Shorter Survival Period Research Articles

High-Grade B-Cell Lymphomas, Not Otherwise Specified: A Study of 41 Cases.

PurposeTo analyze the clinical and pathological characteristics, treatment, and prognosis of high-grade B-cell lymphomas, not otherwise specified (HGBL, NOS), and to increase awareness of this type of lymphoma.Patients and MethodsWe collected clinical and pathological data of 41 cases of newly diagnosed HGBL, NOS, and analyzed diagnosis, prognosis and treatment to examine progression-free survival (PFS) and overall survival (OS).ResultsAmong the 41 cases studied, the median PFS was 6.0 months and the median OS was 18.0 months. Compared with patients treated with the R-CHOP regimen, patients treated with a high-intensity chemotherapy (DA-EPOCH-R, R-CODOX-M/IVAC, or R-Hyper-CVAD) had superior PFS and OS (PFS: χ2=4.173, P=0.041; OS: χ2=5.200, P=0.023). A subgroup analysis showed that the OS for the double-expressor lymphoma (DEL) was inferior to that for the non-DEL (χ2=4.563, P=0.033), and this trend was also seen for the single-hit lymphoma with MYC rearrangement (SHL) and the non-SHL (χ2=4.955, P=0.026). Patients with low International Prognostic Index (IPI) scores (≤2) had better survival rates than those with high scores (>2) (PFS: χ2=6.482, P=0.011; OS: χ2=10.156, P=0.001).ConclusionHGBL, NOS is associated with a high degree of malignancy, short survival period, and substantial extranodal involvement. High-intensity chemotherapy may improve patient prognosis. While IPI scores statistically correlated with the prognosis, SHL and DEL correlated with an inferior survival rate. New and improved treatments will be needed for HGBL, NOS.

PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway.

Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biological function, clinical significance, and therapeutic targeted value of PELP1 in gastric cancer (GC).Methods: The expression status of PELP1 in GC cell lines or tissues was analyzed through bioinformatics data mining. Thirty-six GC tissue chip was applied to demonstrate the results of bioinformatics data mining assayed by immunohistochemical method. The expression status of PELP1 in GC cell lines was also analyzed using western blot. Correlation analysis between PELP1 expression and clinicopathological parameter was performed. Kaplan-Meier survival analysis was applied to analyze the relationship between PELP1 expression and total survival time. Three pairs of siRNA were designed to silence the expression of PELP1 in GC. After PELP1 was silenced by siRNA or activated by saRNA, the growth, plate colony formation, migration and invasion ability of the GC cell or normal gastric epithelium cell line was tested in vitro. Cell cycle was tested by flow cytometry. Nude mice xenograft experiment was performed after PELP1 was silenced. The downstream molecular pathway regulated by PELP1 was explored. Molecular docking tool was applied to combine chlorpromazine with PELP1. The inhibitory effect of chlorpromazine in GC was assayed, then it was tested whether PELP1 was a therapeutic target of chlorpromazine in GC.Results: PELP1 expression was elevated in GC cell lines and clinical GC tissue samples. PELP1 silence by siRNA compromised the malignant traits of GC. PELP1 expression positively correlated with tumor invasion depth, lymph node metastasis, tissue grade, TNM stage, but had no correlation with patient age, sex, tumor size, and tumor numbers. Kaplan-Meier survival analysis revealed high PELP1 expression had a shorter survival period in GC patients after follow-up. Q-PCR and western blot revealed PELP1 suppression in GC decreased expression of the c-Src-PI3K-ERK pathway. It was also implied that chlorpromazine (CPZ) can inhibit the malignant traits of GC and downregulate the expression of PELP1.Conclusions: In a word, PELP1 is an oncogene in gastric cancer and c-Src-PI3K-ERK pathway activation may be responsible for its tumorigenesis, PELP1 may be a potential therapeutic target of chlorpromazine in GC.

