Esophageal cancer: current status and new insights from inflammatory markers - a brief review.

Esophageal cancer (EC) poses a significant challenge to the healthcare system due to its profound impact on cancer-related morbidity and mortality worldwide. This malignancy ranks among the most arduous conditions confronting the surgeon. EC arises from a complex interplay of genetic predispositions and environmental factors. While the incidence of esophageal adenocarcinoma (EAC) is on the rise in the West, esophageal squamous cell carcinoma (ESCC) remains prevalent in the East. Chronic inflammation plays a pivotal role in the initiation and progression of EC. Accordingly, serum inflammatory markers, growth factors, and cytokines have been shown to be clinically useful. Thus, evaluating serum cytokine levels for EC prediction is a safe and feasible screening method. Given the aggressive nature and poor prognosis of the disease, innovative approaches to diagnosis, prognosis, and management of EC are indispensable. This review discusses the major risk factors and the current landscape of EC, with a specific focus on the potential contributions of new inflammatory markers to enhance disease management and improve patient outcomes.

Studies on the association of malondialdehyde as a biomarker for oxidative stress and degree of malignancy in dogs with mammary adenocarcinomas.

BACKGROUND: Mammary adenocarcinomas are one of the most common tumour diseases in bitches. The relationship between oxidative stress and the degree of malignancy of the tumour has not been sufficiently researched in veterinary medicine. OBJECTIVES: The main objective was to investigate the potential role of MDA as a practice-relevant biomarker for the assessment of systemic oxidative stress and to determine whether this parameter can indicate the malignancy grade of a mammary adenocarcinoma. METHODS: In the present pilot study, MDA plasma concentrations were analysed in 55 bitches with (n = 28) and without (n027) malignant adenocarcinomas of the mammary gland using two different measurement methods and the relationship to tumour size was investigated. RESULTS: The mean MDA concentration measured by enzyme-linked immunosorbent assay (ELISA) was 289 ng/mL (range 365-634 ng/mL) in dogs with grade 1 adenocarcinoma (n = 13), 288.5 ng/mL (range 85-752 ng/mL) in dogs with grade 2 adenocarcinoma (n = 10), 332 ng/mL (range 239-947 ng/mL) in dogs with grade 3 (n = 5) adenocarcinoma and 293 ng/mL (range 175-549 ng/mL) in dogs without a mammary tumour (n = 27). When MDA was measured by HPLC, the average MDA concentration in the study group (n = 11) was 0.24 µmol/L (range 0.16-0.37) and that of the control group (n = 15) was 0.27 µmol/L (range 0.16-1.62). Thus, there were no significant differences between the study group with malignant adenocarcinomas and the control group in both examination methods (p > 0.05). Furthermore, there was no correlation between the MDA concentrations and the approximate volume of the mammary tumour. CONCLUSION: The results highlight the challenges of providing a prognosis for the malignancy of a mammary adenocarcinoma based on MDA concentrations in plasma using ELISA or HPLC. As a result, histopathological examination remains the gold standard for diagnosing and differentiating adenocarcinomas of the mammary gland.

THE VALUE OF PREOPERATIVE PROGNOSTIC NUTRITIONAL INDEX IN GASTRIC CANCER AFTER CURATIVE RESECTION.

BACKGROUND: Predicting short- and long-term outcomes of oncological therapies is crucial for developing effective treatment strategies. Malnutrition and the host immune status significantly affect outcomes in major surgeries. AIMS: To assess the value of preoperative prognostic nutritional index (PNI) in predicting outcomes in gastric cancer patients. METHODS: A retrospective cohort analysis was conducted on patients undergoing curative-intent surgery for gastric adenocarcinoma between 2009 and 2020. PNI was calculated as follows: PNI=(10 x albumin [g/dL])+(0.005 x lymphocytes [nº/mm3]). The optimal cutoff value was determined by the receiver operating characteristic curve (PNI cutoff=52), and patients were grouped into low and high PNI. RESULTS: Of the 529 patients included, 315 (59.5%) were classified as a low-PNI group (PNI<52) and 214 (40.5%) as a high-PNI group (PNI≥52). Older age (p=0.050), male sex (p=0.003), American Society of Anesthesiologists score (ASA) III/IV (p=0.001), lower hemoglobin level (p<0.001), lower body mass index (p=0.001), higher neutrophil-lymphocyte ratio (p<0.001), D1 lymphadenectomy, advanced pT stage, pN+ and more advanced pTNM stage were related to low-PNI patient. Furthermore, 30-day (1.4 vs. 4.8%; p=0.036) and 90-day (3.3 vs. 10.5%; p=0.002) mortality rates were higher in low-PNI compared to high-PNI group. Disease-free and overall survival were worse in low-PNI patients compared to high-PNI (p<0.001 for both). ASA III/IV score, low-PNI, pT3/T4, and pN+ were independent risk factors for worse survival. CONCLUSIONS: Preoperative PNI can predict short- and long-term outcomes of patients with gastric cancer after curative gastrectomy. Low PNI is an independent factor related to worse disease-free and overall survival.

