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Background and Objectives: KRAS genes are among the most prominent oncogenes that trigger tumor formation in colorectal cancer (CRC) and serve as predictive biomarkers for resistance to anti-EGFR therapies in metastatic colorectal cancer (mCRC) patients. However, the prevalence and mutation spectrum of the KRAS gene family in mCRC patients in Turkey have not been sufficiently analyzed. This study investigates the frequency and distribution of mutations in the KRAS gene family across different regions of Turkey and examines gender-related variations. Materials and Methods: This multicenter observational study included 2458 histologically confirmed mCRC patients collected from 52 centers across Turkey. In a central laboratory, KRAS mutations in codons 12 and 13 were analyzed using polymerase chain reaction (PCR). Statistical analyses were performed using chi-square tests and Monte Carlo simulations, with a significance threshold set at p < 0.05. Results: Depending on the region, KRAS mutations were detected in 45% of patients, ranging from 39.6% to 47.5%. The mutation rate was significantly higher in female patients (48.8%) compared to male patients (42.6%) (p = 0.002). Codon 12 mutations were more frequent than codon 13 mutations. G12D, G12V, and G13D mutations accounted for 80% of all detected mutations. The G12V mutation was prevalent in female patients (p = 0.007). Based on region, mutation diversity was similar, and no statistically significant difference was found (p > 0.05). Conclusions: This large-scale, multicenter study provides the most comprehensive dataset of KRAS mutations in mCRC patients in Turkey. This study revealed regional trends, as well as gender differences. The findings highlight the importance of routine KRAS genotyping in guiding personalized treatment strategies, especially regarding candidate selection for anti-EGFR therapies. Further research is required to elucidate the prognostic and therapeutic implications of specific KRAS mutations.

Highly selective inhibitors of cyclin-dependent kinase 4 and 6 (CDK4/6is) have emerged as a standart of care for first- and second-line therapies in combination with endocrine therapy (ET) for HR+/HER2- metastatic breast cancer (MBC) patients. It has been reported that combination therapy is more effective than ET alone and is safe in elderly patients as well as young patients. Nevertheless, elderly and very old patients with HR+/HER2-MBC treated with CDK4/6 inhibitor (CDK4/6i) combinations are relatively underrepresented in randomized controlled trials. To contribute to the literature, we investigated the real-world efficacy, factors associated with survival and the rates of adverse events (AEs) of the treatment with palbociclib or ribociclib plus ET in the HR+/HER2- MBC patient cohort over the age of 65 for age subgroups. In this retrospective study, 348 patients were divided into subgroups: 65–69 years old, 70–79 years old and 80 years and older. Median PFS (mPFS) for whole group was 18.3 (95% CI,14.3–22.3) months. There was no significant difference in mPFS between age groups ( p  = 0.75). The estimated median OS (mOS) was 39.5 (95% CI, 24.9–54.1) months and there was no significant difference between age groups ( p  = 0.15). There was a meaningfull numerical difference that did not reach statistical significance in patients who received CDK4/6i treatment as the first line for MBC. Grade 3–4 AEs were reported in 42.7% for the entire group, and neutropenia was the most common (37.3%). It can be concluded that combination therapy with palbociclib or ribociclib with an ET partner has similar efficacy and is safe among subgroups of older patients diagnosed with HR+/HER2-MBC.

Metastatic gastric cancer (GC) and gastroesophageal junction (GEJ) cancer are associated with a poor prognosis. Recent advancements in treatment have incorporated trastuzumab, anti-PD-1 agents, and anti-claudin therapies alongside chemotherapy (ChT), significantly improving outcomes. Contemporary studies predominantly employ doublet ChT as the backbone for these regimens, although historically triplet ChT regimens have been favored, particularly in younger patients requiring rapid tumor shrinkage. The aim of this study was to compare the efficacy of mFOLFOX-6 and mDCF regimens in the treatment of advanced GC and GEJ adenocarcinoma. This was a retrospective multicenter study. Patient data were obtained from the databases of 25 hospitals across Turkey. Demographic and clinicopathological characteristics were documented. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and group discrepancies were assessed with log-rank test. A total of 493 patients were included in the analysis, with similar baseline characteristics between the two groups. The objective response rate was 36.3% in the mDCF group and 38% in the mFOLFOX-6 group (  = 0.7). The median PFS was 6 months for mDCF and 7 months for mFOLFOX-6 (  = 0.2), while the median OS was 12 months for mDCF and 11 months for mFOLFOX-6 (  = 0.4). Grade 3-4 neutropenia occurred in 27.6% of patients treated with mDCF versus 17.8% with mFOLFOX-6 (  = 0.01). Likewise, grade 3-4 anemia was more frequent in the mDCF group (9.5%) compared to the mFOLFOX-6 group (4.8%;  = 0.04). Modified FOLFOX-6 demonstrated comparable efficacy to mDCF in the treatment of advanced GC and GEJ adenocarcinoma. Moreover, mFOLFOX-6 was associated with a lower incidence of hematological adverse effects.

