory impairment in patients with subclinical hypothyroidism (SCH) performing an n-back task. Methods: Sixteen patients with SCH before and after being treated with levothyroxine (LT₄) for 6 months and 16 matched euthyroid subjects were scanned by fMRI under the n-back task. Results: The fMRI scan found that a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal lobe (PA) and right caudate nucleus/thalamus was activated, with right hemisphere dominance. In euthyroid subjects, all these regions of interest (ROIs) showed load effect; however, only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in Pre-SCH patients. Furthermore, activation intensities of most ROIs (especially DLPFC and right PA) for Pre-SCH patients were lower than those in the euthyroid subjects (F <3.046, p > 0.062). Importantly, after a 6-month treatment with LT₄, the load effect in SCH patients appeared the same as in the euthyroid subjects in all the ROIs (F >13.176, p < 0.0001). Conclusion: Our previous study shows that verbal working memory of SCH patients is impaired with abnormal activity in bilateral frontal areas. In this study, the results indicated that SCH patients may also have spatial working memory impairments, and the altered activities of right DLPFC and right posterior parietal lobe may be one of the underlying neural mechanisms. Most importantly, this study shows that LT₄ replacement therapy can improve the memory impairment and reverse the altered neural activity network.

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