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The prognosis of clear cell renal cell carcinoma (ccRCC) is typically based on clinical stage, but it can vary for some patients. Transcriptomic analysis is vital for understanding ccRCC progression, though its correlation with the clinical stage in predicting prognosis is uncertain. We aim to employ trajectory inference to study ccRCC's molecular progression and identify potential new markers for judging disease progression and prognosis. Using a trajectory inference approach, we characterize the molecular progression profile of ccRCC based on transcriptome profiling. Additional pathway activity, immune response, and miRNA profiling scoring were integrated to identify possible drivers of trajectory progression. Scoring based on the trajectory demonstrates a significant improvement in patient prognosis prediction and identifies 10 risk factors in patients with low-grade tumors, and nine protective factors in patients with high-grade tumors. Mechanistically, we demonstrate an association between solute light carrier transporters are associated with ccRCC progression, with SLC7A5 expression being validated through immunohistochemistry to increase in metastatic patients. Trajectory analysis of ccRCC transcriptomes can be used to model the molecular progression of disease and may assist in ccRCC prognosis. SLC7A5 is aberrantly expressed in ccRCC and may be a risk factor for poor prognosis. [ABSTRACT FROM AUTHOR]

Objective: To undertake a comprehensive assay of PDCD11 expression in colorectal cancer (CRC) and its association with prognosis and immune cell infiltration (ICIN) utilizing bioinformatics tools. Methods: The PDCD11 expression in CRC and pan-cancer was quantified through datasets from TCGA and GEO databases, and the assay was conducted through R software and the GEPIA database. Moreover, mRNA and protein expression data of PDCD11 were attained from the HPA database. It was attempted to establish protein-protein interaction networks of PDCD11 via the STRING and GeneMANIA databases. The association of PDCD11 expression with CRC staging was evaluated through R software, while its association with CRC and pan-cancer prognosis was figured out via the GEPIA database. Furthermore, the relationship of PDCD11 expression with ICIN was assayed using R software and the TIMER database. Additionally, the influences of PDCD11 knockdown on the proliferation, apoptosis, and migration of colon cancer RKO cell lines was evaluated. Results: PDCD11 exhibited elevated expression in CRC and various other malignancies, potentially indicating a promotive role in cancer progression. Overexpression of PDCD11 was found to correlate with attenuated overall survival in CRC and other malignancies. Moreover, PDCD11 demonstrated promising predictive capabilities for distinguishing between tumor and non-tumor tissues. The positive association of high PDCD11 expression with the infiltration of neutrophils, dendritic cells, CD8+ T cells, CD4+ T cells, and macrophages, as well as with the expression of immune checkpoint molecules CTLA4 and PD-1 was noteworthy. Lentivirus-mediated PDCD11 knockdown suppressed RKO cell proliferation, colony formation, and migration, while triggered apoptosis in these cells. Conclusion: The outcomes unveiled the noticeable function of PDCD11 in CRC and various other malignancies, emphasizing its potential as a prognostic biomarker and therapeutic target.

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. In this study, we comprehensively analyzed the expression of 14 PANoptosis-related genes (PANRGs) in 28 types of tumors. Most PANRGs are upregulated in tumors, including Z-DNA binding protein 1 (ZBP1), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase (CASP) 1, CASP6, CASP8, PYCARD, FADD, MAP3K7, RNF31, and RBCK1. PANRGs are highly expressed in GBM, LGG, and PAAD, while their levels in ACC are much lower than those in normal tissues. We found that both the CNV and SNV gene sets in BLCA are closely related to survival performance. Subsequently, we conducted clustering and LASSO analysis on each tumor and found that the inhibitory and the stimulating immune checkpoints positively correlate with ZBP1, NLRP3, CASP1, CASP8, and TNFAIP3. The immune infiltration results indicated that KIRC is associated with most infiltrating immune cells. According to the six tumor dryness indicators, PANRGs in LGG show the strongest tumor dryness but have a negative correlation with RNAss. In KIRC, LIHC, and TGCT, most PANRGs play an important role in tumor heterogeneity. Additionally, we analyzed the linear relationship between PANRGs and miRNA and found that MAP3K7 correlates to many miRNAs in most cancers. Finally, we predicted the possible drugs for targeted therapy of the cancers. These data greatly enhance our understanding of the components of cancer and may lead to the discovery of new biomarkers for predicting immunotherapy response and improving the prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: TRIpartite motif (TRIM) proteins are important members of the Really Interesting New Gene‐finger‐containing E3 ubiquitin‐conjugating enzyme and are involved in the progression of hepatocellular carcinoma (HCC). However, the diverse expression patterns of TRIMs and their roles in prognosis and immune infiltrates in HCC have yet to be analyzed. Materials: Combined with previous research, we used an Oncomine database and the Human Protein Atlas to compare TRIM family genes' transcriptional levels between tumor samples and normal liver tissues, as verified by the Gene Expression Profiling Interactive Analysis database. We investigated the patient survival data of TRIMs from the Kaplan–Meier plotter database. Clinicopathologic characteristics associations and potential diagnostic and prognostic values were validated with clinical and expressional data collected from the cancer genome atlas. Results: We identified TRIM28, TRIM37, TRIM45, and TRIM59 as high‐priority members of the TRIMs family that modulates HCC. Low expression of TRIM28 was associated with shorter overall survival (OS) than high expression (log‐rank p = 0.009). The same trend was identified for TRIM37 (p = 0.001), TRIM45 (p = 0.013), and TRIM59 (p = 0.011). Multivariate analysis indicated that the level of TRIM37 was a significant independent prognostic factor for both OS (p = 0.043) and progression‐free interval (p = 0.044). We performed expression and mutation analysis and functional pathways and tumor immune infiltration analysis of the changes in TRIM factors. Conclusion: These data suggested that TRIM28, TRIM37, TRIM45, and TRIM59 could serve as efficient prognostic biomarkers and therapeutic targets in HCC. [ABSTRACT FROM AUTHOR]

Exportins as the key mediators of nucleocytoplasmic transport have been identified as the controllers of the passage of numerous types of crucial cancer-related proteins. Targeting exportins in cancer cells might represent an emerging strategy in cancer intervention with the potential to affect clinical outcomes. Here, we focused on the prognostic and therapeutic values of Exportin-T (XPOT) in neuroblastoma. The correlation between the expression and prognostic values of XPOT in patients with neuroblastoma was investigated based on both published transcriptome data and our clinical data. Then, decision curve analysis (DCA) was implemented to identify a XPOT risk prediction model. In addition, RNA inference was performed to silence the expression of XPOT to further investigate the specific roles of XPOT in the progression of neuroblastoma in vitro. Overexpression of XPOT mRNA was associated with poor clinical characteristics, such as age at diagnosis more than 18 months, amplification of MYCN, and advanced International Neuroblastoma Staging System (INSS) stage, and XPOT expression was identified as an independent poor prognosis factor for neuroblastoma using Cox proportional hazards model (P <.001). DCA suggested that neuroblastoma patients could benefit from XPOT risk prediction model-guided interventions (status of MYCN + INSS stage + XPOT). Experimentally, knockdown of XPOT by small interfering RNA inhibited the proliferation and migration in neuroblastoma cells. XPOT is identified as a novel prognostic predictor and potential therapeutic target for neuroblastoma patients. Further investigation should focus on the profound molecular mechanism underlying the tumor inhibition activity of XPOT inhibitors. [ABSTRACT FROM AUTHOR]

RNA-binding proteins (RBPs) play pivotal roles in carcinogenesis and immunotherapy. Leucine-rich pentapeptide repeat-containing protein (LRPPRC) is crucial for RNA polyadenylation, transport, and stability. Although recent studies have suggested LRPPRC's potential role in tumor progression, its significance in tumor prognosis, diagnosis, and immunology remains unclear. We comprehensively analyzed LRPPRC expression in tumors using various databases, including Human Transcriptome Cell Atlas (HTCA), University of California Santa Cruz (UCSC), Human Protein Atlas (HPA), Sangerbox, TISIDB, GeneMANIA, GSCALite, and CellMiner. We examined the correlation between LRPPRC expression level and prognosis, immune infiltration, immunotherapy, methylation, biological function, and drug sensitivity. Single-cell analysis was performed using Tumor Immune Single Cell Hub (TISCH) and CancerSEA software. Patients with acute myeloid leukemia (AML) were categorized based on LRPPRC levels for functional and immune infiltration analyses. The role of LRPPRC in cancer was validated using in vitro experiments. Our findings revealed that LRPPRC was highly expressed in almost all cancer types, indicating its significant prognostic and diagnostic potential. Notably, LRPPRC was associated with diverse immune features, such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability, suggesting its value in guiding immunotherapy strategies. Within AML, the high-expression group had lower levels of immune cells, including CD8+ T cells. In vitro experiments confirmed the inhibitory effects of LRPPRC knockdown on AML cell proliferation. This study highlights LRPPRC as a reliable pan-cancer prognostic and immune biomarker, particularly in AML. It lays the groundwork for future research on LRPPRC-targeted cancer therapies. [Display omitted] • LRPPRC is highly expressed in almost all cancer types. • LRPPRC exhibits significant prognostic and diagnostic value in most cancers. • LRPPRC significantly correlates with tumor immunity and immunotherapy pan-cancer. • Knockdown of LRPPRC inhibits cell proliferation in AML in vitro. [ABSTRACT FROM AUTHOR]

