Crohn's disease associated with gastric cancer

Received: May 15, 2000 / Accepted: November 10, 2000     

Diet,microbial virulence,and Helicobacter pylori-induced gastric cancer

Gastric adenocarcinoma is a leading cause of cancer-related death worldwide, and Helicobacter pylori infection is one of the strongest known risk factors for this malignancy. H. pylori strains exhibit a high level of genetic diversity, and the risk of gastric cancer is higher in persons carrying certain strain types (for example, those that contain a cag pathogenicity island or type s1 vacA alleles) than in persons carrying other strain types. Additional risk factors for gastric cancer include specific human genetic polymorphisms and specific dietary preferences (for example, a high-salt diet or a diet deficient in fruits and vegetables). Finally, iron-deficiency anemia is a risk factor for gastric cancer. Recent studies have provided evidence that several dietary risk factors for gastric cancer directly impact H. pylori virulence. In this review article, we discuss mechanisms by which diet can modulate H. pylori virulence and thereby influence gastric cancer risk.     

A case of gastric cancer with high pepsinogen II levels in both serum and ascites

The first case of gastric cancer in which pepsinogen (PG) II levels were found to be extremely high not only in the serum but also in the ascites, with values of 603 ng/mL and 1910 ng/mL, respectively, is reported. Pepsinogen I and PG II are normally secreted into the gastric lumen and only 1% of the amount secreted enters the circulation. Although gastric cancer cells are found to produce PG II more often than PG I, elevated PG values in serum are extremely rare, and only one case has ever been reported. That patient had extremely high serum levels of PG I and PG II at the time of gastric cancer relapse. Pepsinogen has never been reported in the ascites, and thus nothing is known about the mechanism of entry into the ascites. In this case report, we postulate two mechanisms to explain the increased PG II in the ascites: (i) a high level of serum PG II infiltrated the ascites and caused elevation of PG II in the ascites; or (ii) disseminated cancer cells directly produced PG II and it elevated PG II levels in the ascites.     

抗结直肠癌单克隆抗体测定胃、肠癌患者血清中癌相关抗原

目的 应用结直肠癌单克隆抗体对胃肠癌患者进行血清学诊断。 方法 采用ELISA法对胃癌、结直肠癌、胃良性疾病和健康供血者血清中结直肠癌抗原(CCA)进行了测定,同时测定了胃癌、结直肠癌患者血清中CEA含量。 结果 正常人血清CCA阳性仅1.5％。胃癌血清阳性率52.8％,CEA阳性率24.5％,CEA阳性病例中CCA阳性率为30.0％。结直肠癌患者CCA阳性率为52.9％,CEA阳性率为20.6％,CEA阴性病例中CCA阳性率为48.2％。胃良性疾病组CCA阳性率为10％。 结论 CCA单抗与CEA无交叉反应,临床上测定CCA可作为CEA的补充,为临床诊断及普查提供了新的诊断指标。     

Serum iron and ferritin levels in patients with colorectal cancer in relation to the size, site, and disease stage of cancer

We investigated blood loss from colorectal cancer in 92 men seen between January 1990 and June 1997, in relation to the size and site of the tumor, Dukes stage, pathologic type of cancer, and serum carcinoembryonic antigen (CEA) positivity. We used indirect methods, measuring serum hemoglobin, iron, and ferritin concentrations. The means of these three concentrations were significantly lower in patients with a tumor >3 cm than in those with a tumor ≤3 cm in largest diameter. The means of the three values were lower in patients with proximal colon cancer than in those with distal colon cancer, but only the difference in serum hemoglobin concentration was significant. Cancers of the ulcerative type were found more often in the proximal colon. The proportion of patients with Dukes stage C or D was not different between those with proximal colon cancer and those with distal colon cancer. There was a positive correlation between tumor size and Dukes stage. There were no differences in serum hemoglobin, iron, and ferritin concentrations with respect to the pathologic type of cancer and CEA positivity. These findings show that blood loss from colorectal cancer is closely related to the size and site of the tumor. (Received: June 12, 1998; accepted: Oct. 23, 1998)     