A novel prognostic biomarker in progression free survival for patients with cervical cancer, glucose to c-reactive protein ratio (GCR).

BACKGROUND: Cervical cancer is a tumor with high morbidity and mortality. The importance of inflammatory and metabolic parameters affecting progression-free survival (PFS) and overall survival (OS) has been investigated more intensively recently. We aimed to investigate the effect of glucose/c-reactive protein (CRP) ratio [GCR], which shows these two parameters together, on PFS in cervical cancer. METHODS: We retrospectively included 90 patients with adenocarcinoma and squamous cell carcinoma of the cervix. The effects of clinical variables, inflammatory and glycemic parameters on PFS and OS were analyzed by Kaplan-Meier method. The data were compared with the healthy control group of 90 individuals using the independent t test. The effect of parameters on mortality was analyzed using ROC curves and cut off values were determined. RESULTS: Glucose, CRP, CRP/lymphocyte ratio (CLR) and GCR were statistically significant in predicting mortality (p < 0.05). Disease stage, glucose, CRP, CLR and GCR were associated with overall survival. CRP, CLR and GCR were associated with progression-free survival (p < 0.05). In multivariate analysis, GCR was prognostic for PFS (p = 0.025). GCR was statistically significant while compared with the patient and healthy control group (p < 0.001). CONCLUSION: In cervical cancer, GCR rate was found to be prognostic independent of stage. Higher GCR rate was associated with longer PFS duration.

[Clinical characteristics and prognosis analysis of gastric cancer patients with bone metastasis].

Objectives: To investigate the clinical characteristics and prognosis of bone metastasis of gastric cancer, analyze the influencing factors of bone metastasis and the effects of different treatment methods, and provide a basis for early detection and treatment optimization of bone metastasis of gastric cancer. Methods: A total of 142 gastric cancer patients with bone metastasis admitted to the First Hospital of Lanzhou University from January 2011 to December 2021 were enrolled, including 60 cases of simple bone metastasis and 82 cases of bone metastasis combined with extraosseous metastasis. 142 patients with stage Ⅲgastric cancer without distant metastasis and 142 gastric cancer patients with visceral metastasis admitted to this hospital during the same period were also enrolled for comparison. Logistic regression analysis was used to determine the influencing factors of bone metastasis, and the Cox proportional hazards regression model was used to evaluate the influencing factors of overall survival (OS) of patients with bone metastasis. Results: Among the 142 patients with bone metastasis, poorly differentiated adenocarcinoma was the main type (123 cases), and 45 patients had simultaneous bone metastasis. Rib metastasis (100 cases), spine metastasis (88 cases), and pelvis metastasis (84 cases) were more common. A total of 110 patients had multiple bone metastasis, and 82 patients had extraosseous metastasis. Results of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extraosseous metastasis group were compared. There were significant differences in age, degree of differentiation, Borrmann type, alkaline phosphatase, lactate dehydrogenase, serum calcium, alanine aminotransferase, aspartate aminotransferase, creatine kinase isoenzyme, lymphocyte, hemoglobin, platelet, CEA, CA19-9, and CA724 (all P<0.05). Multivariate logistic regression analysis showed that Borrmann type was an independent protective factor of bone metastasis of gastric cancer (type 3: OR=0.07, 95%CI: 0.01-0.64, P=0.018). Alkaline phosphatase (OR=2.54, 95% CI: 1.07-6.01, P=0.034), serum calcium (OR=2.71, 95% CI: 1.15-6.41, P=0.023), creatine kinase isoenzyme (OR=16.33, 95% CI: 1.83-145.58, P=0.012), platelet (OR=10.08, 95% CI:1.89-53.85, P=0.007), and CA19-9 (OR=2.40, 95% CI: 1.14-5.05, P=0.021) were independent risk factors of bone metastasis of gastric cancer. The median OS of the stage Ⅲ gastric cancer group, the visceral metastasis group, the bone metastasis group, and the bone metastasis with extrabony group were 47, 13, 18, and 6 months, respectively, and the difference was statistically significant (P<0.001). The median OS of patients with bone metastasis only who underwent primary tumor surgery was 33 months, better than 6 months of patients without surgery (P=0.048). Multivariate Cox regression analysis showed that extraosseous metastasis (HR=2.45, 95% CI: 1.56-3.85, P<0.001) and decreased hemoglobin (HR=1.54, 95%CI: 1.02-2.34, P=0.042) were independent risk factors of OS of gastric cancer patients with bone metastasis. Conclusions: The prognosis of gastric cancer patients with bone metastasis alone is significantly better than that of other stage Ⅳ patients. For such patients, surgery on the primary site combined with chemotherapy after full evaluation may prolong the survival time.

