[Desmoid tumors in an adolescent girl with familial adenomatous polyposis]. / Tumeurs desmoïdes dans le cadre d'une polypose adénomateuse familiale chez une adolescente.

Desmoid tumors (DT) are rare and nonmetastasizing fibroblastic neoplasms, characterized by local invasiveness. They occur sporadically or arise in the context of familial adenomatous polyposis (FAP; 5-10% of cases). Most cases develop sporadically in young adults, but some cases also occur in children. We report the case of an adolescent girl with FAP and DT, and we discuss the therapeutic strategies. An adolescent girl with FAP underwent surgery at the age of 14 years with total proctocolectomy. She had a neo-mutation in the APC gene at codon 1068, which is not usually associated with DT. Three years later, she had painful defecations. Imaging showed two abdominal DT. After a multidisciplinary team meeting, the patient was refused for surgery, and medical treatment with antihormonal agents and nonsteroidal anti-inflammatory drugs was started. Imaging 18 months later showed DT stabilization, but the patient had difficulties to control chronic pains, which required morphine treatment, hypnotic sessions, and transcutaneous electric nerve stimulation. This case highlights the importance of DT screening in patients with FAP, mainly after surgery, regardless of their age and genetic mutation. Progress remains to be made in determining DT risk factors and in developing treatment. DT are still difficult to cure because of their potential for local invasion and local recurrence, and need to be managed by a multidisciplinary team.

Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS: Expression of HER2, ß-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of ß-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.

Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment.

OBJECTIVES: The most commonly used schedules are 5-FU in combination with CDDP with or without epirubicin (ECF) or docetaxel (TCF) in treatment of MGA patients (pts), independently of HER status. We evaluated the efficacy of FOLFIRI regimen in a large retrospective series of MGA pts. METHODS: Two hundred and twelve pts from 13 French centers were treated with at least one cycle of FOLFIRI (irinotecan 180 mg/m2 intravenous (i.v.) over 90 minutes on day 1 with folinic acid (FA) 400mg/m2 i.v. over two hours followed by 5-FU 400mg/m2 i.v. bolus then 5- FU 2400 mg/m2 continuous infusion over 46 hours on day 1, repeated every 14 days). Primary tumour sites were 120 (58%) stomach and 92 (42%) gastroesophageal junction. FOLFIRI was administered as first-line in 137 (65%) pts and as later-line in 75 (35%) pts for MGA. RESULTS: There was no difference between chemonaive and not chemonaive pts treated as firstline in terms of response rate 37% (95% CI: 25-50) vs 44% (95% CI: 21-69), median PFS, 6.7 (95% CI: 5.5-9.9) vs 5.3 months (95% CI: 3.6-6.9) (P = 0.25), and OS, 13.1 (95% CI: 11.7-18.7) vs 8.8 months (95% CI: 7.3­15.6) (P = 0.19), respectively. There was no difference between pts treated as second or later-line in terms of response rate 20% (95% CI: 8-39) vs 22% (95% CI: 6-48), median PFS, four months (95% CI: 2.8-5.4) vs 3.5 months (95% CI: 2.3-4.5) (P = 0.56), and OS, 10.4 months (95% CI: 5.4-14.4) vs 5.3 months (95% CI: 3.5-11.3) (P = 0.58), respectively. The global grade 3-4 toxicities were: diarrhea 11%, vomiting 9%, neutropenia 18%, febril neutropenia 4% (one toxic death). CONCLUSIONS: This retrospective study confirms the activity and good tolerance of FOLFIRI regimen in MGA as first-line as well as later-line.

[Nasal septum perforation and bevacizumab]. / Perforation de la cloison nasale et bevacizumab.

A 52-year-old woman, with a metastatic breast cancer, presented with a nasal septum perforation while receiving a treatment combining paclitaxel and bevacizumab. This is the fifth reported case of nasal septum perforation probably related to an anti-angiogenic therapy. A literature review and a discussion concerning the different causes of nasal septum perforation were performed.

[Small bowel adenocarcinoma]. / Adénocarcinome de l'intestin grêle.

Small bowel adenocarcinoma is a rare tumor. These tumors are more often sporadic but there is some predisposing disease (Crohn disease, genetic syndrome and rarely celiac disease). Diagnosis is usually performed at an advanced stage because of non-specific nature of clinical manifestations. New methods of radiological and endoscopic exploration of small intestine should allow earlier diagnosis. Surgical resection remains the only potentially curative treatment for non-metastasic tumors. The main prognosis factor is lymph nodes involvement. The role of adjuvant chemotherapy is unclear. For metastatic tumors, 5-fluorouracil and platinum salt combination appears to be the most effective chemotherapy despite of the absence of randomized studies. A national prospective cohort study is currently evaluating the results of chemotherapy (recommended protocol: FOLFOX) as adjuvant and palliative treatment of small bowel adenocarcinoma.

Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study.

