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Biomedical subjects

D Pezet

Publications and source records attributed to D Pezet.

At least 19 recordsLinked to original sources

Phase II trial of chronomodulated infusion of high-dose fluorouracil and l-folinic acid in previously untreated patients with metastatic colorectal cancer.

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status less-than-or-equal 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 PM to 10:00 AM with peak at 4:00 AM). 5-FU dose was escalated from 900 to 1,100 mg/m(2)/d with fixed dose of l-FA at 150 mg/m(2)/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses). Objective response rate (ORR) was 41% (95% confidence interval, 31.5% to 50.5%). Twenty patients underwent metastases surgery; among these, 12 had a complete resection. Median progression-free survival was 7 months. Median survival was 17 months; 28% of the patients were alive at 2 years and 18.6% at 3 years. CONCLUSION: The ORR achieved with intensified chronomodulated delivery of 5-FU/l-FA was nearly twice as high as that earlier obtained by our cooperative group using less intensive 5-FU/FA chronotherapy.

Adult↗

[Carbon dioxide pneumoperitoneum and peritoneal carcinosis: review].

OBJECTIVE: The aim of this work was to demonstration the relations between CO(2) laparotomy and peritoneal carcinosis. The first part of this review presents published observations of disseminated peritoneal carcinosis after laparoscopy with CO(2) insufflation. The second part deals with the possible effects of CO(2) laparoscopy on the mechanism of carcinosis. MATERIAL AND METHODS: We made a Medline search for cases of peritoneal dissemination after CO(2) laparoscopy. We present here the published results as well as data from comparative studies conducted in humans and animals on the effects of each step of CO(2) laparoscopy on carcinogenesis and the progress of carcinosis. RESULTS: Most of the published cases on peritoneal dissemination after CO(2) laparoscopy concerned management of ovarian carcinomas where malignancy was not diagnosed before the operation and not treated immediately with laparotomy. The significance of peritoneal dissemination appears to be related to the delay between laparoscopy and laparotomy. No comparative study in humans has been published. For animal studies, it has been difficult to design valid animal modes. Those we present show that laparoscopy has no negative influence on tumor growth but that it may affect peritoneal dissemination. Laparoscopy can participate in diffusion of tumor cells either due to repeated manipulation with contaminated instruments or because of the insufflation itself. These cells can be seeded on traumatized areas of the peritoneum or parietal wall or on the port tracts. The recent work by Volz has proven the effect of CO(2) which can cause a change in the ultra-structure of the peritoneum. This may facilitate peritoneal seeding of the malignant cells. No other study has shown any evidence of increased intraperitoneal tumor growth. Only primary results of post-laparoscopy liver metastasis have diverged. Laparoscopy does not seem to have a negative effect on general immunity, but possible changes in intraperitoneal immunity remain to be elucidated. CONCLUSION: Observations concerning peritoneal dissemination are found in cases where CO(2) insufflation was used for laparoscopy, but no studies have proven certain risk greater for laparoscopy than for laparotomy. Maximum precautions must be taken during the management of suspicious ovarian lesions.

Animals↗

Determination of microsatellite instability, p53 and K-RAS mutations in hepatic metastases from patients with colorectal cancer: relationship with response to 5-fluorouracil and survival.

In vitro and clinical studies have suggested that high-frequency microsatellite instability (MSI-H) phenotype, p53 and K-ras mutations might influence the response to chemotherapy in a variety of tumors, including primary colorectal cancers (CRC). Unresectable hepatic metastases from CRC are commonly treated with 5-fluorouracil (5FU) and folinic acid. Since several new active drugs are now used for treating CRC, molecular determinants predictive to response to 5FU would thus be crucial for optimizing indications of chemotherapy to those patients. MSI-H phenotype, p53 and K-ras status were characterized in a prospective study of 56 patients with CRC metastatic to the liver and treated with 5FU-based chemotherapy. The objective response rate after a 3-month treatment was 32.1%. The prevalence of p53 mutations, K-ras mutations and MSI-H phenotype was 62.5%, 30.3% and 1.8%, respectively. No significant association was found between response to chemotherapy and p53 mutations (78% mutated tumors in responders vs. 55% in nonresponders; p = 0.10) and K-ras mutations (39% mutated tumors in responders vs. 26% in nonresponders; p = 0.34). Survival was longer for patients with p53-mutated metastases than for patients with unresected wild-type p53 metastases (median survival 15 months vs. 17 months; p = 0.06). The determination of the MSI-H phenotype, p53 and K-ras status in hepatic metastases from CRC does not discriminate a group of patients that should preferentially benefit from 5FU-based chemotherapy. The prognosis of patients with treated liver metastases is better when p53 is mutated.

Adult↗

[Aneurysm of the duodeno-pancreatic arcades. Diagnostic imagery and therapeutic indications].

