Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02).

BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.

Antral motility in patients with cirrhosis with or without gastric antral vascular ectasia.

Gastric motility has not been extensively studied in patients with cirrhosis and gastric antral vascular ectasia (GAVE) may be associated with antropyloric dysfunction. This study therefore looked at antral motility using ultrasound in patients with alcoholic cirrhosis with or without GAVE. Twenty six patients were included: 10 patients with cirrhosis without GAVE, eight patients with cirrhosis and GAVE, and eight controls without liver disease. Measurement of antral area and antral contractions (amplitude and frequency) was performed for three hours after ingestion of a standardised solid-liquid meal. Antral area half time (mean (SD)) was not significantly increased in patients with cirrhosis without GAVE (84 (42) min), but increased by 120% (123 (43) min; p < 0.01) in patients with GAVE compared with controls (56 (26) min). GAVE patients exhibited the same frequency and amplitude of antral contractions at each time point as controls and had the same tendency to increase these values over time although this was attenuated in the late postprandial phase. In contrast, cirrhotic patients without GAVE exhibited a significantly higher frequency and amplitude of antral contractions during the initial postprandial phase but showed no change in either frequency or amplitude over time. In conclusion, in cirrhosis there is an abnormal antral motor response to a meal, which has a different pattern over time in patients with or without GAVE.

[Analysis of cellular DNA content by flow cytometry in epidermoid carcinoma of the esophagus]. / Analyse du contenu cellulaire en ADN par cytométrie en flux dans le carcinome épidermoïde de l'oesophage.

Flow cytometric DNA analysis was performed in 35 patients with squamous cell carcinoma of the esophagus. The aim of this study was a) to establish a tumoral DNA pattern, b) to determine an objective parameter correlating with tumoral response to chemotherapy (5 FU-cisplatin). DNA analysis was performed in perendoscopic ranged tumoral biopsy specimens to determine the DNA ploidy (DNA index) and S phase fraction. Tumor diameter and length were evaluated by computed tomography (CT) before and after chemotherapy in 24 patients. The relative variation of this product determined a CT index. Before chemotherapy, 82 percent (76/93) of the specimens were available for assessment; 72 percent (26/36) of the tumors were aneuploid. In these tumors, the DNA index ranged from 1.23 to 2.80. Five tumors had two distinct and simultaneous aneuploid populations. CT index values were not significantly different according to the ploidy (diploid, aneuploid), the S phase fraction (low, high), the DNA content modification after chemotherapy (absent, present). In this study, DNA analysis did not allow to select patients with higher response to chemotherapy. The inter- and intratumoral phenotypic heterogeneity may be one of the responsible factors.

Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy.

We conducted a prospective randomized controlled study to evaluate the effectiveness of propranolol and sclerotherapy, compared to a control group, in the prevention of variceal rebleeding in alcoholic cirrhotic patients. Among the 79 patients included, the distribution of patients according to Child-Pugh classification was: A, 22%; B, 40%; and C, 38%. Propranolol was given twice daily with a mean final dose of 54 +/- 16 mg/day, this resulted in a mean reduction in resting heart rate of 26 +/- 7%. Sclerotherapy was performed weekly using 1% polidocanol. End points were rebleeding or death. During the mean follow up of 19 +/- 16 months, 43 patients bled and 22 patients died. The cumulative percentages of patients free of rebleeding at 1 year were: propranolol, 81% (95% confidence interval (CI): 63-92); sclerotherapy, 64% (95% CI: 45-82); control, 54% (95% CI: 36-71); these differences did not reach statistical significance. The cumulative percentages of patients alive at 1 year were: propranolol, 92% (95% CI: 76-98); sclerotherapy, 79% (95% CI: 58-91); control, 81% (95% CI: 60-93); these differences were not statistically significant. Alcohol withdrawal, which occurred in 66% of patients, was an independent predictive factor associated with a decreased risk of rebleeding or death. In conclusion, a life table analysis of patients free of rebleeding, as well as of patients surviving, revealed a tendency in favour of propranolol. The lack of a statistical support for these two favorable effects could be due to poor statistical power.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe hemorrhagic radiation proctitis advancing to gradual cessation with hyperbaric oxygen.

We report a case of a male patient suffering from a severe hemorrhagic radiation proctitis which gradually ceased with hyperbaric oxygen. We discuss the mechanisms of chronic radiation injury and the effect of the hyperbaric oxygen. This therapy is proposed as an alternative to surgical intervention for this abnormality.

Pancreas divisum and pancreatitis: a coincidental association?