进展期胃癌术后调强放疗加同期口服替吉奥胶囊化疗的临床疗效

目的:评价调强放疗加替吉奥胶囊配合中药调理胃肠道方案治疗进展期胃癌术后的临床疗效与不良反应.方法:68例进展期胃癌患者按先后入院顺序半随机分成观察组35例,术后4wk开始行靶区调强放射治疗(每日180Cgy,每周5次,总剂量45-55GY),对照组33例行常规放疗.两组均加口服替吉奥胶囊80mg/(m2·d),分2次口服,连服14d、21d为1周期,连用2个周期,放化疗期间给予中药调理胃肠道.治疗后进行两组临床疗效不良反应比较,治疗后3mo分析疗效和不良反应,治疗前、治疗后3mo、6mo、12mo随访进行Karnofsky生活质量评分.结果:两组临床疗效比较,观察组总有效率为51.43%,对照组为30.30%,两组临床疗效无统计学差异(P>0.05).Karnofsky评分结果表明,观察组与对照组分别治疗前与治疗后3mo、6mo、12mo比,有统计学差异(P<0.01,P<0.05),治疗后3mo、6mo、12mo观察组与对照组比,有统计学意义(P<0.02,P<0.05).两组血液学不良反应、胃肠道反应、周围神经不良反应比较,观察组比对照组小.结论:经过临床对照研究分析结果表明,进展期胃癌患者术后行调强放疗...     

Polymorphisms of matrix metalloproteinase-7 and chymase are associated with susceptibility to and progression of gastric cancer in Japan

Background  Matrix metalloproteinases (MMPs) are a family of enzymes that degrade most macromolecules making up the extracellular matrix. MMPs are involved in not only the gastric mucosal inflammatory response but also the pathogenesis of Helicobacter pylori-associated diseases. In the renin-angiotensin system, chymase (CMA) is related to gastric carcinogenesis and angiogenesis in H. pylori-infected patients. We aimed to clarify the association of MMP-7-181 and CMA/B polymorphisms with susceptibility to gastric cancer and cancer progression in H. pylori-infected patients. Methods  We assessed the MMP-7-181 and CMA/B polymorphisms in H. pylori-positive patients with gastric cancer (n = 160), gastric ulcer (n = 157), duodenal ulcer (n = 121), and H. pylori-positive gastritis alone as controls (n = 156). Results  For gastric cancer risk, the age-and sex-adjusted odds ratio (OR) of the MMP-7-181 G allele carrier relative to the A/A genotype was significantly increased [OR, 2.32; 95% confidence interval (CI), 1.24–4.35], especially in patients with noncardia cancer (OR, 2.31; 95% CI, 1.22–4.36) and those with clinical stage III or IV cancer (OR, 3.66; 95% CI, 1.54–8.73). Carriage of the CMA/B A allele was significantly associated with gastric cancer development (OR, 1.73; 95% CI, 1.10–2.71). Simultaneous carriage of both the MMP-7-181 G allele and the CMA/B A allele dramatically increased the gastric cancer risk (OR, 8.18; 95% CI, 2.79–23.93). Conclusions  In Japan, carriage of the MMP-7-181 G allele and of the CMA/B A allele were each associated with an increased risk for H. pylori-related noncardia gastric cancer development. MMP-7-181 and CMA/B genotyping tests might be useful tools for screening for individuals with higher gastric cancer risk.     

