Is SUVmax of 18F-FDG PET/CT Predictive Factor for Malignancy in Gastrointestinal Tract?

BACKGROUND: Increasing use of 18F-FDG PET/CT in cancer patients, has led to more common detection of 18F- FDG uptake in the gastrointestinal tract (GIT). AIMS: The objective of this study was to assess 18F-FDG uptake in incidental and known GIT malignancy. METHODS: A total of 6500 patients followed-up in a single and tertiary center between January 2010 and September 2016 were retrospectively reviewed. Of 2850 patients assessed with 18FDG-PET/CT, known GIT malignancy and 18F-FDG uptake cases during follow-up were included in the study. RESULTS: Of 658 patients with 18F-FDG uptake, 150 patients who underwent endoscopy were included in the study. Seventy-seven of these patients had known GIT malignancy and 73 had incidental 18F-FDG uptake. Among these 73 patients; 7 (9.6%) had malignancy, 20 (27,2%) adenoma and 24 (32.9%) inflammation that were confirmed. Endoscopy was normal in 22 (30.2%) patients. One hundred forty-three (95.3%) patients had focal and 7 (4.7%) had diffuse uptake. While no malignancy was detected in patients with diffuse uptake, 58.7% (84/143) of the patients with focal uptake presented malignancy. Mean the standardized uptake value (SUV) max values were found as 15.0 ± 10.6 (range, 3.8-56.5) in malignant disease, 10.2 ± 4.3 (range, 2.4-19.7) in adenoma, 7.3 ± 3.6 (range, 3.6-18.7) in inflammation, and 9.8 ± 4.2 (range, 3.8-19.9) in normal endoscopy groups (p < 0.001, rho = 0.378). CONCLUSION: Although this study demonstrated high probability of malignant disease with increased 18F-FDG uptake in the GIT, it would be a more appropriate approach to confirm all patients with 18F-FDG uptake through endoscopy as SUVmax values vary in a wide range.

Efficacy of second-line targeted agents in kras wild metastatic colorectal cancer patients who received prior targeted agent: First anti-epidermal growth factor receptor or vascular endothelial growth factor in right and left colon?

INTRODUCTION: We aimed to investigate the impact of first biological agents on second-line biological agents in kras wild-type metastatic colon patients in right and left colon. PATIENTS AND METHODS: The patients received anti-EGFR compared with anti-VEGF in right and left colon separately according to progression-free survival and overall survival in second line. RESULTS: A total of 84 patients were included in the study. In left colon, progression-free survival and overall survival were 9 and 14 months for anti-EGFR and 9 and 16 months for anti-VEGF in the second line. In right colon, progression-free survival and overall survival were 5 and 9 months for anti-EGFR and 4 and 6 months for anti-VEGF in the second line. CONCLUSIONS: Progression-free survival was higher in patients who received bevacizumab first followed by anti-EGFR than reverse sequencing in right colon. Overall survival was similar between two groups.

The association between the route of nutrition and serum levels of adipokines in critical illness: a pilot study

Background/aim: Adipokines play an important role in the regulation of metabolism. In critical illness, they alter serum levels and are suspected to worsen clinical outcomes. But the effect of the route of nutrition on adipokines is not known. The purpose of this study was to evaluate the association between the route of nutrition and adipokine levels in critically ill patients. Materials and methods: This prospective study was performed in an intensive care unit (ICU). Patients admitted to the ICU for least 72 h and receiving either enteral nutrition (EN) via tube feeding or parenteral nutrition (PN) were enrolled. Serum was obtained at baseline, 24 h, and 72 h for concentrations of leptin, adiponectin, resistin, glucagon­like peptide 1 (GLP­1), insulin­like growth factors 1 (IGF­1), and ghrelin. Results: A total of 26 patients were included in the study. Thirteen patients received EN and 13 patients received PN. In the PN group, leptin level significantly increased (P = 0.037), adiponectin and ghrelin significantly decreased during follow up (P = 0.037, P = 0.008, respectively). There was no significant change between all adipokines in the EN group and resistin, IGF­1 and GLP­1 in the PN group during follow up. Resistin levels were markedly lower in the EN group at both 24 h (P = 0.015) and 72 h (P = 0.006) while GLP­1 levels were higher in the EN group at baseline, 24 h, and 72 h (P = 0.018, P = 0.005, and P = 0.003, respectively). There were no differences in leptin, adiponectin, IGF­1, and ghrelin levels over time. Conclusion: The delivery of EN in critical illness was associated with decreased resistin levels and increased GLP­1 levels. Thus, the route of nutrition may impact the clinical outcome in critical illness due to adipokines.

