Enhanced Cell Surface Expression of Matrix Metalloproteinases and Their Inhibitors, and Tumor-Induced Host Response in Progression of Human Gastric Carcinoma

The cell surface and/or intracellular expression of the matrix metalloproteinases (MMP -2, 7, and -9 and MT1-MMP) and their inhibitors (TIMP-2 and -4) were investigated in tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (n = 15) from the primary locus, metastatic gastric carcinoma (n = 20) from malignant ascites, and benign gastric mucosa (n = 20) for the control. The quantitative analysis was based on the percentage of positive cells by flow cytometry. The results clearly showed increased cell surface expression of MMP-2, -7, and -9, MT1-MMP, and TIMP-2 and -4 in both tumor cells and TIL during the development of invasion and/or metastasis of gastric carcinoma. There were equilateral correlations with cancer progression and frequency of cell surface expression of MMPs and their inhibitors, TIMPs, suggesting not only the aggressive nature of particularly metastatic gastric carcinoma, but also the presence of MMPs complexed with TIMPs on tumor cells and TIL. The enhanced cell surface expression of MMPs and TIMPs on TIL within metastatic carcinoma nests showed the result of a host response induced by tumors. These suggest that the increased cell surface expression of MMPs and TIMPs, and tumor-induced host response play a key role in gastric cancer invasion and/or metastasis.     

DIFFERENTIAL DIAGNOSIS OF GASTRIC LESIONS BY MAGNIFYING ENDOSCOPY

We performed magnifying endoscopy for patients with suspected gastric diseases. Among these patients, 67 patients with early gastric cancer and 31 benign gastric diseases were enrolled in this study. The patients with early gastric cancer included 46 differentiated tubular adenocarcinoma (33 mucosal cancer, 13 submucosal cancer) and 21 non‐differentiated tubular adenocarcinoma (12 mucosal cancer, 9 submucosal cancer). The benign gastric lesions included 23 gastric ulcer or gastric ulcer scars, three gastritis, and five gastric adenomas. Small regular patterns were observed; 39% in differentiated adenocarcinoma, 5% in undifferentiated adenocarcinoma, and 19% in benign gastric diseases. Irregular patterns were observed 37%, 52%, and 6%. Lack of visible structure was observed 18%, 90%, and 10%. Abnormal vessels were observed 26%, 81%, and 16%. Small regular patterns were observed significantly more frequently in differentiated adenocarcinoma than in undifferentiated adenocarcinoma (P < 0.001). Lack of visible structure and Irregular patterns were observed significantly more frequently in undifferentiated adenocarcinoma than in differentiated adenocarcinoma (P < 0.001). In order to spread this useful endoscopy widely easy recognition of abnormality, histological backbone, and further technical developments in hardware and software should be required.     

Fas receptor counterattack against tumor-infiltrating lymphocytes in vivo as a mechanism of immune escape in gastric carcinoma

We investigated the presence and functional status of surface expression of the Fas receptor (FasR) and its ligand (FasL) in tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (n=36) from the primary locus, metastatic gastric carcinoma (n=30) from malignant ascites, and benign gastric mucosa (n=30) for the control. The quantitative analysis was based on the percentage of positive cells by a flow cytometry. The results showed that the membrane-bound FasL molecule was constitutively expressed in primary and metastatic gastric carcinomas as well as normal gastric epithelium in nearly all the patients. In particular, metastatic carcinoma proved to aberrantly express the FasL molecule. On the other hand, FasR expression ranged from minimal or absent in primary and metastatic gastric carcinomas, suggesting that the carcinoma might be rendered less sensitive toward FasR-induced killing. Apoptotic tumor cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick and labeling (TUNEL) were barely identified in primary and metastatic carcinomas. In the analysis of TIL, the expression of FasR and FasL, and apoptotic TIL could not usually be observed in primary gastric carcinoma. In metastatic carcinoma, however, there was significant overexpression of FasR and FasL in immune TIL associated with a higher frequency of apoptotic cell death detected by TUNEL. The results suggest that metastatic carcinoma expressing FasL, but not FasL⁺ primary carcinoma, might evade the immune attack by apoptotic depletion of activated TIL through the FasR/FasL systems. These results provide the direct and quantitative evidence of FasR counterattacks and/or paracrine fratricides as a mechanism of tumor-immune escape in vivo in human cancer. Received: 29 March 2000 / Accepted: 30 June 2000     