BACKGROUND: Small-bowel adenocarcinoma (SBA) is a rare tumor of poor prognosis. Data on the efficacy of chemotherapy for advanced SBA are scarce. PATIENTS AND METHODS: All patients with advanced SBA who received frontline chemotherapy from 1996 to 2008 were eligible for this retrospective multicenter study. RESULTS: Ninety-three consecutive patients were included. In the entire population, the median progression-free survival (PFS) and overall survival (OS) times were 6.6 and 15.1 months, respectively. Median PFS times among patients treated with LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) and LV5FU2-cisplatin (n = 16) were 7.7, 6.9, 6.0 and 4.8 months, respectively, while median OS times were 13.5, 17.8, 10.6 and 9.3 months, respectively. In multivariate analysis, World Health Organization performance status (PS) (P < 0.0001) and elevated serum levels of carcinoembryonic antigen (CEA) (P = 0.02) and carbohydrate antigen 19-9 (CA 19-9) (P = 0.03) were the only variables significantly associated with poor OS. In the subgroup of patients treated with platinum-based chemotherapy, multivariate analysis showed that LV5FU2-cisplatin was associated with poorer PFS (P < 0.0001) and OS (P = 0.02) compared with FOLFOX. CONCLUSIONS: This is the largest study of chemotherapy in advanced SBA. Baseline PS and CEA and CA 19-9 levels were the main prognostic factors. FOLFOX seems to be the most effective platinum-based chemotherapy regimen.

First-line simplified GEMOX (S-GemOx) versus classical GEMOX in metastatic pancreatic cancer (MPA): results of a GERCOR randomized phase II study.

PURPOSE: GemOx was defined as a D1-D2 schedule, based on preclinical data. In order to improve convenience for patients, we evaluated a simplified D1-D1 GemOx regimen (S-GemOx) in MPA. PATIENTS AND METHODS: Patients (pts) with MPA were 2:1 randomly assigned for first-line treatment to S-GemOx (gemcitabine 1,000 mg/m(2), 100-minute infusion D1 immediately followed by oxaliplatin 100 mg/m(2), 120-minute infusion) or to GemOx (Gem D1 and ox D2). Treatment was repeated in each arm every 2 weeks until disease progression. Stratification was performed on center and PS. RESULTS: Fifty-seven pts were enrolled, S-GemOx = 37 (PS 2: 22%), GemOx = 20 (PS 2: 20%). Populations were well balanced for age (64.9 vs 66.6 years); gender (57 vs 65% male), location of primary tumor (pancreas head: 49 vs 50%), and metastatic sites (liver 76 vs 85%; peritoneum 24 vs 20%; lung 16 vs 10%; lymph nodes 14 vs 15%; other 5 vs 5%). Tumor differentiation significantly differed between the 2 groups (S-GemOx: 8% poorly differentiated vs GemOx: 36%). Response rate was 27% (95% CI: 12-42) in arm S-GemOx and 10% (95% CI: 0-23) in GemOx. Median PFS was 4.0 and 2.5 months in S-GemOx and GemOx, respectively. Median OS was 7.6 and 3.2 months in S-GemOx and GemOx, respectively. Since more cycles were administered in S-GemOx (8.5 [1-29] vs 5.8 [2-12]), grade 3 oxaliplatin-induced neuropathy was higher in S-GemOx [21.6 vs 0%]). CONCLUSIONS: Activity and tolerance of S-GemOx are in the same range as compared to our previous experiences of classical GemOx in metastatic pancreatic cancer. The very bad outcome of patients randomized in GemOx arm could at least be in part explained by the high-rate of poorly differentiated tumors.

Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery.

BACKGROUND/AIM: Immunosuppressants are now used much earlier in the course of Crohn's disease; however their effect on the natural history of the disease, especially on the need for surgery, is not known. The aim of this study was to assess the evolution of the need for surgery in Crohn's disease during the last 25 years. PATIENTS AND METHODS: The medical charts of 2573 patients were reviewed retrospectively. The use of immunosuppressants (azathioprine or methotrexate), the need for intestinal resection, and the occurrence of intestinal complications were assessed using Kaplan-Meier analysis in five consecutive cohorts of patients defined by the date of diagnosis of Crohn's disease (1978-82; 1983-87; 1988-92; 1993-97; 1998-2002). RESULTS: In 565 patients seen in the authors' unit within the first three months after diagnosis, characteristics of Crohn's disease at diagnosis did not differ from one cohort to another. The five year cumulative probability to receive immunosuppressants increased from 0 in the 1978-82 cohort to 0.13, 0.25, 0.25, and 0.56 in the 1983-87, 1988-92, 1993-97, and 1998-2002 cohorts, respectively (p<0.001). Concomitantly, the cumulative risk of intestinal resection remained unchanged (from 0.35 to 0.34 at five years; p=0.81). The cumulative risk of developing a stricturing or a penetrating intestinal complication remained also unchanged. Similar results were obtained in the 2008 patients seen during the same period who were referred to us more than three months after diagnosis. CONCLUSION: Although immunosuppressants have been used more frequently over the last 25 years, there was no significant decrease of the need for surgery, or of intestinal complications of Crohn's disease.