Why is the coexistence of gastric cancer and duodenal ulcer rare? Examination of factors related to both gastric cancer and duodenal ulcer

The coexistence of gastric cancer with duodenal ulcer has been found empirically to be rare, but why it is rare is difficult to explain satisfactorily. To elucidate this question, we carried out a literature review of the subject. The frequency with which the two diseases coexist is 0.1–1.7%, and the main factor associated with both gastric cancer and duodenal ulcer is Helicobacter pylori infection. However, there are marked differences between the disorders of hyperchlorhydria in duodenal ulcer, and hypochlorhydria in gastric cancer. The most acceptable view of the reason for the difference may be that the acquisition of H. pylori infection occurs mainly in childhood, so that the time of acquisition of atrophic gastritis may be the most important, and if atrophic gastritis is not acquired early, high levels of gastric acid may occur, and consequently acute antral gastritis and duodenal ulcer may occur in youth, whereas, in elderly individuals, persistent H. pylori infections and the early appearance of atrophic gastritis may be the causes of low gastric acid, and consequently gastric cancer may occur. In patients with duodenal ulcer, factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and dupA-H. pylori strains may contribute to preventing the early acquisition of atrophic gastritis, while acid-suppressive therapy and vascular endothelial growth factor and other entities may inhibit atrophic gastritis. In contrast, in gastric cancer, factors such as excessive salt intake, acid-suppressive therapy, polymorphisms of inflammatory cytokines, and the homB-H. pylori strain may contribute to the early acquisition of atrophic gastritis, while factors such as NSAIDs; fruits and vegetables; vitamins A, C, and E; and good nutrition may inhibit it.     

The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease

Although Helicobacter pylori (H. pylori) seropositivity is linked to an excess risk of pancreatic cancer, the biologic mechanism is unknown. Gastric ulcer is primarily associated with corpus colonization of H. pylori, atrophic gastritis and formation of N-nitrosamines. Duodenal ulcer is a marker of antral colonization, hyperacidity and uninhibited secretin release. We estimated relative risks for pancreatic cancer among patients with gastric or duodenal ulcer, based on a register-based retrospective cohort study with 88,338 patients hospitalized for gastric ulcer and 70,516 patients for duodenal ulcer recorded in the Swedish Inpatient Register between 1965 and 2003. Following operation, the 14,887 patients who underwent gastric resection and 8,205 with vagotomy were analyzed separately. Multiple record-linkages allowed complete follow-up and identification of all incident cases of pancreatic cancer until December 31, 2003. Standardized incidence ratios (SIRs) estimated relative risks. During years 3-38 of follow-up, we observed a 20% excess risk (95% confidence interval [CI] 10-40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10-110%) 15 years after first hospitalization (p for trend = 0.03). SIR was 2.1 (95% CI 1.4-3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy. Our results lend indirect support to the nitrosamine hypothesis, but not to the hyperacidity hypothesis in the etiology of pancreatic cancer.     

Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease

Two recent genome‐wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection‐related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated. Genomic DNA from 603 Spanish patients with primary GC, 139 with DU and 675 healthy controls was typed for the PSCA rs2294008C>T polymorphism by PCR‐TaqMan assays. H. pylori infection [odds ratio (OR): 8.27; 95% confidence interval (CI): 3.45–15.33] and nonsteroidal anti‐inflammatory drugs (OR: 6.54; 95% CI: 3.19–12.43) were identified as independent risk factors for DU whereas the rs2294008T allele was associated with reduced risk of developing the disease (OR: 0.52; 95% CI: 0.33–0.82). Infection with CagA strains (OR: 2.10; 95% CI: 1.63–2.34), smoking (OR: 1.93; 95% CI: 1.54–2.61), family history of GC (OR: 2.83; 95% CI: 2.01–3.83), and the rs2294008T allele (OR: 1.46; 95% CI: 1.07–1.99) were associated with increased risk of GC. Interestingly, the association with the rs2294008T allele was restricted to noncardia GC (OR: 1.43; 95% CI: 1.12–1.82), particularly of the diffuse histotype (OR: 1.59; 95% CI: 1.16–1.92). Finally, Cox regression analysis identified the rs2294008T variant as a prognosis factor associated with worse overall survival in patients with diffuse‐type GC (hazard ratio: 1.85; 95% CI: 1.12–3.06). From these results we conclude that the PSCA rs2294008 polymorphism is involved in the susceptibility to GC and DU, as well as in the prognosis of the diffuse‐type of GC in Caucasians.     

