Associations between calcium and magnesium intake and the risk of incident gastric cancer: A prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study.

Gastric cancer remains a leading cause of cancer-related mortality. Identifying dietary and other modifiable disease determinants has important implications for risk attenuation in susceptible individuals. Our primary aim was to estimate the association between dietary and supplemental intakes of calcium and magnesium and the risk of incident gastric cancer. We conducted a prospective cohort analysis of the National Institutes of Health-American Association of Retired Persons Diet and Health Study. We used Cox proportional hazard modeling to estimate the association between calcium and magnesium intakes with risk of incident gastric adenocarcinoma (GA) overall and by anatomic location, noncardia GA (NCGA) and cardia GA (CGA). A total of 536,403 respondents (59% males, 41% females) were included for analysis, among whom 1,518 incident GAs (797 NCGA and 721 CGA) occurred. Increasing calcium intake was associated with lower risk of GA overall (p-trend = 0.05), driven primarily by the association with NCGA, where the above median calcium intakes were associated with a 23% reduction in risk compared to the lowest quartile (p-trend = 0.05). This magnitude of NCGA risk reduction was greater among nonwhite ethnic group and Hispanics (hazard ratio [HR] 0.51, 95% confidence interval [CI]: 0.24-1.07, p-trend = 0.04), current/former smokers (HR 0.58, 95% CI: 0.41-0.81), obese individuals (HR 0.54, 95% CI: 0.31-0.96) and those with high NCGA risk scores (HR 0.50, 95% CI: 0.31-0.80). Among men only, increasing magnesium intake was associated with 22-27% reduced risk of NCGA (p-trend = 0.05), while for the cohort, dietary magnesium intake in the highest vs. lowest quartile was associated with a 34% reduced risk of NCGA (HR 0.66, 95% CI: 0.48-0.90). These findings have important implications for risk factor modification. Future investigations are needed not only to confirm our results, but to define mechanisms underlying these associations.

Lymph node invasion might have more prognostic impact than R status in advanced esophageal adenocarcinoma.

BACKGROUND: Advanced esophageal adenocarcinomas are associated with 5-year survival rates ranging from 14% to 35%. Nodal status and tumor clearance are the main prognostic factors. However, their respective prognostic values have not been compared to date. METHODS: Seventy consecutive patients with stage T3 adenocarcinomas of the esophagus or gastric cardia were retrospectively assessed. Neoadjuvant therapy was indicated in all cases. Prognostic values of R0 resection and nodal status were evaluated using univariate and multivariate analyses. RESULTS: Neoadjuvant therapy was achieved in 62 patients, 41 with radiochemotherapy and 21 with perioperative chemotherapy. Transthoracic esophagectomy and transhiatal esophagectomy were performed in 54 and 15 patients, respectively. Clavien-Dindo grade III or IV complications occurred in 16 patients (23%). Two patients died in the hospital (3%). In univariate and multivariate analyses, nodal status was the main independent factor predicting overall survival; tumor clearance (R0 or R1) had less prognostic impact and was not statistically significant. Furthermore, R1 resection was a prognostic indicator for metastatic recurrence. CONCLUSIONS: These results indicate that nodal status has more prognostic impact than R status in stage T3 adenocarcinomas of the esophagus or gastric cardia. Thus, local control in R1 patients by postoperative radiotherapy is not justified.

Opium: an emerging risk factor for gastric adenocarcinoma.

Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.

[Modern diagnostics and stage-oriented surgery: therapy of adenocarcinoma of the esophagogastric junction]. / Moderne Diagnostik und stadiengerechte Chirurgie : Therapie des Adenokarzinoms des ösophagogastralen Übergangs.

The basis for decision-making about an individualized surgical treatment of adenocarcinoma of the esophagogastric junction is tumor staging and exact evaluation of the topography of the tumor in the small junctional area. The diagnostics mainly comprise endoscopy, biopsy, endosonography, computed tomography and partially diagnostic laparoscopy. This results in a clinical TNM staging and an evaluation according to the AEG classification from oral to aboral in type I (esophagus), type II (cardia) and type III (subcardia). Endoscopic resection is only appropriate for the infrequent mucosal carcinomas whereas the majority of the junctional carcinomas are treated by surgical resection. This is combined with neoadjuvant treatment in case of T3 or resectable T4 carcinomas. A type I carcinoma is removed by radical transthoracic en bloc esophagectomy with high intrathoracic esophagogastrostomy after gastric pull-up. In case of type II or III carcinomas, a transhiatal extended gastrectomy including distal esophageal resection is performed with reconstruction by Roux en Y esophagojejunostomy in the lower mediastinum. However, some advanced type II carcinomas which cannot be resected R0 at the esophagus need esophagectomy and gastric pull-up. This surgical strategy is justified by the topography of the lesion and the corresponding lymphatic drainage. Very rare indications are seen for a limited resection with interposition of small bowel in some mucosal carcinomas or total esophagogastrectomy with colon interposition in very advanced tumors. The neoadjuvant treatment comprises especially chemoradiation for type I and chemotherapy for type II and III carcinomas and leads to a significant survival benefit compared to surgery alone.

