Ricardo Artigiani-Neto

Ki67 and p53 in gastrointestinal stromal tumors - GIST

CONTEXT Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor. Cellular proliferation and apoptosis is gaining importance for predicting prognosis in several cancers. OBJECTIVE To investigate the Ki67 and p53 immunostaining in GISTs. METHODS Specimens from 40 patients with GIST were assessed for immunohistochemical expression of Ki67 and p53. The tumors were divided according the risk of recurrence in two groups: I with high or intermediate risk and; II with low or very low risk. RESULTS Among the 40 patients, 21 were men, the mean age was 56 years, 16 occurred in the small intestine and 13 in the stomach, 5 in the retroperitonium, 4 in the colon or rectum and 2 in the mesenterium. Thirty two tumors were from group I and 8 from group II. Half of the patients developed recurrence, being 90% of the group I (P = 0.114). The tumor Ki67 labelling index ranged from 0.02 to 0.35 (mean level 0.12). This index was marginally higher in the group I patients with recurrence (P = 0.09) compared to the patients of the same group without recurrence. p53 staining was expressed in 65% of the GISTs. A higher frequency of p53 and Ki67 had been found in the group I tumors when compared to the other group (P = 0.022; OR = 8.00 - IC 95%: 1.32-48.65). CONCLUSION The most common site was the small intestine and 80% had a malignant potential justifying the high recurrence observed. No significant correlation was found between p53 and overall outcome of the patients. In group I patients, the evaluation Ki67LI may be a marker of prognosis. The positivity of both markers is higher among the patients with worst prognosis than in the others.

NM23 protein expression in colorectal carcinoma using TMA (tissue microarray): association with metastases and survival

CONTEXT NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma. OBJECTIVE To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma. METHODS One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fishers exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001). NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57), vascular invasion (P = 0.85), lymphatic invasion (P = 0.41), perineural infiltration (P = 0.46), staging (P = 0.19), lymph node metastases (P = 0.08), or liver metastases (P = 0.59). Disease-free survival showed significant association (P = 0.01) with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13). CONCLUSIONS NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma staging, or overall survival. Disease-free survival was higher in patients with increased NM23 expression.

Adenocarcinoma da vesícula biliar: avaliação dos fatores prognósticos em 100 casos ressecados no Brasil

BACKGROUND: In spite its relative rarity, gallbladder adenocarcinoma is a neoplasm who presents an aggressive biologic behavior. The single curative treatment has been radical surgical resection with free margin. Prognostic factors has been studied because are very important to identify long-term survival patients which may benefit of aggressive surgical resection. AIM: To evaluate long-term prognostic predictors from gallbladder cancer. METHODS: The medical records of all patients that presented confirmed histological diagnosis of gallbladder adenocarcinoma operated over a 14 year period were identified and retrospectively reviewed. Uni and multivariate analysis was done. RESULTS: Total sample was 100 patients. Median age was 71 years (34 to 93). There were 17 men and 83 women. Lesion distribution according to TNM stage system was: I (n=22), II (n=59), III (n=6), IV (n=4) and unknown (n=9). Fifty two patients underwent radical resection (R0) while 48 to palliative surgery (R1-R2). Overall major morbidity was 14%, while postoperative surgical mortality rate (30th postoperative day) was 12 %. Five-year survival rate was 28% while median of survival was 10 months. Multivariate analysis identified six prognostic factors: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort (after 2002) and hilar lymphadenectomy. CONCLUSION: Prognostic factors were: T stage, serum level of CA 19.9, gallbladder perforation, lymphatic embolization, surgical historical cohort and hilar lymphadenectomy.

Evaluation of P53, E-cadherin, Cox-2, and EGFR protein imunnoexpression on prognostic of resected gallbladder carcinoma

Background Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. Aim To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. Methods Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. Results Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. Conclusion Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue.

ASSESSMENT OF THE RESPONSE OF PATIENTS WITH CROHN'S DISEASE TO BIOLOGICAL THERAPY USING NEW NON-INVASIVE MARKERS: lactoferrin and calprotectin

CONTEXT The use of fecal markers to monitor Crohns disease is crucial for assessing the response to treatment. OBJECTIVE To assess the inflammatory activity of Crohns disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohns disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. METHODS Seventeen patients were included who had been previously diagnosed with Crohns disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32). RESULTS The calprotectin levels exhibited significant reductions (P=0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P=0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01). CONCLUSION Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohns disease patients who are subjected to biological therapy.