Polymorphisms in TNF and HSP‐70 show a significant association with gastric cancer and duodenal ulcer

Tumour Necrosis Factor (TNF) and Heat Shock Protein 70 (HSP70) are important molecules in inflammatory, infectious and tumoral processes. The genes codifying these molecules are polymorphic and certain alleles have been associated with susceptibility to disease. Gastric cancer is associated with an Helicobacter pylori‐induced chronic inflammatory response. The aim of this work was to analyze whether polymorphisms in inflammation‐related genes are associated with the development of gastric cancer. We studied 447 Mexican adult patients including 228 with non‐atrophic gastritis, 98 with intestinal metaplasia, 63 with gastric cancer and 58 with duodenal ulcer, and 132 asymptomatic individuals as well. DNA from peripheral white blood cells was typed for the Single Nucleotide Polymorphisms (SNPs) ?308 of TNF‐α, +252 of TNF‐β, +190 of HSP70‐1, +1267 of HSP70‐2 and +2437 of HSP70‐HOM. Compared with the asymptomatic group, we found a significant association of TNF‐β*A and HSP70‐1*C alleles with gastric cancer (OR 5.69 and 3.76, respectively) and HSP70‐1*C with duodenal ulcer (OR 3.08). Genotype TNF‐β G/G showed a significant gene‐dose effect with gastric cancer (OR 0.09); whereas HSP70‐1 C/G showed significant association with both, gastric cancer (OR 13.31) and duodenal ulcer (OR 16.19). Polymorphisms in TNF and HSP70 showed a significant severity‐dose‐response as risk markers from preneoplastic lesions to gastric cancer in Mexican population, probably because of their association with an intense and sustained inflammatory response.     

A case of a perforated duodenal ulcer coincident with a gastric carcinoma

A 44-year-old male patient under treatment for a duodenal ulcer for the past 9 years visited our clinic because of a sudden pain in the epigastric region. He was diagnosed as having a perforated duodenal ulcer, so an emergency laparotomy was performed. In this operation, the coexistence of a gastric carcinoma was clarified, and a subtotal gastrectomy with an R2 dissection was done at the same time. The coexistent gastric carcinoma was localized to a size of 20 x 12 mm within the gastric proper mucosa. The infiltrated range of the cancer was as wide as 120 x 80 mm, extending to the proper tunica muscularis. This case was seen as manifesting a relative early stage of scirrhous carcinoma.     

Monitoring gastric cancer progression with circulating tumour DNA

Background:

Circulating tumour DNA (ctDNA) is an emerging candidate biomarker for malignancies and may be useful for monitoring the disease status of gastric cancer.

Methods:

We performed targeted deep sequencing of plasma cell-free DNA (cfDNA) by massively parallel sequencing in patients with tumours harbouring TP53 mutations. The quantitative values of TP53-ctDNA during the clinical course were compared with the tumour status.

Results:

Three out of ten patients with TP53 mutations in primary tumours showed detectable TP53 mutation levels in preoperative cfDNA. Although the cfDNA concentrations were not always reflective of the disease course, the ctDNA fraction correlated with the disease status.

Conclusions:

ctDNA may serve as a useful biomarker to monitor gastric cancer progression and residual disease.     

Lipid peroxidation in patients with gastric ulcer and cancer

Levels of certain metabolites of peroxidation of lipids such as diene conjugates malonic dialdehyde, ascorbic acid, dehydroascorbic acid and diketogulonic acid were compared in 39 cases of gastric ulcer, 25 patients with gastric cancer and 14 healthy subjects. Diene conjugates and malonic dialdehyde levels appeared to be increased in cases of gastric ulcer and cancer. This was matched by a decrease in ascorbic acid and dehydroascorbic acid levels. Ulcer patients revealed enhanced diketogulonic acid concentration.     

