Adalimumab and Infliximab in Crohn's disease - real life data from a national retrospective cohort study.

AIM: to compare the efficacy and safety of Adalimumab(ADA) and Infliximab(IFX), in a large Romanian population and to identify predictors of response. Methods We performed a national retrospective cohort study including 265 patients (136 ADA, 129 IFX) between 2008-2014. Binary logistic regression was performed with the statistical program Minitab. RESULTS: Patients were half women, with a median age of 36, a median disease duration of 2.5 years, 80% received Azathioprine. Mean therapy duration was 20 months in ADA group and 36 months in IFX group. Complete response to Adalimumab respectively Infliximab was recorded in 77%vs.65%, secondary loss of response in 18%vs.28%, statistically comparable. We failed to identify predictors of response. In 79.2%of patients with secondary loss of response to ADA, the dose was escalated, 12.5% were switched to Infliximab. In 70%of patients that lost response to IFX, the dose was increased, 30% were switched to Adalimumab. CONCLUSIONS: Adalimumab and Infliximab have similar efficacy, with a complete response rate of~70%. In case of secondary loss of response to IFX, the best solution is to switch to ADA, with 83% response rate, while in case of secondary loss of response to ADA, increasing the dose leads to 84 % response rate.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm - volume 3.

The total number, morbidity and mortality attributed to viraemic hepatitis C virus (HCV) infections change over time making it difficult to compare reported estimates from different years. Models were developed for 15 countries to quantify and characterize the viraemic population and forecast the changes in the infected population and the corresponding disease burden from 2014 to 2030. With the exception of Iceland, Iran, Latvia and Pakistan, the total number of viraemic HCV infections is expected to decline from 2014 to 2030, but the associated morbidity and mortality are expected to increase in all countries except for Japan and South Korea. In the latter two countries, mortality due to an ageing population will drive down prevalence, morbidity and mortality. On the other hand, both countries have already experienced a rapid increase in HCV-related mortality and morbidity. HCV-related morbidity and mortality are projected to increase between 2014 and 2030 in all other countries as result of an ageing HCV-infected population. Thus, although the total number of HCV countries is expected to decline in most countries studied, the associated disease burden is expected to increase. The current treatment paradigm is inadequate if large reductions in HCV-related morbidity and mortality are to be achieved.

Treatment Steps, Surgery, and Hospitalization Rates During the First Year of Follow-up in Patients with Inflammatory Bowel Diseases from the 2011 ECCO-Epicom Inception Cohort.

BACKGROUND AND AIMS: The ECCO-EpiCom study investigates the differences in the incidence and therapeutic management of inflammatory bowel diseases [IBD] between Eastern and Western Europe. The aim of this study was to analyse the differences in the disease phenotype, medical therapy, surgery, and hospitalization rates in the ECCO-EpiCom 2011 inception cohort during the first year after diagnosis. METHODS: Nine Western, five Eastern European centres and one Australian centre with 258 Crohn's disease [CD], 380 ulcerative colitis [UC] and 71 IBD unclassified [IBDU] patients [female/male: 326/383; mean age at diagnosis: 40.9 years, SD: 17.3 years] participated. Patients' data were registered and entered in the web-based ECCO-EpiCom database [www.epicom-ecco.eu]. RESULTS: In CD, 36 [19%] Western Europe/Australian and 6 [9%] Eastern European patients received biological therapy [p = 0.04], but the immunosuppressive [IS] use was equal and high in these regions [Eastern Europe vs Western Europe/Australia: 53% vs 45%; p = 0.27]. Surgery was performed in 17 [24%] CD patients in Eastern Europe and 13 [7%] in Western Europe/Australia [p < 0.001, pLogRank = 0.001]. Of CD patients from Eastern Europe, 24 [34%] were hospitalized, and 39 [21%] from Western Europe/Australia, [p = 0.02, pLogRank = 0.01]. In UC, exposure to biologicals and colectomy rates were low and hospitalization rates did not differ between these regions during the 1-year follow-up period [16% vs 16%; p = 0.93]. CONCLUSIONS: During the first year after diagnosis, surgery and hospitalization rates were significantly higher in CD patients in Eastern Europe compared with Western Europe/Australia, whereas significantly more CD patients were treated with biologicals in the Western Europe/Australian centres.

Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia: results of the 2011 ECCO-EpiCom inception cohort.

BACKGROUND AND AIMS: The aim of the present study was to validate the IBD (inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom (European Crohn's and Colitis Organization-Epidemiological Committee) inception cohort by including a second independent inception cohort from participating centers in 2011 and an Australian center to investigate whether there is a difference in the incidence of IBD between Eastern and Western European countries and Australia. METHODS: Fourteen centers from 5 Eastern and 9 Western European countries and one center from Australia participated in the ECCO-EpiCom 2011 inception cohort. Patients' data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu. RESULTS: A total of 711 adult patients were diagnosed during the inclusion year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72 (10%) from Australia; 259 (37%) patients were diagnosed with Crohn's disease, 380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000 in Western Europe and 30.3/100,000 in Australia. Significantly more patients were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (43% vs. 27%, p=0.02). CONCLUSION: Incidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different from that reported in the 2010 cohort.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Nutritional risk screening and prevalence of malnutrition on admission to gastroenterology departments: a multicentric study.

BACKGROUND AND AIMS: There is little awareness and a lack of data on the prevalence of hospital malnutrition in gastro-enterology departments. Since part of these patients are referred for surgical treatment and poor nutritional status is a known risk factor for perioperative morbidity, we conducted a prospective study aimed to screen for the nutritional risk and assess the prevalence and risk factors of malnutrition in gastro-enterology departments in Romania. METHODS: We included patients consecutively admitted to 8 gastroenterology units over a period of three months in our study. Nutritional risk was evaluated using NRS 2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in the last six months. RESULTS: 3198 patients were evaluated, 51.6% males and 48.4% females, with the mean age of 54.5 Â+- 14.3 years. Overall percentage of patients at nutritional risk was 17.1%, with the highest risk for patients with advanced liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%), and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of 20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a higher (A ≥ 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001). CONCLUSIONS: One in five patients admitted to gastroenterology units could benefit from prompt nutritional intervention. Correction of nutritional status is mandatory before any surgical procedure. Emphasis on nutritional evaluation at admission and beginning of nutritional therapy where needed are particularly required in patients with advanced liver diseases, digestive neoplasms, inflammatory bowel diseases and pancreatic diseases. ABBREVIATIONS: NRS= nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases.

Polyp and endoscopist-related factors influencing complication rates in difficult colonic polypectomies: results of a multicenter observational study.

BACKGROUND: Current polypectomy practices are highly variable. Endoscopists report increased size, nonpolypoid lesion type and unfavorable position as characteristic of difficult polypectomies. We studied reported difficult colonic polypectomies to determine polyp-related and operator-dependent factors influencing complication rates. PATIENTS AND METHODS: We conducted an international multicenter observational prospective study of difficult colonic polypectomies. Endoscopists reported difficult cases of colonic polypectomies, techniques and complication rates. Per-polyp and per-endoscopist analyses were performed. RESULTS: Ninety procedures were reported at 4 participating centers by 19 endoscopists. 43% of the lesions were pedunculated, 39% were sessile and 18% were flat. Lesion size ranged between 5-60 mm. Bleeding occurred in 18 out of 90 procedures (17 immediate, 1 delayed); no perforations were reported. Bleeding rate was independent of patient age or sex, polyp type, size and histology or resection method. Procedures were deemed difficult due to polyp size (37/90), unfavorable position (23/90), bleeding risk (12/90), lesion type (12/90) or other reasons (6/90) with no statistically significant difference between expert and beginner endoscopists (p = 0.14). CONCLUSION: Difficult colonic polypectomies are unpredictable with a complication rate independent of polyp type or size. There was no difference between experts and beginners with regard to technical aspects of resection or complication rates.

