Course Of Gastric Cancer Research Articles

Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Nursing and caring problems of a patient with gastric cancer - a case study

Gastric cancer is a malignant tumor that originates from the cells of the inner layer of the organ. It is characterized by a long asymptomatic period. The incidence of gastric cancer increases after the age of 50, especially in the male population. The aim of the study was to analyze selected aspects of nursing care provided to a patient after total gastrectomy in the course of gastric cancer. Materials and methods. The study used the case study method and an individual case study of a patient diagnosed with gastric cancer. Results and conclusions. The patient has problems in the biopsychosocial sphere. The role of a nurse in caring for a sick person is comprehensive care, education and preparation for self-care, and above all mental support. Constant monitoring of the patient's health greatly helps to prevent possible complications.

TUMOR MICROENVIRONMENT AND BODY MASS INDEX: CORRELATION WITH THE PROGRESSION OF GASTRIC CANCER

Summary. Obesity increases the risk of developing malignant tumors contributes to the worsening of the progression of the disease. Today, the relationship between the course of gastric cancer (GC) and obesity is considered to have been proven, however the epidemiological data pertaining to this relationship is marked by contradictions and uncertainties. The identification of tumor microenvironment factors that are associated with obesity (taking into account the age and gender of patients) will allow to group patients in accordance to the risk of adverse progression of the disease. Aim: to determine the levels of the metastasis of regional and distant cancer as well as the survival of patients with GC depending on their body mass index (BMI), taking into account their age and gender; to analyze the correlation of these indicators to the aggressiveness of the tumor microenvironment, which was determined by us previously by grouping patients with GC by BMI, age and sex. Object and methods: the clinico-pathological indicators and the overall 3-year survival of 246 patients (171 men, 75 women) with primary esophageal cancer were studied using clinical, oncological and statistical methods. Results: it was found that there was no significant statistical difference (p > 0.05) between the frequency of the metastasis of distant cancer in the groups of patients, regardless of weight, sex and age. Patients with normal weight had a 1.4 times significantly higher (p = 0.012) frequency of regional cancer metastasis than patients with excess weight. Significantly highest survival rates were observed in middle-aged men of normal weight, elderly women of normal weight, and middle-aged women who were overweight/obese, there was no significant statistical difference (p > 0.05) between the frequency of distant cancer metastasis in the groups of patients regardless of weight, sex and age. Patients with normal weight had a 1.4 times significantly higher (p = 0.012) frequency of regional cancer metastasis than patients with excess weight. The highest survival rates were observed in middle-aged men of normal weight, elderly women of normal weight, and middle-aged women who were overweight/obese and the lowest in overweight/ obese middle-aged men and overweight/obese elderly women. It was determined that in cases of patients who were overweight, survival is correlated with the nature of aggressiveness of the tumor as it relates to the age and gender of the patients with GC (a high frequency of pro-tumor factors of the GC microenvironment is associated with low survival (direct negative correlation; k = –0.93)), as it relates to patients with normal weight — no correlation (direct positive correlation; correlation coefficient = 0.98). Conclusions: the study of tumor microenvironment factors that are associated with obesity, taking into account patients’ age and gender, will allow to group patients with GC according to the risk of adverse progression of the disease at the stage of initial tumor detection, and in a technically accessible and economical way, to improve the determination of a prognosis and the efficiency of anticancer therapy.

Protein Phosphatase 5-Recruiting Chimeras for Accelerating Apoptosis-Signal-Regulated Kinase 1 Dephosphorylation with Antiproliferative Activity

A normal phosphorylation state is essential for the function of proteins. Biased regulation frequently results in morbidity, especially for the hyperphosphorylation of oncoproteins. The hyperphosphorylation of ASK1 at Thr838 leads to a persistently high activity state, which accelerates the course of gastric cancer. Under normal conditions, PP5 specifically dephosphorylates p-ASK1T838 in cells, thereby weakening ASK1 to a low-basal activity state. However, in tumor types, PP5 shows low activity with a self-inhibition mechanism, making p-ASK1T838 remain at a high level. Thus, we aim to design phosphatase recruitment chimeras (PHORCs) through a proximity-mediated effect for specifically accelerating the dephosphorylation of p-ASK1T838. Herein, we describe DDO3711 as the first PP5-recruiting PHORC, which is formed by connecting a small molecular ASK1 inhibitor to a PP5 activator through a chemical linker, to effectively decrease the level of p-ASK1T838 in vitro and in vivo. DDO3711 shows preferable antiproliferative activity (IC50 = 0.5 μM) against MKN45 cells through a direct binding and proximity-mediated mechanism, while the ASK1 inhibitor and the PP5 activator, used alone or in combination, exhibit no effect on MKN45 cells. Using DDO3711, PHORCs are identified as effective tools to accelerate the dephosphorylation of POIs and provide important evidence to achieve precise phosphorylation regulation, which will promote confidence in the further regulation of abnormally phosphorylated oncoproteins.