Although signet-ring cell (SRC) adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer.

Objectives: Most research in this field has highlighted the significance of the fibrinolytic system in essential hypertension, revealing anomalies within the coagulation and fibrinolytic pathways that contribute to a hypercoagulable condition. We aim to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) levels in individuals diagnosed with high blood pressure. Methods: We compared 40 newly diagnosed cases of essential hypertension, who were not receiving antihypertensive medication, with 40 normotensive individuals as controls. Various parameters and TAFI levels were assessed in all subjects and compared between the groups. Additionally, hypertensive patients were classified based on whether they exhibited high or normal cholesterol levels (≥200 mg/dL). Results: The concentrations of TAFI were significantly higher in the hypertensive cohort compared to the normotensive counterparts (116.95±29.76 and 77.72±32.78 (ng/mL) , respectively; P<0.001). In addition, the high blood pressure cohort exhibited a notably higher mean body mass index (BMI) in contrast to the normotensive group (29.55±4.82 vs. 24.93±3.07 kg/m2, respectively; P<0.001). On the other hand, the remaining results showed no statistically significant differences between the two cohorts. Linear regression analysis revealed that blood pressure status and BMI independently correlated with plasma TAFI levels. Conclusions: The concentrations of TAFI are elevated in patients with high blood pressure compared to individuals with normal blood pressure, irrespective of high cholesterol levels. Further exploration is necessary to clarify the involvement of TAFIs in the pathophysiology of primary hypertension, necessitating advanced investigatory initiatives.

ABSTRACT Introduction: Crizotinib is a tyrosine kinase inhibitor used in patients with non-small cell lung cancer, and there are uncertainties about its effect on kidney function. In this study, it was aimed to document the possible adverse effect of the drug on kidney functions. Materials and Methods: The estimated glomerular filtration rates (eGFRs) of the patients were calculated by creatinine-based Chronic Kidney Disease Epidemiology Collaboration and compared by months using the paired samples t-test. Kaplan-Meier survival method was used for progression-free survival and overall survival (OS) analysis. Results: Twenty-six patients who received crizotinib were included in the study, and the median progression-free survival time with crizotinib was 14.2 months and the median OS time was 27.4 months. There was a significant reduction of eGFR after the 1st month of crizotinib treatment when compared to the rate before treatment initiation (P < 0.001). The eGFR values at the end of the 1st month and the 2nd month of treatment and the 2nd and 3rd months of treatment were statistically similar (P = 0.086, P = 0.663; respectively). This decrease in eGFR values was reversible, and there was no difference detected between pretreatment and posttreatment discontinuation (P = 0.100). Conclusion: A reversible decrease in renal functions was detected in patients using crizotinib. When the literature data are examined, it is thought that the reason for this decrease may be related to the increase in renal inflammation or a pseudo decrease due to the decrease in creatinine excretion. When evaluating renal functions in these patients, using noncreatine-based (iothalamate, etc.) calculations can give more accurate results.

Although involvement of pancreas is a common finding in small cell lung cancer (SCLC), metastasis-induced acute pancreatitis (MIAP) is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status.

Approximately 10%-20% of all systemic lymphomas have central nervous system (CNS) involvement, which has been correlated to a worsened prognosis. It is well known that secondary involvement of the adrenal glands may occur in up to 25% of patients during the course of diffuse lymphoma. Primary adrenal lymphoma (PAL), however, is a different entity, and it is defined as the presence of adrenal lymphoma without evidence of either nodal involvement or leukemia. It has been shown that this occurrence is rarely accompanied by extranodal involvement, such as in the CNS. PAL exhibits a tendency for CNS relapse and this possibility should be examined even before symptoms are present. Herein we present a patient with PAL and secondary CNS involvement.