Pure hepatoid adenocarcinoma of the stomach with spleen and lymph-node metastases.

The authors report a rare case of hepatoid adenocarcinoma of the stomach, presenting initially with spleen and lymph node metastases.

Histochemical, ultrastructural, and biochemical evidences for Azadirachta indica-induced apoptosis in benzo(a)pyrene-induced murine forestomach tumors.

The present study reports aqueous Azadirachta indica leaf extract (AAILE)-mediated induction of apoptosis in a murine forestomach tumorigenesis model. Histochemistry-based quantification of apoptosis revealed enhanced apoptotic index in the forestomach tumors of mice receiving AAILE along with benzo(a)pyrene (B(a)P). Transmission electron microscopy confirmed the presence of classical morphological features of apoptosis including chromatin condensation/marginalization, nuclear fragmentation, and formation of apoptotic bodies. Scanning electron microscopy showed surface modifications on the transformed squamous epithelial cells and certain mitotic cells among them over the forestomach tumors of mice receiving only B(a)P. In tumors of the mice receiving AAILE along with B (a)P, such mitotic cells were found to be absent; however, certain cells showing shrinkage and blebbings (characteristics of apoptosis) were observed. DNA fragmentation was observed to increase exclusively in the tumors of mice that received AAILE along with B(a)P. Lipid peroxidation (LPO) levels decreased in forestomach tissues of mice in all the groups studied when compared to control counterparts. However, levels of LPO were found to increase in the tumorous tissue of mice that received AAILE along with B(a)P when compared to mice receiving only B(a)P. Taken together, observations of the present study suggest that A. indica induces apoptosis in B(a)P-induced murine forestomach tumors.

Adenosine diphosphate ribosyl transferase and x-ray repair cross-complementing 1 polymorphisms in gastric cardia cancer.

BACKGROUND & AIMS: Adenosine diphosphate ribosyl transferase (ADPRT) and x-ray repair cross-complementing 1 (XRCC1) are major DNA base excision repair proteins acting interactively in repair processes. This study examined the effects of ADPRT Val762Ala and XRCC1 Arg399Gln polymorphisms on ADPRT-XRCC1 interaction in vitro in cells and their contributions to gastric cardia adenocarcinoma (GCA) risk. METHODS: The ADPRT-XRCC1 interaction in cells transfected with ADPRT and XRCC1 variant complementary DNA (cDNA) constructs were examined by immunoprecipitation and immunoblotting analysis. Genotypes were analyzed in 500 patients and 1000 controls, and odds ratios (ORs) were estimated by logistic regression. RESULTS: Interactions between ADPRT-762Val and XRCC1-399Arg or XRCC1-399Gln were robust, but interactions between ADPRT-762Ala and either XRCC1-399Arg or XRCC1-399Gln were very weak. A case-control analysis showed ORs of 2.17 (95% CI, 1.55-3.04) and 1.61 (95% CI, 1.06-2.44) for GCA in the ADPRT Ala/Ala or XRCC1 Gln/Gln genotype carriers, respectively, compared with noncarriers. Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased the OR of GCA in a multiplicative manner (OR for the presence of both ADPRT Ala/Ala and XRCC1 Gln/Gln genotypes, 6.43; 95% CI, 1.80-22.97). A supermultiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CIs) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or = 24 or > 24 pack-years were 1.44 (0.89-2.32), 2.00 (1.09-3.67), or 3.19 (1.59-6.42), respectively (Ptrend test = .008). CONCLUSIONS: The ADPRT and XRCC1 polymorphisms confer host susceptibility to GCA, which might result from reduced ADPRT-XRCC1 interaction and attenuated base excision repair capacity.