Biweekly cisplatin and gemcitabine with two different doses in non small cell lung cancer patients: A retrospective singlecenter experience.

PURPOSE: Non-small-cell lung cancer (NSCLC) constitutes 80-85% of all lung cancers. Patients with advanced-stage NSCLC may benefit from chemotherapy. Gemcitabine and cisplatin is a well-established therapy for this malignancy. Recently, biweekly administration is becoming more acceptable, but the most effective and tolerable dose remains unclear. The purpose of this study was to compare the toxicity and efficacy of 1000 mg/m2 gemcitabine (GEM 1000) and 1500 mg/m2 gemcitabine (GEM 1500) in combination with 50 mg/m2 cisplatin. METHODS: Gemcitabine was administered at a dose of 1000 or 1500 mg/m2 with cisplatin administered at a dose of 50 mg/m2 on day 1. The treatment was repeated every 2 weeks for a total of 4 courses. Response rates, progression-free survival (PFS), overall survival (OS) and toxicities were assessed. RESULTS: 114 patients with IIIB and IV stages of NSCLC were included. Seventy two patients (63%) received GEM 1000 and 42 (37%) received GEM 1500. The overall reponse rate (ORR), PFS and OS were 24%, 6 months and 13 months respectively in the GEM 1000 group and 36%, 6 months and 15 months in the GEM 1500 group, respectively. Grade 3-4 neutropenia and thrombocytopenia were observed in 4% of the GEM 1000 group and 9% of the GEM 1500 group (p=0.41). CONCLUSION: Biweekly administration of GEM 1000 and 1500 is a well tolerated regimen. Although the GEM 1000 group showed a lower response rate than the GEM 1500 group, PFS and OS were similar.

The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression in Patients Receiving Racotumomab Immunotherapy.

Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p < 0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.

Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.

PURPOSE: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting. METHODS: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included. RESULTS: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85). CONCLUSION: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.

Impact of neutrophil-lymphocyte and platelet-lymphocyte ratio on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer.

PURPOSE: The purpose of this study was to determine the influence of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer patients. METHODS: All metastatic colorectal cancer patients who had received chemotherapy and biological agents as first-line treatment at Erciyes University Hospital were retrospectively reviewed. NLR and PLR were each divided into two groups, as high and low. The NLR high group was compared with the low group and the PLR high group was compared with the low group in patients in terms of progression-free survival (PFS) and overall survival (OS), separately. Cox regression and the Kaplan Meier method were used. RESULTS: One hundred and thirty (58%) of the patients had received bevacizumab and 94 (42%) had received antiEGFR therapy (cetuximab or panitumumab). In the bevacizumab group, PFS was 9 months in the NLR high group and 11 months in the NLR low group (p=0.013). OS was 23 months in the NLR high group and 27 months in the NLR low group (p=0.734). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to NLR. There was no statistically significant PFS difference in patients who received bevacizumab according to PLR. In the antiEGFR group, PFS was 9 months (95% CI, 8.07-13.55) in the PLR high group and 18 months (95% CI, 12.02-18.68) in the PLR low group, with statistically significant difference (p=0.040). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to PLR. CONCLUSIONS: NLR and PLR are important inflammatory markers. In patients who had received bevacizumab, PFS was longer in the NLR low group than in the high group. In patients who had received antiEGFR, PFS was longer in the PLR low group than in the high group.

The prognostic value of the change in neutrophil-to-lymphocyte ratio during first-line palliative chemotherapy in patients with metastatic gastric cancer: A retrospective study.

PURPOSE: Metastatic gastric cancer (mGC) is linked with worse prognosis, and tools are needed for predicting disease course and chemotherapy response. The value of the change in the neutrophil-to-lymphocyte ratio (NLR) during first-line palliative chemotherapy on the outcomes in patients with mGC is not fully explained. This study aimed to investigate the importance of changes in NLR in predicting disease course and chemotherapy response in mGC. METHODS: We retrospectively reviewed 194 patients diagnosed with mGC between August 2005 and November 2016. The NLR was assessed before and after chemotherapy to evaluate its relationship with survival. According to threshold values determined by receiver operating characteristics (ROC) analysis, the NLR was divided into two groups with <2.6 and ≥2.6. RESULTS: Elevated prechemotherapy NLR was significantly correlated with worse overall survival (OS) on univariate analysis (p=0.01). On multivariate analysis, elevated prechemotherapy NLR (HR 1.43, p=0.036) was an independent prognostic element for worse OS, but not for progression-free survival (PFS). Constantly elevated NLR or an increase in NLR after chemotherapy was correlated with poor OS, PFS and chemotherapy response. In the multivariate analysis, constantly elevated NLR was identified to be independent predictor of reduced OS and PFS. CONCLUSION: NLR change during chemotherapy is a better index than prechemotherapy NLR for predicting survival in patients with mCG.

