Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma.

1984 ◽  
Vol 2 (11) ◽  
pp. 1249-1254 ◽  
Author(s):  
C G Moertel ◽  
D S Childs ◽  
J R O'Fallon ◽  
M A Holbrook ◽  
A J Schutt ◽  
...  

Sixty-two patients with resectable but poor-prognosis gastric carcinoma were randomized to either no surgical adjuvant therapy or treatment with 5-fluorouracil (15 mg/kg by rapid intravenous injection X 3) plus radiation (3,750 rad in 24 fractions) initiated 3 1/2 to six weeks postoperatively. Informed consent was obtained after randomization and only from the 39 randomized to treatment. Ten patients refused their treatment assignment. The five-year survival rate for patients randomized to treatment was 23%, and for those randomized to no treatment, 4% (P less than .05). Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups (P = .024) and favored treatment assignment. When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing, five-year survival rates were: treated, 20%; treatment refusal, 30%; controls, 4%; the three survival distributions were not significantly different. Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54% of those who received no treatment. This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research. This study also illustrates the potential problems that may be encountered in interpreting results when patients are randomized to a study before consent is obtained.

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110184
Author(s):  
Yi Wang ◽  
Peiqing Ma ◽  
Kan Liu ◽  
Dongkui Xu ◽  
Qian Liu

Poorly differentiated gastric adenocarcinoma is commonly associated with lymph node metastasis, peritoneal spread, and liver metastasis but rarely with intraintestinal metastasis. Most patients with metastatic gastric carcinoma are unable to undergo surgical treatment and have a poor prognosis. A 42-year-old man with hunger-related abdominal pain was diagnosed as having gastric cancer. After the first surgery (distal partial gastrectomy) and the second surgery (gastric stump carcinoma (GSC) resection), the patient suffered repeated multiple intracolonic metastases and underwent three additional resection operations. The patient survived for 154 months after the first operation. In patients with gastric carcinoma that metastasizes to the colonic lumen, radical resection, if possible, can extend survival. Once patients develop extensive extraintestinal metastasis, radical resection cannot be performed, and patients often exhibit a poor prognosis.


2021 ◽  
Vol 6 ◽  
pp. 30-46
Author(s):  
Juhi Singh ◽  
Puneet Kumar ◽  
Khushi Verma ◽  
Satyender Kumar Tiwary ◽  
Gopeshwar Narayan ◽  
...  

Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality and this is associated with poor survival rates. Understanding the molecular genetic changes of gastric carcinoma may offer an insight into its pathogenesis helps in identifying new biomarkers, aid prognostication, and novel treatment targets. Over a past few decades, advances in technology and high throughput analysis have improved understanding of the molecular genetic aspects of gastric cancer. In this article, hierarchy of the changes at genetic and molecular level including several aspects which are heterogenous and represents a wide spectrum such as tumor suppressor genes, oncogenes, cellcycle regulators, apoptosis, cell-adhesion molecules, loss of heterozygosity, microsatellite instability, and epigenetic changes. The classification of gastric carcinoma at molecular and genetic level as well as hereditary gastric carcinoma is elaborated. The molecular genetic aspects regarding pathogenesis, changes and aberrations of all genes and pathways which are involved in gastric cancer are addressed in this review.


2020 ◽  
Vol 7 (47) ◽  
pp. 2747-2751
Author(s):  
Lekshmi Vijayakumaran Nair Lilly ◽  
Geetha Sukumaran

BACKGROUND Gastric carcinoma is an important cause of cancer related mortality worldwide. Majority of the patients are diagnosed in the advanced stage of the disease. The main treatment modalities are surgery and chemotherapy, but the survival rate of patients with advanced resectable gastric cancer remains poor. For patients with unresectable gastric cancer, chemotherapy remains the treatment of choice. Into this scenario comes the importance of newer targeted therapeutic agents which improve survival rates with acceptable toxicity effects. HER2 is a growth factor implicated in disease initiation and progression, and its expression is associated with a poor prognosis. The aim of this study is detection of HER2 expression in gastric carcinoma and evaluate its relationship with the histopathological characteristics. This would be the stepping stone for patients with tumours that are HER2 positive who could benefit from targeted therapeutical agents like Trastuzumab. METHODS Gastrectomy specimens which were diagnosed as Gastric Carcinoma in the Department of Pathology, Government Medical College, Trivandrum, during a period of two years were included in this study. Routine Haematoxylin and Eosin staining and immunohistochemistry for HER2 were done. RESULTS Thirty eight cases of gastric carcinoma were received during the study period. Intestinal type adenocarcinoma formed the bulk of the tumours (68.42 %), followed by the diffuse type adenocarcinoma (18.42 %). Of the 38 cases, 10 cases showed HER2 positivity. All the positive cases were intestinal type of adenocarcinomas. CONCLUSIONS Our study concluded that 26 % of gastric carcinomas showed positive immunoreaction for HER2 and HER2 overexpression was more in intestinal type adenocarcinomas. HER2 overexpression was also associated with higher stage tumours. There was no association with the patient’s age, gender, location of tumour and tumour differentiation. KEYWORDS Gastric Carcinoma, HER2 expression, Immunohistochemistry, Lauren Classification


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 154-154
Author(s):  
Hiroko Hasegawa ◽  
Seiichiro Mitani ◽  
Takeru Wakatsuki ◽  
Hiroki Hara ◽  
Motohiro Hirao ◽  
...  