¿Qué hacen y qué hacemos en el cáncer de esófago y cardias? / What do others do and what do we do in esophagus and cardia cancer

A pesar de los avances en las técnicas quirúrgicas para las resecciones esofágicas en el cáncer de esófago y en los cuidados perioperatorios a los pacientes en este tipo de cirugía, los resultados continúan siendo heterogéneos y variados los procedimientos en la terapéutica quirúrgica de esta enfermedad. Se exponen las principales controversias sobre el tratamiento quirúrgico y las evidencias científicas relevantes respecto a cada caso en particular y se realiza un análisis crítico de cada una de ellas. Finalmente se presentan los resultados obtenidos por nuestros grupos de trabajo en el tratamiento de esta afección(AU)

In spite of the advances in the surgical techniques for the resections esofágicas in the esophagus cancer and in the cares perioperatorios to the patients in this surgery type, the results continue being heterogeneous and varied the procedures in the surgical therapy of this illness. The main controversies are exposed in particular on the surgical treatment and the excellent scientific evidences regarding each case and he/she is carried out a critical analysis of each one of them. Finally the results are presented obtained by our work groups in the treatment of this affection(AU)

Essential role of magnesium ion in water for colonization of Helicobacter pylori in 2-week-old miniature pigs.

This study was designed to determine whether magnesium ion in water would influence the colonization of Helicobacter pylori in 2-week-old miniature pigs. Groups A (2 pigs) and B (1 pig) were both fed a milk diet dissolved in drinking water, Group C (2 pigs) was fed a milk diet dissolved in deionized distilled water (DDW), and Group D (1 pig) was fed a milk diet dissolved in DDW supplemented with MgCl2. Groups B, C, and D were all challenged with H. pylori, and Group A was not. Necropsy was performed on the pigs on postinfection Day 5, and biopsy specimens were taken from 16 sites of the stomach. H. pylori were recovered from 11 of 16 sites in Group B, 1 of 32 sites in Group C, and 13 of 16 sites in Group D. On the other hand, the degree of lymphocyte infiltration increased in the order of Group A < Group B < Group C < Group D. These observations suggest that magnesium ion in drinking water is essential for the colonization of H. pylori in the pig stomach. Possible mechanisms for the lymphocyte infiltration are discussed.

[Surgical treatment of Barrett carcinoma]. / Die operative Therapie des Barrett-Karzinoms.

Barrett-carcinoma is a type of adenocarcinoma of the distal esophagus and the cardia. Barrett-esophagus is defined by the histologic presence of specialized epithelium with intestinal metaplasia. As a consequence Barrett-carcinoma has a close relationship to the adenocarcinoma of the cardia and is very often part of the cardiacarcinoma type I. The aim of the surgical therapy is a radical R0-resection of the tumor including the lymphatic drainage area. This aim is accomplished among different authors by different surgical concepts. One is the radical transhiatal subtotal esophagectomy with lymphadenectomy in the lower mediastinum and the upper abdominal compartments. The other concept is a transthoracic en-bloc esophagectomy. Both resection procedures are usually completed by gastric pull up reconstruction. Currently a sophisticated preoperative staging is followed by distinguished indication and therapy depending on tumor status, risk factors of the patient and on the international classification of the cardia carcinoma (Siewert). When a R0-resection is impossible, a neoadjuvant radiochemotherapy should be performed.

Antioxidants and cancers of the esophagus and gastric cardia.

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.

Sequence-dependent toxicity profile in modified FAMTX (fluorouracil-adriamycin-methotrexate) chemotherapy with lenograstim support for advanced gastric cancer: a feasibility study.

For advanced irresectible gastric cancer, sequential high-dose methotrexate and 5-fluorouracil (both on day 1) combined with adriamycin on day 15 (FAMTX regimen), cycled every 28 days, is a fairly effective but toxic treatment, with a high incidence of neutropenic fever, dose reductions and dose delays. In order to improve FAMTX toxicity, we studied the feasibility of two modified FAMTX regimens with lenograstim support. Seven advanced gastric cancer patients were treated with all three FAMTX drugs on day 1 followed by lenograstim 150 microgm(-2)for 10 days, in 21-day cycles (FUMA regimen). The next seven patients were treated with the same drugs at the same doses, but with adriamycin 1 day prior to methotrexate and 5-fluorouracil administration (AFUM regimen). Patients were monitored for toxicity, response, and survival. The total number of courses was 27 for FUMA and 35 for AFUM with a median of four courses per patient in each cohort. In the FUMA regimen, considerable toxicity consisting of mucositis and fatigue as well as grade 4 neutropenia occurred, and forced four out of seven patients to stop treatment. The consecutive AFUM regimen showed only mild toxicity, and all patients could finish treatment without dose reductions or delays. We found unanticipated and probably sequence-dependent toxicity profiles in two investigational, modified FAMTX schedules with lenograstim support, leading to high rates of dose-limiting toxicity in the FUMA regimen as opposed to mild toxicity in the AFUM regimen, even though the same total drug doses and treatment cycle length (dose intensity) were employed.