Severe gastric and duodenal ulcer after chemotherapy of mFOLFOX6 and bevacizumab

A 74-year-old female had metastatic left inguinal lymph nodes 20 months after rectal amputation for cancer, and an attempt to adapt chemotherapy of mFOLFOX6/bevacizumab was made after resection of the nodes. She felt nausea 2 days and continued 1 week after starting chemotherapy. Then, an endoscopic examination revealed both active gastric and duodenal ulcers. Clipping and proton pump inhibitor medication was started. The ulcers healed to the healing stage at 18 days and to the scar stage at 28 days. Gastrointestinal complications often occur after chemotherapy, but severe ulcers are rarely reported. The chemotherapy included anti-VEGF antibody, but the ulcers have healed back to normal.     

Association of thymidylate synthase polymorphisms with gastric cancer susceptibility

We investigated in a case-control study a possible role of thymidylate synthase gene (TS) polymorphisms for gastric cancer susceptibility. Lymphocyte genomic DNA from 134 Italian gastric cancer patients and 139 controls was used for genotyping two polymorphisms in the TS 5'-untranslated region (5'-UTR); a double (2R) or triple (3R) 28-bp repeat and a G/C polymorphism within the triple repeats allele (3G allele). Samples were also genotyped at a 6-bp deletion/insertion (del6 or ins6) polymorphism at position 1494 in the TS 3'-untranslated region (3'-UTR). Unconditional regression with odd ratios (OR) and 95% confidence intervals (CI), haplotype and linkage disequilibrium analyses were used to investigate the association of the polymorphisms with the disease. The global allelic distribution was in Hardy-Weinberg equilibrium. Genotypes with the 3G allele (2R/3G, 3C/3G, 3G/3G) were significantly more frequent in patients than controls and were associated with gastric cancer risk (OR = 2.06; 95% CI = 1.26-3.35). A significant risk was also observed for carriers of the del6 allele in the 3'-UTR. Odds ratios for combined 3G-del6/ins6 and 3G-del6/del6 genotypes were 2.59 (95% CI = 1.36-4.94) and 2.81 (95% CI = 1.22-6.64), respectively. The 3G-del6 haplotype showed a significant association with the disease (p = 0.01). Polymorphisms in the TS gene may contribute to gastric cancer susceptibility and this finding deserve further investigation in the context of novel strategies for gastric cancer prevention. In vitro, 3G genotypes have been related to high TS mRNA expression, which may underlie one of the possible etiologic mechanisms.     

胃癌患者循环肿瘤细胞的检测及临床意义

  目的  探讨胃癌患者外周血中循环肿瘤细胞的临床意义。  方法  采集45例胃癌患者的外周血,应用密度梯度离心法和免疫荧光法检测外周血中的循环肿瘤细胞(circulating tumor cells,CTCs),并比较其临床病理意义。  结果  应用密度梯度离心法和免疫荧光法检测胃癌患者外周血中的CK19阳性肿瘤细胞即为CTCs。45例胃癌患者中27例为CTCs阳性,CTCs阳性与淋巴结转移(P=0.007)、远处转移(P=0.035)和复发密切相关(P=0.035),而与性别、年龄、肿瘤部位和TNM分期、肿瘤分化程度无关(P> 0.05)。  结论  CTCs与胃癌的不良预后相关。      

Monoclonal antibodies against human gastric cancer

Spleen cells from Balb/c mice immunized with five human gastric cancer cell lines in sequence were fused with murine myeloma cell line SP2/0, and hybridomas 3F4, 3G9 and 3H11, secreting monoclonal antibodiees (MoAbs) against gastric cancer, were obtained through selective culture and screening. These MoAbs have both good selectivity and a high positive rate of reaction for gastric cancer, reaching 5/5 and 84.8% to 93.5% for gastric cancer cells and tissues respectively. The reaction of MoAbs with normal cells and tissues was neglible. The corresponding antigens of the MoAbs were sensitive to digestion by trypsin and pronase and resistant to treatment with sodium periodate, indicating their nature as proteins. The antigen 3G9 could be visualized with Western blotting as two bands with molecular weights of 100KD and 70KD, however no band was found for antigens 3F4 and 3H11. There was a high expression of antigens in the majority of gastric cancer cells and tissues independent of histopathological type of gastric cancer. A low expression of antigens was seen with other tumors and fetal gastrointestinal tissues. These could be considered as gastric cancer-associated antigens or oncofetal antigens with a quite extensive distribution.     