GROWTH FACTORS AND COX2 IN WOUND HEALING: AN EXPERIMENTAL STUDY WITH EHRLICH TUMORS

ABSTRACT Background: Healing is an innate biological phenomenon, and carcinogenesis acquired, but with common humoral and cellular elements. Carcinogenesis interferes negatively in healing. Aim: To evaluate the histological changes in laparotomy scars of healthy Balb/c mice and with an Ehrlich tumor in its various forms of presentation. Methods: Fifty-four mice were divided into three groups of 18 animals. First group was the control; the second had Ehrlich tumor with ascites; and the third had the subcutaneous form of this tumor. Seven days after tumor inoculation, all 54 mice were submitted to laparotomy. All of the animals in the experiment were operated on again on 7th day after surgery, with resection of the scar and subsequent euthanasia of the animal. The scars were sent for histological assessment using immunohistochemical techniques to evaluate Cox-2 (cyclooxygenase 2), VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor). Semi-quantitatively analysis was done in the laparotomy scars and in the abdominal walls far away from the site of the operation. Results: Assessing the weight of the animals, the correct inoculation of the tumor and weight gain in the group with tumoral ascites was observed. The histological studies showed that groups with the tumor showed a statistically significant higher presence of Cox-2 compared to the control. In the Cox-2 analysis of the abdominal wall, the ascites group showed the most significant difference. VEGF did not present any significant differences between the three groups, regardless of the site. The FGF showed a significant increase in animals with the tumor. Conclusion: Histological findings in both laparotomy scar and the abdominal wall showed that with Ehrlichs neoplasia there was an exacerbated inflammatory response, translated by more intense expression of Cox-2 and greater fibroblast proliferation, translated by more intense expression of FGF, that is, it stimulated both the immediate inflammatory reactions, observed with Cox-2 reactions, and late scarring by fibroblasts and FGF.

INTRA-ABDOMINAL SEMINOMA TESTIS IN ADULT: CASE REPORT.

The available evidence demonstrates that both laparoscopic and open ligament release associated with celiac ganglionectomy are effective in provide celiac artery revascularization and sustained symptom relief in the majority of patients with the syndrome2,3,5. The laparoscopic approach is feasible, safe, and successful, if performed by experienced laparoscopic surgeons. Although the laparoscopic treatment of celiac axis compression syndrome is a new technique, several authors have demonstrated its affectivity in providing symptom relief in patients1,2,8. In addition, this access has several advantages, such as reduction of postoperative pain and blood loss, shorter hospital stay and faster recovery. More recently, this syndrome has been effectively treated with robot-assisted surgery3. The advantages of this approach compared to the laparoscopic access have not yet been completed evaluated. The high cost of robot-assisted surgery is an important drawback in our country.

The Role of COX-2 Inhibitors on Experimental Colitis

Since the introduction of acetylsalicylic acid (aspirin) as the first nonsteroidal antiinflammatory drug (NSAID) in 1897, NSAIDs have been widely used in the management of pain and inflammation (Botting, 2010; Vane et al., 1990; Wallace, 1997). Today, they are classified as traditional nonsteroidal antiinflammatory drugs (tNSAIDs), characterized by differing degrees of antiinflammatory, analgesic and antipyretic activity. tNSAIDs are among the most widely used medicines in the world. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia (10-20%) to symptomatic and complicated ulcers (1-4%) (Scheiman, 2006; Wolfe et al., 1999). The mechanism of tNSAIDs action is attributed to the cyclooxygenase (COX) inhibition (Botting, 2010; Vane, 1971). Cyclooxygenase is a key rate-limiting enzyme that exists in at least two isoforms: COX-1 is observed constitutively expressed in various tissues, whereas COX-2 does not appear to be expressed except at very low levels in most tissues and is rapidly upregulated in response to growth factors and cytokines. More recently, COX-2 has been implicated in several distinct cellular mechanisms, such as angiogenesis, proliferation and the prevention of apoptosis (Dempke et al., 2001). New antiinflammatory drugs have been synthesized, such as selective COX-2 inhibitors (anti-COX-2), however, these drugs may present side effects, such as the ability to modify the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. The precise etiology of IBD, including Crohn s disease (CD) and ulcerative colitis (UC), remains unclear. However, environmental factors, immunological disturbances, genetic influences and the presence of certain chemical mediators (cytokines) have been established as putative participants in the pathogenesis of the disease (Barbieri, 2000; Lashner, 1995; Podolsky, 2002). In the last few decades, the development of experimental models for studying IBD has greatly contributed to enhance understanding of the immunological mechanisms involved, such as changes in the gut epithelial barrier (Colpaert et al, 2001; Shorter et al, 1972). IBD seems to occur when luminal antigens from the bacterial flora stimulate the immune system