BACKGROUND: Aneurysms of the duodenopancreatic arcades account for 2 to 3% of all aneurysms of the digestive arteries. Mortality is high due to the risk of rupture and the difficult diagnostic situation. CASE REPORTS: The first case involved a short wide collar aneurysm implanted on the first centimeter of the superior mesenteric artery, associated with tight stenosis of the celiac trunk. The patient complained of diffuse abdominal pain and was treated surgically. In the second case, there was a false aneurysm of the gastroduodenal artery which developed a few months after acute biliary pancreatitis. The aneurysm was treated by exclusion using a transcutaneously delivered endovascular coil prosthesis. CONCLUSION: These cases illustrate the importance of imaging (magnetic resonance angiography) both for diagnosis and treatment monitoring, allowing early care with very limited morbidity and mortality.

Abdominal Pain↗

Quality of life before and after laparoscopic fundoplication.

BACKGROUND: Laparoscopic fundoplication is a well-established surgical option for the treatment of gastroesophageal reflux disease. The aim of this study was to assess the surgical outcomes from the patient's point of view by using a validated quality of life instrument. METHODS: Fifty patients have been prospectively included. All patients underwent a standardized 270-degree posterior fundoplication. Quality of life was measured by the Gastrointestinal Quality of Life Index (GIQLI), a 36-item-questionnaire. The patients received the questionnaire before surgery, and 3 months and 1 year after surgery. RESULTS: Preoperative score was 95.6+/-21 points. The score increased significantly (P <0.0005) at 3 months (103.6+/-16) and 1 year (111.4+/-22) after surgery. This improvement concerned the four domains of the questionnaire (symptoms, social functioning, physical status, and emotions). The score in patients at 1 year remained, however, significantly lower than that in healthy persons (126+/-18). CONCLUSIONS: GIQLI is a sensitive tool to assess surgical outcomes after fundoplication. The quality of life after surgery did not reach the level of healthy population, not because of failure of surgery to treat GERD but probably because of functional dyspepsia that was present prior to surgery and did not change after fundoplication.

Dyspepsia↗

Effect of CO(2) gas warming on pain after laparoscopic surgery: a randomized double-blind controlled trial.

BACKGROUND: Previous studies have suggested that gas temperature has an influence on postlaparoscopy pain. This trial therefore was conducted to study the effect of gas warming on pain after upper abdominal laparoscopic surgery. METHODS: Patients who underwent laparoscopic cholecystectomy, fundoplication, or Heller's myotomy were included and randomly allocated to receive either warm or cold gas. Primary end point was shoulder tip pain, and secondary end points were subcostal, trocar wound, and visceral pains, as well as other postoperative events. Criteria of pain assessment were the visual analog scale, verbal rating scale, and amount of analgesics. RESULTS: A total of 100 patients were suitable for postoperative evaluation. The groups were well matched. Shoulder tip and subcostal pains were significantly more intense after gas warming (p < 0.05). The three assessment criteria showed the same differences. No difference was observed concerning trocar wound and visceral pains and the other secondary end points. Subdiaphragmatic temperature was not significantly different (34.4 degrees with warming vs. 34 degrees without warming). CONCLUSIONS: Gas warming does not reduce, and probably increases, postoperative shoulder tip and subcostal pains.

Carbon Dioxide↗

[Use of lanreotide in the prevention of pancreatic fistula after cephalic duodeno-pancreatectomy. Preliminary study].

STUDY AIM: Dehiscence of pancreatic anastomosis is the main complication after pancreatoduodenectomy. The efficacy of somatostatin analogue to prevent complications after pancreatic resections is at present well-established by several randomized trials. The aim of this preliminary prospective study was to assess the role of lanreotide (a long acting somatostatin analogue) in this field. PATIENTS AND METHOD: Forty patients with pancreatic head tumour have been included in a prospective study. Criteria for pancreatic fistula were: high concentration of amylase in the drainage fluid (> 3 times that in the serum), or intra-abdominal fluid collection adjacent to the pancreatic anastomosis, or reoperation (or postmortem verification) showing an anastomotic dehiscence. The patients received 12 h before the operation 30 mg of lanreotide intramuscularly. RESULTS: Of the 40 patients included prospectively, 34 underwent a pancreatic resection. Parenchyma of pancreatic remnant was crumbly in 28 cases. Six patients experienced a pancreatic fistula (17.6%) which healed in all cases. CONCLUSION: This preliminary study shows clearly the feasibility of a long acting somatostatin analogue (lanreotide) to prevent pancreatic fistula after pancreatectomy. This agent appears simple to use and its efficacy needs obviously to be assessed by randomized trials.

Humans↗

[First validation of the French version of the Gastrointestinal Quality of Life Index (GIQLI)].