Predictive value of preoperative CT enhancement rate and CT perfusion parameters in colorectal cancer.

BACKGROUND: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers. METHODS: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers. RESULTS: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 - 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05). CONCLUSIONS: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.

Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC. METHODS: Patients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups. RESULTS: Among 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). CONCLUSIONS: Only patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.

BCAT1, IKZF1 and SEPT9: methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas.

INTRODUCTION: Methylated circulating tumour DNA (ctDNA) blood tests for BCAT1/IKZF1 (COLVERA) and SEPT9 (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize BCAT1, IKZF1 and SEPT9 methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection. METHODS: Tissue DNA methylation data from colorectal (COAD, READ), gastroesophageal (ESCA, STAD), pancreatic (PAAD) and cholangiocarcinoma (CHOL) adenocarcinoma cohorts within The Cancer Genome Atlas were used for differential methylation analyses. Clinicodemographic predictors of BCAT1, IKZF1 and SEPT9 methylation, and the selectivity of hypermethylated BCAT1, IKZF1 and SEPT9 for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression. RESULTS: Hypermethylated BCAT1, IKZF1 and SEPT9 were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. IKZF1 was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers BCAT1, IKZF1 and SEPT9 were largely stable across different stages of disease and were highly selective for gastrointestinal adenocarcinomas relative to other cancer types. DISCUSSION: Existing CRC methylated ctDNA blood tests for BCAT1/IKZF1 and SEPT9 might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies.

Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma.

Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients' serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.

Tumor Size Combined With CA-19 Level Improves Prediction of Survival of Patients With Pancreatic Adenocarcinoma Undergoing Perioperative Chemotherapy and Resection.

BACKGROUND AND OBJECTIVE: Five-year survival in pancreatic adenocarcinoma is less than 20%. While previous studies have postulated that a carbohydrate antigen 19-9 (CA19-9) threshold could predict outcome of resection, the role for CA19-9 in decision-making remains unclear. This study aims to assess whether CA19-9 levels combined with tumor size improve prediction of post-resection survival. METHOD: A retrospective analysis was conducted on 109 patients with pancreatic adenocarcinoma who underwent perioperative chemotherapy followed by resection. The primary outcome of mortality was, divided into short (<1 year) or prolonged (>2 years). Univariate and multivariable analyses compared the tumor size-adjusted CA19-9 between the outcome groups. RESULTS: Twenty-seven (24.78%) and eighty-two (75.23%) patients were in the short survival and prolonged-survival groups, respectively. The mean CA19-9 was significantly greater in the short vs prolonged group (P < .001). Analyzing CA19-9 level by tumor size, the association of high CA19-9 and short survival was significant for small (≤2 cm) and large tumor (>4 cm), but not for intermediate-size tumors (2-4 cm). Adjusting for preoperative variable did not change this association. CONCLUSION: CA 19-9 in combination with tumor size better identifies patients with prolonged post-resection survival. This prediction is most accurate in patients with either small (≤2 cms) or large (>4 cms) tumors compared to intermediate-size tumors.

A systematic review of circulating predictive and prognostic biomarkers to aid the personalised use of radiotherapy in the radical treatment of patients with oesophageal cancer.