Pachydermoperiostosis associated with juvenile polyps of the stomach and gastric adenocarcinoma

Pachydermoperiostosis (PDP) is a rare syndrome, and the presence of digital clubbing, radiographic periostosis, and coarse facial features are the main diagnostic criteria. Here, we report patient with the primary form of PDP in whom juvenile polyps and gastric cancer developed within 9 years of follow-up. A 27-year-old Japanese man, diagnosed as having the primary form of PDP at 14 years of age, was referred to our department for assessment of chronic anemia. On upper gastrointestinal endoscopic examination, multiple polypoid lesions with a huge polyp were found in the stomach, and biopsy findings indicated juvenile polyps, although no polypoid lesion had been present at the age of 18 years. Bleeding from these polyps was suspected, and endoscopic mucosal resection of the polypoid lesions was performed. Histology of the huge polyp showed hamartoma, adenoma, and adenocarcinoma in part. This is the first case report of the primary form of PDP associated with gastric cancer. In this patient, juvenile polyps and gastric cancer developed within 9 years of follow-up, indicating that the primary form of PDP may be a high risk factor for gastric cancer, and that periodical follow-up with upper gastrointestinal endoscopy is important.     

Pre-operative serum levels of tissue polypeptide antigen in patients with gastric cancer

Abstract Pre-operative serum tissue polypeptide antigen (TPA) levels were measured in cases of gastric cancer from December 1987 to December 1992. All 351 cases received gastrectomies. The clinicopathological factors were analysed. The significant factors that correlated with the elevation of pre-operative serum TPA levels included tumour size (> 7 cm), Borrmann-type cancers, late stages (III and IV), lymph node metastasis, hepatic metastasis and Ming's expanding type cancers. Multivariate analysis showed that the tumour size (> 7 cm) and the presence of hepatic metastasis are significant factors. To clarify the relationships between gastric cancer per se and the pre-operative serum TPA levels, we selected cases without evidence of metastasis (n = 139). The tumour size was the only significant factor when multivariate analysis was applied. Possibilities of hepatic recurrence were found in cases with high pre-operative serum TPA levels (> 220 U/L), even radical gastrectomies were performed. A high pre-operative serum TPA level did not display a poor survival prognosis, if the radical gastrectomy was possible. We thus concluded that: (i) elevated pre-operative serum levels of TPA are associated with either a large size tumour (> 7 cm) or the presence of hepatic metastasis and the tumour size is the most important factor relating to the serum TPA levels; (ii) high pre-operative serum TPA levels (> 220 U/L) may serve as indicators of later hepatic recurrence; and (iii) elevated serum TPA levels were not indicators of survival prognosis.     

A low 13C-urea breath test value is associated with increased risk of gastric cancer

Purpose. The ¹³C-urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Values are affected by H. pylori infection and by the severity of atrophic gastritis. Our objective was to determine the association of UBT values with gastric cancer, and to evaluate the risk of gastric cancer in terms of UBT values. Methods. Our study involved 413 consecutive patients who had undergone esophagogastroduodenal examination and the UBT test. Results. Of the 398 patients with positive UBT results, atrophy and intestinal metaplasia scores in both antrum and corpus were significantly higher in patients with gastric cancer than in those with gastritis, duodenal ulcer, and gastric ulcer. The UBT value related to gastric cancer (22.01 ± 1.89‰) was significantly lower than that for gastritis (35.19 ± 1.53‰; P < 0.01), duodenal ulcer (29.01 ± 1.97‰; P < 0.05), or gastric ulcer (30.79 ± 2.83‰; P < 0.05). When the UBT values were less than 20‰, increases in the risk of gastric cancer correlated with decreasing UBT values. Conclusions. These findings indicate that the UBT value related to gastric cancer is significantly lower than that for gastritis, duodenal ulcer, or gastric ulcer in H. pylori-positive patients. Low UBT values were associated with the risk of gastric cancer. Received: October 26, 2000 / Accepted: March 30, 2001     

