Ulcer Gastric Cancer Research Articles

A Proposed New Clinical Classification of Metastatic Gastric Cancer: Pyloric and Antral Gastric Cancer

We aimed to classify metastatic pyloric/antral gastric cancer in terms of macroscopic morphology and metastatic form.Thirty-eight patients with pyloric/antral gastric cancer were included in the study. Patients were classified according to a combination of Borrmann classification type and metastatic type, and the clinicopathological characteristics of each group were compared.Of the 38 patients, 33 (type II: 9 and type III: 24) (87%) had ulcerative gastric cancer. Ulcerative gastric cancer was classified into four groups: lymphatic only group (L+H-P-), lymphatic + hematogenous group (L+H+P-), disseminated ± lymphatic group (L±H-P+), and lymphatic + hematogenous + disseminated group (L+H+P+). In the L+H-P- group, all patients had bulky lymph nodes and serum levels of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were high; the condition of patients was good, and the therapeutic response was good. In the L+H+P- group, metastases other than liver metastases were rare, and serum CEA levels were high. In the L±H-P+ group, the predominant histological type was signet ring cell carcinoma; both serum CEA and CA19-9 levels were low. Patients in the L+H+P+ group had higher serum CA19-9 levels and were more prone to hematogenous metastasis to various organs; these patients had worse patient status and lower treatment response. Gastric cancer other than ulcerative type was only detected in five patients (type V: 3, type IV: 1, type I: 1).Classification by a combination of macroscopic and metastatic form in pyloric/antral metastatic gastric cancer might be useful for diagnosis and treatment.

Endoscopic therapies are ever-changing strategies and neverending challenges for gastroenterological neoplasia and the refractory conditions.

Endoscopic mucosal resection (EMR) is accepted as a treatment of choice for early gastrointestinal (GI) cancers and tumors. Nevertheless, snaring-based procedure of the EMR is limited in the lesion size and is not reliable for lesions with ulcer findings. Endoscopic submucosal dissection (ESD) has been developed as an endoluminal therapeutic technique for superficial GI neoplasia. ESD has the advantage over EMR with respect to curative resection, removing even extensive GI tumors or ulcerated gastric cancer in the early stage in an en bloc manner. ESD allows precise histological assessment of the resected one-piece specimens in order to guide further management and to stratify a patient’s risk for developing metastasis.

Value of CT perfusion imaging in differential diagnosis between Borrmann types II( and III( gastric cancer

To investigate the value of CT perfusion imaging in differential diagnosis between Borrmann types II( and III( gastric cancer. All the patients were proven as ulcerated gastric cancer by preoperative gastroscopy and underwent CT perfusion scanning with Aquilion ONE 320 spiral CT from October 2013 to June 2014 in The First Affiliated Hospital of Zhengzhou University, including 19 patients as Borrmann type II( gastric cancer and 23 patients as Borrmann type III( gastric cancer by pathology. Lesions were divided into three parts by two tangent lines perpendicular to the gastric wall of the ulcer edge, including proximal part (close to cardia), ulcer part and distal part (close to pylorus). All the perfusion images were analyzed in the Toshiba 4.7 post processing workstation. Blood flow (BF), blood volume (BV), and clearance (CL) were measured according to Patlak-plot mode, and arterial flow (AF) was measured according to Single-input maximum mode. Differences in all the parameters between Borrmann type II( and III( groups were analyzed. Receiver operating characteristic (ROC) curve was used to determine the threshold of perfusion parameters for differentiating Borrmann type II( and III( gastric cancer. There were no significant differences in AF, BV and BF of ulcer part between the two groups (all P>0.05). While the CL of ulcer part in Borrmann type III( group was (7.17±2.41) L/s, which was significantly higher than (4.82±2.26) L/s in Borrmann type II( group (P=0.00). There were no significant differences for all the parameters at proximal part and distal part between the two types (all P>0.05). According to the ROC curve, area under the curve of CL was 0.78. Taking 0.59 L/s as the threshold of CL value, the corresponding sensitivity and specificity for diagnosing Borrmann type III( were 70% and 80%, respectively. The CL value has certain diagnostic value in differential diagnosis between Borrmann types II( and III( gastric cancer.