Factores pronósticos del carcinoma del cardias / Prognostic factors of cardia adenocarcinoma

El carcinoma localizado en la unión esofagogástrica es una entidad clínica distinta a las de los carcinomas localizados en otras regiones del estómago. Este estudio tiene por objeto analizar las características biológicas del carcinoma del cardias. En el período 1983-1998 hemos operado 93 pacientes con carcinomas localizados en el cardias, de los cuales 69 correspondían a hombres (74,2 por ciento) y 24 a mujeres (25,8 por ciento). El promedio de edad fue de 59,7 años, con un rango de 30 a 80 años. La mortalidad operatoria de esta serie fue de 7,5 por ciento. Sesenta y siete pacientes tenían metástasis ganglionares (72 por ciento); 35,7 por ciento de los enfermos tenían tumores bien o moderadamente diferenciados y 64,3 por ciento tenían tumores poco diferenciados o indiferenciados. Se realizó una gastrectomía total ampliada en 74 pacientes y una esofagogastrectomía total ampliada en 19 enfermos. El tumor estaba confinado al cardias en 48 casos (22,5 por ciento). Se comprobó que la presencia de tumor residual en el margen de sección esofágico (19,4 por ciento de los pacientes) se relaciona con un muy mal pronóstico. La sobrevida actuarial a los 5 años fue 14,7 por ciento. La sobrevida a 5 años de los pacientes es estadio I (2 pacientoes), II (20) IIIA (32) y IIIB (23) fue de 100 por ciento, 32,7 por ciento; 11 por ciento y 2,8 por ciento respectivamente, mientras que ningún paciente es estadio IV (6) alcanzó los 5 años de sobrevida

Current trends in the surgical treatment of esophageal and cardia adenocarcinoma.

Since adenocarcinoma of the esophagus and cardia is increasing at an alarming rate, major efforts are currently oriented to identify patients who may benefit from extensive resection. Between November 1992 and May 1998, 218 patients with histologically proven adenocarcinoma of the distal esophagus or cardia were referred to our Department. In six patients (10.2%) with Barrett's adenocarcinoma, cancer was discovered during endoscopic surveillance program for Barrett's metaplasia. Overall, one hundred-forty-seven patients (67%) underwent resection. Fifty-one underwent an extended mediastinal lymphadenectomy. Median cumulative survival was 25.9+/-3.1 months in patients undergoing resection, and 7+/-1.3 months in patients having palliation (p<0.01). Survival was significantly longer in patients with negative nodes than in those with lymph node metastases (54+/-12.9 versus 17+/-2.8 months, p<0.01). Six of the 51 patients (11.8%) undergoing extended lymphadenectomy had metastatic upper mediastinal nodes. Additional serial sections and immunohistochemistry were performed in 46 patients. In 6 of 18 patients (33.3%) with negative nodes at conventional hematoxylin-eosin examination, immunohistochemistry demonstrated micrometastases in the lesser curve, paracardial, peripancreatic, or lower mediastinal nodes. Early diagnosis remains the prerequisite for curative treatment of adenocarcinoma of the esophagus and cardia. When a curative resection is attempted, extended lymphadenectomy improves tumor staging and may prevent local recurrences. Serial sections and immunohistochemistry provide additional accuracy in the staging of the disease and may prove useful to select patients for adjuvant therapy.

[Precancerous and cancerous lesions of the esophagus and forestomach in mice with skin exposure to a heavy catalytic gas oil]. / Predrakovye i rakovoe porazheniia pishchevoda i predzheludka u myshei pri nakozhnom vozdeistvii tiazhelym kataliticheskim gazoilem.

Painting with heavy catalytic gas oil was followed by skin tumor development in 97 (84.3%) mice: benign lesions--21 and carcinoma--76 cases. Pathologic changes in the upper part of the digestive tract were found in 55 out of 106 mice (51.9%): precancerous lesions (leukoplakia, dysplasia and papilloma) in 54 cases and cancer in one animal. Frequency of development of papilloma in the cardia was 27 times that in the esophagus. Multicentric growth was typical of precancerous lesions. Papilloma of the cardia was found in one control animal. Resorptive as well as direct action of gas oil seem to have been the causative factors of the development of precancerous and neoplastic lesions of the upper part of the gastrointestinal tract. The agent found its way into the digestive tract as animals licked each other in the course of the experiments.