A UK cost-effectiveness analysis of trifluridine/tipiracil for heavily pretreated metastatic gastroesophageal cancers.

Background: The current work was designed to estimate the cost-effectiveness of trifluridine/tipiracil (T/T) versus best supportive care (BSC) for patients with advanced stage or metastatic gastroesophageal cancer (mGC) from a UK perspective. Materials & methods: A partitioned survival analysis was undertaken using data from the phase III TAGS trial. A jointly fitted lognormal model was selected for overall survival and individual generalized gamma models were chosen for progression-free survival and time-to-treatment-discontinuation. The primary outcome was the cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were undertaken to investigate uncertainty. Results: Compared with BSC, T/T was associated with a cost per QALY gained of £37,907. Conclusion: T/T provides a cost-effective treatment option for mGC in the UK setting.

Retroperitoneal liposarcoma with pancreatic metastasis and gastric cancer: a case report.

On computed tomography scanning, a 63-year-old man with vomiting and anorexia was discovered to have a mass in the pancreatic body and a retroperitoneal mass extending to the right lobe of the liver. An esophagogastroduodenoscopy revealed an advanced gastric carcinoma in the middle gastric body, and a biopsy specimen revealed a poorly differentiated adenocarcinoma. The pancreatic and retroperitoneal masses were considered metastatic lesions of gastric cancer, and a biopsy was taken from the pancreatic lesion using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The histology of the EUS-FNA pancreatic specimen revealed atypical spindle-shaped cells and increased stromal collagen fibrosis, and liposarcoma was considered. Conversely, a percutaneous ultrasound-guided biopsy was taken for the retroperitoneal lesion, and the histology revealed that it was a dedifferentiated liposarcoma. On the basis of histopathological and imaging findings, the retroperitoneal liposarcoma was identified as the primary lesion, the pancreatic lesion as a metastasis of the primary liposarcoma, and the gastric carcinoma as an independent tumor. As far as we know, there have only been three reports of metastatic pancreatic liposarcoma diagnosed via EUS-FNA. In this case, the patient also had gastric cancer, and EUS-FNA was helpful in differentiating metastatic pancreatic tumors from gastric cancer.

Gastric fundic gland metastasis of renal cell carcinoma 14 years after the primary diagnosis.

Gastric metastasis from renal cell carcinoma (RCC) is rare and associated with poor outcomes. In this case, we report gastric fundic gland metastasis presenting with upper gastrointestinal bleeding in a patient who had a history of nephrectomy due to RCC 14 years ago. Metastasis of any cancer to the stomach is relatively uncommon. Gastric metastasis from RCC, especially isolated fundic gland metastasis, is extremely rare. However, although rare, metastatic RCC to the stomach should be suspected in any patient with a history of RCC who presents with gastrointestinal symptoms.

RAB27A and RAB27B Expression May Predict Lymph Node Metastasis and Survival in Patients With Gastric Cancer.

BACKGROUND/AIM: RAB27A and RAB27B are involved in exosome secretion. To date, there have been many attempts to elucidate the roles of RAB27A and RAB27B in the prognosis of various cancer types. The association of RAB27A and RAB27B expression with the clinical and pathological features was evaluated in patients with stomach cancer. MATERIALS AND METHODS: A total of 360 patients who had undergone surgery for stomach cancer between January 1999 and December 2007 at Gyeongsang National University were enrolled in the study. Disease-free survival (DFS) and disease-specific survival (DSS) were compared according to immunohistochemistry of tumor samples. RAB27A and RAB27B mRNA and protein were also extracted from four stomach cancer cell lines using quantitative polymerase chain reaction and western blotting. RESULTS: Strong nuclear RAB27A expression in tumor samples was statistically significantly correlated with lymph node metastasis. Cytoplasmic RAB27B expression was related to poor disease-free survival and its combined cytoplasmic and membranous expression was related to disease-specific survival of patients with different histopathological types of stomach cancer. High RAB27A expression and high RAB27B expression was found in four stomach cancer cell blocks. Among the four cell lines, NCI-N87 exhibited the lowest relative mRNA density and HS746T exhibited the highest relative protein density for both RAB27A and RAB27B. CONCLUSION: RAB27A and RAB27B expression may help predict lymph node metastasis and survival of patients with gastric cancer.