Association of circulating leukocyte telomere length with survival in patients with colorectal cancer

IntroductionTelomere shortening, as seen with aging, can cause chromosomal instability and promote cancer progression. We investigated the association between circulating telomere length and overall and disease-free survival in a sub-cohort of patients with colorectal cancer.MethodsBaseline genomic DNA from blood leukocytes was extracted from N = 92 newly diagnosed stage I-IV patients with colorectal cancer enrolled at the ColoCare Study site in Heidelberg, Germany. Detailed information on clinicodemographic (including age) and lifestyle risk factors, and clinical outcomes (including recurrence and survival) was collected. Telomere length was measured in DNA using multiplex quantitative polymerase chain reaction. Kaplan Meier survival curves were generated comparing shorter to longer telomere lengths with log-rank testing.ResultsThe mean T/S ratio for study patients was 0.5 (range: 0.3–0.9). Shorter telomeres were associated with older age at baseline. Patients with shorter telomeres experienced a worse overall and disease-free survival, although this association did not reach statistical significance. Kaplan-Meier survival curves for those with circulating telomere length below vs. above the median showed poorer overall (log-rank p = 0.31) and disease-free survival (long-rank p = 0.23).ConclusionsOur results suggest that individuals with shorter telomeres, as seen with aging, may experience a worse overall and disease-free survival after colorectal cancer diagnosis. Larger sample sizes with longer follow-up are needed to further evaluate telomere length as a prognostic biomarker in colorectal cancer progression.     

Clinical significance of circulating plasma DNA in gastric cancer

With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5‐year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5‐year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer.     

Relative value of repeat gastric ulcer surveillance gastroscopy in diagnosing gastric cancer

Background Gastric cancer can present with the endoscopic appearances of a benign gastric ulcer (GU). Opinion remains divided on the need for follow-up of patients diagnosed with GU, and the aim of this study was to examine the long-term outcomes of patients whose GU proved malignant on follow-up gastroscopy. Methods Between October 1, 1995, and September 30, 2003, 25 579 gastroscopies were performed in one unit. These identified 544 patients with apparently benign GU, of whom 277 (51%) underwent 334 elective follow-up endoscopies. Twelve of these patients (4.3%) were shown to have a malignant ulcer; their outcomes were compared to those of the 296 other patients diagnosed with gastric cancers in this time frame. Results The patients in the GU cancer group had earlier stage disease (stage I, 33% vs 6.4%; χ² = 11.2; DF1; P = 0.001), and were more likely to undergo R0 gastrectomy (50% vs 30%; χ² = 2.064; DF1; P = 0.151) and to survive long term (46% vs 16%; log-rank χ², 5.79; DF1; P = 0.0162) than patients in the comparison cohort. Conclusion Gastroscopic follow-up of 50 patients with an apparently benign GU will identify 1 patient with a malignancy destined to survive for 5 years following R0 gastrectomy. This justifies the diagnostic effort of repeat gastroscopy to ensure complete healing of GU. Presented at: The British Society of Gastroenterology, Birmingham, 2005; The Association of Surgeons of Great Britain and Ireland, Glasgow, 2005; The 6th International Gastric Cancer Congress, Yokohama, 2005.     

Innate IgM antibodies to mannose in patients with gastric cancer

<正>Gastric cancer(GC) remains one of the most common lethal diseases. Every year, about 1 million people fall ill and almost 800 thousand people die worldwide¹. Surgical treatment has reached its limit. The current advances in immunology and detection of epidermal growth factor molecules(EGFR) in gastric cancer cells allowed to improve the treatment results; however, the metastatic form of this disease is still incurable.     