Background: The tumor microenvironment is highly heterogeneous, and it is understood to affect tumor progression and patient outcome. A number of studies have reported the prognostic significance of tumor-infiltrating lymphocytes and tumor budding in colorectal cancer (CRC). However, the significance of the intratumoral heterogeneity present in the spatial distribution of these features within the tumor immune microenvironment (TIME) has not been previously reported. Evaluating this intratumoral heterogeneity may aid the understanding of the TIME's effect on patient prognosis as well as identify novel aggressive phenotypes which can be further investigated as potential targets for new treatment. Methods: In this study, we propose and apply two spatial statistical methodologies for the evaluation of the intratumor heterogeneity present in the distribution of CD3 + and CD8 + lymphocytes and tumor buds (TB) in 232 Stage II CRC cases. Getis-Ord hotspot analysis was applied to quantify the cold and hotspots, defined as regions with a significantly low or high number of each feature of interest, respectively. A novel spatial heatmap methodology for the quantification of the cold and hotspots of each feature of interest, which took into account both the interpatient heterogeneity and the intratumor heterogeneity, was further developed. Results: Resultant data from each analysis, characterizing the spatial intratumor heterogeneity of lymphocytes and TBs were used for the development of two new highly prognostic risk models. Conclusions: Our results highlight the value of applying spatial statistics for the assessment of the intratumor heterogeneity. Both Getis-Ord hotspot and our proposed spatial heatmap analysis are broadly applicable across other tissue types as well as other features of interest. [ABSTRACT FROM AUTHOR]

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Background: CD63 has been described as a key factor in extracellular vesicle production and endosomal cargo sorting, and there have been certain reports suggesting an association between CD63 expression and survival in patients with tumors including gastric, colon and lung cancer. However, the prognostic value of CD63 expression remains contradictory. Hence, we performed this meta-analysis to assess the prognostic value of CD63 expression in solid tumors. Materials and Methods: Eligible studies were collected by searching the PubMed, Embase and Cochrane libraries. The hazard ratio (HR) with 95% confidence interval (CI) were evaluated to reveal the association between CD63 expression and survival in solid tumors. Results: Five studies with a total of 1,454 patients were included. The HR evaluating CD63 expression on survival was 1.34 (95%CI=0.92-1.97, p=0.129). In subgroup analysis, the HRs of lung cancer and other tumors were 0.50 (95% CI=0.32-0.77, p=0.002) and 2.16 (95% CI=1.93-2.42, p<0.001) respectively. CD63 expression was significantly associated with poor disease-specific survival (HR=1.69, 95% CI=1.15-2.49, p=0.008), but not with disease–free survival and overall survival. Also, there was a significant association between CD63 expression with poor survival in the group of sample size more than 150 patients (HR=2.15, 95% CI=2.92-2.41, p<0.001), but not in the group of sample size with fewer than 150 patients. Conclusion: This metaanalysis suggested that CD63 expression may be a potential prognostic marker in solid tumors. [ABSTRACT FROM AUTHOR]

Glioblastoma Multiforme (GBM) without IDH mutation has lower overall survival rate, despite having been treated by the standard treatment regimen. Nimotuzumab was expected to improve survival. Expression of EGFR and PD-L1 protein can be used as biomarkers to evaluate the prognosis in patients treated with nimotuzumab. This study aimed to demonstrate the correlation between EGFR and PD-L1 expression with the prognosis (survival rate) of GBM without IDH mutation treated with nimotuzumab. The method of this study are cross-sectional analytic observational study. Total of 26 patients newly diagnosed with GBM without IDH mutation, where 13 were treated with nimotuzumab and 13 were treated without nimotuzumab. EGFR and PDL-1 expression were evaluated using immunohistochemistry. The results is patients treated with nimotuzumab showed significantly higher mean overall survival in comparison with those without treatment (12.23 ± 10.25 vs 6.31 ± 3.33 months, p<0.05). Patients treated with nimotuzumab also showed significantly higher 1- and 2-year survival rate (30.8% vs 15.4% and 7.7% vs 0%, p<0,05). Mean overall survival in the nimotuzumab treatment group was higher in patients with negative in comparison with positive EGFR expression (26.50 ± 24.75 vs 9.64 ± 4.08 months, p>0.05), with negative in comparison with moderate PD-L1 expression (13.80 ± 17.02 vs 11.25 ± 3.41 months, p>0.05). EGFR and PD-L1 expression has not been proven useful as prognostic markers. [ABSTRACT FROM AUTHOR]

Background: Cancer is the first cause of death in developed countries. The heterogeneous nature of cancer requires patient-specified treatment plans. One reliable approach is collecting Circulating Tumour Cells (CTCs) and using them for prognosis and drug response assessment purposes. CTCs are rare and their separation from normal cell requires high-accuracy methods. Methods: A microfluidic cell capture device to separate CTCs from peripheral blood is presented in this study. The CTC separation device applies hydrodynamic forces to categorize cells according to their sizes. The proposed device is designed and evaluated by numerical simulations and validated experimentally. The simulation modified design was fabricated by soft lithography which allows prototyping the device in a few hours. For experimental setup two solutions: 1) fixed cells spiked in Phosphate Buffered Saline (PBS), and 2) fixed cells in blood were used. The CTC separation device was validated by tracking the flow and separation of cancer cell lines in the solutions. Results: It is demonstrated that the setup is capable of CTC enrichment up to 50 times. Conclusion: The presented CTC enrichment method reduces costs by eliminating the use of antibodies. The high-throughput method has the potential to be used in preclinical studies of cancer. [ABSTRACT FROM AUTHOR]

Background: The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. Materials and Methods: A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician‐predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG‐PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C‐reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. Results: Data were available on 478 patients, and the median survival was 4.27 (1.86–7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG‐PS, mGPS, WCC, NC (all p <.001), dyspnea, global health (both p ≤.001), cognitive impairment, anorexia, LDH (all p <.01), and weight loss (p <.05). On multivariate analysis ECOG‐PS, mGPS, and NC were independent predictors of survival at 1 and 3 months (all p <.01). Conclusion: The simple combination of ECOG‐PS and mGPS is an important novel prognostic framework which can alert clinicians to patients with good performance status who are at increased risk of having a higher symptom burden and dying at 3 months. From the recent literature it is likely that this framework will also be useful in referral for early palliative care with 6–24 months survival. Implications for Practice: This large cohort study examined all validated prognostic factors in a head‐to‐head comparison and demonstrated the superior prognostic value of the Eastern Cooperative Oncology Group performance status (ECOG‐PS)/modified Glasgow Prognostic Score (mGPS) combination over other prognostic factors. This combination is simple, accurate, and also relates to quality of life. It may be useful in identifying patients who may benefit from early referral to palliative care. It is proposed ECOG‐PS/mGPS as the new prognostic domain in patients with advanced cancer. This article examines prognostic factors in patients with advanced cancer, comparing validated factors to determine which are optimal. [ABSTRACT FROM AUTHOR]