Ki-67 expression in gastric cancer. Results from a prospective study with long-term follow-up.

BACKGROUND: The characteristics of the cellular kinetic reflect the aggressiveness of the tumors and even their prognosis, many studies proving the correlation between the increased proliferation activity and a poor prognosis in a variety of neoplasms. AIM: The analysis of immunohistochemical expression of the Ki-67 antigen using the monoclonal antibody MIB1 in 61 patients with gastric cancer, the correlation with clinicopathological factors and the prognosis of the patients. MATERIAL AND METHODS: We used the primary MIB1 antibody pre-diluted, using the LSAB technique, DAB visualization. The quantification of the reaction was performed by appreciating the marking index Ki-67 (MI Ki-67). Although all the lesions were positive, we noticed a marked intratumoral heterogeneity regarding the distribution of the Ki-67 score. The tumor cells were considered Ki-67 positive in the presence of brown nuclear staining of granular or diffuse type. The tumor invasion front has shown the most numerous Ki-67 positive cells. RESULTS: In the gastric carcinomas, we remarked various Ki-67 scores. For a proper grouping of the results, we classified gastric carcinomas into two categories: carcinomas with high MI Ki-67 (≥45%) and carcinomas with low MI Ki-67 (≤45%). We noticed an increased frequency of high MI Ki-67 carcinomas in elderly patients (p=0.03) and also in the tumors developed at cardia level and those extended in the entire stomach in the moment of diagnosis (p<0.001). The histological forms associated to high Ki-67 values are represented by the anaplastic carcinoma (100% of cases) and papillary adenocarcinoma (60% of cases).We observed a close correlation between the degree of tumor differentiation and the Ki-67 score (p<0.001). The results of our study do not reveal any correlation between the Lauren's Classification of gastric carcinomas, the lymphovascular invasion, the depth of tumor invasion, the TNM stage and the Ki-67 score (p>0.05). CONCLUSIONS: In our study, immunohistochemical assessment of the tumor proliferation does not represent a prognostic factor, but seems to be useful in identifying of a group of patients with aggressive tumors, needing adjuvant postoperatory chemotherapy.

The immunohistochemical expression of the p53-protein in gastric carcinomas. Correlation with clinicopathological factors and survival of patients.

BACKGROUND: P53-tumor suppressor gene has an essential role in controlling cell cycle and initiating carcinogenesis. In the case of gastric cancer, the role of p53-protein accumulation as prognostic factor is controversy. Various results are due to the different methods of study regarding patients' selection, immunohistochemical techniques used and the quantifying systems for immunoreactions. AIM: Assessment of p53-immunohistochemical expression in 61 patients with gastric carcinomas and the correlation with clinicopathological factors (gender, age, location, macroscopic, and histological type, degree of tumor differentiation and TNM-stage) and patients' survival. MATERIAL AND METHODS: From the total number of 265 patients (186 males and 79 females) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of five years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). We used the monoclonal antibody DO7 that detects the wild and mutant form of p53-protein, by EnVision technique and DAB-visualization. We considered positive reaction only in the presence of brown staining of the nuclei. RESULTS: P53-immunoreactions were positive in 25 gastric cancers (41%). We obtained positive stainings in 41.9% cases in men and 38.9% women. We found positive p53-immunoreactions in all the carcinomas developed in the upper third of the stomach (100%), in 53.3% of the corporeal tumors, 50% of the pangastric tumors; according to Lauren's classification, we noticed a significantly increased immunoreaction of p53 in the intestinal-type carcinomas. Among histological types, papillary, mucinous, anaplastic and tubular adenocarcinomas presented a relatively increased percentage of p53-positive immunoreactions. P53-positive stainings are more frequently encountered in moderate/poor differentiated carcinomas and those associated with lymphovascular invasion; according to pT- and pN-stage, we remarked a significantly increase of the number of p53-positive cases (p=0.02291 and p=0.038264). Five-year survival rate for patients with p53-positive carcinomas was significantly lower in comparison to the patients p53-negative (8% vs. 22.2%, p=0.0326). CONCLUSIONS: Immunohistochemical evaluation of p53-protein represents in our study an important prognostic factor, allowing the selection of a group of patients with an aggressive therapeutic indication, such as extensive lymphadenectomy and adjuvant chemotherapy.