Comparison of induction of B45 Helicobacter pylori prophage by acid and UV radiation

Helicobacter pylori is a Gram-negative microorganism that grows on microaerophilic conditions and has only one known natural reservoir: the gastric mucosa. The infection by H. pylori is very common worldwide and this bacterium is associated with the development of gastritis, peptic ulcer gastric cancer or gastric Mucosa Associated Lymphoid Tissue (MALT) lymphoma. Although its natural habitat is the acidic gastric mucosa, H. pylori is considered to be a neutralophile. The bacterium survives brief exposure to pHs of <4, but growth occurs only at the relatively narrow pH range of 5.5 to 8.0, with optimal growth at neutral pH. Recently we have identified a prophage sequence (prophage phiHP33) in the strain B45, isolated from a patient diagnosed with gastric MALT lymphoma. This prophage revealed to be very difficult to induce. In fact, only few phage particles were observed on electron microscopy micrographs after exposure to UV radiation.In the present work we have compared the exposure to UV and to acidic environment in the induction of the prophage into a lytic cycle. We have tested two strains, the strain B45 carrying the prophage phiHP33 and a clinical strain 1152, isolated from a patient with peptic ulcer, that was revealed to be negative for the presence of integrase gene (a prophage gene essential for genome integration of prophage) by PCR, as negative control. Since the H. pylori reservoir is the human stomach the exposition to acid is very common, and with this experiment we intended to test if acid can trigger a phage lytic cycle.The induction using UV radiation has been previously described. For acid induction we have used a protocol adapted from Karita and Blaser. A 48 hours culture of H. pylori was grown in Brucella broth (Oxoid) supplemented with 10% of fetal bovine serum (Gibco) and 1% of Polivitex (BioMérieaux) in microaerophilic conditions at 37ºC. The liquid culture was centrifuged and the cell pellet ressuspended in citrate-phosphate buffer pH 6 and incubated 15 minutes, centrifuged again and ressuspended in citrate-phosphate buffer pH 3 and incubated for 30 minutes. After centrifugation the supernatant was recovered and incubated for 3 hours in phage precipitant (33% polyethylene glycol [PEG], 3M NaCl). After centrifugation at 10000 rpm for 10 minutes at 4ºC the pellet was ressuspended in phage buffer. These samples were analysed by transmission electron microscopy (TEM) after negative staining with 1% aqueous uranyl acetate, using a JEOL 100SX electron microscope.For B45 strain the induction using UV radiation (previously reported in Lehours, 2011) and acid exposure produced similar results (Figure 1 and Figure 2) showing numerous phage-like particles of about 100 nm diameter, apparently lacking a tail, after UV or acid exposition, respectively. These particles were not observed in the control strain 1152. Currently we are analysing the samples using molecular biology techniques and fixation embedding followed by ultrathin sectioning for TEM analysis, to detect the presence of phages.These preliminary results suggest that acid also appears to induce the H. pylori prophage phiHP33. However, since the number of phage particles observed is small, we can not rule out that the observed particles were released spontaneously. The exposition to the natural acidic environment of the human stomach may induce H. pylori prophage into a lytic cycle and to the propagation of phages among different H. pylori strains colonizing the same individual. Although highly speculative, transduction may be another form of horizontal gene transfer, which has not been described for this bacterium yet.Financial support received from the Portuguese Science and Technology foundation under the contract PTDC/EBB-EBI/119860/2010.

Helicobacter pyloricagA 12‐bp insertion can be a marker for duodenal ulcer in Okinawa, Japan

