High Tumor-Infiltrating Lymphocyte Count Is Associated with Distinct Gene Expression Profile and Longer Patient Survival in Advanced Ovarian Cancer.

Cancer-related immunity plays a significant role in the outcome of ovarian cancer, but the exact mechanisms are not fully explored. A retrospective, real-life observational study was conducted including 57 advanced ovarian cancer patients. Immunohistochemistry for CD4+, CD8+, and CD45+ was used for assessing tumor-infiltrating immune cells. Furthermore, an immune-related gene expression assay was performed on 12-10 samples from patients with less than and more than 1-year overall survival (OS), respectively. A higher number of CD4+ (p = 0.0028) and CD45+ (p = 0.0221) immune cells within the tumor microenvironment were associated with longer OS of patients. In a multivariate setting, higher CD4+ T cell infiltration predicted longer OS (p = 0.0392). Twenty-three differentially expressed genes-involved in antigen presentation, costimulatory signaling, matrix remodeling, metastasis formation, and myeloid cell activity-were found when comparing the prognostic groups. It was found that tumor-infiltrating immune cell counts are associated with peculiar gene expression patterns and bear prognostic information in ovarian cancer. SOX11 expression emerged and was validated as a predictive marker for OS.

[The occurrence and impact on survival of type 2 diabetes mellitus and thrombocytosis in colorectal cancer, before and after the surgical resection of the primary tumor]. / Colorectalis daganatokban a 2-es típusú cukorbetegség és a thrombocytosis elofordulása, a túlélésre gyakorolt hatásuk, a primer tumor mutéti eltávolítása elott és után.

INTRODUCTION: The relationship between platelets and metastatic tumor cells is an ongoing research area. Pre- and postoperative thrombocytosis are suggested predictive survival markers. Colorectal cancer and type 2 diabetes are characterized by various changes to platelets. The occurrence of colorectal cancer is more frequent in diabetes. AIM: Our aim was to determine the occurrence of type 2 diabetes in colorectal cancer patients, who attended the Semmelweis University 2nd Department of Internal Medicine's Oncology Department in the last three years. Further goals included the evaluation of anamnestic, pre- and postoperative laboratory data, and whether diabetes can be a significant survival factor. METHOD: A retrospective study was conducted with 86 randomly selected colorectal cancer patients' preoperative (86 patients) and paired postoperative (66, who were operable) data. Patients were monitored no later than September 30, 2017 or until their death. RESULTS: Preoperatively, elevated (over 400 Giga/L) platelet counts were present in 22.1% of the patients (323.5 ± 128.63 Giga/L, mean ± SD) which decreased to 10.6% postoperatively (χ2: p = 0.0351; 289.2 ± 82.45 Giga/L, p = 0.0232). Negative correlation was found between platelet counts and overall survival (R: -0.35, p = 0.0085). One third of the patients had diabetes. Laboratory results (i.e., blood counts, creatinine) between diabetic and non-diabetic patients were not significant. Diabetes is a significant five-fold postoperative risk factor for shorter overall survival (relative risk: 5.1612, p = 0.0165). Average survival was 30.6 ± 26.78 months. CONCLUSION: Persistent consequential postoperative thrombocytosis may indicate shorter survival time. Our observations suggest elevated platelet counts and type 2 diabetes as prognostic markers for survival at the recognition of colorectal tumors. Orv Hetil. 2018; 159(19): 756-767.

[Electromagnetic procedures in the treatment of pancreatic cancer: eminent or resentful?] / Elektromágneses eljárások a hasnyálmirigyrák kezelésében: eminens vagy renitens?

The treatment of advanced-stage pancreatic cancers is limited. Previous studies have found that the use of modulated electro-hyperthermia (mEHT) is beneficial in this patient population. However, there is no data on the optimal treatment number and initiation period. Therefore, a retrospective study was conducted with the inclusion of 96 mEHT-treated and 86 age- and sex-matched control pancreatic cancer patients. 76, 57, 38 and 33 patient pairs were enrolled into propensity score matched cohorts, whether they received at least 10, 20, 30 and 40 mEHT treatments, respectively. The survival of patients with at least 30 (HR: 0.5011; p = 0.0041) and 40 (HR: 0.5048; p = 0.0085) mEHT treatments was significantly longer, median survival was almost twice as long (10 vs. 18 months). The introduction of mEHT had the greatest benefit in the first (HR: 0.5382; p = 0.0056) and second (HR: 0.7861; p = 0.0031) 6 months after diagnosis.