154 Background: S-1 monotherapy is one of the standard adjuvant treatments for stage II or III gastric cancer patients (pts). Early recurrence after adjuvant therapy has a poor prognosis and the optimal regimen remains to be established. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens for gastric cancer pts with early recurrence. Methods: We retrospectively reviewed gastric cancer pts at four institutions who underwent curative gastrectomy followed by adjuvant S-1 monotherapy and identified pts who developed recurrence during the adjuvant therapy or within 6 months after completion between 2005 and 2015. Other main eligibility criteria were Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2, adequate organ function and no massive ascites. The Cox proportional hazards model was used to evaluate the survival outcomes, adjusting for relevant factors. Results: A total of 112 pts were included. Pts characteristics were as follows: median age (range), 62 (29-83) years; male/female, 84/28; ECOG-PS 0/1/2, 39/63/10; diffuse/intestinal, 73/39; HER2 status positive/negative/unknown, 17/46/49; metastatic site liver/peritoneum, 32/44; and number of metastatic sites 1/≥2, 94/18. The taxane-based regimens were as follows: weekly paclitaxel (PTX) (38), nab-PTX (4), trastuzumab (Tmab) + PTX (4), S-1 + PTX (3), and the others (4). The platinum-based regimens were irinotecan + cisplatin (IP) (31), capecitabine + cisplatin (XP) (7), S-1 + cisplatin (5), Tmab + XP (4), and the others (2). For all pts, the median PFS and OS were 3.7 months (M) and 11.4 M, respectively. After excluding HER2-positive pts, there were no statistically significant differences between the taxane-based and platinum-based regimens in survival outcomes (median OS, 7.6 M vs. 12.2 M; adjusted HR = 0.93, 95% CI 0.58-1.49), nor between IP and the other platinum-based regimens (median OS, 11.8 M vs. 13.3 M; adjusted HR = 0.64, 95% CI 0.28-1.46). Multivariate analysis showed treatment regimen was not a prognostic factor. Conclusions: The regimens so far selected for gastric cancer with early recurrence resulted in similar, poor prognosis.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 5-5
Author(s):  
N. Didwaniya ◽  
R. J. Edmonds ◽  
P. T. Silberstein ◽  
S. Subbiah

5 Background: Gastric cancer is one of the leading causes of cancer related deaths worldwide with the incidence declining in the United States. However the prognosis remains poor with variable survivals being reported among different races. We analyzed the effect of race on patterns of disease presentation and survival rates using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: A total of 9,851 patients were diagnosed with gastric cancer from year 2004 to 2007 were identified from SEER database. Age, race, TNM staging, grade, treatment modalities utilized and cancer specific survival was collected. Results: Out of 9,851 patients, 64.63% were white, 12.17% were black, and 13.04% were Asian-Pacific islanders. Median age was 73 years for whites, 70 years in blacks, and 71 years in Asians. Sex distribution amongst races was more or less similar with 58.83% of whites, 59.47% of blacks, and 54.24% of Asians being men. 23.62% of whites had T1 lesions, 28.10% had T2, 19.58% were T3 and 28.70% had T4 lesions. 26.76% of blacks presented with T1 lesions, 26.63% with T2, 16.08% with T3 and 30.53% with T4. 18.69% of Asians had T1 lesions, 26.84% with T2, 23.44% had T3 and 31.03% had T4 lesions. 37.80% of whites, 36.70% of blacks, and 44.44% of Asians had lymph node involvement. Tumor grade was similar among all races. Surgery was performed in 31.49% of whites, 33.13% of blacks, and 40.48% of Asians. 14.68% of whites, 14.10% of blacks, and 19.43 % of all Asians underwent radiation therapy. Median overall survival in localized disease was 44 months, 43 months and 98 months (p < 0.0001) while in regional disease it was 16 months, 15 months and 23 months in whites, blacks and Asians respectively (p < 0.0001). Median survival in distant disease was 4 months in both whites and blacks; it was 5 months in Asians (p < 0.0001). Conclusions: Cancer-specific survival in gastric carcinoma is significantly better in localized, regional and metastatic disease in Asians when compared to whites and blacks independent of T stage, grade, nodal involvement and treatment modalities utilized. The reason for this observation is unclear, exposure and genetic factors are potential causes and this needs to be investigated. No significant financial relationships to disclose.


2020 ◽  
Vol 22 (2) ◽  
pp. 79-82
Author(s):  
Md Azizur Rahman ◽  
Abdullah Md Abu Ayub Ansari ◽  
Kazi Mazharul Islam ◽  
Md Aminur Rahman ◽  
ABM Abdul Matin ◽  
...  