Helicobacter pylori cagA can be classified into mainly two types (East-Asian-type and Western-type cagA) according to the repeat regions located in the 3' region. Recent studies showed that the Western-type cagA in strains from Okinawa, Japan formed a different cluster (J-Western-type cagA subtype). It has also been reported that J-Western-type cagA possesses a 12-bp insertion located in the 5' region of cagA sequence. The prevalence of 12-bp insertion in cagA in Okinawa and the United States (U.S.) was examined by DNA sequencing. The primer pair that can detect the 12-bp insertion only by polymerase chain reaction was then designed. The prevalence of strains with 12-bp insertion was examined in 336 strains isolated from Okinawa by polymerase chain reaction. In case of Western-type cagA/vacA s1m2 strains, the prevalence of 12-bp insertion was significantly higher in strains isolated from Okinawa than that from the U.S. (P = 0.002). Phylogenetic tree showed that strains with 12-bp insertion formed two individual clusters within J-Western-type cagA subtype; one is from Okinawa and another is from the U.S. The designed primer set showed high sensitivity (100%) and specificity (90.8%) in Okinawa. The 12-bp insertion was found in 23.7%, 14.3%, 4.2%, and 4.0% of strains with duodenal ulcer (DU), gastritis, gastric cancer, and gastric ulcer (GU), respectively (P < 0.001 for DU vs GU) in Okinawa. Although the mechanisms are unknown, the presence of 12-bp insertion was associated with the presence of DU and might have a suppressive action on GU and gastric cancer.

Expression and significance of trefoil factor 1 protein and serum pepsinogen in benign and malignant gastric ulcers

To explore the clinical significance of trefoil factor 1 (TFF1) protein expression and serum pepsinogen (PG) concentration in benign and malignant gastric ulcers. The TFF1 protein expression was evaluated by immunohistochemistry in biopsies of gastric mucosa from 18 normal controls, 25 patients with gastric ulcer and 13 patients with ulcerative gastric cancer at our hospital during January to June 2011. The serum concentrations of PGI and PGII were detected by enzyme-linked immunosorbent assay (ELISA) and PG/PGII (PGR) was subsequently calculated. The expression of TFF1 protein increased significantly in ulcerative and peripheral gastric mucosa and peripheral mucosa of gastric cancers versus that in normal controls and the ulcerocancer group (3.04% ± 0.20%, 3.00% ± 0.20%, 3.23% ± 0.26% vs 1.67% ± 0.18%, 0.46% ± 0.18%, all P < 0.01). The elevated expression of TFF1 increased the risk of gastric ulcer (OR: 1.365, 95%CI: 1.065 - 1.749, P = 0.014) while the down-regulation of TFF1 significantly increased the risk of ulcerocancer (OR: 3.067, 95%CI: 1.391 - 6.757, P = 0.005). The serum levels of PGI and PGII in gastric ulcer group were significantly higher than that in normal control and ulcerocancer group ((150 ± 27), (28 ± 9) vs (121 ± 22), (17 ± 7), (79 ± 12), (20 ± 5) µg/L,all P < 0.01). The PGI level and PGR decreased significantly in the ulcerocancer group versus normal control (both P < 0.01). But there was no statistical difference in PGII (P > 0.05). Receiver operating characteristic curve analysis revealed that PGI and PGR were valuable for the diagnosis of malignant gastric cancer with an area under curve of 0.975 and 0.914 respectively. The expression of TFF1 protein increases in gastric ulcer but decreases in gastric ulcerocancer. The elevated serum levels of PGI and PGII indicate benign ulcer while a marked decline of serum PG I and PGR serves as a risk signal of malignant gastric ulcer. The evaluation of expression profiles of TFF1 protein and PGs is helpful for the differentiation of benign gastric ulcer from malignant ulcerocancer.

Simultaneous surgery for obstructive coronary artery disease and ulcerated gastric cancer.

A patient with ulcerated gastric cancer causing mild anaemia and simultaneous three-vessel coronary artery disease (CAD) underwent “off pump” coronary artery bypass grafting (OP-CABG) and total D2 gastrectomy.

Impact of Malignant Ulcer Size on Lymph Node Stages in Gastric Cancer with Ulcerative Growth

Although malignant ulcers have been documented in gastric cancer, the specific relationship between ulcer size and lymph node stages in gastric cancer remains uncertain. The aim of this study was to investigate the relationship between ulcer size and lymph node stages in gastric cancer patients. The diameter of the malignancy ulcer was measured, the patients were divided into three groups based on the presence of ulcer and its median size: U0 no ulcer; U1 ulcer size 0-3cm, U2 the ulcer size >3cm. Univariate and multivariate analyses were performed. The distribution of lymph node stages differed significantly between U0 and U1+U2 (p<0.001), and the similar difference was present between U1 and U2 (p<0.001). In all patients, the presence of ulcer correlated with lymph node stages (pN- vs. pN+). In ulcerative gastric cancer patients the stage pN2-3 was more common in patients with U2 (14.1%, 19/135) than in U1 (6.4%, 12/188; p< 0.001). A logistic regression model revealed that lymph node metastases were associated with presence of malignant ulcer (p=0.002), and the ulcer size still emerges as a significant variable ulcer size in ulcerative cancer (p=0.022). For gastric cancer patients, the presence of ulcer and ulcer size might be a potential biomarker of lymph node metastasis.