Effect of treatment of tumor-infiltrating lymphocytes on gastric cancer

AIM To study the effect of immune treatment on gastric cancer.METHODS Thirteen patients with advanced gastric cancer were given TIL adoptive immunotherapy in thisstudy. Histological findings showed that 13 patients had gastric adenocarcinoma. Patients received operationson their primary tumor, which could not be resected. Small tumor tissue and metastic lymph nodes were gotduring the operation for TIL preparation. Ten patients were treated as control group. During TILtreatment, the patients did not received any other treatment. Surgical speciments (metastatic lymph nodes )with pathological diagnosis were obtained from operating room. The lymph nodes were minced anddissociated in RPMI 1640 with 0.03% hyaluronidase type V (1500U/g), 0.05% collagenase type Ⅳ(200 U/g), and 0.008% deoxyribonuclease type I (100 U/g) (Sigma, USA) at 37℃ for 12 h. The cellmixture was then filtered through 4-layer gauge, washed twice in Hank's and separated on Ficoll-Hypague(Shanghai ist Chemical Reagent Factory) at 900×g for 20min. Finally, the cells were harvested andcounted. Cells suspension containing TIL and tumor cells were extensively washed and resuspended at a finalconcentration of 106 lymphocytes/mL in complete medium containing 15% human AB serum, 100 U/mLpenicillin and 100 μg/mL streptomycin in RPMI 1640 (Gibco). The final concentration of rIL-2 (Military Medical Institute, Nanjing ) was 500 U/mL. Cultured after 3 d-4 d, lymphoid cells were counted andculture was separated into more flasks when the concentration of lymmphoid cells reached or exceeded 2×106/mL until the total amount reached about 5×109/mL cells. Cytotoxic activities of TIL were tested by 6 h51Cr-release assay. Target cells (5×10s/mL) (human gastric adenocarcinoma) in 1 mL of culture mediumwere labelled with 100 μci of Na251CrO4(Beijing Atomic Energy Research Institute, Beijing), washed andadjusted to 105cells/mL. Labelled cells (E/T: 50: 1, 25: 1 and 12.5: 1) were seeded in round-bottom microtest plates (Corning, Japan) at 104cells/well. Isotope release was measured in a gamma counter (Packard,USA). The percentage of cytotoxicity was calculated according to the following formula: Cytotoxicity% = (Experimental- Spontaneous)/ (Maximum-Spontaneous)×100. Target cells without effective cells weremixed with 0.1 mL of culture media to obtain spontaneous release, and with 0.1 mL of 0.1 mol/L HCl toobtain maximum 51Cr release. TIL cells so induced were counted, washed twice, resupended in 100 mL 0.9%NaC1 solution and intravenouslly transferred. The number of total autologous TIL cells injected was morethan 5×109 cells for one patient and usually separated into 2 - 3 injection during the treatment, rIL-25000 U/d (Nanjing Military Medical institute, Nanjing) in 2 mL of 0.9% NaCl solution was intramuscularlyinjected starting from 5 days before TIL cells transfer to 5 days after transfer of TIL cells. All patients weregiven scheduled gastric roentgenograms. CT scanning, B type ultrasound, histological examination andimmune function were used to observe the changes before, during and after treatment. The curative effectswere judged by the standard of WHO. The methods of the assays of SIL-2R, NK cytotoxicity and CD4/CD8were carried out respectively according to the references.RESULTS The Nk cytotoxicity and CD4/CD8 were significantly increased (P<0.01) after 3- 6 monthstreatment. The soluble IL-2 receptor in sera of patients was significantly decreased (P<0.01) after 3- 6months treatment. There were no significantly differences in the test of CD4/CD8, the cytotoxicity of Nkcells and the soluble IL-2 receptor in serum between the group before treated by TIL and the control group(P >0.05). The NK cytotoxicity and CD4/CD8 in patients treated by TIL were significantly more than thosein the control group. On the contrary, the soluble IL-2 receptor in serum of patients treated by TIL wassignificantly less than those in serum of the control group. The patients of control group survived from 4.5months to 9 months (less than one year) after operation. However seven of the thirteen patients treated byTIL after operation survived over one year. Appetite was improved, sinew enhanced, weight increased andpain relieved in most of patients treated by TIL. On the contrary, the symptoms and signs of patients ofcontrol group were not improved. According to the standard of WHO, there were significantly differences ofPD(Disease Progress), MR (Minor remission), and PR(partial remission) between TIL group and controlgroup. The results indicated that tumor focus completely disapeared in 1(80%) of 13 patients, significantlydecreased in 4 (30%) of 13 patients and slightly decreased in 7 (53%) of 13 patients, suggesting that thetreatment of TIL in the patients with advanced cancer was effective. No side effects were found except fortransient fever in 2 patients.CONCLUSION TIL should be one of the fundamental therapies for the advanced gastric cancer, it canregulate the balance of immunity, relieve pain, improve symptoms and signs and prolong survival time.     

Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia

Background  

Recent evidence suggests that CD4⁺CD25⁺FoxP3⁺ regulatory T-cells (Treg) may be responsible for the failure of host anti-tumour immunity by suppressing cytotoxic T- cells. We assessed the prognostic significance of tumour infiltrating lymphocytes (TIL) in intestinal-type gastric cardiac cancer.     

Helicobacter pylori secreted peptidyl prolyl cis,trans-isomerase drives Th17 inflammation in gastric adenocarcinoma

Helicobacter pylori infection is characterized by an inflammatory infiltrate, consisting mainly of neutrophils and T cells. This study was undertaken to evaluate the type of gastric T cell response elicited by the secreted peptidyl prolyl cis, trans-isomerase of H. pylori (HP0175) in patients with distal gastric adenocarcinoma. The cytokine profile and the effector functions of gastric tumor-infiltrating lymphocytes (TILs) specific for HP0175 was investigated in 20 patients with distal gastric adenocarcinoma and H. pylori infection. The helper function of HP0175-specific TILs for monocyte MMP-2, MMP-9, and VEGF production was also investigated. TILs cells from H. pylori infected patients with distal gastric adenocarcinoma produced Interleukin (IL)-17 and IL-21 in response to HP0175. HP0175-specific TILs showed poor cytolytic activity while expressing helper activity for monocyte MMP-2, MMP-9 and VEGF production. These findings indicate that HP0175 is able to drive gastric Th17 response. Thus, HP0175, by promoting pro-inflammatory low cytotoxic TIL response, matrix degradation and pro-angiogenic pathways, may provide a link between H. pylori and gastric cancer.     

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer： Results of a randomized controlled clinical trial

AIM: To study the effects of perioperative administration of cimetidine (CIM) on peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS: Forty-nine GI cancer patients were randomized into treatment group, who took CIM in perioperative period, and control group, who did not take the drug. The treatment was initiated 7 days before operation and continued for 10 days after surgery. At baseline examination before operation, on the 2nd and 10th postoperative days, total T lymphocytes, T helper cells, T suppressor cells, and NK cells in peripheral blood were measured respectively by immunocytochemical method using mouse-anti human CD(3), CD(4), CD(8) and CD(57) monoclonal antibodies. Blood samples from 20 healthy volunteers were treated in the same way as normal controls. Surgical specimens were examined during routine histopathological evaluation for the presence of TIL in tumor margin. Immunohistochemical study was performed to measure the proportion of T and B lymphocytes in TIL population. T and B lymphocytes were detected respectively using mouse-anti-human CD(3) and CD(20) monoclonal antibodies. RESULTS: In comparison with normal controls, both the treatment and control groups had decreased T cells, T helper cells and NK cells at baseline. In control group, total T cells, T helper cells and NK cells declined continuously with the disease progression and the decrease became more obvious after operation. From baseline to the 2nd postoperative day, the proportion of total T cells, T helper cells, and NK cells went down from 60.5+/-4.6% to 56.2+/-3.8%, 33.4+/-3.7% to 28.1+/-3.4%, and 15.0+/-2.8% to 14.2+/-2.2%, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative day, the treatment group had significantly higher percentages of total T cells, T helper cells and NK cells than control group. Moreover, CIM treatment also boosted TIL response, as was reflected by findings that 68% (17/25) of the patients in treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL responses (P<0.01). CONCLUSION: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity induced by tumor burden and surgical maneuver. The drug could also boost TIL responses to tumor. These effects suggest that the drug be used as an immunomodulator for GI cancer patients.     

