Correlations Between the Density of Tryptase Positive Mast Cells (DMCT) and that of New Blood Vessels (CD105+) in Patients with Gastric Cancer.

Mast cells proteases, tryptase and chymase are directly involved in the growth and progression of solid tumors due to their important role in tumor angiogenesis. We examined the density of tryptase positive mast cells and the mean density of new blood vessels in gastric malignant tumors of patients with and without Helicobacter pylori infection, using immunohistochemical staining for tryptase (for mast cells) and CD 105 (for new vessels). Tryptase and CD 105 expression was detected in gastrectomy specimens. In this study, mast cell density correlates with angiogenesis and the growth and progression of gastric cancer. It also shows that the participation of Helicobacter pylori infection in the growth and progress of gastric neoplasia is due to an increase of peritumoral angiogenesis, with subsequent local and distant tumor spread and perivascular growth, but without perineural and nodal involvement.

Density of Tryptase-Positive Mast Cells Correlated with the Presence of H. pylori in Gastric Neoplasia.

BACKGROUND: Gastric cancer continues to be a platoon leader of mortality causes. A significant number of recent studies show direct or indirect involvement of mast cells (MC), with a complex role both pro- and anti-tumor growth. AIM: To objectify the correlations between expression of MC and presence of Helicobacter pylori (HP) infection depending on neoplastic nature of the gastric damage. SUBJECTS AND METHODS: The study was carried out on archival samples of gastric wall from 30 patients with gastric cancer versus 30 age and sex-matched subjects with gastric surgery for non-neoplastic diseases. The inclusion criteria for the case group were histologically proven stage T3/T4 malignancies with regional lymph node metastases. For each case of the study group, distribution and number of MC tryptase positive (DMC-TP) were analyzed in five different areas from the same gastrectomy specimen: intratumor area, deep and side tumor invasion front, normal gastric tissue sample 5-10 cm or more distant from the tumor and furthest resection margin. RESULTS: Independently of HP infection, the study recorded a significantly lower value of DMC-TP in male patients. In regions with inflammatory lesions and preneoplastic changes and in control cases with non-gastric neoplasia, the DMC-TP level was higher than controls with HP-related inflammatory pathology, thus removing bacterial etiology from the forefront of MC mobilizing causes. CONCLUSION: The presence of H. pylori infection was not found to cause significant changes in terms of mobilizing mast cells in the gastric wall with advanced tumors, with minimal stage III TNM.

The influence of Helicobacter pylori presence on the immunophenotype of inflammatory infiltrate in gastric diseases.

The first medical hypothesis about the possible relationship between chronic inflammatory response and carcinogenesis belongs to Virchow and it was published in 1893. In these days, multiple studies demonstrate the certain involvement of chronic inflammation as trigger of progression towards malignancy. The fact that in 1994, the International Agency for Research on Cancer considered Helicobacter pylori as first class carcinogenic agent, is postulating the existence of the pathogenical chain carcinogenesis, of chronic inflammatory lesions as it was described by Correa, as a first step. Our study including 75 patients who underwent surgical procedures for gastric lesions uses immunohistochemical studies for lymphocytes phenotyping, to identify the nature of inflammatory cells involved, correlating the results with the presence of Helicobacter pylori. We tried to bring new information needed for establish to what extent the chronic inflammation of gastric mucosa is a response to the presence of bacteria and is implicated in tumorigenesis. We used T cells antibodies: CD3, CD4, CD5, CD8, CD57, GranzymeB and B cells antibodies: Cd20 and CD23. Our results revealed the presence of immune cellular response to Helicobacter pylori in gastric mucosa, based on T helper, cytotoxic and NK cells. B cells have a minor role in this response. CD4+ cells seem to be involved in local protection response as well as in carcinogenesis, while CD8+ have a minor or no role in carcinogenesis.

Regression of precancerous epithelial alteration in patients with Helicobacter pylori chronic gastritis.