Gastric cancer: correlation between clinicopathological factors and survival of patients (III).

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (histological type according to the WHO classification; degree of tumor differentiation; tumor location; stage of disease; pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). According to the maximum level of tumor invasion we identified: pTis - one case (1.6%); pT1 - four cases (6.6%); pT2 - nine cases (14.7%); pT3 - 17 cases (27.9%); most gastric cancers were included in the pT4 category (49.2%). We identified 43 gastric carcinomas with metastases in regional lymph nodes (70.5% of the cases). According to the number of lymph nodes involved: pN0 - 18 cases (29.5%); pN1 - 16 cases (26.2%); pN2 - 23 cases (37.7%); pN3 - four cases (6.6%). Distance synchronous metastases were present in 14 gastric carcinomas (pM1 - 23% of the cases), nine cases with hepatic metastases and five cases with distance peritoneal disseminations. Classification of gastric carcinomas: we identified one single case listed in the 0 stage, three cases in the IA stage, five cases in the IB stage, seven cases in the II stage, 11 cases in the IIIA stage, eight cases in the IIIB stage, and 26 cases in the IV stage. From the total of carcinomas, stage IV consisted of the greatest number of tumors, representing 42.6%. We generally remarked the increase of the number of cases in advanced stages. CONCLUSIONS: In the studied group, we noted a great number of gastric carcinomas diagnosed in stages T3 and T4 (77.1% of cases). Cardial tumor locations and gastric stump locations, as well as "signet-ring" cell and undifferentiated carcinomas prove to be aggressive, being diagnosed in advanced stages. 70.5% of gastric neoplasms presented lymph node metastases, most cases representing pN2 tumors (37.7%). 23% of neoplasms studied presented distance metastases at the time of diagnosis. We noted a significant correlation between the degree of tumor differentiation and the level of invasion, as well as the presence of distance and lymph node metastases. Survival at 5 years of patients included in the study was correlated significantly with the level of tumor invasion, the presence of lymph node and distance metastases, and the TNM stage.

Gastric cancer: correlation between clinicopathological factors and survival of patients. II.

PURPOSE: The purpose of this study was to identify the clinicopathological factors that influence the prognosis of patients having undergone surgery for gastric cancer. The analysis of the potential prognosis factors has included in this study parameters concerning the patient (sex, age), as well as parameters related with the tumor (macroscopic aspect of the tumor according to the Borrman's classification, histological type according to the WHO and Lauren's classifications, degree of tumor differentiation, tumor location, stage of disease, pT and pM parameters according to the TNM classification of AJCC/UICC). MATERIAL AND METHODS: From the total number of 265 patients (186 men and 79 women) diagnosed with gastric cancer in the period 1998-2002, 61 operated patients were selected. On this group, we performed a prospective study regarding the evolution and aggressiveness of gastric cancer, on a duration of 5 years. Survival time was calculated from the month of the surgical intervention until the month of death or confirmation of survival, and survival rate was represented by the percentage of survivals at the end of the observed interval (in years and months). RESULTS: The studied group consisted of 61 patients (43 men and 18 women), with ages between 30 and 80 (average age = 59.34 years). We have identified five papillary adenocarcinomas (8.2%), 28 tubular adenocarcinomas (46%), 17 "signet-ring" cell carcinomas (27.8%), eight mucinous adenocarcinomas (13.1%), and three undifferentiated or anaplastic carcinomas. Most gastric carcinomas examined were included in the category of poorly differentiated carcinomas (63.9%). According to the Lauren's classification, we have identified 38 intestinal type gastric carcinomas (62.3%), 17 diffuse type carcinomas (27.9%), and six mixed carcinomas (9.8%). We have identified aspects of lymphovascular invasion in 38 cases (62.3%). CONCLUSIONS: "Signet-ring" cells carcinomas, and the anaplastic ones, prove in our study to be extremely aggressive histological forms, characterized through low rates of survival. We remarked a significant correlation between the degree of tumor differentiation and survival of patients, the values recorded being significantly lower in medium and poorly differentiated carcinomas (p = 0.00871194 FS). Average survival, calculated in months, is significantly lower in patients with diffuse type carcinomas (11.3 months), in comparison with patients presenting intestinal type carcinomas (20.4 months) (p = 0.0415 S). There is a direct proportional relationship between the lymphovascular invasion and the number of positive lymph nodes. Survival after 5 years decreases significantly in the presence of lymphovascular invasion.