Heparanase expression, degradation of basement membrane and low degree of infiltration by immunocytes correlate with invasion and progression of human gastric cancer

AIM： To disclose the mechanisms that accelerate or limit tumor invasion and metastasis in gastric cancer patients. METHODS： The heparanase expression, continuity of basement, degree of infiltration by dendritic cells and lymphocytes in gastric cancer tissues from 33 the early and late stage patients were examined by immunohistochemistry, in situ hybridization and transmission electron microscopy. RESULTS： Heparanase mRNA expression in the late stage patients with gastric cancer was stronger than that in the early stage gastric cancer patients. In the early stage gastric cancer tissues, basement membrane （BM） appeared intact, whereas in the late stage, discontinuous BM was often present. The density of Sl00 protein positive tumor infiltrating dendritic cells （TIDC） in the early stage gastric cancer tissues was higher than that in the late stage. The infiltrating degree of tumor infiltrating lymphocytes （TIL） in the early stage patients whose tumor tissues contained a high density of TIDC was significantly higher than that in the late stage gastric cancer tissues patients with a low density of TIDC. There were few cancer cells penetrated through the continuous BM of cancer nests in the early stage gastric cancers, but many cancer cells were found outside of the defective BM of cancer nests in the late stage. CONCLUSION： Our results suggest that strongheparanase expression is related with the degradation of BM which allows or accelerates tumor invasion and metastasis. However, high density of TIDC and degree of infiltration by TIL are associated with tumor progression in human gastric cancers.     

Differential Expression of Intracellular Apoptotic Signaling Molecules in Tumor and Tumor-Infiltrating Lymphocytes During Development of Invasion and/or Metastasis of Gastric Carcinoma

The presence and functional status of intracellular expression of caspase 8, caspase 10, cFLIP, caspase 3, survivin, and NF-kappaB was investigated in permeabilized tumor and tumor-infiltrating lymphocytes (TIL) in gastric carcinoma (N = 20) from primary locus, metastatic gastric carcinoma (N = 22) from malignant ascites, and benign gastric mucosa (N = 20) for the control. The quantitative analysis was based on the percentage of positive cells by a flow cytometry. The results showed that the six intracellular molecules were constitutively expressed in primary and metastatic carcinomas as well as normal epithelium in nearly all the patients. In particular, metastatic carcinoma revealed to significantly overexpress these molecules. In the analysis of TIL, the expression of these six molecules could usually be observed in carcinoma and normal epithelium. There was aberrant expression of these molecules in immune TIL within metastatic carcinoma nests. Taken together, the results showed the significantly different expression of the signaling molecules in both tumor and TIL between primary and metastatic carcinoma nests. Increased expression of cFLIP, survivin, and NF-kappaB in carcinoma might play an important role in hindering an intracellular apoptotic process, followed by accelerating the cancer invasion and/or metastasis.     

Enhancement of tumor cell susceptibility to tumor-infiltrating lymphocytes by cisplatin

Some means of enhancing the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TIL) are required in adoptive immunotherapy. This study was designed to investigate whether or not tumor cell lysis by TIL was enhanced by treatment of the tumor cells with cisplatin, and also to clarify the mechanism of cisplatin's action on tumor cells. Autologous tumor cells and established cancer cell lines, including KATO-III and MKN-28, were used. Cytotoxic activities of TIL, the surface antigens of tumor cells, conjugation of TIL and tumor cells, and the production of TNF from TIL were analyzed. Tumor cells treated with 2 g/ml cisplatin for 12 h in vitro were more susceptible to bulk-cultured TIL and TIL clones. The surface antigens of tumor cells were not altered by the treatment with cisplatin. Cisplatin-treated tumor cells showed a higher binding ratio to TIL than did non-treated tumor cells. The anti-(tumor necrosis factor) (anti-TNF) or anti-TNF receptor antibody blocked the enhancement of cytotoxic activity by cisplatin. Thus, it was clarified that cisplatin enhanced the susceptibility of tumor cells to bulk-cultured TIL and TIL clones. Furthermore, the enhancement of cytotoxic activity by TIL in cisplatin-treated tumor cells was caused by a higher binding ratio to TIL and higher susceptibility to the TNF produced by TIL.Abbreviations TIL tumor-infiltrating lymphocytes - LAK lymphokine-activated killer - NK natural killer - NC naturally cytotoxic - TNF tumor necrosis factor - ELISA enzyme-linked immunosorbent assay - IL interleukin     