IL-6和IL-8在正常胃组织、胃溃疡及胃癌组织中的表达

目的 探讨白细胞介素（IL）-6和IL-8在正常胃组织、胃溃疡及胃癌组织中的表达情况.方法 采用酶联免疫吸附法（ELISA）测定正常对照组（33例）、胃溃疡患者（30例）和准备手术的胃癌患者（52例）血浆中IL-6和IL-8的表达水平,并随访胃癌患者术后1周的IL-6、IL-8表达水平;免疫组织化学法检测胃癌周围正常组织（45例）、胃溃疡组织（35例）和胃癌组织（45例）标本中IL-6和IL-8的表达.结果 胃癌患者（术前和术后）血浆中IL-6、IL-8的表达明显高于胃溃疡和正常对照组（均P＜0.0l）,胃癌患者术后IL-6和IL-8水平较术前明显降低（P＜0.01）.癌周正常组织、胃溃疡和胃癌组织中IL-6和IL-8蛋白阳性表达率依次上升,且差异有统计学意义（x2=38.87,P＜0.01;x2=42.23,P＜0.01）.结论 IL-6和IL-8在胃癌患者血浆和胃癌组织中均表达上调,检测患者血浆和病理组织中的IL-6、IL-8水平有助于判断病情和评估预后.     

Wallflex duodenal stenting for gastric outlet obstruction caused by inoperable advanced gastric cancer

INTRODUCTION: Wallflex duodenal stent (WDS) placement for gastric outlet obstruction caused by malignant disease has been covered by health insurance in Japan since April 2010. We have placed five-WDS for three gastric outlet obstructions caused by inoperable advanced gastric cancer. CASE 1: A 67-year-old male diagnosed as having Stage IV gastric cancer with liver, lung, and lymph node metastases underwent a WDS placement during first-line chemotherapy. He was able to consume a soft diet orally for about five months thereafter. He underwent a WDS replacement for stent obstruction by tumor ingrowth and finally died due to the primary tumor 11 months after the first visit. CASE 2: A 63-year-old male diagnosed as having Stage IV gastric cancer with liver and lymph node metastases underwent a WDS placement during the first-line chemotherapy. He was able to consume a soft diet orally for about three months thereafter. He died due to the primary tumor six months after the first visit. CASE 3: A 72-year-old male diagnosed as having Stage IV gastric cancer with liver and lymph node metastases underwent a WDS placement during the first-line chemotherapy. He was able to consume a soft diet orally for about four months and subsequently received the fourth-line chemotherapy. He underwent a WDS replacement for stent obstruction by tumor ingrowth and finally died due to the primary tumor nine months after the first visit. CONCLUSIONS: WDS stent placements for gastric outlet obstruction caused by inoperable advanced gastric cancer were performed safely and enabled the consumption of a soft diet orally for at least three months. This approach is expected to be a safe and effective treatment option.     

Early gastric cancer located just above Dieulafoy's ulcer, with massive bleeding

In 2003, a 69-year-old man visited our emergency department because of hematemesis and anemia. Emergency gastroscopy revealed massive bleeding from Dieulafoy's ulcer in the upper body of the stomach. The arterial bleeding was successfully controlled by endoscopic clipping. Blood transfusion and a proton-pump inhibitor were administered and his condition recovered smoothly. Two weeks after the treatment, type IIa early gastric cancer was detected at the previous bleeding point by follow-up endoscopy. He underwent distal gastrectomy with systematic lymph node dissection (D2), and he had no sign of recurrence until 2005. Histopathological examination revealed an early gastric cancer with submucosal invasion located just above the Dieulafoy's disease. The characteristic finding of Dieulafoy's disease was an enlarged and tortuous artery arising from the subserosa, penetrating the muscle layer, and spreading in the submucosa. Abnormal Dieulafoy's artery coexisting with gastric cancer has been reported in only 17 cases until now. Our clinical and pathological findings led us to the following speculation on the pathogenesis in our patient. Repeated regeneration of the mucosal membrane would have been caused by circulatory disturbance in Dieulafoy's vessels. This regeneration and mucosal dysplasia may have been a factor in promoting the gastric cancer. In the previously reported cases of the coexistence of abnormal Dieulafoy's artery and gastric cancer, the initial gastroscopic examination rarely diagnosed the gastric cancer. Thus, follow-up gastroscopy is essential, so as not to miss such coexisting diseases.