Meta-Analysis of Modulated Electro-Hyperthermia and Tumor Treating Fields in the Treatment of Glioblastomas.

BACKGROUND: Glioblastoma is one of the most difficult to treat and most aggressive brain tumors, having a poor survival rate. The use of non-invasive modulated electro-hyperthermia (mEHT) and Tumor Treating Fields (TTF) devices has been introduced in the last few decades, both of which having proven anti-tumor effects. METHODS: A meta-analysis of randomized and observational studies about mEHT and TTF was conducted. RESULTS: A total of seven and fourteen studies about mEHT and TTF were included, with a total number of 450 and 1309 cases, respectively. A 42% [95% confidence interval (95% CI): 25-59%] 1-year survival rate was found for mEHT, which was raised to 61% (95% CI: 32-89%) if only the studies conducted after 2008 were investigated. In the case of TTF, 1-year survival was 67% (95% CI: 53-81%). Subgroup analyses revealed that newly diagnosed patients might get extra benefits from the early introduction of the devices (mEHT all studies: 73% vs. 37%, p = 0.0021; mEHT studies after 2008: 73% vs. 54%, p = 0.4214; TTF studies: 83% vs. 52%, p = 0.0083), compared with recurrent glioblastoma. CONCLUSIONS: Our meta-analysis showed that both mEHT and TTF can improve glioblastoma survival, and the most benefit may be achieved in newly diagnosed cases.

Influence of the duration of type 2 diabetes mellitus on colorectal cancer outcomes.

Type 2 diabetes mellitus (T2DM) is a progressive disease, which affects colorectal cancer (CRC) survival. However, data on the relationship between CRC survival and T2DM duration is scarce and controversial. A retrospective observational study was conducted. Sub-cohorts were created based on the duration of T2DM as follows, ≤ or > 5/10/15/20 years. 204 of the 817 (24.95%) included study participants had T2DM at any point of CRC. 160 of the 204 CRC + T2DM patients had detailed T2DM duration data. At the time of CRC diagnosis, 85, 50, 31, and 11 patients had T2DM for > 5/10/15/20 years, respectively, which increased to 110, 71, 45, and 17 during the course of the study. Despite constant glycated hemoglobin values throughout the study, shorter overall and disease-specific survival times were observed for the > 5/10/15 years cohorts and longitudinal survival modeling techniques confirmed the significant effect of T2DM duration in all cohorts. While in the first 3 years after CRC diagnosis, the best survival was found for the ≤ 5 years cohort, all diabetes cohorts had the same survival thereafter. T2DM duration affected CRC survival significantly, therefore, a closer follow-up of this sub-populations is suggested.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases.

BACKGROUND: Advanced gastric cancer with synchronous peritoneal metastases (GC-PM) is associated with a poor prognosis. Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising approach, only a limited number of Western studies exist. AIM: To investigate the clinicopathological outcomes of patients who underwent CRS-HIPEC for GC-PM. METHODS: A retrospective analysis of patients with GC-PM was conducted. All patients were seen at the Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany between January 2011 and July 2021 and underwent CRS-HIPEC. Preoperative laboratory results, the use of neoadjuvant trastuzumab, and the details of CRS-HIPEC, including peritoneal carcinomatosis index, completeness of cytoreduction, and surgical procedures were recorded. Disease-specific (DSS), and overall survival (OS) of patients were calculated. RESULTS: A total of 73 patients were included in the study. Patients treated with neoadjuvant trastuzumab (n = 5) showed longer DSS (P = 0.0482). Higher white blood cell counts (DSS: P = 0.0433) and carcinoembryonic antigen levels (OS and DSS: P < 0.01), and lower hemoglobin (OS and DSS: P < 0.05) and serum total protein (OS: P = 0.0368) levels were associated with shorter survival. Longer HIPEC duration was associated with more advantageous median survival times [60-min (n = 59): 12.86 mo; 90-min (n = 14): 27.30 mo], but without statistical difference. To obtain additional data from this observation, further separation of the study population was performed. First, propensity score-matched patient pairs (n = 14 in each group) were created. Statistically different DSS was found between patient pairs (hazard ratio = 0.2843; 95% confidence interval: 0.1119-0.7222; P = 0.0082). Second, those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity (median survival: 12.68 mo vs 24.02 mo), or had to undergo the procedure before 2016 (median survival: 12.68 mo vs 27.30 mo; P = 0.0493) were removed from the original study population. CONCLUSION: Based on our experience, CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients. Prolonged HIPEC duration may serve as a good therapy for these patients.