Expression of intercellular adhesion molecule 1 (ICAM-1) during the development of invasion and/or metastasis of gastric carcinoma

Summary In this study, using two-color flow-cytometric analysis, we examined the expression of histocompatibility locus antigens (HLA) classes I and II, and intercellular adhesion molecule 1 (ICAM-1) in 10 cases of normal gastric mucosa, 13 cases of primary carcinoma on the stomach, 16 cases of metastatic carcinoma from malignant ascites in patients with gastric carcinoma and 14 samples of their cultured carcinoma cells. Compared with normal gastric mucosa, HLA class I were highly expressed in a considerable number of tumor cells in each experimental group. The expression of HLA class II tended to reduce in the order of normal gastric mucosa, primary gastric carcinoma and peritoneal-effusion-associated carcinoma. Altogether, 85.7% of cases of cultured tumor cells showed abrogation and loss of HLA class II. The ICAM-1 molecule was not detected on normal gastric epithelial cells. In few cases, carcinoma cells from large volumes of tumor located in the stomach showed detectable amounts of ICAM-1. On the other hand, all of the metastatic carcinoma cells from peritoneal effusions showed a high level of expression of the ICAM-1 molecule. The expression of ICAM-1 on adenocarcinoma cells was maintained and/or augmented by in vitro cultivation with tumor-infiltrating lymphocytes (TIL). Furthermore, twocolor fluorescence-activated cell sorting analysis of TIL revealed that significant correlation was observed between the expression of ICAM-1 and the degree of TIL, composed mainly of CD3⁺ T cells including CD8⁺ CD11b^–, CD8⁺CD28⁺, CD8⁺S6F1⁺ and CD4⁺Leu8⁺, and CD57⁺CD16^– and CD57⁺CD16⁺ NK cells, and HLA-DR⁺LeuM3⁺ macrophages.Abbreviations ICAM-1 intercellular adhesion molecule 1 - CTL cytotoxic T lymphocytes - TIL tumor-infiltrating lymphocytes     

Pedunculated gastric carcinoma demonstrating a gastric foveolar phenotype

We report a case of gastric cancer complicated with very well differentiated adenocarcinoma containing signet ring cells. An endoscopic examination revealed a pedunculated polyp in the fornix of the stomach. A surgical operation was performed and the pathological findings showed very well differentiated adenocarcinoma mimicking gastric foveolae with a poorly differentiated component containing signet ring cells. This is the first case of pedunculated gastric cancer complicated with very well differentiated adenocarcinoma containing signet ring cells and also demonstrating a gastric foveolar phenotype.     

Spasmolytic polypeptide-expressing metaplasia (SPEM) associated with gastric cancer in Iceland

