Jean Francois Flejou

Regression of Liver Fibrosis after Biliary Drainage in Patients with Chronic Pancreatitis and Stenosis of the Common Bile Duct

BACKGROUNDnChronic obstruction of the common bile duct may cause hepatic fibrosis and secondary biliary cirrhosis.nnnMETHODSnWe studied liver-biopsy specimens from 11 patients with chronic stenosis of the common bile duct due to chronic pancreatitis; all the patients had undergone liver biopsy before or at the time of surgical biliary decompression and underwent a subsequent liver biopsy for various clinical reasons. The patients were followed as part of a prospective study of 501 patients who had been treated for chronic pancreatitis. Two pathologists, who were unaware of the sequence of specimens, graded fibrosis on a scale of 0 (none) to 3 (cirrhosis).nnnRESULTSnThe 11 patients were all men. Chronic pancreatitis was due to alcohol abuse in 10 of the men; 1 had idiopathic disease. The median age at diagnosis was 38 years. The median interval between the first and second liver biopsies was 2.5 years (range, 0.3 to 9.0). The two patients who had restenosis of the biliary anastomosis were excluded from the analysis of fibrosis. In the group of nine patients without restenosis, the second specimen showed significant improvement in fibrosis (P=0.01). The fibrosis improved by two grades in two patients and by one grade in four patients; in three patients, the grade did not change. The pathologists agreed on the grading of specimens from 10 of the 11 patients.nnnCONCLUSIONSnIn patients with chronic pancreatitis and stenosis of the common bile duct, liver fibrosis may regress after biliary drainage.

Risk of colorectal high-grade dysplasia and cancer in a prospective observational cohort of patients with inflammatory bowel disease.

BACKGROUND & AIMSnThere is an unclear risk of colonic high-grade dysplasia (HGD) and colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD) treated with immunosuppressants. We analyzed data on CRC development among patients with IBD enrolled in the observational cohort Cancers et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME).nnnMETHODSnWe followed and collected data from 19,486 patients with IBD (60.3% with Crohns disease, 30.1% receiving thiopurine therapy) enrolled in CESAME from May 2004 and June 2005, and followed them until December 2007. When the study began, 2841 patients (14.6%) were characterized as having long-standing extensive colitis (ie, >10 years and involving ≥50% of the colon). Early lesions (HGD and CRC) were defined as those diagnosed within 10 years after diagnosis of IBD.nnnRESULTSnThirty-seven patients developed CRC during the follow-up period, and 20 developed colorectal HGD. The standardized incidence ratios of CRC were 2.2 for all IBD patients (95% confidence interval [CI]: 1.5-3.0; P < .0001), 7.0 for patients with long-standing extensive colitis (95% CI: 4.4-10.5; P < .001), and 1.1 for patients without long-standing extensive colitis (95% CI: 0.6-1.8; Pxa0= .84). Among patients with long-standing extensive colitis, the multivariate adjusted hazard ratio for colorectal HGD and cancer was 0.28 for those who received thiopurines compared with those who never received thiopurine therapy (95% CI: 0.1-0.9; Pxa0= .03). Twenty-two patients developed early lesions; 7 of these were related to IBD, based on histologic analysis.nnnCONCLUSIONSnPatients with IBD and long-standing extensive colitis are at increased risk for CRC, although the risk is lower among patients receiving thiopurine therapy. Patients without long-standing extensive colitis have a risk for CRC similar to that of the general population, but they can develop IBD-related lesions within 10 years after diagnosis of IBD.

Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study

PURPOSEnThe MOSAIC (Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer) study has demonstrated 3-year disease-free survival (DFS) and 6-year overall survival (OS) benefit of adjuvant oxaliplatin in stage II to III resected colon cancer. This update presents 10-year OS and OS and DFS by mismatch repair (MMR) status and BRAF mutation.nnnMETHODSnSurvival actualization after 10-year follow-up was performed in 2,246 patients with resected stage II to III colon cancer. We assessed MMR status and BRAF mutation in 1,008 formalin-fixed paraffin-embedded specimens.nnnRESULTSnAfter a median follow-up of 9.5 years, 10-year OS rates in the bolus/infusional fluorouracil plus leucovorin (LV5FU2) and LV5FU2 plus oxaliplatin (FOLFOX4) arms were 67.1% versus 71.7% (hazard ratio [HR], 0.85; P = .043) in the whole population, 79.5% versus 78.4% for stage II (HR, 1.00; P = .980), and 59.0% versus 67.1% for stage III (HR, 0.80; P = .016) disease. Ninety-five patients (9.4%) had MMR-deficient (dMMR) tumors, and 94 (10.4%) had BRAF mutation. BRAF mutation was not prognostic for OS (P = .965), but dMMR was an independent prognostic factor (HR, 2.02; 95% CI, 1.15 to 3.55; P = .014). HRs for DFS and OS benefit in the FOLFOX4 arm were 0.48 (95% CI, 0.20 to 1.12) and 0.41 (95% CI, 0.16 to 1.07), respectively, in patients with stage II to III dMMR and 0.50 (95% CI, 0.25 to 1.00) and 0.66 (95% CI, 0.31 to 1.42), respectively, in those with BRAF mutation.nnnCONCLUSIONnThe OS benefit of oxaliplatin-based adjuvant chemotherapy, increasing over time and with the disease severity, was confirmed at 10 years in patients with stage II to III colon cancer. These updated results support the use of FOLFOX in patients with stage III disease, including those with dMMR or BRAF mutation.

Colorectal neoplasia in Crohn's colitis: a retrospective comparative study with ulcerative colitis.

Aims:u2002 To determine the clinicopathological features of colorectal cancer (CRC) in Crohns disease (CD).