Introduction: Although various phrases to communicate prognoses based on a certain concept have been proposed, no study has systematically investigated preferences of patients with cancer for actual phrases. We investigated whether phrases with a wider range and additional "hope for the best, and prepare for the worst" (hope/prepare) statement would be more preferable and explored variables associated with patients' preferences. Materials and Methods: In a cross‐sectional survey, 412 outpatients with cancer self‐assessed their preferences for 13 phrases conveying prognostic information (e.g., phrases with or without median, typical range, and/or best/worst cases, and those with or without a hope/prepare statement) on a 6‐point scale (1 = not at all preferable; 6 = very preferable). We evaluated demographic data and the Coping Inventory for Stressful Situations and conducted multivariate regression analysis. Results: Regarding phrases with various ranges, the one including the median, typical range, and best/worst cases was more preferable (mean ± SD, 3.8 ± 1.3; 95% confidence interval [CI], 3.6–3.9) than the one with the median and typical range (3.4 ± 1.2; 3.3–3.6) or the one with only the median (3.2 ± 1.3; 3.1–3.3). Concerning the hope/prepare statement, the phrase including the median, typical range, uncertainty, and hope/prepare statement was more preferable (3.8 ± 1.4; 3.7–3.9) than the one without the statement (3.5 ± 1.2; 3.4–3.6). In multivariate analyses, task‐oriented coping was significantly correlated with preferences for phrases with explicit information. Conclusion: Overall, phrases with a wider range and the hope/prepare statement were preferable to those without them. When patients with cancer ask about prognoses, especially those with task‐oriented coping, clinicians may provide explicit information with a wider range and the hope/prepare statement. Implications for Practice: Discussing prognoses with patients with advanced cancer is among the most important conversations for clinicians. In this cross‐sectional survey to systematically investigate preferences of 412 patients with cancer for phrases conveying prognostic information, phrases with the median, typical range, and best/worst cases and those with the "hope for the best and prepare for the worst" (hope/prepare) statement were the most preferred. When patients with cancer ask about prognoses, clinicians may provide explicit information with a wider range and include the hope/prepare statement. Honest prognoses discussions with advanced cancer patients are important conversations for clinicians. This article reports on patient preferences for the wording of prognostic information. [ABSTRACT FROM AUTHOR]

The surprise question (SQ), "Would you be surprised if your patient died within a year?", has been studied in the cancer population as a prognostic prompt. Studies have almost exclusively directed the SQ to physicians, whereas perspectives of nurses remain underevaluated. We asked the SQ for patients admitted to an inpatient medical oncology service to medical oncology, palliative care, and hospital medicine teams and bedside nurses. We performed a 1-year retrospective chart review to identify how concordant various provider types were in their prognostic estimations and identified the missed opportunity rate (MOR) defined as the number of patients who died within a particular time frame but who the providers had predicted would be alive and may not have had a palliative approach. Oncologists had higher MORs for the 6-month and 1-year SQ when compared with hospital medicine providers. Bedside nurses were least concordant in their estimations of prognosis and had higher MORs for all time frames of the SQ. Missed opportunities might have significant implications for the end-of-life care for cancer patients, and continued research is needed to understand what influences provider prognostication and how this impacts palliative care utilization for patients with life-limiting disease. [ABSTRACT FROM AUTHOR]

Background and objective Pneumonic-type lung carcinoma is a special type of lung cancer both clinically and radiologically. Here we present our experience on pneumonic-type lung carcinoma in an attempt to investigate the clinical, radiological and pathological features, diagnostic procedures, treatment, and prognosis of this type of tumor. Methods Pathologically confirmed lung cancer with a chest CT characterized by ground glass opacity or consolidation was defined as pneumonic-type lung carcinoma. Cases with advanced pneumonic-type lung carcinoma admitted to Peking Union Medical College Hospital (PUMCH) from January 1, 2013 to August 30, 2018 were enrolled. Retrospective analysis of clinical data and survival follow-up of these patients was conducted. Results A total of 46 cases were enrolled, all of which were adenocarcinoma. Cough (41/46, 89.1%) and expectoration (35/46, 76.1%) were the most prominent symptoms. The most frequent chest CT findings were ground glass attenuation (87.0%), patchy consolidation (84.8%), and multiple ground-glass nodules (84.8%). Multiple cystic changes (40%) and cavitation (13%) were also quite frequent. Ipsilateral and contralateral intrapul-monary metastasis were noted in 95.3% and 84.8% of cases respectively. The median duration from symptom onset to diagnosis was 214 days (95%CI: 129-298). Both surgical lung biopsy and CT-guided percutaneous lung biopsy had a diagnostic yield of 100%. Transbronchial lung biopsy (TBLB) combined with bronchoalveolar lavage (BAL) had a diagnostic yield of 80.9% (17/21). Sputum cytology had a diagnostic yield of 45% (9/20). Twenty-six cases were invasive mucinous adenocarcinoma (26/46, 56.5%) and the remainder were unable to identify pathological subtypes due to lack of adequate biopsy sample size. EGFR mutation was detected in 15.8% (6/38) of patients and ALK rearrangement was detected in 3.0% (1/33) of patients. The median overall survival for these patients was 522 d (95%CI: 424-619). In patients without EGFR mutation or ALK rearrangement, chemotherapy significantly improved survival (HR=0.155, P=0.002,2). The median overall survival was 547 d (95%CI: 492-602 d) with chemotherapy and 331 d (95%CI: 22-919) without chemotherapy. Conclusion Diagnosis of pneumonic-type carcinoma is usually delayed due to clinical and radiological features mimicking pulmonary infection. TBLB combined with BAL has a quite high diagnostic yield. The most frequent histological type is invasive mucinous adenocarcinoma. The incidence of EGFR mutation or ALK rearrangement is low in pneumonic-type carcinoma. For patients without cancer driver genes, chemotherapy is recommended to improve overall survival. [ABSTRACT FROM AUTHOR]

Background: Phase angle is a prognostic factor in patients with months of survival, but its accuracy has not been examined in patients with weeks/days of survival. We determined the association between phase angle and survival in patients with advanced cancer admitted to an acute palliative care unit (APCU). Subjects, Materials, and Methods: We prospectively assessed phase angle in consecutive patients with advanced cancer admitted to our APCU. We conducted univariate and multivariate survival analyses adjusting for established prognostic factors. Post hoc subgroup analyses examined patients with and without edema. Results: Among 204 patients, the median overall survival was 10 days (95% confidence interval [CI] 8–11 days). Seventy‐four (36%) did not have edema. The median phase angle was 3.7° for the entire cohort, 3.9° for the nonedematous subgroup and 3.6° for the edematous subgroup. In univariate analysis, a low phase angle was associated with decreased survival for the entire cohort (≤3° vs. >3°, median survival 7 vs. 10 days, p =.045) and the nonedematous subgroup (5 vs. 18 days, p <.001) but not the edematous subgroup (9 vs. 9 days, p =.84). In multivariate analysis, phase angle did not reach significance for the entire cohort but remained significant in the nonedematous subgroup (hazard ratio 2.46, 95% CI 1.14–5.31, p <.001). Specifically, phase angle ≤3° had an accuracy of 86% (95% CI 77%–93%) for 3‐day survival in patients without edema. Conclusion: Phase angle had limited prognostic utility in unselected APCU patients but was significant in the nonedematous subgroup. Further studies are required to confirm these preliminary findings. Implications for Practice: In this prospective study involving 204 patients with advanced cancer, phase angle as measured by bioelectric impedance analysis was a significant predictor of mortality independent of known prognostic factors in patients without edema but not patients with edema. Among patients without edema, a phase angle ≤3° had an accuracy of 86% for 3‐day survival, which may inform the diagnosis of impending death and potentially end‐of‐life decision making. This article reports on the association between phase angle, which is measured by bioelectric impedance analysis and reflects cellular integrity and hydration level, and survival in patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Objective and Background: Survival predictions by subjective evaluations are important for end-stage patients. However, subjective evaluations based on experience are difficult. Therefore, we investigated whether the Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and C-reactive protein (CRP)/albumin ratio (CRP/Alb ratio) calculated from the laboratory values of objective evaluations are useful for predicting survival times in end-stage patients. Methods: We retrospectively investigated the age, sex, death cause, CRP levels, Alb levels, and lymphocyte counts in 363 cancer and noncancer patients who died in the 12-month period between April 2015 and March 2016. A multivariate analysis was performed to calculate GPS, PNI, and the CRP/Alb ratio from laboratory values and adjusted for confounding factors. Results: PNI and CRP/Alb ratio exhibited negative and positive correlations with survival days, respectively. All GPS, PNI, and CRP/Alb ratio were useful to predict two to four remaining weeks. Interestingly, CRP/Alb ratio, but not GPS or PNI, was higher in patients with predicted short-term survival of zero to two weeks than in that of two to four weeks (odds ratio 2.32; 95% confidence interval 1.61–3.34). Discussion: These results suggest that the CRP/Alb ratio is an independent factor that is beneficial to predict short-term survival of within two weeks. [ABSTRACT FROM AUTHOR]

The article discusses the ethics of chemotherapy on an 18-year-old pregnant women with complaints of persistent pelvic pain at 10 weeks' gestation. She underwent removal of the intraabdominal masses at 14 weeks' gestation. The impact of chemotherapy exposure during pregnancy is based on the specific agents being administered and the gestational age of the fetus. The risk of fetal malformation is highly dependent on the timing of drug exposure.