Morphological changes in gastric carcinoma with progression

By combining morphological two indices, namely, (1) the degree of differentiation of glandular tubules (well or poor) and (2) the amount of intracellular mucus (rich or poor), we previously classified histological types of gastric carcinoma into four types. Using this histological classification, we studied the morphological changes of gastric carcinoma according to extra-gastric invasion in 200 autopsy and 200 resected cases. In cases in which the predominant histological type in the lamina propria was “tubular differentiation—well, mucus in cytoplasm—poor,” there was a greater incidence of co-existence with other histological types. In many of these cases, the predominant histological findings changed to “tubular differentiation—poor” in the subserosa, followed by direct invasion into neighboring extra-gastric tissues. In all cases in which the predominant histological type in the lamina propria was “tubular differentiation —poor”, the predominant histological type in the subserosa was also “tubular differentiation—poor”. To understand the mode of extension of gastric carcinoma in relation to the histological type, we must consider not only the characteristics of the predominant histological types of carcinoma but also those of coexisting types, especially in cases of “tubular differentiation—well, mucus in cytoplasm—poor”.     

Early gastric cancer with Krukenberg tumor and review of cases of intramucosal gastric cancers with Krukenberg tumor

A 47-year-old woman was admitted because of hypermenorrhea. Transvaginal ultrasonography revealed an ovarian tumor and myoma uteri, and total hysterectomy with bilateral salpingo-oophorectomy was performed. Histology revealed signet-ring cell carcinoma in the right ovary. In order to find out the primary site of this tumor, gastroendoscopy was performed after the operation, and showed a IIc lesion in the lower body of the stomach; biopsy specimens showed signet-ring cell carcinoma similar to that in the right ovary. Total gastrectomy revealed that the lesion was an early gastric cancer confined to the mucosa, but there was lymphatic invasion slightly beneath the muscularis mucosa, with regional lymph node metastasis. In the light of a review of the seven cases of early gastric cancer with Krukenberg tumor previously reported, lymphatic metastasis seemed to be the most likely pathway of ovarian metastasis in early gastric cancers.     

胃微生态与胃癌的研究进展

胃微生态平衡是人体健康的重要前提,幽门螺杆菌(Helicobacter pylori,Hp)是目前已发现的与胃癌相关的关键病原体之一,普遍存在于人胃黏膜上皮。Hp感染可引起胃内其他菌群的改变,还可引起长期慢性的胃黏膜损伤,导致一系列胃黏膜上皮恶性进展和胃癌的发生。本文就胃微生态与Hp感染的关系、Hp感染在胃癌发生中的作用、胃内其他菌群在胃癌发生中的作用及微生态制剂在胃癌治疗的作用进行综述。进一步揭示Hp感染对胃微生态平衡的影响,胃微生态平衡和Hp感染在胃癌发生发展中的作用及微生态制剂在胃癌治疗中的意义。     

Endoscopic and clinicopathologic characteristics of early gastric cancer with high microsatellite instability

AIM: To investigate endoscopic and clinicopathologic characteristics of early gastric cancer (EGC) according to microsatellite instability phenotype.METHODS: Data were retrospectively collected from a single tertiary referral center. Of 981 EGC patients surgically treated between December 2003 and October 2007, 73 consecutive EGC patients with two or more microsatellite instability (MSI) mutation [high MSI (MSI-H)] and 146 consecutive EGC patients with one or no MSI mutation (non-MSI-H) were selected. The endoscopic and clinicopathologic features were compared between the MSI-H and non-MSI-H EGC groups.RESULTS: In terms of endoscopic characteristics, MSI-H EGCs more frequently presented with elevated pattern (OR 4.38, 95% CI: 2.40-8.01, P < 0.001), moderate-to-severe atrophy in the surrounding mucosa (OR 1.91, 95% CI: 1.05-3.47, P = 0.033), antral location (OR 3.99, 95% CI: 2.12-7.52, P < 0.001) and synchronous lesions, compared to non-MSI-H EGCs (OR 2.65, 95% CI: 1.16-6.07, P = 0.021). Other significant clinicopathologic characteristics of MSI-H EGC included predominance of female sex (OR 2.77, 95% CI: 1.53-4.99, P < 0.001), older age (> 70 years) (OR 3.30, 95% CI: 1.57-6.92, P = 0.002), better histologic differentiation (OR 2.35, 95% CI: 1.27-4.34, P = 0.007), intestinal type by Lauren classification (OR 2.34, 95% CI: 1.15-4.76, P = 0.019), absence of a signet ring cell component (OR 2.44, 95% CI: 1.02-5.86, P = 0.046), presence of mucinous component (OR 5.06, 95% CI: 1.27-20.17, P = 0.022), moderate-to-severe lymphoid stromal reaction (OR 3.95, 95% CI: 1.59-9.80, P = 0.003), and co-existing underlying adenoma (OR 2.66, 95% CI: 1.43-4.95, P = 0.002).CONCLUSION: MSI-H EGC is associated with unique endoscopic and clinicopathologic characteristics including frequent presentation in protruded type, co-existing underlying adenoma, and synchronous lesions.     