Gastric cancer: the correlation between the clinicopathological factors and patients' survival (I).

INTRODUCTION: The prognosis of the gastric cancer is generally reserved. The purpose of this study consists in the identification of the clinicopathological parameters that influence the prognosis of the patients that underwent surgery for gastric cancer. MATERIAL AND METHODS: Out of a total amount of 265 patients (186 males and 79 females) clinically and histopathologically diagnosed with gastric cancer, 61 patients operated for this disease have been selected from the Surgical Departments of the Emergency County Hospital in Timisoara. A prospective study was conducted on this group, regarding the gastric cancer's evolution and aggressiveness, for a period of 5 years. The survival time was calculated starting with the month when the surgery took place, and up to the month of death or that of the survival confirmation, and the survival rate was represented by the percentage of survivals at the end of the tracked period (in years and months). RESULTS: The study group was formed of 61 patients (43 males and 18 females) of ages between 30 and 80 years (mean age = 59.34 years). Gastric cancer was encountered more frequently in males (70.5%) than in females (29.5%) (p<0.001 ES). The amount of gastric cancer cases grows with age, the highest percent being observed in patients from the 51-70 years age group. However, the incidence is significantly lower after the age of 71 - 8.2% (p<0.001 ES). Antral localization of the gastric cancer predominates in both males and females, for all the age groups (50.8%). The average 5 years survival rate, for the whole group has been of 16.4%. We remark the extremely low survival rate for the older patients. In our study, we have identified five early gastric carcinomas (8.2%), classified as being type I protrusive tumors of intestinal type and 56 advanced gastric carcinomas, 16 cases in females (28.6%) and 40 cases in males (71.4%). The average survival for the patients with advanced gastric cancers was of 13.9 months, significantly lower than the average survival value of the patients with early gastric cancers (57.2 months). According to Borrmann's classification, we have identified five type I carcinomas (8.9%), 20 type II carcinomas (35.7%), 22 type III carcinomas (39.3%), and nine type IV carcinomas (16.1%). We did not notice any significant differences between the survival values of the patients with tumors of types I, II and III (p>0.05 NS), but the patients with diffuse infiltrative gastric cancers had an average survival of only 4.9 months after the surgery. CONCLUSIONS: The prognosis for gastric cancer is reserved, the 5 years average survival rate is of 16.4%. We have noticed a significantly decrease of survival rate with age (p = 0.024688 S). The 5 years survival is of 10.7% for patients with advanced cancers, significantly lower than the 5 years survival of 80% for patients with early gastric cancers (p<0.001 ES).The ulcerative-infiltrative type of cancer is predominant (39.3%). The patients with diffuse infiltrative forms of gastric cancers survived for an average period of only 4.9 months after surgical intervention.

Peptic upper gastrointestinal bleeding: diagnosis and treatment. A monocentric experience on a 5 years period.