The aim of the present study is to assess the frequency of pancreas divisum and the features of patients with pancreas divisum in order to assess the role of this anomaly in the occurrence of pancreatitis. A total of 1049 endoscopic retrograde pancreatographies were studied between 1978 and 1988. Patients with pancreas divisum were studied in terms of their clinical findings and their disease (pancreatitis or not). Pancreas divisum was diagnosed in 62 patients (5.9%). No statistical differences with regard to age and sex were found between patients with and without pancreas divisum. The frequency of pancreas divisum was similar in the different groups of disease, especially chronic pancreatitis, acute pancreatitis, recurrent pancreatitis and idiopathic pancreatitis. The study of pancreatograms showed that dorsal ductal abnormalities alone were found as frequently as ventral alterations alone. Our results show that pancreas divisum cannot be directly implicated in the occurrence of pancreatitis, and should not prompt a systematic sphincterotomy of the accessory papilla. This treatment should only be considered in the rare cases of acute recurrent idiopathic pancreatitis with dorsal ductal dilatation and stenosis of the accessory papilla.

[Rectal micropolyps after total colectomy in familial polyposis. Efficacy of sulindac]. / Micropolypes rectaux après colectomie totale pour polypose familiale. Efficacité du sulindac.

The aim of this study was to assess the effectiveness of sulindac therapy for eradication of micropolyps in 8 patients with familial polyposis coli. All patients had undergone colectomy and ileoproctostomy 4.5 years (range 3 months-20 years) before and had tubulous adenomas micropolyps in the rectum. Initial sulindac therapy 200 mg or 300 mg daily was started in all patients and was continued in 7 patients. In these 7 patients macroscopic and microscopic eradication of micropolyps was obtained within 3.4 months (1-8). After discontinuation of sulindac therapy, recurrence of micropolyps occurred in 4 patients within 3 to 4 months. Three patients had no recurrence with a follow-up of 1 to 19 months. A new eradication of micropolyps was obtained in these 4 patients with a second sulindac cure within 3 to 6 months. These observations confirm the effectiveness of sulindac therapy for eradication of tubulous adenomas micropolyps in familial polyposis, but after discontinuation of therapy, recurrence is frequent. Continuous or intermittent therapy might reduce recurrence.

[Assay of serum elastase 1 in adenocarcinoma of the pancreas: diagnostic value, compared and combined study with serum CEA and CA 19-9]. / Dosage sérique de l'élastase 1 dans l'adénocarcinome du pancréas: intérêt diagnostique, étude comparée et combinée avec l'ACE et le CA 19-9 sériques.

Serum elastase 1, CEA and, CA 19-9 titers were determined by radioimmunoassay in 113 patients with benign non pancreatic digestive disease, 88 patients with non pancreatic carcinoma, 25 patients with chronic pancreatitis and 40 patients with pancreatic carcinoma (of whom 34 were classified according to Fortner's staging classification), respectively: a) to evaluate the diagnostic value of elastase in pancreatic carcinoma, b) to compare and to study the value of its association with CEA and CA 19-9 for earlier detection of this type of cancer. The specificity of serum elastase (greater than 500 ng/dl) was greater than that of CA 19-9 (greater than 37 U/ml), (93.3 p. 100 vs 64.6 p. 100, p less than 0.01), but its sensitivity was significantly lower than that of CA 19-9 (27.5 p. 100 vs 82.5 p. 100; p less than 0.001). The sensitivity of CA 19-9 (greater than 37 U/ml) and/or elastase (greater than 500 ng/dl) was 85.2 p. 100 (greater, but not significantly, than CA 19-9 alone) and 91.6 p. 100 in Fortner stage I or II tumors (greater, but not significantly, than Fortner stage III tumors which were at 83.6 p. 100). The specificity of the combined test was 62 p. 100, lower (but not significantly) than CA 19-9 alone. As serum CEA (greater than 5 ng/ml) alone and in association with CA 19-9 was disappointing, it might be replaced by the elastase assay. The combined CA 19-9-elastase assay coupled with morphologic investigations could represent an attractive approach for earlier detection of this cancer.

[Bilateral abscess of the psoas with aero-anaerobic digestive flora in advanced tuberculosis]. / Abcès bilatéral du psoas à flore digestive aéro-anaérobie lors d'une tuberculose évolutive.

The authors report a case of bilateral psoas abscess without spondylodiscitis, occurring in the course of an advanced pleuro-pulmonary tuberculosis. The dual bacteriological composition of the pus with an aero-anaerobic flora on direct examination, and mycobacterium tuberculosis in the culture, as well as the presence of an obstructive appendicitis noticed during the surgery, open the discussion of its pathogenesis.