BACKGROUND: The availability of circulating biomarkers that are predictive of treatment response or prognostic of overall outcome could enable the personalised and adaptive use of radiotherapy (RT) in patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). METHODS: A systematic review was carried out following Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane Library, CINAHL, Scopus and the Web of Science databases were searched for studies published between January 2005-February 2023 relating to circulating biomarkers evaluated in the context of neoadjuvant or definitive RT delivered for OAC/OSCC. Study quality was assessed using predefined criteria. RESULTS: A total of 3012 studies were screened and 57 subsequently included, across which 61 biomarkers were reported. A majority (43/57,75.4%) of studies were of Asian origin and retrospective (40/57, 70.2%), with most (52/57, 91.2%) biomarkers reported in the context of patients with OSCC. There was marked inter-study heterogeneity in patient populations, treatment characteristics, biomarker measurement and the cut points used to define biomarker positivity. Nevertheless, there is evidence for the prognostic and predictive value of circulating tumour DNA and numerous miRNAs in OAC and OSCC, as well as for the prognostic and predictive value of circulating levels of CYFRA21.1 in OSCC. CONCLUSIONS: There is consistent evidence for the potential predictive and prognostic value of a small number of biomarkers in OSCC and OAC, though these data are insufficient for translation to current clinical practice. Well-designed prospective studies are now required to validate their role in stratified and personalised RT treatment approaches.

Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer.

PURPOSE: This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). METHODS: A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. RESULTS: The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. CONCLUSION: The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials.

PURPOSE: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. METHODS AND MATERIALS: This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. RESULTS: Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .05). CONCLUSIONS: Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

Role of IL4 and GMCSF in Predicting Survival in Esophageal Cancer.

BACKGROUND: Esophageal cancer (EC) originates in the setting of chronic inflammation. Although previous studies have sought to understand the role of inflammatory signaling in EC, the effect of these immunologic changes on patient outcomes remains understudied. This study's objective was to identify relationships between cytokine levels and prognosis in a mixed cohort of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) patients. STUDY DESIGN: A total of 37 serum cytokines were profiled at the time of resection using multiplex ELISA in 47 patients (42 esophageal adenocarcinoma, 5 esophageal squamous cell carcinoma). Cytokine levels were median-binarized and assessed using Cox regression models. Findings were validated at the RNA level using The Cancer Genome Atlas EC cohort (81 esophageal adenocarcinoma, 81 esophageal squamous cell carcinoma). RESULTS: Univariable analysis revealed high serum interleukin 4 (IL4) and granulocyte-macrophage colony-stimulating factor (GMCSF) were negatively associated with overall survival (p = 0.046, p = 0.040). Multivariable analysis determined both high serum IL4 or high serum GMCSF were negatively associated with survival independent of important clinical factors (hazard ratio [HR] 7.55, p < 0.001; HR 5.24, p = 0.001). These findings were validated at the RNA level in The Cancer Genome Atlas EC cohort, where multivariable analysis identified high IL4 expression, high CSF2 expression (encodes GMCSF), and advanced pathologic stage as independent negative predictors of survival when controlled for clinical factors (HR 2.35, p = 0.012; HR 1.97, p = 0.040). CONCLUSIONS: These results show that high IL4/GMCSF levels are negatively associated with survival in EC. These relationships are independent of pathologic stage and are identified across modalities, histologic subtypes, and the presence/absence of neoadjuvant therapy.

Comprehensive RNA dataset of tissue and plasma from patients with esophageal cancer or precursor lesions.

In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett's esophagus. Per patient, a blood plasma sample, and a healthy and disease esophageal tissue sample were included. In total, this comprehensive dataset consists of 102 sequenced libraries from 51 samples. Based on this data, 119 expression profiles are available for three biotypes, including miRNA (51), mRNA (51) and circRNA (17). This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations, fusion genes, and circular RNAs.

Perioperative FOLFOX in Patients With Locally Advanced Oesogastric Adenocarcinoma.

BACKGROUND: We hypothesized that perioperative FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) might be used as an alternative to standard FLOT (docetaxel, 5-fluorouracil, leucovorin, and oxaliplatin) in patients with locally advanced oesogastric adenocarcinomas (OGA), particularly those with frailties. PATIENTS AND METHODS: We reviewed the charts of 61 consecutives patients treated with FOLFOX for resectable OGA to estimate overall survival, recurrence-free survival, and safety. RESULTS: The median follow-up was 69.7 (range=3.6-97.9) months. Few patients experienced grade 3 adverse events during the preoperative (n=6; 10%) and postoperative (n=6; 16%) phases. One patient experienced a fatal grade 5 adverse events (cardiogenic shock). Median overall survival was 51.7 months [95% confidence interval (CI)=31.6-93.2 months] and the 5-year survival rate was 44.4% (95% CI=30.3%-57.5%). CONCLUSION: Regarding its comparable efficacy and its favourable toxicity profile, perioperative FOLFOX is a reasonable alternative to FLOT for frail patients with resectable OGA.

IL-6 and IL-8 cytokines are associated with elevated prostate-specific antigen levels among patients with adenocarcinoma of the prostate at the Uganda Cancer Institute.

