Peritoneal lavage cytology in gastric cancer: An independent predictor of outcome
Background: The prevalence and significance of free cancer cells in the peritoneal cavity of clinically M0 gastric cancer patients is unknown. We reviewed our results with peritoneal washings to determine (1) the prevalence of positive cytology in M0 and M1 disease and (2) the influence of positive cytology on the pattern of failure and survival.
Methods: Laparoscopic washings were obtained from 127 patients with gastric cancer at Memorial Sloan-Kettering Cancer Center from December 1, 1990 to August 1, 1996. Cytology was performed by the Papanicolau technique.
Results: The prevalence of positive cytology was as follows: 0% (0/45) in T1/T2 M0 disease; 10% (3/31) in T3/T4 M0 disease; and 59% in M1 disease. The three M0 patients with positive cytology recurred intra-abdominally (median follow up of 8.5 months). Survival was significantly less compared with stage-matched controls with negative cytology resected for cure (P<.03), and the same as those patients with stage IV disease.
Conclusion: Patients with positive lavage cytology are stage IV, even in the absence of macroscopic peritoneal disease. Laparoscopic lavage cytology is a rapid technique for identifying the subset of M0 patients who are unlikely to benefit from resection alone. Such patients require additional treatment strategies to improve survival. 
Magnifying Endoscopy Combined with Narrow Band Imaging System for Early Gastric Cancer: Correlation of Vascular Pattern with Histopathology (including video)
Background and Study Aims: The narrow band imaging (NBI) system consists of a sequential electronic endoscope system and a source of light equipped with new narrow band filters, yielding very clear images of microvessels on mucosal surfaces. The aim of this prospective study was to measure the correlation between the magnified images obtained with the NBI system and the histological findings, especially with regard to the vascular pattern. In addition, three-dimensional images of microvessels were reconstructed using a laser scanning microscope.
Patients and Methods: Between July 2001 and August 2003, 165 patients with depressed-type early gastric cancer lesions were enrolled in the study. The lesions were carefully observed with magnification using the NBI system. The images, the pathological characteristics of the lesions, and three-dimensionally reconstructed images of the microvascular networks in biopsied specimens were carefully analyzed. The microvascular patterns were classified into three groups: A, fine network; B, corkscrew; and C, unclassified pattern. The endoscopic images were compared with the histological findings.
Results: Of the three types of filter available for use with the NBI system, microvascular formation was best enhanced in B mode images produced using short wavelengths, which focus on the superficial mucosal layer. Among 109 cases of differentiated adenocarcinoma, the group A microvascular pattern was observed in 72 cases (66.1 %). Among 56 cases of undifferentiated adenocarcinoma, the group B pattern was observed in 48 cases (85.7 %; P = 0.0011) The microvascular structure observed using the NBI system corresponded with the superficial mucosal layer in the three-dimensional images obtained using laser scanning microscopy and the resected specimens.
Conclusions: Magnifying endoscopy performed in combination with the NBI system is not sufficient to replace conventional histology, but is capable of predicting the histological characteristics of gastric cancer lesions. 
Modified therapy with 5‐fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer
Background . In an attempt to decrease the toxic effects of fluorouracil, doxorubicin, and methotrexate (FAMTX) by reducing the dose of methotrexate from 1500 mg/m2, according to the original regimen, to 1000 mg/m2, the authors designed the modified FAMTX treatment that was evaluated in a prospective Phase II‐III randomized trial.
Methods . Patients with advanced gastric cancer were randomized to receive modified FAMTX treatment or supportive measures only (control group). In the middle of the study, the randomization was interrupted because of strong evidence of benefit in terms of tumor reduction and projected survival in the treatment arm receiving chemotherapy. By the end of the study, 30 assessable patients had received chemotherapy and 10 had received supportive treatment.
Results . The overall response rate was 50% (15 patients); 12 patients (40%) had partial responses and 3 (10%) had complete responses (CR). One patient with extensive peritoneal carcinomatosis attained a CR pathologically documented by laparoscopic examination and peritoneal biopsy. The median overall survival time of the treated group was 9 months, whereas that of the control group was only 3 months (P = 0.001). The median overall survival time of the responders was 16 months, and their median remission duration was 8 months. The regimen was well tolerated, with a very acceptable toxicity profile. There was one toxic death resulting from neutropenia and sepsis in a patient who did not receive adequate leucovorin rescue.