Context: Prognosis communication is one hypothesized mechanism by which effective palliative care (PC) promotes preference-concordant treatment near end of life (EOL), but little is known about this relationship. Methods: This is a multisite cohort study of 231 hospitalized patients with advanced cancer who consulted with PC. We audio-recorded the initial consultation with the PC team and coded conversations for all statements regarding expectations for how long the patient will live. We refer to these statements as length-of-life talk. We followed patients for up to six months to determine EOL treatment utilization, including hospice enrollment. Patients completed a brief interviewer-facilitated questionnaire at study enrollment. Results: Forty-four percent (101/231) of observed conversations contained at least one statement about expectations for length of life, and 60% of patients (139/231) enrolled in hospice during the six months following these conversations. The association between length-of-life talk and hospice enrollment was strong among those (155/231) who endorsed treatment preferences favoring comfort over longevity in the last weeks to months of life (odds ratio [OR]adj = 2.98; 95% confidence interval [CI] = 1.34–6.65) and weak/absent among others (69/231; ORadj = 0.70; 95% CI = 0.16–3.04). Conclusions: Talking about expectations for remaining length of life during PC consultations is associated with six-month hospice enrollment among people with advanced cancer who endorse preferences for EOL treatment that favor comfort over longevity. [ABSTRACT FROM AUTHOR]

Background: Population-based assessment of long-term survival prospects of cancer patients in Germany have, so far, been mainly based on estimating relative 5-or 10-year survival rates. Alternatively, parametric cure models allow for determining the proportion of patients who although being affected by cancer do not exhibit higher mortality rates compared to the general population. These patients are thus considered as cured from cancer. Internationally, cure models are highly established in the monitoring of longterm survival of cancer patients. Methods: For the present analysis, population-based cancer registry data from patients aged 15 to 79 years (N=453,666) in Germany were used. In order to obtain up-to-date estimates on cure proportions of cancer patients, period analyses with a period window from 2013 to 2014 and a maximal follow-up time of 10 years were conducted. Based on parametric modelling of survival times, sex-specific estimates on cured proportions of cancer patients were calculated for all cancers as well as for the three most common cancer sites among women (breast, colon, lung) and among men (prostate, lung, colon) were calculated. In additional analyses, the extent to which the cured proportion of all cancer patients might have been overestimated due to the exclusion of DCO (Death Certificate Only) cases were quantified. Results: Overall, 64.0%(95°/crconfidence interval; 63.4-64.6) of women and 56.8% (56.3-57.4) of men were considered as statistically cured of their cancer in the sense that their mortality did not differ significantly from that of the general population. Parametric cured models also converged in all site-specific analyses except breast cancer among women. The cure proportions for colon and lung cancer were higher in women than in men (62.3%vs. 56.2%and 18.5%vs. 14.9%). Moreover, the estimated cure proportion of prostate cancer among men was 94.5%. After correctingthe cure fraction of all cancers for the proportion of DCO cases, a maximal drop of 3% was observed among both genders. Conclusions: Based on nation-wide data for the period window 2013-2014, significant sex difference in long-term cancer survival for common cancers can be observed in Germany. Parametric cured models can provide additional insights on remainingor new challenges of cancer care in Germany. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have an important role in various life processes of the body, especially cancer. The analysis of disease prognosis is ignored in current prediction on lncRNA–disease associations. In this study, a multiple linear regression model was constructed for lncRNA–disease association prediction based on clinical prognosis data (MlrLDAcp), which integrated the cancer data of clinical prognosis and the expression quantity of lncRNA transcript. MlrLDAcp could realize not only cancer survival prediction but also lncRNA–disease association prediction. Ultimately, 60 lncRNAs most closely related to prostate cancer survival were selected from 481 alternative lncRNAs. Then, the multiple linear regression relationship between the prognosis survival of 176 patients with prostate cancer and 60 lncRNAs was also given. Compared with previous studies, MlrLDAcp had a predominant survival predictive ability and could effectively predict lncRNA–disease associations. MlrLDAcp had an area under the curve (AUC) value of 0.875 for survival prediction and an AUC value of 0.872 for lncRNA–disease association prediction. It could be an effective biological method for biomedical research. [ABSTRACT FROM AUTHOR]

Background. Previous literatures have investigated the change of miR-20a expression level in the progression of multiple cancers and its influence on patients’ survival outcome, but results of now-available evidence are inconsistent. Objective. To elucidate the prognostic value of circulating and tissue-based miR-20a for patients with various cancers. Methods. A systematic search and review of eligible publications were carried out in three electronic databases including the Cochrane Library, PubMed, and Embase, and the methodological quality of included studies was assessed according to Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and progressive-free survival (PFS) of each study were pooled using a random effect model. Results. In total, 24 studies involving 4186 samples of multiple cancers published in 20 articles were included in the statistical analysis. As for circulating miR-20a, five kinds of cancers containing gastric cancer, lymphoma, glioblastoma, prostate cancer, and non-small-cell lung cancer reported upregulated level in patients compared with normal healthy control, and overexpressed circulating miR-20a could confer an unfavorable factor for OS (HR = 1.71, 95% CIs: 1.43 -2.04, p < 0.01) and DFS (HR = 1.90, 95% CIs: 1.45-2.49, p < 0.01). As for tissue-based samples, 6 kinds of malignancies including colorectal cancer, salivary adenoid cystic carcinoma, gallbladder carcinoma, colon cancer, gastrointestinal cancer, and alveolar rhabdomyosarcoma revealed upregulated miR-20a expression level compared with paired nontumorous tissue, of which high expression of miR-20a was significantly associated with poor OS (HR = 2.74, 95% CIs: 1.38-5.42, p < 0.01) and DFS (HR = 2.68, 95% CIs: 1.32-5.45, p < 0.01); meanwhile, other 5 tumors containing breast cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and epithelial ovarian cancer demonstrated downregulated miR-20a expression level compared with benign tissue, of which low miR-20a expression was significantly related to shorter OS (HR = 3.48, 95% CIs: 2.00-6.06, p < 0.01) and PFS/RFS (HR = 4.05, 95% CIs: 2.89-5.66, p < 0.01). Conclusion. Change of circulating and tissue-based miR-20a expression possesses vital prognostic implication for human cancers. Augmented expression of circulating miR-20a predicts poor survival outcome for patients with cancers. Tissue-based miR-20a level may be upregulated or downregulated depending on cancer types; in the former condition, high expression of tissue miR-20a is a risk factor for unfavorable prognosis and in the latter condition low expression of tissue miR-20a is associated with shorter survival. [ABSTRACT FROM AUTHOR]

Background Accumulating studies have demonstrated that Krüppel-like factor 4 (KLF4) can act as a tumor suppressor or oncogene in the carcinogenesis of diverse cancers. The prognostic value of KLF4 in various human solid cancers remains controversial. Thus, the present meta-analysis was conducted to evaluate the prognostic value of KLF4 in solid tumors. Methods Eligible literature was retrieved by searching the PubMed, Embase, and Cochrane Library. Combined hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were assessed using fixed-effects and random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. In addition, publication bias was assessed using Begg's funnel plot and Egger's regression asymmetry test. Results The 22 eligible studies finally enrolled a total of 2988 patients to assess the prognostic value of KLF4 in solid tumors. Low KLF4 expression was clearly related to worse OS (HR = 1.71, 95% confidence interval [CI] = 1.30–2.24, P  < 0.001) and DFS (HR = 1.74, 95% CI = 1.34–2.26, P  < 0.001), indicating that low KLF4 expression could be an independent prognostic factor for poor survival in solid cancers. Conclusion KLF4 might be a potential marker to predict prognosis in solid cancer patients. [ABSTRACT FROM AUTHOR]

Purpose This meta-analysis aims to assess the prognostic value of long non-coding RNA ZEB1-AS1 in human solid tumors. Methods We searched the available databases up to January 2018. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to examine the prognostic impact of ZEB1-AS1 on patient survival. Results Eight eligible studies with a total of 586 patients were enrolled. A significant association was observed between ZEB1-AS1 overexpression and poor overall survival (OS; HR = 2.195, 95% CI: 1.749–2.755) as well as unfavorable recurrence-free survival (pooled HR = 2.205, 95% CI: 1.486–3.270), and no heterogeneity was found across these studies ( p  = .962, I 2  = 0%). Subsequent subgroup analyses showed that cancer type, sample size, follow up months, and HR estimation method did not alter the significant prognostic value of ZEB1-AS1. ZEB1-AS1 expression was indicated to be an independent prognostic factor for tumor OS (pooled HR = 2.177, 95% CI:1.545–3.069). Furthermore, we found that increased ZEB1-AS1 expression was significantly associated with tumor stage [III-IV vs. I-II: odds ratio (OR) = 1.644, 95% CI: 1.201–2.249] and lymph node metastasis (Positive vs. Negative: OR = 2.413, 95% CI: 1.504–3.873). Conclusion High expression level of ZEB1-AS1 was associated with unfavorable survival outcome for cancer patients, and ZEB1-AS1 could be used as a prognostic predictor for cancers. [ABSTRACT FROM AUTHOR]