[Value of dual-layer spectral detector CT in preoperative prediction of lymph node metastasis of gastric cancer].

Objective: To investigate the value of dual-layer spectral detector CT(SDCT) in preoperative prediction of lymph node (LN) metastasis of gastric cancer. Methods: From January 2019 to January 2021, the clinical and imaging data of 130 gastric cancer patients(93 males and 37 females, aged from 37 to 84 years)confirmed by pathology in the Zhongshan hospital of Xiamen University were retrospectively collected. According to the status of lymph node metastasis, those patients were divided into metastatic LNs group (n=104) and nonmetastatic LNs group (n=26). The maximum diameter of gastric cancer on spectral CT images, CT Values of lesions in 40, 50, 60, 70. KeV monoenergetic image of arterial and Venous phase (CT40 keV, CT50 keV, CT60 keV, CT70 keV), iodine concentration (IC) and effective atomic number (Zeff) were measured, then the normalized IC(NIC) and spectral curve(K(40-70)) value were calculated. The differences of each parameter derived from spectral CT between the two groups were compared, and a logistic regression model was constructed. The ROC curves and area under the curve (AUC) were conducted to evaluate the diagnostic performance of each parameter and Delong test was used to compare the difference of each AUC. Results: Compared to nonmetastatic LNs group, metastatic LNs group had higher maximum diameter of tumor, CT40 keV, CT50 keV, CT60 keV, CT70 keV, IC, NIC, Zeff, and K(40-70) values on venous phase (the representative parameter is Zeff: 8.4 (8.2, 8.5) vs 8.2 (8.1, 8.3)) (all P<0.05). The proportion of patients with lower histology differentiated degree, higher T grade and positive carcino embryonic antigen (CEA)were higher than that in nonmetastatic LNs (the representative parameter was CEA: 34.6%(36/104) vs 7.7%(2/26) (all P<0.05). The regression model constructed by CEA and Zeff had the highest predictive value in predicting metastatic LNs, with an AUC of 0.835(0.759-0.894), sensitivity and specificity of 83.65% and 73.08%, respectively. Conclusion: SDCT quantitative parameters on venous phase and CEA facilitate the accurate prediction of metastatic LNs in patients with gastric cancer, and the multi-parameter regression model has the highest diagnostic performance.

The lncRNA SEMA3B-AS1/HMGB1/FBXW7 Axis Mediates the Peritoneal Metastasis of Gastric Cancer by Regulating BGN Protein Ubiquitination.

Peritoneal metastasis (PM) is one of the main causes of a poor prognosis in patients with advanced gastric cancer (GC). lncRNAs have been confirmed to play a very crucial role in the occurrence, development, and metastasis of many human cancers, including gastric cancer. However, the mechanism of lncRNA in PM of GC is rarely studied. We explored the mechanism of PM of GC through lncRNA gene sequencing and protein profiling analysis to detect PM-associated lncRNAs and proteins. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to identify the mRNA expression of SEMA3B-AS1 and BGN in GC tissues and adjacent normal tissues. The biological function of SEMA3B-AS1 in the PM of GC was identified through gain- and loss-of-function assays. Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and coimmunoprecipitation (co-IP) assays was carried out to demonstrate the potential mechanism between SEMA3B-AS1 and its downstream genes, including HMGB1, FBXW7, and BGN. Finally, the biological function of SEMA3B-AS1 was demonstrated in animal experiments. The mRNA expression level of SEMA3B-AS1 was downregulated in GC and PM tissues compared to normal stomach tissues; however, BGN was highly expressed at the mRNA level. SEMA3B-AS1 was closely related to PM and the overall survival (OS) of GC patients. Functionally, the overexpression of SEMA3B-AS1 was related to GC progression, PM, and prognosis. Mechanistically, SEMA3B-AS1 could combine with HMGB1 to regulate the transcription of FBXW7, thus facilitating the ubiquitination of BGN. In conclusion, our study demonstrated that the SEMA3B-AS1/HMGB1/FBXW7 axis plays an inhibitory role in the PM of GC by regulating BGN protein ubiquitination. It also provides a new biological marker for the diagnosis and treatment of the PM of GC.