Comparison of the effectiveness of integrative immunomodulatory treatments and conventional therapies on the survival of selected gastrointestinal cancer patients.

In the last decade, the use of immunomodulating treatments (IMT) at integrative oncology providers (IOP) increased. IMTs are used to modulate the tumor microenvironment, which might lead to increased response-to-treatment, and the indication of immune checkpoint inhibitors might also be widened. The efficacy and safety of IMTs in advanced/metastatic gastrointestinal cancers were compared with conventional chemo(radio)therapy (CT). 21 colorectal- (CRC), 14 pancreatic- (PC), 5 cholangiocellular- (CCC), 5 gastric- (GC) and 4 esophageal cancer (EC) patients received IMT. IMT and CT were compared in CRC and PC. CT was administered at an academic oncology center. After the initiation of IMT, a median survival of ~ 20 (CRC, PC and EC) and ~ 10 months (CCC and GC) was observed. Of the IMTs, locoregional modulated electro-hyperthermia had the most positive effect on overall survival (HR: 0.3055; P = 0.0260), while fever-inducing interleukin-2, and low-dose ipilimumab showed a positive tendency. IMT was superior to CT in PC (HR: 0.1974; P = 0.0013), while modest effect was detected in CRC (HR: 0.7797; P = 0.4710). When the whole study population was analyzed, IMTs showed minimal effect on patient survival, still CT had the greatest effect if introduced as early as possible (HR: 0.0624; P < 0.0001). The integrative IMTs in the presented form have mild impact on gastrointestinal cancer patients' survival, however, we observed its benefit in PC, which warrants further investigations.

The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience.

BACKGROUND: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna® Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing. We also examined the impact of various PAM50 parameters on overall survival (OS) and progression-free survival (PFS). RESULTS: We analyzed 42 unilateral breast cancer samples, with 18 classified as luminal A, 10 as luminal B, 8 as Human epidermal growth factor receptor 2 (HER2)-positive, and 6 as basal-like using PAM50. Interestingly, 17 out of the 42 samples (40.47%) showed discordant results between histopathological assessment and the PAM50 classifier. While routine IHC/FISH resulted in classification differences for a quarter to a third of samples within each subtype, all basal-like tumors were misclassified. Hormone receptor-positive tumors (hazard rate: 8.7803; p = 0.0085) and patients who had higher 10-year recurrence risk scores (hazard rate: 1.0539; p = 0.0201) had shorter OS and PFS. CONCLUSIONS: Our study supports the existing understanding of molecular subtypes in breast cancer and emphasizes the overlap between clinical characteristics and molecular subtyping. These findings underscore the value of gene expression profiling, such as PAM50, in improving treatment decisions for breast cancer patients.

New therapeutic approaches for type 1 diabetes: Disease-modifying therapies.