Recent studies have described a spasmolytic polypeptide-expressing metaplastic cell lineage (SPEM) in the gastric fundic mucosa associated with both chronic H. pylori infection and gastric adenocarcinoma. We investigated the association of SPEM both with early gastric adenocarcinoma and in biopsies taken from patients prior to diagnosis of cancer. Two cohorts were examined. First, gastric resections from 29 patients with early gastric cancer were examined. Second, biopsies taken from 18 patients prior to the diagnosis of gastric cancer were compared with their respective resection specimens as well as with control biopsies from a cohort of 19 patients diagnosed with gastritis without subsequent development of cancer. The presence of SPEM and intestinal metaplasia (IM) adjacent to and distant from the cancer was compared and spasmolytic polypeptide (SP) immunostaining within dysplastic/cancerous cells was identified. SPEM was present adjacent to cancer in all early cancer cases where the tumor was located in the body or at the body/antrum junction, and was present in the body mucosa distant from the cancer in 76% of cases. Intestinal metaplasia was found adjacent to the tumor in 76% of cases and in body sections in 52% of resections. SP immunostaining was noted within cancer cells in 62% of tumors, and within dysplastic cells in 76% of resections where dysplasia was present. SPEM was present in 82% of the biopsies obtained prior to the diagnosis of cancer, compared with only 37% in the gastritis cohort. IM was present in only 57% of biopsies. In conclusion, SPEM is strongly associated with early gastric cancers and is observed in gastric biopsies prior to the development of cancer. In addition, early gastric cancers demonstrated a high incidence of SP expression. These results suggest that SPEM merits consideration as an important pre-neoplastic gastric lesion.     

Gastric adenocarcinoma masquerading endoscopically as benign gastric ulcer

The pathologic features and five-year survival of patients in whom gastric cancer masquerades at endoscopy as a benign gastric ulcer has been poorly characterized. We reviewed retrospectively all cases of gastric adenocarcinoma in three hospitals for a five-year period. Of 266 patients with gastric adenocarcinoma, 169 (63.5%) had endoscopy with biopsy prior to diagnosis of cancer. In 159 of these 169 patients (94.1%), the endoscopic findings suggested cancer, while in the remaining 10 patients (5.9%) the endoscopic appearance suggested benign ulcer. In six of these 10 patients, the initial endoscopic biopsies did not reveal cancer and correct diagnosis was delayed for as long as 14 months. Three of the 10 patients had early gastric cancer by pathologic criteria at gastrectomy, although one had lymph node metastasis. The other seven patients had pathologic criteria for advanced gastric cancer, and three had lymph node metastasis. In spite of advanced cancer and/or lymph node metastasis in eight of our 10 patients, five-year survival in these patients with benign-appearing ulcers was 70%, as compared to 17% in patients whose gastric lesions appeared malignant at endoscopy.This work was supported by grants from the National Institutes of Health (AM 16816 and AM 26794), the Veterans Administration, Southwestern Medical Foundation's Abbie K. Dreyfuss Fund, and the Berta M. and Cecil O. Patterson Endowment Fund in Digestive Disease.     

Unclassified mucin phenotype of gastric adenocarcinoma exhibits the highest invasiveness

Background and Aim:  Gastric cancers present with distinctive carcinogenesis pathways that vary with the mucin phenotypes. We attempted to elucidate the relations between the characteristics of the mucin phenotypes of gastric cancer and the tumor invasiveness.
Methods:  Gastric adenocarcinomas that were resected surgically between August 2005 and April 2007 were included in the present study. The gastric cancers were subclassified into gastric and intestinal mucin phenotypes if more than 10% of cancer cells exhibited gastric (MUC5AC and/or MUC6) and intestinal (MUC2 or CD10) markers, respectively.
Results:  The mucin phenotypes of 123 gastric cancers were gastric ( n  = 31), intestinal ( n  = 43), mixed ( n  = 28) and unclassified ( n  = 21). The mucin phenotype was related to histological type ( P  < 0.001), Lauren's classification ( P  = 0.001) and size ( P  = 0.014) of the gastric adenocarcinoma, but not to its location or to the presence of Helicobacter pylori infection. The unclassified mucin phenotype exhibited the largest number of lymph node metastases ( P  = 0.007), lymphatic invasions ( P  < 0.001) and neural invasions ( P  = 0.026), whereas the intestinal mucin phenotype exhibited the lowest invasiveness.
Conclusion:  The mucin phenotype reflects the biological behavior of gastric cancer, with the intestinal and unclassified mucin phenotypes exhibiting the lowest and highest invasiveness, respectively.     