AIM: We evaluated all the cases of upper gastrointestinal hemorrhages admitted in the Department of Endoscopy of our Clinic during a 5 years period. MATERIAL AND METHOD: 810 patients were included in our study, 64.3% males and 36.7% females, mean age 58.7 +/- 15.2 years (17-96 years). The main cause of the upper digestive hemorrhage was peptic ulcer (82.6%), equally divided in gastric and duodenal. All the ulcers were assessed according to the Forrest classification. RESULTS: Endoscopic haemostasis was performed in 40% of all cases, only epinephrine injection (1/10,000) in 44.4% of cases; combined therapy (injection + clip or thermocoagulation) in 40.3% of the cases and clip or thermocoagulation alone in 15.3% of the cases. A marked reduction of haemostasis using epinephrine injection alone (as monotherapy) was observed during the period of study. Postendoscopic treatment rebleeding occurred in 19.8% of cases; 3.6% of the patients have had a fatal outcome and surgical treatment was needed in 2.7% of cases. CONCLUSION: In an experienced Department of Endoscopy, the majority of upper gastrointestinal hemorrhages can be endoscopically treated with good results. In the last years, endoscopical haemostatic bitherapy (adrenaline injection+clipping or bipolar coagulation) replaced injection of adrenaline like monotherapy for ulcer hemostasis.

Immunohistochemical evaluation of the tumor neoangiogenesis as a prognostic factor for gastric cancers.

INTRODUCTION: The angiogenesis, the process by which new blood vessels are formed, plays an essential role in the survival of the malignant cells, in the local expansion and tumor invasion, as well as in the appearance of distant metastases. MATERIAL AND METHODS: We evaluated the relation between MVD, the VEGF expression, the clinicopathologic factors and the survival in patients with gastric cancer. A prospective study has been carried out, regarding the evolution and aggressiveness of the gastric cancer, with a duration of 5 years, 61 patients that underwent a surgery for gastric cancer being included in the study. The immunohistochemical reactions for CD34 and VEGF were performed for all gastric cancers cases included in the study group. RESULTS: MVD has shown in the gastric carcinomas an average value significantly higher in comparison to the normal mucosa (38.7 vs. 12.5, p<0.001 ES). In the intestinal type we have noticed a much lower average MVD than the average MVD in the diffuse type of gastric carcinomas (36.8 vs. 41.6) (p=0.02478 S). The anaplastic carcinoma and the signet ring cell carcinoma are detaching themselves as histological forms associated to an intense neoangiogenesis activity. The neoangiogenesis activity is correlated with: the histologic grade, the lymphovascular invasion, the level of extend, the lymph node metastasizing, the distant metastasizing and the TNM stage. The positive immunoreactions for VEGF are significantly more frequent in the gastric carcinomas, in comparison to the normal gastric mucosa (65.6% vs. 6.5%, p<0.001 ES). The immunoreactions to the VEGF protein were positive in 71.1% of the intestinal carcinomas, significantly more frequent in comparison to the diffuse type carcinomas (52.9%) (p=0.018178 S). Our results show a tight correlation between the histologic grade, the level of the tumor invasion and the VEGF expression. CONCLUSIONS: Our results prove the major correlation between the VEGF expression and the 5-year survival rate of the patients with gastric cancer, the survival rate for the carcinomas with VEGF +~++ being significantly lower than for the VEGF negative ones (12.5% vs. 23.8%) (p=0.027983 S). Our study proves a tight correlation between the VEGF expression and the MVD (p=0.03986 S), these factors playing an important role in the tumoral biologic conduct, in the progression and the prognostic.

Tumor angiogenesis in gastric cancer.

Growth of solid tumors, including gastric cancer, and the formation of metastasis depend on the induction of new blood vessels; in tumors, angiogenesis is uncontrolled and immature. This is a complex process, depending on a great variety of angiogenic factors, one of the most important being the vascular endothelial growth factor. In order to suppress the tumor development and the occurrence of metastasis, clinical trials have been developed with angiogenesis inhibitors, many of them with encouraging results. Further research is needed in regard to the idea of combined antiangiogenic therapy with conventional chemotherapy, or even immune or genetic therapies, in order to increase treatment efficiency and to suppress side effects.