S3563 Immunosuppression and the Course of Gastric Cancer: A Role for Closer Surveillance

S3563 Immunosuppression and the Course of Gastric Cancer: A Role for Closer Surveillance

Preservation of Epstein-Barr virus status and mismatch repair protein status along the metastatic course of gastric cancer.

Epstein-Barr virus (EBV) in-situ hybridisation and mismatch repair (MMR) protein immunohistochemistry identifies two subgroups of gastric cancer (GC) with high immunogenicity and likelihood for response to immune check-point inhibition. As tumour biology may change during the metastatic course, which can negatively influence the success of therapeutic decisions made on primary tissue, we investigated the consistency of GC EBV and MMR status within primary tumours and metastases. We investigated a cohort of 415 primary resected GC, including 111 cases with corresponding distant metastases and 297 cases with lymph node metastases. Tumours were analysed by EBV in-situ hybridisation and MLH1, PMS2, MSH2 and MSH6 immunohistochemistry using tissue microarray technique. Primary tumours were grouped as EBV-positive MMR-proficient, EBV-negative MMR-deficient and EBV-negative MMR-proficient. Eleven of 415 (2.7%) of primary tumours were EBV-positive MMR-proficient, whereas 49 of 415 (11.8%) of tumours were EBV-negative MMR-deficient. EBV and MMR protein status showed full concordance with that of the primary tumours. MMR-deficient tumours were of lower pT-category (P<0.001), had fewer lymph node metastases [24 of 49 (49%) versus 273 of 361 (75.6%) cases; P<0.001] and a lower rate of distant metastases [six of 49 (12.2%) versus 105 of 366 (28.7%) cases; P=0.015]. We demonstrate a strong correlation of EBV and MMR status between primary tumours, lymph node and distant metastases in a large series of primary resected GC. The cases showed the expected frequency of EBV-positive MMR-deficient and EBV-negative MMR-proficient tumours. We conclude that tissue testing for molecular subtyping for therapeutic decision-making can be reliably performed on primary tumours and metastases in GC.

The Symptom-Free Course of Gastric Cancer

Gastric cancer is one of the most common neoplasms in the world. The morbidity and mortality rates of this pathology in the Republic of Belarus are high. This is often associated with late case detection due to the absence of clinical manifestations. Recurrent thromboembolism of the pulmonary artery branches may be the only clinical manifestation in patients with malignant tumors. This necessitates cancer screening on patients with thrombosis of unknown etiology.

Prognostic value of CEA mRNA in the peritoneal lavage of patients undergoing curative surgery for gastric cancer.

e16090Background: Most patients have peritoneal metastasis over the course of gastric cancer. The prognosis of these patients with peritoneal metastasis is extremely poor. The aim of this study is ...

Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

ПАЛЛИАТИВНО-КУРАТИВНЫЕ ХИРУРГИЧЕСКИЕ ВМЕШАТЕЛЬСТВА У БОЛЬНЫХ РАКОМ ЖЕЛУДКА С МЕТАСТАЗАМИ В ПЕЧЕНЬ

Objective: To assess the effectiveness of relatively curative surgical interventions in the treatment of patients with gastric cancer with metastases to the liver and to show the role of active surgical tactics in improving the quality of life of patients. Methods: The study included 28 patients with gastric cancer with metastases to the liver. Patients with type I and type II Borrmann’s tumor growth (17 (85.7%) patients) were prevalent. It was found that in the predominant majority of patients had lesions of regional lymph nodes (91.6%). Detection of ultrasound and CT studies of enlarged retroperitoneal lymph nodes, lymph nodes of the aortocaval space, as well as massive invasion of the serous cover of the stomach with the extra organ component detected by laparoscopy, is a contraindication for performing simultaneous operations on the stomach and liver. In 14 (50%) patients,surgical interventions were carried out against the background of a complicated clinical course of gastric cancer: in the presence of pylorostenosis in 9 (32%) cases and torpid (sluggish) bleeding in 5 (17.85%) cases. Results: Analyzing the primary tumour and metastatic hearth in the liver, we came to the conclusion that gastric cancer with gastric metastases in the liver should be resected in cases of highly or moderately differentiated adenocarcinoma that has exophytic or mixed forms of growth, preferably with the intactness of the serous cover of the stomach. Practically in half of the patients in our series, the metastasis in regional lymph nodes are revealed,however, only in two, the defeat of lymph nodes of the second – order was diagnosed. Thus, “resectable” liver metastases can occur even at the N0 stages. In the studied group, patients with type I and II Borrmann’s prevailed with type I and II, most of them showed the intestinal histological type of a tumour. Conclusion: Liver resection for gastric cancer metastases should be performed under the following conditions: the absence of other distant metastases (peritoneum, non-regional lymph nodes, etc.); performing “radial” gastrectomy with D2-D3 lymphadenectomy; the possibility of carrying out macroscopic radical resection of the liver; functional portability of the operation; physiological operability. Keywords: Gastric cancer with liver metastases, palliative operations, indications, prognosis.

A case of IgG4-related tubulointerstitial nephritis and membranous glomerulonephritis during the clinical course of gastric cancer: Imaging features of IgG4-related kidney disease

We describe an 81-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with submandibular gland, lymph node, lung, kidney, aortic wall, and prostate lesions with concomitant gastric cancer. After curative surgical treatment of the gastric cancer, corticosteroid therapy for progressively decreasing renal function was started. Before starting steroid therapy, fluorodeoxyglucose positron emission tomography-computed tomography revealed multiple lesions of IgG4-RD but no metastasis of the cancer. However, the patient died 3 months after initiation of corticosteroid therapy because of recurrence of the gastric cancer. In this case, the imaging features of IgG4-tubulointerstitial nephritis dramatically changed during the clinical course of co-existing gastric cancer. The imaging features of the present case may provide clues to the pattern of spread of IgG4 lesions in the kidney.

Pulmonary lymphangitic carcinomatosis in the course of gastric cancer – Case report

Pulmonary lymphangitic carcinomatosis is a special type of diffuse metastasis of carcinoma in the lymphatic vessels of the lungs. Lymphangitic carcinomatosis is commonly observed in malignancies of the breast, lung, pancreas, colon and cervix as a strong marker for poor prognosis. Presenting with common respiratory symptoms, it may be easily misdiagnosed as other pulmonary interstitial diseases. Pulmonary lymphangitic carcinomatosis is a rare manifestation of metastatic gastric cancer. The presented case describes a patient with pulmonary lymphangitic carcinomatosis in the course of stomach cancer. The primary diagnosis was established based on the exclusion of other interstitial lung diseases, with the use of imaging techniques as well as biochemical, microbiological and cytological findings. The patient's general condition was very severe, rendering him bedridden and therefore not eligible for any treatment, including chemotherapy. He died suddenly before final verification of the diagnosis. Pulmonary lymphangitic carcinomatosis should be suspected in patients with advanced gastric cancer, presenting with symptoms and signs of respiratory disease. Imaging techniques are mostly helpful to establish the diagnosis.

The course of gastric cancer following surgery is associated with genetic variations of the interleukin-1 receptor antagonist and interleukin-1β

Inflammation, especially the cytokine response of the IL-1 family, has been shown to influence susceptibility to gastric cancer. In addition, several other pro-inflammatory cytokines have been demonstrated to influence metastasis and resistance to chemotherapy. Therefore, genetic variations within these genes may not only affect susceptibility but also influence the outcome of gastric cancer patients. A limited number of studies showed indeed an association of IL-1β and IL-1RN variations with survival of gastric cancer patients. However, results are inconsistent, possibly because of different patient cohorts and different therapies. In this retrospective cohort study we genotyped 154 patients with gastric cancer for IL-1β and IL-1RN variations. Patients had undergone pathologically proven R0 resection and had received no additional adjuvant treatment. We show here a protective association with disease-free survival for both heterozygous genotypes, IL-1β SNP C-511T (rs16944) and IL-1RN VNTR. The combination of both heterozygous genotypes is the strongest predictor independent of UICC stage. Genetic variations in the IL-1β and IL-1RN genes influence disease progression in gastric cancer. Screening for these genetic variations might help to stratify therapies for gastric cancer patients in the future.