Abdominal radiotherapy is a cause for chronic pancreatitis

We report a series of five patients with nonalcoholic chronic pancreatitis who underwent abdominal radiotherapy for Hodgkins disease (n = 4) or seminoma (n = 1) at doses ranging from 3600 to 4050 rads, 6 to 20 years (median, 7 years) before the onset of pancreatitis. Patients were in complete remission for their malignant disease. Other causes of chronic pancreatitis were excluded. The manifestations of chronic pancreatitis (median follow-up after the diagnosis of pancreatitis, 5 years) were pancreatic pain (n = 5), acute pancreatitis (n = 3), pseudocysts (n = 3), common bile duct stenosis (n = 2), duodenal stenosis (n = 1), splenic vein obstruction (n = 1), diabetes mellitus (n = 4), steatorrhea (n = 4), and pancreatic calcifications (n = 1). Other abdominal radiation injuries were severe chronic ulcer of the genu superius (n = 1), stenosis at the junction of the right and left hepatic ducts (n = 1), and splenic and left renal atrophy (n = 1). In one patient, pathological examination of the pancreas showed signs of chronic pancreatitis, severe fibrous endarteritis, and lack of inflammation. Abdominal radiotherapy should be added to the list of causes of chronic pancreatitis. We suggest that the physiopathology of postradiotherapy chronic pancreatitis is a vascular process.

Pathology Analysis Reveals That Dysplastic Pancreatic Ductal Lesions Are Frequent in Patients With Hereditary Pancreatitis

BACKGROUND & AIMSnHereditary pancreatitis (HP) is a risk factor for pancreatic adenocarcinoma. We performed a retrospective, multicenter study to characterize and evaluate the frequency of pancreatic intraepithelial neoplasia (PanIN) and to describe the characteristics of fibrosis in pancreatic surgical specimens from patients with HP.nnnMETHODSnSamples from partial pancreatectomies (n = 13) of patients with HP complications (n = 12; 7 males; mean age, 24 y; 1 patient underwent 2 surgeries over 16 years) were analyzed by histologic and immunohistologic analyses; patients with suspected or proven pancreatic adenocarcinoma were excluded. HP diagnosis was confirmed by analysis of PRSS1 mutations. Dysplastic lesions were described according to the PanIN classification.nnnRESULTSnEleven patients were found to have the R122H mutation in PRSS1 and 1 patient was found to have the N29I mutation in PRSS1. Fifty-one PanIN lesions were observed in 10 specimens (77%): PanIN lesions 1a, 1b, 2, and 3 were observed in 8, 5, 8, and 5 specimens, respectively. The median number of PanIN lesions was 3.5 for each specimen. The density of the lesions was 2.6 per 10 cm(2). The size of lesions was greater than 0.5 mm in 55% of the samples. Two patients with PanIN-3 developed pancreatic cancer, 18 months and 44 years after surgery.nnnCONCLUSIONSnPanIN lesions are frequent, severe, and occur early in the course of HP. Among patients with PanINs, 50% had PanIN-3 lesions. Pancreatectomy could be considered as a prophylactic against pancreatic cancer in patients with high-grade dysplasia.

Regulation of colon cancer cell proliferation and migration by MD-2 activity.

Evidence suggests that signalling through lipopolysaccharide (LPS) has a significant role in the development of gastrointestinal malignancies. We previously demonstrated the critical role of myeloid differentiation (MD)-2, the essential co-receptor of LPS, for induction of cyclooxygenase (Cox)-2 in intestinal epithelial cells. Cyclooxigenase-2 was suggested to play a key role in colorectal cancer through the effects of prostaglandin (PG) E2 generated. We, therefore, addressed the role of MD-2 in several parameters related to malignancy, namely cell proliferation and migration, using colon cancer cells (HT-29). We found that overexpression of MD-2 confers a significantly greater proliferation and migration capacity to these cells. MD-2-dependent proliferation and migration appeared independent of Cox-2 activity but was reduced by endothelial growth factor receptor (EGFR) neutralizing antibodies as well as by pharmacological inhibition of EGFR tyrosine phosphorylation. We propose that MD-2 overexpression contributes to tumour aggressiveness via a Cox-2-independent excessive EGFR signalling. Moreover, MD-2 expression levels were higher in tissue from patients with colorectal cancer as compared with paired control colorectal mucosa. Our data attest to a role of MD-2 activity in colon cancer epithelial cell proliferation and migration, which may be important in the general correlation between innate immune response, chronic inflammation, and cancer.

Bipolar hypertrophic herpes: an unusual presentation of acyclovir-resistant herpes simplex type 2 in a HIV-infected patient.

Hypertrophic pseudo tumoral herpetic lesion is an uncommon presentation in immunocompromized hosts that can be refractory to established therapies. We describe bipolar anal and tonsilar herpetic tumoral lesions related to acyclovir-resistant HSV-2 in a human immunodeficiency virus-infected patient. Treatment with valacyclovir, cidofovir, and thalidomide failed and surgical excision was required.

Prognostic value and characteristics of N1c colorectal cancer

The presence of tumour deposits (TDs) in colorectal cancer (CRC) is associated with poor prognosis. The seventh edition of TNM subclassified a new nodal stage, N1c, characterized by the presence of TDs without any concurrent positive lymph node (LN). It is not clear if the N1c category is or is not equal to LN metastasis. We aimed to examine the prevalence, characteristics and prognostic significance of this new subcategory.

Azathioprine May Not be Associated With Development of Colorectal Tumors With Microsatellite Instability in Patients With Inflammatory Bowel Disease

Azathioprine May Not be Associated With Development of Colorectal Tumors With Microsatellite Instability in Patients With Inflammatory Bowel Disease