It has been 100 years since the first successful clinical use of insulin, yet it remains the only treatment option for type 1 diabetes mellitus (T1DM) patients. Advances in diabetes care, such as insulin analogue therapies and new devices, including continuous glucose monitoring with continuous subcutaneous insulin infusion have improved the quality of life of patients but have no impact on the pathogenesis of the disease. They do not eliminate long-term complications and require several lifestyle sacrifices. A more ideal future therapy for T1DM, instead of supplementing the insufficient hormone production (a consequence of ß-cell destruction), would also aim to stop or slow down the destructive autoimmune process. The discovery of the autoimmune nature of type 1 diabetes mellitus has presented several targets by which disease progression may be altered. The goal of disease-modifying therapies is to target autoimmune mechanisms and prevent ß-cell destruction. T1DM patients with better ß-cell function have better glycemic control, reduced incidence of long-term complications and hypoglycemic episodes. Unfortunately, at the time symptomatic T1DM is diagnosed, most of the insulin secreting ß cells are usually lost. Therefore, to maximize the salvageable ß-cell mass by disease-modifying therapies, detecting autoimmune markers in an early, optimally presymptomatic phase of T1DM is of great importance. Disease-modifying therapies, such as immuno- and regenerative therapies are expected to take a relevant place in diabetology. The aim of this article was to provide a brief insight into the pathogenesis and course of T1DM and present the current state of disease-modifying therapeutic interventions that may impact future diabetes treatment.

High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is often associated with elevated platelet count (> 400 × 109/L), known as thrombocytosis. The role of CD40 ligand (CD40L), a member of the tumor necrosis factor family, is controversial in CRC. Circulating CD40L is higher in CRC, but its relationship with disease staging and local and distant metastasis is not clear. Although most of the circulating CD40L is produced by platelets, no previous study investigated its relationship with CRC-related thrombocytosis. AIM: To investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis. METHODS: A total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study. Anamnestic data including comorbidities and histopathological data were collected. Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor. Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay, while plasma interleukin-6 was measured via electrochemiluminescence immunoassay. Patient follow-ups were terminated on January 31, 2021. RESULTS: Plasma CD40L of CRC patients was tendentiously higher, while platelet count (P = 0.0479), interleukin-6 (P = 0.0002), and thrombopoietin (P = 0.0024) levels were significantly higher as opposed to the control subjects. Twelve of the 106 CRC patients (11.3%) had thrombocytosis. Significantly higher CD40L was found in the presence of distant metastases (P = 0.0055) and/or thrombocytosis (P = 0.0294). A connection was found between CD40L and platelet count (P = 0.0045), interleukin-6 (P = 0.0130), and thrombocytosis (P = 0.0155). CD40L was constant with the course of CRC, and all baseline differences persisted throughout the whole study. Both pre- and postoperative elevated platelet count, CD40L, and interleukin-6 level were associated with poor overall and disease-specific survival of patients. The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis. CONCLUSION: CD40L levels of CRC patients do not change with the course of the disease. The CD40L level is strongly correlated with platelet count, interleukin-6, thrombocytosis, and the presence of distant metastases.

Longitudinal Analysis of 1α,25-dihidroxyvitamin D3 and Homocysteine Changes in Colorectal Cancer.

BACKGROUND: 1α,25-dihydroxycholecalciferol (1,25(OH)2D3) and homocysteine are known to play a role in the pathophysiology of colorectal cancer (CRC). In health, the two changes are inversely proportional to each other, but little is known about their combined effect in CRC. METHODS: The serum 1,25(OH)2D3 and the homocysteine levels of eighty-six CRC patients were measured, who were enrolled into four cohorts based on the presence of metastases (Adj vs. Met) and vitamin D3 supplementation (ND vs. D). RESULTS: 1,25(OH)2D3 was constant (Adj-ND), increased significantly (Adj-D, p = 0.0261), decreased (Met-ND), or returned close to the baseline after an initial increase (Met-D). The longitudinal increase in 1,25(OH)2D3 (HR: 0.9130, p = 0.0111) positively affected the overall survival in non-metastatic CRC, however, this effect was cancelled out in those with metastasis (p = 0.0107). The increase in homocysteine negatively affected both the overall (HR: 1.0940, p = 0.0067) and the progression-free survival (HR: 1.0845, p = 0.0073). Lower 1,25(OH)2D3 and/or higher homocysteine level was characteristic for patients with higher serum lipids, albumin, total protein, white blood cell and platelet count, male sex, and right-sided tumors. No statistically justifiable connection was found between the target variables. CONCLUSIONS: A measurement-based titration of vitamin D3 supplementation and better management of comorbidities are recommended for CRC.

Does diabetes affect paraneoplastic thrombocytosis in colorectal cancer?

