Romana

English

PREVALENCE, MACROSCOPIC AND MICROSCOPIC FEATURES IN GASTRIC CANCER - A RETROSPECTIVE STUDY

Authors: Ligia Bancu, D. Marian, T. Bara, Corina Ureche, D. Georgescu, Simona Bataga, Simona Mocan

Received for publication: 2009-10-01
Revised: 2009-11-12

SUMMARY: (Hide the summary)

Key Words:

According to the National Cancer Institute (NCI),approximately 760,000 cases of stomach cancer arediagnosed worldwide and more than 24,000 cases arediagnosed in the United States each year. Incidence ishighest in Japan, South America, Eastern Europe, and partsof the Middle East. Worldwide, stomach cancer is the secondleading cause of cancer-related deaths.[15, 19]Stomach cancer occurs twice as often in men and is morecommon in people over the age of 55. In the United States,incidence is higher in African Americans than inCaucasians.

Changes in diet and food preparation have led to arecent decrease in the incidence of cancer of the lowerstomach (distal gastric cancer). However, incidenceof cancer of the upper stomach (proximal gastriccancer) has increased, primarily as a result of theprevalence of obesity and gastroesophageal refluxdisease (GERD).[20]

Several factors are implicated in the development ofgastric cancer, including diet, Helicobacter pyloriin fec tion, pre vi ous gas tric sur gery, per ni cious ane mia,adenomatous pol yps, chronic atro phic gas tri tis, priorra di a tion ex po sure or in her ited syn dromes. Gas triccan cer may of ten be multifactorial in volv ing bothin her ited pre dis po si tion and en vi ron men tal fac tors.. (5)

•  Diet (2, 4)
  •  A diet rich in pickled vegetables, salted fish,excessive dietary salt, and smoked meatscorrelates with an increased incidence ofgastric cancer.
  •  A diet that includes fruits and vegetables rich invitamin C may have a protective effect.
•  Smoking (10)
  •  Smoking is associated with an increasedincidence of stomach cancer in adose-dependent manner, both for number ofcigarettes and duration of smoking.
  •  Smoking increases the risk of cardiac andnoncardiac forms of stomach cancer.
  • Cessation of smoking reduces the risk.
  •  A meta-analysis of 40 studies estimated thatthe risk was increased by approximately 1.5- to1.6-fold and was higher in men.[5]
•  Helicobacter pylori in fec tion (6)
  •  Chronic bacterial infection with H pylori is thestron gest risk fac tor for stom ach can cer.
  •  H pylori may in fect 50% of the world’spop u la tion, but much less than 5% of in fectedin di vid u als de velop can cer. It may be that onlya par tic u lar strain of H pylori, one of which isca pa ble of pro duc ing the great est amount ofinflammation, is especially associated with therisk of ma lig nancy. The full ma lig nanttrans for ma tion of af fected parts of the stomachmay re quire that the hu man host have aparticular genotype of interleukin-Ibeta tocause the in creased in flam ma tion and anin creased sup pres sion of gas tric acidse cre tion.
  •  H pylori infec tion is associated with chronicatro phic gas tri tis, and pa tients with a his tory ofpro longed gas tri tis have a 6-fold in crease intheir risk of de vel op ing gas tric can cer.Interestingly, this association is particularlystrong for tu mors lo cated in the antrum, body,and fundus of the stom ach but does not seemto hold for tu mors orig i nat ing in the cardia.[6]
•  Previous gastric surgery
  •  Previous surgery is implicated as a risk factor.The rationale is that surgery alters the normalpH of the stomach, which may in turn lead tometaplastic and dysplastic changes in luminalcells.[7]
  •  Retrospective studies demonstrate that a smallpercentage of patients who undergo gastricpolyp removal have evidence of invasivecarcinoma within the polyp. This discovery hasled some researchers to conclude that polypsmight represent premalignant conditions.
•  Genetic factors ( 1, 13)
  •  Some 10% of stomach cancer cases are familialin origin.
  •  Genetic factors involved in gastric cancerremain poorly understood, though specificmutations have been identified in a subset ofgastric cancer patients. For example, germ-linetruncating mutations of the E-cadherin gene aredetected in 50% of diffuse-type gastric cancersand families that harbor these mutations havean autosomal dominant pattern of inheritancewith a very high penetrance.[8]
  •  Other hereditary syndromes with apredisposition for stomach cancer includehereditary nonpolyposis colorectal cancer,Li-Fraumeni syndrome, familial adenomatouspolyposis, and Peutz-Jeghers syndrome.
  •  Ebstein-Barr virus: The Epstein-Barr virus maybe associated with an unusual form of stomachcancer (<1%), lymphoepitheliomalikecarcinoma.
  •  Pernicious anemia: Pernicious anemiaassociated with advanced atrophic gastritisand intrinsic factor deficiency is a risk factor forgastric carcinoma.
•  Gastric ulcers
  •  Gastric cancer may develop in the remainingportion of the stomach following a partialgastrectomy for gastric ulcer.
  •  Benign gastric ulcers may themselves developinto malignancy.
•  Obesity: Obesity increases the risk of gastriccardiac cancer.
•  Radiation exposure: Atomic bomb survivorsexposed to radiation have had an increased risk ofstomach cancer. Other populations exposed toradiation may also have an increased risk ofstomach cancer.