Treatment of gastric cancer with situs invertsus totalis : A case report

Situs inversus totalis (SIT) is a relatively rare congenital anomaly with a reported incidence of 1 in 5,000 to 10,000 live births. Although some reports of SIT with malignancy have been published, there have been few reports on SIT with gastric cancer or on the potential complications of surgical intervention in such cases. We here report the case of a patient who underwent surgical treatment for gastric cancer with SIT. The patient was a 54-year-old male, who had been an outpatient with chronic hepatitis and diabetes mellitus. He received an upper endoscopic examination for follow-up of esophageal varices and type 2 ulcerative gastric cancer was found at the posterior wall of the lower stomach. Biopsy was performed and the patient was diagnosed with moderately differentiated gastric cancer. Distal gastrectomy was performed with precise preoperative anatomical analysis in order to confirm that there was no another anomaly, such as cardiovascular or congenital anatomical anomalies except for the inverted position of all of the viscera. Adequate anatomical examination and analysis of the inverted position of related vascular for surgical treatment could lead to safer interventional treatment for malignancies with SIT.

Clinical Outcomes and Prognostic Factors of Metastatic Gastric Carcinoma Patients Who Experience Gastrointestinal Perforation During Palliative Chemotherapy

We conducted the current study to investigate the clinical outcomes of metastatic gastric carcinoma (MGC) patients who experienced gastrointestinal (GI) perforation during palliative chemotherapy and to examine the prognostic factors associated with survival after perforation. We reviewed the medical records of patients at the Center for Gastric Cancer of the National Cancer Center, Korea who developed GI perforation during palliative chemotherapy between January 2001 and December 2008. Of the 1,856 patients who received palliative chemotherapy for MGC, 32 patients (1.7%) developed GI perforation during chemotherapy. Patients with perforation at the primary gastric site were more likely to have ulcerative gastric cancer lesion (90.5 vs. 40.0%, P = 0.034) or gastric tumor bleeding (28.6 vs. 0%, P = 0.298), and less likely to have Bormann type IV (14.3 vs. 60.0%, P = 0.062), than patients with perforation at nongastric sites. In 14 patients (43.8%) who resumed chemotherapy after perforation, the disease control rate was 57.1%, and median overall survival (OS) after perforation was 7.5 months [95% confidence interval (CI), 6.0-9.0 months]. In all patients, median OS following perforation was 4.0 months (95% CI, 1.5-6.6 months), and multivariate analysis revealed that differentiated tumor histology, response to chemotherapy before perforation, and absence of septic shock at time of perforation were significantly associated with favorable OS after perforation. As patients experiencing GI perforation during palliative chemotherapy have heterogeneous clinical presentation, we need to adopt different approaches in the management of the patients that are compatible with the favorable prognostic factors.

Establishment and identification of a rabbit model of peritoneal carcinomatosis from gastric cancer.

