Pathophysiology of acute experimental pancreatitis: Lessons from genetically engineered animal models and new molecular approaches

The incidence of acute pancreatitis is growing and worldwide population-based studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis are severe and associated with histological changes of necrotizing pancreatitis. There is still no specific medical treatment for acute pancreatitis. The average mortality resides around 10%. In order to develop new specific medical treatment strategies for acute pancreatitis, a better understanding of the pathophysiology during the onset of acute pancreatitis is necessary. Since it is difficult to study the early acinar events in human pancreatitis, several animal models of acute pancreatitis have been developed. By this, it is hoped that clues into human pathophysiology become possible. In the last decade, while employing molecular biology techniques, a major progress has been made. The genome of the mouse was recently sequenced. Various strategies are possible to prove a causal effect of a single gene or protein, using either gain-of-function (i.e., overexpression of the protein of interest) or loss-of-function studies (i.e., genetic deletion of the gene of interest). The availability of transgenic mouse models and gene deletion studies has clearly increased our knowledge about the pathophysiology of acute pancreatitis and enables us to study and confirm in vitro findings in animal models. In addition, transgenic models with specific genetic deletion or overexpression of genes help in understanding the role of one specific protein in a cascade of inflammatory processes such as pancreatitis where different proteins interact and co-react. This review summarizes the recent progress in this field. Copyright (c) 2005 S. Karger AG, Basel

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology

Background: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. Methods: In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m2 at week 1, then 250 mg/m2/week) and Gemcitabine (1 g/m2 on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. Results: Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect =grade 2 was associated with increased PFS (P = 0.05).Conclusion(s): Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy

Immunomodulation de la pancreatite experimentale

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Adjuvant therapy in gastric and cardia cancer: should we irradiate?

The purpose of this review is to comment on the current status and the place of the (neo)adjuvant therapy of gastric cancer, and on the standardization of care in this setting.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Adjuvant chemotherapy for colorectal cancer.

Colorectal cancer is the second leading cause of cancer death in Western countries. If surgery remains the only cure, recurrence rates for colon cancer range from 30% to 60% for stage III tumors. Adjuvant chemotherapy is the standard treatment for stage III colon tumors and consists of monthly administration of bolus 5-fluorouracil and leucovorin for 5 consecutive days a month over a 6-month period (Mayo regimen). Adjuvant chemotherapy for stage II colon cancer remains controversial, and its administration is not routinely recommended except in certain high-risk and selected patients. Immunotherapy, new drug-based therapies or combinations, and cyclooxygenase-2 inhibitors are being tested in the adjuvant setting. Total mesorectum excision is now the gold standard surgical technique for rectal cancer resection, and this procedure has dramatically decreased local recurrence. Nevertheless, adjuvant chemoradiotherapy is commonly indicated in the United States. In Europe, neoadjuvant radiotherapy is recommended for stage II and III resectable rectal cancers; the role of chemotherapy remains mostly investigational.Journal ArticleReviewinfo:eu-repo/semantics/publishe

Vitrectomie dans l'oedème maculaire diabétique associé à une hyaloïde postérieure tractionnelle.

The vitreomacular relationship has been demonstrated to play a role in the physiopathology of the diabetic macular edema. We review the functional and anatomic results of vitrectomy performed on four eyes of three patients with diabetic cystoid macular edema unresolved by photocoagulation. The preoperative visual acuity was "finger counting" at one meter to 1/20. After surgery, for three eyes, the visual acuity raised between 2/10 and 4/10. There was no change for one eye, which presented a subretinal fibrosis. The macular edema resolved in three eyes and improved in one eye. The mean postoperative follow-up is 13 months. The vitrectomy may be effective in cases of diabetic macular traction and edema without posterior vitreous detachment.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Personalized medicine in pancreatic cancer: The revolution has begun

Pancreatic ductal adenocarcinoma carries a dismal prognosis. Both chemotherapy and targeted therapies have been disappointing when administered to unselected populations. Recently, progress has been made in our understanding of the genomic landscape of this cancer which displays remarkable heterogeneity suggesting a reorientation of management and research strategies based on molecular characterization and adapted personalized therapy. Resectable disease offers new opportunities for translational research through functional imaging response evaluation and tumor tissue acquisition before and after neoadjuvant therapy. There is urgent need for clinical trials based on molecular profiling in pancreatic ductal adenocarcinoma. In this review we discuss opportunities and limitations of these new strategies, underlining the importance of tissue acquisition and integration of molecular biomarkers in future molecularly driven clinical trials.SCOPUS: re.jinfo:eu-repo/semantics/publishe