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Background: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have benefits for survival in some cancers with peritoneal metastasis. Hematologic toxicity described rate is 2 to 38%. Methods: Patients admitted to an intensive care unit (ICU) after CRS and HIPEC over 78 months. The data recorded were demographic characteristics, the severity of illness, complete blood samples, the type of cancer and extension, HIPEC drug and temperature, ICU and hospital stay and mortality, bleeding, and the need for transfusion of blood products. Results: Of the 96 patients included, 77.1% presented hematological complications: 8.3% leukopenia (<4000/mm3 leucocytes), 66.7% anemia (hemoglobin < 10 mg/dL), and 22.9% coagulopathy (INR < 1.5, or/and aPTT < 45 s, or/and platelet count < 100,000/mm3, or/and <100 mg/dL of serum fibrinogen). Leukopenia was higher in ovarian cancer or those treated with doxorubicin. Females with anemia, ovarian cancer, and those treated with cisplatin or doxorubicin had longer ICU stays. Bleeding complications were low-corrected in a conservative manner. The median ICU stay was 5 (4.0–5.0) days. The ICU mortality rate was 1.0%. Conclusions: In our study, 77.1% of patients treated with CRS and HIPEC developed hematological complications during the postoperative period; the majority of them were not severe and resolved spontaneously, without an effect on mortality or hospital stay.

Background Gastric cancer (GC) with peritoneal carcinomatosis (PC) is traditionally considered a terminal stage of the disease. The use of a multimodal treatment, including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), can benefit these patients. Our goal was to evaluate the morbidity and survival outcomes of these patients. Methods This is a retrospective, multicenter study from a prospective national database of patients diagnosed with PC secondary to GC treated with CRS and HIPEC from June 2006 to October 2017. Results Eighty-eight patients from seven specialized Spanish institutions were treated with CRS and HIPEC, with median age of 53 years; 51% were women. Median Peritoneal Cancer Index (PCI) was 6, and complete cytoreduction was achieved in 80 patients (90.9%). HIPEC was administered in 85 cases with 4 different regimens (Cisplatin + Doxorubicin, Mitomycin-C + Cisplatin, Mitomycin-C and Oxaliplatin). Twenty-seven cases (31%) had severe morbidity (grade III–IV) and 3 patients died in the postoperative period (3.4%). Median follow-up was 32 months. Median overall survival (OS) was 21.2 months, with 1-year OS of 79.9% and 3-year OS of 30.9%. Median disease-free survival (DFS) was 11.6 months, with 1-year DFS of 46.1% and 3-year DFS of 21.7%. After multivariate analysis, the extent of peritoneal disease (PCI ≥ 7) was identified as the only independent factor that influenced OS (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.26–4.46, p  = 0.007). Conclusions The multimodal treatment, including CRS and HIPEC, for GC with PC can improve the survival results in selected patients (PCI < 7) and in referral centers.

We have applied two PCR techniques, differential PCR (diffPCR) and qPCR for the identification of HER2 gene amplifications in genomic DNA of tumor and distal gastric samples from patients with gastric cancer. The diffPCR technique consists of the simultaneous amplification of the HER2 gene and a housekeeping gene by conventional PCR and the densitometric analysis of the bands obtained. We established a cut-off point based on the mean and standard deviation analyzing the DNA of 30 gastric tissues from patients undergoing non-cancer gastrectomy. diffPCR and qPCR yielded consistent results. HER2-overexpression was detected in 25% of patients and was further confirmed by immunohistochemistry and immunofluorescence. The approaches herein described may serve as complementary and reliable methods to assess HER2 amplification.

Gastric cancer ranks fifth in both world prevalence and lethality, with a 5-year survival of less than 30%. HLA-G, a non-classical class I HLA gene, has emerged as a potential marker for cancer susceptibility and prognosis due to its immunomodulatory properties. Its level of expression is regulated by polymorphisms in the 3’ untranslated region (3’UTR) polymorphisms, which form various combined haplotypes (UTR-1 to -9). In this study, we examined HLA-G 3’UTR polymorphisms in paired tissue samples from 111 patients with gastric adenocarcinoma and 119 healthy controls. Polymorphism analysis was performed using PCR and Sanger sequencing, followed by statistical analysis using SNPStats software. Survival analysis was conducted using Kaplan–Meier curves and multivariate Cox regression models. High-expressor HLA-G 3’UTR haplotypes (UTR-1 and UTR-6) were significantly associated with gastric cancer susceptibility, indicating a potential role in tumor immune evasion. Additionally, the 14 base pair insertion/deletion polymorphism (14 bp I/D) emerged as a prognostic marker, with D/D genotype carriers showing lower survival rates compared to I/D and I/I genotype carriers. Our study highlights the clinical relevance of HLA-G polymorphisms in gastric cancer, suggesting their potential as prognostic markers and therapeutic targets. Further elucidation of HLA-G-related pathways could lead to personalized treatment strategies and improved patient outcomes in gastric cancer.

HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune system. The HLA-G gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the HLA-G gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1% vs 44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral vs non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a de novo , tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.

TGF‐β1 is involved in tumour growth. Four TGFB1 SNPs and TGF‐β1 production by stimulated PBMC were determined in seventy‐eight gastric adenocarcinoma patients. In addition, TGF‐β1 levels were measured in the plasma of further thirty patients. rs1800471‐G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP‐G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP‐T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469‐C/rs1800470‐T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five‐year life expectancy (P = .03). TGF‐β1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF‐β1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF‐β1 levels serves to identify patients at risk of developing a more aggressive disease.