AIM OF STUDY

In this study we wanted to assess the prevalence ofgastric cancer (GC), upon patients who underwent upperdigestive endoscopy ( UDE), in a period of five years –January 2003- December 2007- in the digestiveendoscopy laboratory of the Mures County UniversitaryHospital , Romania. We also analyzed the macroscopicand microscopic features, sex ratio, age, medium of lifefor all these patients ( pts).

MATERIAL AND METHODS

In the above mentioned period, 14,348 pts werereferred for UDE. Among these we diagnosed 404 withgastric cancer. In all cases we performed biopsies,analyzed in the pathology laboratory. In our endoscopyunit pts from central part of Romania are routinelyreferred.

RESULTS

The prevalence of males was 73.26% which leads to asex ratio M: F of 3:1 compared to most of the studies inwhich the ratio is 2:1. ( fig. 1) [16]56% of the pts were living at countryside while the restof 42% were of urban provenience ( fig.2)

Most of the cases of GC are discovered between theages of 60 and 70. In our study, age ranges between 20 to87 are covered with a high prevalence in the 7th decade,and 1 case below 19 years old. ( fig.3)

Regarding the location of the lesions usually ½ arelocalized in the antrum, ¼ in fundical region while theother ¼ invades both these regions. In our study, thelocation of the lesions was as in figure 4. [17]

Histological aspects in our study showed thepredominance of tubular adenocarcinomas. ( fig 5)Among tubular adenocarcinomas, the weaklydifferentiated were predominant.

A particular attention should be given to the cases ofsignet-cell carcinoma in our study. From all the cases, 55,(27%) of patients were diagnosed with this aggressivetype. All of them were under 55 years and what wasmore interesting and also very important in not skippingthe diagnose was the fact that the endoscopic featureswere equivocal, with minimal lesions, small andsuperficial ulcerations or small areas of hyperemia,suggesting benign lesions. [8, 14]

DISCUSSION

Adenocarcinoma of the stomach is subclassifiedaccording to histologic description as follows: tubular,papillary, mucinous, or signet-ring cells, andundifferentiated lesions. [11, 9]

Pathology specimens are also classified by grossappearance. In general, researchers consider gastriccancers ulcerative, polypoid, scirrhous (ie, diffuse linitisplastica), superficial spreading, multicentric, or Barrettectopic adenocarcinoma..

Researchers also employ a variety of otherclassification schemes. The Lauren system classifiesgastric cancer pathology as either Type I (intestinal) orType II (diffuse). An appealing feature of classifyingpatients according to the Lauren system is that thedescriptive pathologic entities have clinically relevantdifferences.

Intestinal, expansive, epidemic-type gastric cancer isassociated with chronic atrophic gastritis, retainedglandular structure, little invasiveness, and a sharpmargin. The pathologic presentation classified asepidemic by the Lauren system is associated with mostenvironmental risk factors, carries a better prognosis,and shows no familial history.

The second type, diffuse, infiltrative, endemic cancer,consists of scattered cell clusters with poordifferentiation and dangerously deceptive margins.Margins that appear clear to the operating surgeon andexamining pathologist often are determinedretrospectively to be involved. The endemic-type tumorinvades large areas of the stomach. This type of tumor isalso not recognizably influenced by environment or diet,is more virulent in women, and occurs more often inrelatively young patients. This pathologic entity isassociated with genetic factors (such as E-cadherin),blood groups, and a family history of gastric cancer. [12]

CONCLUSIONS

Diagnosing forms of early gastric cancer remains agoal to achieve, which implies a better medicaleducation among pts and physicians and neverthelessthe use of modern endoscopic techniques such asmagnification, chromoendoscopy, narrow band imagingand probably conphocal microscopy.

We consider that the great number of advancedgastric cancer in our study is the result of still poor/medium social-economic conditions and medicaleducation in our geographic region.

A special attention is to be accorded to signet cellcarcinomas, that occur at young age and have equivocalendoscopic features, often suggesting a benign disease.

The fact that most of our cases had an antral location,make these cases easier to diagnose and with a betteroutcome. The prevalence of antral located tumors canprobably be explained by the dietary habits in this part ofthe country, with salted and smoked meat products.

Cigarette smoking was also frequent among the pts. [ 3,10, 17]

Nevertheless we want to emphasize the importance ofupper digestive endoscopy in the diagnosis of gastriccancer.