Ipilimumab-associated cholestatic hepatitis: a case report and literature review.

Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes. It is frequently used for the treatment of unresectable or metastatic melanoma. Ipilimumab may lead to several immune-related disease including colitis, thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited number of cases with hepatic damage as an ipilimumab-related adverse event has been reported in the literature. This agent has been implicated in causing acute hepatitis-like liver injury. Here, we presented a case in which cholestatic hepatitis developed during ipilimumab use for the treatment of metastatic melanoma.

The serum YKL-40 level is associated with vascular injury and predicts proteinuria in nephrotic syndrome patients.

AIM: Nephrotic syndrome (NS) is associated with an increased rate of cardiovascular events. The YKL-40 level is associated with atherosclerosis, endothelial dysfunction and proteinuria in renal and non-renal populations. The aim of this study was to investigate the relationships between the YKL-40 level and both vascular injury and proteinuria in NS patients. METHODS: Sixty-nine NS patients and 20 healthy subjects were enrolled in the present study. The endothelial function was assessed according to the flow mediated dilatation (FMD) and the degree of arterial stiffness was determined based on the pulse wave velocity (PWV). The serum YKL-40 levels were measured using ELISA. RESULTS: The YKL-40 levels and PWV values were higher and the FMD values were lower in the NS patients than in the healthy controls. However, the CA-IMT and LVEF levels were not statistically different between the two groups. The patients were divided into three groups with respect to the extent of proteinuria: the normoproteinuria group (n:18), non-nephrotic proteinuria group (n:33) and nephrotic proteinuria group (n:18). Consequently, the YKL-40 levels and PWV values were significantly increased and the FMD values were decreased in the nephrotic proteinuria group compared to that observed in both the non-nephrotic proteinuria and normoproteinuria groups. Furthermore, the YKL-40 level correlated with the FMD and PWV values in the NS patients. In addition, proteinuria correlated with the YKL-40, FMD, PWV, eGFR and fasting LDL cholesterol values in this patient group. Multivariate linear regression analyses showed that the YKL-40 and eGFR values were effective in predicting proteinuria in the NS patients. CONCLUSIONS: The serum YKL-40 level is associated with endothelial dysfunction and increased arterial stiffness in NS patients and may be an indicator of the level of proteinuria in this patient population.

Effects of dialysis solution on the cardiovascular function in peritoneal dialysis patients.

Objective Peritoneal dialysis (PD) patients have an increased cardiovascular burden. In this study, we aimed to compare certain PD solutions (Physioneal(®) and Dianeal(®)) in terms of the ambulatory blood pressure, echocardiographic parameters (ECHO), carotid atherosclerosis, endothelial function and serum asymmetric dimethylarginine (ADMA) level. Methods A total of 45 PD patients were enrolled in this prospective randomized controlled study: 23 patients in the Dianeal(®) group and 22 patients in the Physioneal(®) group. Ambulatory blood pressure measurements, echocardiography, carotid artery intima-media thickness measurements and flow mediated dilatation (FMD) and ADMA values were obtained at baseline and 12 months. Results The baseline parameters were similar between the groups with respect to the echocardiographic parameters, 24-hour ambulatory blood monitoring measurements and ADMA and FMD levels. All 24-hour blood pressure monitoring measurements, except for the average daytime systolic blood pressure, were significantly decreased in both groups at the first year. In the Physioneal(®) group, a significant decrease was observed with regard to the ADMA levels. Considering the FMD values, significant augmentation was seen at the end of the first year in both groups. Improvements in the FMD measurements were prominent in the Physioneal(®) group; however, this finding was not statistically significant. Conclusion The use of solutions with a neutral pH in PD patients results in decreased ADMA levels, which may be an important contributor to reductions in the incidence of cardiovascular events and deaths in this population.