Protein Signatures of Centenarians and Their Offspring Suggest Centenarians Age Slower than Other Humans

We used a high-throughput Somascan platform to quantify 4116 proteins in the serum of 224centenarians, offspring, and controls (mean ages: 105, 80, 79 years) from the New England Centenarian Study, and to characterize the serum proteome of aging and longevity. We identified 1312 proteins that significantly differ between centenarians and their offspring and controls (FDR<1%), and replicated the association of 484 of these using 2 independent proteomic studies of aging. By comparing the patterns of proteins associated with aging to protein profiles of centenarians, we also identified serum-protein signatures of extreme old age and of immune senescence. We then searched for protein signatures that distinguish between short and long survival within various age groups and we identified two differentprotein signatures that predict longer survival in older people and in centenarians. The data suggest that centenarians acquire similar aging patterns as seen in younger cohorts that have short survival periods, suggesting that centenarians do not escape normal aging markers, but rather acquire them much later than usual. For example, centenarian signatures are significantly enriched for senescence-associated secretory phenotypes, consistent with those seen with younger aged individuals, and from this findingwe provide a new list of serum proteins that can be used to measure cellular senescence. Consistently with this findings, protein co-expression network analysis showed that the serum proteome of offspring and controls clusters in a small number of modules of correlated proteins, some of which are conserved in centenarians’ serum while others break down in smaller modules thus suggesting that a small number of biological drivers may regulate aging and that changes in gene regulation may be important to reach extreme old age. This centenarian study thus provides additional signatures that can be used to measure aging, and provides specific biomarkers of healthy aging and longevity, suggesting potential mechanisms that could help prolong health and support longevity.

Decision-making factors for best supportive care alone and prognostic factors after best supportive care in non-small cell lung cancer patients

Among patients with non-small cell lung cancer (NSCLC), best supportive care (BSC) is well-known to improve patient’s quality of life and prolong survival. This study aimed to clarify (1) the decision-making factors of BSC alone and (2) the prognostic factors after selection of no further anticancer therapies. We retrospectively reviewed the clinical data of patients with NSCLC between November 2004 and February 2014, who received BSC as only therapy and BSC after completion of anticancer therapies. One hundred eighteen patients received BSC alone. Among 860 patients treated with anticancer therapies, 236 were selected as control group, 160 of whom received BSC after anticancer therapy. The significant reasons for receiving BSC alone were: comorbidities of dementia, poor Eastern Cooperative Oncology Group performance status (ECOG-PS), patients’ wishes, pulmonary comorbidities, wild type epidermal growth factor receptor (EGFR), relevant social background and psychiatric comorbidities. Poor prognostic factors at the start of BSC were poor ECOG-PS, presence of disseminated intravascular coagulation (DIC), and history of anticancer therapy. NSCLC patients with comorbidities, wild type EGFR, and relevant social background factors tended to receive BSC alone. Post-cancer therapy NSCLC patients and those with DIC and declining ECOG-PS have a shorter survival period from the start of BSC.

MiR-181a/b-5p ameliorates inflammatory response in monocrotaline-induced pulmonary arterial hypertension by targeting endocan.

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by vascular remodeling, endothelial cell (EC) dysfunction, and inflammation. The roles of microRNAs have received much critical attention. Thus, this study was attempted to show the biological function of miR-181a/b-5p (miR-181a/b) in monocrotaline (MCT)-induced PAH. Here, rats injected with MCT were used as PAH models. The expression of miR-181a/b and its effect on PAH pathologies were examined using miR-181a/b overexpression lentivirus. A luciferase reporter analysis was performed to measure the relationships between miR-181a/b and endocan. Additionally, primary rat pulmonary arterial endothelial cells (rPAECs) treated with tumor necrosis factor-α (TNF-α) were employed to further validate the regulatory mechanism of miR-181a/b in vitro. Our results showed that miR-181a/b expression was reduced in PAH, and its upregulation significantly attenuated the short survival period, right ventricular systolic pressure and mean pulmonary artery pressure increments, right ventricular remodeling, and lung injury. Furthermore, the increase of intercellular cell adhesion molecule-1 (ICAM1) and vascular cell adhesion molecule-1 (VCAM1) in PAH rats was inhibited by miR-181a/b overexpression. Similarly, our in vitro results showed that inducing miR-181a/b suppressed TNF-α-stimulated increase of ICAM1 and VCAM1 in rPAECs. Importantly, the increased expression of endocan in PAH model or TNF-α-treated rPAECs was restored by miR-181a/b upregulation. Further analysis validated the direct targeting relationships between miR-181a/b and endocan. Collectively, this study suggests that miR-181a/b targets endocan to ameliorate PAH symptoms by inhibiting inflammatory states, shedding new lights on the prevention and treatment of PAH.