Gastric and colonic metastasis from NSCLC: A very unusual case report.

RATIONALE: Lung cancer is the most common cause of cancer-related deaths worldwide. Approximately 50% of patients is metastatic at diagnosis and the most common metastatic sites are bone, lungs, brain, adrenal glands, liver, and extra thoracic lymph nodes. The occurrence of gastrointestinal metastasis from lung carcinoma is rare and seems more commonly related to small cell lung cancer compared to non-small cell lung cancer (NSCLC). PATIENT INFORMATION AND DIAGNOSIS: A 78-year-old man with completely surgically resected NSCLC and no initial evidence of distant metastases developed colon and gastric metastases 7 months after diagnosis, confirmed by serial radiological examinations and endoscopic biopsies. INTERVENTIONS: The patient was subjected to total gastrectomy with D2 lymph node dissection plus partial colectomy for intraoperative detection of a transverse colon neoformation. Subsequent instrumental imaging showed bilateral lung tumor recurrence, treated with gemcitabine monotherapy for 8 months as first line chemotherapy for lung adenocarcinoma. RESULTS: The patient presented complete response to therapy and was disease-free for 4 years. LESSONS: Colonic and gastric metastasis are very infrequent in NSCLC. The resection of gastrointestinal metastasis may provide benefits in terms of both symptom control and survival in patients properly selected.

Amelanotic metastatic gastric malignant melanoma: a case report.

Melanoma is a malignant form of cutaneous cancer with an increasing incidence since 1970s, accounting for nearly 75% of the death related to skin cancer especially in western countries. Highest recurrence and mortality were observed for the subtype with distal metastasis, demonstrating poor outcomes. However, high incidence of gastrointestinal metastasis of malignant melanoma is frequently misdiagnosed due to lack of specific clinical manifestations, especially for the rare observed cases presented amelanotic appearance, accounting for about 2% of all metastatic cases. In the present study, we reported a 36-year-old male patient, who was firstly diagnosed as gastric cancer, and then was confirmed as amelanotic melanoma metastasis by pathological examination, demonstrating positive for melanoma markers including Melan A, S-100, Hmb45 and CD79a. In conclusion, for the amelanotic neoplasm observed during gastroscopy in patients with melanoma history, pathological examination should be carried out to confirm the possibility of melanoma metastasis, providing evidences for the following treatment.

Gastric metastasis and transformation of primary lung adenocarcinoma to small cell cancer after acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors: A case report.

RATIONALE: Transformation to small cell lung cancer (SCLC) is one of the mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, no standard treatment is available after the transformation. In addition, gastric metastasis of primary lung cancer is rarely observed; thus, little is known about its metastatic characteristics. PATIENT CONCERNS: A 58-year-old male patient was treated with gefitinib (0.25 g /day) as the 1st line treatment due of recurrence after surgical resection for EGFR exon 19 mutation pulmonary adenocarcinoma. However, he experienced recurrence with positive T790 M, and osimertinib (80 mg/day) was administered as the 2nd line therapy. DIAGNOSIS: One year and 6 months after osimertinib initiation, he complained of stomachache, and a diagnostic gastroscopy biopsy confirmed small cell lung cancer in the gastric body, indicating osimertinib-induced phenotypic transformation. INTERVENTIONS AND OUTCOMES: The patient was treated with etoposide and platinum chemotherapy and maintenance therapy with osimertinib. Finally, the patient achieved a partial response after 4 cycles. LESSONS: Timely second biopsies should be considered in the diagnosis of phenotypic transformation. After transformation, chemotherapeutic treatment with etoposide and platinum and maintenance therapy with osimertinib inhibited the progression of the disease.