BACKGROUND: A large variety of factors can affect colorectal cancer (CRC) survival, including type 2 diabetes mellitus (T2DM) and paraneoplastic thrombocytosis. Although several common factors play a role in their development and platelets are damaged in both diseases, the combined relationship of the three conditions was never investigated previously. METHODS: A prospective, real-life observational cohort study was conducted with the inclusion of 108 CRC patients and 166 voluntary non-CRC subjects. Plasma interleukin-6 and thrombopoietin levels were measured. RESULTS: Study participants were divided into cohorts based on the presence of T2DM. Platelet count (p < 0.0500) and interleukin-6 (p < 0.0100) level were significantly higher in the CRC groups. Thrombopoietin level was higher in the T2DM, CRC, and CRC + T2DM groups (p < 0.0500). Analysis of parameter changes over time and survival models revealed that neither platelet count, interleukin-6, nor thrombopoietin levels were affected by T2DM. Death of patients was associated with higher baseline platelet count (p = 0.0042) and interleukin-6 level (p < 0.0001). CONCLUSION: Although the independent, disease-worsening effect of paraneoplastic thrombocytosis and T2DM is known, the coexistence of the two did not further impair the survival of CRC patients, suggesting that T2DM has no significant effect over paraneoplastic thrombocytosis.

Does Elevated Pre-Treatment Plasma PD-L1 Level Indicate an Increased Tumor Burden and Worse Prognosis in Metastatic Colorectal Cancer?

BACKGROUND: Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) have been reported as possibly favorable prognostic factors in colorectal cancer (CRC). However, their longitudinal effect is unknown. METHODS: A pilot study was performed to investigate whether baseline PD-1/PD-L1 levels are associated with further laboratory changes and/or shorter survival. RESULTS: A total of 506 laboratory measurements from 37 metastatic CRC patients were analyzed. The baseline plasma PD-1 and PD-L1 levels were 27.73 ± 1.20 pg/mL and 16.01 ± 1.09 pg/mL, respectively. Disease progression (p = 0.0443) and baseline high-sensitivity C-reactive protein (p = 0.0011), aspartate transaminase (p = 0.0253), alanine transaminase (p = 0.0386), and gamma-glutamyl transferase (p = 0.0103) were associated with higher PD-L1 levels. Based on the baseline PD-1/PD-L1 levels, low and high PD-1/PD-L1 groups were created. Constant, pathological levels of complete blood count values, high-sensitivity C-reactive protein, serum albumin, high-density lipoprotein cholesterol, and lactate dehydrogenase were characteristic for patients with high baseline PD-L1. High PD-L1 levels were significantly associated with increased tumor burden. Disease-specific survival and progression-free survival were significantly shorter in patients with high PD-L1. CONCLUSIONS: Abnormal levels of laboratory parameters and intensified tumor burden can be expected if elevated baseline plasma PD-1/PD-L1 levels are found.

Longitudinal changes in personalized platelet count metrics are good indicators of initial 3-year outcome in colorectal cancer.

BACKGROUND: Platelet count or complete blood count (CBC)-based ratios including lymphocyte-to-monocyte (LMR), neutrophil-to-lymphocyte (NLR), hemoglobin-to-platelet (HPR), red blood cell count distribution width-to-platelet (RPR), and platelet-to-lymphocyte (PLR) ratio are good predictors of colorectal cancer (CRC) survival. Their change in time is not well documented, however. AIM: To investigate the effect of longitudinal CBC ratio changes on CRC survival and their possible associations with clinicopathological properties, comorbidities, and anamnestic data. METHODS: A retrospective longitudinal observational study was conducted with the inclusion of 835 CRC patients, who attended at Semmelweis University, Budapest. CBC ratios and two additional newly defined personalized platelet count metrics (pPLTD and pPLTS, the platelet counts relative to the measurement at the time of CRC diagnosis and to the one 4-6 wk after tumor removal surgery, respectively) were recorded. RESULTS: The 835 CRC patients had a total of 4608 measurements (5.52 visits/patient, in average). Longitudinal survival models revealed that the increases/decreases in LMR [hazard ratio (HR): 0.4989, P < 0.0001], NLR (HR: 1.0819, P < 0.0001), HPR (HR: 0.0533, P = 0.0038), pPLTD (HR: 4.9229, P < 0.0001), and pPLTS (HR: 4.7568, P < 0.0001) values were poor prognostic signs of disease-specific survival. The same was obtained for all-cause mortality. Most abnormal changes occurred within the first 3 years after the diagnosis of CRC. RPR and PLR had an only marginal effect on disease-specific (P = 0.0675) and all-cause mortality (Bayesian 95% credible interval: 0.90-186.05), respectively. CONCLUSION: LMR, NLR, and HPR are good metrics to follow the prognosis of the disease. pPLTD and pPLTS perform just as well as the former, while the use of RPR and PLR with the course of the disease is not recommended. Early detection of the abnormal changes in pPLTD, pPLTS, LMR, NLR, or HPR may alert the practicing oncologist for further therapy decisions in a timely manner.