Abstract Background Metastasectomy is routinely performed in selected patients with metastatic clear-cell renal cell carcinoma (ccRCC) as an alternative to systemic therapy. In the absence of randomized trials, the benefit and best way of patient selection remain unclear. Earlier, we described four molecular ccRCC-subtypes (ccrcc1–4) that have a prognostic and predictive value upon first-line sunitinib or pazopanib. Objective Assess the prognostic value of ccrcc1–4 subtypes after complete metastasectomy. (1) Compare outcomes of good-prognosis ccrccc2&3-tumors with intermediate/poor-prognosis ccrcc1&4-tumors. (2) Compare outcomes of the four subtypes separately. Design, setting, and participants Single-center retrospective study (1995–2017), assessing 43 ccRCC patients undergoing complete metastasectomy without systemic treatment. Intervention Molecular subtype determined with established 35-gene expression classifier. Outcome measurements and statistical analysis Median disease-free survival (DFS), time to systemic therapy, cancer-specific (CSS) and overall survival (OS) from metastasectomy, estimated with Kaplan-Meier method and tested against other predictors with multivariable Cox regression. Results and limitations Median DFS was 23 mo for ccrcc2&3-tumors versus 9 mo for ccrcc1&4-tumors (p = 0.011, hazard ratio [HR] = 2.6). Median time to systemic therapy was 92 mo versus 28 mo (p = 0.003, HR = 3.3). Median CSS was 133 mo versus 50 mo (p < 0.001, HR = 2.7). Median OS was 127 mo versus 50 mo (p = 0.011, HR = 2.5). The classification remained independent upon multivariable analysis. Outcomes remained significantly different when comparing four subtypes separately. The intrinsic heterogeneity of expression profiles is a limitation of this approach. Conclusion Even after clinical patient selection, patients with a ccrcc1- or ccrcc4-tumor are at a higher risk of relapse after complete metastasectomy. Patients with a ccrcc2- or ccrcc3-tumor usually experience a long DFS. These results need validation in a larger cohort to establish the subtypes as prognostic marker. Patient summary Metastasectomy is recommended for some patients with metastatic clear-cell kidney cancer; however, we do not know who will benefit the most. We show that molecular subtypes increase the possibility to predict which patients are at risk for early relapse after metastasectomy and who may benefit more from other treatment options. Take Home Message Molecular subtypes of clear-cell renal cell carcinoma are prognostic for outcome after complete metastasectomy even after clinical patient selection. If validated on in a larger cohort, the ccrcc1–4 molecular classification could become a tool for patient selection. [ABSTRACT FROM AUTHOR]

Background: Primary central nervous system (CNS) solitary fibrous tumour/hemangiopericytoma (SFT/HPC) is a rare neoplasm and its classification criteria have been redefined by the latest WHO Classification of CNS Tumours. Outcome can vary significantly among patients, thus reliable prognostic markers are warranted. Methods: Primary CNS SFT/HPC diagnosed at the Pathology Unit of our Institution between 2006 and 2016 were retrospectively collected. Tumour grade along with immunohistochemistry for Ki67, STAT6, PHH3, CD34 and Bcl-2 were assessed. TERT promoter status was evaluated by Sanger sequencing. Results: Fifteen SFT/HPC were analysed: 9/15 (60%) female, median age at diagnosis 60 (range: 10–67). Six (40%) cases showed a SFT phenotype and mean H&E-mitotic count was 4.8/10 HPF. Tumour grade was I in 6, II in 4 and III in 5 cases. Mean PHH3-mitotic count was higher than H&E count (8.4 versus 4.8/10 HPF), but it would have determined a change in tumour grade in a sole case. Nuclear staining for STAT6 was present in 14/15 (93.3%). CD34 and Bcl-2 expression rates were lower in higher grade tumours. TERT promoter was mutated in two cases. Median follow up time was 2.4 years (6 months-7.4 years) and 5/15 (33%) patients developed local disease recurrence. Partial resection (p = 0.0185), higher WHO grade (p = 0.038), lower CD34 (p = 0.038) and Bcl-2 (p = 0.010) expressions were significantly associated with a poorer disease-free interval. Conclusions: WHO grade is the main prognostic tool in CNS SFT/HPC, but it could be integrated by other markers, like CD34 and Bcl-2, in the clinical practice. The relevance of TERT promoter mutations in this subset of CNS tumours needs further evaluation. [ABSTRACT FROM AUTHOR]

CIP2A, cancerous inhibitor of protein phosphatase 2A, was initially recognized as an oncoprotein. Recently several studies revealed that CIP2A could function as a prognosis biomarker, however, the result remained not comprehensive, partly due to small number of patients included individually. Here we carried out a meta-analysis of published studies to assess the prognostic significance of CIP2A in solid tumors. All eligible studies were identified through searching PubMed, Embase and Web of Science database. In this meta-analysis, 22 studies involving 4,579 participants were included, and we verified that CIP2A over-expression was significantly related with poor overall survival (pooled HR = 1.844, 95% CI = 1.528–2.225, P<0.001) and short disease free survival (pooled HR = 1.808, 95% CI = 1.591–2.055, P<0.001) in solid tumors. Additionally, subgroup analysis suggested that the trend of a poor overall survival with an increased CIP2A expression was present in East-Asian and European patients, as well as in lung cancer and colorectal cancer. To sum up, CIP2A over-expression was associated with poor survival in human solid tumors and might be a predictive factor of poor prognosis. [ABSTRACT FROM AUTHOR]

Metastasis requires cellular changes related to cell-to-cell and cell-to-matrix adhesion, immune surveillance, activation of growth and survival signalling pathways, and epigenetic modifications. In addition to tumour cells, tumour stroma is also modified in relationship to the primary tumour as well as to distant metastatic sites (forming a metastatic niche). A common denominator of most stromal partners in tumour progression is CD36, a scavenger receptor for fatty acid uptake that modulates cell-to-extracellular matrix attachment, stromal cell fate (for adipocytes, endothelial cells), TGFβ activation, and immune signalling. CD36 has been repeatedly proposed as a prognostic marker in various cancers, mostly of epithelial origin (breast, prostate, ovary, and colon) and also for hepatic carcinoma and gliomas. Data gathered in preclinical models of various cancers have shown that blocking CD36 might prove beneficial in stopping metastasis spread. However, targeting the receptor in clinical trials with thrombospondin mimetic peptides has proven ineffective, and monoclonal antibodies are not yet available for patient use. This review presents data to support CD36 as a potential prognostic biomarker in cancer, its current stage towards achieving bona fide biomarker status, and knowledge gaps that must be filled before further advancement towards clinical practice. [ABSTRACT FROM AUTHOR]

Background: Histone H3 lysine 4 methylation (H3K4 methylation), including mono‐methylation (H3K4me1), di‐methylation (H3K4me2), or tri‐methylation (H3K4me3), is one of the epigenetic modifications to histone proteins, which are related to the transcriptional activation of genes. H3K4 methylation has both tumor inhibiting and promoting effects, and the prognostic value of H3K4 methylation in cancer remains controversial. Therefore, we performed a systematic review and meta‐analysis to examine the association between H3K4 methylation and cancer prognosis. Methods: A comprehensive search of PubMed, Web of Science, ScienceDirect, Embase, and Ovid databases was conducted to identify studies investigating the association between H3K4 methylation and prognosis of patients with malignant tumors. The data and characteristics of each study were extracted, and the hazard ratio (HR) at a 95% confidence interval (CI) was calculated to estimate the effect. Results: A total of 1474 patients in 10 studies were enrolled in this meta‐analysis. The pooled HR of 1.52 (95% CI 1.02–2.26) indicated that patients with a lower level of H3K4me2 expression were expected to have shorter overall survival, while the pooled HR of 0.45 (95% CI 0.27–0.74) indicated that patients with a lower level of H3K4me3 expression were expected to have longer overall survival. Conclusion: This meta‐analysis indicates that increased H3K4me3 expression and decreased H3K4me2 expression might be predictive factors of poor prognosis in cancer. Further large cohort studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment of malignant ascites (MA) and feasibility of the management with free drainage remain unclear. Objective: To study the success of drainage, complications, and survival after paracentesis or insertion of an indwelling tunneled catheter (TC) for the MA performed on a day-case basis. Design and Setting: We evaluated 118 paracenteses and 48 insertions of TCs performed in 104 patients with MA at the Palliative Care Outpatient Unit of Tampere University Hospital. Results: Drainage of ascites fluid (median 3700 mL; range 300–13,200 mL) was successful in all cases. The complication rates were 7% and 25% for paracenteses and TCs, respectively. Most of the complications were minor. Repeated procedures were needed in 64% and 10% of the paracenteses and insertions of TCs, respectively, (p < 0.001). Median survival after the first procedure was 40 days (interquartile range, IQR: 17–115). Patients with pancreatic cancer had shorter median survival (19 days; IQR: 9–35) compared with other patients (47 days; IQR: 23–143) (age-adjusted HR 2.73; 95% CI: 1.65–4.52), whereas patients receiving chemotherapy had longer median survival (112 days; IQR: 43–205) compared with patients without chemotherapy (25 days; IQR: 14–52) (age-adjusted HR 2.48; 95% CI: 1.58–3.89). The volume of removed ascites fluid was not associated with survival. Conclusions: Free drainage of MA seems feasible in an outpatient clinic. Early insertion of TC should be considered to avoid repeated paracenteses. However, in patients with pancreatic cancer, paracentesis might be an accepted alternative due to their short life expectancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE To analyze the clinical and histopathological characteristics and treatment outcomes of patients treated and followed up for mucinous breast cancer (MBC). METHODS We retrospectively analyzed the clinical and histopathological characteristics and treatment outcomes of 22 patients who were diagnosed with and treated for MBC at our center between 2004 and 2016. RESULTS The mean age was 50 (range: 26-68) years. Ten (47.6%) patients were premenopausal. The tumor was in the right side in 11 patients (50%), and 64% of the patients had early-stage disease. There were six patients with the mixed subtype and 16 with the pure subtype. Except for the two patients with metastatic disease, all patients underwent surgery. Axillary lymph node involvement was detected in seven (36%) patients, and the proportion of patients with the pure subtype was 18%. The average duration of follow-up was 59 months, during which, four patients had recurrent disease. At 5 years, 81% of the patients were alive. The 5-year overall survival rate with pure MBC was 93%. CONCLUSION MBC is a rare condition and carries a good prognosis. Pure MBC has low axillary lymph node metastasis and a higher survival rate. [ABSTRACT FROM AUTHOR]