COX-2在胃溃疡与胃癌的表达及其与幽门螺杆菌的关系

[目的]探讨COX-2在幽门螺杆菌(Hp)感染和非感染胃溃疡与胃癌的表达。[方法]选择胃病患者共285例,分为胃溃疡患者(胃溃疡组)200例(病理分型:肠上皮化生96例和异型增生104例),胃癌患者(胃癌组)85例;以正常胃黏膜者50例为对照组。根据胃镜检查和组织病理学检查受试者胃黏膜中COX-2蛋白的表达,并比较各病理分型及Hp感染与非感染者COX-2蛋白表达的差异。[结果]COX-2蛋白在胃溃疡组的肠上皮化生、异型增生中及胃癌组癌细胞中均有表达,在正常胃黏膜组织中不表达。胃溃疡组和胃癌组的COX-2阳性表达均强于对照组,差异有统计学意义(P0.05);胃癌组的COX-2阳性表达强于胃溃疡组,差异有统计学意义(P0.05);胃溃疡组异型增生者COX-2阳性表达强于肠上皮化生者,差异有统计学意义(P0.05);胃癌组Hp阳性COX-2阳性表达强于胃溃疡组Hp阳性者,差异有统计学意义(P0.05);胃癌组Hp阴性者COX-2阳性表达强于胃溃疡组Hp阴性者,差异有统计学意义(P0.05);胃溃疡组和胃癌组中Hp阳性者COX-2阳性表达均强于Hp阴性者,差异有统计学意义(P0.05)。[结论]Hp感染会促进胃溃疡COX-2的表达,Hp感染和COX-2过度表达会使胃溃疡患者癌变的概率大大增加。     

Helicobacter pylori and gastric cancer

Abstract This review focuses on the similarities between the epidemiology of gastric cancer and the epidemiology of Helicobacter pylori. Their demographic patterns and the results of studies regarding familial and environmental risk factors are described. The association of gastric cancer and H. pylori infection with both gastric ulcer and chronic atrophic gastritis is also characterized and the possibility that a H. pylori infection could lead to gastric cancer is discussed.     

Influence of endoscopic submucosal dissection on serum levels of pepsinogens in patients with early gastric cancer

Background: The serum levels of pepsinogens (PG) have been considered to be a useful marker for assessing the risk of metachronous gastric cancer in patients who undergo endoscopic submucosal dissection. However, the influence of endoscopic submucosal dissection (ESD) on serum levels of PG has not yet been examined. The aim of this study was to examine whether the level of PG after ESD can be used to predict the risk of metachronous cancer. Patients and Methods: The study included of 100 consecutive patients who underwent ESD for gastric cancer at Hirosaki University Hospital from September 2009 to February 2011. Serum levels of PG I and II on the day before and after ESD were compared. Stool antigen test was also performed to examine the presence of Helicobacter pylori infection. Results: The mean serum level of PG I before and after ESD was 34.3 ± 31.6 ng/mL and 70.5 ± 100.0 ng/mL (P < 0.001), respectively. PG I/II ratio before and after ESD was 2.40 ± 1.51 and 2.79 ± 1.70 (P < 0.001). The serum level of PG I and the PG I/II ratio were significantly changed after ESD, regardless of the use of proton pump inhibitor, Helicobacter pylori infection or the location of the tumor. Conclusions: ESD treatment modulates the serum level of PG I and significantly increases the PG I/II ratio. Serum levels of PG should be measured before the ESD procedure is performed to predict the risk of developing metachronous gastric cancer after ESD.     