Background: The possible clinical application of specific cytokines and chemokines contributing to tumorigenesis and the clinical outcome of several cancers has been reported. However, less invasive and easily applicable biomarkers in prostate cancer diagnosis and prognostication are still lacking. This study assessed the levels of plasma cytokines in prostate cancer patients as potential biomarkers for noninvasive early diagnosis. Methods: The plasma levels of nine cytokines, IL-6, IL-8, IL-10, IL-1ß, IL-17A, IL-2, M-CSF, IL-12 and IFN-α, were detected by Luminex© liquid array-based multiplexed immunoassays in 56 prostate cancer patients on androgen deprivation therapy and radiotherapy and 27 normal healthy controls. Results: Levels of plasma proinflammatory cytokines IL-6 and IL-8 were markedly increased in prostate cancer patients compared with controls. There was, however, no significant difference in the concentrations of all cytokines in prostate cancer patients compared with controls. Increasing levels of IL-6 and IL-8 were significantly associated with high levels of plasma prostate-specific antigen (p < 0.05). Conclusion: Proinflammatory cytokines IL-6 and IL-8 are potential biomarkers for prostate cancer pathogenesis and could serve as markers of disease progression.

A phase II study of docetaxel plus lycopene in metastatic castrate resistant prostate cancer.

We carried out a phase II study to investigate the activity of docetaxel plus lycopene in advanced castrate resistant adenocarcinoma of the prostate. Patients were chemotherapy and biological therapy naive. Docetaxel 75 mg/m2 was given every 21 days with daily oral lycopene 30 mg. The primary endpoint was a ≥50% reduction in PSA. Secondary endpoints were median time to PSA progression, duration of response and overall survival. Thirteen patients were initiated on protocol therapy. Median age was 77 (range 55-90). Twelve patients (92%) had bone metastases. Four patients (30%) had both bone and visceral metastases. PSA response was seen in 10 patients (76.9% [95% confidence interval (CI), 46.2-94.9%]). Two patients had stable disease (SD), yielding a disease control rate of 92%. Median time to PSA progression was 8 months [95% CI, 3.5-8.7]. Median duration of response (DOR) was 7.3 months [95% CI, 4.8-13.2]. Median overall survival at 5 years was 35.1 months [95% CI 25.7-57.7]. No new safety signals were noted. No patients experienced grade 3 or above anemia. One patient (7%) experienced febrile neutropenia. A PSA response rate of 76.9% and median survival of 35.1 months compares favorably to the 45% PSA response rate and 17.4 months median survival reported for the TAX 237 trialists. While our study was limited due to small sample size, our results suggest that the combination of docetaxel and lycopene merits further study.

Preoperative Alkaline Phosphatase-to-Cholesterol Ratio as a Predictor of Overall Survival in Pancreatic Ductal Adenocarcinoma Patients Undergoing Radical Pancreaticoduodenectomy.

BACKGROUND The value of alkaline phosphatase and cholesterol for predicting overall survival (OS) in cancer patients has been previously studied. However, the predictive value of these variables in patients with pancreatic ductal adenocarcinoma (PDAC) was limited. Hence, we conducted this study to investigate the prognostic value of the alkaline phosphatase-to-cholesterol ratio (ACR) in patients undergoing radical pancreaticoduodenectomy (PD) for PDAC. MATERIAL AND METHODS A total of 102 PDAC patients undergoing radical PD at the Cancer Hospital Chinese Academy of Medical Sciences were retrospectively enrolled based on medical records from June 2009 to June 2019. R programming language was used for the optimal cutoff value of biological markers such as preoperative ACR. Kaplan-Meier method and log-rank test were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis. RESULTS The optimal cutoff value of preoperative ACR was 32.988. Patients with higher preoperative ACR values had worse OS (P<0.001). Higher preoperative ACR was significantly correlated with the degree of tumor differentiation (P<0.018); levels of alanine aminotransferase (P<0.001), aspartate aminotransferase (P<0.001), total bilirubin (P<0.001), and carbohydrate antigen 19-9 (P=0.016); and clinical symptoms (P=0.001). Multivariate analysis showed that tumor differentiation (P<0.001), ACR value (hazard ratio [HR]: 2.225, 95% confidence interval [CI]: 1.33-3.724, P=0.002), and sex (HR, 1.725, 95% CI: 1.1-2.704, P=0.018) were independent factors associated with the prognosis of PDAC patients undergoing radical PD. CONCLUSIONS The preoperative ACR was correlated with OS in pancreatic cancer patients undergoing radical pancreaticoduodenectomy. Elevated ACR was correlated with poor OS.