Risk Factors for Poor Survival in Metastatic Castration-resistant Prostate Cancer Treated With Cabazitaxel in Japan

Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). This retrospective study aimed at assessing the efficacy and prognostic markers of cabazitaxel treatment in Japanese CRPC patients. The medical records of 44 consecutive Japanese patients with CRPC who started cabazitaxel at our Institution between January 2011 and February 2019 were reviewed and statistically analysed. The median follow-up period after cabazitaxel initiation was 13.2 [interquartile range (IQR)=6.9-21.5] months. The objective response rate, median progression-free survival period, and median overall survival period (OS) were 45.5%, 4.3 months, and 20.7 months, respectively. On multivariate analysis, higher prostate-specific antigen (PSA; >100 ng/ml), lower haemoglobin (<10 g/dl), and lower number of prior docetaxel therapy cycles (<10) were predictors for shorter OS. Patients with anemia, high PSA, and lower number of docetaxel therapy cycles might have shorter survival period from introduction of cabazitaxel therapy. In addition, PSA decline might still be a useful indicator as a predictor of prognosis of the metastatic CRPC patients treated with cabazitaxel.

Elevated expression of G protein-coupled receptor 30 (GPR30) is associated with poor prognosis in patients with uterine cervical adenocarcinoma.

Uterine cervical adenocarcinoma has a worse prognosis than that of squamous cell carcinoma and useful diagnostic and prognostic markers are needed. Estrogen is one of the key regulators of several cancers, however, the estrogen signaling has not been focused on in cervical adenocarcinoma. Here, we shows expression profile of classical estrogen receptor (ER) and a novel membrane type estrogen receptor, G protein-coupled receptor 30 (GPR30), in surgical specimens (n=53). GPR30 was strongly expressed on the cell membrane and in the cytoplasm in adenocarcinoma in situ (AIS) and adenocarcinoma, and its expression was especially strong at the invasion front in most of the cases of GPR30-positive adenocarcinoma. Nuclear staining of ER was strong in non-neoplastic glands, whereas it was almost absent in most of the AIS and adenocarcinoma cases. There was a weak but statistically significant negative correlation between immunoreactivity of GPR30 and that of ER in cervical AIS and adenocarcinoma lesions (Spearman's correlation, r=-0.324, p=0.017). ROC curve analysis revealed that immunoreactivity of GPR30 successfully distinguished neoplasms from non-neoplastic glands with high specificity (100%) and sensitivity (75.5%). GPR30 positivity was significantly correlated with histological type (p=0.009), tumor diameter (p=0.003), tumor size (p<0.001), lymphovascular infiltration (p=0.005) and UICC stage (p<0.001). ER expression was correlated only with tumor factor (p=0.047). GPR30-high patients had poor prognosis with a significantly shorter overall survival (OS) period (p=0.0309). GPR30 expression is a potential diagnostic and prognostic marker.

The Expression of TMEM74 in Liver Cancer and Lung Cancer Correlating With Survival Outcomes.

Transmembrane 74 (TMEM74), a transmembrane protein as an autophagy inducer, has been proven to promote tumor cell (including cervical cancer cell line HeLa and hepatic carcinoma cell line HepG2) proliferation by triggering autophagy. To further determine the role of TMEM74 in cancer, we performed immunohistochemical staining on tissue array, and the results showed that TMEM74 exhibited significantly higher expression in several tumor types, especially in hepatocellular carcinoma, lung adenocarcinoma, and squamous carcinoma. Furthermore, higher expression level of TMEM74 in HepG2, A549, and H1299 cell lines were also detected compared with the corresponding normal cell lines, as detected by western blot. Meanwhile, further analysis showed that the levels of TMEM74 expression were closely correlated to survival period of patients-the higher expression of TMEM74 was correlated with shorter survival period. Moreover, the in vitro experiments showed that overexpression of TMEM74 led to accelerated proliferation of A549 and H1299 cells, while knockdown of TMEM74 reversed the outcomes. In conclusion, the results suggested that TMEM74 acts as an oncogene and a potential diagnostic marker and a therapeutic target for liver cancer and lung cancer.