Metastases to the Stomach: Clinicopathologic Features of Metastases Mimicking Gastric Primaries.

OBJECTIVE: Metastatic involvement of the stomach is a rare event. Our aim in this study was to document the clinicopathological findings in patients with gastric metastases and find out if there are any potentially significant features to be used in the differential diagnosis. MATERIAL AND METHOD: Our cohort consisted of 17 histologically verified gastric metastasis cases. Clinical, endoscopic and microscopic features were retrospectively analyzed. RESULTS: The primary sites were the breast, skin, lungs, ovaries, colon, and gluteal soft tissue. Three patients were symptomatic because of the metastatic involvement of the stomach and 9 patients had concomitant metastasis in other sites. Invasive lobular breast carcinoma and malignant melanoma were the most common metastatic malignancies. The most common macroscopic appearance was the diffuse infiltrative type (Borrmann Type 4). Most of the metastatic lesions endoscopically mimicked primary gastric cancer. Furthermore, some of the metastatic lesions, particularly invasive lobular carcinoma of the breast and malignant melanoma, displayed histopathologic features similar to the primary gastric malignancies to a certain extent. CONCLUSION: The possibility of metastatic involvement of stomach must be kept in mind while dealing with a gastric mass lesion in a cancer patient, even though the clinical and endoscopic features suggest primary gastric cancer. Our study points out the importance of conveying the information about medical history and clinical findings of the patients for correct pathologic differential diagnosis.

A risk signature with inflammatory and immune cells infiltration predicts survival and efficiency of chemotherapy in gastric cancer.

OBJECTIVE: Tumor immune microenvironment biomarkers might add predictive value for outcomes. This study aimed to construct a risk signature with tumor infiltration immune and inflammatory cells to improve the prediction of survival. METHODS: A risk signature model in combination with CD66b + neutrophils, CD3+ T, CD8+ T lymphocytes, and FOXP3 + regulatory T cells was developed in a training cohort of 327 GC patients undergoing surgical resection between 2011 and 2012, and validated in a validation cohort of 285 patients from 2012 to 2013. RESULTS: The high CD66b expression predicted the poor disease special survival (DSS) and inversely correlated with the CD8 (P < 0.05) and FOXP3 expression (P < 0.05) in the training cohort. This was comparable to the disease-free survival (DFS) findings observed in the validation cohort. Furthermore, a risk stratification was developed from the integration of CD66b + neutrophils and T immune cells. For DFS and DSS, both demonstrated the worse prognosis in the high-risk group, when compared to the low-risk group in both the training cohort and validation cohort (all P < 0.05). In addition, the high-risk group was associated with post-operative relapses, and this risk signature model increased the predictive accuracy and efficiency for post-operative relapses. Moreover, the high-risk group identified a subgroup of GC patients who tended not to benefit from the adjuvant chemotherapy. CONCLUSIONS: The incorporation of neutrophils into T lymphocytes could provide more accurate prognostic information in GC and this risk stratification has potential for identifying the subgroup of GC patients who could benefit from adjuvant chemotherapy.

Atrial reconstruction, distal gastrectomy with Ante-situm liver resection and autotransplantation for hepatocellular carcinoma with atrial tumor thrombus: A case report.