At which stage of gastric cancer progression do levels of carcinoembryonic antigen and carbohydrate antigen 19-9 increase? Application in advanced gastric cancer treatment.

PurposeSince there are no proven tumor markers that reflect the course of gastric cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are commonly used alternatives. However, the degree of progression that corresponds to an increase in these markers, and the values of these markers at different cancer stages, remains unclear.Materials and MethodsThis study enrolled 1,733 gastric cancer patients who underwent surgery and whose pre-operative CEA and CA19-9 levels were known. Survival curves and mean values of the two markers were compared according to the degree of cancer progression: serosa-unexposed (SU), serosa-exposed (SE), direct invasion (DI), localized seeding (P1), and extensive seeding (P2).ResultsThe 5-year overall survival rates at each stage differed significantly, except between DI and P1 patients (17.1% vs. 10.5%, P=0.344). The mean CEA values in SU, SE, DI, P1, and P2 patients were 5.80, 5.48, 13.36, 8.06, and 22.82, respectively. The CA19-9 values for these patients were 49.40, 38.97, 101.67, 73.77, and 98.57, respectively. The increase in CEA in P2 patients was statistically significant (P=0.002), and the increases in CA19-9 in DI and P2 patients were significant (P=0.025, 0.007, respectively). There was a fair correlation between the two markers in P2 patients (r=0.494, P<0.001).ConclusionsCA19-9 can be used to assess DI of gastric cancer into adjacent organs. Both markers are useful for predicting the presence of extensive peritoneal seeding.

Evaluation of HER2-based biology in 1,006 cases of gastric cancer in a Japanese population

The ToGA trial demonstrated the beneficial effect of trastuzumab in gastric cancer patients with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors. Therefore, evaluation of the relationship between HER2 expression and gastric cancer biology using a validated system has become an even more important task. Herein, we verified the correlation between HER2 overexpression in the tumor and the clinical course of gastric cancer patients. A total of 1,006 consecutive patients with gastric cancer who underwent surgery at the National Cancer Center Hospital East between January 2003 and July 2007 were examined using the tissue microarrays approach. HER2 expression was determined based on an immunohistochemistry score of 3+, or an immunohistochemistry score of 2+ plus HER2 gene amplification as detected by double-color fluorescent in situ hybridization. A retrospective review of the medical records was conducted to determine the correlation between the presence of HER2 overexpression and clinicopathological factors. Then, in 948 patients who had undergone curative resection, HER2 status was compared with the survival. HER2 overexpression was detected in 118 (11.7 %) patients. HER2 overexpression was correlated with age, gender, grade of differentiation, expanding growth pattern, and nodal status. In the survival analysis, HER2 overexpression was not found to be correlated with either disease-specific survival or recurrence-free survival. HER2 overexpression in the tumor was not identified as a significant prognostic factor in patients with operable gastric cancer. The HER2-targeted therapy may be beneficial in a proportion of cases.

Enhancement of tumor growth by drugs with some common molecular actions

A group of structurally related drugs representing diverse therapeutic classes share, among a number of pharmacological properties, enhancement of tumor growth in several rodent models of malignancy. One common action, the inhibition of histamine binding to and catalytic activity of cytochrome P450 monooxygenases, is highly correlated with potency to enhance tumor growth. Among members of this drug ensemble, the antiestrogen tamoxifen has been shown in controlled clinical studies to increase the incidence of uterine and gastrointestinal cancer and to accelerate the course of gastric cancer, and the tamoxifen analogue clomiphene has been linked to neuroblastoma and the tricyclic group of antidepressants to ovarian cancer. The determination of drug affinities for protein modulators of cell growth, proliferation, and transformation suggests a strategy for identifying at least some classes of chemicals that impart oncologic risks to humans.

Psychosocial Factors in the Course of Gastric Cancer

A recent trend in the research in chronic disease is to consider the possible impact of psychosocial aspects. They are taken into account on the side of the predictors and on the side of criteria. Behavioral oncology suggests that social support and education might influence the course of disease to a certain extent. In an ongoing study of 1444 gastric cancer patients this hypothesis could not be confirmed. The role of other, more important psychological variables is discussed.