Long non-coding RNA LUCAT1 promotes proliferation and invasion in gastric cancer by regulating miR-134-5p/YWHAZ axis

PurposeThe aim of this study was to research the function of lncRNA LUCAT1 in gastric cancer. MethodsHuman gastric cancer tissues and paracancer tissues were obtained from 98 patients undergoing surgical resection in our hospital. The human gastric cancer cell lines (HGC27, BGC823, MGC803, SGC7901 and AGS), and normal gastric mucosal cell line GSE1 were used to research the role of lncRNA LUCAT1. ShRNAs specifically targeting lncRNA LUCAT1, miR-134-5p mimic, miR-134-5p inhibitor and their related controls were transfected into cells. Quantitative real-time PCR was used to detect the expression of lncRNA LUCAT1, miR-134-5p and YWHAZ. The cell proliferation of SGC7901 cells was determined by CCK8 kit. Colony formation assay was undertaken. Cell apoptosis assay was processed using the Annexin V-FITC / propidium iodide (annxinV/PI) apoptosis detection kit. Migration and invasion were detected by transwell assay. Tumor xenograft model was conducted to calculate the size and weight of the tumors. Luciferase reporter assay was used to confirm the interactions among lncRNA LUCAT1, miR-134-5p and YWHAZ. ResultsLncRNA LUCAT1 was confirmed to be highly expressed in gastric cancer. Patients with high LUCAT1 level displayed short overall survival and disease-free survival periods. LUCAT1 knockdown or miR-134-5p overexpression decreased the proliferation, colony formation, migration and invasion of SGC7901 cells. ConclusionsLncRNA LUCAT1 could promote proliferation and invasion of gastric cancer by regulating miR-134-5p/YWHAZ axis.

Prognostic Significance of Cyclin D1 Over-expression in Colorectal Cancer: An Experience from Madinah, Saudi Arabia.

Background and study aim: Cyclin D1 is a key regulatory protein in the cell cycle and is over-expressed in many tumors, including endometrial, thyroid, urothelial, breast, brain gliomas, and esophageal cancers. The main aim of the present study is to examine the expression pattern of cyclin D1 and its correlation with the different clinicopathological features in patients with colorectal camcer (CRC) from the Madinah region of Saudi Arabia. Patients and methods:The archival tumor blocks were analyzed using immunohistochemistry for Cyclin D1 over-expression in 324 CRC patients diagnosed from January 2006 to December 2017, at the Department of Pathology, King Fahad Hospital, Madinah, Saudi Arabia.Results: Cyclin D1 over-expression was absent in normal mucosa, while 15% cases of adenoma showed its over-expression. In CRC, Cyclin D1 was expressed at high levels in 24.1% of case. No significant correlation was observed between Cyclin D1 over-expression and age, gender, tumor size, type and location. However, Cyclin D1 over-expression exhibited a significant correlation with tumor differentiation (p=0.04), lymph node involvement (p=0.001), lymphovascular invasion (p=0.001), distant metastasis (p=0.006) and AJCC staging (p=0.001). The Kaplan-Meir analysis revealed a shorter period of survival with Cyclin D1 over-expression (p=0.000). The Cox-regression model analysis showed that Cyclin D1 over-expression was an independent prognostic marker in CRC (p=0.000). Conclusion: Cyclin D1 over-expression increases during normal-adenoma-carcinoma sequence. The significant association observed between Cyclin D1 over-expression, advanced tumor stage and short survival period clearly suggest the role of Cyclin D1 in the carcinogenesis and progression of CRC.