Purpose: Cancer is a significant health concern for adolescents and young adults (AYAs; aged 15–24 years). Monitoring population-level changes in incidence, mortality, and survival is complicated by the lack of published data presenting statistics separately for AYAs. This study synthesizes and reviews data on AYA cancers in Australia, including trends in incidence and mortality. Methods: National data were extracted for 1980–2012, primarily from the Australian Cancer Database and Australian National Mortality Database. Incidence, mortality, and survival trends are described, and incidence and mortality projections are reported. Results: In 2000–2009, the annual all-cancer incidence was 31.7 cases per 100,000 population, and the mortality rate was 4.1 per 100,000. Incidence, mortality, and survival varied widely, indicating areas of concern. Melanoma was the most common cancer, and bone cancer had the highest mortality and poorest survival rates. All-cancer incidence rates peaked in the late 1990s, but then declined, largely due to melanoma. All-cancer mortality decreased throughout the study period, but showed no improvements for some common sites (i.e., brain, bone, soft tissue). Further reductions in all-cancer incidence and mortality are projected for the next decade, although specific cancers (colorectal cancers and lymphomas) were projected to increase in incidence. Conclusions: Observed Australian cancer trends are largely consistent with trends for other high-income populations. While overall decreases in incidence and mortality are encouraging, consistently high mortality and poor survival for some cancers remain concerning. Planned data initiatives for AYAs with cancer will aid in resolving whether trends continue and projections are realized in the future. [ABSTRACT FROM AUTHOR]

Introduction: Cerebrovascular disease is the second most common cause of central nervous system involvement in cancer patients after metastases. Procoagulant substances secreted by tumour cells, cancer therapy, and embolus from tumour have been implicated in ischemic stroke (IS) in cancer patients. Methods: Four thousand twenty patients with IS were prospectively recorded to the Istanbul Medical School Stroke Registry from August 1997 to May 2016. Ninety-two patients with IS and cancer and 3928 IS patients without cancer constituted the two groups. Results: Hypertension, hyperlipidemia, and congestive heart failure were less commonly encountered in cancer stroke patients. Lacunar and posterior circulation syndromes were less common and total anterior circulation syndrome was more common in cancer patients (p<0.001). Multiple territory infarcts were more frequently seen in patients having overt or non-overt disseminated intravascular coagulopathy (DIC) compared to those without DIC. Median survival was significantly shorter in patients with cancer-related stroke. Conclusion: Cancer associated stroke without other underlying etiology is a specific group of stroke patients presenting with multiple territorial infarcts, overt or non-overt disseminated intravascular coagulopathy, and poor prognosis. [ABSTRACT FROM AUTHOR]

Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial-mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical significance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defined renal tumor tissues, including 173 (68.7%) clear cell renal cell carcinomas (ccRCC), 45 (17.9%) papillary renal cell carcinomas (pRCC) and 34 (13.5%) chromophobe renal cell carcinoma, by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters and survival outcomes were then analyzed. Twist1 was mainly localized to the cytoplasm of tumor cells (98.8%). Increased cytoplasmic expression of Twist1 was associated with higher grade tumors (P = 0.045), renal vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was positively correlated with higher grade tumors (P = 0.026), shorter progression-free survival time (P = 0.027) in patients with ccRCC, and also with higher stage in pRCC patients (P = 0.036). Significantly higher cytoplasmic expression levels of Twist1 were found in ccRCC and pRCC subtypes, due to their more aggressive tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in worse prognosis in ccRCC. These findings suggest that cytoplasmic, rather than nuclear expression of Twist1 can be considered as a prognostic and therapeutic marker for targeted therapy of RCC, especially for ccRCC patients. [ABSTRACT FROM AUTHOR]

MicroRNA-32 (miR-32) is associated with tumor progression and poor prognosis in certain malignant tumors. However, the function and clinical relevance of miR-32 in human hepatocellular carcinoma (HCC) has not yet been elucidated. The present study aimed to investigate the expression and prognostic value of miR-32 from liver samples in patients with HCC. The expression of miR-32 was analyzed in HCC and healthy tissues using Gene Expression Omnibus datasets. Reverse transcription-quantitative polymerase chain reaction was used to analyze the levels of miR-32 mRNA in 154 HCC liver samples, 33 of which were paired with adjacent non-tumor tissues. The overall survival (OS) rate in patients with HCC was evaluated using Kaplan-Meier survival analysis, and the factors that may affect the prognosis and survival of patients with HCC were analyzed using univariate (log-rank test) and multivariate Cox proportional hazard models. The present results demonstrated that miR-32 expression levels were significantly upregulated in HCC liver biopsies compared with normal tissues (P<0.05). miR-32 expression was significantly associated with the number of foci and tumor diameter (P<0.05). In addition, Kaplan-Meier analysis revealed that patients with low miR-32 expression had longer OS and disease-free survival compared with those with high miR-32 expression (P<0.01). Altogether, to the best our knowledge, the present study is the first study to indicate the association between increased miR-32 expression with HCC progression and poor prognosis in patients. This suggests that miR-32 may have potential prognostic value and may be used as a tumor biomarker for the diagnosis of patients with HCC. [ABSTRACT FROM AUTHOR]

Abstract: Background: Tumor volume in head and neck squamous cell carcinoma (HNSCC) was mainly measured in nonsurgically treated patients. We analyzed the influence of tumor volume on complete response (CR), overall survival (OS), and clear surgical margins also in primarily surgically treated patients. Methods: In contrast‐enhanced CTs, the tumor volumes of patients with incident HNSCC were measured. Results: The tumor volumes of 259 patients were measured, of which 125 patients (48%) underwent primary surgery and 102 patients (84%) had clear margins. The tumor volume was not an independent factor for CR at the primary tumor site. Risk of death increased by 1.4% per mL of tumor volume (95% confidence interval [CI] 0.8%‐2.0%; P < .001). The OS was better in patients treated with primary surgery, if the tumor volume was ≤12 mL (P < .001). Risk of involved margins increased by 4.5% per mL of tumor volume (95% CI 0.9%‐8.3%; P = .003). The predicted probability of clear margins was ≥80% in tumor volumes ≤ 16 mL. Conclusion: The tumor volume had an impact on CR, OS, and clear margins. The tumor volume may also aid in selecting HNSCC treatment. [ABSTRACT FROM AUTHOR]