As a Group 1 carcinogen for gastric cancer, Helicobacter pylori (H. pylori) was involved in many studies and researches focused on physiopathology and morphopathologic changes induced by this bacterium. The study included 3069 gastric endoscopies performed between January 2005 and December 2009 in "Colentina" Clinical Hospital. During upper endoscopy biopsies from antro-pyloric and corporeo-fundic region were collected. Histopathologic diagnosis of these biopsies was made using Sydney criteria. The patients were divided in two groups, based on the presence or absence of H. pylori: group A included 1414 H. pylori positive patients and group B included 1653 H. pylori negative patients. We evaluated several histopathological parameters, correlating the degree of inflammation, atrophy, metaplasia, regenerative hyperplasia and dysplasia with the presence of H. pylori infection. Our study identifies an overall tendency towards regression of premalignant lesions of gastric epithelium (regenerative epithelial hyperplasia, atrophy and intestinal metaplasia) after H. pylori eradication, as well an increasing number of patients diagnosed with early gastric cancer, thus consolidating the results of studies who foretell the significant decrease of gastric cancer mortality. These lesions are present years before becoming clinically manifest, and consequently treatable. In respect of carcinogenic mechanisms, some of our results confirm the carcinogenic cascade triggered by the H. pylori infection, as it was proposed by Correa et al. in 1975. However, we obtained data leading to the idea that the "precursor lesions" could appear (and subsequently histopathologically evaluated) independent one to the other, through other steps then Correa's model.

Diagnosis and treatment in Helicobacter pylori infection.

In our days, Helicobacter pylori is considered to be the bacterium responsible for the most frequent and persistent chronic infection worldwide, involving half of the entire world population. Untreated, the infection is lasting for the whole life. In Romania, the number of carrying people is variable between 90-94%, while in western countries, the prevalence of this infection is much lower, under 50-60%, with a high tendency to decrease, due both to the higher socio-economic level and to advanced methods of diagnosis and treatment, with a special focus on prevention. Because a percentage of 10-11% of the infected people develop in time an ulcerous disease, and 5-6% will have premalignant changes on the gastric mucosa and even gastric cancer in 1% of the cases, the goal to detect and treat H. pylori infection is, in our opinion, very much justified by both theoretical and practical reasons. Diagnosis methods for the infection's detection are numerous and diverse, the choice for one or another depending on several factors, among which: accessibility, advantages and disadvantages specific to each method (particularly the method's invasive or non invasive character), the cost, the aim (diagnosis, epidemiological, the treatment's efficiency, etc.). From a clinical point of view the patient's age, antecedents and digestive symptoms, as well as his psychological state and associated treatments are also important. Once the diagnosis of infection is proved, the treatment of the Helicobacter pylori infection supposes the simultaneous administration of antibiotics and proton pump inhibitors. The idea to create a vaccine for Helicobacter pylori is the evident result of the need to avoid the costs imposed by the diagnosis and treatment of the infection, especially in view of the high percentage of failure in eradicating the infection. If we add to these the socio-economic costs brought by the treatment of gastric ulcers and cancers, the idea of using a vaccine with double role, both in preventing, as well as in treating the infection, is even more attractive.

E-cadherin and beta-catenin expression in gastric neoplastic and non-neoplastic lesions--correlations with H. pylori infection.

Gastric cancer is one of the most aggressive malignancies, as incidence and as evolution as well. Although, due to the new findings about etiology, carcinogenesis, precancerous conditions and their detection, as well as the treatment, in the latest decade, there is an improvement in these data, gastric cancer remains a redoubtable enemy because of its incidence, prevalence and mortality. Researches are focusing on early detection of precursor lesions and on establishing their reversibility potential by bringing more clinical and statistical information and by setting new clinical hypotheses. In this context, the present article is trying to study immunohistochemical expression of two oncogenic markers, the cell adhesion protein antibodies E-cadherin and beta-catenin. Cell to cell and cell to extracellular matrix interactions are crucial for neoplastic transformation and for metastasizing process. The importance of these antibodies in maintaining cell adhesion suggests that their abnormal expression is playing an important role in tumorigenesis. In this article, authors are presenting a study about E-cadherin and beta-catenin expression in 75 patients who underwent gastrectomy for suspicions of gastric malignancies. The variables of the study are the presence or absence of Helicobacter pylori, type I carcinogenetic agent for gastric carcinoma (especially intestinal type adenocarcinoma) and the presence of tumoral or non-tumoral gastric lesions.

