Antonio Grassi

Basophil-bound and serum immunoglobulin E directed against Helicobacter pylori in patients with chronic gastritis.

The immunoglobulin (Ig) E immune response in patients with Helicobacter pylori-associated chronic gastritis has been evaluated. Of 26 patients with H. pylori infection, 22 (84%) tested positive for basophil-bound specific IgE (determined by the histamine release test) and 18 (69%) for serum specific IgE (determined by an enzyme-linked immunosorbent assay). In contrast, only 1 of 17 persons in whom the bacterium was not detected presented cell-bound and serum specific IgE. In the 4 histamine release test--positive but enzyme-linked immunosorbent assay--negative patients, removal of antibody from the basophil surface by acid elution showed that histamine release occurred through an IgE-dependent mechanism. When normal basophils, passively sensitized with serum from IgE-positive patients, were exposed to the H. pylori antigen, a significant release was observed, confirming the class specificity of the response. Inhibition experiments with bacteria other than H. pylori showed that the IgE antibody was specifically directed against this organism. The percentage of antigen-induced histamine release did not correlate with serum specific IgE level. However, the response of basophils to antigenic challenge was proportional to IgE-dependent cellular releasability. This finding suggests that target cell sensitivity may be the most important factor in determining the entity of biological response to the antigenic challenge. The ability of H. pylori to induce a specific IgE immune response could answer key questions regarding the mechanisms inducing gastric inflammation.

TAG-72 (CA 72-4 assay) as a complementary serum tumor antigen to carcinoembryonic antigen in monitoring patients with colorectal cancer

Background. Serum carcinoembryonic antigen (CEA) is the most frequently chosen tumor marker in the clinical diagnosis of colorectal carcinoma and in the long‐term monitoring of patients after tumor resection. In recent years, monoclonal antibody technology has identified several new markers of neoplasia, two of which, TAG‐72 and CA 19‐9, are found in the sera of patients with adenocarcinoma. Serum CEA, TAG‐72, and CA 19‐9 were evaluated in 300 patients with either malignant (n = 200) or benign (n = 100) colorectal disease.

Learning curve for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal surface malignancies: analysis of two centres.

We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process.

Pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic chemotherapy: a 7-year single-center experience

AIMS AND BACKGROUND Pseudomyxoma peritonei (PMP) is a rare clinical entity characterized by diffuse intraabdominal gelatinous collections with mucinous implants on the peritoneal surfaces and omentum. This condition should be considered a borderline malignancy with disease progression over time. Encouraging treatment results have been recently reported with the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS . From December 2003 to December 2010, 18 patients with PMP were referred to our institution. All patients underwent peritonectomy and CRS combined with HIPEC in accordance with Sugarbakers procedure. RESULTS The mean Peritoneal Cancer Index score was 27.6 (range, 5-39). Twelve (67%) patients had disseminated peritoneal adenomucinosis and 6 (33%) peritoneal mucinous carcinomatosis. Optimal cytoreduction with no visible residual disease or residual disease ≤2.5 mm in diameter was achieved in all patients. The mean duration of the surgical procedure including HIPEC was 9 hours and 30 minutes (range, 5-13 hours); major morbidity occurred in 30% of patients and the mortality was 11%. The mean follow-up was 27 months (range, 1-72) and the 5-year overall survival 66%. CONCLUSIONS In line with the existing literature, our experience suggests that patients with PMP could benefit from CRS + HIPEC in terms of survival and locoregional disease control.

Campylobacter pylori et gastrite: étude biologique, immunologique, histologique et endoscopique

RÉSUMÉLe rôle pathogène du Campylobacterpylori) dans l’étiologie de la gastrite a été suspecté par de nombreuses investigations. La présente étude a pour but une meilleure compréhension de ce problème. 83 patients examinés en ambulatoire ont subi une gastroscopie avec biopsies de la muqueuse antrale pour examen histologique et culture deC. pylori. Les anticorps anti-C. Pylori spécifiques ont été dosés dans le sérum.C. pylori était présent chez 79 % des patients présentant une gastrite superficielle, 68 % de ceux porteurs d’une gastrite atrophique. Aucun patient à muqueuse normale ne s’est révélé porteur duC. pylori. Les taux d’anticorps IgG anti-C. pylori étaient élevés chez les patients souffrant de gastrite, tant superficielle qu’atrophique, mais étaient absents chez les porteurs d’une muqueuse normale. Ces résultats suggèrent que l’immunoassay sérique peut constituer une méthode de diagnostic non invasive, fiable, particulièrement adaptée au dépistage de ce type de gastrite. Des investigations ultérieures seront nécessaires à la confirmation de cette hypothèse.SummaryThe possible role of Campylobacter pylori (Cp) in the aetiology of gastritis has been suspected in many investigations. The present study is a further contribution to a better understanding of this problem. In 83 outpatients we performed gastroscopy associated with biopsy of antral mucosa for histological and cultural search of Cp. Blood samples was also taken to determine specific circulating IgG anti-Cp. Campylobacter Pylori was present in 79 % of the patients with superficial gastritis, and in 68 % of those with atrophic gastritis. No patients with normal mucosa was found to be bearer of Cp. The level of anti-CP IgG was found elevated in patients with gastritis, superficial as well as atrophic, and absent in those with normal mucosa. It is suggested that immunological assay in serum might constitute a valid non invasive diagnostic tool that could be particularly useful for the screening of gastritis. Further investigations are in progress to obtain more data to support this hypothesis.ResumenEl papel del Campylobacter pylori) en la etiología dela gastritis ha sido motivo desospecha en numerosas investigaciones. El presente estudio tiene como objetivo una mejor comprensión de éste problema. 83 pacientes examinados ambulatoriamente sufrieron una gastroscopio con biopsia de la mucosa antral para examen histológico y cultivo de C. pylori. Se dosificaron los anticuerpos anti-C. pylori específicos en suero. El C. pylori se detectó en el 79 % de pacientes que presentaban una gastritis superficial, y en el 68 % de los que sufrían una gastritis atrófica. Ningun paciente con mucosa normal era portador de C. pylori. La tasa de anticuerpos IgG anti-C. pylori era alta en el grupo de pacientes que tenian gastritis, tanto superficial como atrófica, pero no habia trazas de los mismos en los pacientes con mucosa normal. Estos resultados sugieren que el inmunoensayo sérico puede ser un método de diagnóstico no invasivo, fiable, adaptado muy especialmente al despistaje de éste tipo de gastritis. Serum necesarias posteriores investigaciones que confirmen ésta hipótesis.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Techniques