Objectives: The aim of this study was to analyze the prognostic factors of survival in patients with peritoneal metastasis (PM) from colorectal cancer (CRC). The type of relationship between survival and the PM time of detection was used to determine whether it was synchronous with the primary tumor or metachronous. Patients and Methods: Retrospective observational study. It included patients treated for colorectal adenocarcinoma diagnosed between January 2005 and December 2019 who presented PM at the time of diagnosis or during follow-up. Variables, such as sex, age, differentiation grade, positive adenopathy (pN+), tumor size (pT), tumor location, mucinous component, peritoneal carcinomatosis index (PCI), and KRAS mutational status, were analyzed. Results: During the study period, 1882 patients were surgically treated for CRC in our hospital. Of these, 240 patients (12.8%) were included in the study after evidence of PM. The mean age was 67 ± 12 years (range: 32–92 years), and 114 patients were female (47.5%). The mean follow-up was 20 ± 13 months (median 12 months). The Kaplan–Meier survival at 36 months was higher in patients with metachronous PM (24% vs. 8%; p = 0.002), WT-KRAS tumors (31% vs. 15%; p < 0.001), N0 stage (30% vs. 19%; p < 0.001), T3 stage tumors (18% vs. 19% in T4A and 3% in T4B; p > 0.001), and tumors with classic adenocarcinoma histology (18% vs. 8%; p = 0.011). Patients with a PCI of 1–10 showed a likelihood of survival at 36 months of 56%, which was longer than that found in patients with a PCI of 11–20 (8%) or a PCI of >20 (0%) (p < 0.001). In the multiple regression analysis, the factors with an independent prognostic value were: poor grade of differentiation (HR 1.995; 95% CI: 1.294–3.077), KRAS mutation (HR 1.751; 95% CI: 1.188–2.581), PCI 11–20 (HR: 9.935; 95% CI: 5.204–18.966) and PCI > 20 (HR: 4.011; 95% CI: 2.291–7.023). Conclusions: PCI should continue as the as the most useful prognostic indicator in order to assess prognostic estimations as well as therapeutic and surgical decisions, but tumor grade and KRAS mutational status may help in the treatment decision process by providing complementary information. The time of PM detection did not achieve statistical significance in the multiple regression analysis.

Background. Reduced TCRζ chain surface has been reported in T cells from patients with different inflammatory conditions and cancer. However, the causes of this diminished expression in cancer remain elusive. Methods. T cell-enriched populations of blood or tissue (tumoral and nontumoral) origin from 44 patients with gastric adenocarcinoma and 33 healthy subjects were obtained. Samples were subjected to cytofluorimetry, Western blot analysis, TCRζ cDNA sequencing experiments, measurement of TCRζ mRNA levels, and caspase-3 activity assays. Results. Cytofluorimetry revealed a decreased TCRζ expression in T cells of patients, assessed either as percentage of cells expressing this chain (blood: control subjects 99.8±0.1%, patients 98.8±1.1%P<0.001; tissue: control subjects 96.7±0.9%, patients tumoral tissue 67.9±27.0%, patients nontumoral tissue 82.8±12.6%, P=0.019) or mean fluorescence intensity (MFI) value (blood: control subjects 102.2±26.0; patients 58.0±12.3, P=0.001; tissue: control subjects 99.4±21.4; patients tumoral tissue 41.6±21.4; patients nontumoral tissue 62.3±16.6, P=0.001). Other chains pertaining to the TCR-CD3 complex (CD3ε) showed no significant differences (MFI values). Subsequent TCRζ cDNA sequencing experiments or measurements of TCRζ mRNA levels disclosed no differences between patients and control subjects. Evaluation of caspase-3 activity showed higher levels in T cell extracts of patients, and this activity could be decreased by 70% with the use of the inhibitor Ac-DEVD-FMK, although CD3ζ expression levels did not recover. Conclusions. These results further place the defect responsible for the low TCRζ expression in cancer at the posttranscriptional level and suggests contrary to what has been proposed in other pathologies that elevated caspase-3 activity is not the causative agent.

Objective. The main objective of the study was to determine the effect of the presence of mutation in the KRAS gene on the survival in patients with colorectal cancer (CRC) and peritoneal metastases (PM). Materials and Methods. A retrospective cohort study was performed. Patients diagnosed with CRC with synchronous or metachronous PM between January 2006 and December 2019 were included. Data on the histopathological, clinical, and treatment factors were collected. The effect of each variable on survival was evaluated by Cox regression. Results. A total of 149 patients were included (64 women (43%) and 85 men (57%); mean age, 63 years). The long-term survival rate at 36 months was 24% (median, 21 months). KRAS mutation was detected in 75 patients (50.3%). Kaplan–Meier analysis estimated that likelihood of survival was higher in patients with wild-type KRAS tumours (35%) than in mutated-type KRAS (14%) (median: 28 vs. 15, respectively) (P=0.001). Within the categories into which the peritoneal cancer index (PCI) was classified, survival at 36 months depended on the KRAS status. Survival in wild-type KRAS tumours with PCI 1–10 was 71% and with PCI 11–20 was 26%, while in mutant-type KRAS tumours, survival was 41% and 4%, respectively (P=0.025). In the multiple regression analysis, the KRAS mutation was revealed to have an independent prognostic value (HR: 2.144; 95% CI: 1.342–3.424). Conclusion. The mutational status of the KRAS gene has demonstrated a strong association with survival and prognostic utility in patients with CRC with PM.