BackgroundGastric cancer peritoneal carcinomatosis is a common clinical problem, but there are no suitable large animal models to study this problem. This study was to establish a stable rabbit peritoneal carcinomatosis model of gastric cancer using VX2 tumor, and analyze the clinico-pathological features.MethodsVX2 tumor was implanted into 36 New Zealand rabbits by 3 methods: laparotomic orthotopic injection of cancer cells into the submucosal layer of the stomach (Group A), laparotomic implantation of tumor tissue into the greater omentum immediately beneath the gastric antrum (Group B), and percutaneous injection of tumor cells directly into the peritoneal cavity (Group C), 12 rabbits in each group. The animals were closely observed and detailed clinico-pathological studies were conducted.ResultsThe success rates of peritoneal carcinomatosis formation were 100% (12/12), 91.7% (11/12) and 58.3% (7/12), respectively, for Groups A, B and C (P = 0.019, A versus C; P = 0.077, B versus C; P = 0.500, A versus B, Fisher's exact test). Two weeks after submucosal cancer cells injection in Group A, ulcerative gastric cancer with peritoneal carcinomatosis showed typical VX2 tumor pathology, with widespread intraperitoneal metastatic nodules, bloody ascites and perspicuous pulmonary metastases. The clinico-pathological progression pattern was very similar to patients of advanced gastric cancer with peritoneal carcinomatosis. Groups B and C showed similar pattern of cancer progression, but less aggressive.ConclusionsFirst large animal model of peritoneal carcinomatosis from gastric cancer has been established by laparotomic orthotopic injection of VX2 cancer cells into the submucosal layer of the stomach, providing a more suitable model for surgical interventional studies. The clinico-pathological features of this model resemble human peritoneal carcinomatosis.

Ulcer Size as a Novel Indicator Marker Is Correlated with Prognosis of Ulcerative Gastric Cancer

Aims: The objective of this study was to assess the significance of ulcer size for the survival of gastric cancer patients. Methods: A total of 260 patients with ulcerative gastric cancer who had undergone curative resection were reviewed. The diameter of the malignant ulcer was measured. Patients were divided into group U1 (≤3 cm) and group U2 (>3 cm) according to the diameter of the ulcer. The prognostic significance of ulcer size was assessed by uni- and multivariate analyses. Results: Patient survival was correlated with age, gender, tumor location, tumor size, ulcer size, serosal invasion, node involvement and synchronism distant metastasis. The 5-year overall survival rate in U1 patients was 84.3% as compared with 67.5% in U2 patients (p < 0.001), and the 5-year recurrence-free survival rates were 82.9% for group U1 and 62.5% for group U2 (p = 0.001). Multivariate analysis revealed that ulcer size is an independently significant predictive factor for survival rates (overall: hazard ratio 1.222, p = 0.003; recurrence-free: hazard ratio 1.205, p = 0.006). Conclusion: Ulcer size might be a potential indicator for advanced disease and the use of minimal local treatments must be considered carefully in larger ulcer size patients.

Endoscopic Submucosal Dissection (ESD) for Early Gastric Cancer (GC) - Long-Term Outcomes of a Prospective Study in Its Expanded Indication

Introduction: Endoscopic mucosal resection (EMR) is recognized as a minimally invasive treatment for superficial GC without metastasis. ESD is a new technique developed to obtain en bloc resection even for large and/or ulcerative lesions. The aim of this study was to assess efficacy and safety of ESD against some conditions of GC which are hardly associated with nodal metastasis, as proposed by Soetikno R., Gotoda T., et al. (J Clin Oncol.23: 4490-98, 2005). Aims and Methods: We designed a prospective study in which ESD was applied in patients with differentiated-type GC up to 30 mm in diameter regardless of ulceration or above 30 mm without ulceration, but definite signs of submucosal invasion. According to final diagnosis after the ESD, GCs below, considered to have hardly metastasis, were enrolled and followed up and otherwise were advised to be operated on additionally; differentiated-type mucosal GC above 30 mm in diameter without ulceration, and GC up to 30 mm with ulceration and/or minute submucosal invasion. The protocol was approved by the ethics committee of our hospitals, and consent to take part in the study was obtained from patients. Complete resection was defined if the lateral and basal margins were free of tumor pathologically. Followed-up endoscopic examinations are performed 1, 3, 6 months later, and then every six months. Results: Between Nov. 2001 and Sep. 2008 ESD was performed in 624 patients. Among them 543 were enrolled, and the followed-up period was median 36 months. Complete resection was achieved in 513 patients (94%), and perforation and bleeding were encountered in 6% and 5%, respectively. No emergent surgery and no immediate mortality were noted. Six patients (1.3%) recurred locally during follow-up period of median 18 months (range: 3-32). In all cases histological evaluation of the margin were tumor-positive or not evaluable because of piecemeal resection. No distant metastasis was noted. The remaining 81 patients were advised to receive additional operation mainly because of massive submucosal invasion or lymphovascular involvement. Nodal metastasis was recognized in 3 of 49 patients who were actually operated on, and local recurrence occurred in 3 of 32 patients who rejected operation and were followed up. Totally 9 recurrent lesions were managed to treat by repeated ESD in spite of severe fibrosis in the submucosa, and histologically they were all mucosal cancer. Conclusion: ESD achieves complete resection even in large or ulcerative GC, providing the precise histological assessment. However, the long-term prognosis such as 5-year survival should continuously be investigated.