Background: Prognostic uncertainty is common in advanced cancer and frequently addressed during palliative care consultation, yet we know little about its impact on quality of life (QOL). Objective: We describe the prevalence and distribution of distress due to prognostic uncertainty among hospitalized patients with advanced cancer before palliative care consultation. We evaluate the association between this type of distress and overall QOL before and after palliative care consultation. Design: Observational cohort study. Setting & Participants: Hospitalized patients with advanced cancer who receive a palliative care consultation at two geographically distant academic medical centers. Measurements: At the time of enrollment, before palliative care consultation, we asked participants: "Over the past two days, how much have you been bothered by uncertainty about what to expect from the course of your illness?" (Not at all/Slightly/Moderately/Quite a Bit/Extremely). We defined responses of "Quite a bit" and "Extremely" to be indicative of substantial distress. Results: Two hundred thirty-six participants completed the baseline assessment. Seventy-seven percent reported being at least moderately bothered by prognostic uncertainty and half reported substantial distress. Compared with others, those who were distressed by prognostic uncertainty (118/236) reported poorer overall QOL before palliative care consultation (mean QOL 3.8 out of 10 vs. 5.3 out of 10, p=<0.001) and greater improvement in QOL following consultation (Adjusted difference in mean QOL change = 1.1; 95% confidence interval = 0.2, 2.0). Conclusions: Prognostic uncertainty is a prevalent source of distress among hospitalized patients with advanced cancer at the time of initial palliative care consultation. Distress from prognostic uncertainty is associated with lower levels of preconsultation QOL and with greater pre-post consultation improvement in the QOL. [ABSTRACT FROM AUTHOR]

Although obesity is a well‐known risk factor for cancer, the association between obesity and cancer survival remains controversial. This is partially due to the inability of conventional obesity measures to directly assess adiposity or adipose tissue distribution. As a metabolic organ, visceral adipose tissue (VAT) secrets a variety of cytokines and cytokine‐like factors, potentially affecting cancer survival. The objective of this review was to investigate the influence of imaging‐assessed VAT on cancer survival. A total of 22 studies assessing the impact of visceral adiposity on survival were included. Negative associations between VAT and survival were more frequently observed among patients with colorectal (four of six studies) and pancreatic (three of five studies) cancers, compared to higher VAT predicting longer survival in most studies of renal cell carcinoma patients (four of five studies). Methodological limitations, including unstandardised VAT measurement methods, lack of other body composition measurement (i.e. muscle mass), small sample size and heterogeneous cohort characteristics, may explain controversial findings related to the impact of VAT on cancer survival. [ABSTRACT FROM AUTHOR]

Context: Survival predictions for advanced cancer patients impact many aspects of care, but the accuracy of clinician prediction of survival (CPS) is low. Prognostic tools such as the Palliative Prognostic Index (PPI) have been proposed to improve accuracy of predictions. However, it is not known if PPI is better than CPS at discriminating survival.Objective: We compared the prognostic accuracy of CPS to PPI in patients with advanced cancer.Methods: This was a prospective study in which palliative care physicians at our tertiary care cancer center documented both the PPI and CPS in hospitalized patients with advanced cancer. We compared the discrimination of CPS and PPI using concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index, and integrated discrimination improvement for 30-day survival and 100-day survival.Results: Two hundred fifteen patients were enrolled with a median survival of 109 days and a median follow-up of 239 days. The AUC for 30-day survival was 0.76 (95% CI 0.66-0.85) for PPI and 0.58 (95% CI 0.47-0.68) for CPS (P < 0.0001). Using the net reclassification index, 67% of patients were correctly reclassified using PPI instead of CPS for 30-day survival (P = 0.0005). CPS and PPI had similar accuracy for 100-day survival (AUC 0.62 vs. 0.64; P = 0.58).Conclusion: We found that PPI was more accurate than CPS when used to discriminate survival at 30 days, but not at 100 days. This study highlights the reason and timing for using PPI to facilitate survival predictions. [ABSTRACT FROM AUTHOR]

Objective Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome. Methods In a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other. Results We identified 45 patients with 53 AIDs in REISAMIC. The cancer diagnoses included melanoma (n = 36), non–small-cell lung cancer (n = 6) and others (n = 3). The most frequent pre-existing AIDs were vitiligo (n = 17), psoriasis (n = 12), thyroiditis (n = 7), Sjögren syndrome (n = 4) and rheumatoid arthritis (n = 2). Twenty patients (44.4%) presented with at least one irAE: eleven of these were associated with a pre-existing AID (‘AID flare’). Treatment with anti-PD-1 antibodies was maintained in 15 of the 20 patients with an irAE. The IrAE-free survival time was significantly shorter in AID patients (median: 5.4 months) than in AID-free patients (median: 13 months, p = 2.1 × 10 −4 ). The AID and AID-free groups did not differ significantly with regard to the overall survival time and objective response rate (p = 0.38 and 0.098, respectively). Conclusion In patients treated with anti-PD-1 antibody, pre-existing AID was associated with a significantly increased risk of irAEs. Our results indicate that cancer treatments with anti-PD-1 antibodies are just as effective in AID patients as they are in AID-free patients. [ABSTRACT FROM AUTHOR]

Background/Aims: Elevated pretreatment plasma D-dimer level has been reported as an unfavorable prognostic indicator in several malignancies. The aim of this meta-analysis was to evaluate the prognostic value of elevated D-dimer level in solid tumors. Methods: A comprehensive search of electronic databases up to June 10, 2017 was carried out by two independent reviewers. We included studies exploring the association between pretreatment plasma D-dimer level and patients' survival outcomes in solid tumors. Overall survival (OS) was regarded as primary outcome and progression-free survival (PFS), disease-free survival (DFS) as well as cancer-specific survival (CSS) were chosen as secondary outcomes. Hazard ratio and 95% confidence interval (CI) were extracted directly or indirectly from included studies. Results: 49 studies with 13001 patients were included in our meta-analysis. Elevated D-dimer was markedly associated with poor OS (pooled HR = 1.90, 95% CI = 1.63 - 2.20, P < 0.001). The effect was observed in all different tumor sites, disease stages, cut-off values and ethnicities. Meanwhile, patients with a high plasma D-dimer had a shorter PFS (HR = 1.46, 95% CI = 1.22-1.76; P < 0.001), DFS (HR = 2.02, 95% CI = 1.56-2.62) and CSS (HR = 2.04, 95% CI= 1.58 - 2.64). Conclusions: Analysis of the pretreatment plasma D-dimer might provide useful information to predict prognosis in patients with solid tumors. [ABSTRACT FROM AUTHOR]

Background:The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer. Method:This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009–2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations. Results:Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n = 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n = 195) or other/multiple (n = 187) distant metastases (p = .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99,p = .001) or other/multiple distant sites (HR 2.67,p = .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p = .245). Conclusion:Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: No series had been reported focusing on the results of fertility‐sparing surgery in stage I mucinous ovarian cancers according to histotype (infiltrative vs. expansile). Investigating such outcomes was the aim of the present study. Materials and Methods: The present study was a retrospective analysis of patients treated conservatively with preservation of the uterus and contralateral ovary from 1976 to 2016. The pathology of the tumors was reviewed by two expert pathologists according to the 2014 World Health Organization (WHO) classification criteria. Oncologic and fertility results were analyzed. Results: Twenty‐one patients fulfilled the inclusion criteria, twelve with expansile and nine with infiltrative cancer. All patients had a unilateral tumor and underwent unilateral salpingo‐oophorectomy in one‐step (n = 6) or two‐step (n = 15) surgeries. All but one had complete peritoneal staging surgery based on cytology, omentectomy, and random peritoneal biopsies. Ten had nodal staging surgery. The International Federation of Gynecology and Obstetrics stages were IA (n = 9), IC1 (n = 6), and IC2 (n = 6); the nuclear grades were grade 1 (n = 9), grade 2 (n = 5), and grade 3 (n = 1). Two patients recurred (one expansile and one infiltrative type) 19 and 160 months after surgery, respectively. One stage IA, nuclear grade 2 expansile tumor recurred on the spared ovary; the patient remains alive. The other stage IA infiltrative tumor recurred as peritoneal spread; the patient is alive with disease. Six patients became pregnant; four with expansile tumors and two with infiltrative tumors. Conclusion: The type of mucinous cancer has no impact on the oncologic outcome in this series of patients treated conservatively. Fertility‐sparing surgery should be considered for early‐stage infiltrative‐type tumors. Implications for Practice: According to the most recently updated World Health Organization classification guidelines, mucinous cancers should be classified as either expansile or infiltrative. The infiltrative type has a poorer prognosis, but there are no data about the safety of fertility‐sparing surgery (FSS) in this context. A collection of 21 cases reviewed by two expert pathologists this study is the first devoted to the conservative treatment of mucinous tumors according to both subtypes. The key result was that the type of mucinous cancer has no impact on the oncologic outcome; thus, FSS may be considered in both subtypes. [ABSTRACT FROM AUTHOR]