Progression of remnant gastric cancer is associated with duration of follow-up following distal gastrectomy

AIM: To re-evaluate the recent clinicopathological features of remnant gastric cancer (RGC) and to develop desirable surveillance programs.METHODS: Between 1997 and 2008, 1149 patients underwent gastrectomy for gastric cancer at the Department of Digestive Surgery, Kyoto Prefectural University of Medicine, Japan. Of these, 33 patients underwent gastrectomy with lymphadenectomy for RGC. Regarding the initial gastric disease, there were 19 patients with benign disease and 14 patients with gastric cancer. The hospital records of these patients were reviewed retrospectively.RESULTS: Concerning the initial gastric disease, the RGC group following gastric cancer had a shorter interval [P < 0.05; gastric cancer vs benign disease: 12 (2-22) vs 30 (4-51) years] and were more frequently reconstructed by Billroth-I procedure than those following benign lesions (P < 0.001). Regarding reconstruction, RGC following Billroth-II reconstruction showed a longer interval between surgical procedures [P < 0.001; Billroth-II vs Billroth-I: 32 (5-51) vs 12 (2-36) years] and tumors were more frequently associated with benign disease (P < 0.001) than those following Billroth-I reconstruction. In tumor location of RGC, after Billroth-I reconstruction, RGC occurred more frequently near the suture line and remnant gastric wall. After Billroth-II reconstruction, RGC occurred more frequently at the anastomotic site. The duration of follow-up was significantly associated with the stage of RGC (P < 0.05). Patients diagnosed with early stage RGC such as stage I-II tended to have been followed up almost every second year.CONCLUSION: Meticulous follow-up examination and early detection of RGC might lead to a better prognosis. Based on the initial gastric disease and the procedure of reconstruction, an appropriate follow-up interval and programs might enable early detection of RGC.     

Early gastric stump cancer following distal gastrectomy

Background—Gastric stump cancer(GSC) is usually diagnosed at an advanced stage, and consequently theprognosis is poor.
Aims—To investigate theclinicopathological characteristics of GSC at an early stage to assistin its identification, and thereby improve its prognosis.
Methods—Forty three patients withresected early GSC were compared with 156 patients with resectedprimary early cancer in the upper third of the stomach.
Results—Sixty five per cent (28/43)of the early GSC patients showed the elevated type endoscopically,although the frequency of the depressed type in GSC has tended toincrease in the past five years. This occurred in less than 26%(40/156) of the primary early cancers. Half of the early GSCs werelocated on the lesser curvature (47%), and revealed differentiatedadenocarcinoma (81%) histologically. The male:female ratio of earlyGSC cases was about 6:1, which was much higher than that in patientswith primary early cancer. The five year survival rates of patientswith early GSCs and early primary cancers were 84% and 95%,respectively. GSC had a favourable prognosis, if it was detected at anearly stage.
Conclusion—To detect early GSC, ourresults suggest that special attention should be given to elevated aswell as depressed lesions on the lesser curvature of the stomach,particularly in men, during endoscopic examinations.

Keywords:gastric stump cancer; early gastric cancer; prognosis; endoscopy

     

Multiple early gastric cancer associated with sarcoid-like reaction in the regional lymph nodes

2 and more extensive lymph node dissection were performed. Subsequently, the histology of permanent sections revealed not tumor metastasis but a sarcoid-like reaction in the lymph nodes. The patient recovered uneventfully; however, he was killed in an accident 38 months after the surgery. A postmortem examination was not performed, but there had been no clinical signs of either recurrence of gastric cancer or sarcoidosis. Received: May 11, 2000 / Accepted: October 6, 2000