The role of P2X7 receptor in prognosis and metastasis of colorectal cancer

PurposeColorectal cancer (CRC) is one of the leading causes of cancer mortality in the world. P2X7 receptor (P2X7R), encoded by the P2rx7 gene, is a trimeric ion channel activated by extracellular Adenosine triphosphate and is widely expressed in various types of tissues and tumors to regulate inflammation, cell proliferation, or death. The discovery of new biomarkers and understanding the role of P2X7R in CRC are therefore critical to improving the prognosis and treatment of CRC. Materials and methodsP2X7R expression was analyzed in CRC tumor samples and normal colorectal tissues from 97 patients and various colon cancer cell lines. The correlation of tumor antigens, survival periods, and P2X7R expression were documented. ResultsP2X7RHigh and P2X7RLow populations were observed in CRC patients. P2X7RHigh patients had relatively shorter survival periods, higher levels of serum carcinoembryonic antigen, and greater numbers of advanced tumors. In addition, P2X7R expression had a significant up-regulation in metastatic CRC and metastatic CRC cell lines, which indicates that P2X7R expression is positively associated with metastasis. ConclusionsP2X7R expression might be a potential biomarker for prognosis and metastasis of CRC.

Characterization of Mucosa-Associated Microbiota in Matched Cancer and Non-neoplastic Mucosa From Patients With Colorectal Cancer.

Colonic microbiota play important roles in the development of colorectal cancer. We aim to characterise the mucosa-associated microbiota in the tumour as well as the matched non-neoplastic mucosa from patients with colorectal cancer. Microbiota profiling in these samples was done using high-throughput 16S rRNA amplicon sequencing. Our results showed that the microbiota richness and diversity were similar between the tumour and non-neoplastic mucosae. Linear discriminant analysis effect size (LEfSe) analysis identified Fusobacterium and Campylobacter as the key genera of the tumour while Brevundimonas as the key genus of the non-neoplastic mucosa. In patients with shorter survival period, the relative abundance of Fusobacterium and Campylobacter was significantly higher in the tumour. Besides, regardless of the sites, tumour showed higher abundance of Fusobacterium. On the other hand, the relative abundance of Brevundimonas was significantly lower in the tumour. When validated with quantitative ddPCR, we found the absolute numbers of both Fusobacterium and F. nucleatum were significantly higher in the carcinoma from patients with shorter survival period, conventional type of adenocarcinoma in the distal portion of the large intestine (descending colon, sigmoidal colon, and rectum). In conclusion, our study showed a compositional alteration in the mucosa-associated microbiota in the tumour, which may contribute to the progression of colorectal cancer.

Present status and research progresses in treatment of acute myeloid leukemia patients aged over 80 years

The number of acute myeloid leukemia (AML) patients aged over 80 years are increasing year by year. They have poor treatment effects and shorter survival period because of elderly age, more underlying diseases, poor tolerance to chemotherapy. At present, there are many treatments reported, including supportive therapy, standard-dose chemotherapy, reduced-dose chemotherapy, demethylation therapy, hematopoietic stem cell transplantation(HSCT) and adoptive cellular immunotherapy, and various treatments have achieved some good effects in AML patients aged over 80 years. However, the survival of this group of patients is still poor. And there are lack of unified and effective therapeutic strategies for elderly patients with AML. This article reviewed the present status and research progresses on treatment of AML aged over 80 years. Key words: Leukemia, myeloid, acute; Aged; Life support care; Prognosis; Drug therapy

Malignant hepatic vascular tumors in adults: Characteristics, diagnostic difficulties and current management.

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation (LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma (HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation Association-European Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma (HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient. Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches, alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.

The role of IRAK1 in breast cancer patients treated with neoadjuvant chemotherapy.

BackgroundIRAK1 has been shown to be abnormally expressed in a set of tumors leading to tumorigenesis and progression. IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel. However, the exact role of IRAK1 in neoadjuvant chemotherapy (NCT) for breast cancer remains unclear. The aim of this study was to investigate the relationship between the expression of IRAK1 and the clinicopathological parameters and survival prognosis of breast cancer patients treated with NCT.Patients and methodsBased on the clinical data and mRNA microarray data from 1,085 breast cancer patients in The Cancer Genome Atlas, the correlation between IRAK1 expression and clinicopathological parameters of breast cancer was analyzed. Immunohistochemistry was performed to evaluate the expression of IRAK1. The Human Protein Atlas and the String database were used to analyze the expression of IRAK1 protein and its interaction with altered neighboring proteins in breast cancer. IRAK1 alteration was analyzed in cBioPortal database. GEO enrichment of IRAK1 was performed using WEB-based Gene SeT AnaLysis Toolkit.ResultsThe expression of IRAK1 was significantly downregulated following NCT. The decreased expression of IRAK1 following NCT was positively correlated with reduced tumor size. Finally, survival analysis confirmed that a shorter survival period was correlated to higher expression of IRAK1 both before and after NCT.ConclusionThese findings advanced our understanding about the expression pattern of IRAK1 in breast cancer, especially in those patients who were treated with NCT, suggesting that IRAK1 could be used as a prognostic indicator, as well as a potential indicator for evaluating NCT efficacy for breast cancer patients.