Background: Carcinoma of the stomach is a major cause of cancer mortality worldwide. Due to social impact of gastric carcinoma (GC), there is a need to stratify patients into appropriate screening, surveillance and treatment programs. Although histopathology remains the most reliable and less expensive method, numerous efforts have been made to identify and validate novel biomarkers to accomplish the goals. In recent years, several molecules have been identified and tested for their clinical relevace in GC management. Among the biomarkers with the exception of HER2, none of the biomarkers is currently used in clinical practice, and some of them were described in single studies. Materials and Methods: This prospective type of observational study was performed in the Department of Surgery, Dhaka Medical College Hospital, Dhaka, 6 months from approval of protocol. Total 45 consecutive patients aged 18 years and above without consideration of gender were selected purposefully. Every patient was evaluated by clinical examination, appropriate investigations and after a confirm diagnosis of the tissue from the cancer. All patients have undergone operative intervention and Gastrectomy specimens were subtotal (including cardiac and pylorus), subtotal (including the pylorus), total radical gastrectomy and oesophago-gastrectomy sample. All specimens obtained were immersed in 10% formalin. Samples of whom were sent to the department of pathology, DMCH for histopathology examination. Portion of representative tissue/block was sent to AFIP (Armed Forces Institute of Pathology, Dhaka) for immunohistochemistry to find out the HER2 expression in gastric cancer and gastro-oesophageal cancer. Data was collected in a pre-designed questionnaire by face to face interview. Result and observation: In this study when 45 cases were categorized according to WHO grading system it was observed that majority (30) patients were found in grade II, among them 3(10%) were HER2 positive. But with grade III tumour the HER2 positivity were found more i,e; 37.5% (3/8). Grade- I tumor show HER2 neu expression 28.57% (2/7) and according to location most of the cases with HER2 positive expression was located in the gastro-esophageal junction which is 27.27% (3/11) than gastric carcinoma which is 14.70% (5/34). Conclusion: Most of the patients of gastric and gastrooesophageal junction adenocarcinoma are diagnosed at a very late stage, so they require special attention in treatment protocol, including chemotherapy and immunotherapy for increasing their survivability. The study showed with poorly differentiated (high grade) tumour, the HER2 positivity were found more. Journal of Surgical Sciences (2018) Vol. 22 (2) : 79-82


2019 ◽  
Vol 19 (23) ◽  
pp. 2128-2142 ◽  
Author(s):  
Hao He ◽  
Chang Xu ◽  
Zhao Cheng ◽  
Xiaoying Qian ◽  
Lei Zheng

: KRAS is the most common oncogene to be mutated in lung cancer, and therapeutics directly targeting KRAS have proven to be challenging. The mutations of KRAS are associated with poor prognosis, and resistance to both adjuvant therapy and targeted EGFR TKI. EGFR TKIs provide significant clinical benefit for patients whose tumors bear EGFR mutations. However, tumors with KRAS mutations rarely respond to the EGFR TKI therapy. Thus, combination therapy is essential for the treatment of lung cancers with KRAS mutations. EGFR TKI combined with inhibitors of MAPKs, PI3K/mTOR, HDAC, Wee1, PARP, CDK and Hsp90, even miRNAs and immunotherapy, were reviewed. Although the effects of the combination vary, the combined therapeutics are one of the best options at present to treat KRAS mutant lung cancer.


2021 ◽  
pp. 1-10
Author(s):  
Zhongyin Yang ◽  
Chao Yan ◽  
Wentao Liu ◽  
Wei Xu ◽  
Chen Li ◽  
...  

BACKGROUND: Gastric cancer (GC) patients with peritoneal metastasis usually have extremely poor prognosis. Intraperitoneal infusion of paclitaxel (PTX) provides an effective treatment, but relapse and PTX-resistance are unavoidable disadvantages, and it is difficult to monitor the occurrence of PTX-resistance. OBJECTIVE: The aim of this study was to explore novel autoantibodies in the ascites of individuals with relapsed PTX-resistant GC with peritoneal metastasis. METHODS: Ascites samples were collected before PTX infusion and after the relapse in 3 GC patients. To determine the expression of significantly changed proteins, we performed autoantibody profiling with immunome protein microarrays and tandem mass tag (TMT) quantitative proteomics, and then, the overlapping proteins were selected. RESULTS: Thirty-eight autoantibodies that were differentially expressed between the ascites in the untreated group and relapsed PTX-resistant group were identified. For confirmation of the results, TMT quantitative proteomics was performed, and 842 dysregulated proteins were identified. Four proteins, TPM3, EFHD2, KRT19 and vimentin, overlapped between these two assays. CONCLUSIONS: Our results first revealed that TPM3, EFHD2, KRT19 and vimentin were novel autoantibodies in the ascites of relapsed PTX-resistant GC patients. These autoantibodies may be used as potential biomarkers to monitor the occurrence of PTX-resistance.


2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


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