Conclusions . This regimen appears to prolong survival in patients with advanced gastric cancer, and the reduction of the methotrexate dose does not seem to compromise its efficacy. Cancer 1993; 72:37–41. 
The Expression of Human Epididymis Protein 4a (HE4) in the Normal Gastric Epithelia and Its Role in the Development of Intestinal Metaplasia and Gastric Cancer
Background: Biomarkers that allow early diagnosis of gastric carcinoma (GC) patients are limited. Human epididymal protein 4 (HE4) is a novel biomarker for epithelial ovarian and lung cancer. This study was designed to evaluate the role of HE4 in the development of intestinal metaplasia (IM) and gastric carcinoma.
Methods: A total of 41 patients with a diagnosis of GC and 48 patients with a diagnosis of IM were enrolled. Gastric cancer samples were taken from patients who underwent gastric resection due to GC. For IM, biopsies obtained from patients who underwent endoscopic examination for non-tumoral reasons were used. Intestinal metaplasia adjacent to GC was also examined separately. For HE4 expression, immunohistochemistry was used and the results were compared to demographic, clinic, pathologic and prognostic parameters.
Results: The patients were 38–90 years-old (mean: 65.6). Tumor localization were antrum in 37.8%, corpus in 27%, lesser curvature in 21.6%, greater curvature in 5.4%, and cardia in 8.1% of patients. Tumor sizes ranged between1-13 cm (mean 5.54). There were 37.8% well to moderately, and 62.2% poorly differentiated carcinoma. Pathological T evaluations were as follows: pT1=13.5%; pT2=8.1%; pT3=59.4%; pT4=18.9% patients. The expression of HE4 was seen in 50% of tumors. Among the tumor samples that harbor intestinal metaplasia, HE4 expression in metaplastic cells was seen in 61.1% of the cases. Diffuse type carcinoma had more HE4 expression than intestinal type cancers and there was an inverse correlation between depth of tumor invasion and the presence of HE4 (p=0.037).
Conclusions: Human epididymal protein 4 was expressed in normal oxyntic glands and metaplastic cells as well as GC cells but not in the surface foveolar epithelium. It was expressed mostly in diffuse type carcinoma. HE4 may be involved in personalized treatment in gastric cancer. 
The Morphological Features of “Cavitary” Type Angiogenesis in Diffuse and Intestinal Types of Gastric Cancer and Its Relationship with Tumor-Infiltrating Immune Cells
Background: Previously we have described the “cavitary” type of angiogenesis by gastric cancer (GC) consisting of the formation of “cavitary structures” (CS) in tumor stroma, which are then lined by endothelial cells and merged into the blood vessels of the organ. The morphological features of the “cavitary” type of angiogenesis in intestinal and diffuse types of GC and the relations of CS with the tumor-infiltrating immune cells, was the purpose of this study.
Materials and Methods: The samples of tumor and adjacent gastric mucosa (GM) in 73 patients with GC who had undergone radical surgery were being studied. The sections were stained with hematoxylin and eosin and immunohistochemically using antibodies to CD34, CD4, CD8, CD20 Ð¸ CD68.
Results: The differences of “cavitary” type of angiogenesis in the intestinal and diffuse types of GC are only associated with CS type-1 that are formed as a result of the abruption of epithelial cells from the underlying stroma. In the intestinal type of GC the basis for the formation of CS type-1 are the tumor glands. The wall of such CS is most likely the basement membrane bordering the connective tissue. In the diffuse type of GC the CS type-1 are presented as the structures limited from outside by the tumor cells. In their lumen the fragments of tumor tissue having the same structure as the surrounding one are being detected. The performed analysis showed that the number of CS type-1 was associated with the density of CD68, whereas the presence of CS type-2 – with the presence of lymphoid follicles (LF) and B-cell infiltrations at the boundary of tumor and GM. The density of CD68 in GM was higher in cases with multiple CS type-1 (72.6±47.0 vs. 41.6±15.4 cells per unit area, P= .03). In turn, CS type-2 were more often met in the presence of multiple LF (72,3% vs. 33,3%, P= ,04) and B-cell infiltrations (90% vs. 26,3%, P= ,001).
Conclusion: The obtained data testify about the relation of CD20 lymphocytes and CD68 macrophages with the “cavitary” type of angiogenesis. 
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