Effectiveness of ZnPc and of an amine derivative to inactivate Glioblastoma cells by Photodynamic Therapy: an in vitro comparative study

Glioblastoma multiforme is considered to be one of the most aggressive types of tumors of the central nervous system, with a poor prognosis and short survival periods of ~ one year. The current protocol for glioblastoma treatment includes the surgical excision of the primary tumor followed by radio and chemotherapy. Photodynamic therapy (PDT) is considered a promising strategy for the treatment of several types of tumors. Phthalocyanines (Pcs) are good photosensitizers (PSs) for PDT because they induce cell death in several cellular models. ZnPc (Zn(II)phthalocyanine) is a well-known Pc, extensively tested in different cells and tumor models, but its evaluation on a glioblastoma model has been poorly studied. Herein, we compare the capacity of ZnPc and one of its derivatives, Zn(II)tetraminephthalocyanine (TAZnPc), to photoinactivate glioblastoma cells (T98G, MO59, LN229 and U87-MG) in culture. We measured the cellular uptake, the toxicity in the dark and the subcellular localization of the different Pcs, as well as the clonogenic capacity of surviving cells after PDT. The mechanism of cell death induced after PDT was determined by measuring caspase 3 activation, DNA fragmentation, phosphatidylserine externalization, mitochondrial morphological changes and loss of mitochondrial membrane potential as well as lysosomal membrane integrity. Overall, ZnPc and TAZnPc present good properties to be used as PSs with photoinactivation capacity on glioblastoma cells.

Immunocytochemistry on Sputum Samples Predicts Prognosis of Lung Cancer.

Context:Despite sputum cytology being accepted as a simple and noninvasive diagnostic method for lung cancer, the clinical usefulness of sputum for evaluation of prognosis is yet to be explored. Validation of some of the markers in sputum for prognosis prediction will be highly useful for selective therapy.Aims:This study was aimed to evaluate a reliable panel of immunocytochemical markers for their significance to predict survival.Materials and Methods:We have analyzed the expression of p53, p16, galectin-3, and epidermal growth factor receptor (EGFR) proteins in sputum samples processed in a mucolytic agent/cellblock and compared the same with that of the corresponding tissue samples.Results:Overexpression of p16 and EGFR was found to have a better survival benefit, whereas positive p53 and galectin-3 expressions had shorter period of survival. Expression patterns of all these four proteins were more or less similar in smears, cellblocks of sputum, and tissue samples except for slight changes in staining intensity which was not found to be statistically significant. No significant difference was found in the association of these proteins with survival pattern between sputum and tissue samples.Conclusion:This is the first report of immunocytochemistry of a panel of markers on cells exfoliated in sputum samples which suggests that analysis of immunocytochemical markers in sputum samples can be attempted as a cost-effective and reliable predictor of prognosis and survival. Accumulation of mutated p53, overexpression of galectin-3, and lower expression of p16 and EGFR proteins were found to predict poor prognosis for lung cancer.

Diagnostic and Prognostic Impact of Neutrophil-to-Lymphocyte Ratio for Intraductal Papillary Mucinous Neoplasms of the Pancreas With High-Grade Dysplasia and Associated Invasive Carcinoma.