Modulated Electro-Hyperthermic (mEHT) Treatment in the Therapy of Inoperable Pancreatic Cancer Patients-A Single-Center Case-Control Study.

Our present oncological treatment arsenal has limited treatment options for pancreatic ductal adenocarcinoma (PDAC). Extended reviews have shown the benefits of hyperthermia for PDAC, supporting the perspectives with the improvements of the treatment possibilities. METHODS: A retrospective single-center case-control study was conducted with the inclusion of 78 inoperable PDAC patients. Age-, sex-, chemotherapy-, stage-, and ascites formation-matched patients were assigned to two equal groups based on the application of modulated electro-hyperthermia (mEHT). The EHY2030 mEHT device was used. RESULTS: A trend in favor of mEHT was found in overall survival (p = 0.1420). To further evaluate the potential beneficial effects of mEHT, the presence of distant metastasis or ascites in the patients' oncological history was investigated. Of note, mEHT treatment had a favorable effect on patients' overall survival in metastatic disease (p = 0.0154), while less abdominal fluid responded to the mEHT treatment in a more efficient way (p ≤ 0.0138). CONCLUSION: mEHT treatment was associated with improved overall survival in PDAC in our single-center retrospective case-control study. The outcome measures encourage us to design a randomized prospective clinical study to further confirm the efficiency of mEHT in this patient cohort.

Lower serum chromogranin B level is associated with type 1 diabetes and with type 2 diabetes patients with intensive conservative insulin treatment.

BACKGROUND: Chromogranin B (CgB) plays an important role in the physiological insulin secretion of pancreatic beta cells. Serum CgB levels were investigated in type 1 and type 2 diabetes patients in a cross-sectional study. METHODS: An observational cross-sectional study was performed with the inclusion of 94 control subjects, 100 type 1 and 100 type 2 diabetes patients, at the Metabolic Outpatient Clinic of the Department of Internal Medicine and Hematology, Semmelweis University. Serum CgB levels were measured with enzyme-linked immunosorbent assay. RESULTS: Serum CgB level was lower in type 1 diabetes patients than in matched control subjects (p = 0.0241), while they were equal in type 2 diabetes patients and controls (p = 0.1698). The subgroup of type 2 diabetes patients who received intensive conservative insulin treatment had significantly lower CgB levels compared to those with other regimens of antidiabetic therapies (p = 0.0283). CONCLUSION: The lower serum CgB levels in the patients with type 1 diabetes and the type 2 diabetes patients with progressed disease stage suggested that the CgB production might be decreased due to the beta cell destruction and depletion.

Personalized Indicator Thrombocytosis Shows Connection to Staging and Indicates Shorter Survival in Colorectal Cancer Patients with or without Type 2 Diabetes.