RATIONALE: Hepatocellular with tumor thrombi extending into 3 hepatic veins (HVs) and right atrium presents as a real clinical challenge. We report the first documented case of surgical resection of an advanced hepatocellular carcinoma (HCC) with extensive invasion to distal stomach, atrium and hepatic vasculatures. PATIENT CONCERNS: We present a case of 48-years old man with abdominal mass accompanying shortness of breath after activities. DIAGNOSES: Preoperative examination revealed giant HCC with tumor thrombi extending into portal vein, HVs, inferior vena cava, and atrium. INTERVENTIONS: Distal stomach involvement was confirmed at surgery and, distal gastrectomy, atrial reconstruction and ante-situm liver resection and autotransplantation under cardio-pulmonary bypass were performed. OUTCOMES: The operation time was 490 minutes, extracorporeal circulation time 124 minutes, and anhepatic time 40 minutes. Postoperative follow-up revealed normal hepatic and cardiac function with no sign of recurrence. LESSONS: This case illustrates that the extensive invasion of HCC to major vasculature and adjacent organs may not necessarily preclude the liver autotransplantation with multi-visceral resection as the treatment option of extremely advanced HCC patients.

Long-term response on letrozole for gastric cancer: A case report.

RATIONALE: Hormone therapies, particularly those targeting estrogen and its receptors, are a key treatment modality for patients with estrogen receptor (ER)-positive breast or ovarian cancer. Some gastric cancers (GCs) express ERs, and preclinical studies suggest the potential of estrogen-targeting hormone therapy on GC; however, the clinical relevance of this hormone therapy on GC treatment has not been well elucidated. PATIENT CONCERNS: An 80-year-old female was admitted to our department with hypogastric pain and vomiting. Computed tomography demonstrated small bowel obstruction, and laparotomy after bowel decompression revealed peritoneal dissemination consisting of a poorly-differentiated adenocarcinoma. Intestinal bypass between the ileum and transverse colon was performed. DIAGNOSES: The tumor was ER- and mammaglobin-positive, indicating that it originated from a breast cancer. Diagnostic imaging revealed no evidence of breast cancer; however, right axillary ER- and mammaglobin-positive lymphadenopathy was found. INTERVENTIONS: The patient received hormone therapy using letrozole based on a clinical diagnosis of occult breast cancer with peritoneal dissemination and right axillary lymph node metastasis. OUTCOMES: The patient remained disease free until 37 months but deceased at 53 months from the onset of disease. An autopsy revealed no tumor cells in the right breast tissue; however, there was a massive invasion of cancer cells in the stomach. LESSONS: A patient with ER positive GC with peritoneal dissemination and right axillary lymph node metastasis presented remarkable response to letrozole. The long-term survival obtained using letrozole for a patient with GC with distant metastasis suggests the potential of estrogen targeting hormone therapies for GC.

YY1-modulated long non-coding RNA SNHG12 promotes gastric cancer metastasis by activating the miR-218-5p/YWHAZ axis.

Long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) plays important roles in the pathogenesis and progression of cancers. However, the role of SNHG12 in the metastasis of gastric cancer (GC) has not yet been thoroughly investigated. In the present study, we demonstrated that SNHG12 was upregulated in GC tissues and cell lines. In addition, the expression level of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM stage and lymph node metastasis and was associated with disease-free survival (DFS) and overall survival (OS) in GC patients. In vivo and in vitro assays indicated that SNHG12 promotes GC metastasis and epithelial-mesenchymal transition (EMT). Bioinformatics and mechanistic analyses revealed that SNHG12 can directly target miR-218-5p to regulate YWHAZ mRNA, forming an SNHG12/miR-218-5p/YWHAZ axis and decreasing the ubiquitination of ß-catenin. In addition, SNHG12 stabilizes CTNNB1 mRNA by binding with HuR, thus activating the ß-catenin signaling pathway. Further analysis also revealed that the transcription factor YY1 negatively modulates SNHG12 transcription. In conclusion, SNHG12 is a potential prognostic marker and therapeutic target for GC. Negatively modulated by YY1, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and stabilizing CTNNB1 via activation of the ß-catenin signaling pathway.