The aim of this study was to evaluate the diagnostic and prognostic impact of systemic inflammatory markers for IPMN with high-grade dysplasia (HGD)/invasive carcinoma. Neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio, and C-reactive protein-to-albumin ratio were compared across the different histological grades of 205 IPMN cases. We also tested the diagnostic performance for IPMN with HGD/invasive carcinoma. The median (interquartile range) preoperative NLR was higher in IPMN with HGD/invasive carcinoma (2.03 [1.48-2.93]) than IPMN with low-grade dysplasia (1.74 [1.42-2.24], P = 0.0137). The C-reactive protein-to-albumin ratio and derived NLR values were also significant higher in cases with HGD/invasive carcinoma. A combination assay of NLR, carcinoembryonic antigen, and carbohydrate antigen 19-9 revealed a 58.8% sensitivity and 76.8% specificity. Among the cases with worrisome features, the high NLR values increased the positive predictive value (68.8%) compared with low values (31.8%). In IPMN cases with the associated invasive carcinoma, high NLR values showed association with the deeper vertical invasion and shorter survival periods. Preoperative NLR, combined with tumor markers and image findings, can be a useful predictive marker for the presence of HGD/invasive carcinoma in IPMNs. Preoperative NLR also predicts the long-term outcomes in IPMN cases with invasive carcinoma.

The relationship between aspirin use and mortality in colorectal cancer.

Aspirin use lengthens survival in patients with colorectal cancer (CRC). We aimed to add to the evidence examining this relationship and to compare the survival benefit between aspirin started before CRC diagnosis with those started after CRC diagnosis. The study involved 173 consecutive patients who had a histopathologic diagnosis of colorectal carcinoma between 1996 and 2014. The electronic medical record was used to collect data on demographic characteristics (age, sex, and race), family history of cancer, use or non-use of aspirin before and after cancer diagnosis, cancer stage at diagnosis, and days from cancer diagnosis to death. Patients were divided into aspirin using and non-aspirin using groups. Aspirin users (ASAU, n=90) were older than non-aspirin users (NASAU, n=83; 70.8±9.1 vs. 66.2±10.2 years; P=0.004). The two groups were similar in sex, race, and family history of cancer, but the non-users of aspirin were more likely to have stage III or stage IV CRC (NASAU =57.5%; ASAU =38.6%; P=0.014). Aspirin users survived more than twice the number of days than non-users (ASAU median =941 days; NASAU median =384 days; P=0.003). Patients who used aspirin only before their CRC diagnosis had a short survival period from diagnosis to death (median =149). Our findings support the relationship of aspirin use and duration of use with enhanced survival in patients with CRC. Physicians may want to recommend that patients at increased risk for CRC and those already diagnosed, but not yet on aspirin, start an aspirin regimen.

Gamma Knife Radiosurgery for Metastatic Brain Tumors from Cancer of Unknown Primary

We retrospectively analyzed treatment efficacy and identified prognostic factors impacting tumor control and survival in patients with brain metastases from cancer of unknown primary (CUP) treated with gamma knife radiosurgery (GKRS). We retrospectively reviewed the medical records of 87 patients with 520 tumors who underwent GKRS for brain metastases from CUP. The median overall survival time after initial GKRS was 6 months. The 6- and 12-month overall survival rates were 79.3% and 14.9%, respectively. Older age (P=0.002), lower Karnofsky Performance Status Index score (P= 0.026), extracranial metastases (P= 0.013), and multiple brain metastases (P= 0.007) were significantly correlated with shorter survival periods. The 6- and 12-month neurologic death rates were 25.3% and 32.2%, respectively. The 6- and 12-month neurologic deterioration rates were 24.1% and 27.6%, respectively. The 6- and 12-month distant brain control failure rates were 21.8% and 24.1%, respectively. The median tumor volume was 1.7 cm3. The median marginal prescription dose was 18 Gy. The 6- and 12-month tumor recurrence rates were 5.1% and 15.7%, respectively. Larger tumor volume (P < 0.0001) and lower prescription dose (P= 0.001) were significantly correlated with local tumor control failure. Seven patients had symptomatic radiation injury. The 6- and 12-month GKRS-related complication rates were both 6.9%. Our findings suggest that GKRS is a relatively effective and safe treatment for control of tumor progression in patients with brain metastases from CUP. Overall and neurologic survivals were short, but we recommend GKRS treatment to prevent early neurologic dysfunction and death in patients with CUP.