Background: Prognosis is one of the most challenging questions with which physicians are confronted. Accuracy in the prediction of survival is necessary for clinical, ethical, and organizational reasons. Aim: Evaluate young doctors' clinical prediction of survival and the aids they could get: expert opinion, Palliative Prognostic score, and Palliative Prognostic Index. Design: Prospective, observational study. Setting/participants: Advanced cancer patients under observation of an inhospital palliative care team, from April to July 2014. A total of 38 patients were included, mostly male (65.8%), average age 68.5 years. Average survival time was 24 days. Follow-up concluded with death or after 90 days. Results: Young doctors' clinical prediction of survival was adequate at 10.5%, with 55.3% severe errors in an optimistic direction. Palliative care experts were more adequate (23.7%) and made less severe errors (42.1%). Palliative Prognostic score and Palliative Prognostic Index were even more adequate (47% and 55%, respectively) and made even less severe errors (0% and 11%, respectively). The best correlation with observed survival was achieved when palliative care experts used palliative prognostic score (rs = -0.629; p < 0.01). Conclusion: Young doctors' clinical prediction of survival is often inadequate. Palliative Prognostic score, which includes clinical prediction of survival, calculated by palliative care experts had the best performance. Our results support the recommendation of using clinical prediction of survival together with prognostic scores. [ABSTRACT FROM AUTHOR]

Objective: Our aim is to examine the clinical characteristics of patients in a palliative care center and to investigate the factors associated with long-term hospitalization and hospital discharge status. Methods: The study is described as a cross-sectional-retrospective study. The files of who applicate patients were examined between August 1, 2015 and July 30, 2017 term in palliative care center. Demographic characteristics, comorbid conditions, numbers of medication, complaints of hospitalization, nutritional, pressure sore, and pain status at first hospitalization were evaluated for whole patients. Variables were analyzed using Spearman's correlation test that factors associated with long-term hospitalization (≥15 days) and discharge status (go home, referred to advance intensive care unit, and ex). Results: The mean age of 319 patients (55% male, 45% females) was 71±15.8 and mean duration of hospitalization was 15.4±15.7 days. The most common comorbid diseases were malnutrition (59%), malignancy (44%), and infectious disease (33%). The most frequent admission complaints were oral intake impairment (35%), general condition impairment (15%), and fever (17%). Positive factors associated with long-term hospitalization were advanced stage pressure sore (r=0,366; p<0,001), cerebrovascular disease (r=0,175; p=0,002), hypertension (r=0,158; p=0,005), and diabetes mellitus (r=0,129; p=0,021). Positive factors related to discharge status (referred to intensive care unit and/or ex) were malignancy (r=0,234; p<0,001), using opioid (r=0,204; p<0,001), parenteral nutrition (r=0, 20; p<0.001) and weakness-fatigue symptoms (r=0.115, p=0.041). Conclusion: Advanced stage pressure sore are the most important factor that prolongs the length of hospital stay. The most effective factors for patients with discharge status are malignancy, using opioid, parenteral nutrition and the symptoms of weakness-fatigue. [ABSTRACT FROM AUTHOR]

Purpose: The Palliative Performance Scale (PPS) is a widely used prognostic tool in patients with advanced cancer. This study examines the association between changes in PPS score and survival in patients with advanced cancer. Methods: We identified a cohort of 606 inpatients who died at a Korean university hospital's hospice/palliative care center. For each patient, the PPS score was measured twice according to a standard procedure: 1) upon admission, and 2) three days after admission (D3). "Change on D3" was defined as a difference between initial PPS and PPS on D3. We used a Cox regression modeling approach to explore the association between this score change and survival. Results: The changes in scores were associated with survival. A score change of >30% yielded a hazard ratio for death of 2.66 (95% CI 2.19 ~ 3.22), compared to a score change of ≤30%. PPS of ≤30 on D3 also independently predicted survival, with a hazard ratio of 1.67 (95% CI 1.38 ~ 2.02) compared to PPS of >30. Conclusion: A change of over 30% in PPS appears to predict survival in hospitalized patients with terminal cancer, even after adjustment for confounders. Changes in PPS may be a more sensitive indicator of impending death than a single PPS measured on the day of admission in terminal cancer patients. Further prospective study is needed to examine this important finding in other populations. [ABSTRACT FROM AUTHOR]

The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc . Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin's potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients. [ABSTRACT FROM AUTHOR]

Background NDUFA4L2 ( NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2, also called NADH-ubiquinone oxidoreductase MLRQ subunit homologue) was clearly enriched in the mitochondrial fraction under hypoxic conditions, and immunofluorescence showed a clear colocalization of NDUFA4L2 and cytochrome c in some tumour cells. However, little study has investigated its prognostic value in colorectal cancer ( CRC). Methods In our study, mRNA-NDUFA4L2 and protein expression were analysed in 150 cases of CRC and adjacent normal tissues using immunohistochemistry, semi-quantitative reverse transcriptase-polymerase chain reaction. The correlation between NDUFA4L2 expression and clinicopathological factors was evaluated by the Chi-square test. Overall survival of patients was analysed by the Kaplan-Meier method. Results NDUFA4L2 overexpression was observed in 84% (126/150) of CRC tissues, but only in 24.7% (37/150) of adjacent normal tissues ( P < 0.05). Semi-quantitative reverse transcriptase-polymerase chain reaction showed average mRNA expression levels to be 23.34 ± 1.356 and 4.34 ± 1.132 for CRC tissue and adjacent normal tissue ( P < 0.05). Statistical analysis showed a significant correlation of NDUFA4L2 expression with histological grade, Dukes' stages, lymph node metastasis and liver metastasis. More importantly, multivariate analysis indicated that overexpression of NDUFA4L2 was an independent prognostic factor for CRC patients ( P = 0.002). NDUFA4L2-negative patients had a higher tumour-free/overall survival rate than patients with high NDUFA4L2 expression ( P = 0.001 and 0.002, respectively). Conclusions Our data suggest that NDUFA4L2 overexpression is associated with tumour progression and a poor prognosis in CRC patients. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to elucidate the clinicopathological significance and prognostic role of microvessel density (MVD) in gastric cancer (GC) through a meta-analysis. Methods This meta-analysis included 4094 patients from 26 eligible studies. We investigated the correlation between MVD and clinicopathological characteristics, including survival rate. In addition, subgroup analysis based on microscopic magnification among evaluation criteria of MVD was performed. Results High MVD was significantly correlated with worse overall and disease-free survival rates [hazard ratio (HR), 3.028, 95% confidence interval (CI) 2.105–4.357 and HR 2.045, 95% CI 1.530–2.732, respectively]. MVD was significantly increased in GC with diffuse type of Lauren’s classification [mean difference (MD) 3.091, 95% CI 0.615–5.567], lymphatic invasion (MD 8.262, 95% CI 3.310–13.214), lymph node metastasis (MD 5.730, 95% CI 2.444–9.016), higher pT stage (pT3-4) (MD 7.093, 95% CI 0.060–14.126) and higher pTNM stage (III–IV) (MD 3.023, 95% CI 0.181–5.865). However, MD of MVD was not significantly different in regard to vascular invasion (MD 7.430, 95% CI 1.015–15.875), tumor differentiation (MD 5.501, 95% CI 1.353–12.355) and tumor size (MD 4.731, 95% CI 2.003–11.465). Conclusion Taken together, higher MVD was significantly correlated with worse prognosis. In addition, MVD was significantly higher in GC with aggressive tumor behavior than in GC without aggressive features. [ABSTRACT FROM AUTHOR]

Objectives: The classification of pathological tumor-node-metastasis (pTNM) staging of gastric cancer was revised in the 8th American Joint Committee on Cancer (AJCC) edition. The major revision was the separation of pN3a and pN3b in the pTNM staging. The current study evaluated the prognostic impact of this change. Methods: A total of 1,517 patients who underwent curative surgery for gastric cancer with a retrieved lymph node number ≥15 at our institution from January 1995 to December 2011 were enrolled. Survival was compared for the disease classified according to both the 7th and 8th editions. Results: After separation of pN3a and pN3b in the pTNM stage definition, the 8th edition still provides significant survival differences between each stage. The multivariate analysis demonstrated that the pTNM stage in both the 7th and 8th editions was an independent prognostic factors of overall survival and disease-free survival. The 8th edition has a better homogeneity than the 7th edition with a significantly higher likelihood ratio chi-square test. Regarding the OS and DFS, the time-dependent receiver operating characteristic (ROC) curves of the two staging systems are almost overlapping, indicating that the prognostic performance is comparable between the two staging systems. Conclusions: Both the 7th and 8th edition-based stages are independent prognostic factors for gastric cancer. The 8th edition has a better homogeneity than the 7th edition; the 8th edition provides discriminant survival differences among each pTNM stage that are comparable to those in the 7th edition. [ABSTRACT FROM AUTHOR]