Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: A comprehensive analysis of systemic inflammatory markers

Objectives

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have been approved as a standard therapy for metastatic non-small cell lung cancer (NSCLC). Although PD-L1 expression serves as a predictive biomarker for the efficacy of immunotherapy, there are no established biomarkers to predict the expression of PD-L1. The inflammatory markers C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) were recently shown to predict the efficacy of nivolumab for NSCLC patients. Therefore, here we investigated the potential association of PD-L1 expression with systemic inflammatory markers, including CRP, NLR, lymphocyte-monocyte ratio and platelet-lymphocyte ratio.

Long-term functional outcome after untethering surgery for a tethered spinal cord in patients with anorectal malformations

Background

Anorectal malformation (ARM) is associated with a tethered spinal cord (TSC). Long-term functional outcome of untethering surgery for TSC in patients with ARM has not been well evaluated.

Methods

Patients aged 7 years and older who underwent repair of ARM and spinal magnetic resonance imaging from January 1995 to December 2008 were reviewed retrospectively. Untethering surgery was performed in all patients who were diagnosed with TSC, regardless of the presence or of neurological symptoms. Clinical symptoms reflecting anorectal, urinary, and lower limb function were compared between patients complicated with TSC (TSC group, n = 17) and those without TSC (non-TSC group, n = 14).

Results

The median age at functional evaluation was 11.7 and 12.9 years in the TSC and non-TSC groups, respectively (p = 0.52). Untethering surgery for TSC was performed at a median age of 1.3 years. Preoperative urinary and lower limb dysfunction, except for vesicoureteral reflux in the TSC group in one patient, was improved after surgical detethering. Current anorectal function was comparable between the groups.

Conclusions

Long-term functional outcome in patients with ARM and TSC undergoing untethering surgery is equivalent to that in those without TSC. Prophylactic surgical detethering for patients with ARM and TSC can be a treatment of choice to maximize neurological functional outcome.

     

Association between the age and the development of colorectal cancer in patients with familial adenomatous polyposis: a multi-institutional study

Purpose

To investigate the incidence of colorectal cancer among familial adenomatous polyposis (FAP) patients by phenotype using the latest modalities.

Methods

We collected data on 303 patients who underwent surgery for FAP at one of 23 institutions between 2000 and 2012. The incidence of colorectal cancer was investigated by phenotype.

Results

Colorectal cancer was diagnosed in 115 (38.0 %) of the 303 patients. Overall, colorectal cancer with the attenuated, sparse, and profuse phenotypes was diagnosed at 30, 31, and 28 years of age, respectively, in 10 % of the patients and at 59, 48, and 41 years of age, respectively, in 50 % of the patients (P = 0.013). The patients with colorectal cancer were older than those without colorectal cancer for all phenotypes. The optimal cut-off age for predicting the development of colorectal cancer in the attenuated, sparse, and profuse phenotypes was 46, 31, and 27 years, respectively.

Conclusions

Patients with profuse and sparse phenotypes should undergo prophylactic proctocolectomy before their mid-to-late 20 s. On the other hand, the timing and type of surgery for patients with attenuated FAP (AFAP) should be decided individually with reference to the colonoscopic findings.

     

Type IIIb Endoleak Is Not Extremely Rare and May Be Underdiagnosed after Endovascular Aneurysm Repair

PurposeTo investigate the real incidence of type IIIb endoleaks associated with the Zenith stent graft, currently the most widely used third-generation polyester stent graft, in a Japanese multicenter database.Materials and MethodsRetrospective analysis was conducted of 433 patients who underwent endovascular aneurysm repair (EVAR) of aortoiliac aneurysms with the use of Zenith stent grafts from 2007 to 2016. The mean age of patients was 75.6 y ± 7.8, and 85.2% of patients were men. Mean transverse diameters of abdominal aortic aneurysms and common iliac artery aneurysms were 50.8 mm ± 9.9 and 42.2 mm ± 10.3, respectively.ResultsDuring a mean follow-up period of 41.9 mo, 7 type IIIb endoleaks (1.6%) were identified. Four patients were definitively diagnosed during repeat intervention, and 3 were diagnosed based on postoperative CT images. Three patients were treated surgically, 2 were treated by relining with an additional stent graft, and 2 were conservatively followed with CT imaging. Only 1 of 5 patients who underwent repeat intervention had a preoperative diagnosis of type IIIb endoleak, reflecting the difficulty in its diagnosis.ConclusionsThe incidence of type IIIb endoleak in Zenith stent grafts was 1.6% in this study, suggesting that type IIIb endoleaks are not extremely rare. In addition, type IIIb endoleak may be underdiagnosed or misdiagnosed as a different type of endoleak. Type IIIb endoleaks should always be considered in patients with sac expansion after EVAR.     