Peritoneal carcinomatosis has long been considered a terminal condition and constitutes a difficult therapeutic challenge given the dismal prognosis associated with this entity and the debilitating effect it exerts on affected patients. Over the past decade, novel therapeutic approaches to peritoneal surface malignancies have emerged. These new approaches are all based on a strong rationale: most frequently, peritoneal carcinosis is a locoregional condition that should be approached with locoregional treatments, such as cytoreductive surgery and peritonectomy procedures for macroscopic disease in combination with perioperative intraperitoneal chemotherapy for microscopic residual disease. In order to take advantage of this synergistic effect, different devices and techniques have been developed. Perioperative intraperitoneal chemotherapy is a milestone of the combined approach to peritoneal surface malignancy. Two main modalities for administering chemotherapeutic agents have been described: intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), and early postoperative normothermic; the former has gained greater acceptance among peritoneal surface malignancy centers.

Hepatobiliary cystoadenoma: a wolf in sheep’s clothing

Hepatobiliary cystoadenoma is a rare cystic tumor of the liver that can undergo malignant change and become lethal. Accurate diagnosis of such lesions, even though not always possible, is of importance as the management is totally different from that of other nonneoplastic cysts. We report a case of a 60-year-old woman with aspecific symptoms, which was diagnosed using ultrasound scan and CT scan and treated with hepatic resection, and review the main features of this tumor.

Abstract 2709: Peritoneal carcinomatosis from ovarian cancer: tissue markers as predictors of response to chemotherapy

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Epithelial ovarian cancers represent 80 to 90% of all ovarian malignancies and are the most common cause of death from gynecological tumors in the Western world. The absence of specific symptoms in the early stages of disease means that around two-thirds of patients are initially diagnosed with advanced disease and/or peritoneal dissemination. Although standard primary treatment now exists for advanced ovarian cancer, there is still no single accepted therapeutic strategy for those who develop recurrent intra-abdominal disease more than 6 months after a complete response. The present study aimed to identify a panel of genes whose expression is correlated with sensitivity or resistance to platinum compounds. Material and methods: Fresh surgical biopsy specimens were obtained from 22 patients with advanced epithelial ovarian cancer during intra-abdominal cytoreductive surgery. Expression levels of ERCC1, GSTP1, MGMT, XPD, BRCA1 were determined by Real Time RT-PCR. Relative gene expression was quantified according to the comparative threshold cycle method (2-ΔΔCτ) using β2-microglobulin and HPRT as endogenous controls and commercial RNA controls derived from normal ovarian tissue mRNA as calibrators. The correlation between pre- and post-surgery expression levels of these markers and response to platinum treatment was examined. Results: Time to progression (TTP) was calculated from the first day of treatment to the date on which objective disease progression was first documented, or death in the absence of progressive disease. At univariate analysis, estimated hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated using the Cox proportional hazard model. In particular, the risk of progression increased significantly as ERCC1 (HR=12.00, 95% CI 1.08-133.35, p=0.04), GSTP1 (HR=6.01, 95% CI 1.09-33.01, p=0.004), XPD (HR=10.37, 95% CI 1.26-85.52, p=0.003), MGMT (HR=10.26, 95% CI 1.18-88.94, p=0.035) and BRCA1 (HR= 7.52, 95% CI 1.32-42.74, p=0.023) levels increased. Conclusions: Our results indicate that these biomarkers could be useful predictors of clinical response to platinum compounds in patients with advanced ovarian cancer who develop recurrent intra-abdominal disease. It is now planned to compare tailored and empiric therapy in a well-designed randomized trial. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2709.