The Helicobacter pylori duodenal ulcer promoting gene, dupAin China

BackgroundThe prevalence of H. pylori is as high as 60–70% in Chinese population. Although duodenal ulcer and gastric cancer are both caused by H. pylori, they are at opposite ends of the spectrum and as such are considered mutually exclusive. Duodenal ulcer promoting (dupA) gene was reported to be associated with duodenal ulcer development. The aim of this study was to determine the prevalence of dupA gene of Helicobacter pylori in patients with various gastroduodenal diseases and to explore the association between the gene and other virulence factors.MethodsH. pylori were isolated from gastric biopsies of patients with chronic gastritis, duodenal ulcer (DU), gastric ulcer (GU), or non-cardia gastric carcinoma. The dupA, cagA, vacA, iceA and babA2 genotypes were determined by polymerase chain reaction. Histological features of gastric mucosal biopsy specimens were graded based on the scoring system proposed by the updated Sydney system. IL-1β polymorphism was investigated using restriction fragment length polymorphism.ResultsIsolates from 360 patients including 133 with chronic gastritis, 101 with DU, 47 with GU, and 79 with non-cardia gastric carcinoma were examined. The dupA gene was detected in 35.3% (127/360) and the prevalence DU patients was significantly greater than that in gastric cancer or GU patients (45.5% vs. 24.1% and 23.4%, P < 0.05). Patients infected with dupA-positive strains had higher scores for chronic inflammation compared to those with dupA-negative strains (2.36 vs. 2.24, p = 0.058). The presence of dupA was not associated with the cagA, vacA, iceA and babA 2 genotypes or with IL-1β polymorphisms.ConclusionIn China the prevalence of dupA gene was highest in DU and inversely related to GU and gastric cancer.

Inducement of canine gastric cancer by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG).

Achievements in the experimental inducement of canine gastric cancer in Japan are reviewed. Canine gastric cancer was initially induced experimentally by the administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water. However, intestinal sarcoma caused death before the gastric cancer was detected. By giving an N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-soaked diet to dogs, we specifically induced gastric cancer and followed the process of carcinogenesis by X-ray, endoscopy, and biopsy. The initial macroscopic findings were areas of discoloration, with erosion or mucosal unevenness which became visible from approximately the 9th to 10th experimental months in mongrel dogs and around the 13th to 17th months in beagle dogs. The protruded type of cancer occurred in mongrel dogs early in the experimental period, while the less protruded but more ulcerated gastric cancer occurred in beagle dogs later. Histological examination of the autopsied stomachs 277, 395, 546 and 813 day in mongreal dogs and 804, 946, and 1591 day in beagle dogs revealed well differentiated, poorly differentiated, and undifferentiated adenocarcinoma. In animals with a lengthy survival (more than 600 days from the start of the experiment), metastases to lymph nodes, and, rarely, to liver, lung, bones, and other organs, were observed, as well as peritonitis carcinomatosa. Heterotransplantation of gastric cancer to nude mice succeeded to the fifth passage. Development of scirrhous cancer was induced in dogs by the combined use of ENNG and subcutaneous injection of gastrin, indicating that the experimentally induced canine gastric cancer resembled human gastric cancer. Although the induction of canine gastric cancer takes 2-3 years and the macroscopic type and time period differs among individual dogs, our results in the experimental induction of canine gastric cancer should be useful in various areas of research that require an animal model, such as genetic alteration during carcinogenesis, modulation of carcinogenesis, and prevention of gastric cancer.

Endoscopic determination of the extent of early ulcerated gastric cancer by the Congo red test.

Endoscopic determination of the extent of early ulcerated gastric cancer by the Congo red test.