肝癌患者细胞因子分泌和肿瘤浸润巴细胞杀伤肝癌细胞的研究

和为探讨肝癌肿瘤浸润淋巴细胞（ＴＩＬ）杀途肝癌细胞的作用机制,用航向电镜观察了ＴＩＬ与肝癌细胞共同培养后,ＴＩＬ吸附、包绕和吞噬自体和ＥＢＬ－７４０２肝癌细胞、促使肝癌细胞凋亡。接受ＴＩＬ治疗的肝癌术后患者,外周血单个核细胞（ＰＢＭＣ）产生干扰素（１ＦＮγ）活性和血清肿瘤坏死因子（ＴＮＦ－α）活性,明显高于手术对照组。与单纯手术治疗组比较,ＴＩＬ组生存时间明显延长。肝癌术后应用ＴＩＬ的疗效显著优于     

Relationship between gastric xanthoma,gastric precancerous lesions,and gastric cancer: A retrospective study

Objective

To evaluate the relationship between gastric cancer and its precancerous lesions and gastric xanthoma.

Methods

Medical records of 47 736 patients who underwent gastroscopy in our center from January 2020 to December 2021 were reviewed. Patients’ age, sex, endoscopic and histopathological findings, and the presence, number and location of gastric xanthoma were recorded. To investigate the detection rate of gastric xanthoma at different stages of gastric lesions, the participants were further divided into the chronic gastritis group (n = 42 758), the precancerous lesion group (n = 3672), and the gastric cancer group (n = 1306), respectively.

Results

The overall detection rate of gastric xanthoma was 2.85%, and it was most commonly observed in the gastric antrum (52.50%). In addition, gastric xanthoma was more common in men and more likely to be single lesion. It was most detected in the precancerous lesion group (8.39%), followed by the gastric cancer group (5.44%), and least in the chronic gastritis group (2.29%). Multivariate analysis showed that gastric xanthoma was closely related to precancerous lesions (odds ratio [OR] 3.197, 95% confidence interval [CI] 2.791–3.662, P < 0.001) and gastric cancer (OR 1.794, 95% CI 1.394–2.309, P < 0.001).

Conclusion

Gastric xanthoma is closely related to gastric precancerous lesions and gastric cancer.     

Case of early gastric cancer with nodular gastritis

A case of depressed early gastric cancer with nodular gastritis is described. A 47‐year‐old Japanese man was referred to our hospital and admitted for surgical treatment of gastric cancer. Barium upper gastrointestinal study and endoscopy examination showed a 4.5 × 3.0 cm depressed lesion with a deep central ulceration in the anterior wall of the lower corpus. An unusual miliary pattern resembling ‘goose flesh’ was observed endoscopically in the antrum. Biopsy specimens from the tumor showed poorly differentiated adenocarcinoma, and specimens from the antrum showed many lymphoid follicles with a germinal center. Immunoglobulin G antibody and histological tests (Giemsa stain) for Helicobacter pylori were both positive. Early gastric cancer with nodular gastritis was diagnosed and a subtotal gastrectomy was performed. Histological examination of the resected specimen showed a stage I tumor infiltrating a poorly differentiated adenocarcinoma with a depressed lesion in the corpus (type 0 IIc + III) and nodular gastritis in the antrum. The patient is doing well 1 year after surgery.     

Helicobacter pylori Infection in a Randomly Selected Population,Healthy Volunteers,and Patients with Gastric Ulcer and Gastric Adenocarcinoma: A Seroprevalence Study in Taiwan

To investigate the association of Helicobacter pylori and gastric ulcer and adenocarcinoma, IgG antibodies against H. pylori were examined in 823 randomly selected subjects, 92 healthy volunteers, 117 patients with gastric ulcer, and 148 with gastric adenocarcinomas in Taiwan, where the prevalence of gastric adenocarcinoma is high. The seropositivity of this population in Taiwan was 54.4%. Gastric ulcer patients had a higher seropositivity (83.8%) than healthy volunteers (62.0%) and gastric adenocarcinoma patients (62.2%) (P< 0.001). Gender difference, blood type, and habit of smoking were not associated with the seroprevalence in any study groups. Gastric ulcer coexistent with duodenal ulcer had a higher seropositivity (94.7%) (P < 0.05). The seropositivity of H. pylori in gastric adenocarcinoma patients was higher than in healthy volunteers only in younger age and was not associated with histologic type, invasion, and location of major tumors. The results reemphasize the association of H. pylori infection with gastric ulcer but not with gastric adenocarcinoma in Taiwan.