Increased CYP1A2 content and capacity to activate Glu-P-1 and Trp-P-2 in liver microsomes of scorbutic ODS rats

Osteogenic Disorder Shionogi (ODS) rats, which cannot synthesizeascorbic acid due to a deficiency of L-gulonolactone oxidase,become scorbutic when not supplied with dietary ascorbic acid.We used the deficient rats to study the effects of ascorbicacid on the amount of cytochrome P450 enzymes in liver microsomes.The total amount of hepatic cytochrome P450 in ODS rats deprivedof ascorbic acid was lower by 40%, whereas ODS rats fed withascorbic acid and the wild strain had the same level of totalhepatic cytochrome P450. Western blot analysis for various formsof cytochrome P450 in liver microsomes indicated that the amountof CYP1A2 was significantly higher in ascorbic acid deficientrats. On the other hand, amounts of CYP2B2 and 3A were lower,and those of CYP2E1 and CYP2C6/11 were unaffected. In accordancewith the higher amount of CYP1A2, Northern blot analysis showedincreased expression of CYP1A2 mRNA. The capacity of microsomesto produce mutagens from 2-amino-6-methyl-dipyrido[1, 2-a:3',2'-d]imidazole acetate (Glu-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) was higher in scorbutic ODS ratsby the Ames test. These results indicate that the effects ofascorbic acid deficiency on the expression of cytochrome P450in ODS rat livers are form-specific and that the increased CYP1A2is associated with increased metabolic activation of promutagensin the scorbutic state.     

Diffuse subendocardial ischemia in a patient with aortic valve stenosis without coronary artery disease by exercise 201Tl SPECT]

A case of aortic valve stenosis without coronary artery disease was confirmed to have diffuse subendocardial ischemia by exercise Thallium-201 myocardial single photon emission computed tomography. A 72-year-old woman, who had been diagnosed as aortic valve stenosis, was admitted because of chest pain during exercise. In cardiac catheterization findings, the patient angiographically had normal coronary arteries and no asynergy of left ventricular wall motion. The peak flow velocity in continuous wave Doppler echocardiography was about 5.0 m/sec at aortic valve level, providing a pressure drop of 100 mmHg across a stenotic valve with calculating on a modified Bernoulli equation (PG = 4V2). Thallium-201 myocardial SPECT images during exercise showed a transient "dilation and a widespread wall thinning" of left ventricle with apical perfusion defect. Simultaneous electrocardiogram showed further ST depression and the patient had chest pain. In 6 months after aortic valve replacement the patient no longer demonstrated both apical perfusion defect and "wall thinning" in postoperative thallium-201 myocardial SPECT images and also had neither ST depression nor chest pain. Thus; a transient "dilation and wall thinning" of left ventricle in this patient is suspected to be a sign of diffuse subendocardial ischemia.     

Tumor‐derived exosomes influence the cell cycle and cell migration of human esophageal cancer cell lines

Our laboratory previously reported the usefulness as biomarkers of exosomes in the plasma of esophageal squamous cell carcinoma (ESCC) patients. However, the influence of tumor‐derived exosomes on the tumor itself and underlying mechanisms remain unclear. We here report changes in the phenotype and gene expression when cancer cells exist in an environment with tumor‐derived exosomes. The exosomes were isolated from the culture medium of human ESCC cells (TE2, T.Tn) by ultracentrifugation; cell proliferation assay, wound‐healing assay, and fluorescence imaging of the cell cycle were performed to clarify the phenotypic changes in the high concentration of tumor‐derived exosomes. Gene expression changes were also assessed by mRNA microarray, and the data were analyzed by gene set enrichment analysis (GSEA). The data revealed that the proliferation of both TE2 and T.Tn was inhibited, and cell migration ability was upregulated in the exosome exposure group (P < .05). Fluorescence imaging using a fluorescent ubiquitination‐based cell cycle indicator expressing ESCC cells revealed that the ratio of G1‐phase cells was significantly increased in the exosome exposure group (P < .05). Findings of the GSEA clarified that high‐density exposure of cancer‐derived exosomes to their parent cancer cells downregulated the expression of genes related to cell proliferation and cell cycle, and upregulated the expression of genes related to actin filament length and extracellular structure organization. In conclusion, an environment of high‐density tumor‐derived exosomes induces changes in the gene expression and phenotype of tumor cells and may lead to tumor progression or malignant transformation.     

Overexpression of enhancer of zeste homolog 2 and MUC1 may be related to malignant behaviour in intraductal papillary neoplasm of the bile duct

Aims: Intraductal papillary neoplasm of the bile duct (IPNB) usually has a favourable prognosis, but occasionally is associated with invasive carcinoma. Overexpression of the polycomb group protein enhancer of zeste homolog 2 (EZH2) is involved in the progression of malignant tumours. In this study, we examined the significance of EZH2 expression in IPNB and its association with clinicopathological features and the expression of p16^INK4a, p53 and mucin core proteins. Methods and results: We examined immunohistochemically the expression of EZH2, p16^INK4a, MUC mucin core proteins and p53 in 15 patients with IPNB without invasion, including the cystic variant [male/female ratio (M/F) = 9/6], and in 19 with IPNB associated with invasive carcinoma (M/F = 13/6). The expression levels of EZH2, p53 and MUC1 were significantly lower (P < 0.01), and of MUC6 were significantly higher (P < 0.05), in IPNB without invasion than in IPNB with invasion. Expression of EZH2 was significantly correlated with expression of MUC1 (P < 0.01) and inversely correlated with expression of MUC6 (P < 0.05). In cholangiocarcinoma cells (HuCTT‐1 and TFK‐1), knockdown of EZH2 and MUC1 by small interfering RNA decreased invasion and proliferation, whereas knockdown of MUC6 increased invasion. Conclusions: Overexpression of EZH2 may be associated with malignant behaviour in IPNB in parallel with up‐regulated MUC1 expression and down‐regulated MUC6 expression.