BACKGROUND: Pre- and postoperative thrombocytosis was reported to have significant effect on patient survival. However, the definition of thrombocytosis throughout the literature is not unified. METHODS: A retrospective longitudinal observational study has been conducted with the inclusion of 150 colorectal cancer (CRC) patients and 100 control subjects. A new measure of platelet changes at an individual level, named personalized indicator thrombocytosis (PIT) was defined, including 4 anemia adjusted variants. RESULTS: In concordance with the literature, PIT values of control subjects showed a slow decrease in platelet counts, while PIT values of CRC patients were significantly higher (p < 0.0001). More advanced staging (p < 0.0001) and both local (p ≤ 0.0094) and distant (p ≤ 0.0440) metastasis are associated with higher PIT values. Higher PIT values suggested shorter survival times (p < 0.0001). Compared to conventional, a PIT-based definition resulted in approximately 3-times more patients with thrombocytosis. 28% and 77% of the deceased patients had conventional- and PIT-based thrombocytosis, respectively. CONCLUSIONS: Compared to conventional thrombocytosis, as an individual metric, PIT values may indicate the condition of patients more precisely. Possible future applications of PIT may include its usage in therapy decision and early cancer detection; therefore, further investigations are recommended.

Histopathological Chromogranin A-Positivity Is Associated with Right-Sided Colorectal Cancers and Worse Prognosis.

BACKGROUND: Colorectal cancer (CRC) is known to be affected by paraneoplastic thrombocytosis and chromogranin A-positive neuroendocrine-cell differentiation (CgA+). Their combined effect has never been previously investigated. METHODS: A prospective cohort pilot study of 42 CRC patients and 42 age- and sex-matched controls was carried out. Plasma interleukin-6, thrombopoietin, and serum chromogranin A and -B were measured; furthermore, tumor tissue was immunohistochemically stained for CgA+. RESULTS: Twenty-seven and 15 patients were assigned to the chromogranin A-negative (CgA-) and CgA+ groups, respectively. Within the CgA+ group, right-sided tumors were more frequent (18.5% vs. 53.3%), no stage I cancer was found, and patients of this group were in worse general condition. Compared to control subjects, chromogranin A level was higher in the CgA+ group (p = 0.0086), thrombopoietin (p = 0.0040) and chromogranin B (p = 0.0070) in the CgA- group, while interleukin-6 was high in both tumor groups (p ≤ 0.0090). Survival was significantly worse in the CgA+ group (hazard ratio: 5.73; p = 0.0378). CONCLUSIONS: Different thrombopoietin levels indicated distinct thrombocytosis types. Within the two CRC groups, serum levels of chromogranins changed in different directions suggesting two well-distinguishable pathophysiologies. Based on these observations we propose a new subtype of CRC, which can be characterized by chromogranin A-positive neuroendocrine-cell differentiation.

Serum chromogranin A level continuously rises with the progression of type 1 diabetes, and indicates the presence of both enterochromaffin-like cell hyperplasia and autoimmune gastritis.

AIMS/INTRODUCTION: The relationship of chromogranin A (CgA) levels above the normal range with various outcomes, such as glycated hemoglobin levels, enterochromaffin-like cell hyperplasia and autoimmune gastritis, was investigated in type 1 diabetes patients with special regard to the progression of comorbidities. MATERIALS AND METHODS: A cohort study on 153 type 1 diabetes patients was carried out with a prospective branch on clinical and laboratory data, and a retrospective branch on histological data obtained by gastroscopy. RESULTS: Patients with CgA levels above the upper limit of the normal range (n = 28) had significantly higher glycated hemoglobin levels (P = 0.0160) than those with CgA in the normal range (n = 125). The correlation between CgA and glycated hemoglobin was significant (P < 0.0001), but weak (R = +0.32). A slight, but steady elevation (P = 0.0410) in CgA level was observed to co-vary with the duration of type 1 diabetes. Enterochromaffin-like cell hyperplasia and autoimmune gastritis was significantly more frequent (P = 0.0087 for both) in the high CgA group. Detailed analyses on gastric tissue samples confirmed a progression of enterochromaffin-like cell hyperplasia (P = 0.0192) accompanied by CgA elevation (P = 0.0316). CONCLUSIONS: The early detection and follow up of the later progression of enterochromaffin-like cell hyperplasia and autoimmune gastritis into gastric neuroendocrine tumors, which have ~100-fold greater incidence in type 1 diabetes patients, can be achieved by assessment of CgA levels. Therefore, the use of CgA could be considered as a novel auxiliary biomarker in the care of these type 1 diabetes complications.

Regular chromogranin A monitoring facilitated the early detection of a gastrointestinal neuroendocrine tumour in a patient with type 1 diabetes.

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