Carcinogenesis and infection with Helicobacter pylori.

It was accepted several years ago that, in the carcinogenesis process of human cancers, biologic agents, especially the viruses, are playing an etiologic role. This is the case of lymphomas (retroviruses), hepatocarcinoma (hepatic viruses) and cervical carcinoma (papilloma viruses). Helicobacter pylori is the first bacteria recognized as a first class carcinogen for gastric cancer. Nevertheless, comparing with the most validated human carcinogens, the activity of H. pylori is very little studied. As a consequence, at this moment, in its case, explanation of carcinogenesis mechanism is more or less hypothetical.

Helicobacter pylori: pathological mechanism involved in gastric colonization.

Since 1982, when Marshall and Warren highlighted the presence of H. pylori at the apical pole of the epithelial gastric cells, the medical literature has registered a cascade of subsequent researches concerning this amazing bacterium, its action on the human body and the body response. The apogee of these studies and conclusions about the pathogenic role of HP was touched with its certain recognition as class one carcinogenic agent (Peura 1997, WHO), becoming the first bacteria with such an action. The data gathered in the last period identify different virulence factors of HP, but fail to fully explain the relatively low incidence of gastric cancer in HP carriers; therefore, it is now considered that the carcinogenic potential related to HP infection in humans is due to the synergic and complementary association of the bacterial genetic equipment with diet and host response.

Malignancy and overdiagnosis of malignancy in Peutz Jeghers polyposis.

Peutz Jeghers (PJ) polyps are rare hamartomatous tumors of the gastrointestinal tract frequently associated with skin and mucosal pigmentation. Despite their benign nature there is a certain increased risk of progression to malignancy in some cases, justifying a sustained follow-up of the patients. We present 3 cases of Peutz Jeghers syndrome (PJS) diagnosed in our hospital on gastrointestinal specimens obtained by endoscopy and opened surgery. We analyzed different degrees of dysplastic changes, epithelial intussusception, association with other types of polypoid lesions and other various aspects possibly related with disease progression. Clinico-pathological correlations were made. Two of these cases were related (mother and daughter); both of them were operated in another hospital for small bowel tumors with a subsequent diagnosis of adenocarcinoma. The daughter (28 years old) was referred to our hospital for endoscopic follow-up; a small polyp of the transverse large bowel was excised by colonoscopy with a histopathologic diagnosis of PJ polyp; a careful histopathologic reevaluation of both specimens of enterectomy (slides and paraffin blocks) revealed an overdiagnosis of cancer due to the epithelial cystic dilatation and pseudoinvasion in both patients. The other case showed diagnostic changes of PJS and also various aspects of adenomatous polyps some of them with mild and moderate dysplastic changes. When a PJ polyp is diagnosed, the possibility of pseudoinvasion should be kept in mind, in order to avoid overdiagnosis of malignancy; also, due to the fact that the malignant transformation of a PJ polyp is still on debate (hamartoma-dysplasia-carcinoma sequence versus malignant transformation of an adenomatous aria of a hamartoma versus coincidental association of a digestive cancer due to genetic aberrations of PJS), all the other associated microscopic aspects of the lesion should be carefully analyzed.

Cutaneous metastases of malignant melanoma--how difficult can it be?

Malignant melanoma is one of the most aggressive skin neoplasms with histopathological-based therapeutic approach. Unfortunately, in some cases, even the elementary issue of dealing with a primary or metastatic lesion may be sometimes incredible difficult to settle. We studied 11 cases of malignant melanomas that required careful histopathological and immunohistochemical analysis to differentiate between primary and secondary tumor. We evaluated epidermotropism of primary MM including synchronous tumors, local recurrences and metastases.