The necessity of implementing strategies for thediagnose of high grade dysplasias and early gastriccancers.

REFERENCES

1. Tsugane S, Sasazuki S. Gastric Can cer. 2007;10(2):75-83. Diet and the risk of gas tric can cer: re view of ep i de mi o log i calevidence.

2. Shibata A, Parsonet J. Stomach cancer. In: Schottenfeld D, Fraumeni J, eds. Cancer. Epidemiology and Prevention. 3rd ed.Oxford University Press; 2006:707-720.

3. Yanaoka K, Oka M, Yoshimura N, Mukoubayashi C, Enomoto S, Iguchi M, Magari H, Utsunomiya H, Tamai H, Arii K,Yamamichi N, Fujishiro M, Takeshita T, Mohara O, Ichinose M. Risk of gastric cancer in asymptomatic, middle-agedJapanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Int J Can cer. 2008 Aug15;123(4):917-26.

4. Pourhoseingholi A, Pourhoseingholi MA, Vahedi M, Safaee A, Moghimi-Dehkordi B, Ghafarnejad F, Zali MR. Relationbetween demographic factors and type of gastrointestinal cancer using probit and logit regression. Asian Pac J Can cer Prev.2008 Oct-Dec;9(4):753-5.

5. Liu C, Russell RM. Nutrition and gastric cancer risk: an update.Nutr Rev. 2008 May;66(5):237-49.

6. Lunet N, Valbuena C, Vieira AL, Lopes C, Lopes C, David L, Carneiro F, Barro Eur J. Cancer Prev. 2007Aug;16(4):312-27.

7. González CA, Pera G, Agudo A, Palli D, Krogh V, Vineis P, et al. Smoking and the risk of gastric cancer in the EuropeanProspective Investigation Into Cancer and Nutrition (EPIC). Int J Cancer. Nov 20 2003;107(4):629-34.

8. Sharma SP. H. pylori and gastric cancer in Asia: enigma, or a play on words? Lancet Oncol. 2008 Sep;9(9):827.

9. Hemminki K, Sundquist J, Ji J. Familial risk for gastric carcinoma: an updated study from Sweden. Br J Can cer. 2007 Apr23;96(8):1272-7.

10. Howe HL, Wu X, Ries LA, Cokkinides V, Ahmed F, Jemal A, Miller B, Williams M, Ward E, Wingo PA, Ramirez A,Edwards BK. Annual report to the nation on the status of cancer, 1975-2003, featuring cancer among U.S. Hispanic/Latinopopulations.Cancer. 2006 Oct 15;107(8):1711-42.

11. de Vries AC, van Grieken NC, Looman CW, Casparie MK, de Vries E, Meijer GA, Kuipers EJ. Gastric cancer risk inpatients with premalignant gastric lesions: a nationwide cohort study in the Netherlands.Gastroenterology. 2008Apr;134(4):945-52.

12. Lambert R. Upper gastrointestinal tumors. En dos copy. 2009 Jan;41(1):46-50.

13. Melo Barbosa HP, Martins LC, Dos Santos SE, Demachki S, Assumpção MB, Aragão CD, de Oliveira Corvelo TC.Interleukin-1 and TNF-alpha polymorphisms and Helicobacter pylori in a Brazilian Amazon population. World J Gastroenterol.2009 Mar 28;15(12):1465-71.

14. Yamaji Y, Watabe H, Yoshida H, Kawabe T, Wada R, Mitsushima T, Omata M. High-risk population for gastric cancerdevelopment based on serum pepsinogen status and lifestyle factors.Helicobacter. 2009 Apr;14(2):81-6.

15. Greene FL, Compton CC, Fritz AJ, et al. AJCC Cancer Staging Manual. 6th ed. 2002.16. Gastrointestinal Tumor Study Group. The concept of locally advanced gastric cancer. Effect of treatment on outcome. 2004,up-to-date.

17. Mãrgineanu E, Cotrutz CE, Cotrutz C. Correlation between E-cadherin abnormal expressions in different types ofcancer and the process of metastasis. Rev Med Chir Soc Med Nat Iasi. 2008 Apr-Jun;112(2):432-6.

18. Makola D, Peura DA, Crowe SE. Helicobacter pylori infection and related gastrointestinal diseases. J Clin Gastroenterol.2007 Jul;41(6):548-58.

19. González CA, Pera G, Agudo A, Palli D, Krogh V, Vineis P, et al. Smoking and the risk of gastric cancer in the EuropeanProspective Investigation Into Cancer and Nutrition (EPIC). Int J Cancer. Nov 20 2003;107(4):629-34.

20. Rembacken B, Fujii T, Kondo H. The recognition and endoscopic treatment of early gastric and colonic cancer. Best PractRes Clin Gastroenterol. 2001;15:317–336.