AIM: Gastrointestinal quality of life index (GIQLI) was initiated in Germany. The aim of this study was to validate its French version (translation). METHODS: The questionnaire includes 36 items asking about symptoms, physical status, emotions, social dysfunction, and effects of medical treatment. The questionnaire has been applied to 615 persons: 335 healthy individuals and 280 patients. Responsiveness and absolute and relative scores were calculated in both groups. Psychometric analysis was done by measuring the validity (convergent and discriminant) and internal consistency. RESULTS: The responsiveness was 93%. The mean score was 126 for healthy individuals and 96 for patients (P < 0.00001). The validity of the questionnaire (both convergent and discriminant) and the internal consistency were demonstrated. Clinical validity was also suggested by the differences between healthy individuals and patients. CONCLUSION: This study allowed the psychometric validation of the French version of GIQLI. This index could be used in France as a reliable method for measuring quality of life related to gastrointestinal diseases.

Adult↗

[Is laparoscopic surgical practice "factual" (evidence based)? Results of a prospective regional survey].

OBJECTIVE: Evidence-based medicine is a growing paradigm in health care. We conducted a prospective study to determine whether laparoscopic surgery is truly evidence-based in everyday practice. METHODS: A prospective regional survey was performed in 11 French hospitals (one university and 10 district hospitals) to ascertain how general laparoscopic surgery was conducted during the last 3 months of 1997. We also searched the electronic databases for original articles on laparoscopic procedures. The methodology of randomized trials was analyzed and procedures were classed by level of evidence. We assumed that an evidence-based procedure was which had been validated by well-designed randomized controlled or prospective trials giving homogeneous results. RESULTS: One half of the procedures performed had been evaluated by randomized controlled trials. Among the 428 laparoscopic procedures, 334 (78%) were found to be evidence-based (CI 74.1-81.9%). Twelve of the 18 indications for laparoscopy (67%) were evidence based (CI: 62.5%-71.5). There was no difference between university teaching hospitals and general district hospitals. CONCLUSION: Contrary to initial criticisms, the practice of laparoscopic surgery appears to be truly evidence-based in the majority of cases.

Evidence-Based Medicine↗

Laparoscopic or open appendectomy? Critical review of randomized, controlled trials.

PURPOSE: A randomized, controlled trial is considered to be the "gold standard" to evaluate a new procedure. Thus, this critical review assessed whether the published randomized trials on laparoscopic appendectomy show that it is superior to the open approach. METHODS: Twelve original articles involving a randomized, controlled trial on laparoscopic appendectomy in adults published between January 1990 and December 1996 were selected. We studied first whether each trial was positive (a procedure is superior to the other) or negative (no difference). We reviewed for each trial the methodology used and the following outcomes: operating time, intraoperative and postoperative complications, time until resumption of diet, postoperative pain, hospital stay, cost, and quality of life analyses. Postoperative morbidity was considered as the major primary outcome. RESULTS: There were six positive and six negative trials. Postoperative complication rates were similar, but the two approaches had specific potential complications, wound infections following open appendectomy, and intra-abdominal abscesses following laparoscopic appendectomy. This review failed to show a superiority of the laparoscopy for the other outcomes, particularly postoperative pain. CONCLUSION: Differences in positive trials concerned subjective and controversial outcomes, and the flaw in negative trials was their lack of power. Thus, nothing is definitively well established, even after 12 randomized trials.

Appendectomy↗

[Does neoadjuvant radiochemotherapy augment the resectability of pancreatic cancers?].

PURPOSE OF THE STUDY: Pre-operative radiochemotherapy is the most recent therapeutic option in the pre-operative downstaging of pancreatic cancer and in decreasing the rate of positive resection margins. The purpose of the study was to evaluate tolerance and efficacy of pre-operative radiochemotherapy in unresectable pancreatic cancers. MATERIAL AND METHODS: This study included seven cases of pancreatic cancer considered unresectable. The patients received preoperatively 50 grays within a 5-week period associated with 5 FU and Platin during the 1st and 5th weeks. RESULTS: After radiochemotherapy, tomodensitometric evaluation showed a minor response in two cases. A pancreatico-duodenectomy could be performed in these two patients without any increase of pre- or post-operative morbidity or mortality. CONCLUSIONS: The results of the study suggest that preoperative radiochemotherapy may increase pancreatic cancer resectability. This hypothesis should be confirmed by a prospective randomised trial.

Adenocarcinoma↗

[Segmental absence of colonic muscularis propria. Report of a case in an adult].

We report a case of segmental defect of colonic muscularis propria revealed by perendoscopic perforation in a 64-year-old woman. Segmental absence of intestinal musculature is well documented in new-borns and infants and is more frequent in small bowel. It is characterized by localised absence of muscularis propria without fibrous scar. The remaining layers of the bowel wall are intact. The pathogenesis of this lesion is discussed.

Colon↗